Cancers

14 pages, 1166 KiB

Open AccessArticle

Dosimetric and Clinical Prognostic Factors in Single-Isocenter Linac-Based Stereotactic Radiotherapy for Brain Metastases

by Valeria Faccenda, Riccardo Ray Colciago, Sofia Paola Bianchi, Elena De Ponti, Denis Panizza and Stefano Arcangeli

Cancers 2024, 16(18), 3243; https://doi.org/10.3390/cancers16183243 - 23 Sep 2024

Viewed by 739

Abstract

Background/Objectives: To report on predictive factors in Linac-based SRT for single and multiple BM. Methods: Consecutive patients receiving either one or three fractions of single-isocenter coplanar VMAT SRT were retrospectively included. The GTV-PTV margin was 1–2 mm. The delivered target dose was estimated [...] Read more.

Background/Objectives: To report on predictive factors in Linac-based SRT for single and multiple BM. Methods: Consecutive patients receiving either one or three fractions of single-isocenter coplanar VMAT SRT were retrospectively included. The GTV-PTV margin was 1–2 mm. The delivered target dose was estimated by recalculating the original plans on roto-translated CT according to errors recorded by post-treatment CBCT. The Kaplan–Meier method estimated local progression-free survival (LPFS), intracranial progression-free survival (IPFS), and overall survival (OS). Log-rank and Wilcoxon–Mann–Whitney tests evaluated inter-group differences, whereas Cox regression analysis assessed prognostic factors. Results: Fifty females and fifty males, with a median age of 69 years, received 107 SRTs. A total of 213 BM (range, 1–10 per treatment) with a median volume of 0.22 cc were irradiated with a median minimum BED of 59.5 Gy. The median delivered GTV D95 reduction was −0.3%. The median follow-up was 11 months. Nineteen LP events and a 1-year LC rate of 90.1% were observed. The GTV coverage did not correlate with LC, while the GTV volume was a risk factor for LP, with the 1-year rate dropping to 73% for volumes ≥ 0.88 cc. The median LPFS, IPFS, and OS were 6, 5, and 7 months, respectively. Multivariate analysis showed that patients with melanoma histology and those receiving a second or subsequent systemic therapy line had the worst outcomes, whereas patients with adenocarcinoma histology and mutations showed better results. Conclusions: The accuracy and efficacy of the Linac-based SRT approach for BM were confirmed, but the dose distribution alone failed to predict the treatment response, suggesting that other factors must be considered to maximize SRT outcomes. Full article

(This article belongs to the Special Issue Stereotactic Radiotherapy in Tumor Ablation (Volume II))

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10 pages, 458 KiB

Open AccessArticle

Optimizing the Sensitivity of a Pelvic Sentinel Node Algorithm Requires a Hybrid Algorithm Combining Indocyanine Green Based Mapping and the Removal of Non-Mapped Nodes at Defined Anatomic Positions

by Michele Bollino, Barbara Geppert, Petur Reynisson, Celine Lönnerfors and Jan Persson

Cancers 2024, 16(18), 3242; https://doi.org/10.3390/cancers16183242 - 23 Sep 2024

Viewed by 500

Abstract

Aim of the study: to investigate the incidence of non-mapped isolated metastatic pelvic lymph nodes at pre-defined anatomical positions. Patients and Methods: Between June 2019 and January 2024, women with uterine-confined endometrial cancer (EC) deemed suitable for robotic surgery and the detection of [...] Read more.

Aim of the study: to investigate the incidence of non-mapped isolated metastatic pelvic lymph nodes at pre-defined anatomical positions. Patients and Methods: Between June 2019 and January 2024, women with uterine-confined endometrial cancer (EC) deemed suitable for robotic surgery and the detection of pelvic sentinel nodes (SLNs) were included. An anatomically based, published algorithm utilizing indocyanine green (ICG) as a tracer was adhered to. In women where no ICG mapping occurred in either the proximal obturator and/or the interiliac positions, defined as “typical positions”, those nodes were removed and designated as “SLN anatomy”. Ultrastaging and immunohistochemistry were applied to all SLNs. The proportion of isolated metastatic “SLN anatomy” was evaluated. Results: A non-mapping of either the obturator or interiliac area occurred in 180 of the 620 women (29%). In total, 114 women (18.4%) were node-positive and five of these women (4.3%) had isolated metastases in an “SLN anatomy”, suggesting a similar lower sensitivity of the ICG-only algorithm. Conclusion: In an optimized SLN algorithm for endometrial cancer, to avoid undetected nodal metastases in 4.3% of node-positive women, if mapping fails in either the proximal obturator or interiliac area, nodes should be removed from those defined anatomic positions, despite mapping at other positions. Full article

(This article belongs to the Special Issue Unlocking Precision and Minimizing Morbidity: Sentinel Lymph Node Mapping in Gynecological Cancer)

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18 pages, 4885 KiB

Open AccessArticle

Induction of Invasive Basal Phenotype in Triple-Negative Breast Cancers by Long Noncoding RNA BORG

by Farshad Niazi, Kimberly A. Parker, Sara J. Mason, Salendra Singh, William P. Schiemann and Saba Valadkhan

Cancers 2024, 16(18), 3241; https://doi.org/10.3390/cancers16183241 - 23 Sep 2024

Viewed by 591

Abstract

Background/Objectives: Long noncoding RNAs (lncRNAs) are known to play key roles in breast cancers; however, detailed mechanistic studies of lncRNA function have not been conducted in large cohorts of breast cancer tumors, nor has inter-donor and inter-subtype variability been taken into consideration for [...] Read more.

Background/Objectives: Long noncoding RNAs (lncRNAs) are known to play key roles in breast cancers; however, detailed mechanistic studies of lncRNA function have not been conducted in large cohorts of breast cancer tumors, nor has inter-donor and inter-subtype variability been taken into consideration for these analyses. Here we provide the first identification and annotation of the human BORG lncRNA gene. Methods/Results: Using multiple tumor cohorts of human breast cancers, we show that while BORG expression is strongly induced in breast tumors as compared to normal breast tissues, the extent of BORG induction varies widely between breast cancer subtypes and even between different tumors within the same subtype. Elevated levels of BORG in breast tumors are associated with the acquisition of core cancer aggression pathways, including those associated with basal tumor and pluripotency phenotypes and with epithelial–mesenchymal transition (EMT) programs. While a subset of BORG-associated pathways was present in high BORG-expressing tumors across all breast cancer subtypes, many were specific to tumors categorized as triple-negative breast cancers. Finally, we show that genes induced by heterologous expression of BORG in murine models of TNBC both in vitro and in vivo strongly overlap with those associated with high BORG expression levels in human TNBC tumors. Conclusion: Our findings implicate human BORG as a novel driver of the highly aggressive basal TNBC tumor phenotype. Full article

(This article belongs to the Collection Application of Bioinformatics in Cancers)

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16 pages, 2254 KiB

Open AccessArticle

Unique Gene Expression Profiles within South Africa Are Associated with Varied Chemotherapeutic Responses in Conventional Osteosarcoma

by Phakamani G. Mthethwa, Thilona Arumugam, Veron Ramsuran, Anmol Gokul, Reitze Rodseth and Leonard Marais

Cancers 2024, 16(18), 3240; https://doi.org/10.3390/cancers16183240 - 23 Sep 2024

Viewed by 458

Abstract

Background: We determined the predictive gene expression profiles associated with chemo-response in conventional osteosarcomas (COS) within South Africa. Materials and methods: In 28 patients, we performed an RNA extraction, cDNA synthesis, and quantitative analysis using the RT-PCR 2^−∆∆CT method to determine the [...] Read more.

