Cancers

12 pages, 1511 KiB

Open AccessArticle

Sex-Based Differences in Lung Cancer Incidence: A Retrospective Analysis of Two Large US-Based Cancer Databases

by Kalyan Ratnakaram, Sai Yendamuri, Adrienne Groman and Sukumar Kalvapudi

Cancers 2024, 16(19), 3244; https://doi.org/10.3390/cancers16193244 (registering DOI) - 24 Sep 2024

Background/Objectives: Non-small cell lung cancer (NSCLC) has seen a relative rise in incidence among females versus males in recent years, although males still have a higher overall incidence. However, it is unclear whether this trend is consistent across all populations. Therefore, we retrospectively [...] Read more.

Background/Objectives: Non-small cell lung cancer (NSCLC) has seen a relative rise in incidence among females versus males in recent years, although males still have a higher overall incidence. However, it is unclear whether this trend is consistent across all populations. Therefore, we retrospectively examined this relationship in two large high-risk clinical cohorts. Methods: First, we analyzed lung cancer incidence among individuals with a smoking history of over 40 pack-years in the National Lung Screening Trial (NLST). Then, we investigated the incidence of second primary NSCLC in patients who underwent lobectomy for previous stage I lung cancer using the Surveillance, Epidemiology, and End Results (SEER) database. We performed both univariate and multivariable time-to-event analyses to investigate the relationship between sex and lung cancer incidence. Results: In the NLST cohort (n = 37,627), females had a higher risk of developing primary NSCLC than males (HR = 1.11 [1.007–1.222], p = 0.035) after adjusting for age and pack-year history. In the SEER cohort (n = 19,327), females again exhibited an increased risk of developing a second primary lung cancer (HR = 1.138 [1.02–1.269], p = 0.021), after adjusting for age, race, grade, and histology. Conclusions: Our analysis reveals that females have a modestly higher lung cancer incidence than males in high-risk populations. These findings underscore the importance of further researching the underlying cellular processes that may cause sex-specific differences in lung cancer incidence. Full article

(This article belongs to the Special Issue Advancements in Lung Cancer Surgical Treatment and Prognosis)

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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 (registering DOI) - 23 Sep 2024

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 (registering DOI) - 23 Sep 2024

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 (registering DOI) - 23 Sep 2024

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 (registering DOI) - 23 Sep 2024

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, 989 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 (registering DOI) - 23 Sep 2024

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)

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 (registering DOI) - 23 Sep 2024

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 (registering DOI) - 23 Sep 2024

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 (registering DOI) - 23 Sep 2024

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 (registering DOI) - 23 Sep 2024

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 (registering DOI) - 23 Sep 2024

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 (registering DOI) - 23 Sep 2024

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 (registering DOI) - 23 Sep 2024

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 (registering DOI) - 22 Sep 2024

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 (registering DOI) - 22 Sep 2024

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 (registering DOI) - 22 Sep 2024

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 (registering DOI) - 22 Sep 2024

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 (registering DOI) - 22 Sep 2024

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 (registering DOI) - 22 Sep 2024

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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