Cancers doi: 10.3390/cancers16061202
Authors: Vuong Trieu Anthony E. Maida Sanjive Qazi
LGG tumors are characterized by a low infiltration of immune cells, requiring therapeutic interventions to boost the immune response. We conducted a study analyzing mRNA expression datasets from the UCSC Xena web platform. To screen for upregulated genes, we sought to compare normal brain tissue with LGG tumor samples. We also used cBioportal to determine the relationship between mRNA expression levels of 513 LGG patients and their overall survival (OS) outcomes. Three tumor-associated macrophage (TAM) markers, MSR1/CD204, CD86, and CD68, exhibited a 6-fold (p < 0.0001), 8.9-fold (p < 0.0001), and 15.6-fold increase in mRNA expression levels, respectively, in LGG tumors. In addition, both TGFB1 (4.1-fold increase, p < 0.0001) and TGFB2 (2.2-fold increase, p < 0.0001) ligands were also upregulated in these tumors compared to normal brain tissue, suggesting that TGFB ligands are pivotal in establishing an immunosuppressive, angiogenic, and pro-tumorigenic TME in gliomas mediated through TAMs. In addition, mRNA upregulation of interferon-gamma receptors, IFNGR1 and IFNGR2, and the downstream signaling molecules STAT1, IRF1, and IRF5, pointed to an essential role for IFN-γ mediated remodeling of the TME. Interestingly, the mRNA expression of a tumor-associated antigen, CD276/B7-H3, showed a significant (p < 0.0001) 4.03-fold increase in tumor tissue, giving further insights into the roles of macrophages and tumor cells in supporting the immunosuppressive TME. Multivariate Cox proportional hazards models investigating the interaction of TGFB2 and activation of IFNGR2, STAT1, IRF1, or IRF5 showed that the prognostic impact of high mRNA levels (25th percentile cut-off) of TGFB2 was independent of IFNGR2, STAT1, IRF1, or IRF5 mRNA levels (TGFB2high HR (95% CI) = 4.07 (2.35–7.06), 6 (3.62–10.11), 4.38 (2.67–7.17), and 4.48 (2.82–7.12) for models with IFNGR2, STAT1, IRF1, or IRF5, respectively) and age at diagnosis. Patients with high levels of TGFB2 and IFNGR2 were over-represented by LGG patients with isocitrate dehydrogenase wild-type (IDHwt) mutation status. The prognostic impact of high levels of TGFB2 and IDH wild-type observed by the increases in hazard ratios for TGFB2 (HR (95% CI range) = 2.02 (1.05–3.89)) and IDH wild-type (HR (95% CI range) = 4.44 (1.9–10.4)) were independent predictors of survival, suggesting that risk stratification of patients identifies LGG patients with IDH wild-type and high levels of TGFB2 in the design of clinical trials. Furthermore, we have additional IRF5 and CD276/B7-H3 as prognostic markers that can also be targeted for combination therapies with TGFB2 inhibitors. In support of these findings, we demonstrated that low levels of gene methylation in TGFB2, IFNGR2, IRF1, IRF5, STAT1, and CD276 were associated with significantly worse overall survival (OS) outcomes. This suggests that potential mechanisms to increase the expression of these prognostic markers occur via the action of demethylation enzymes.
]]>Cancers doi: 10.3390/cancers16061203
Authors: Jongsoo Park Changwoon Kim Jong Geol Jang Seok Soo Lee Kyung Soo Hong June Hong Ahn
Diagnosing ground-glass opacity (GGO) pulmonary lesions poses challenges. This study evaluates the utility of radial probe endobronchial ultrasound-guided transbronchial lung biopsy (RP-EBUS-TBLB) in diagnosing GGO pulmonary lesions. A total of 1651 RP-EBUS procedures were performed during the study period. This study analyzed 115 GGO lesions. The EBUS visualization yield was 80.1%. Of 115 lesions, 69 (60%) were successfully diagnosed. The average size of diagnosed lesions was significantly larger than that of undiagnosed lesions (21.9 ± 7.3 vs. 17.1 ± 6.6 mm, p < 0.001). Diagnostic yield varied by lesion size: 50.0% for lesions <20 mm, 65.1% for 20–30 mm lesions, and 85.7% for lesions >30 mm. The mixed blizzard sign on EBUS appeared in 60.6% of mixed GGO lesions, with no cases in pure GGO lesions. Multivariable analyses showed that lesion size (odds ratio [OR], 1.10; 95% confidence interval [CI], 1.00–1.16; p < 0.001) and mixed blizzard sign on EBUS (OR, 20.92; CI, 7.50–58.31; p < 0.001) were significantly associated with diagnostic success. Pneumothorax and hemoptysis occurred in 1.7% and 2.6% of patients, respectively. RP-EBUS-TBLB without fluoroscopic guidance is a viable diagnostic approach for GGO pulmonary lesions with acceptable complications.
]]>Cancers doi: 10.3390/cancers16061201
Authors: Gyanendra Pokharel Qinggang Wang Momtafin Khan Paula J. Robson Lorraine Shack Karen A. Kopciuk
Background: Breast cancer is the most common cancer in Canadian women; nearly 25% of women diagnosed with cancer have breast cancer. The early detection of breast cancer is a major challenge because tumours often grow without causing symptom. The diagnosis of breast cancer at an early stage (stages I and II) improves survival outcomes because treatments are more effective and better tolerated. To better inform the prevention of and screening for breast cancer, simulations using modifiable rather than non-modifiable risk factors may be helpful in shifting the stage at diagnosis downward. Methods: Breast cancer stages were simulated using the data distributions from Alberta’s Tomorrow Project participants who developed breast cancer. Using multivariable partial proportional odds regression models, modifiable lifestyle factors associated with the stage of cancer at diagnosis were evaluated. The proportions or mean levels of these lifestyle factors in the simulated population were systematically changed, then multiplied by their corresponding estimated odds ratios from the real data example. The effects of these changes were evaluated singly as well as cumulatively. Results: Increasing total dietary protein (g/day) intake was the single most important lifestyle factor in shifting the breast cancer stage downwards followed by decreasing total dietary energy intake (kcal/day). Increasing the proportion of women who spend time in the sun between 11 am and 4 pm in the summer months, who have had a mammogram, who have been pregnant or reducing the proportion who are in stressful situations had much smaller effects. The percentage of Stage I diagnoses could be increased by approximately 12% with small modifications of these lifestyle factors. Conclusion: Shifting the breast cancer stage at diagnosis of a population may be achieved through changes to lifestyle factors. This proof of principle study that evaluated multiple factors associated with the stage at diagnosis in a population can be expanded to other cancers as well, providing opportunities for cancer prevention programs to target specific factors and identify populations at higher risk.
]]>Cancers doi: 10.3390/cancers16061200
Authors: Stergios Kopatsaris Aikaterini Apostolopoulou Ioannis Tsakiridis Antigoni Tranidou Fotios Zachomitros Evangelos Papanikolaou Alexandros Daponte Ioannis Kalogiannidis Themistoklis Dagklis
The early and accurate diagnosis of endometrial cancer is of paramount importance for the survival of these patients. The aim of this study was to systematically appraise the available data regarding the accuracy of frozen section biopsy in diagnosing endometrial cancer. A thorough literature search was performed in PubMed/Medline, Scopus and the Cochrane Central Register of Controlled Trials databases from inception up to January 2023, with the use of specific, relevant key terms. A quality evaluation for each study was performed with the QUADAS-2 tool, whereas a bivariate random-effect model was performed to generate a summary receiver-operated curve. Heterogeneity was evaluated with Cochrane Q and Higgins’ I2 statistics. Subgroup analyses were performed for studies focused on atypical hyperplasia and those focused on endometrial cancer. The search yielded 47 studies, involving 7790 patients with endometrial cancer. Among them, only 11 could be included in the quantitative analysis. QUADAS-2 evaluation resulted in rather high quality among the included studies. Quantitative synthesis resulted in a pooled sensitivity of 0.863 and pooled specificity of 0.916. The AUC was 0.948, the Q statistic was 10.488 (10 df, p = 0.399) and Higgins’ I2 (4.655%) reported no significant heterogeneity. Subgroup analyses based on the diagnosis revealed a pooled sensitivity 0.886, specificity 0.862 and AUC 0.934 for endometrial cancer versus a sensitivity of 0.816, specificity of 0.962 and AUC 0.939 for atypical hyperplasia. Frozen section appears as a valid and reliable diagnostic tool for endometrial cancer. Its reliability seems to be even higher for the diagnosis of atypical hyperplasia. Therefore, this method may be considered in clinical practice and in settings with appropriate resources.
]]>Cancers doi: 10.3390/cancers16061199
Authors: Ziad Hussein Robert W. Slack Stephanie E. Baldeweg Evangelos B. Mazomenos Hani J. Marcus
Post-operative tumour progression in patients with non-functioning pituitary neuroendocrine tumours is variable. The aim of this study was to use machine learning (ML) models to improve the prediction of post-operative outcomes in patients with NF PitNET. We studied data from 383 patients who underwent surgery with or without radiotherapy, with a follow-up period between 6 months and 15 years. ML models, including k-nearest neighbour (KNN), support vector machine (SVM), and decision tree, showed superior performance in predicting tumour progression when compared with parametric statistical modelling using logistic regression, with SVM achieving the highest performance. The strongest predictor of tumour progression was the extent of surgical resection, with patient age, tumour volume, and the use of radiotherapy also showing influence. No features showed an association with tumour recurrence following a complete resection. In conclusion, this study demonstrates the potential of ML models in predicting post-operative outcomes for patients with NF PitNET. Future work should look to include additional, more granular, multicentre data, including incorporating imaging and operative video data.
]]>Cancers doi: 10.3390/cancers16061198
Authors: Camille Nicolas Claire Petit Agnès Tallet Jean-Marie Boher Leonel Varela Cagetti Veronique Favrel Laurence Gonzague Casabianca Morgan Guenole Hugues Mailleux Julien Darreon Marie Bannier Monique Cohen Laura Sabiani Camille Tallet Charlene Teyssandier Anthony Gonçalves Alexandre De Nonneville Leonor Lopez Almeida Nathan Coste Marguerite Tyran Gilles Houvenaeghel
Background. An incidental axillary dose of adjuvant radiotherapy using tangential beams is usually given after breast-conserving surgery for breast cancer. The goal of this sub-study was to evaluate this incidental dose in the setting of post-mastectomy radiotherapy (PMRT) according to two different radiotherapy techniques. Methods. Patients participating in a randomized SERC trial who received PMRT in a single center were included. We collected the incidental axillary dose delivered to the Berg level 1 using different dosimetric parameters and compared two techniques using Student’s t-test: three-dimensional conformal radiotherapy (3D-CRT) and volumetric arc therapy (VMAT). Results. We analyzed radiotherapy plans from 52 patients who received PMRT from 2012 to 2021. The mean dose delivered to the Berg level 1 was 37.2 Gy. It was significantly higher with VMAT than with 3D-CRT—43.6 Gy (SD = 3.1 Gy) versus 34.8 Gy (SD = 8.6 Gy) p < 0.001. Eighty-four percent of the Berg level 1 was covered by 40 Gy isodose in the VMAT group versus 55.5% in the 3D-CRT group p < 0.001. Conclusions. On the Berg level 1, PMRT gives a dose at least equivalent to the one given by post-breast-conserving surgery radiotherapy, making it possible to limit completion axillary lymph node dissections in select pN1a patients treated with a mastectomy. Modern radiotherapy techniques like VMAT tend to increase this incidental dose.
]]>Cancers doi: 10.3390/cancers16061197
Authors: Rugile Pikturniene Alvydas Cesas Sonata Jarmalaite Arturas Razbadauskas Vincas Urbonas
Cutaneous melanoma, an aggressive malignancy, has undergone significant transformation in clinical management with the introduction of immune checkpoint inhibitors (ICIs) and targeted therapies. Current monitoring methods, such as imaging scans, present limitations, prompting exploration of alternative biomarkers. This review comprehensively explores the role of circulating tumor DNA (ctDNA) in advanced melanoma, covering technical aspects, detection methods, and its prognostic and predictive value. Recent findings underscore ctDNA’s potential applications and implications in clinical practice. This review emphasizes the need for precise and dynamic biomarkers in melanoma care, positioning ctDNA as a promising blood-based tool for prognosis, treatment response, and resistance mechanisms. The technical nuances of ctDNA detection, association with melanoma mutations, and its role in guiding therapeutic decisions for immunotherapy and targeted therapy underscore its multifaceted utility, marking a paradigm shift in clinical decision-making and offering a promising trajectory for personalized and informed care in advanced melanoma.
]]>Cancers doi: 10.3390/cancers16061196
Authors: Maria Effrosyni Livanou Vasiliki Nikolaidou Vasileios Skouras Oraianthi Fiste Elias Kotteas
Immune checkpoint inhibitors (ICIs) are at the forefront of advanced non-small-cell lung cancer (NSCLC) treatment. Still, only 27–46% of patients respond to initial therapy with ICIs, and of those, up to 65% develop resistance within four years. After disease progression (PD), treatment options are limited, with 10% Objective Response Rate (ORR) to second or third-line chemotherapy. In this context, ICI rechallenge is an appealing option for NSCLC. Most data on the efficacy of ICI rechallenge are based on retrospective real-world studies of small, heavily pretreated, and heterogeneous patient groups. Despite these limitations, these studies suggest that ICI monotherapy rechallenge in unselected NSCLC patient populations who discontinued initial ICI due to PD is generally ineffective, with a median Progression-Free Survival (PFS) of 1.6–3.1 months and a Disease Control Rate (DCR) of 21.4–41.6%. However, there is a subpopulation that benefits from this strategy, and further characterization of this subgroup is essential. Furthermore, immunotherapy rechallenge in patients who discontinued initial immunotherapy following treatment protocol completion and progressed after an immunotherapy-free interval showed promising efficacy, with a DCR of 75–81%, according to post hoc analyses of several clinical trials. Future research on ICI rechallenge for NSCLC should focus on better patient stratification to reflect the underlying biology of immunotherapy resistance more accurately. In this review, we summarize evidence regarding rechallenge immunotherapy efficacy following NSCLC disease progression or relapse, as well as ongoing trials on immunotherapy rechallenge.
]]>Cancers doi: 10.3390/cancers16061195
Authors: Jason Duex Dan Theodorescu
The glycoprotein CD44, with its many isoforms and variations in carbohydrate patterning, participates in a diverse set of cellular functions. This fact leads to the protein playing a role in many normal and pathologic cellular processes including a role in cancer progression and metastasis. These same facts make CD44 a strong therapeutic target in many cancer types, including bladder cancer.
]]>Cancers doi: 10.3390/cancers16061194
Authors: Johanna W. Meyer-Knees Janina Falkenthal Dominik Geisel Christopher C. M. Neumann Georg Hilfenhaus Lars U. Stephan Wenzel Schöning Thomas Malinka Johann Pratschke Sebastian Stintzing Uwe Pelzer
Background: Pancreatic adenocarcinoma (PDAC) is still a complex, devastating disease. Cachexia symptoms frequently impair patient survival. This accompanying syndrome is commonly diagnosed late, when clinical signs become evident. Early diagnosis using conventional measurement methods is often difficult, and the discrimination of this disease from cancer progression is challenging and often overlaps. The aim of this study was to analyze whether conventional nutritional assessments or laboratory biomarkers are better predictive tools for the early detection of patients at risk of reduced survival. Methods: We analyzed a prospective predefined cohort of 182 patients with gastrointestinal cancer, 120 patients with PDAC and—as controls—62 patients with other gastrointestinal adenocarcinoma (oAC), from whom we have sufficient data of protocol-defined conventional nutritional assessments, clinical data, and specific laboratory parameters. Results: at the time of tumor diagnosis, high inflammatory biomarkers (c-reactive protein (CRP), interleukin-6 (IL-6)) and albumin serum levels were associated with impaired OS in PDAC patients, but not in patients with oAC. Hemoglobin, body mass index (BMI), and bioelectrical assessments alone did not have a prognostic impact at the time of diagnosis. In a multivariate analysis, only CRP (HR 1.91 (1.25–2.92), p = 0.003) was found to be an independent prognostic factor in PDAC patients. Over the course of the disease in PDAC patients, inflammatory biomarkers, albumin, hemoglobin, and bioelectrical assessments were associated with impaired OS. In multivariate testing, CRP (HR 2.21 (1.38–3.55), p < 0.001) and albumin (HR 1.71 (1.05–2.77), p = 0.030) were found to be independent prognostic factors in PDAC patients. Conclusion: Specifically for PDAC patients, high inflammatory index and albumin serum levels potentially represent a sufficient early surrogate marker to detect patients at high risk of impaired OS better than complex conventional methods. These findings could help to identify patients who may benefit from early therapeutic interventions.
]]>Cancers doi: 10.3390/cancers16061193
Authors: Robbert S. Puijk Madelon Dijkstra Susan van der Lei Hannah H. Schulz Danielle J. W. Vos Florentine E. F. Timmer Bart Geboers Hester J. Scheffer Jan J. J. de Vries Maarten L. J. Smits Rutger C. G. Bruijnen Frédéric Deschamps Thierry de Baère Bruno C. Odisio Martijn R. Meijerink
With the rapidly evolving field of image-guided tumor ablation, there is an increasing demand and need for tools to optimize treatment success. Known factors affecting the success of (non-)thermal liver ablation procedures are the ability to optimize tumor and surrounding critical structure visualization, ablation applicator targeting, and ablation zone confirmation. A recent study showed superior local tumor progression-free survival and local control outcomes when using transcatheter computed tomography hepatic angiography (CTHA) guidance in percutaneous liver ablation procedures. This pictorial review provides eight clinical cases from three institutions, MD Anderson (Houston, TX, USA), Gustave Roussy (Paris, France), and Amsterdam UMC (Amsterdam, The Netherlands), with the intent to demonstrate the added value of real-time CTHA guided tumor ablation for primary liver tumors and liver-only metastatic disease. The clinical illustrations highlight the ability to improve the detectability of the initial target liver tumor(s) and identify surrounding critical vascular structures, detect ‘vanished’ and/or additional tumors intraprocedurally, differentiate local tumor progression from non-enhancing scar tissue, and promptly detect and respond to iatrogenic hemorrhagic events. Although at the cost of adding a minor but safe intervention, CTHA-guided liver tumor ablation minimizes complications of the actual ablation procedure, reduces the number of repeat ablations, and improves the oncological outcome of patients with liver malignancies. Therefore, we recommend adopting CTHA as a potential quality-improving guiding method within the (inter)national standards of practice.