Background: We determined the predictive gene expression profiles associated with chemo-response in conventional osteosarcomas (COS) within South Africa. Materials and methods: In 28 patients, we performed an RNA extraction, cDNA synthesis, and quantitative analysis using the RT-PCR 2^−∆∆CT method to determine the fold change in gene expression alongside GAPDH (housekeeping gene). Results: We observed a significant downregulation in the mRNA expression profiles of ABCB1-p-glycoprotein (p = 0.0007), ABCC3 (p = 0.002), ERCC1 (p = 0.007), p-53 (p = 0.007), and RFC1 (p = 0.003) in the COS patients compared to the healthy donors. Furthermore, ABCB1-p-glycoprotein (p = 0.008) and ABCC3 (p = 0.020) exhibited a significant downregulation in the COS tumour tissues when compared to the healthy donors. In our univariate logistic regression, the predictors of chemotherapeutic response comprised ERCC1 [restricted cubic spline (RCS) knot: OR −0.27; CI −0.504 to −0.032; p = 0.036]; osteoblastic subtype [OR −0.36; CI −0.652 to −0.092; p = 0.026); fibroblastic subtype [OR 0.91; CI 0.569 to 1.248; p < 0.001]; and mixed subtype [OR 0.53; CI 0.232 to 0.032; p = 0.032]. In our multivariable logistic regression, the significant predictors of chemotherapeutic response comprised age [RCS knot: OR −2.5; CI −3.616 to −1.378; p = 0.022]; ABCC3 [RCS knot: OR 0.67; CI 0.407 to 0.936, p = 0.016]; ERCC1 [RCS knot: OR 0.57; CI 0.235 to 0.901; p = 0.044]; RFC1 [RCS knot: OR −1.04; CI −1.592 to −0.487; p = 0.035]; chondroblastic subtype [OR −0.83; CI −1.106 to −0.520; p = 0.012]; and osteoblastic subtype [OR −1.28; CI −1.664 to −0.901; p = 0.007]. Conclusions: In this South African cohort, we observed the unique gene expression profiles of osteosarcoma tumourigenesis and chemotherapeutic responses. These may serve as prognostication and therapeutic targets. Larger-scale research is needed on the African continent. Full article

(This article belongs to the Section Pediatric Oncology)

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19 pages, 5731 KiB

Open AccessArticle

The Potential of Human Pulmonary Mesenchymal Stem Cells as Vectors for Radiosensitizing Metallic Nanoparticles: An In Vitro Study

by Angélique Arcambal, Axelle Septembre-Malaterre, Sabrina Pesnel, Anne-Laure Morel, Philippe Gasque, Mickael Begue and Youssef Slama

Cancers 2024, 16(18), 3239; https://doi.org/10.3390/cancers16183239 - 23 Sep 2024

Viewed by 483

Abstract

Background/Objectives: Metallic nanoparticles (NPs) exhibit interesting radiosensitizing effects, and finding a way to accurately deliver them appears to be crucial. Due to their tumor tropism, mesenchymal stem cells (MSCs) represent a strategic approach. Therefore, we aimed to evaluate the impact of core–shell Fe [...] Read more.

Background/Objectives: Metallic nanoparticles (NPs) exhibit interesting radiosensitizing effects, and finding a way to accurately deliver them appears to be crucial. Due to their tumor tropism, mesenchymal stem cells (MSCs) represent a strategic approach. Therefore, we aimed to evaluate the impact of core–shell Fe₃O₄@Au NPs on the functionality of human pulmonary MSCs (HPMSCs). Methods/Results: The results showed that 100 µg/mL Fe₃O₄@Au NPs, accumulated in HPMSCs (revealed by Prussian blue staining), did not alter cell viability as assessed by cell counting, MTT, and LDH assays. However, caspase 9 and Bcl2 gene expression, evaluated by RT-qPCR, was regulated 72 h after exposure to the NPs. Moreover, the NPs also decreased proinflammatory cytokine/chemokine secretions, except for CXCL8 (ELISA). These modulations were associated with the downregulation of AMPK gene expression at 24 h. In contrast, the NPs did not modulate VEGF, PI3K, or PDGF gene expression. Nevertheless, a decrease in VEGF secretion was observed after 24 h of exposure to the NPs. Interestingly, the Fe₃O₄@Au NPs did not modulate Nrf2 gene expression, but they did regulate the expression of the genes encoding Nox4 and HMOX-1. Additionally, the NPs increased ROS production, suggesting a redox imbalance. Conclusions: Finally, the Fe₃O₄@Au NPs did not affect the HPMSCs’ viability or proangiogenic/tumorigenic markers. These findings are encouraging for investigating the effects of Fe₃O₄@Au NPs delivered by HPMSCs to tumor sites in combination with radiation. Full article

(This article belongs to the Special Issue Drug Delivery for Cancer Therapy)

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19 pages, 5218 KiB

Open AccessArticle

Raman Spectroscopy for Instant Bladder Tumor Diagnosis: System Development and In Vivo Proof-Of-Principle Study in Accordance with the European Medical Device Regulation (MDR2017/745)

by Ines Latka, Karin Mogensen, Florian Knorr, Cansu Kuzucu, Florian Windirsch, Dragan Sandic, Jürgen Popp, Gregers G. Hermann and Iwan W. Schie

Cancers 2024, 16(18), 3238; https://doi.org/10.3390/cancers16183238 - 23 Sep 2024

Viewed by 448

Abstract

This work reports on an in vivo Raman-based endoscopy system, invaScope, enabling Raman measurements of healthy and tumor bladder tissue during an endoscopic procedure in the operating theatre. The presented study outlines the progression from the initial concept (validated through previously performed ex [...] Read more.

This work reports on an in vivo Raman-based endoscopy system, invaScope, enabling Raman measurements of healthy and tumor bladder tissue during an endoscopic procedure in the operating theatre. The presented study outlines the progression from the initial concept (validated through previously performed ex vivo studies) to the approval and implementation of a clinical investigational device according to the requirement within the framework of the European Medical Device Regulation (MDR2017/745). The study’s primary objective was to employ the invaScope Raman system within the bladder, capturing in vivo spectroscopic Raman data followed by standard histo- and cytopathological examinations of urological tissue (considered the gold standard). The collected data were analyzed and correlated with histopathological findings post-procedure. Additionally, the study aimed to assess the feasibility of using diagnostic equipment, probes, and software for application in a clinical setting, evaluating usability aspects that are important during surgical procedures. This research represents a pivotal step toward advancing Raman spectroscopy for routine clinical use in characterizing bladder lesions. Full article

(This article belongs to the Section Methods and Technologies Development)

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20 pages, 984 KiB

Open AccessReview

Optimizing Hearing Outcomes in Nasopharyngeal Cancer Survivors in the Era of Modern Radiotherapy and Systemic Therapy

by Jason C. S. Ho, Brigette B. Y. Ma and James C. H. Chow

Cancers 2024, 16(18), 3237; https://doi.org/10.3390/cancers16183237 - 23 Sep 2024

Viewed by 707

Abstract

Intensity-modulated radiation therapy (IMRT) improves disease control and reduces treatment-related toxicity in patients with localized nasopharyngeal carcinoma (NPC). However, due to the proximity of the auditory apparatus to the treatment volume and the frequent incorporation of cisplatin-based chemotherapy, treatment-related sensorineural hearing loss (SNHL) [...] Read more.

Intensity-modulated radiation therapy (IMRT) improves disease control and reduces treatment-related toxicity in patients with localized nasopharyngeal carcinoma (NPC). However, due to the proximity of the auditory apparatus to the treatment volume and the frequent incorporation of cisplatin-based chemotherapy, treatment-related sensorineural hearing loss (SNHL) remains a common debilitating complication among NPC survivors. The reported crude incidence of SNHL following IMRT for NPC varies widely at 1–46% due to differences in auditory assessment methods and thresholds, follow-up durations, chemotherapy usage, and patient compositions. International guidelines and radiation dosimetric studies have recommended constraining the cochlear mean dose to less than 44–50 Gy, but the risk of SNHL remains high despite adherence to these constraints. Potential strategies to improve hearing outcomes in NPC survivors include cautious de-escalation of radiotherapy dose and volume, individualization of cochlear constraints, optimization of radiotherapy planning techniques, and the use of substitutes or alternative schedules for cisplatin-based chemotherapy. The addition of immune checkpoint inhibitors to chemoradiotherapy did not impact ototoxicity. Prospective studies that employ both objective and patient-reported auditory outcomes are warranted to test the long-term benefits of various approaches. This article aims to provide a comprehensive review of the incidence and radiation dose–toxicity relationship of SNHL in NPC survivors and to summarize potential strategies to optimize hearing outcomes in relation to nuances in radiotherapy planning and the selection of systemic therapy. Full article

(This article belongs to the Special Issue New Insights into Clinical and Translational Research in Nasopharyngeal Carcinoma)

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31 pages, 598 KiB

Open AccessReview

Shifting the Paradigm: The Transformative Role of Neoadjuvant Therapy in Early Breast Cancer

by Nader Hirmas, Johannes Holtschmidt and Sibylle Loibl

Cancers 2024, 16(18), 3236; https://doi.org/10.3390/cancers16183236 - 23 Sep 2024

Viewed by 1261

Abstract

The use of neoadjuvant systemic therapy (NST) has become increasingly important in the treatment of breast cancer because of its various advantages. These include the ability to downstage tumors without compromising locoregional control and the potential to obtain valuable information about clinical and [...] Read more.

