Current Oncology

14 pages, 523 KiB

Open AccessArticle

Epidemiology, Treatment Patterns, Survival, Healthcare Resource Utilization, and Costs of Dedifferentiated Liposarcoma (DDLPS) in Canada: A Retrospective Cohort Study Using Administrative Databases in Ontario

by Soo Jin Seung, Anisia Wong, Raymond Milan, Nisha Chandran and Albiruni R. Abdul Razak

Curr. Oncol. 2025, 32(5), 273; https://doi.org/10.3390/curroncol32050273 - 9 May 2025

Abstract

Background: Dedifferentiated liposarcoma (DDLPS) is a rare, aggressive tumour with poor survival outcomes in advanced settings. This study assessed the incidence/prevalence, treatment patterns, survival, healthcare resource utilization (HCRU), and costs for DDLPS patients in Ontario, Canada. Methods: A retrospective cohort study was conducted [...] Read more.

Background: Dedifferentiated liposarcoma (DDLPS) is a rare, aggressive tumour with poor survival outcomes in advanced settings. This study assessed the incidence/prevalence, treatment patterns, survival, healthcare resource utilization (HCRU), and costs for DDLPS patients in Ontario, Canada. Methods: A retrospective cohort study was conducted among DDLPS patients between 2010 and 2022 using administrative databases. Overall survival, all-cause HCRU, and costs (2023 Canadian dollars, CAD) were compared based on advanced disease and resection status. Results: The overall incidence and cumulative prevalence of DDLPS was 0.465 and 1.995 per 100,000 people, respectively. Of all 611 DDLPS cases (64.3% male, median age [IQR]: 67 [57–76] years), 40.3% and 61.0% had advanced and unresected disease, respectively. The median overall survival (mOS) was 69 months [IQR = 15–151] for the entire cohort, but this was significantly lower for advanced and unresected disease (p < 0.0001). Among patients receiving systemic treatments (N = 117), 81.2% were prescribed doxorubicin as first-line treatment. All-cause healthcare costs (2023 CAD) amounted to CAD 34,448 per person-year (PPY), with inpatient hospitalizations being the highest cost driver at CAD 14,522 PPY and 0.8 inpatient hospitalization PPY for all years. Advanced disease had higher HCRU and costs. Conclusions: This is the first comprehensive real-world evidence study that quantifies the high mortality and cost burden associated with DDLPS in Canada. Full article

(This article belongs to the Special Issue Cost Effectiveness vs. Affordability in the Age of Targeted Drug Therapies)

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10 pages, 1726 KiB

Open AccessArticle

Impact of Multileaf Collimator Width and Normal Tissue Objective on Radiation Dose Distribution in Stereotactic Radiosurgery Using HyperArc for Single Brain Lesions

by Se An Oh, Jae Won Park, Ji Woon Yea, Jaehyeon Park and Yoon Young Jo

Curr. Oncol. 2025, 32(5), 272; https://doi.org/10.3390/curroncol32050272 - 7 May 2025

Abstract

This study retrospectively investigated the impact of stereotactic radiosurgery (SRS) normal tissue objective (NTO) and multileaf collimator (MLC) width on radiation dose distribution in patients with brain metastasis treated using HyperArc. In total, 21 patients who underwent SRS using the HyperArc of the [...] Read more.

This study retrospectively investigated the impact of stereotactic radiosurgery (SRS) normal tissue objective (NTO) and multileaf collimator (MLC) width on radiation dose distribution in patients with brain metastasis treated using HyperArc. In total, 21 patients who underwent SRS using the HyperArc of the TrueBeam linear accelerator from November 2022 to June 2024 were included. All patients received radiotherapy with HA_SH planned with SRS NTO and HD MLC. HyperArc(HA_AH) combined with the auto NTO and HD MLC and HyperArc(HA_AM) with auto NTO and millennium MLC were generated and compared. Monitor units (MU), conformity index (CI), radical dose homogeneity index (rDHI), moderate DHI (mDHI), and gradient index (GI) were evaluated as target factors, and V₂(Gy), V₁₀(Gy), V₁₂(Gy), V₁₈(Gy), V₁₀(cc), and V₁₂(cc) were evaluated as normal brain factors. Dosimetric comparisons were performed between HA_SH, HA_AH, and HA_AM and between target and normal brain tissues. Between HA_SH and HA_AH, average MU was 7206 and 5798, respectively; the difference was significant (p < 0.001). The MU of HA_AM was 5835. Among HA_SH, HA_AH, and HA_AM, CI and mDHI were not significantly different, but there were significant differences in rDHI, GI, and normal brain tissues. When treating a single lesion using HyperArc, SRS NTO influences MU and GI, and the MLC width influences rDHI and GI. In HyperArc for single metastatic brain lesions, SRS NTO and MLC width have a significant effect on the radiation dose delivered to the target and normal brain tissues. Full article