]]>Cancers doi: 10.3390/cancers16061192
Authors: Andromachi Kougioumtzopoulou Nick Syrigos Anna Zygogianni Ioannis Georgakopoulos Kalliopi Platoni George Patatoukas Kimon Tzannis Aristotelis Bamias Nikolaos Kelekis Vasileios Kouloulias
Background: Moderate hypofractionated radiotherapy (MHRT) has emerged as the preferred treatment modality for localized prostate cancer based on randomized controlled studies regarding efficacy and toxicity using contemporary radiotherapy techniques. In the setting of MHRT, available data on dosimetric parameters and late rectal toxicity are limited. Aim: To present the effects of MHRT on late rectal toxicity while conducting an extensive dosimetric analysis in conjunction with rectoscopy results. Methods: This is a prospective study including patients with intermediate-risk prostate adenocarcinoma. All patients were treated with MHRT 44 Gy in 16 fractions to the seminal vesicles and to the prostate, followed by a sequential boost to the prostate alone of 16.5 Gy in 6 fractions delivered with three-dimensional conformal radiation therapy (3DCRT). Acute and late toxicity were assessed. Endoscopy was performed at baseline, every 3 months post-therapy for the first year, and every 6 months for the year after. The Vienna Rectoscopy Score (VRS) was used to assess rectal mucosal injury related to radiotherapy. Dosimetric analysis for the rectum, rectal wall, and its subsegments (upper, mid, and low 1/3) was performed. Results: Between September 2015 and December 2019, 20 patients enrolled. Grade 1 late gastrointestinal toxicity occurred in 10% of the patients, whereas 5% had a grade ≥2. Twelve months post radiotherapy: 4 (20%) patients had VRS 1; 2 (10%) patients had VRS 2; 1(5%) patient had VRS 3. 24 months post radiotherapy, VRS 1 was observed in 4 patients (20%) and VRS 2 in 3 (15%) patients. The dosimetric analysis demonstrated noticeable variations between the rectum, rectal wall, and rectal wall subsegments. The dosimetric analysis of the rectum, rectal wall, and its mid and low segments with respect to rectoscopy findings showed that the higher dose endpoints V52.17Gy and V56.52Gy are associated with rectal mucosal injury. Conclusions: A thorough delineation of the rectal wall and its subsegments, together with the dosimetric analysis of these structures, may reduce late rectal toxicity. Dosimetric parameters such as V52.17Gy and V56.52Gy were identified to have a significant impact on rectal mucosal injury; additional dose endpoint validation and its relation to late GI toxicity is needed.
]]>Cancers doi: 10.3390/cancers16061191
Authors: Laurenția Nicoleta Galeș Mihai-Andrei Păun Rodica Maricela Anghel Oana Gabriela Trifănescu
Cancer continues to pose a considerable challenge to global health. In the search for innovative strategies to combat this complex enemy, the concept of universal cancer screening has emerged as a promising avenue for early detection and prevention. In contrast to targeted approaches that focus on specific populations or high-risk individuals, universal screening seeks to cast a wide net to detect incipient malignancies in different demographic groups. This paradigm shift in cancer care underscores the importance of comprehensive screening programs that go beyond conventional boundaries. As our understanding of the complex molecular and genetic basis of cancer deepens, the need to develop comprehensive screening methods becomes increasingly apparent. In this article, we look at the rationale and potential benefits of universal cancer screening.
]]>Cancers doi: 10.3390/cancers16061190
Authors: Sofie Skovlund Petersen Stine Møller Cecilie Slott Jesper Krogh Carsten Palnæs Hansen Andreas Kjaer Pernille Holmager Peter Oturai Rajendra Singh Garbyal Seppo W. Langer Ulrich Knigge Mikkel Andreassen
Background: Given the rarity and heterogeneity of pancreatic neuroendocrine neoplasms (pNEN), treatment algorithms and sequencing are primarily guided by expert opinions with limited evidence. Aim: To investigate overall survival (OS), median progression-free survival (mPFS), and prognostic factors associated with the most common medical treatments for pNEN. Methods: Retrospective single-center study encompassing patients diagnosed and monitored between 2000 and 2020 (n = 192). Results: Median OS was 36 (95% CI: 26–46) months (99 months for grade (G) 1, 62 for G2, 14 for G3, and 10 for neuroendocrine carcinomas). Patients treated with somatostatin analogues (SSA) (n = 59, median Ki-67 9%) had an mPFS of 28 months. Treatment line (HR (first line as reference) 4.1, 95% CI: 1.9–9.1, p ≤ 0.001) emerged as an independent risk factor for time to progression. Patients with a Ki-67 index ≥10% (n = 28) had an mPFS of 27 months. Patients treated with streptozocin/5-fluorouracil (STZ/5FU) (n = 70, first-line treatment n = 68, median Ki-67 10%) had an mPFS of 20 months, with WHO grade serving as an independent risk factor (HR (G1 (n = 8) vs. G2 (n = 57)) 2.8, 95% CI: 1.1–7.2, p-value = 0.031). Median PFS was 21 months for peptide receptor radionuclide therapy (PRRT) (n = 41, first line n = 2, second line n = 29, median Ki-67 8%), 5 months for carboplatin and etoposide (n = 66, first-line treatment n = 60, median Ki-67 80%), and 3 months for temozolomide-based therapy (n = 56, first-line treatment n = 17, median Ki-67 30%). Conclusion: (1) Overall survival was, as expected, highly dependent on grade; (2) median PFS for SSA was around 2.5 years without difference between tumors with Ki-67 above or below 10%; (3) STZ/5FU as first-line treatment exhibited a superior mPFS of 20 months compared to what has historically been reported for targeted treatments; (4) PRRT in G2 pNEN achieved an mPFS similar to first-line chemotherapy; and (5) limited treatment efficacy was observed in high-grade tumors when treated with carboplatin and etoposide or temozolomide.
]]>Cancers doi: 10.3390/cancers16061189
Authors: Ettore Bidoli
The impact of air pollution on lung cancer (LC) is difficult to detect in low-populated areas due to the potentially unfocused detection of pollutants and/or limited statistical power. This study identified and measured the harmful effect of pollution in small areas by considering the early onset of LC as a signature of pollution. This novel method requires a Bayesian standard curve calculated from the median age at LC onset and the corresponding median age of reference populations. Similar medians gathered from the area/s under investigation permits a probabilistic comparison with the standard curve. Statistically significant divergences can be interpreted as early or late LC onset. The method is exemplified in the Trieste municipality (northeast Italy) using data from the Friuli Venezia Giulia Cancer Registry (study population) and from the International Agency for Research on Cancer (reference population). Early LC onset has been observed near the pollution sources. Within 600 m of the iron foundry, onset ranged between 3.2 and 7.7 years earlier in men and between 11.7 and 16.8 years earlier in women. Near the shipyard, early onset was around 4 years in men and 7 years in women, while in the industrial area, early onset was 5 years in women only. Examining early LC onset may speed up the investigation of potential environmental hazards.
]]>Cancers doi: 10.3390/cancers16061188
Authors: Prashant Sakharkar Sonali Kurup Subrata Deb Kaitlin Assaad Dayna Gesinski Erysa J. Gayle
Introduction: The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in combination with anti-vascular endothelial growth factor receptor (VEGFR) agents have shown improved survival outcomes in recent studies. However, its efficacy related to survival outcomes as a first- or second-line agent and based on generations remains to be explored. This study estimated the survival outcomes of EGFR-TKIs plus anti-VEGFR in combination in defined populations of advanced non-small cell lung cancer (NSCLC) patients overall, as a first- or second line of treatment, with different generations of EGFR-TKIs and EGFR-TKIs plus bevacizumab combination as a subgroup. Methods: A literature search was conducted using PubMed, SCOPUS, Cochrane Library, and ClinicalTrials.gov databases through June 2023 to identify primary research reporting the survival outcomes of EGFR-TKIs in combination with anti-VEGFR agents in patients with advanced NSCLC. Studies that were single-arm, published in non-English languages, and had missing data on survival outcomes were excluded. A meta-analysis was conducted to generate pooled hazard ratios (HRs) with 95% confidence intervals (CI) for overall survival (OS) and progression-free survival (PFS). Methodological quality and risk of bias in studies were assessed using the Cochrane Handbook for Systematic Reviews of Interventions risk of bias tool. Results: A total of 20 randomized controlled trials were included in the qualitative synthesis, and 11 (2182 participants) were included in the meta-analysis. Patients’ median age ranged from 58 to 68 years; 36% to 70% of patients were female; most of them had IIIa/b to IV stage cancer. In meta-analyses, the EGFR-TKIs plus anti-VEGFR combination resulted in improved PFS (HR, 0.73; 95% CI: 0.61, 0.86; p < 0.00001) in patients with advanced NSCLC but had no impact on OS (HR, 0.93; 95% CI: 0.79, 1.10; p = 0.41). The first line of treatment and first-generation EGFR-TKIs with the combination also improved the PFS (HR, 0.64; 95% CI: 0.57, 0.71; p < 0.00001; HR, 0.63; 95% CI: 0.56, 0.71; p < 0.00001) respectively, however, had no impact on OS. Conclusions: Our meta-analysis indicated EGFR-TKIs with anti-VEGFR in combination not only improved overall PFS but also showed similar results to a first line and first-generation agent compared to EGFR-TKI alone.
]]>Cancers doi: 10.3390/cancers16061187
Authors: Takuya Yoshimura Yuka Hirano Taiji Hamada Seiya Yokoyama Hajime Suzuki Hirotaka Takayama Hirono Migita Takayuki Ishida Yasunori Nakamura Masahiro Ohsawa Akihiro Asakawa Kiyohide Ishihata Akihide Tanimoto
Major advances have been made in cancer treatment, but the prognosis for elderly cancer patients with sarcopenia and frailty remains poor. Myokines, which are thought to exert preventive effects against sarcopenia, have been reported to be associated with the prognosis of various cancers, but their effect on head and neck squamous cell carcinoma (HNSCC) is unknown. The aim of this study was to clarify the influence of exercise on the control of HNSCC and to examine the underlying mechanism involved. Mice were injected with HSC-3-M3 cells, a human cell line of highly metastatic and poorly differentiated tongue cancer, at the beginning of the study. Just prior to transplantation, blood was collected from the mice, and the levels of myokines were measured by ELISA. Oncostatin M (OSM), a selected myokine, was added to HSC-3-M3 cells, after which the cell proliferation ability, cell cycle, and protein expression were analyzed in vitro. Tumor cell viability was lower (control: 100%, exercise: 75%), tumors were smaller (control: 26.2 mm3, exercise: 6.4 mm3), and survival was longer in the exercise group than in the control group in vivo. OSM inhibited HSC-3-M3 cell proliferation in a concentration-dependent manner in vitro. The addition of OSM increased the proportion of cells in the G0/G1 phase, decreased the proportion of cells in the G2/M phase, and increased the expression of the CDK inhibitors p21 and p27. These results indicate that exercise may directly inhibit the proliferation of HNSCC cell lines via OSM.
]]>Cancers doi: 10.3390/cancers16061185
Authors: Yasmine Ghantous Shiraz Mozalbat Aysar Nashef Murad Abdol-Elraziq Shiran Sudri Shareef Araidy Hagar Tadmor Imad Abu El-naaj
Background: Epithelial–mesenchymal transition (EMT) enables tumor cell invasion and metastasis. Many studies have demonstrated the critical role of EMT in lymph node metastasis in oral squamous cell carcinoma (OSCC). During EMT, epithelial cancer cells lose intercellular adhesion and apical–basal polarity and acquire mesenchymal properties such as motility and invasiveness. A significant feature of EMT is cadherin switching, involving the downregulation of E-cadherin and upregulation of N-cadherin. The TGF-β/SMAD pathway can also induce EMT. We aimed to evaluate EMT markers as predictors of lymph node metastasis in OSCC. Methods: We performed genetic profiling of 159 primary OSCCs from TCGA and analyzed the expression of EMT markers, including cadherin switch genes (CDH1, CDH2), and TGF-β/SMAD pathway genes. Samples were divided into advanced (stage III–IV) and early (stage I–II) stage groups. Differential expression analysis was performed, as well as an independent validation study containing fresh OSCC samples. Results: TGF-β/SMAD pathway genes such as SMAD6 were upregulated in advanced stage tumors. N-cadherin and SNAIL2 were overexpressed in node-positive tumors. Keratins were downregulated in these groups. Conclusion: Our findings demonstrate that EMT marker expression correlates with lymph node metastasis in OSCC. Developing therapies targeting regulators such as N-cadherin may prevent metastasis and improve outcomes.
]]>Cancers doi: 10.3390/cancers16061186
Authors: Shaun Haran Kantaraja Chindera May Sabry Nafisa Wilkinson Rupali Arora Agnieszka Zubiak Thomas E. Bartlett Iona Evans Allison Jones Daniel Reisel Chiara Herzog Twana Alkasalias Mark Newman Jaeyeon Kim Angelique Flöter Rådestad Kristina Gemzell-Danielsson Adam N. Rosenthal Louis Dubeau Mark W. Lowdell Martin Widschwendter
Background: Tissue-specificity for fimbrial fallopian tube ovarian carcinogenesis remains largely unknown in BRCA1 mutation carriers. We aimed to assess the cell autonomous and cell-nonautonomous implications of a germline BRCA1 mutation in the context of cancer immunosurveillance of CD3− CD56+ natural killer (NK) cells. Methods: Premenopausal BRCA1 mutation carriers versus age-matched non-carriers were compared. Daily urinary 5β-pregnanediol levels were used to determine progesterone metabolomics across an ovarian cycle. Using peripherally acquired NK cells the cell-mediated cytotoxicity of tumor targets (OVCAR-3, K-562) was determined using live cellular impedance (xCELLigence®) and multicolor flow cytometry. Hypoxia-inducible factor 1-alpha (HIF-1α) immunohistochemistry of cancer-free fallopian tube specimens allowed a comparison of proximal versus distal portions. Utilizing these findings the role of environmental factors relevant to the fimbrial fallopian tube (progesterone, hypoxia) on NK cell functional activity were studied in an ovarian phase-specific manner. Results: BRCA1 mutation carriers demonstrate a differential progesterone metabolome with a phase-specific reduction of peripheral NK cell functional activity. Progesterone exposure further impairs NK cell-mediated cytotoxicity in a dose-dependent manner, which is reversed with the addition of mifepristone (1.25 µM). The fimbrial fallopian tube demonstrated significantly higher HIF-1α staining, particularly in BRCA1 mutation carriers, reflecting a site-specific ‘hypoxic niche’. Exposure to hypoxic conditions (1% O2) can further impair tumor cytotoxicity in high-risk carriers. Conclusions: Phase-specific differential NK cell activity in BRCA1 mutation carriers, either systemically or locally, may favor site-specific pre-invasive carcinogenesis. These cumulative effects across a reproductive lifecycle in high-risk carriers can have a detrimental effect further supporting epidemiological evidence for ovulation inhibition.
]]>Cancers doi: 10.3390/cancers16061184
Authors: Akiko Arimura Kazuko Sakai Kazuhisa Kaneshiro Takafumi Morisaki Saori Hayashi Kimihisa Mizoguchi Mai Yamada Masaya Kai Mayumi Ono Kazuto Nishio Masafumi Nakamura Makoto Kubo
Precise biomarkers for predicting the therapeutic efficacy of molecularly targeted drugs are limited at the protein level; thus, it has been important to broadly scrutinize individual cancer driver gene mutations for effective cancer treatments. Multiplex cancer genome profiling can comprehensively identify gene mutations that are therapeutic targets using next-generation sequencing (NGS). In addition, circulating tumor DNA (ctDNA) is a DNA fragment released into the blood by tumor cell-derived cell death or apoptosis. Liquid biopsy with ctDNA is a novel clinical test for identifying genetic mutations in an entire population noninvasively, in real-time, and heterogeneously. Although there are several reports on ctDNA, fewer have evaluated ctDNA with NGS before an initial treatment for breast cancer patients. Therefore, we examined whether analyzing tumor-associated gene mutations in primary breast cancer based on ctDNA could serve as a biomarker for prognosis and optimal treatment selection. Ninety-five primary breast cancer patients treated at our department from January 2017 to October 2020 were included. Pretreatment plasma samples were subjected to NGS analysis of ctDNA, and correlations with patients’ clinicopathological characteristics were evaluated. Fifty-nine (62.1%) patients were positive for ctDNA. ctDNA tended to be positive in hormone receptor-negative, and TP53 (34%), BRCA1 (20%), and BRCA2 (17%) gene mutations were more frequent. Regarding recurrence-free survival, the prognosis was poor in the TP53 and/or BRCA1 mutation-positive groups, especially in triple-negative breast cancer (TNBC) patients. In conclusion, the results of this study indicate that ctDNA with liquid biopsy could identify the poor prognosis group before treatment among TNBC patients and for those for whom optimal treatment selection is desirable; additionally, optimal treatment could be selected according to the ctDNA analysis results.
]]>Cancers doi: 10.3390/cancers16061183
Authors: Yan Hu Dan Jones Ashwini K. Esnakula Somashekar G. Krishna Wei Chen
The malignant progression of pancreatic cystic lesions (PCLs) remains understudied with a knowledge gap, yet its exploration is pivotal for effectively stratifying patient risk and detecting cancer at its earliest stages. Within this review, we delve into the latest discoveries on the molecular level, revealing insights into the IPMN molecular landscape and revised progression model, associated histologic subtypes, and the role of inflammation in the pathogenesis and malignant progression of IPMN. Low-grade PCLs, particularly IPMNs, can develop into high-grade lesions or invasive carcinoma, underscoring the need for long-term surveillance of these lesions if they are not resected. Although KRAS and GNAS remain the primary oncogenic drivers of neoplastic development in IPMNs, additional genes that are important in tumorigenesis have been recently identified by whole exome sequencing. A more complete understanding of the genes involved in the molecular progression of IPMN is critical for effective monitoring to minimize the risk of malignant progression. Complicating these strategies, IPMNs are also frequently multifocal and multiclonal, as demonstrated by comparative molecular analysis. Algorithms for preoperative cyst sampling and improved radiomic techniques are emerging to model this spatial and temporal genetic heterogeneity better. Here, we review the molecular pathology of PCLs, focusing on changes associated with malignant progression. Developing models of molecular risk stratification in PCLs which can complement radiologic and clinical features, facilitate the early detection of pancreatic cancer, and enable the development of more personalized surveillance and management strategies are summarized.
]]>Cancers doi: 10.3390/cancers16061182
Authors: Marco Tonello Carola Cenzi Elisa Pizzolato Riccardo Fiscon Paola Del Bianco Pierluigi Pilati Antonio Sommariva
Background. For patients with colorectal cancer (CRC) peritoneal metastases (PM) who are eligible for cytoreductive surgery (CRS), the indication and timing of systemic chemotherapy (SC) are still under debate. This study aims to analyze the role of pre, post or perioperative SC on the survival and surgical complications of patients treated with CRS-HIPEC. Methods. After a systematic search in MEDLINE, Cochrane Database of Systematic Reviews, Scopus, Web of Science and Embase, a meta-analysis was performed to compare postoperative complications, disease-free survival (DFS) and overall survival (OS) according to SC administration and timing. PROSPERO: CRD42023478977. Results. Of 1203 studies screened, 15 were included in the meta-analysis (4523 patients). Post-operative SC was associated with increased overall survival (post-SC vs. no post-SC: HR 0.81, p = 0.00001, I2 = 0%; pre-SC vs. post-SC: HR 0.65, p = 0.01, I2 = 28%), whereas SC (pre or post) or pre-SC compared to surgery alone was not (SC vs. no SC: p = 0.29, I2 = 80%; pre-SC vs. no pre-SC: p = 0.59, I2 = 58%). Similar results were seen for DFS. SC was not associated with an increased complication rate (p = 0.47, I2 = 64%). Conclusions. Systemic chemotherapy administration in patients undergoing radical surgery for colorectal peritoneal metastases is associated with increased survival only in the adjuvant/post-operative setting. Considering the limitations of the included studies, further trials are needed to answer this unresolved question.