The use of neoadjuvant systemic therapy (NST) has become increasingly important in the treatment of breast cancer because of its various advantages. These include the ability to downstage tumors without compromising locoregional control and the potential to obtain valuable information about clinical and biological response to therapy with implications for individual prognoses. Surgical response assessment paves the way for response-adapted therapy, and pathological complete response (pCR; defined as ypT0/is ypN0) serves as an additional endpoint for drug development trials. Recommended NST regimens commonly consist of anthracyclines and taxane, with dose-dense anthracyclines and weekly paclitaxel often preferred, whenever feasible. For patients with human epidermal growth factor receptor-2 (HER2)-positive tumors, dual anti-HER2 therapy (trastuzumab and pertuzumab) is indicated together with NST in case of elevated risk of recurrence. For patients with triple-negative breast cancer (TNBC), adding carboplatin to NST correlates with improved pCR and survival rates, as does the addition of immune checkpoint inhibitors. For hormone receptor (HR)-positive/HER2-negative cancers, emerging data on NST including immune checkpoint inhibitors may elevate the significance of NST in high-risk luminal breast cancer. Here, we present a synthesis of the results from neoadjuvant clinical trials that aim at optimizing treatment options for patients with high-risk breast cancer. Full article

(This article belongs to the Special Issue Clinical Research and Progress in the Treatment of Breast Cancer)

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12 pages, 574 KiB

Open AccessArticle

Allostatic Load, Cigarette Smoking, and Lung Cancer Risk

by Yufan Guan, Jie Shen, Kai Zhang, Bernard F. Fuemmeler and Hua Zhao

Cancers 2024, 16(18), 3235; https://doi.org/10.3390/cancers16183235 - 23 Sep 2024

Viewed by 637

Abstract

Background: Allostatic load (AL) is a biomarker of chronic stress associated with various chronic diseases. No study has evaluated the relationship between AL and lung cancer risk. Methods: To address this gap, we analyzed the association between AL and the development of lung [...] Read more.

Background: Allostatic load (AL) is a biomarker of chronic stress associated with various chronic diseases. No study has evaluated the relationship between AL and lung cancer risk. Methods: To address this gap, we analyzed the association between AL and the development of lung cancer in 344,380 participants from the UK Biobank. Results: During the follow-up period from 2006 to 2020, 2517 participants were diagnosed with incident lung cancer. Participants who developed lung cancer had significantly higher AL compared to cancer-free controls (mean: 3.49 vs. 2.87, p < 0.001). In the multivariate analysis, a marginally significant association was observed between higher AL and increased lung cancer risk (per one AL unit: Hazard Ratio [HR] = 1.02, 95% Confidence Interval [CI]: 0.99, 1.04). In the categorical analysis, individuals with high AL (AL > 2) had a 15% higher risk of lung cancer compared to those with low AL (AL ≤ 2) (HR = 1.15, 95% CI: 1.05, 1.25). Stratified analyses revealed that this increased risk was only observed in former (HR = 1.38, 95% CI: 1.06, 1.43) and current smokers (HR = 1.25, 95% CI: 1.10, 1.42) but not in never-smokers (HR = 0.93, 95% CI: 0.74, 1.17). Moreover, we found that demographics, socioeconomics, and other health behaviors could modify the risk association. Finally, among cigarette smoking-related variables, a significant trend of increasing AL was observed with higher pack-years, longer smoking duration, earlier age of smoking initiation, and later age of smoking cessation. Conclusions: These findings suggest that higher AL is associated with an increased risk of lung cancer. The results need to be further confirmed in additional studies. Full article

(This article belongs to the Special Issue Lung Cancer: From Mechanisms of Action and Risk Factors in Disease Onset to Management)

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15 pages, 818 KiB

Open AccessArticle

Real-World Survival Outcomes of First-Line Therapies in Patients with Metastatic Clear Cell Renal Cell Carcinoma: A Retrospective Analysis from Two Centres in Saudi Arabia

by Mubarak M. Al-Mansour, Syed Sameer Aga, Hanin A. Alharbi, Maria N. Alsulami, Halah A. Fallatah, Tarfah B. Albedaiwi, Lujain K. Anbari, Taleen R. Surrati, Ashwag A. Algethami, Alaa Althubaiti, Turki M. Alfayea and Ashwaq Alolayan

Cancers 2024, 16(18), 3234; https://doi.org/10.3390/cancers16183234 - 23 Sep 2024

Viewed by 764

Abstract

Background: Metastatic renal cell carcinoma (mRCC) represents a challenging condition characterised by poor prognosis and limited response to chemoradiotherapy. In this retrospective study, we compared the survival outcomes of first-line ICI regimens versus single-agent TKIs in patients with mRCC from two centres [...] Read more.

Background: Metastatic renal cell carcinoma (mRCC) represents a challenging condition characterised by poor prognosis and limited response to chemoradiotherapy. In this retrospective study, we compared the survival outcomes of first-line ICI regimens versus single-agent TKIs in patients with mRCC from two centres in Saudi Arabia. Methods: This study included 84 patients diagnosed with clear cell mRCC between January 2016 and December 2023. Patients were grouped based on treatment regimens. Progression-free survival (PFS) and overall survival (OS) were analysed using Kaplan–Meier curves and Cox proportional hazards regression. Results: The median first-line PFS was 9.7 months (95% CI: 5.3–14.1) for the overall cohort, with no significant difference between the single-agent tyrosine kinase inhibitor (TKI) group (9.4 months; 95% CI: 6.4–12.4), combination ICI group (9.0 months; 95% CI: 0.0–24.9), and single-agent ICI group (21.2 months; 95% CI: 2.6–39.8; p = 0.591). The median OS for the overall cohort was 42.0 months (95% CI: 14.9–69.2), with the single-agent TKI group having a median OS of 33.3 months (95% CI: 0.0–71.7), the combination ICI group, 42.0 months (95% CI: 0.06–84.0), and the single-agent ICI group, 23.0 months (95% CI: 19.2–26.7; p = 0.73). In comparison, the ICI-based combination therapy group exhibited a higher ORR of 41.0% (95% CI: 26.3–57.8%), while the single-agent ICI group had an ORR of 20.0% (95% CI: 3.5–55.8%). Cox regression identified liver metastasis as a significant independent predictor of PFS (HR = 1.8, p = 0.043), while a lower Karnofsky Performance Status was a significant independent predictor of OS (HR = 3.5, p < 0.001). Conclusions: In real-world practice from Saudi Arabia, first-line, single-agent ICI therapy offers promising anti-tumour activity and non-inferior survival outcomes compared to standard ICI-based combinations and single-agent TKIs. Full article

(This article belongs to the Section Clinical Research of Cancer)

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9 pages, 221 KiB

Open AccessArticle

Tolerability and Outcomes for Treatment of Older Myxoid Liposarcoma Population

by Reilly A. Coombs, Judith Jebastin Thangaiah, Brittany L. Siontis, Steven I. Robinson, Scott H. Okuno, Matthew T. Houdek, Meng Xu-Welliver and Thanh P. Ho

Cancers 2024, 16(18), 3233; https://doi.org/10.3390/cancers16183233 - 23 Sep 2024

Viewed by 467

Abstract

Background: Myxoid liposarcoma predominantly affects young and middle-aged individuals, and little is known regarding treatment tolerability and outcomes in older patients. This study aims to better understand this older patient population. Methods: This single institution retrospective study included patients aged 70 years and [...] Read more.

Background: Myxoid liposarcoma predominantly affects young and middle-aged individuals, and little is known regarding treatment tolerability and outcomes in older patients. This study aims to better understand this older patient population. Methods: This single institution retrospective study included patients aged 70 years and older with localized (non-metastatic) myxoid liposarcoma. Results: Sixteen patients were included. The median age was 75 years, and 9 (56%) were female. Fourteen (88%) were extremity tumors and two (12%) were trunk. The median tumor size was 10.4 cm (range, 3.6 to 28 cm). Five (31%) tumors had a round cell component. All patients had surgery. Fourteen (88%) had perioperative radiation, and three (19%) had perioperative chemotherapy. One patient had postoperative infection, and one patient had neutropenic fever from preoperative chemotherapy. The median follow up from surgery was 6.3 years. Eight (50%) patients died from MLPS. The median relapse-free survival and overall survival were 34 months and 75 months, respectively. Conclusions: Most older patients with localized MLPS received perioperative radiation therapy with surgery, and few serious toxicities were reported. Even with treatment, half of the patients relapsed. Full article

(This article belongs to the Special Issue Clinical and Surgical Outcomes in the Management of Extremity Soft Tissue Sarcomas)

26 pages, 1561 KiB

Open AccessReview

Advancing Cholangiocarcinoma Care: Insights and Innovations in T Cell Therapy

by Neda Dadgar, Arun K. Arunachalam, Hanna Hong, Yee Peng Phoon, Jorge E. Arpi-Palacios, Melis Uysal, Chase J. Wehrle, Federico Aucejo, Wen Wee Ma and Jan Joseph Melenhorst

Cancers 2024, 16(18), 3232; https://doi.org/10.3390/cancers16183232 - 23 Sep 2024

Viewed by 930

Abstract

Cholangiocarcinoma (CCA) is a rare and aggressive malignancy originating from the bile ducts, with poor prognosis and limited treatment options. Traditional therapies, such as surgery, chemotherapy, and radiation, have shown limited efficacy, especially in advanced cases. Recent advancements in immunotherapy, particularly T cell-based [...] Read more.