(This article belongs to the Special Issue Stereotactic Radiosurgery for Brain Tumors)

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10 pages, 1292 KiB

Open AccessCase Report

Drug Sensitivity Testing in Osteosarcoma: A Case Report

by Ines Lohse, Giselle Dutcher, Hassan Al-Ali, Warren Alperstein, Donald W. Coulter, Matteo Trucco, Jonathan C. Trent and Claes Wahlestedt

Curr. Oncol. 2025, 32(5), 271; https://doi.org/10.3390/curroncol32050271 - 7 May 2025

Abstract

Precision medicine approaches using ex-vivo drug sensitivity testing (DST) have received attention in the cancer research community as a means to improve treatment stratification in populations where multiple treatment attempts are not feasible, or no standard-of-care treatment exists, such as ultra-rare cancers with [...] Read more.

Precision medicine approaches using ex-vivo drug sensitivity testing (DST) have received attention in the cancer research community as a means to improve treatment stratification in populations where multiple treatment attempts are not feasible, or no standard-of-care treatment exists, such as ultra-rare cancers with a significant clinical need for effective treatment options, like osteosarcoma. DST has the potential to supplement existing patient stratification approaches by providing tumor-specific response data to aid in treatment selection at the time of treatment decision. We present the case of a pediatric osteosarcoma patient who was evaluated using DST at the time of standard-of-care treatment to evaluate treatment sensitivity. The DST screen indicated significant treatment sensitivity to anthracyclines and methotrexate, consistent with the first-line standard-of-care therapy (MAP). Clinical follow-up showed treatment sensitivity to standard-of-care MAP treatment and pathology results of 90% necrosis. The present case shows that DST screening is feasible from a technical standpoint, can be performed in a clinically relevant time frame that does not delay treatment start, and provides personalized drug sensitivity information on clinically available agents, and the DST results align with the clinical treatment response. Full article

(This article belongs to the Section Bone and Soft Tissue Oncology)

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Graphical abstract

7 pages, 3451 KiB

Open AccessCase Report

Combination of Osimertinib and Brigatinib in the Treatment of EGFR Triple-Mutated Lung Adenocarcinoma: A Case Report

by Daphnée Demers and Marie Florescu

Curr. Oncol. 2025, 32(5), 270; https://doi.org/10.3390/curroncol32050270 - 7 May 2025

Abstract

Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is widely used in treating patients with EGFR-mutated non-small-cell lung cancers (NSCLCs), especially in cases with secondary resistance mutations. However, tertiary resistance mutations often arise, and there is currently no established [...] Read more.

Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is widely used in treating patients with EGFR-mutated non-small-cell lung cancers (NSCLCs), especially in cases with secondary resistance mutations. However, tertiary resistance mutations often arise, and there is currently no established standard of care for NSCLC harboring triple EGFR mutations. In recent years, brigatinib, an anaplastic lymphoma kinase (ALK) TKI, has shown effectiveness in treating EGFR triple-mutated NSCLC. Despite this, the combined use of osimertinib and brigatinib remains largely unstudied. This case report describes a 51-year-old woman with EGFR-mutated NSCLC who was initially treated with first- and second-generation EGFR TKIs, then switched to osimertinib upon development of an exon 20 T790M mutation. When an exon 20 C797S mutation emerged, the decision was made to add brigatinib to the osimertinib regimen. The combined treatment of osimertinib and brigatinib offers a promising new approach. Nonetheless, it is important to consider the potential risk of off-target toxicities. Full article