]]>Cancers doi: 10.3390/cancers16061181
Authors: Yen-Min Huang Hsuan-Jen Shih Yi-Chan Chen Tsan-Yu Hsieh Che-Wei Ou Po-Hsu Su Shih-Ming Chen Yun-Cong Zheng Li-Sung Hsu
In the original publication [...]
]]>Cancers doi: 10.3390/cancers16061180
Authors: Iuliia Topchu Igor Bychkov Ekaterina Roshchina Petr Makhov Yanis Boumber
Head and neck squamous cell carcinoma (HNSCC) ranks among the most prevalent global cancers. Despite advancements in treatments, the five-year survival rate remains at approximately 66%. The histone methyltransferase NSD1, known for its role in catalyzing histone H3 lysine 36 di-methylation (H3K36me2), emerges as a potential oncogenic factor in HNSCC. Our study, employing Reverse Phase Protein Array (RPPA) analysis and subsequent validation, reveals that PIP4K2B is a key downstream target of NSD1. Notably, PIP4K2B depletion in HNSCC induces downregulation of the mTOR pathway, resulting in diminished cell growth in vitro. Our investigation highlights a direct, positive regulatory role of NSD1 on PIP4K2B gene transcription through an H3K36me2-dependent mechanism. Importantly, the impact of PIP4K2B appears to be context-dependent, with overexpression rescuing cell growth in laryngeal HNSCC cells but not in tongue/hypopharynx cells. In conclusion, our findings implicate PIP4K2B as a novel NSD1-dependent protein in HNSCC, suggesting its potential significance for laryngeal cancer cell survival. This insight contributes to our understanding of the molecular landscape in HNSCC and establishes PIP4KB as a promising target for drug development.
]]>Cancers doi: 10.3390/cancers16061179
Authors: Vasileios S. Skouras Ioannis Gkiozos Andriani G. Charpidou Konstantinos N. Syrigos
Background: The widespread use of chest CT has increased the number of detected pulmonary nodules. Nodules with intermediate risk of malignancy warrant further evaluation with PET-CT or sampling. Although sampling with conventional bronchoscopy presents lower complication rates compared to transthoracic needle biopsy (TTNB), it is limited by the inability to reach distal airways. To overcome this shortcoming, a new bronchoscopic technique named robotic bronchoscopy (RB) has emerged. Methods: A literature review was used to clarify the rationale behind RB emergence, describe RB procedure, and summarize data regarding its efficacy and safety. Results: The FDA has approved three RB platforms for clinical use. RB is safe, presenting a mortality and complication rate of 0% and 0–8.1%, respectively. Common complications include pneumothorax (0–5.7%) and minor bleeding (0–3.2%). However, its diagnostic yield remains lower than that of TTNB. Conclusions: RB is a promising bronchoscopic technique that aims to overcome the limitations of conventional bronchoscopy and improve upon the current techniques of guided bronchoscopy for the investigation of pulmonary nodules. Despite the lower complication rate, current evidence suggests a lower diagnostic yield compared to TTNB. Additional studies are required to adequately evaluate the role of RB in the diagnosis of pulmonary nodules.
]]>Cancers doi: 10.3390/cancers16061178
Authors: Sarmad Al-Marsoummi Aaron A. Mehus Scott H. Garrett Donald A. Sens Seema Somji
Bladder cancer (BC) is the eighth most common cause of cancer death in the United States of America. BC is classified into non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Genetically, MIBCs are categorized into the more aggressive basal subtype or less aggressive luminal subtype. All-trans retinoic acid (tretinoin), the ligand for the RAR-RXR retinoic acid receptor, is clinically used as a differentiation therapy in hematological malignancies. This study aims to determine the effects of retinoic acid on arsenite-transformed malignant urothelial cells (UROtsa As), serving as a model for basal muscle-invasive bladder cancer. We treated three independent isolates of arsenite-transformed malignant human urothelial UROtsa cells (UROtsa As) with tretinoin for 48 h. Cell viability, proliferation, and apoptosis were analyzed using crystal violet staining and flow cytometry. mRNA and protein level analyses were performed using RT-qPCR and the Simple Western™ platform, respectively. Tretinoin was found to reduce cell proliferation and urosphere formation, as well as decrease the expression of basal markers (KRT1, KRT5, KRT6, EGFR) and increase the expression of luminal differentiation markers (GATA3, FOXA1). Mechanistically, the antiproliferative effect of tretinoin was attributed to the downregulation of c-myc. Our results suggest that targeting the retinoic acid pathway can diminish the aggressive behavior of basal muscle-invasive urothelial cancer and may enhance patient survival.
]]>Cancers doi: 10.3390/cancers16061177
Authors: Georgios Evangelou Ioannis Vamvakaris Anastasia Papafili Maximilian Anagnostakis Melpomeni Peppa
Lung neuroendocrine tumors (LNETs) and gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are two distinct types of neuroendocrine tumors (NETs) that have traditionally been treated as a single entity despite originating from different sources. Although they share certain phenotypic characteristics and the expression of neuroendocrine markers, they exhibit differences in their microenvironment, molecular mutations, and responses to various therapeutic regimens. Recent research has explored the genetic alterations in these tumors, revealing dissimilarities in the frequently mutated genes, the role of EGFR in carcinogenesis, the presence of transcription factors, and the immunogenicity of the tumor and its microenvironment. Spread Through Air Spaces (STAS), a phenomenon unique to lung carcinomas, appears to play a crucial role in LNET prognosis. These distinctions are also evident in the cascade response of lung and GI tract neuroendocrine tumors to somatostatin analogs, Peptide Receptor Radionuclide Therapy (PRRT), chemotherapy, and immunotherapy. Identifying similarities and differences between the two groups may improve our understanding of the underlying mechanisms and facilitate the development of more effective treatment strategies.
]]>Cancers doi: 10.3390/cancers16061176
Authors: Elissavet Ntemou Emily Delgouffe Ellen Goossens
In recent years, immune checkpoint inhibitors (ICIs) have become a viable option for many cancer patients, including specific subgroups of pediatric patients. Despite their efficiency in treating different types of cancer, ICIs are responsible for a number of immune-related adverse events, including inflammatory toxicities, that can affect several organs. However, our knowledge of the impact of ICIs on the testis and male fertility is limited. It is possible that ICI treatment affects testicular function and spermatogenesis either directly or indirectly (or both). Treatment with ICIs may cause increased inflammation and immune cell infiltration within the seminiferous tubules of the testis, disturbing spermatogenesis or testosterone deficiency (primary hypogonadism). Additionally, the interference of ICIs with the hypothalamic–pituitary–gonadal axis may alter testosterone production, affecting testicular function (secondary hypogonadism) and spermatogenesis. This review provides an overview of the available evidence on the potential association between ICIs and the disruption of spermatogenesis, with special focus on ICIs targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1). Moreover, it highlights the need for further investigations and encourages the discussion of associated risks and fertility-preservation considerations between clinicians and patients.
]]>Cancers doi: 10.3390/cancers16061174
Authors: Maja Guberina Christoph Pöttgen Nika Guberina Christian Hoffmann Marcel Wiesweg Cedric Richlitzki Martin Metzenmacher Clemens Aigner Servet Bölükbas Thomas Gauler Wilfried E. E. Eberhardt Michael Forsting Ken Herrmann Dirk Theegarten Kaid Darwiche Verena Jendrossek Martin Stuschke Martin Schuler
Background: In patients with oligometastatic NSCLC, a cT3–cT4 primary tumor or an cN2/cN3 lymph node status was reported to be associated with unfavorable outcome. The aim of this study was to assess the importance of definitive or neoadjuvant thoracic radiochemotherapy for long-term outcome of these patients in order to find more appropriate treatment schedules. Methods: Analysis of the West Cancer Centre (WTZ) institutional database from 08/2016 to 08/2020 was performed. Patients with primary synchronous OMD, all without actionable driver mutations, who received definitive thoracic radiochemotherapy (RCT) or neoadjuvant RCT followed by surgery (trimodality treatment) were included. Survival outcome is compared with stage III NSCLC. Results: Altogether, 272 patients received concurrent radiochemotherapy. Of those, 220 presented with stage III (158 with definitive RCT, 62 with trimodality approach). A total of 52 patients had OMD patients with cT3/cT4 or cN2/cN3 tumors. Overall survival (OS) at five years for OMD patients was 28.3% (95%-CI: 16.4–41.5%), which was not significantly different from OS of patients with stage III NSCLC treated with definitive or neoadjuvant RCT (34.9% (95%-CI: 27.4–42.8%)). However, the PFS of OMD patients at five years or last follow-up was significantly worse than that of stage III patients (13.0% vs. 24.3%, p = 0.0048). The latter was due to a higher cumulative incidence of distant metastases in OMD patients (50.2% vs. 20.4% at 48 months, p < 0.0001) in comparison to stage III patients. A cross-validated classifier that included severe comorbidity, ECOG performance status, gender and pre-treatment serum CRP level as the most important factors in the univariable analysis, was able to divide the OMD patient group into two equally sized groups with a four-year survival rate of 49.4% in the good prognosis group and 9.9% in the poor prognosis group (p = 0.0021). Laboratory chemistry and clinical parameters, in addition to imaging and high-precision therapies, can help to predict and improve prognosis. Conclusions: A multimodality treatment approach and local metastases-directed therapy in addition to chemoimmunotherapy can lead to good long-term survival in patients with cT3/cT4 or cN2/cN3 OMD NSCLC without severe comorbidities and in good performance status and is therefore recommended.
]]>Cancers doi: 10.3390/cancers16061175
Authors: Łukasz Nowak Dawid Janczak Jan Łaszkiewicz Maciej Guziński Francesco Del Giudice Anas Tresh Benjamin I. Chung Joanna Chorbińska Wojciech Tomczak Bartosz Małkiewicz Tomasz Szydełko Wojciech Krajewski
Percutaneous cryoablation (PCA) can be an alternative to partial nephrectomy (PN) in selected patients with stage T1 renal tumours. Existing meta-analyses regarding ablative techniques compared both laparoscopic and PCA with PN. That is why we decided to perform a meta-analysis that focused solely on PCA. The aim of this study was to compare the complications and functional and oncological outcomes between PCA and PN. A systematic literature search was performed in January 2024. Data for dichotomous and continuous variables were expressed as pooled odds ratios (ORs) and mean differences (MDs), both with 95% confidence intervals (CIs). Effect measures for the local recurrence-free survival (LRFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS) were expressed as pooled hazard ratios with 95% CIs. Among 6487 patients included in the 14 selected papers, 1554 (23.9%) and 4924 (76.1%) underwent PCA and PN, respectively. Compared with the PN group, patients undergoing PCA had significantly lower overall and major postoperative complication rates. There was no difference in renal function between PCA and PN groups. When analysing collective data for cT1 renal carcinoma, PCA was associated with worse LRFS compared with PN. However, subgroup analysis revealed that in the case of PCA, LRFS was not decreased in patients with cT1a tumours. Moreover, patients undergoing robotic-assisted PN had improved LRFS compared with those undergoing PCA. No significant differences were observed between PCA and PN in terms of MFS and CSS. Finally, PCA was associated with worse OS than PN in both collective and subgroup analyses. In conclusion, PCA is associated with favourable postoperative complication rates relative to PN. Regarding LRFS, PCA is not worse than PN in cT1a tumours but has a substantially relevant disadvantage in cT1b tumours. Also, RAPN might be the only surgical modality that provides better LRFS than PCA. In cT1 tumours, PCA shows MFS and CSS comparable to PN. Lastly, PCA is associated with a shorter OS than PN.
]]>Cancers doi: 10.3390/cancers16061173
Authors: Minsoo Kim Wonhee Yang Dawon Hong Hye Sung Won Seokhyun Yoon
Triple-negative breast cancer (TNBC) is a significant clinical challenge due to its aggressive nature and limited treatment options. In search of new treatment targets, not only single genes but also gene pairs involved in protein interactions, we explored the tumor microenvironment (TME) of TNBC from a retrospective point of view, using public single-cell RNA sequencing datasets. A High-resolution Cell type Annotation Tool, HiCAT, was used first to identify the cell type in 3-level taxonomies. Tumor cells were then identified based on the estimates of copy number variation. With the annotation results, differentially expressed genes were analyzed to find subtype-specific markers for each cell type, including tumor cells, fibroblast, and macrophage. Cell–cell interactions were also inferred for each cell type pair. Through integrative analysis, we could find unique TNBC markers not only for tumor cells but also for various TME components, including fibroblasts and macrophages. Specifically, twelve marker genes, including DSC2 and CDKN2A, were identified for TNBC tumor cells. Another key finding of our study was the interaction between the DSC2 and DSG2 genes among TNBC tumor cells, suggesting that they are more tightly aggregated with each other than those of other subtypes, including normal epithelial cells. The overexpression of DSC2 in TNBC and its prognostic power were verified by using METABRIC, a large bulk RNA-seq dataset with clinical information. These findings not only corroborate previous hypotheses but also lay the foundation for a new structural understanding of TNBC, as revealed through our single-cell analysis workflow.
]]>Cancers doi: 10.3390/cancers16061172
Authors: Joy Ogunmuyiwa Vonetta Williams
Since the 2009 FIGO staging update, focused exclusively on the anatomic extent of disease, there have been several advances in the understanding of the pathologic and molecular features of endometrial cancer. In a significant departure from the 2009 FIGO staging system, the 2023 FIGO staging update integrates both histopathological and molecular classification. With the inclusion of non-anatomic pathologic parameters such as histology, tumor grade, lymphovascular space invasion, and molecular subtype, the 2023 FIGO staging update aims to create more clinically relevant substages that improve prognostic value and allows for more individualized treatment paradigms. This review will evaluate the clinical impact of the 2023 FIGO staging update, describe the stage shifts that lead to higher prognostic precision, and illustrate the current state of molecular analysis in clinical practice. Furthermore, this review will explore how incorporating factors such as molecular subtype into endometrial cancer staging can offer valuable insights into the racial disparities seen in morbidity and mortality.
]]>Cancers doi: 10.3390/cancers16061171
Authors: Can Chen Ji Zhang
Cancer cells demand amino acids beyond their usage as “building blocks” for protein synthesis. As a result, targeting amino acid acquisition and utilization has emerged as a pivotal strategy in cancer treatment. In the setting of leukemia therapy, compelling examples of targeting amino acid metabolism exist at both pre-clinical and clinical stages. This review focuses on summarizing novel insights into the metabolism of glutamine, asparagine, arginine, and tryptophan in leukemias, and providing a comprehensive discussion of perturbing their metabolism to improve the therapeutic outcomes. Certain amino acids, such as glutamine, play a vital role in the energy metabolism of cancer cells and the maintenance of redox balance, while others, such as arginine and tryptophan, contribute significantly to the immune microenvironment. Therefore, assessing the efficacy of targeting amino acid metabolism requires comprehensive strategies. Combining traditional chemotherapeutics with novel strategies to perturb amino acid metabolism is another way to improve the outcome in leukemia patients via overcoming chemo-resistance or promoting immunotherapy. In this review, we also discuss several ongoing or complete clinical trials, in which targeting amino acid metabolism is combined with other chemotherapeutics in treating leukemia.
]]>Cancers doi: 10.3390/cancers16061170
Authors: Yunxia Ma Miljana Nenkov Alexander Berndt Mohamed Abubrig Martin Schmidt Tim Sandhaus Otmar Huber Joachim H. Clement Susanne M. Lang Yuan Chen Nikolaus Gaßler
Abnormal expression of ACSL members 1, 3, 4, 5, and 6 is frequently seen in human cancer; however, their clinical relevance is unclear. In this study, we analyzed the expression of ACSLs and investigated the effects of the ACSL inhibitor Triacsin C (TC) in lung cancer. We found that, compared to normal human bronchial epithelial (NHBE) cells, ACSL1, ACSL4, and ACSL6 were highly expressed, while ACSL3 and ACSL5 were lost in the majority of lung cancer cell lines. ACSL activity was associated with the expression levels of the ACSLs. In primary lung tumors, a higher expression of ACSL1, ACSL4, and ACSL5 was significantly correlated with adenocarcinoma (ADC). Moreover, ACSL5 was significantly reversely related to the proliferation marker Ki67 in low-grade tumors, while ACSL3 was positively associated with Ki67 in high-grade tumors. Combination therapy with TC and Gemcitabine enhanced the growth-inhibitory effect in EGFR wild-type cells, while TC combined with EGFR-TKIs sensitized the EGFR-mutant cells to EGFR-TKI treatment. Taken together, the data suggest that ACSL1 may be a biomarker for lung ADC, and ACSL1, ACSL4, and ACSL5 may be involved in lung cancer differentiation, and TC, in combination with chemotherapy or EGFR-TKIs, may help patients overcome drug resistance.
]]>Cancers doi: 10.3390/cancers16061169
Authors: Corrado Tinterri Erika Barbieri Andrea Sagona Alberto Bottini Giuseppe Canavese Damiano Gentile
Background: Neoadjuvant therapy (NAT) has become increasingly employed for the treatment of cT3-4 breast cancer (BC), enabling breast-conserving surgery (BCS) in cases traditionally considered for mastectomy. This study aims to identify predictors for breast conservation post-NAT and to evaluate whether BCS influences long-term oncological outcomes. Methods: We retrospectively analyzed data from patients with cT3-4 BC who received NAT at the Breast Unit of IRCCS Humanitas Research Hospital, Milan, Italy, from October 2009 to April 2020. Surgical outcomes and long-term oncological results, such as disease-free survival (DFS), distant DFS (DDFS), overall survival (OS), and BC-specific survival (BCSS), were compared between the BCS and mastectomy groups. Results: Among 114 patients analyzed, 37 (32.5%) underwent BCS, and 77 (67.5%) had a mastectomy. The key predictors for opting for BCS included absence of vascular invasion, reduced tumor size post-NAT, and achieving ypT0 status. No significant differences in DFS, DDFS, OS, and BCSS were observed between the two surgical groups (log-ranks, p = 0.520, p = 0.789, p = 0.216, p = 0.559, respectively). Conclusions: BCS after NAT is a feasible and safe option for patients with cT3-4 BC, without adversely affecting long-term oncological outcomes. Identifying predictors of breast conservation can guide surgical decision-making, ensuring that patients receive optimal treatment.