Cholangiocarcinoma (CCA) is a rare and aggressive malignancy originating from the bile ducts, with poor prognosis and limited treatment options. Traditional therapies, such as surgery, chemotherapy, and radiation, have shown limited efficacy, especially in advanced cases. Recent advancements in immunotherapy, particularly T cell-based therapies like chimeric antigen receptor T (CAR T) cells, tumor-infiltrating lymphocytes (TILs), and T cell receptor (TCR)-based therapies, have opened new avenues for improving outcomes in CCA. This review provides a comprehensive overview of the current state of T cell therapies for CCA, focusing on CAR T cell therapy. It highlights key challenges, including the complex tumor microenvironment and immune evasion mechanisms, and the progress made in preclinical and clinical trials. The review also discusses ongoing clinical trials targeting specific CCA antigens, such as MUC1, EGFR, and CD133, and the evolving role of precision immunotherapy in enhancing treatment outcomes. Despite significant progress, further research is needed to optimize these therapies for solid tumors like CCA. By summarizing the most recent clinical results and future directions, this review underscores the promising potential of T cell therapies in revolutionizing CCA treatment. Full article

(This article belongs to the Special Issue Cell Therapy in Solid Cancers: Current and Future Landscape)

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19 pages, 2530 KiB

Open AccessArticle

The Phenotypical Characterization of Dual-Nature Hybrid Cells in Uveal Melanoma

by Emily Marcotte, Alicia Goyeneche, Mohamed Abdouh, Julia Valdemarin Burnier and Miguel Noel Burnier, Jr.

Cancers 2024, 16(18), 3231; https://doi.org/10.3390/cancers16183231 - 22 Sep 2024

Viewed by 777

Abstract

Background: Metastasis, occurring years after primary diagnosis, represents a poor prognosis in uveal melanoma (UM)-affected individuals. The nature of cells involved in this process is under debate. Circulating hybrid cells that have combined tumor and immune cell features found in blood were predictive [...] Read more.

Background: Metastasis, occurring years after primary diagnosis, represents a poor prognosis in uveal melanoma (UM)-affected individuals. The nature of cells involved in this process is under debate. Circulating hybrid cells that have combined tumor and immune cell features found in blood were predictive of metastasis and may correspond to dual-nature cells (DNC) in the primary tumor. Herein, we sought to determine the presence of DNCs in primary UM tumors, the cell types involved in their genesis, and their ability to be formed in vitro. Methods: UM lesions (n = 38) were immunolabeled with HMB45 in combination with immune-cell-specific antibodies. In parallel, we co-cultured UM cells and peripheral blood mononuclear cells (PBMCs) to analyze DNC formation. Results: HMB45⁺/CD45⁺ DNCs were present in 90% (26/29) of the tumors, HMB45⁺/CD8⁺ DNCs were present in 93% (26/28), and HMB45⁺/CD68⁺ DNCs were present in 71% (17/24). DNCs formed with CD8⁺ and CD68⁺ cells were positively correlated to the infiltration of their respective immune cells. Notably, UM cells were prone to hybridize with PBMCs in vitro. Conclusions: This phenotypical characterization of DNCs in UM demonstrates that CD8⁺ T-cells and macrophages are capable of DNC formation, and they are important for better understanding metastatic dissemination, thus paving the path towards novel therapeutic avenues. Full article

(This article belongs to the Special Issue Advances in Uveal Melanoma)

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9 pages, 879 KiB

Open AccessArticle

Adverse Obstetric Outcomes after Breast Cancer Diagnosis: An Observational Database Study in Germany

by Anna Sophie Scholz, Alexandra von Au, Raphael Gutsfeld, Tjeerd Maarten Hein Dijkstra, Dominik Dannehl, Kathrin Hassdenteufel, Markus Hahn, Sabine Hawighorst-Knapstein, Ariane Chaudhuri, Armin Bauer, Markus Wallwiener, Sara Yvonne Brucker, Andreas Daniel Hartkopf and Stephanie Wallwiener

Cancers 2024, 16(18), 3230; https://doi.org/10.3390/cancers16183230 - 22 Sep 2024

Viewed by 566

Abstract

Background/Objectives: Breast cancer may negatively affect later pregnancy and childbirth. We aimed to analyze the impact of previous breast cancer on obstetric outcomes in postdiagnosis pregnancies. Methods: Insurance claims data in Southern Germany were used to identify breast cancer (BC) survivors with at [...] Read more.

Background/Objectives: Breast cancer may negatively affect later pregnancy and childbirth. We aimed to analyze the impact of previous breast cancer on obstetric outcomes in postdiagnosis pregnancies. Methods: Insurance claims data in Southern Germany were used to identify breast cancer (BC) survivors with at least one subsequent delivery after cancer diagnosis between 2010 and 2020. In total, 74 BC survivors were compared to 222 age-matched controls with frequency matching on their age at their postdiagnosis delivery. Results: Endocrine therapy was associated with a significantly lower probability of birth compared to BC survivors without endocrine therapy (HR 0.36; 95% CI 0.18–0.53; p < 0.0001). The risks of preterm birth, low birth weight (LBW), gestational diabetes, hypertensive disorders, and cesarean section were not significantly increased among BC survivors compared to healthy controls. BC survivors were at an increased risk for a small-for-gestational-age (SGA) fetus (OR 3.24; 95% CI 1.17–8.97, p = 0.03). Delivery in less than 2 years after diagnosis increased the risk for SGA (OR 5.73; 95% CI 1.37–24.02, p = 0.03) and LBW (OR 4.57; 95% CI 1.32–15.87, p = 0.02). Conclusions: Our findings are encouraging regarding the risks of preterm delivery, gestational diabetes, hypertensive disorders, and cesarean section to women who consider pregnancy after BC. Delivery in less than 2 years after diagnosis was associated with an increased risk for SGA and LBW. Full article

(This article belongs to the Special Issue Cancer Survivorship: During and after Treatment)

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12 pages, 2697 KiB

Open AccessArticle

Complex Relationships between Diagnostics and Survival in Chronic Lymphocytic Leukemia in Denmark, Finland, Norway, and Sweden

by Kari Hemminki, Frantisek Zitricky, Asta Försti, Tuija Tapaninen, Akseli Hemminki, Gunnar Juliusson and Carsten Utoft Niemann

Cancers 2024, 16(18), 3229; https://doi.org/10.3390/cancers16183229 - 22 Sep 2024

Viewed by 596

Abstract

Background: Chronic lymphocytic leukemia (CLL) is a common hematological malignancy with highly variable clinical presentation. Many patients never require any treatment but for the others, chemotherapy, immunochemotherapy, and newer targeted therapies have changed the treatment landscape. Diagnostic age influences the applied treatment, and [...] Read more.

Background: Chronic lymphocytic leukemia (CLL) is a common hematological malignancy with highly variable clinical presentation. Many patients never require any treatment but for the others, chemotherapy, immunochemotherapy, and newer targeted therapies have changed the treatment landscape. Diagnostic age influences the applied treatment, and we thus wanted to analyze age-specific survival trends through 50 years up to 2020s. Methods: We used 1- and 5-year relative survival from the NORDCAN database, with data from Denmark (DK), Finland (FI), Norway (NO), and Sweden (SE). Because of the variable presentation of CLL, we also considered incidence and mortality trends. For comparison, US SEER data were used. Results: The large age-specific survival differences in 1972–76 almost disappeared by 2017–21. While 5-year survival in younger patients exceeded 90%, for those diagnosed at age 80–89 years, survival reached 90% in DK and SE women, 80% in NO and SE men, but only 50% in FI. DK 5-year overall survival for men was 92.4%, and for women, it was 96.3%. These survival figures were higher than age-group-specific US survival data. Conclusions: The DK data are probably global top figures for national survival which could be achieved by boosting survival even among the oldest patients. The qualification to these figures and international comparisons is that survival needs to be considered in terms of incidence, which is high in DK and NO. Low survival of the FI 80–89-year-old patients, even in the first year after diagnosis, may suggest delayed diagnosis, which should call for a closer national scrutiny. Full article

(This article belongs to the Section Cancer Survivorship and Quality of Life)

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20 pages, 2717 KiB

Open AccessArticle

Increased Frequency of Circulating Activated FOXP3⁺ Regulatory T Cell Subset in Patients with Chronic Lymphocytic Leukemia Is Associated with the Estimate of the Size of the Tumor Mass, STAT5 Signaling and Disease Course during Follow-Up of Patients on Therapy

by Zlatko Roškar, Mojca Dreisinger, Evgenija Homšak, Tadej Avčin, Sebastjan Bevc and Aleš Goropevšek

Cancers 2024, 16(18), 3228; https://doi.org/10.3390/cancers16183228 - 22 Sep 2024

Viewed by 626

Abstract

Introduction: Advanced chronic lymphocytic leukemia (CLL) is accompanied by increased circulating regulatory T cells (Tregs) and increased susceptibility to severe infections, which were also shown to entail a striking induction of FOXP3 expression in Tregs. As homeostasis of the most suppressive CD45RA⁻ [...] Read more.