(This article belongs to the Section Thoracic Oncology)

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13 pages, 1762 KiB

Open AccessArticle

Treatment Patterns, Clinical Outcomes and Quality of Life in BRCA1/2-Associated Breast Cancer Patients: A Retrospective Analysis

by Anna-Maria Parger, Paulina Gebhart, Daniela Muhr, Christian F. Singer and Yen Y. Tan

Curr. Oncol. 2025, 32(5), 269; https://doi.org/10.3390/curroncol32050269 - 2 May 2025

Abstract

Background: Breast cancer (BC) patients with germline BRCA1/2 pathogenic variants (PVs) often face unique challenges compared to non-carriers. However, the impact of PVs on treatment patterns, clinical outcomes, and quality of life (QoL) remains insufficiently explored. This study aims to assess these [...] Read more.

Background: Breast cancer (BC) patients with germline BRCA1/2 pathogenic variants (PVs) often face unique challenges compared to non-carriers. However, the impact of PVs on treatment patterns, clinical outcomes, and quality of life (QoL) remains insufficiently explored. This study aims to assess these factors in these individuals. Methods: A retrospective analysis was conducted using data from the Medical University of Vienna Center for Familial Breast and Ovarian Cancer between 2011 and 2021. Among 1285 individuals identified, 338 were included (120 BRCA1 PVs, 47 BRCA2 PVs, and 171 non-carriers). Clinical data including treatment patterns and outcomes were collected; QoL was assessed in BRCA1/2 PV carriers using the SF-12 questionnaire. Results: Among 338 BC patients, BRCA1 PV carriers were significantly younger at disease onset and more likely to present with triple-negative BC, with higher Ki-67 (>10%) than BRCA2 or non-carriers. Platinum-based chemotherapy was more frequently administered to BRCA PV carriers for neoadjuvant treatment (OR 7.7, p < 0.001), and therapeutic bilateral mastectomy was more common in BRCA1 carriers (44.7%) compared to BRCA2 (37.8%, p = 0.114) and non-carriers (25.2%, p = 0.003). Epirubicin was the primary agent for adjuvant chemotherapy across all groups compared to other chemotherapeutic agents. QoL assessments revealed significant physical health challenges, particularly among those who underwent neoadjuvant chemotherapy and surgery, while mental health scores remained relatively high. Conclusions: This study highlights the distinct treatment patterns and tumor characteristics associated with BRCA1/2 carriers, including the impact of treatments on quality of life. Nevertheless, our findings ought to be interpreted with caution due to the small sample size. Larger prospective studies with more complete treatment data, including PARP inhibitor use, and further research on supportive care strategies are needed for this high-risk population. Full article

(This article belongs to the Special Issue Advanced Research on Breast Cancer Genes in Cancers)

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13 pages, 1455 KiB

Open AccessArticle

Real-World Treatment Patterns and Survival Outcomes of Patients with Relapsed/Refractory Multiple Myeloma Treated with a Selinexor-Containing Triplet-Based Regimen

by Andrew Whiteley, Stephen C. Ijioma, David Ray, Spencer S. Langerman, Ellen Hu, Amy Pierre, Tomer Mark and Habte Yimer

Curr. Oncol. 2025, 32(5), 268; https://doi.org/10.3390/curroncol32050268 - 2 May 2025

Abstract

Treatment for relapsed/refractory multiple myeloma (RRMM) is complex, with several classes of drugs that can be combined into doublet, triplet, or quadruplet regimens. Real-world studies can help to determine the optimal treatment sequences and dosing through observed usage of drugs outside of clinical [...] Read more.