]]>Cancers doi: 10.3390/cancers16061168
Authors: Michael Oertel Priska Hölscher Dominik Hering Christopher Kittel Michael Fuchs Uwe Haverkamp Peter Borchmann Hans Theodor Eich
Purpose: Hodgkin lymphoma is a hematologic malignancy with excellent outcomes even in advanced stages. Consequently, the importance of treatment-associated toxicity increases. However, the exact estimation of individualized rates is difficult due to different disease extents, treatment strategies and techniques. The following analysis aims at a pre-treatment estimation of relevant mediastinal toxicities. Methods: Normal tissue complication probability calculations were used to evaluate the toxicity rates for the heart, lungs and female breast of patients undergoing radiotherapy for early-stage Hodgkin lymphoma. Overall, 45 Patients of the HD16 and HD17 trials by the German Hodgkin study group were included and risks were calculated using the Lyman–Kutcher–Burman model. Results: The median values for pericarditis, pneumonitis and fibrosis of the left or right breast were 0.0%, 0.0%, 0.7% and 0.6% in the HD16 cohort, and 0.0%, 0.1%, 1.1% and 1.0% in the HD17 cohort, respectively. Correspondingly, none of the included patients displayed any of the evaluated toxicities during clinical follow-up. The use of higher doses (30 Gy) in the HD17 cohort led to an increase in toxicity compared to the HD16 cohort (20 Gy). No significant influence of the planning target volume size or the radiation technique could be found in this study. Conclusion: Both the clinically observed and calculated toxicity rates corroborate the overall low-risk profile of radiotherapy for Hodgkin lymphoma. Further treatment individualization will be attempted in the future.
]]>Cancers doi: 10.3390/cancers16061167
Authors: Lucía Cayuela José-Juan Pereyra-Rodríguez Juan-Carlos Hernández-Rodriguez Aurelio Cayuela
Aim: This study aims to elucidate the factors driving melanoma incidence trends in Spain by analyzing the GBD-2019 dataset (1990–2019) and investigating the age-specific, birth cohort, and period effects on incidence rates. Materials and Methods: This study analyzed melanoma incidence trends in Spain from 1990 to 2019 using an ecological design. Data were sourced from the Global Burden of Disease Study 2019 and Spain’s National Statistics Institute. Age-standardized incidence rates (ASIRs) were calculated using joinpoint regression analysis, and age–period–cohort (A-P-C) modeling was employed to assess the effects of age, time period, and birth cohort on incidence rates. Results: Between 1990 and 2019, an estimated 147,823 melanoma cases were diagnosed in Spain. The ASIRs showed a steady increase for both sexes, with slightly higher rates observed in men. Both men (average annual percentage change (AAPC): 2.8%) and women (AAPC: 2.4%) showed a steady increase in the ASIR over the period. Joinpoint analysis revealed distinct periods of incidence rate changes, with significant upward trends in earlier years followed by stabilization in recent years. Incidence rates increased steadily with age, with the highest rates in the 80–84 age group. Women tended to have slightly higher rates in younger age groups, while men had higher rates in older age groups. Both men and women experienced a steady increase in relative risk of melanoma throughout the 30-year study period, with significant upward trends across birth cohorts. Conclusions: Despite limitations, this study provides valuable insights into factors influencing melanoma incidence in Spain. By understanding age, period, and cohort effects, effective prevention strategies can be developed to reduce melanoma incidence.
]]>Cancers doi: 10.3390/cancers16061166
Authors: Monique A. Hartley-Brown Clifton C. Mo Omar Nadeem Shonali Midha Jacob P. Laubach Paul G. Richardson
Mezigomide is an oral cereblon E3 ligase modulator (CELMoD) that is under clinical investigation in patients with relapsed/refractory (RR) multiple myeloma (MM). Like other CELMoD compounds, mezigdomide acts by altering the conformation of cereblon within the cullin 4A ring ligase–cereblon (CRL4CRBN) E3 ubiquitin ligase complex, thereby recruiting novel protein substrates for selective proteasomal degradation. These include two critical lymphoid transcription factors, Ikaros family zinc finger proteins 1 and 3 (IKZF1 and IKZF3), also known as Ikaros and Aiolos, which have important roles in the development and differentiation of hematopoietic cells, in MM pathobiology, and in suppressing the expression of interferon-stimulating genes and T-cell stimulation. Among the CELMoDs, mezigdomide has the greatest cereblon-binding potency, plus the greatest potency for the degradation of Ikaros and Aiolos and subsequent downstream antimyeloma effects. Preclinical studies of mezigdomide have demonstrated its anti-proliferative and apoptotic effects in MM, along with its immune-stimulatory effects and its synergistic activity with other antimyeloma agents, including in lenalidomide-/pomalidomide-resistant MM cell lines and mouse xenograft models. Early-phase clinical trial data indicate notable activity in heavily pretreated patients with RRMM, including those with triple-class-refractory disease, together with a tolerable and manageable safety profile. This review summarizes current preclinical and clinical findings with mezigdomide and its potential future roles in the treatment of MM.
]]>Cancers doi: 10.3390/cancers16061165
Authors: Hayden Shuster Avery Funkhouser Lorie Allen Moonseong Heo Julie C. Martin W. Jeffery Edenfield Anna V. Blenda
Galectins play a pivotal role in lung cancer oncogenic pathways, influencing apoptosis, angiogenesis, and tumor metastasis. Biomarkers that diagnose, prognose, and guide cancer treatment are crucial, with galectins having the biomarker potential for non-small cell lung cancer (NSCLC). Using enzyme-linked immunosorbent assay (ELISA), we assessed serum galectin-1, -3, and -9 levels in NSCLC patients. A retrospective chart review was performed to examine patient demographics, cancer stage, tumor biology, cancer treatment, and patient outcomes. Galectin levels were then compared across these factors. In this exploratory analysis, galectin-3 levels were significantly lower in patients with squamous cell lung cancer (p = 0.0019) and in patients exposed to chemotherapy (p = 0.0375). Galectin-1 levels were significantly lower in patients with previous metastasis but had no correlation with future metastasis. Abnormal galectin-1 levels were significantly correlated with decreased overall survival (OS) in NSCLC (p = 0.0357) and specifically in patients with surgically resectable NSCLC (p = 0.0112). However, abnormal galectin-1 levels were not found to correlate with decreased OS in multivariable analysis (p = 0.0513). These findings may have clinical implications as galectin-3 inhibitors are in trials for NSCLC. Additionally, they suggest that galectin-1 has potential as a prognostic marker for surgically resectable NSCLC.
]]>Cancers doi: 10.3390/cancers16061164
Authors: Klementina Črepinšek Nika Klobučar Tine Tesovnik Robert Šket Barbara Jenko Bizjan Jernej Kovač Marko Kavčič Tomaž Prelog Lidija Kitanovski Janez Jazbec Maruša Debeljak
In this study, we aimed to identify patients within our B-ALL cohort with altered PAX5. Our objective was to use a comprehensive analysis approach to characterize the types of genetic changes, determine their origin (somatic/germline), and analyze the clinical outcomes associated with them. A consecutive cohort of 99 patients with B-ALL treated at the Children’s Hospital of the UMC Ljubljana according to the ALL IC-BFM 2009 protocol was included in our study. We used RNA sequencing data for gene expression analysis, fusion gene detection and single nucleotide variant identification, multiplex-ligation dependent probe amplification for copy number variation assessment, and Sanger sequencing for germline variant detection. PAX5 was impacted in 33.3% of our patients, with the genetic alterations ranging from CNVs and rearrangements to SNVs. The most common were CNVs, which were found in more than a third of patients, followed by point mutations in 5.2%, and gene rearrangements in 4.1%. We identified eight patients with a PAX5-associated genetic subtype that were previously classified as “B-other”, and they showed intermediate outcomes. We showed higher minimal residual disease values at the end of induction and poorer event-free survival in hyperdiploid cases carrying duplications in PAX5 compared to other hyperdiploid cases. We also report an interesting case of a patient with PAX5::FKBP15 and a pathogenic variant in PTPN11 who underwent an early relapse with a monocytic switch. In conclusion, this study provides valuable insights into the presence, frequency, and prognostic significance of diverse PAX5 alterations in B-ALL patients, highlighting the complexity of genetic factors and their impact on patient outcomes.
]]>Cancers doi: 10.3390/cancers16061163
Authors: Agnieszka Maria Mazurek Iwona Jabłońska Marek Kentnowski Urszula Kacorzyk Mirosław Śnietura Tomasz Wojciech Rutkowski
Background: There are definite reasons to implement molecular diagnostics based on the measurement of human papillomavirus (HPV) DNA in liquid biopsy into clinical practice. It is a quick, repeatable, and health-safe test for cancer biomarkers in the blood. In this study, we investigated whether the circulating tumor-related HPV16 (ctHPV16) viral load (VL) in patients with oropharyngeal squamous cell carcinoma (OPSCC) was important for determining the risk of locoregional recurrence-free survival (LRFS), metastasis-free survival (MFS), and overall survival (OS). Methods: This study included 91 patients with ctHPV16-positive OPSCC who had been treated with radical radiotherapy and chemotherapy. The VL was measured using quantitative PCR (qPCR) and a probe specific for HPV16. Based on 10 years of follow-up, the 2-, 3-, 5-, and 9-year LRFS, MFS, and OS were estimated. Results: The 5-year actuarial LRFS, MFS, and OS rates of patients with ctHPV16-positive/OPSCC were 88%, 90%, and 81%, respectively. The VL was significantly higher in patients who subsequently developed distant metastases (DM) than in those who did not (VL 4.09 vs. 3.25; p = 0.009). In a Cox proportional hazards regression model for MFS, a higher ctHPV16 VL appeared to be a significant independent prognostic factor for the occurrence of DM (HR 2.22, p = 0.015). The ROC curve revealed a cutoff value of 3.556 for VL (p = 0.00001). Conclusions: A high VL before treatment indicates patients with a significant risk of DM, and should be used in OPSCC treatment stratification.
]]>Cancers doi: 10.3390/cancers16061162
Authors: Mizuki Sato Kazumasa Odagiri Yuya Tabuchi Hiroaki Okamoto Tsuneo Shimokawa Yukiko Nakamura Masaharu Hata
Durvalumab consolidation after chemoradiotherapy for stage III non-small cell lung cancer (NSCLC) has become the standard of care. Single-center results were examined for treatment outcomes and patterns of pneumonitis in clinical practice. Patients with stage III NSCLC who underwent chemoradiotherapy at our institution (n = 150) were included. The patients were treated with chemoradiotherapy and durvalumab consolidation (Group D, n = 69) or chemoradiotherapy alone (Group N, n = 81). The overall survival (OS), progression-free survival (PFS), and the incidence of and risk factors for 12-month pneumonitis grade ≥ 2 (G2) were investigated. Two-year OS rates were 71.6% in Group D and 52.7% in Group N (p = 0.052). Two-year PFS rates were 43.0% in Group D and 26.5% in Group N (p = 0.010), although a propensity score matched analysis showed no significant difference. The incidence of 12-month pneumonitis ≥ G2 tended to be higher in Group D than in Group N (41.9% vs. 26.3%, p = 0.080). However, there was no difference in pneumonitis ≥ G3 rates (10.5% vs. 12.6%, p = 0.657). A multivariate analysis showed that the lung volume spared from 5 Gy (VS5) < 1800 cm3 was a risk factor for pneumonitis ≥ G2 in Group D. Durvalumab consolidation showed the potential to prolong PFS without increasing the severity of pneumonitis.
]]>Cancers doi: 10.3390/cancers16061161
Authors: Dilshod Muhammadvalievich Mamadaliev Ryuta Saito Kazuya Motomura Fumiharu Ohka Gianluca Scalia Giuseppe Emmanuele Umana Alfredo Conti Bipin Chaurasia
Awake surgery has become a standard practice for managing diffuse low-grade gliomas (LGGs), particularly in eloquent brain areas, and is established as a gold standard technique for left-dominant-hemisphere tumors. However, the intraoperative monitoring of functions in the right non-dominant hemisphere (RndH) is often neglected, highlighting the need for a better understanding of neurocognitive testing for complex functions in the right hemisphere. This article aims to comprehensively review the current literature on the benefits of awake craniotomy in gliomas of the non-dominant right hemisphere. A systematic review was conducted using the PubMed and ScienceDirect databases with keywords such as “right hemisphere”, “awake surgery”, “direct electrical brain stimulation and mapping”, and “glioma”. The search focused on anatomical and surgical aspects, including indications, tools, and techniques of awake surgery in right cerebral hemisphere gliomas. The literature search identified 74 sources, including original articles, books, monographs, and review articles. Two papers reported large series of language assessment cases in 246 patients undergoing awake surgery with detailed neurological semiology and mapping techniques, while the remaining studies were predominantly neuroradiological and neuroimaging in nature. Awake craniotomy for non-dominant-hemisphere gliomas is an essential tool. The term “non-dominant” should be revised, as this hemisphere contributes significantly to essential cognitive functions in the human brain.
]]>Cancers doi: 10.3390/cancers16061160
Authors: Alexandra Ghiaur Cristina Doran Mihnea-Alexandru Gaman Bogdan Ionescu Aurelia Tatic Mihaela Cirstea Maria Camelia Stancioaica Roxana Hirjan Daniel Coriu
The hallmark of acute promyelocytic leukemia (APL) is the presence of the characteristic fusion transcript of the promyelocytic leukemia gene with the retinoic acid receptor α gene (PML::RARA). The PML::RARA fusion is a molecular target for all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Therapies based on ATRA plus ATO have excellent outcomes in terms of complete remission rates, overall survival, and achievement of deep and durable molecular responses with a very low incidence of relapse. However, although the combination of ATRA and ATO has lower hematologic toxicity than standard chemotherapy, its use is associated with a spectrum of distinctive toxicities, such as differentiation syndrome, liver toxicity, QT interval prolongation, and neurotoxicity. Rigorous monitoring of patients’ clinical evolution is indispensable for identifying and addressing each complication. The objective is to maintain an equilibrium between treatment-induced adverse events and therapeutic efficacy. This paper focused on non-hematologic complications associated with the combination of ATRA and ATO. Additionally, we discuss late-onset complications of this therapy. In summary, the majority of treatment-related adverse events are manageable, self-limiting, and reversible. More so, there seems to be a lower incidence rate of secondary neoplasms compared to standard chemotherapy. However, further research is required to assess how the ATRA plus ATO regimen affects the emergence of additional comorbidities.
]]>Cancers doi: 10.3390/cancers16061159
Authors: Shuang Niu Kyle Molberg Diego H. Castrillon Elena Lucas Hao Chen
Endometrial carcinoma stands as the most prevalent gynecological cancer and the fourth most common cancer affecting women. The incidence of endometrial cancer has been steadily increasing over the past decade, posing a significant threat to public health. The early detection of its precancers remains a critical and evolving concern to reduce mortality associated with endometrial carcinoma. In the last decade, our understanding of endometrial carcinoma and its precancers has advanced through systematic investigations into the molecular genetics of endometrial carcinoma and its precancers. In this review, we focus on advances in precancers associated with the endometrioid subtype, by far the most common histologic variant of endometrial adenocarcinoma. Recent investigations have led to the identification of new biomarkers, and the proposed incorporation of these biomarkers or biomarker panels into the diagnostic framework of endometrial carcinoma precancers. Here, we review these recent advances and their relevance to the histopathologic diagnosis of endometrial carcinoma precancers.
]]>Cancers doi: 10.3390/cancers16061158
Authors: Vincent-Béni Sèna Zossou Freddy Houéhanou Rodrigue Gnangnon Olivier Biaou Florent de Vathaire Rodrigue S. Allodji Eugène C. Ezin
Liver malignancies, particularly hepatocellular carcinoma and metastasis, stand as prominent contributors to cancer mortality. Much of the data from abdominal computed tomography images remain underused by radiologists. This study explores the application of machine learning in differentiating tumor tissue from healthy liver tissue using radiomics features. Preoperative contrast-enhanced images of 94 patients were used. A total of 1686 features classified as first-order, second-order, higher-order, and shape statistics were extracted from the regions of interest of each patient’s imaging data. Then, the variance threshold, the selection of statistically significant variables using the Student’s t-test, and lasso regression were used for feature selection. Six classifiers were used to identify tumor and non-tumor liver tissue, including random forest, support vector machines, naive Bayes, adaptive boosting, extreme gradient boosting, and logistic regression. Grid search was used as a hyperparameter tuning technique, and a 10-fold cross-validation procedure was applied. The area under the receiver operating curve (AUROC) assessed the performance. The AUROC scores varied from 0.5929 to 0.9268, with naive Bayes achieving the best score. The radiomics features extracted were classified with a good score, and the radiomics signature enabled a prognostic biomarker for hepatic tumor screening.
]]>Cancers doi: 10.3390/cancers16061157
Authors: Julia Feldheim Marvin Darkwah Oppong Jonas Alexander Feldheim Ramazan Jabbarli Philipp Dammann Anne-Kathrin Uerschels Oliver Gembruch Yahya Ahmadipour Cornelius Deuschl Andreas Junker Ulrich Sure Karsten Henning Wrede
In patients with primary central nervous system lymphoma (PCNSL), the choice of surgical strategy for histopathologic assessments is still controversial, particularly in terms of preoperative corticosteroid (CS) therapy. To provide further evidence for clinical decision-making, we retrospectively analyzed data from 148 consecutive patients who underwent surgery at our institution. Although patients treated with corticosteroids preoperatively were significantly more likely to require a second or third biopsy (p = 0.049), it was only necessary in less than 10% of the cases with preoperative (but discontinued) corticosteroid treatment. Surprisingly, diagnostic accuracy was significantly lower when patients were treated with anticoagulation or dual antiplatelet therapy (p = 0.015). Preoperative CSF sampling did not provide additional information but was associated with delayed surgery (p = 0.02). In conclusion, preoperative CS therapy can challenge the histological diagnosis of PCNSL. At the same time, our data suggest that preoperative CS treatment only presents a relative contraindication for early surgical intervention. If a definitive diagnosis cannot be made after the first surgical intervention, the timing of a repeat biopsy after the discontinuation of CS remains a case-by-case decision. The effect of anticoagulation and dual antiplatelet therapy on diagnostic accuracy might have been underestimated and should be examined closely in future investigations.
]]>Cancers doi: 10.3390/cancers16061156
Authors: Marzena Szwed Agnieszka Marczak
Hyperthermia (HT) is an anti-cancer therapy commonly used with radio and chemotherapies based on applying heat (39–45 °C) to inhibit tumor growth. However, controlling heat towards tumors and not normal tissues is challenging. Therefore, nanoparticles (NPs) are used in HT to apply heat only to tumor tissues to induce DNA damage and the expression of heat shock proteins, which eventually result in apoptosis. The aim of this review article is to summarize recent advancements in HT with the use of magnetic NPs to locally increase temperature and promote cell death. In addition, the recent development of nanocarriers as NP-based drug delivery systems is discussed. Finally, the efficacy of HT combined with chemotherapy, radiotherapy, gene therapy, photothermal therapy, and immunotherapy is explored.