Introduction: Advanced chronic lymphocytic leukemia (CLL) is accompanied by increased circulating regulatory T cells (Tregs) and increased susceptibility to severe infections, which were also shown to entail a striking induction of FOXP3 expression in Tregs. As homeostasis of the most suppressive CD45RA⁻FOXP3^high activated Treg (aTreg) subset differs, it is critical to analyse homeostatic signalling in Treg subsets. Materials and Methods: In this study, by using conventional and imaging flow cytometry, we monitored STAT5 signalling/phosphorylation (pSTAT5) and investigated Treg subsets in relation to the Binet stage, the total tumor mass score (TTM) and the disease course during a follow-up of 37 patients with CLL. Results: The aTreg percentage was significantly increased among CD4⁺ T cells from patients with advanced disease and significantly correlated with the TTM. A subgroup of patients with higher aTreg percentages among CD4⁺FOXP3⁺ T cells at the start of therapy was characterised by more frequent episodes of severe infections during follow-up. Conclusions: The results suggesting that an aTreg fraction could represent a possible marker of a severe disease course with infectious complications. Augmented homeostatic STAT5 signalling could support aTreg expansion, as higher pSTAT5 levels were significantly correlated with an increased aTreg frequency among CD4⁺FOXP3⁺ T cells during the follow-up of patients on therapy, as well as following SARS-CoV-2 antigen-specific stimulation in vitro. Full article

(This article belongs to the Special Issue Therapies and Clinical Outcomes of Chronic Lymphocytic Leukemia)

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12 pages, 1129 KiB

Open AccessArticle

Robotic Stereotactic Ablative Radiotherapy for Patients with Early-Stage Lung Cancer: Results of an Interim Analysis

by Anna Zygogianni, Ioannis M. Koukourakis, John Georgakopoulos, Christina Armpilia, Zoi Liakouli, Dimitra Desse, Georgios Ntoumas, Foteini Simopoulou, Maria Nikoloudi and Vassilis Kouloulias

Cancers 2024, 16(18), 3227; https://doi.org/10.3390/cancers16183227 - 22 Sep 2024

Viewed by 562

Abstract

Background/Objectives: Surgery is the primary treatment for early-stage lung cancer. Patients with medically inoperable lung carcinomas and patients who refuse to undergo surgery are treated with definite radiotherapy. Stereotactic ablative radiotherapy (SABR) is a compelling non-invasive therapeutic modality for this group of patients [...] Read more.

Background/Objectives: Surgery is the primary treatment for early-stage lung cancer. Patients with medically inoperable lung carcinomas and patients who refuse to undergo surgery are treated with definite radiotherapy. Stereotactic ablative radiotherapy (SABR) is a compelling non-invasive therapeutic modality for this group of patients that confers promising results. Methods: We report an interim analysis of an ongoing trial. Eighty-one patients with medically inoperable early-stage (T1,2N0) lung cancer underwent SABR in our institution. SABR was delivered via the CyberKnife M6 robotic radiosurgery system. The endpoints of the analysis were treatment efficacy and tolerance. Results: There were no acute or late toxicities from the skin or the connective tissue of the thorax. A grade 2/3 lung injury of non-clinical significance was noted in 6% of patients, which was directly related to a higher biologically effective dose (BED_{α/β = 3}) and larger irradiation lung volumes in both univariate and multivariate analyses. A local control (LC) was achieved in 100% of the patients at the first follow-up, and the projected 24-month local progression-free survival (LPFS) rate was 95%. The projected 24-month disease-specific overall survival (OS) was 94%. Conclusions: High LC and OS rates can be achieved with SABR for early-stage lung cancer, with minimal toxicity. This study continues to recruit patients. Full article

(This article belongs to the Section Cancer Therapy)

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13 pages, 15027 KiB

Open AccessArticle

The Solute Carrier (SLC) Transporter Superfamily as Therapeutic Targets for the Treatment of Head and Neck Squamous Cell Carcinoma

by Sang Yeon Cho and Nam Sook Kang

Cancers 2024, 16(18), 3226; https://doi.org/10.3390/cancers16183226 - 22 Sep 2024

Viewed by 556

Abstract

Background: Head and neck squamous cell carcinoma (HNSC) is the most prevalent cancer in the head and neck region, originating from the mucosal epithelium of the oral cavity, pharynx, and larynx. The solute carrier (SLC) transporter superfamily, consisting of over 400 proteins [...] Read more.

Background: Head and neck squamous cell carcinoma (HNSC) is the most prevalent cancer in the head and neck region, originating from the mucosal epithelium of the oral cavity, pharynx, and larynx. The solute carrier (SLC) transporter superfamily, consisting of over 400 proteins across 65 families, plays a crucial role in cellular functions and presents promising targets in precision oncology. This study aims to analyze the expression of SLC transporters in HNSC and their potential as biomarkers and therapeutic targets. Methods: We leveraged mRNA and protein expression data from The Cancer Genome Atlas (TCGA) and The Human Protein Atlas (HPA) to examine SLC transporter expression in HNSC. Gene Set Enrichment Analysis (GSEA) was conducted to assess the involvement of SLC transporters in various oncogenic pathways. Results: Significant upregulation of SLC transporters was observed in tumor tissues compared to normal tissues, with notable increases in SLC16A3, SLC53A1, SLC25A32, and SLC2A3. This upregulation correlated with poorer overall survival (OS) and disease-specific survival (DSS). GSEA revealed that these transporters are significantly involved in critical oncogenic pathways, including epithelial-mesenchymal transition (EMT), angiogenesis, and hypoxia, which are vital for cancer progression and metastasis. Conclusions: The study identifies SLC transporters as potential biomarkers and therapeutic targets in HNSC. Targeting these transporters with small molecule inhibitors could disrupt essential supply routes for cancer cells, enhancing treatment efficacy and improving patient outcomes. This study paves the way for developing SLC-based target therapies in precision oncology, with the goal of improving survival rates for patients with HNSC. Full article

(This article belongs to the Section Molecular Cancer Biology)

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22 pages, 932 KiB

Open AccessReview

The Role of Whole-Gland and Focal Cryotherapy in Recurrent Prostate Cancer

by Faozia Pio, Andeulazia Murdock, Renee E. Fuller and Michael J. Whalen

Cancers 2024, 16(18), 3225; https://doi.org/10.3390/cancers16183225 - 22 Sep 2024

Viewed by 732

Abstract

Prostate cancer is the most common non-cutaneous malignancy in men, with the majority of newly diagnosed patients eligible for active surveillance. Despite definitive treatment, a considerable percentage of men will experience biochemical recurrence and even regional and distant metastatic recurrence after radiation therapy [...] Read more.

Prostate cancer is the most common non-cutaneous malignancy in men, with the majority of newly diagnosed patients eligible for active surveillance. Despite definitive treatment, a considerable percentage of men will experience biochemical recurrence and even regional and distant metastatic recurrence after radiation therapy or radical prostatectomy. Salvage prostatectomy, while oncologically effective, poses significant morbidity with poor functional outcomes. Salvage cryotherapy has emerged as a promising alternative for localized recurrence, demonstrating safety and efficacy. This review examines the oncologic and functional outcomes of whole-gland and focal salvage cryotherapy, including disease-free survival, cancer-specific survival, and overall survival. The crucial role of multiparametric prostate MRI and evolving role of next-generation PSMA-targeted PET imaging are also examined. The comparison of outcomes of cryotherapy to other salvage ablation modalities, such as high-intensity focused ultrasound (HIFU), is also explored. Full article

(This article belongs to the Section Cancer Therapy)

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Open AccessArticle

Risk of Esophageal and Gastric Cancer in Patients with Type 2 Diabetes Receiving Glucagon-like Peptide-1 Receptor Agonists (GLP-1 RAs): A National Analysis

by Mark Ayoub, Rafi Aibani, Tiana Dodd, Muhammed Ceesay, Muhammad Bhinder, Carol Faris, Nisar Amin and Ebubekir Daglilar

Cancers 2024, 16(18), 3224; https://doi.org/10.3390/cancers16183224 - 22 Sep 2024

Viewed by 720

Abstract

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are becoming more popular in managing type 2 diabetes mellitus (T2DM). Concerns linger over potential links to malignancies like pancreatic and thyroid cancers, requiring more research to clarify their safety profiles. Additionally, evidence suggests GLP-1 RAs [...] Read more.