]]>Cancers doi: 10.3390/cancers16061155
Authors: Tibor A. Zwimpfer Esra Bilir Khayal Gasimli Andrej Cokan Nicolò Bizzarri Zoia Razumova Joanna Kacperczyk-Bartnik Tanja Nikolova Andrei Pletnev Ilker Kahramanoglu Alexander Shushkevich Aleksandra Strojna Charalampos Theofanakis Tereza Cicakova Marcus Vetter Céline Montavon Gilberto Morgan Viola Heinzelmann-Schwarz
Platinum and taxane chemotherapy is associated with the risk of hypersensitivity reactions (HSRs), which may require switching to less effective treatments. Desensitization to platinum and taxane HSRs can be used to complete chemotherapy according to the standard regimen. Therefore, we aimed to investigate the current management of HSRs to platinum and/or taxane chemotherapy in patients with gynecologic cancers. We conducted an online cross-sectional survey among gynecological and medical oncologists consisting of 33 questions. A total of 144 respondents completed the survey, and 133 respondents were included in the final analysis. Most participants were gynecologic oncologists (43.6%) and medical oncologists (33.8%), and 77.4% (n = 103) were involved in chemotherapy treatment. More than 73% of participants experienced >5 HSRs to platinum and taxane per year. Premedication and a new attempt with platinum or taxane chemotherapy were used in 84.8% and 92.5% of Grade 1–2 HSRs to platinum and taxane, respectively. In contrast, desensitization was used in 49.4% and 41.8% of Grade 3–4 HSRs to platinum and taxane, respectively. Most participants strongly emphasized the need to standardize the management of platinum and taxane HSRs in gynecologic cancer. Our study showed that HSRs in gynecologic cancer are common, but management is variable and the use of desensitization is low. In addition, the need for guidance on the management of platinum- and taxane-induced HSRs in gynecologic cancer was highlighted.
]]>Cancers doi: 10.3390/cancers16061154
Authors: Melissa Barlow Willie Hamilton Sarah E. R. Bailey
Thrombocytosis is a risk marker for lung cancer in primary care. We investigated whether thrombocytosis presents pre-diagnostically for all the histological subtypes of lung cancer and its association with the stage at diagnosis. A matched cohort study used English electronic primary care data linked to the national cancer registry. Patients diagnosed with lung cancer aged ≥40 years with no prior history of malignancy were matched by age, sex, and general practice to five controls without lung cancer. Multivariable logistic regression models quantified the incidence of pre-diagnostic thrombocytosis and advanced-stage diagnoses, adjusting for COPD diagnosis, smoking status, and anti-platelet drug prescriptions. A total of 9504 cases were matched to 45,647 controls, consisting of 3260 (34%) adenocarcinomas (ADC), 2020 (21%) squamous cell carcinomas (SCC), 70 (<1%) large-cell carcinomas (LCC), and 1089 (12%) small-cell lung cancers (SCLC). The patients with lung cancer were 8.9 (95% CI 8.0–9.9) times more likely to exhibit pre-diagnostic thrombocytosis than the controls. The odds ratios were highest for the comparison between SCC and ADC (1.8, 95% CI 1.5–2.1). Thrombocytosis is associated with advanced-stage ADC and SCC but presented equally for early- and advanced-stage SCLC. Pre-diagnostic thrombocytosis may aid in the detection of all the histological subtypes in primary care.
]]>Cancers doi: 10.3390/cancers16061153
Authors: Franco Ionna Ettore Pavone Corrado Aversa Francesco Maffia Raffaele Spinelli Emanuele Carraturo Giovanni Salzano Fabio Maglitto Marco Sarcinella Roberta Fusco Vincenza Granata Secondo Lastoria Francesco Del Prato Maria Grazia Maglione
Oral tongue squamous-cell carcinoma (OTSCC) is the most prevalent malignancy in the head and neck region. Lymphatic spread, particularly to cervical lymph nodes, significantly impacts 5-year survival rates, emphasizing the criticality of precise staging. Metastatic cervical lymph nodes can decrease survival rates by 50%. Yet, elective neck dissection (END) in T1–2 cN0 patients proves to be an overtreatment in around 80% of cases. To address this, sentinel lymph node biopsy (SLNB) was introduced, aiming to minimize postoperative morbidity. This study, conducted at the ENT and Maxillofacial Surgery department of the Istituto Nazionale Tumori in Naples, explores SLNB’s efficacy in early-stage oral tongue squamous-cell carcinoma (OTSCC). From January 2020 to January 2022, 122 T1/T2 cN0 HNSCC patients were enrolled. Radioactive tracers and lymphoscintigraphy identified sentinel lymph nodes, aided by a gamma probe during surgery. Results revealed 24.6% SLN biopsy positivity, with 169 SLNs resected and a 21.9% positivity ratio. The study suggests SLNB’s reliability for T1-2 cN0 OTSCC patient staging and early micrometastasis detection.
]]>Cancers doi: 10.3390/cancers16061151
Authors: Shi-Ming Tu Anup K. Trikannad Sruthi Vellanki Munawwar Hussain Nazish Malik Sunny R. Singh Anusha Jillella Sri Obulareddy Sindhu Malapati Sajjad A. Bhatti Konstantinos Arnaoutakis Omar T. Atiq
Although immunotherapy has revolutionized cancer care, there is still an urgent need to enhance its efficacy and ensure its safety. A correct cancer theory and proper scientific method empower pertinent cancer research and enable effective and efficient drug versus therapy development for patient care. In this perspective, we revisit the concept of immune privilege in a cancer cell versus normal cell, as well as in a cancer stem cell versus normal stem cell. We re-examine whether effective immunotherapies are efficacious due to their anti-cancer and/or immune modulatory mechanisms. We reassess why checkpoint inhibitors (CPIs) are not equal. We reconsider whether one can attribute the utility of immunotherapy to specific cancer subtypes and its futility to certain tumor/immune compartments, components, and microenvironments. We propose ways and means to advance immunotherapy beyond CPIs by combining anti-PD1/L1 with various other treatment modalities according to an appropriate scientific theory, e.g., stem cell origin of cancer, and based on available clinical evidence, e.g., randomized clinical trials. We predict that a stem cell theory of cancer will facilitate the design of better and safer immunotherapy with improved selection of its use for the right patient with the right cancer type at the right time to optimize clinical benefits and minimize potential toxic effects and complications.
]]>Cancers doi: 10.3390/cancers16061152
Authors: Yumeng Zhang Lancia Darville Stephanie Hogue Julie E. Hallanger Johnson Trevor Rose Youngchul Kim Alexis Bailey Jhanelle E. Gray Lary A. Robinson
Background: Sex difference in the immune response may influence patients’ response to immune checkpoint inhibitors (ICIs). We conducted a prospective observation study to determine the correlation between pretreatment sex hormone levels and response to ICIs in metastatic non-small cell lung cancer (NSCLC). Method: Pretreatment plasma samples from 61 patients with newly diagnosed NSCLC prior to ICI therapy were collected. Six sex hormone levels [pyrazole triol, 17 β-estradiol, 5-androstenediol, 3β-androstenediol, dehydroepiandrosterone (DHEA), and S-equol] were measured using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). Overall survival (OS) and progression-free survival (PFS) were compared between the high- and low-level groups in the whole cohort. Result: Among the six sex hormones measured, DHEA levels were significantly higher among patients without clinical benefits in the discovery cohort; the remaining sex hormones did not differ significantly. In the whole cohort, median PFS was 22 months for patients with low DHEA levels vs. 3.8 months for those with high DHEA [hazard ratio, 14.23 (95% CI, 4.7–43); p < 0.001]. A significant association was also observed for OS [hazard ratio, 8.2 (95% CI, 2.89–23.35); p < 0.0001]. Conclusions: High pretreatment plasma DHEA levels were associated with poor clinical outcomes for patients with metastatic NSCLC treated with ICIs.
]]>Cancers doi: 10.3390/cancers16061150
Authors: Esha Vallabhaneni Samuel A. Kareff Reagan M. Barnett Leylah M. Drusbosky Shivani Dalal Luis E. Raez Edgardo S. Santos Federico Albrecht Mike Cusnir Estelamari Rodriguez
Pathogenic germline variants (PGVs) may be under-detected as causative etiologies in patients with non-small cell lung cancer (NSCLC). The prevalence of PGVs has been reported between 1 and 15% of patients, depending on the patient population. The rate within Hispanic/Latinx populations remains unknown. We retrospectively analyzed the genomic results (Guardant360, Redwood City, CA, USA) of 878 patients with advanced or metastatic NSCLC at five centers in South Florida, USA, from 2019 to 2022 to analyze the rate of incidental PGVs (iPGVs) identified via circulating cell-free tumor DNA (ctDNA). We then stratified the results by tumor histology, age, gender, race, ethnicity, genetic pathway, and co-mutations. Twenty-one iPGVs were identified (21/878 = 2.4%). Among the 21 iPGVs identified, 14 patients were female (66.7%) and 7 were male (33.3%), with a median age of 67 years and tobacco history of 2.5 pack-years. In total, 52.4% of patients identified as Hispanic/Latinx (n = 11) of any race; 19.0% as Ashkenazi Jewish (n = 4), 9.5% as non-Hispanic/Latinx black (n = 2), and 19.0% as non-Hispanic/Latinx white (n = 4). iPGVs in the homologous recombination repair pathway were solely expressed in this cohort (10 ATM, 8 BRCA2, and 3 BRCA1). In total, 76% (16/21) of patients with iPGVs co-expressed somatic alterations, with 56% (9/16) demonstrating alterations in targetable genes. Overall, our real-world findings offer a point prevalence of iPGVs in patients with NSCLC of diverse populations, such as patients who report Hispanic/Latinx ethnicity.
]]>Cancers doi: 10.3390/cancers16061149
Authors: Dirk Rades Darejan Lomidze Natalia Jankarashvili Fernando Lopez Campos Arturo Navarro-Martin Barbara Segedin Blaz Groselj Christian Staackmann Charlotte Kristiansen Kristopher Dennis Steven E. Schild Jon Cacicedo
Patients with metastatic epidural spinal cord compression (MESCC) and favorable survival prognoses may benefit from radiation doses exceeding 10 × 3.0 Gy. In a multi-center phase 2 trial, patients receiving 15 × 2.633 Gy (41.6 Gy10) or 18 × 2.333 Gy (43.2 Gy10) were evaluated for local progression-free survival (LPFS), motor/sensory functions, ambulatory status, pain, distress, toxicity, and overall survival (OS). They were compared (propensity score-adjusted Cox regression) to a historical control group (n = 266) receiving 10 × 3.0 Gy (32.5 Gy10). In the phase 2 cohort, 50 (of 62 planned) patients were evaluated for LPFS. Twelve-month rates of LPFS and OS were 96.8% and 69.9%, respectively. Motor and sensory functions improved in 56% and 57.1% of patients, and 94.0% were ambulatory following radiotherapy. Pain and distress decreased in 84.4% and 78.0% of patients. Ten and two patients experienced grade 2 and 3 toxicities, respectively. Phase 2 patients showed significantly better LPFS than the control group (p = 0.039) and a trend for improved motor function (p = 0.057). Ambulatory and OS rates were not significantly different. Radiotherapy with 15 × 2.633 Gy or 18 × 2.333 Gy was well tolerated and appeared superior to 10 × 3.0 Gy.
]]>Cancers doi: 10.3390/cancers16061147
Authors: Yani Berckmans Ann Vankerckhoven Aarushi Audhut Caro Julie Kempeneers Jolien Ceusters Gitte Thirion Katja Vandenbrande Ignace Vergote Damya Laoui An Coosemans
Immune checkpoint inhibitor (ICI) therapy has proven revolutionary in the treatment of some cancers. However, ovarian cancer remains unresponsive to current leading ICIs, such as anti-PD1 or anti-PD-L1. In this article, we explored the potential of an upcoming checkpoint molecule, T-cell immunoglobulin and mucin domain 3 (TIM3), for the treatment of ovarian cancer using a syngeneic orthotopic mouse model (ID8-fLuc). Besides therapeutic efficacy, we focused on exploring immune changes in tumor tissue and peritoneal fluid. Our results showed no improvement in survival in ovarian cancer-bearing mice after anti-TIM3 treatment when used as monotherapy nor when combined with anti-PD1 or standard-of-care chemotherapy (carboplatin/paclitaxel). This was reflected in the unaltered immune infiltration in treated mice compared to control mice. Altering the order of drug administration within the combination treatment altered the survival results, but did not result in a survival benefit over chemotherapy alone. These findings highlight the need for further preclinical studies to find beneficial treatment schemes and combination therapies for ovarian cancer.
]]>Cancers doi: 10.3390/cancers16061148
Authors: Klijs J. de Koning Carleen M. E. M. Adriaansens Rob Noorlag Remco de Bree Robert J. J. van Es
Background: This systematic review investigates techniques for determining adequate mucosal margins during the resection of oral squamous cell carcinoma (SCC). The primary treatment involves surgical removal with ≥5 mm margins, highlighting the importance of accurate differentiation between SCC and dysplasia during surgery. Methods: A comprehensive Embase and PubMed literature search was performed. Studies underwent quality assessment using QUADAS-2. Results: After the full-text screening and exclusion of studies exhibiting high bias, eight studies were included, focusing on three margin visualization techniques: autofluorescence, iodine staining, and narrow-band imaging (NBI). Negative predictive value (NPV) was calculable across the studies, though reference standards varied. Results indicated NPVs for autofluorescence, iodine, and NBI ranging from 61% to 100%, 92% to 99%, and 86% to 100%, respectively. Autofluorescence did not significantly enhance margins compared to white light-guided surgery, while iodine staining demonstrated improvement for mild or moderate dysplasia. NBI lacked comparison with a white light-guided surgery cohort. Conclusions: We recommend studying and comparing the diagnostic accuracy of iodine staining and NBI in larger cohorts of patients with oral SCC, focusing on discriminating between SCC and (severe) dysplasia. Furthermore, we advise reporting the diagnostic accuracy alongside the treatment effects to improve the assessment of these techniques.
]]>Cancers doi: 10.3390/cancers16061146
Authors: Antonio Mazzella Monica Casiraghi Clarissa Uslenghi Riccardo Orlandi Giorgio Lo Iacono Luca Bertolaccini Gianluca Maria Varano Franco Orsi Lorenzo Spaggiari
Backgrounds: Our goal is to evaluate the correct management of broncho-pleural fistula (BPF) after lobectomy for lung cancer. Methods: We retrospectively reviewed our 25-years’ experience and reported our strategies and our diagnostic algorithm for the management of post-lobectomy broncho-pleural fistula. Results: Five thousand one hundred and fifty (5150) patients underwent lobectomy for lung cancer in the period between 1998 and 2023. A total of 44 (0.85%) out of 5150 developed post-operative BPF. In 11 cases, BPF was solved by non-invasive treatment. In nine cases, direct surgical repair of the bronchial stump allowed BPF resolution. In 14 cases, a completion intervention was performed. In six cases, we performed open window thoracostomy (OWT) after lobectomy; in two cases, the BPF was closed by percutaneous injection of an n-butyl cyanoacrylate glue mixture. In two cases, no surgical procedure was performed because of the clinical status of the patient at the time of fistula developing. Thirty-day and ninety-day mortality from fistula onset was, respectively, 18.2% (eight patients) and 22.7% (ten patients). Thirty-day and ninety-day mortality after completion pneumonectomy (12 patients) was, respectively, 8.3% (one patient) and 16.6% (two patients). Conclusions: The correct management of BPF depends on various factors: timing of onset, size of the fistula, anatomic localization, and the general condition of the patient. In the case of failure of various initial therapeutic approaches, completion intervention or OWT could be considered.
]]>Cancers doi: 10.3390/cancers16061145
Authors: Katarzyna Pawińska-Wąsikowska Małgorzata Czogała Karolina Bukowska-Strakova Marta Surman Monika Rygielska Teofila Książek Beata Sadowska Agnieszka Pac Jolanta Skalska-Sadowska Magdalena Samborska Jacek Wachowiak Małgorzata Ciebiera Radosław Chaber Renata Tomaszewska Tomasz Szczepański Karolina Zielezińska Tomasz Urasiński Małgorzata Moj-Hackemer Krzysztof Kałwak Marta Kozłowska Ninela Irga-Jaworska Barbara Sikorska-Fic Paweł Łaguna Katarzyna Muszyńska-Rosłan Maryna Krawczuk-Rybak Anna Fałkowska Katarzyna Drabko Katarzyna Bobeff Wojciech Młynarski Agnieszka Chodała-Grzywacz Grażyna Karolczyk Katarzyna Mycko Wanda Badowska Natalia Bartoszewicz Jan Styczyński Katarzyna Machnik Agnieszka Mizia-Malarz Walentyna Balwierz Szymon Skoczeń
Background: The reports of studies that compare the survival of adolescents and young adults with younger children with acute myeloid leukemia (AML) are contradictory. Patients and Methods: We retrospectively analyzed 220 AML patients aged 0–18 years treated in pediatric oncologic centers in Poland from 2015 to 2022. The evaluated group included 31 infants (below 1 year), 91 younger children (1–9.9 years), 59 older children (10–14.9 years), and 39 adolescents (15–18 years). Results: A 5-year overall survival for adolescents was not significantly inferior compared to younger and older children (74.3 ± 7.6% vs. 80.5 ± 4.4% vs. 77.9 ± 5.1, p = 0.243). However, relapse-free survival was lower in adolescents compared to younger children (76.5 ± 7.8% vs. 65.7 ± 9.0%, p = 0.049), and treatment-related mortality tended to be higher (10.3% vs. 4.4%, p = 0.569). In the univariate analysis, high-risk genetics [HR, 2.0 (95% CI 1.1–3.6; p = 0.014)] and a leukocyte count at diagnosis above 100,000/μL [HR, 2.4 (95% CI 1.3–4.6; p = 0.004)] were found to be unfavorable prognostic factors for survival. Conclusions: Although we have not found that age over 15 years is an unfavorable factor for overall survival, the optimal approach to therapy in adolescents, as in other age groups, is to adjust the intensity of therapy to individual genetic risk and introduce targeted therapies when indicated.
]]>Cancers doi: 10.3390/cancers16061144
Authors: Alba Moratiel-Pellitero María Zapata-García Marta Gascón-Ruiz Andrea Sesma Elisa Quílez Ariel Ramirez-Labrada Luis Martínez-Lostao María Pilar Domingo Patricia Esteban Alfonso Yubero Raquel Barbero-Herranz Ana Moreno-Blanco José Ramón Paño Rodrigo Lastra Julián Pardo Dolores Isla Rosa del Campo Eva Gálvez
Immune checkpoint inhibitors have been proposed as the standard treatment for different stages of non-small-cell lung cancer in multiple indications. Not all patients benefit from these treatments, however, and certain patients develop immune-related adverse events. Although the search for predictors of response to these drugs is a major field of research, these issues have yet to be resolved. It has been postulated that microbiota could play a relevant role in conditioning the response to cancer treatments; however, the human factor of intestinal permeability also needs to be considered as it is closely related to the regulation of host–microbiota interaction. In this article, we analyzed the possible relationship between the response to immune checkpoint inhibitors and the onset of immune-related adverse events, gut microbiota status, and intestinal membrane permeability. In a pioneering step, we also measured short-chain fatty acid content in feces. Although the correlation analyses failed to identify predictive biomarkers, even when all variables were integrated, our patients’ microbial gut ecosystems were rich and diverse, and the intestinal barrier’s integrity was preserved. These results add new knowledge on the composition of microbiota and its correlation with barrier permeability and short-chain fatty acids and suggest that more studies are required before these potential biomarkers can be incorporated into the clinical management of patients via immune checkpoint inhibitor treatment.