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are becoming more popular in managing type 2 diabetes mellitus (T2DM). Concerns linger over potential links to malignancies like pancreatic and thyroid cancers, requiring more research to clarify their safety profiles. Additionally, evidence suggests GLP-1 RAs may lower colorectal and pancreatic cancer risk, especially in obese and overweight individuals, indicating a protective effect beyond weight loss. Current studies leave a gap in comprehensively understanding cancer risks associated with GLP-1 RAs, which prompts further research to enhance our understanding of their overall safety. Methods: We queried the US Collaborative Network (63 health care organizations) of the TriNetX research database. Patients with T2DM were identified and divided into two cohorts: patients on GLP-1 RAs and patients not on GLP-1 RAs. We excluded tobacco use and alcohol use disorders, obese patients with a body mass index (BMI) of >25 kg/m², and those with a family history of gastrointestinal malignancy, infectious mononucleosis, chronic gastritis, pernicious anemia, helicobacter pylori infection, or gastroesophageal reflux disease (GERD). We used a 1:1 propensity score matching (PSM) model using patients’ baseline characteristics, medications, labs, and genetics. We compared the rate of gastric cancer and esophageal cancer at the seven-year mark. Results: A total of 2,748,431 patients with T2DM were identified. Of those, 6% (n = 167,077) were on a GLP-1 RA and 94% (n = 2,581,354) were not on a GLP-1 RA. After PSM, both cohorts included 146,277 patients. Patients with T2DM who were on a GLP-1 RA, compared to those who were not, had a statistically significant lower risk of both gastric cancer (0.05% vs. 0.13%, p < 0.0001) and esophageal cancer (0.04% vs. 0.13%, p < 0.0001) at the seven-year mark. Conclusion: The use of GLP-1 RAs in patients with T2DM does not significantly increase the risk of gastric or esophageal cancer. This finding supports the continued use of GLP-1 analogues as a therapeutic option in managing T2DM, considering their well-established benefits and low risk of complications. Based on the study results, these medications may even have a protective effect against these malignancies. Full article

(This article belongs to the Special Issue Gastrointestinal Malignancy: Epidemiology and Risk Factors)

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10 pages, 579 KiB

Open AccessArticle

The 3-Biomarker Classifier—A Novel and Simple Molecular Risk Score Predicting Overall Survival in Patients with Colorectal Cancer

by Nathaniel Melling, Mohammad H. Fard-Aghaie, Claudia Hube-Magg, Martina Kluth, Ronald Simon, Michael Tachezy, Tarik Ghadban, Matthias Reeh, Jakob R. Izbicki, Guido Sauter and Katharina Grupp

Cancers 2024, 16(18), 3223; https://doi.org/10.3390/cancers16183223 - 22 Sep 2024

Viewed by 563

Abstract

Introduction: Several new molecular markers in colorectal carcinomas have been discovered; however, classical histopathological predictors are still being used to predict survival in patients. We present a novel risk score, which uses molecular markers, to predict outcomes in patients with colorectal carcinoma. Methods: [...] Read more.

Introduction: Several new molecular markers in colorectal carcinomas have been discovered; however, classical histopathological predictors are still being used to predict survival in patients. We present a novel risk score, which uses molecular markers, to predict outcomes in patients with colorectal carcinoma. Methods: The immunohistochemistry of tissue micro arrays was used to detect and quantify H2BUB1, RBM3 and Ki-67. Different intensities of staining were categorized for these markers and a score was established. A multivariate analysis was performed and survival curves were established. Results: 1791 patients were evaluated, and multivariate analysis revealed that our risk score, the 3-biomarker classifier, is an independent marker to predict survival. We found a high risk-score to be associated with dismal median survival for the patients. Conclusions: A more personalized score might be able to better discriminate low- and high-risk patients and suggest adjuvant treatment compared to classical pathological staging. Our score can serve as a tool to predict outcomes in patients suffering from colorectal carcinoma. Full article

(This article belongs to the Section Cancer Biomarkers)

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11 pages, 27353 KiB

Open AccessArticle

Immunological Tumor Microenvironment of Solitary Fibrous Tumors—Associating Immune Infiltrate with Variables of Prognostic Significance

by Emilio Medina-Ceballos, Isidro Machado, Francisco Giner, Álvaro Blázquez-Bujeda, Mónica Espino, Samuel Navarro and Antonio Llombart-Bosch

Cancers 2024, 16(18), 3222; https://doi.org/10.3390/cancers16183222 - 21 Sep 2024

Viewed by 657

Abstract

Background and objectives: Solitary fibrous tumors (SFTs) are morphologically heterogeneous tumors characterized by the NAB2::STAT6 gene fusion. Clinical outcomes may vary widely, and while most cases have favorable outcomes, some can progress to aggressive disease, manifesting as recurrence and metastasis, and ultimately resulting [...] Read more.

Background and objectives: Solitary fibrous tumors (SFTs) are morphologically heterogeneous tumors characterized by the NAB2::STAT6 gene fusion. Clinical outcomes may vary widely, and while most cases have favorable outcomes, some can progress to aggressive disease, manifesting as recurrence and metastasis, and ultimately resulting in patient death. Herein, we analyze the immunological tumor microenvironment (ITME) of SFTs, aiming to determine its prognostic value and correlation with established risk stratification systems (RSSs). Methods: A retrospective observational multicenter study of 52 fusion-confirmed SFTs with clinical follow-up data. Immunohistochemical analysis including CD163, CD68, CD3, CD8, CD20, PDL-1, PD-1, and LAG1 were evaluated in tissue microarrays, using an analog scale with scores ranging from 0 to 3 (0 = ≤9, 1 = 10–49, 2 = 50–99, and 3 = >100 positive cells per 10 high-power fields). The expression of these markers was correlated with clinical outcomes, morphological characteristics previously evaluated in whole slide tissue sections (hypercellularity/hypocellularity, round–oval or spindle dominant constituent cell (DCC) morphology, and necrosis), Ki67, overall survival, and RSS. Results: Only one of the fifty-two cases studied showed progression. In the multivariate analysis, neither the presence nor absence of immune cells (B-lymphocytes, T-lymphocytes, and macrophages) showed any association with the assessed RSSs (Demicco, Sugita, G-score, and Huang). Interestingly, the case that showed progression had high immune infiltrate with expression of CD68, CD163, CD8, and CD20 markers (score of 3). Round–oval cell morphology was associated with the presence of higher levels of CD163 macrophages. Lastly, the scant presence of CD20+ lymphocytes correlated with less necrosis, and cases with higher PDL-1 expression correlated with increased Ki67 values. All cases were negative for LAG-1 and PD-1. Conclusions: SFT ITME components correlated with independent variables with prognostic significance. Nevertheless, ITME did not correlate with RSS scores. Full article

(This article belongs to the Special Issue Molecular Mechanisms in Bone and Soft Tissue Sarcomas)

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15 pages, 1741 KiB

Open AccessArticle

Low-Risk and High-Risk NSMPs: A Prognostic Subclassification of No Specific Molecular Profile Subtype of Endometrial Carcinomas

by Matteo Marchetti, Giulia Spagnol, Tommaso Vezzaro, Sofia Bigardi, Orazio De Tommasi, Emma Facchetti, Marta Tripepi, Diletta Costeniero, Chiara Munerol, Tiziano Maggino, Donato D’Antona, Roberto Tozzi, Carlo Saccardi and Marco Noventa

Cancers 2024, 16(18), 3221; https://doi.org/10.3390/cancers16183221 - 21 Sep 2024

Viewed by 585

Abstract

(1) Background: Endometrial carcinoma (EC) classified as no specific molecular profile (NSMP) represents a heterogeneous group with variable prognoses. This retrospective, single-center study aims to further stratify NSMP ECs to tailor treatment strategies and improve outcomes. (2) Methods: From 2020 to 2023, we [...] Read more.