]]>Cancers doi: 10.3390/cancers16061143
Authors: Andrea Vannini Federico Parenti Cristina Forghieri Gaia Vannini Catia Barboni Anna Zaghini Tatiana Gianni Gabriella Campadelli-Fiume
The role of the interaction with cell-surface glycosaminoglycans (GAGs) during in vivo HSV infection is currently unknown. The rationale of the current investigation was to improve the anticancer efficacy of systemically administered retargeted oHSVs (ReHVs) by decreasing their binding to GAGs, including those of endothelial cells, blood cells, and off-tumor tissues. As a proof-of-principle approach, we deleted seven amino acids critical for interacting with GAGs from the glycoprotein C (gC) of R-337 ReHV. The modification in the resulting R-399 recombinant prolonged the half-life in the blood of systemically administered R-399 and enhanced its biodistribution to tumor-positive lungs and to the tumor-negative liver. Ultimately, it greatly increased the R-399 efficacy against metastatic-like lung tumors upon IV administration but not against subcutaneous tumors upon IT administration. These results provide evidence that the increased efficacy seen upon R-399 systemic administration correlated with the slower clearance from the circulation. To our knowledge, this is the first in vivo evidence that the partial impairment of the gC interaction with GAGs resulted in a prolonged half-life of circulating ReHV, an increase in the amount of ReHV taken up by tissues and tumors, and, ultimately, an enhanced anticancer efficacy of systemically administered ReHV.
]]>Cancers doi: 10.3390/cancers16061142
Authors: Leonie Van Vynckt Philippe Tummers Hannelore Denys Menekse Göker Sigi Hendrickx Eline Naert Rawand Salihi Koen Van de Vijver Gabriëlle H. van Ramshorst Donatienne Van Weehaeghe Katrien Vandecasteele Geert M. Villeirs Pieter J. L. De Visschere
Magnetic resonance imaging (MRI) can be used for the preoperative local staging of endometrial cancer (EC). The presence of ≥pT1b disease (i.e., tumor invasion in ≥50% of the myometrium, into the cervical stroma or spread outside the uterus) has important prognostic value and implications for the decision to perform lymphadenectomy. The purpose of this study was to assess the performance of MRI for the detection of ≥pT1b disease and to evaluate whether tumor size measured via MRI was predictive for ≥pT1b disease, independent of imaging signs of deep invasion. MRI T-staging and tumor diameter and volume were correlated with histopathology of the hysterectomy specimen in 126 patients. MRI had a sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 70.0%, 83.3%, 79.2%, 75.3% and 77.0%, respectively, for the detection of ≥pT1b disease. A tumor diameter of ≥40 mm and volume of ≥20 mL measured via MRI were predictive for ≥pT1b disease at rates of 78.3% and 87.1%, respectively. An EC size of at least 5 mm upon MRI was predictive for ≥pT1b disease in more than 50% of cases. Our results support the use of MRI in the preoperative staging of EC and suggest including size criteria in EC staging guidelines.
]]>Cancers doi: 10.3390/cancers16061141
Authors: Nobuyuki Hamada
On the one hand, ionizing radiation has been used to treat not only cancer, but also non-cancer diseases. On the other hand, associations with radiation exposure have increasingly been reported not only for cancer, but also non-cancer diseases, both at doses or dose rates much lower than previously suggested or considered. This underscores the need for considering both cancer and non-cancer effects of medical (diagnostic or therapeutic), occupational or environmental exposure to radiation. As such, this Special Issue aims to serve as a forum to gather the latest developments and discuss future prospects in the field of normal tissue responses to radiation exposure. The Special Issue is composed of 18 articles outlining the radiation effects arising in various tissues (e.g., those in the circulatory, sensory, nervous, respiratory, and reproductive systems).
]]>Cancers doi: 10.3390/cancers16061138
Authors: Nieves G. Rodríguez-Ibarria Beatriz Pinar Laura García Auxiliadora Cabezón Dolores Rey-Baltar Juan Ignacio Rodríguez-Melcón Marta Lloret Pedro C. Lara
Patients with an early carcinoma of the breast are commonly treated by breast-conserving surgery (BCS) and postoperative radiotherapy. Partial-breast irradiation has gained acceptance in the last few years. Between December 2008 and December 2017, 182 low-risk breast cancer patients treated by BCS in the four university hospitals of the province of Las Palmas and treated with APBI using interstitial multicatheter brachytherapy were included in this study. After a mean follow-up for survivors of 10 years, the treatment was shown to be safe, as no severe acute/late toxicity (grade ≥ 3) was observed. The 10-year IBTR was 1.7% (95%CI: 0.7–2.7%), and the cause-specific survival was 94.9% (95%CI: 93.2–96.6%). We suggest that multicatheter brachytherapy after BCS is safe and effective in early breast cancer patients.
]]>Cancers doi: 10.3390/cancers16061139
Authors: Amalia Sofianidi Ecaterina E. Dumbrava Konstantinos N. Syrigos Azadeh Nasrazadani
Worldwide, breast cancer is the most frequently diagnosed malignancy in women, with triple-negative breast cancer (TNBC) being the most aggressive molecular subtype. Due to the dearth of effective therapeutic options for TNBC, novel agents targeting key mechanisms and pathways in cancer cells are continuously explored; these include ATR inhibitors, which target the ATR kinase involved in the DNA damage response (DDR) pathway, and CHK1/2 inhibitors, which target the Checkpoint Kinase 1/2 (CHK1/2) involved in cell cycle arrest and DNA repair. ATR and CHK1/2 inhibitors show potential as prospective treatments for TNBC by focusing on the DDR and interfering with cell cycle regulation in cancer cells. Preliminary preclinical and clinical findings suggest that when combined with chemotherapy, ATR and CHK1/2 inhibitors demonstrate significant anti-proliferative efficacy against TNBC. In this article, we introduce ATR and CHK1/2 inhibitors as promising therapeutic approaches for the management of TNBC. Preclinical and clinical studies performed evaluating ATR and CHK1/2 inhibitors for the treatment of TNBC and associated challenges encountered in this context to date are reviewed.
]]>Cancers doi: 10.3390/cancers16061140
Authors: Marie-Christine E. Bakker Geertruid J. Brink Alex J. Poot Arthur J. A. T. Braat Geertruida N. Jonges Ronald P. Zweemer
Ovarian cancer mortality rates have not decreased significantly in the past years. As most women are still diagnosed in an advanced stage, there is a need for new treatment strategies for recurrent disease. A potentially new developing targeted approach, theranostics, combines diagnostics and treatment using radiopharmaceuticals. Through target receptors, imaging and treatment of malignant tissue can be achieved. For ovarian malignancy, the follicle-stimulating hormone (FSH) receptor may serve as a possible target since expression appears to be limited to ovarian cells. In this systematic review, we aim to gather all available literature on the expression of the FSH receptor in ovarian tumors. Pubmed, Embase and the Cochrane databases were searched until December 2023 for eligible studies. The search yielded 41 studies, mostly regarding serous carcinomas, sex cord–stromal tumors (SCSTs) and cell lines of serous and SCSTs. Various techniques were used to analyze the expression of the FSH receptor. For serous carcinomas, conflicting results on the expression of the FSH receptor were found. Studies on SCSTs, mainly studying the subtype of granulosa cell tumors, all showed positive expression of the FSH receptor. In the cell lines studies, the KGN cell line derived from a granulosa cell tumor shows positive expression in all studies. Available studies show that SCSTs express the FSH receptor. A theranostic approach targeting the FSH receptor may, therefore, provide a useful new approach for this malignancy with limited therapeutic options in recurrent disease.
]]>Cancers doi: 10.3390/cancers16061137
Authors: Filip Janku Grace M. Choong Mateusz Opyrchal Afshin Dowlati Cinta Hierro Jordi Rodon Andreas Wicki Martin D. Forster Sarah P. Blagden Jun Yin Joel M. Reid Helene Muller Natasa Cmiljanovic Vladimir Cmiljanovic Alex A. Adjei
Background: Bimiralisib is a pan-PI3K/mTOR inhibitor demonstrating antitumor efficacy in preclinical models. The objectives of this study were to identify a maximum tolerated dose (MTD), pharmacokinetics (PK), a dosing schedule, and adverse events (AEs) in patients with advanced solid tumors. Patients and Methods: Patients received oral bimiralisib to determine the MTD of one continuous (once daily) and two intermittent schedules (A: Days 1, 2 weekly; B: Days 1, 4 weekly) until progression or unacceptable AEs occurred. Results: The MTD for the continuous schedule was 80 mg, with grade three fatigue as the dose-limiting toxicity (DLT). No MTD was reached with intermittent schedules, with only one DLT in schedule B. PK analysis suggested that 140 mg (schedule A) was within the biologically active dose range and was selected for further exploration. The most frequent treatment-emergent AEs were hyperglycemia (76.2%) in the continuous schedule, and nausea (56–62.5%) in schedules A and B. The most frequent treatment-emergent > grade three AE for all schedules combined was hyperglycemia (28.6%, continuous schedule; 12.0%, schedule A; 12.5%, schedule B). There was one partial response in a head and neck squamous cancer patient with a NOTCH1T1997M mutation. Conclusions: Bimiralisib demonstrated a manageable AE profile consistent with this compound class. Intermittent schedules had fewer > grade three AEs, while also maintaining favorable PK profiles. Intermittent schedule A is proposed for further development in biomarker-selected patient populations.
]]>Cancers doi: 10.3390/cancers16061136
Authors: Mohamed Rahouma Nathan Mynard Massimo Baudo Sherif Khairallah Shaikha Al-Thani Anas Dabsha Shon Shmushkevich Osama Shoeib Mohamed Hossny Elsayed Eldeeb Hala Aziz Naglaa Abdelkarim Mario Gaudino Abdelrahman Mohamed Leonard Girardi Jun Zhang Luciano Mutti
Immune-checkpoint inhibitors (ICIs) were proven effective in inducing tumor regression. However, its toxicity tends to be fatal. We sought to investigate the hospital volume/outcomes relationship. Databases were searched for studies reporting immune-checkpoint inhibitors adverse events (AEs) in patients with solid-organ malignancies. The outcomes were A) the pooled events rate (PER) of grade 5, grade 3–4, cardiac-related, and pulmonary-related AEs, and B) the assessment of the volume/outcomes relationship. One hundred and forty-seven studies met our inclusion criteria. The PER of grade 5, grade 3–4, and any-grade AEs was 2.75% (95%CI: 2.18–3.47), 26.69% (95%CI: 21.60–32.48), and 77.80% (95%CI: 70.91–83.44), respectively. The PER of pulmonary-related AEs was 4.56% (95%CI: 3.76–5.53). A higher number of annual cases per center was significantly associated with reduced grade 5 (p = 0.019), grade 3–4 (p = 0.004), and cardiac-related AEs (p = 0.035) in the meta-regression. In the current era of cancer immunotherapy, knowledge regarding the early diagnosis and management of immunotherapy-related AEs is essential. Our meta-analysis demonstrates the importance of center volume in improving outcomes and reducing the incidence of severe AEs.
]]>Cancers doi: 10.3390/cancers16061135
Authors: Tomohiro Murakami Eisuke Booka Satoru Furuhashi Yuki Sakai Kenichi Sekimori Ryoma Haneda Mayu Fujihiro Tomohiro Matsumoto Yoshifumi Morita Hirotoshi Kikuchi Yoshihiro Hiramatsu Satoshi Baba Hiroya Takeuchi
The assessment of programmed death-ligand 1 (PD-L1) expression in esophageal squamous cell carcinoma (ESCC) has become increasingly important with the rise of immune checkpoint inhibitors (ICIs). However, challenges persist, including subjective interpretation and the unclear significance of staining intensity, as well as contrasting roles in tumoral and stromal regions. Our study enhances the understanding of PD-L1 in ESCCs by analyzing its expression in tumors and stroma with H-scores, highlighting its distinct clinicopathological impacts. In a retrospective cohort of 194 ESCC specimens from surgical resection, we quantified PD-L1 expression in tumoral and stromal compartments using H-scores, analyzing whole slide images with digital pathology analysis software. Kaplan–Meier analysis demonstrated that higher PD-L1 expression is significantly associated with improved postoperative overall survival (OS) and recurrence-free survival (RFS) in both tumoral and stromal areas. Multivariable analysis identified high tumoral PD-L1 expression as an independent prognostic factor for prolonged OS and RFS (HR = 0.47, p = 0.007; HR = 0.54, p = 0.022, respectively). In a separate analysis, high stromal PD-L1 expression was found to correlate with less advanced pathological stages and a prolonged response to cytotoxic chemotherapy, with no similar correlation found for ICI treatment response. This study reveals PD-L1’s contrasting role in the ESCC tumor immune microenvironment, impacting prognosis, tumor stage, and treatment response.
]]>Cancers doi: 10.3390/cancers16061134
Authors: Victoria Phillips Daniela Franco Montoya E. Kathleen Adams
Purpose: To systematically review published cost-effectiveness analyses of Evidence-Based Interventions (EBIs) recommended by the United States Community Preventive Services Task Force (CPSTF) to increase breast and cervical cancer screening. Methods: We searched PubMed and Embase for prospective cost-effectiveness evaluations of EBIs for breast and cervical cancer screening since 1999. We reviewed studies according to the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) and compared the incremental cost-effectiveness ratio (ICERs), defined as cost per additional woman screened, adjusted to 2021 USD, within and across EBIs by cancer type. Results: We identified eleven studies meeting our review criteria: nine were breast cancer-focused, one breast and cervical cancer combined, and one cervical only, which together reported twenty-four cost-effectiveness assessments of outreach programs spanning eight EBIs. One-on-one education programs were the most common EBI evaluated. The average ICER across breast cancer studies was USD 545 (standard deviation [SD] = USD 729.3), while that for cervical cancer studies was USD 197 (SD = 186.6. Provider reminder/recall systems for women already linked to formal care were the most cost-effective, with an average ICERs of USD 41.3 and USD 10.6 for breast and cervical cancer, respectively. Conclusions: Variability in ICERs across and within EBIs reflect the population studied, the specific EBI, and study settings, and was relatively high. ICER estimate uncertainty and the potential for program replicability in other settings and with other populations were not addressed. Given these limitations, using existing cost-effectiveness estimates to inform program funding allocations is not warranted at this time. Additional research is needed on outreach programs for cervical cancer and those which serve minority populations for either of the female cancer screens.
]]>Cancers doi: 10.3390/cancers16061133
Authors: Laura Bernal Masferrer Tamara Gracia Cazaña Isabel Bernad Alonso Marcial Álvarez-Salafranca Manuel Almenara Blasco María Gallego Rentero Ángeles Juarranz de la Fuente Yolanda Gilaberte
This comprehensive review delves into various immunotherapeutic approaches for the management of actinic keratoses (AKs), precancerous skin lesions associated with UV exposure. Although there are treatments whose main mechanism of action is immune modulation, such as imiquimod or diclofenac, other treatments, apart from their main effect on dysplastic cells, exert some immunological action, which in the end contributes to their efficacy. While treatments like 5-fluorouracil, imiquimod, photodynamic therapy, and nicotinamide are promising in the management of AKs, especially in immunocompetent individuals, their efficacy is somewhat reduced in solid organ transplant recipients due to immunosuppression. The analysis extends to optimal combination, focusing on cryoimmunotherapy as the most relevant. New immunotherapies include resimiquimod, ingenol disoxate, N-phosphonacetyl-L-aspartate (PALA), or anti-PD1 that have shown promising results, although more studies are needed in order to standardize their use.
]]>Cancers doi: 10.3390/cancers16061132
Authors: Nessn Azawi Louise Geertsen Naomi Nadler Karina Sif Soendergaard Mosholt Sofie Staal Axelsen Jane Christensen Niels Viggo Jensen Niels Fristrup Susanne Oksbjerg Dalton Frede Donskov Lars Lund
(1) Background: The role of cytoreductive nephrectomy (CN) is controversial in patients with primary metastatic renal cell carcinoma (mRCC). (2) Methods: We evaluated the impact of CN, or no CN, followed by first-line targeted therapy (TT) in a nationwide unselected cohort of 437 consecutive patients with primary mRCC over a two-year period with a minimum of five years of follow-up. Data sources were national registries supplemented with manually extracted information from individual patient medical records. Cox proportional hazards estimated the hazard ratio (HR) of overall death and cancer-specific death after one and three years. (3) Results: 210 patients underwent CN and 227 did not. A total of 176 patients (40%) had CN followed by TT, 160 (37%) had TT alone, 34 (8%) underwent CN followed by observation, and 67 (15%) received no treatment. After adjustments in Model 2, patients treated with TT alone demonstrated a worsened overall survival (OS) compared to those treated with CN + TT, HR 0.63 (95% CI: 0.19–2.04). (4) Conclusions: In this nationwide study, CN was associated with enhanced outcomes in carefully selected patients with primary mRCC. Further randomized trials are warranted.
]]>Cancers doi: 10.3390/cancers16061131
Authors: Han Zhang Paula M. Mañán-Mejías Hannah N. Miles Andrea A. Putnam Leonard R. MacGillivray William A. Ricke
The DEAD (Asp-Glu-Ala-Asp)-box helicase 3 X-linked (DDX3X) protein participates in many aspects of mRNA metabolism and stress granule (SG) formation. DDX3X has also been associated with signal transduction and cell cycle regulation that are important in maintaining cellular homeostasis. Malfunctions of DDX3X have been implicated in multiple cancers, including brain cancer, leukemia, prostate cancer, and head and neck cancer. Recently, literature has reported SG-associated cancer drug resistance, which correlates with a negative disease prognosis. Based on the connections between DDX3X, SG formation, and cancer pathology, targeting DDX3X may be a promising direction for cancer therapeutics development. In this review, we describe the biological functions of DDX3X in terms of mRNA metabolism, signal transduction, and cell cycle regulation. Furthermore, we summarize the contributions of DDX3X in SG formation and cellular stress adaptation. Finally, we discuss the relationships of DDX3X, SG, and cancer drug resistance, and discuss the current research progress of several DDX3X inhibitors for cancer treatment.
]]>Cancers doi: 10.3390/cancers16061130
Authors: Abhishek Mahajan Vatsal Kania Ujjwal Agarwal Renuka Ashtekar Shreya Shukla Vijay Maruti Patil Vanita Noronha Amit Joshi Nandini Menon Rajiv Kumar Kaushal Swapnil Rane Anuradha Chougule Suthirth Vaidya Krishna Kaluva Kumar Prabhash
Purpose: The authors aimed to develop and validate deep-learning-based radiogenomic (DLR) models and radiomic signatures to predict the EGFR mutation in patients with NSCLC, and to assess the semantic and clinical features that can contribute to detecting EGFR mutations. Methods: Using 990 patients from two NSCLC trials, we employed an end-to-end pipeline analyzing CT images without precise segmentation. Two 3D convolutional neural networks segmented lung masses and nodules. Results: The combined radiomics and DLR model achieved an AUC of 0.88 ± 0.03 in predicting EGFR mutation status, outperforming individual models. Semantic features further improved the model’s accuracy, with an AUC of 0.88 ± 0.05. CT semantic features that were found to be significantly associated with EGFR mutations were pure solid tumours with no associated ground glass component (p < 0.03), the absence of peripheral emphysema (p < 0.03), the presence of pleural retraction (p = 0.004), the presence of fissure attachment (p = 0.001), the presence of metastatic nodules in both the tumour-containing lobe (p = 0.001) and the non-tumour-containing lobe (p = 0.001), the presence of ipsilateral pleural effusion (p = 0.04), and average enhancement of the tumour mass above 54 HU (p < 0.001). Conclusions: This AI-based radiomics and DLR model demonstrated high accuracy in predicting EGFR mutation, serving as a non-invasive and user-friendly imaging biomarker for EGFR mutation status prediction.
]]>Cancers doi: 10.3390/cancers16061129
Authors: Gilles Houvenaeghel Marie Bannier Catherine Bouteille Camille Tallet Laura Sabiani Axelle Charavil Arthur Bertrand Aurore Van Troy Max Buttarelli Charlène Teyssandier Agnès Tallet Alexandre de Nonneville Monique Cohen
Introduction: Immediate breast reconstruction (IBR) techniques are rapidly evolving. We compared the results from a single-center implant IBR cohort between subpectoral and prepectoral implants with and without a mesh. Methods: We analyzed all complications and grade 2–3 complications, the implant loss rate, the surgery time, the length of stay (LOS), patient satisfaction, the interval time to adjuvant therapy and cost, with a comparison between subpectoral and prepectoral implant IBR. Results: Subpectoral implant IBR was carried out in 529 mastectomies (62.0%) and prepectoral in 324, with a significant increase in prepectoral placement in recent years. Mesh was used in 176 prepectoral placements (54.3%). Any grade of complication was reported in 147 mastectomies (17.2%), with a significantly higher rate for prepectoral implant IBR (p = 0.036). Regression analysis showed that prepectoral implant was not significantly associated with any grade of complication or with grade 2–3 complications. Prepectoral implant IBR was associated with a significantly shorter operative time and lower LOS. Grade 2–3 complications were significantly associated with lower satisfaction. Higher costs were significantly associated with the subpectoral placement and mesh. A complication rate predictive score identified five groups with a significant increase in grade 2–3 complications. Conclusions: Prepectoral-M-IBR increased over time with no difference in complication rates compared to subpectoral-M-IBR. Prepectoral implant placement can be considered a safe technique.
]]>Cancers doi: 10.3390/cancers16061128
Authors: Tomas Rendek Rami Saade Ondrej Pos Georgina Kolnikova Monika Urbanova Jaroslav Budis Luboslav Mihok Miroslav Tomas Tomas Szemes Vanda Repiska
Slovakia has one of the highest rates of colorectal cancer among the developed countries, ranking as the second highest in the incidence of this disease for men worldwide. Despite the significant burden on both quality of life and the healthcare system this disease imposes, data on molecular analysis of biomarkers in CRC-diagnosed patients is scarce. In our study, we analyzed confirmed CRC patients from the database of the National Cancer Institute (NCI) and evaluated the presence of 4 biomarkers in tumor tissues. Altogether, 83 FFPE tumor tissues from CRC patients listed in the NCI database were analyzed for microsatellite instability status, presence of BRAF and KRAS/NRAS mutations, and neoplastic cell percentage in tissue samples. We identified 4 MSI-high samples, 39 KRAS/NRAS mutations, and 5 BRAF p.V600E mutations, with one case of coexistence of all three markers in a single tumor sample. We also evaluated possible relationships between biomarkers, their coexistence, and the age and sex of the studied population.
]]>Cancers doi: 10.3390/cancers16061127
Authors: Fionán Donohoe Yvonne O’Meara Aidin Roberts Louise Comerford Ivaila Valcheva Una Kearns Marie Galligan Michaela J. Higgins Alasdair L. Henry Catherine M. Kelly Janice M. Walshe Martha Hickey Donal J. Brennan
Background: Vasomotor symptoms (VMSs) associated with menopause represent a significant challenge for many patients after cancer treatment, particularly if conventional menopausal hormone therapy (MHT) is contraindicated. Methods: The Menopause after Cancer (MAC) Study (NCT04766229) was a single-arm phase II trial examining the impact of a composite intervention consisting of (1) the use of non-hormonal pharmacotherapy to manage VMS, (2) digital cognitive behavioral therapy for insomnia (dCBT-I) using Sleepio (Big Health), (3) self-management strategies for VMS delivered via the myPatientSpace mobile application and (4) nomination of an additional support person/partner on quality of life (QoL) in women with moderate-to-severe VMS after cancer. The primary outcome was a change in cancer-specific global QoL assessed by the EORTC QLC C-30 v3 at 6 months. Secondary outcomes included the frequency of VMS, the bother/interference of VMS and insomnia symptoms. Results: In total, 204 women (82% previous breast cancer) with a median age of 49 years (range 28–66) were recruited. A total of 120 women completed the protocol. Global QoL scores increased from 62.2 (95%CI 58.6–65.4) to 70.4 (95%CI 67.1–73.8) at 6 months (p < 0.001) in the intention to treatment (ITT) cohort (n = 204) and from 62 (95%CI 58.6–65.4) to 70.4 (95%CI 67.1–73.8) at 6 months (p < 0.001) in the per-protocol (PP) cohort (n = 120). At least 50% reductions were noticed in the frequency of VMS as well as the degree of bother/interference of VMS at six months. The prevalence of insomnia reduced from 93.1% at the baseline to 45.2% at 6 months (p < 0.001). The Sleep Condition Indicator increased from 8.5 (SEM 0.4) to 17.3 (SEM 0.5) (p < 0.0005) in the ITT cohort and 7.9 (SEM 0.4) to 17.3 (SEM 0.5) (p < 0.001) in the PP cohort. Conclusions: A targeted composite intervention improves the quality of life for cancer patients with frequent and bothersome vasomotor symptoms with additional benefits on frequency, the bother/interference of VMS and insomnia symptoms.
]]>Cancers doi: 10.3390/cancers16061126
Authors: Yujia Pan Roza Cengiz Joost Kluiver Arjan Diepstra Anke Van den Berg
Classical Hodgkin lymphoma (cHL) is a hematological malignancy of B-cell origin. The tumor cells in cHL are referred to as Hodgkin and Reed–Sternberg (HRS) cells. This review provides an overview of the currently known miRNA–target gene interactions. In addition, we pinpointed other potential regulatory roles of microRNAs (miRNAs) by focusing on genes related to processes relevant for cHL pathogenesis, i.e., loss of B-cell phenotypes, immune evasion, and growth support. A cHL-specific miRNA signature was generated based on the available profiling studies. The interactions relevant for cHL were extracted by comprehensively reviewing the existing studies on validated miRNA–target gene interactions. The miRNAs with potential critical roles included miR-155-5p, miR-148a-3p, miR-181a-5p, miR-200, miR-23a-3p, miR-125a/b, miR-130a-3p, miR-138, and miR-143-3p, which target, amongst others, PU.1, ETS1, HLA-I, PD-L1, and NF-κB component genes. Overall, we provide a comprehensive perspective on the relevant miRNA–target gene interactions which can also serve as a foundation for future functional studies into the specific roles of the selected miRNAs in cHL pathogenesis.
]]>Cancers doi: 10.3390/cancers16061125
Authors: Yuki Kotani Yoshinori Imura Sho Nakai Ryota Chijimatsu Haruna Takami Akitomo Inoue Hirokazu Mae Satoshi Takenaka Hidetatsu Outani Seiji Okada
Synovial sarcoma (SS), a rare subtype of soft-tissue sarcoma distinguished by expression of the fusion gene SS18-SSX, predominantly affects the extremities of young patients. Existing anticancer drugs have limited efficacy against this malignancy, necessitating the development of innovative therapeutic approaches. Given the established role of SS18-SSX in epigenetic regulation, we focused on bromodomain and extra-terminal domain protein (BET) inhibitors and epigenetic agents. Our investigation of the BET inhibitor ABBV-075 revealed its pronounced antitumor effects, inducing G1-phase cell-cycle arrest and apoptosis, in four SS cell lines. Notably, BET inhibitors exhibited regulatory control over crucial cell-cycle regulators, such as MYC, p21, CDK4, and CDK6. Additionally, RNA sequencing findings across the four cell lines revealed the significance of fluctuating BCL2 family protein expression during apoptotic induction. Notably, variations in the expression ratio of the anti-apoptotic factor BCLxL and the pro-apoptotic factor BIM may underlie susceptibility to ABBV-075. Additionally, knockdown of SS18-SSX, which upregulates BCL2, reduced the sensitivity to ABBV-075. These findings suggest the potential utility of BET inhibitors targeting the SS18-SSX-regulated intrinsic apoptotic pathway as a promising therapeutic strategy for SS.
]]>Cancers doi: 10.3390/cancers16061124
Authors: Jacek Calik Katarzyna Calik Natalia Sauer Bogucki Zdzisław Piotr Giedziun Jacek Mackiewicz Marek Murawski Piotr Dzięgiel
This study investigates the impact of bisphosphonate therapy on the stomatognathic system in 80 patients with cancer of the breast and prostate with bone metastases. Bisphosphonates are integral for managing skeletal complications in these malignancies but are associated with bisphosphonate-related osteonecrosis of the jaw (BRONJ), affecting 0.8–18.5% of patients. BRONJ manifests with pain, neuropathy, tissue swelling, mucosal ulceration, tooth mobility, and abscesses, yet its pathogenesis remains elusive, complicating risk prediction. The research employed comprehensive dental and radiological evaluations. Dental status was assessed using DMFT and OHI-S indices, Eichner’s classification, and clinical periodontal measurements like the pocket depth (PD), clinical attachment loss (CAL), and modified Sulcus Bleeding Index (mSBI). A radiological analysis included panoramic X-rays for radiomorphometric measurements and TMJ lateral radiographs. Results indicated a significant decline in oral hygiene in patients with cancer after bisphosphonate therapy, marked by increased DMFT and OHI-S scores. Periodontal health also showed deterioration, with increased PD and CAL readings. The incidence of BRONJ symptoms was noted, although exact figures are not quantified in this abstract. The study also revealed changes in radiomorphometric parameters, suggesting bisphosphonates’ impact on bone density and structure. No substantial alterations were observed in TMJ function, indicating a need for extended observation to understand bisphosphonates’ long-term effects on the stomatognathic system. These findings highlight the importance of continuous dental monitoring and prophylaxis in patients undergoing bisphosphonate therapy. Implementing meticulous oral care protocols is essential for mitigating BRONJ risk and managing the complex oral health challenges in patients with cancer.
]]>Cancers doi: 10.3390/cancers16061123
Authors: Natalia Khromova Maria Vasileva Vera Dugina Dmitry Kudlay Peter Chumakov Sergei Boichuk Pavel Kopnin
Cancer cell aggressiveness, marked by actin cytoskeleton reconfiguration critical for metastasis, may result from an imbalanced ratio favoring γ-actin. Dysfunctional p53 emerges as a key regulator of invasiveness and migration in various cancer cells, both in vitro and in vivo. P53 inactivation (via mutants R175H, R248W, R273H, or TP53 repression) significantly enhanced the migration, invasion, and proliferation of human lung adenocarcinoma A549 cells in vitro and in vivo, facilitating intrapulmonary xenograft metastasis in athymic mice. Conversely, wild-type TP53 (TP53 WT) overexpression in p53-deficient non-small- cell lung cancer (NSCLC) H1299 cells substantially reduced proliferation and migration in vitro, effectively curbing orthotopic tumorigenicity and impeding in vivo metastasis. These alterations in cell motility were closely associated with actin cytoskeleton restructuring, favoring γ-actin, and coincided with ERK1/2-mediated signaling activation, unveiling an innovative regulatory mechanism in malignancy progression. Cancer cell aggressiveness, driven by actin cytoskeleton reorganization and a shift towards γ-actin predominance, may be regulated by p53 dysfunction, thereby providing novel insight into tumor progression mechanisms.
]]>Cancers doi: 10.3390/cancers16061122
Authors: Francesco Dondi Alessandro Antonelli Nazareno Suardi Giorgio Treglia Francesco Bertagna
Background: active surveillance (AS) is a suitable strategy for patients with prostate cancer (PCa). Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging is an established tool used to assess PCa. The aim of this review was to evaluate the role of PSMA imaging to guide correct risk-based classification and the AS approach in PCa patients. Methods: The Scopus, Embase, Web of Science, Cochrane Library, and PubMed/MEDLINE databases were screened to find relevant published articles. Results: 1774 articles were revealed with the literature search. A total of 1764 articles were excluded after applying exclusion criteria (data not within the field of interest, preclinical papers, conference proceedings, reviews, or editorials). Ten studies were finally included in the review, revealing that PSMA PET could have the ability to guide risk-based classification of PCa and the choice of AS, and to guide the execution of biopsies for the research of high-grade PCa, therefore precluding AS. Conclusion: this systematic review underlined a possible role of PSMA PET imaging in patients with PCa by correctly re-classifying them on the basis of their risk and guiding AS.
]]>Cancers doi: 10.3390/cancers16061121
Authors: Nikolas Tauber Christoph Cirkel Anna Claussen Franziska Fick Emmanuel Kontomanolis Natalia Krawczyk Achim Rody Maggie Banys-Paluchowski
De-escalation is currently taking place in both the surgical and systemic treatment of breast cancer. The introduction of trastuzumab, the first monoclonal antibody against the HER2 receptor, over 20 years ago was a milestone in the treatment of HER2-positive breast cancer and marked the beginning of a new era in targeted tumor therapy. In the sense of de-escalation, omitting non-targeted cytotoxic chemotherapy altogether is often hailed as the ultimate goal of oncological research. Especially in cases of small, node-negative, HER2-positive early breast cancer, it remains a challenge for clinicians to establish the safest and most efficient treatment plan while considering the significant potential for toxic side effects associated with chemotherapy and HER2-targeted therapy, and the generally excellent prognosis. In this context, several ongoing studies are currently assessing chemotherapy-free regimens as part of strategies aimed at de-escalating therapy in the field of HER2-positive early breast cancer. Despite the promising early results of these studies, the combination of anti-HER2 treatment with a chemotherapy backbone remains the standard of care.
]]>Cancers doi: 10.3390/cancers16061119
Authors: Sounak Rana Chen Ee Low Manasadevi Karthikeyan Mark Jean Aan Koh Joanne Ngeow Jianbang Chiang
Background: Neurofibromatosis Type 1 is an autosomal dominant tumour-predisposition condition commonly diagnosed in childhood and fully penetrant by adulthood. Long-term monitoring through imaging is inconsistent and varies between high- and low-income countries. Implementation of a clinical practice guideline through a multidisciplinary clinic is instrumental to the care of adult Neurofibromatosis Type 1 patients. We aim to systematically review international diagnostic modalities and strategies to evaluate any association between a country’s socioeconomic status and diagnostic modalities or strategies used for Neurofibromatosis Type 1 patients. Methods: We searched PubMed, Embase, Web of Science, and Cochrane. Relevant clinical information on the surveillance of adult Neurofibromatosis Type 1 patients worldwide was reviewed, extracted, and synthesised. Results: We identified 51 papers reporting on 7724 individuals. Multiple imaging modalities are actively employed in high-income and upper-middle-income countries for surveying adult Neurofibromatosis Type 1 patients. We did not find any relevant papers from low- and middle-income countries. Conclusions: This systematic review suggests that there is robust data on diagnostic modalities for adult Neurofibromatosis Type 1 patients in high-income countries, but not for low- and middle-income countries. There is a lack of data on consolidated diagnostic strategies from both high- and low-income countries. Efforts should be made to publish data on usual clinical practice in low- and middle-income countries to develop clinical practice guidelines describing best medical practice to fit a local context.
]]>Cancers doi: 10.3390/cancers16061120
Authors: Aleksandra Dzieniszewska Piotr Garbat Ryszard Piramidowicz
Skin lesion segmentation plays a key role in the diagnosis of skin cancer; it can be a component in both traditional algorithms and end-to-end approaches. The quality of segmentation directly impacts the accuracy of classification; however, attaining optimal segmentation necessitates a substantial amount of labeled data. Semi-supervised learning allows for employing unlabeled data to enhance the results of the machine learning model. In the case of medical image segmentation, acquiring detailed annotation is time-consuming and costly and requires skilled individuals so the utilization of unlabeled data allows for a significant mitigation of manual segmentation efforts. This study proposes a novel approach to semi-supervised skin lesion segmentation using self-training with a Noisy Student. This approach allows for utilizing large amounts of available unlabeled images. It consists of four steps—first, training the teacher model on labeled data only, then generating pseudo-labels with the teacher model, training the student model on both labeled and pseudo-labeled data, and lastly, training the student* model on pseudo-labels generated with the student model. In this work, we implemented DeepLabV3 architecture as both teacher and student models. As a final result, we achieved a mIoU of 88.0% on the ISIC 2018 dataset and a mIoU of 87.54% on the PH2 dataset. The evaluation of the proposed approach shows that Noisy Student training improves the segmentation performance of neural networks in a skin lesion segmentation task while using only small amounts of labeled data.
]]>Cancers doi: 10.3390/cancers16061118
Authors: Ningjun Duan Yijia Hua Xueqi Yan Yaozhou He Tianyu Zeng Jue Gong Ziyi Fu Wei Li Yongmei Yin
tRNA-derived fragments (tRFs) play crucial roles in cancer progression. Among them, tRF-27 has been identified as a key factor in promoting naïve trastuzumab resistance in HER2-positive breast cancer. However, the origin of tRF-27 remains uncertain. In this study, we propose that the upregulated expression of specific cysteine tRNAs may lead to the increased accumulation of tRF-27 in trastuzumab-resistant JIMT1 cells. Mechanistically, the reduced inhibitory H3K27me3 modification at the promoter regions of tRF-27-related tRNA genes in JIMT1 cells, potentially resulting from decreased EZH2 and increased KDM6A activity, may be a critical factor stimulating the transcriptional activity of these tRNA genes. Our research offers fresh insights into the mechanisms underlying elevated tRF-27 levels in trastuzumab-resistant breast cancer cells and suggests potential strategies to mitigate trastuzumab resistance in clinical treatments.
]]>Cancers doi: 10.3390/cancers16061117
Authors: Razan Mansour Hikmat Abdel-Razeq Maysa Al-Hussaini Omar Shamieh Akram Al-Ibraheem Amal Al-Omari Asem Mansour
This narrative review explores the multifaceted barriers hindering access to quality cancer care in Jordan. A literature-based narrative review was undertaken to explore the current identified barriers to cancer care in Jordan. Four databases were searched using relevant keywords to identify key insights on barriers and proposed solutions. Key challenges and potential solutions were identified based on evidence from studies, reports, and initiatives. Medical services and infrastructure exhibit centralized disparities, impacting rural and underserved areas. Human resources shortages, geopolitical instability, and quality management issues pose significant challenges. Public awareness campaigns face hurdles in addressing the tobacco epidemic and late-stage diagnosis. Socioeconomic disparities, particularly in health insurance and urban–rural divides, further compound barriers. Refugees encounter distinct challenges, including late-stage diagnosis, financial barriers, and psychological distress. Despite multiple challenges, Jordan presents a model for regional development and health equity. This study not only contributes to improving cancer care in Jordan but also offers a roadmap for policymakers, healthcare practitioners, and researchers in similar contexts globally. Government initiatives, financial aspects, and proposed policy measures are examined as potential solutions. Recommendations include coordinated prevention strategies, enhanced screening uptake, training programs, the equitable distribution of facilities, and policy directives aligned with global commitments. The role of digital technologies, telemedicine, and community engagement models is emphasized.