(1) Background: Endometrial carcinoma (EC) classified as no specific molecular profile (NSMP) represents a heterogeneous group with variable prognoses. This retrospective, single-center study aims to further stratify NSMP ECs to tailor treatment strategies and improve outcomes. (2) Methods: From 2020 to 2023, we collected data on 51 patients diagnosed with NSMP EC following the introduction of molecular profiling at our institution. Patients were retrospectively analyzed for estrogen receptor (ER) status, histotype, and grade to identify potential prognostic subgroups. (3) Results: Our analysis identified two distinct subgroups within NSMP EC: low-risk and high-risk, based on ER status, histotype, and grade. The low-risk NSMP group demonstrated significantly better survival outcomes compared to the high-risk group. With a median follow-up time of 16 moths (IQR 13.0–29.7), the disease-free survival (DFS) and overall survival (OS) for the low-risk group were 100%. For the high-risk group, the DFS and OS were 71.4% and 78.6%, respectively, which showed a statistically significantly difference (Log-Rank Mantel-Cox < 0.001). In the high-risk group, four patients experienced recurrence, and three of these patients died. (4) Conclusions: Stratifying NSMP EC into low-risk and high-risk categories based on ER status, histotype, and grade can lead to more accurate prognostic assessments. In time, it may require tailored adjuvant therapies and a personalized treatment. Full article

(This article belongs to the Special Issue Basic Research and Clinical Treatment of Endometrial Cancer)

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17 pages, 433 KiB

Open AccessArticle

Characterization of Patient Activation among Childhood Cancer Survivors in the St. Jude Lifetime Cohort Study (SJLIFE)

by Megan E. Ware, Angelica De La Cruz, Qian Dong, Kyla Shelton, Tara M. Brinkman, I-Chan Huang, Rachel Webster, Brian Potter, Kevin Krull, Sedigheh Mirzaei, Matthew Ehrhardt, Melissa M. Hudson, Gregory Armstrong and Kirsten Ness

Cancers 2024, 16(18), 3220; https://doi.org/10.3390/cancers16183220 - 21 Sep 2024

Viewed by 837

Abstract

Background: Patient activation describes a willingness to take action to manage health and is associated with health outcomes. The purpose of this study was to characterize patient activation and its association with psychological outcomes and health behaviors in childhood cancer survivors. Methods: Participants [...] Read more.

Background: Patient activation describes a willingness to take action to manage health and is associated with health outcomes. The purpose of this study was to characterize patient activation and its association with psychological outcomes and health behaviors in childhood cancer survivors. Methods: Participants were from the St. Jude Lifetime Cohort Study (SJLIFE). Activation levels (1–4, 4 = highest activation) were measured with the Patient Activation Measure (PAM). Psychological outcomes and health behaviors were obtained via self-report. Cognitive function was assessed by trained examiners. ANOVA or chi-squared tests were utilized to assess group-level differences in activation. Multivariable regression models were used to assess associations between PAM scores and outcomes of interest. Results: Among 2708 survivors and 303 controls, more survivors endorsed lower activation levels than the controls (11.3 vs. 4.7% in level 1) and fewer survivors endorsed the highest level of activation than the controls (45.3 vs. 61.5% in level 4). Not endorsing depression (OR: 2.37, 95% CI 1.87–2.99), anxiety (OR: 2.21, 95% CI 1.73–2.83), and somatization symptoms (OR: 1.99, 95% CI 1.59–2.50), general fear (OR: 1.45, 95% CI 1.23–1.71) and body-focused (OR: 2.21, 95% CI 1.83–2.66), cancer-related worry, and physical (OR: 2.57, 95% CI 2.06–3.20) and mental (OR: 2.08, 95% CI 1.72–2.52) HRQOL was associated with higher levels of activation. Lower activation was associated with not meeting physical activity guidelines (OR: 2.07, 95% CI 1.53–2.80). Conclusions: Survivors endorsed lower activation levels than peers. Interventions to improve physical and psychological health outcomes could leverage these results to identify survivors who benefit from support in patient activation. Full article

(This article belongs to the Special Issue Quality of Life and Management of Pediatric Cancer)

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24 pages, 4655 KiB

Open AccessArticle

Dihydrotestosterone Enhances MICA-Mediated Immune Responses to Epstein–Barr Virus-Associated Gastric Carcinoma

by Donghyun Seo, Hyeji Byun, Miyeon Cho, Sun Hee Lee, Sohyun Youn, Junho Lee, Inuk Jung, Hyosun Cho and Hyojeung Kang

Cancers 2024, 16(18), 3219; https://doi.org/10.3390/cancers16183219 - 21 Sep 2024

Viewed by 569

Abstract

Background: Epstein–Barr virus-associated gastric carcinoma (EBVaGC) is a subset of gastric cancers linked to EBV infection. While the role of male hormones in cancers such as prostate, breast, and ovarian cancers is well-studied, their impact on EBVaGC remains less understood. This study aims [...] Read more.

Background: Epstein–Barr virus-associated gastric carcinoma (EBVaGC) is a subset of gastric cancers linked to EBV infection. While the role of male hormones in cancers such as prostate, breast, and ovarian cancers is well-studied, their impact on EBVaGC remains less understood. This study aims to examine the effect of dihydrotestosterone (DHT) on EBVaGC, particularly focusing on its influence on the immune response. Methods: The study utilized the SNU719 EBVaGC cell line. Cells were treated with DHT to assess androgen receptor (AR) expression and the activation of signaling pathways, including NF-κB. The expression of MHC class I polypeptide-related sequence A (MICA) and its interaction with the NKG2D receptor on NK and T cells was evaluated. Cytotoxicity assays were conducted to determine DHT’s effect on NK and T cell-mediated cytotoxicity, and proinflammatory cytokine gene expression was analyzed. Results: DHT significantly increased AR expression in EBVaGC cells and activated the NF-κB pathway, which led to increased transcription of target genes such as MICA and EBNA1. These changes enhanced the interaction with receptors on NK and T cells, thereby boosting their cytotoxicity against EBVaGC cells. Importantly, DHT did not upregulate proinflammatory cytokine genes. Conclusion: DHT enhances the immune response against EBVaGC by upregulating MICA and activating NK and T cells. These findings suggest potential therapeutic strategies targeting androgen signaling to improve anti-tumor immunity in EBVaGC. Full article

(This article belongs to the Special Issue Epstein–Barr Virus (EBV) Associated Cancers)

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21 pages, 2340 KiB

Open AccessSystematic Review

Leucocyte Telomere Length and Lung Cancer Risk: A Systematic Review and Meta-Analysis of Prospective Studies

by Roberto Fabiani, Manuela Chiavarini, Patrizia Rosignoli and Irene Giacchetta

Cancers 2024, 16(18), 3218; https://doi.org/10.3390/cancers16183218 - 21 Sep 2024

Viewed by 438

Abstract

Although numerous epidemiological studies are available, the relationship between leukocyte telomere length (LTL) and lung cancer risk is still controversial. This systematic review and meta-analysis, performed according to the PRISMA statement and MOOSE guidelines, aims to summarize the evidence and calculate the risk [...] Read more.

Although numerous epidemiological studies are available, the relationship between leukocyte telomere length (LTL) and lung cancer risk is still controversial. This systematic review and meta-analysis, performed according to the PRISMA statement and MOOSE guidelines, aims to summarize the evidence and calculate the risk of lung cancer associated with LTL. The literature search was performed on PubMed, Web of Science, and Scopus databases through May 2024. A random-effects model was used to calculate the pooled risk. Heterogeneity was assessed using I² and Cochran’s Q statistic. Begg’s and Egger’s tests were used to detect publication bias. Based on 8055 lung cancer cases and 854,653 controls (nine prospective studies), longer LTL was associated with a significant 42% increment in all types of lung cancer risk (OR 1.42, 95% CI 1.24–1.63). The effect was even more evident for adenocarcinomas (OR 1.98, 95% CI 1.69–2.31), while no association was observed for squamous cell carcinoma (OR 0.87, 95% CI 0.72–1.06). Significantly, no association was found for current smokers (OR 1.08, 95% CI 0.90–1.30), while it remained high for both never-smokers (OR 1.92, 95% CI 1.62–2.28) and former smokers (OR 1.34, 95% CI 1.11–1.62). No significant publication bias was evidenced. Longer LTL is associated with an increment in lung cancer risk particularly in never-smoker subjects. Full article

(This article belongs to the Special Issue Lung Cancer: From Mechanisms of Action and Risk Factors in Disease Onset to Management)

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11 pages, 1099 KiB

Open AccessArticle

Analysis of Calculated Liver Scores for Long-Term Outcome in 423 Cutaneous Melanoma Patients

by Nessr Abu Rached, Mariana Marques da Silva Reis, Eggert Stockfleth, Riina Käpynen and Thilo Gambichler

Cancers 2024, 16(18), 3217; https://doi.org/10.3390/cancers16183217 - 21 Sep 2024

Viewed by 395

Abstract

Background: Neoadjuvant and adjuvant therapies are currently getting increasingly important in cutaneous melanoma (CM) management. However, there is still a lack of prognostic tools to identify which patients have a poor prognosis. There is increasing evidence that the liver score may be a [...] Read more.