]]>Cancers doi: 10.3390/cancers16061116
Authors: Wancheng Guo Christopher Strouse David Mery Eric R. Siegel Manit N. Munshi Timothy Cody Ashby Yan Cheng Fumou Sun Visanu Wanchai Zijun Zhang Clyde Bailey Daisy V. Alapat Hongling Peng Samer Al Hadidi Sharmilan Thanendrarajan Carolina Schinke Maurizio Zangari Frits van Rhee Guido Tricot John D. Shaughnessy Fenghuang Zhan
Autologous stem cell transplantation (ASCT) has been a mainstay in myeloma treatment for over three decades, but patient prognosis post-ASCT varies significantly. In a retrospective study of 5259 patients with multiple myeloma (MM) at the University of Arkansas for Medical Sciences undergoing ASCT with a median 57-month follow-up, we divided the dataset into training (70%) and validation (30%) subsets. Employing univariable and multivariable Cox analyses, we systematically assessed 29 clinical variables, identifying crucial adverse prognostic factors, such as extended duration between MM diagnosis and ASCT, elevated serum ferritin, and reduced transferrin levels. These factors could enhance existing prognostic models. Additionally, we pinpointed significant poor prognosis markers like high serum calcium and low platelet counts, though they are applicable to a smaller patient population. Utilizing seven easily accessible high-risk variables, we devised a four-stage system (ATM4S) with primary stage borders determined through K-adaptive partitioning. This staging system underwent validation in both the training dataset and an independent cohort of 514 ASCT-treated MM patients from the University of Iowa. We also explored cytogenetic risk factors within this staging system, emphasizing its potential clinical utility for refining prognostic assessments and guiding personalized treatment approaches.
]]>Cancers doi: 10.3390/cancers16061115
Authors: Savio Domenico Pandolfo Simone Cilio Achille Aveta Zhenjie Wu Clara Cerrato Luigi Napolitano Francesco Lasorsa Giuseppe Lucarelli Paolo Verze Salvatore Siracusano Carmelo Quattrone Matteo Ferro Eugenio Bologna Riccardo Campi Francesco Del Giudice Riccardo Bertolo Daniele Amparore Sara Palumbo Celeste Manfredi Riccardo Autorino
Background: Upper tract urothelial carcinoma (UTUC) is a rare disease with a potentially dismal prognosis. We systematically compared international guidelines on UTUC to analyze similitudes and differences among them. Methods: We conducted a search on MEDLINE/PubMed for guidelines related to UTUC from 2010 to the present. In addition, we manually explored the websites of urological and oncological societies and journals to identify pertinent guidelines. We also assessed recommendations from the International Bladder Cancer Network, the Canadian Urological Association, the European Society for Medical Oncology, and the International Consultation on Bladder Cancer, considering their expertise and experience in the field. Results: Among all the sources, only the American Urologist Association (AUA), European Association of Urology (EAU), and the National Comprehensive Cancer Network (NCCN) guidelines specifically report data on diagnosis, treatment, and follow-up of UTUC. Current analysis reveals several differences between all three sources on diagnostic work-up, patient management, and follow-up. Among all, AUA and EAU guidelines show more detailed indications. Conclusions: Despite the growing incidence of UTUC, only AUA, EAU, and NCCN guidelines deal with this cancer. Our research depicted high variability in reporting recommendations and opinions. In this regard, we encourage further higher-quality research to gain evidence creating higher grade consensus between guidelines.
]]>Cancers doi: 10.3390/cancers16061114
Authors: Miguel Suárez Sergio Gil-Rojas Pablo Martínez-Blanco Ana M. Torres Antonio Ramón Pilar Blasco-Segura Miguel Torralba Jorge Mateo
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, with an incidence that is exponentially increasing. Hepatocellular carcinoma (HCC) is the most frequent primary tumor. There is an increasing relationship between these entities due to the potential risk of developing NAFLD-related HCC and the prevalence of NAFLD. There is limited evidence regarding prognostic factors at the diagnosis of HCC. This study compares the prognosis of HCC in patients with NAFLD against other etiologies. It also evaluates the prognostic factors at the diagnosis of these patients. For this purpose, a multicenter retrospective study was conducted involving a total of 191 patients. Out of the total, 29 presented NAFLD-related HCC. The extreme gradient boosting (XGB) method was employed to develop the reference predictive model. Patients with NAFLD-related HCC showed a worse prognosis compared to other potential etiologies of HCC. Among the variables with the worst prognosis, alcohol consumption in NAFLD patients had the greatest weight within the developed predictive model. In comparison with other studied methods, XGB obtained the highest values for the analyzed metrics. In conclusion, patients with NAFLD-related HCC and alcohol consumption, obesity, cirrhosis, and clinically significant portal hypertension (CSPH) exhibited a worse prognosis than other patients. XGB developed a highly efficient predictive model for the assessment of these patients.
]]>Cancers doi: 10.3390/cancers16061113
Authors: Firas Batrash Adnan Shaik Rayaan Rauf Mahmoud Kutmah Jun Zhang
The intricate interplay between inflammatory processes and the tumor microenvironment (TME) in lung cancer has garnered increasing attention due to its implications for both oncogenesis and therapeutic strategies. In this review, we explore recent advances in understanding the paracrine regulation and immune system pathways within the inflammatory TME of lung cancer. We delve into the molecular mechanisms underpinning oncogenesis, highlighting the role of immune cell populations, cancer-associated fibroblasts, and endothelial cells, as well as their interactions through immune system pathways regulated in a paracrine pattern. Additionally, we discuss emerging immunotherapeutic strategies with a specific focus on the potential of leveraging the inflammatory TME through these pathways to enhance treatment efficacy in lung cancer.
]]>Cancers doi: 10.3390/cancers16061112
Authors: Sohaib M. Al-Khatib Ayah N. Al-Bzour Mohammad N. Al-Majali Laila M. Sa’d Joud A. Alramadneh Nour R. Othman Abdel-Hameed Al-Mistarehi Safwan Alomari
Serpins are serine proteinase inhibitors, with several serpins being overexpressed in cancer cells. Thus, we aim to analyze the single-nucleotide polymorphism (SNP) of Serpinb11 and its association with GBM survival. A cohort of 63 GBM patients recruited from King Abdullah University Hospital in Jordan underwent polymorphism analysis and overall survival (OS) assessments. The Cancer Genome Atlas (GBM) cohort was useful for validation. We constructed a risk score using the principal component analysis for the following Serpin genes: Serpinb3, Serpinb5, Serpinb6, Serpinb11, and Serpinb12, and patients were grouped into high- vs. low-risk groups based on the median cutoff. Univariable Cox models were used to study the survival outcomes. We identified a significant association between rs4940595 and survival. In the TCGA cohort, Serpinb3 alterations showed worse OS. Univariable Cox showed worse PFS outcomes with higher SERPINB5 and SERPINB6 expression. A Serpin B 5-gene risk score showed a trend towards worse PFS in the high-risk group. Upregulated DEGs showed GO enrichment in cytokine regulation and production, positive regulation of leukocyte activation, and the MAPK cascade. The high-risk group showed a significantly higher infiltration of M2 macrophages and activated mast cells. Our findings showed a significant role of the Serpin B family in GBM survival in the Jordanian population.
]]>Cancers doi: 10.3390/cancers16061110
Authors: Gloria Lin David M. Hein Po-Hong Liu Amit G. Singal Nina N. Sanford
Objectives: The effectiveness of colonoscopy to reduce colorectal cancer (CRC) mortality is extrapolated from cohort studies in the absence of randomized controlled trial (RCT) data, whereas flexible sigmoidoscopy is supported by RCT data and may be easier to implement in practice. We characterized the anatomic distribution of CRC to determine the proportion that is visible with sigmoidoscopy. Methods: Patients with a primary diagnosis of colorectal adenocarcinoma were identified in the Surveillance, Epidemiology, and End Results program (2000–2020). Tumors from the rectum to the descending colon were categorized as visible by sigmoidoscopy, whereas more proximal tumors required colonoscopy. Differential prognosis between tumor locations, stratified by age groups and stage, was assessed using the overall restricted mean survival time (RMST) at 2, 5, and 10 years. Results: Among 309,466 patients, 58% had tumors visible by sigmoidoscopy, including 73% of those under age 50 (OR 2.10, 95% CI 2.03–2.16 age < 45, OR 2.20, 95% CI 2.13–2.27 age 45–49 versus age ≥ 50). Male sex (OR 1.54, 95% CI 1.51–1.56) and Asian or Pacific Islander race (OR 1.60, 95% CI 1.56–1.64) were also positively associated with tumors visualizable by sigmoidoscopy. Across age groups, for local disease, RMST was comparable for tumors visible versus not visible on sigmoidoscopy. For regional and metastatic cancer, patients with tumors visible by sigmoidoscopy had improved RMST versus those with more proximal tumors. Conclusions: 58% of CRC arises in locations visible by flexible sigmoidoscopy. Flexible sigmoidoscopy should be considered as a viable option for CRC screening, particularly in younger patients unwilling or unable to undergo colonoscopy.
]]>Cancers doi: 10.3390/cancers16061111
Authors: Ting-Shen Lin Ci-Wen Luo Tsai-Ling Hsieh Frank Cheau-Feng Lin Stella Chin-Shaw Tsai
Trismus, defined as restricted mouth opening, is a common complication among Taiwanese oral cancer patients, especially those who chew betel quid. However, the impact of trismus on survival outcomes in oral cancer patients undergoing transoral robotic surgery (TORS) is unclear. This study aimed to investigate the associations between trismus and surgical outcomes in Taiwanese male oral cancer patients treated with TORS. We conducted a retrospective propensity score-matched cohort study of 40 Taiwanese male oral cancer patients who underwent TORS between 2016 and 2022. Overall, 20 patients with trismus were matched to 20 patients without trismus. TORS achieved similar operative and short-term clinical outcomes in trismus patients to non-trismus patients. There were no significant differences between groups in operation time, blood loss, margin status, flap reconstruction rates, duration of nasogastric tube feeding, or length of hospital stay. Kaplan–Meier and Cox proportional hazard regression analyses were performed to compare overall survival (OS) and disease-free survival (DFS) between the two groups. The overall survival (OS) rate at three years was significantly lower in patients with trismus than those without trismus (27.1% vs. 95.0%, log-rank p = 0.02). However, there was no significant difference in disease-free survival (DFS) rates between the trismus and non-trismus groups (36.6% vs. 62.7%, log-rank p = 0.87). After adjusting for confounders, trismus was independently associated with a 13-fold increased risk of mortality (adjusted HR 12.87, 95% CI 1.55–106.50, p < 0.05). In conclusion, trismus appears to be an independent prognostic factor for reduced long-term OS in Taiwanese male oral cancer patients undergoing TORS, though short-term surgical outcomes were non-inferior in the trismus patients. Further research is warranted to clarify the mechanisms linking trismus and survival in this population.
]]>Cancers doi: 10.3390/cancers16061109
Authors: Evangelos Tagkalos Peter Grimminger Xing Gao Chien-Hung Chiu Eren Uzun Hauke Lang Yu-Wen Wen Yin-Kai Chao
Purpose: The textbook outcome (TBO), a multidimensional indicator that reflects an optimal perioperative course, has emerged as a significant prognostic variable in surgical oncology. Our study aimed to assess the occurrence and determinants of TBO following minimally invasive esophagectomy (MIE) for cancer. Methods: A total of 945 patients who had undergone MIE at two high-volume centers between 2008 and 2022 were analyzed. Multivariable logistic regression analysis was applied to identify the independent predictors of TBO. The potential selection bias associated with choosing between different MIE techniques—namely, robotic esophagectomy (RE) and video-assisted thoracoscopic esophagectomy (VATE)—was addressed by applying inverse probability of treatment weighting (IPTW). Results: TBO was realized in 46.6% of cases (n = 440), correlating with markedly better overall and disease-free survival. Multivariable analysis showed that treatment with RE (odds ratio (OR) = 1.527; 95% confidence interval (CI) = 1.149–2.028) was associated with a higher likelihood of achieving TBO, whereas a Charlson Comorbidity Index (CCI) of 2 or higher showed an opposite association (CCI2: OR = 0.687, 95% CI = 0.483–0.977; CCI ≥ 3: OR = 0.604, 95% CI = 0.399–0.915). The advantage of RE in attaining a higher rate of TBO, compared to VATE, remained statistically significant after applying IPTW, with rates of 53.3% for RE and 42.2% for VATE. Notably, RE contributed to a greater probability of thorough lymph node dissection, resection with negative margins, and the avoidance of major complications. Conclusion: TBO was realized in 46.6% of the patients who underwent MIE for cancer. Patients with a lower CCI and those who received RE were more likely to achieve TBO.
]]>Cancers doi: 10.3390/cancers16061108
Authors: Gniewko Więckiewicz Sophie Weber Iga Florczyk Piotr Gorczyca
This comprehensive review article examines the complex overlap of affective disorders, psychoses, addictions, anxieties, post-traumatic stress disorder, and somatic symptom disorder in the context of cancer patients, and highlights the intricate interplay between psychiatric and oncological diagnoses. Based on extensive literature, it highlights the profound socioeconomic burdens that result from the coexistence of these disorders. The analysis includes the increased healthcare costs, impaired adherence to treatment, and reduced quality of life for individuals struggling with the co-occurrence of psychiatric and cancer-related problems. By synthesizing the available data through a narrative inquiry, the report aims to provide a nuanced understanding of the multiple socioeconomic challenges faced by this vulnerable patient population. The synthesis of information provides valuable insights for healthcare professionals, policymakers, and researchers alike. The aim is to promote the development of more effective and integrated care strategies tailored to the specific needs of people navigating the complicated environment of psychiatric and cancer diagnoses. Ultimately, this review should enable progress in the provision of holistic, patient-centered care for this complex intersection of health conditions.
]]>Cancers doi: 10.3390/cancers16061107
Authors: Tommaso Bianchi Tommaso Grassi Giampaolo Di Martino Serena Negri Gaetano Trezzi Robert Fruscio Fabio Landoni
The implementation of sentinel lymph node (SLN) biopsy is changing the scenario in the surgical treatment of early-stage cervical cancer, and the oncologic safety of replacing bilateral pelvic lymphadenectomy with SLN biopsy is currently under investigation. Part of the undisputed value of SLN biopsy is its diagnostic accuracy in detecting low-volume metastases (LVM) via pathologic ultrastaging. In early-stage cervical cancer, the reported incidence of LVM ranges from 4 to 20%. The prognostic impact and the role of adjuvant treatment in patients with LVM is still unclear. Some non-prespecified analyses in prospective studies showed no impact on the oncologic outcomes compared to node-negative disease. However, the heterogeneity of the studies, the differences in the disease stage and the use of adjuvant treatment, and the concomitant pelvic lymphadenectomy (PLND) make reaching any conclusions on this topic hard. Current guidelines suggest considering micrometastases (MIC) as a node-positive disease, while considering isolated tumor cells (ITC) as a node-negative disease with a low level of evidence. This review aims to highlight the unanswered questions about the definition, identification, and prognostic and therapeutic roles of LVM and to underline the present and future challenges we are facing. We hope that this review will guide further research, giving robust evidence on LVM and their impacts on clinical practice.
]]>Cancers doi: 10.3390/cancers16061106
Authors: Nektarios I. Koufopoulos Abraham Pouliakis Menelaos G. Samaras Christakis Kotanidis Ioannis Boutas Adamantia Kontogeorgi Dionysios Dimas Kyparissia Sitara Andriani Zacharatou Argyro-Ioanna Ieronimaki Aris Spathis Danai Leventakou Magda Zanelli Ioannis S. Pateras Ioannis G. Panayiotides Andrea Palicelli John Syrios
Background: Malignant Brenner tumors are rare ovarian tumors, accounting for less than 1% of malignant ovarian neoplasms. The aim of this manuscript is to systematically review the current literature concerning malignant Brenner tumors. Methods: We searched three medical databases (PubMed, Scopus, and Web of Science) for relevant articles published until 15 September 2023. Results: After applying inclusion and exclusion criteria, 48 manuscripts describing 115 cases were included in this study from the English literature. Conclusions: We analyzed the demographic, clinical, pathological, and oncological characteristics of 115 patients with malignant Brenner tumors. The statistical analysis showed that recurrence was marginally statistically significantly related to tumor stage and was more common in patients with ascites and in women with abnormal CA-125 levels; patients that were treated with lymphadenectomy had better disease-specific survival.
]]>Cancers doi: 10.3390/cancers16061105
Authors: Javier Burgos-Burgos Víctor Vega David Macias-Verde Virginia Gómez Elena Vicente Carmen Murias Carlos Santana Pedro C. Lara
Background: The current standard of local treatment for patients with localized breast cancer (BC) includes whole breast irradiation (WBI) after breast-conserving surgery (BCS). Ultrahypofractionated WBI schemes (1-week treatment) were shown not to be inferior to the standard WBI. Tumor bed boost using photon intraoperative radiotherapy (IORT) is safe and feasible in combination with standard WBI. The aim of the present study is to assess, for the first time, the feasibility and safety of combining photon IORT with ultrahypofractionated WBI. Methods: Patients diagnosed with low-risk early BC candidates for BCS were included in this prospective study. IORT was administered at a dose of 20 Gy to the surface’s applicator, and WBI was administered 3–5 weeks after surgery at a total dose of 26 Gy in five consecutive days. Results: From July 2020 to December 2022, seventy-two patients diagnosed with low-risk early BC and treated in our institution were included in this prospective study. All patients completed the proposed treatment, and no severe acute or late grade 3 toxicity was observed 3 and 12 months after WBI, respectively. Conclusions: Our results confirm for the first time that the combination of ultrafractionation WBI and photon-IORT after BCS is a feasible and safe option in patients with early BC.
]]>Cancers doi: 10.3390/cancers16061104
Authors: Nivedhitha Mohan Roderick H. Dashwood Praveen Rajendran
Epigenetic ‘reader’ proteins, which have evolved to interact with specific chromatin modifications, play pivotal roles in gene regulation. There is growing interest in the alternative splicing mechanisms that affect the functionality of such epigenetic readers in cancer etiology. The current review considers how deregulation of epigenetic processes and alternative splicing events contribute to pathophysiology. An A–Z guide of epigenetic readers is provided, delineating the antagonistic ‘yin-yang’ roles of full-length versus spliced isoforms, where this is known from the literature. The examples discussed underscore the key contributions of epigenetic readers in transcriptional regulation, early development, and cancer. Clinical implications are considered, offering insights into precision oncology and targeted therapies focused on epigenetic readers that have undergone alternative splicing events during disease pathogenesis. This review underscores the fundamental importance of alternative splicing events in the context of epigenetic readers while emphasizing the critical need for improved understanding of functional diversity, regulatory mechanisms, and future therapeutic potential.
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