Background: Neoadjuvant and adjuvant therapies are currently getting increasingly important in cutaneous melanoma (CM) management. However, there is still a lack of prognostic tools to identify which patients have a poor prognosis. There is increasing evidence that the liver score may be a potential prognostic parameter in different tumour types. The aim was to investigate whether established liver scores can establish the prognosis of CM. Methods: According to established methods, the APRI, the MELD score, the MELD-Na score and the De Ritis ratio were calculated from the laboratory values at the time of the initial diagnosis. Survival was compared with the Kaplan–Meier curve and tested with log-rank tests. Risk factors associated with cutaneous melanoma-specific survival (CMSS) and progression-free survival (PFS) were assessed by using the Cox proportional hazards regression model. To determine the diagnostic accuracy, we performed a time-dependent ROC analysis. Results: A total of 423 patients were included, including 141 patients in AJCC stage (2017) I (33.3%), 82 in stage II (19.4%), 128 in stage III (30.3%) and 72 in stage IV (17%). Median time until melanoma-specific death was 99 months (IQR: 37–126). In addition, 37.6% of patients relapsed with a median time to relapse of 88 months (IQR: 17.5–126). In all stages, tumour thickness and ulceration were independent markers for predicting CMSS and PFS (p < 0.05). The multivariable analysis with all stages showed no significant association with CM outcome for liver scores (p > 0.05). The subgroup analysis revealed that the APRI (≥0.2241) was associated with CMSS and PFS in melanoma stages I and II, independently of tumour thickness, age and ulceration (HR 2.57, 95% CI 1.14–5.75; HR 2.94, 95% CI 1.42–6.09, respectively). Conclusions: The 20-year prognosis of AJCC stage I and II CM was dependent on tumour thickness and the APRI. High tumour thickness and an APRI ≥ 0.2241 at the initial diagnosis were associated with a worse prognosis. Future studies should investigate the independent prognostic value of the APRI in low-stage CM. Furthermore, the APRI score could be a potential biomarker for nomograms. Full article

(This article belongs to the Special Issue Advances in Skin Cancer: Diagnosis, Treatment and Prognosis)

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9 pages, 1859 KiB

Open AccessCommunication

Are Dual-Phase ¹⁸F-Fluorodeoxyglucose PET-mpMRI Diagnostic Performances to Distinguish Brain Tumour Radionecrosis/Recurrence after Cranial Radiotherapy Usable in Routine?

by Axel Cailleteau, Ludovic Ferrer, Delphine Geffroy, Vincent Fleury, Paul Lalire, Mélanie Doré and Caroline Rousseau

Cancers 2024, 16(18), 3216; https://doi.org/10.3390/cancers16183216 - 21 Sep 2024

Viewed by 424

Abstract

Brain metastases or primary brain tumours had poor prognosis until the use of high dose radiotherapy. However, radionecrosis is a complex challenge in the post-radiotherapy management of these patients due to the difficulty of distinguishing this complication from local tumour recurrence. MRI alone [...] Read more.

Brain metastases or primary brain tumours had poor prognosis until the use of high dose radiotherapy. However, radionecrosis is a complex challenge in the post-radiotherapy management of these patients due to the difficulty of distinguishing this complication from local tumour recurrence. MRI alone has a variable specificity and sensibility, as does PET-CT imaging. We aimed to investigate the diagnostic performance of dual-phase ¹⁸F-FDG PET-mpMRI to distinguish cerebral radionecrosis from local tumour recurrence after cranial radiotherapy. A retrospective analysis was conducted between May 2021 and September 2022. Inclusion criteria encompassed patients with inconclusive MRI findings post-radiotherapy and history of cerebral radiotherapy for primary or metastatic brain lesions. Lesions are assessed qualitatively and semi-quantitatively. The gold standard to assess radionecrosis was histopathology or a composite criterion at three months. The study evaluated 24 lesions in 23 patients. Qualitative analysis yielded 85.7% sensitivity and 75% specificity. Semi-quantitative analysis, based on contralateral background noise, achieved 100% sensitivity and 50% specificity. Moreover, using contralateral frontal lobe background noise resulted in higher performances with 92% sensitivity and 63% specificity. Stratification by lesion type demonstrated 100% sensitivity and specificity rates for metastatic lesions. The diagnostic performance of dual-phase ¹⁸F-FDG PET-mpMRI shows promising results for metastatic lesions. Full article

(This article belongs to the Special Issue Brain Metastases: Diagnosis and Treatment)

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27 pages, 2839 KiB

Open AccessReview

Evidence of the Link between Stroma Remodeling and Prostate Cancer Prognosis

by Davide Vecchiotti, Letizia Clementi, Emanuele Cornacchia, Mauro Di Vito Nolfi, Daniela Verzella, Daria Capece, Francesca Zazzeroni and Adriano Angelucci

Cancers 2024, 16(18), 3215; https://doi.org/10.3390/cancers16183215 - 21 Sep 2024

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Abstract

Prostate cancer (PCa), the most commonly diagnosed cancer in men worldwide, is particularly challenging for oncologists when a precise prognosis needs to be established. Indeed, the entire clinical management in PCa has important drawbacks, generating an intense debate concerning the possibility to individuate [...] Read more.

Prostate cancer (PCa), the most commonly diagnosed cancer in men worldwide, is particularly challenging for oncologists when a precise prognosis needs to be established. Indeed, the entire clinical management in PCa has important drawbacks, generating an intense debate concerning the possibility to individuate molecular biomarkers able to avoid overtreatment in patients with pathological indolent cancers. To date, the paradigmatic change in the view of cancer pathogenesis prompts to look for prognostic biomarkers not only in cancer epithelial cells but also in the tumor microenvironment. PCa ecology has been defined with increasing details in the last few years, and a number of promising key markers associated with the reactive stroma are now available. Here, we provide an updated description of the most biologically significant and cited prognosis-oriented microenvironment biomarkers derived from the main reactive processes during PCa pathogenesis: tissue adaptations, inflammatory response and metabolic reprogramming. Proposed biomarkers include factors involved in stromal cell differentiation, cancer-normal cell crosstalk, angiogenesis, extracellular matrix remodeling and energy metabolism. Full article

(This article belongs to the Special Issue Biomarkers in Prostate Cancers)

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Open AccessArticle

Response Rates and Transplantation Impact in Patients with Relapsed Acute Promyelocytic Leukemia

by Alessandro Costa, Carmelo Gurnari, Emilia Scalzulli, Laura Cicconi, Luca Guarnera, Ida Carmosino, Raffaella Cerretti, Maria Laura Bisegna, Saveria Capria, Clara Minotti, Anna Paola Iori, Lorenzo Torrieri, Adriano Venditti, Alessandro Pulsoni, Maurizio Martelli, Maria Teresa Voso and Massimo Breccia

Cancers 2024, 16(18), 3214; https://doi.org/10.3390/cancers16183214 - 21 Sep 2024

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Abstract

Background: The introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has radically improved the prognosis of acute promyelocytic leukemia (APL), with cure rates above 80%. While relapse occurs in less than 20% of cases, addressing this issue remains challenging. Identifying [...] Read more.

Background: The introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has radically improved the prognosis of acute promyelocytic leukemia (APL), with cure rates above 80%. While relapse occurs in less than 20% of cases, addressing this issue remains challenging. Identifying effective salvage therapies for relapsed APL is crucial to improve patient outcomes. Methods: A retrospective analysis was performed on a multicentric cohort of 67 APL patients in first relapse, treated in three Italian hematology centers from June 1981 to November 2021. The overall survival (OS) and cumulative incidence of relapse (CIR) were calculated, and predictive factors were assessed using Cox regression models. Results: Overall, 61 patients (91%) received ATO ± ATRA (40.3%), chemo-based regimens (40.3%), or ATRA ± Gemtuzumab ozogamicin (GO) (10.4%). Complete remission (CR) was achieved in 98.2% of patients (molecular CR, n = 71.4%). With a median follow-up time of 54.5 months, the 5-year OS was 73% in the ATO ± ATRA group, 44% in the chemo-based group, and 29% in the ATRA ± GO group (p = 0.035). The 5-year OS rate was also higher for transplant recipients vs. non-recipients within the chemo-based cohort (50% vs. 33%, p = 0.017), but not in the ATO-based cohort (p = 0.12). ATO-based salvage therapy resulted in better OS in both univariate (p = 0.025) and multivariate analyses (p = 0.026). The 2-year CIR was higher in patients without molecular CR vs. patients in molecular CR (66% vs. 24%, p = 0.034). Molecular CR was a significant predictor of second relapse in both univariate (p = 0.035) and multivariate analyses (p = 0.036). Conclusions: Our findings support the efficacy of ATO-based therapies in first relapse of APL and confirm the achievement of molecular remission as an independent outcome predictor in both first and second APL relapse. Full article

(This article belongs to the Section Cancer Pathophysiology)

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Cancers, Volume 16, Issue 18 (September-2 2024) – 128 articles

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