Treatment for relapsed/refractory multiple myeloma (RRMM) is complex, with several classes of drugs that can be combined into doublet, triplet, or quadruplet regimens. Real-world studies can help to determine the optimal treatment sequences and dosing through observed usage of drugs outside of clinical trials. Previous clinical trials have demonstrated high rates of durable responses in the treatment of patients with triple-class-exposed RRMM with regimens containing selinexor, a first-in-class, orally available selective exportin 1 inhibitor. This study analyzed real-world treatment patterns and survival outcomes using a nationwide electronic health record-derived, deidentified database of patients with RRMM treated with an eligible selinexor-containing, triplet-based regimen, including combinations with dexamethasone and pomalidomide, bortezomib, carfilzomib, or daratumumab. Patients had a real-world overall survival (rwOS) of 14.7 months (95% CI: 10.6, 20.9) and a derived progression-free survival (dPFS) of 4.7 months (95% CI: 3.4, 6.7). Patients with previous exposure to anti-CD38 monoclonal antibodies (mAbs) in the most recent regimen prior to the selinexor treatment had numerically higher survival outcomes (rwOS, 20.9; dPFS, 8.7 months). These data suggest that, in the real-world setting, the use of selinexor triplet regimens is effective in patients with RRMM, especially those with prior exposure to an anti-CD38 mAb in the immediate prior line of therapy. Full article

(This article belongs to the Special Issue Clinical Progression and Treatment Outcome of Multiple Myeloma)

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28 pages, 12877 KiB

Open AccessArticle

Burdens of Breast Cancer and Projections for 2030 Among Women in Asia: Findings from the 2021 Global Burden of Disease Study

by Feng Wang, Sixuan Liu, Jianwei Li, Yuzhen Shi, Zhaohui Geng, Yajie Ji and Jie Zheng

Curr. Oncol. 2025, 32(5), 267; https://doi.org/10.3390/curroncol32050267 - 1 May 2025

Abstract

Background: Employing the most recent dataset from the Global Burden of Disease (GBD) Study 2021, this report sought to delineate the current epidemiologic landscape of breast cancer in Asian women. Methods: We examined the evolving trends in disease prevalence and explored [...] Read more.

Background: Employing the most recent dataset from the Global Burden of Disease (GBD) Study 2021, this report sought to delineate the current epidemiologic landscape of breast cancer in Asian women. Methods: We examined the evolving trends in disease prevalence and explored the correlations between breast cancer and factors such as age, temporal periods, and generational cohorts. We utilized an autoregressive integrated moving average (ARIMA) model to predict the incidence and deaths of breast cancer in Asia. Results: From 1990 to 2021, the age-standardized incidence rate (ASIR), age-standardized DALYs rate (ASDR), and age-standardized mortality rate showed an overall upward trend for Asian women with breast cancer. In 2021, the high-income Asia Pacific region had the highest ASIR value, while South Asia had the lowest ASIR value. The highest age-standardized mortality rate and ASDR values in 2021 occurred in Southeast Asia, while the lowest values for these metrics were in East Asia. In 2021, breast cancer incidence and DALYs were highest in the 50–54 age group, with deaths peaking in the 55–59 age group. The leading risk factor attributed to breast cancer deaths in Asia in 1990 and 2021 was a “diet high in red meat”. Breast cancer incidence and mortality rates are expected to continue to rise in Asia over the next 10 years. Conclusions: The burden of breast cancer in Asian women is increasing, especially in low SDI countries. This study highlighted the differences between populations and regions and predicted the incidence and mortality rates of breast cancer in Asia over the next decade using an ARIMA model. An increased awareness of breast cancer risk factors and prevention strategies is necessary to reduce breast cancer burden in the future. Full article

(This article belongs to the Section Health Economics)

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25 pages, 1332 KiB

Open AccessArticle

Pilot Randomized Controlled Trial of iCanWork: Theory-Guided Return-to-Work Intervention for Individuals Touched by Cancer

by Christine Maheu, Maureen Parkinson, Kyla Johnson, Wing Lam Tock, Naomi Dolgoy, Simon-Pierre Dupuis and Mina Singh

Curr. Oncol. 2025, 32(5), 266; https://doi.org/10.3390/curroncol32050266 - 1 May 2025

Abstract

Background: Recent systematic reviews report a limited number of return-to-work (RTW) interventions for individuals touched by cancer (ITBC), with many falling short in effectiveness and lacking an integrated work-health approach. In response, iCanWork—a theoretically informed, multidisciplinary RTW intervention integrating vocational rehabilitation (VR) and [...] Read more.

Background: Recent systematic reviews report a limited number of return-to-work (RTW) interventions for individuals touched by cancer (ITBC), with many falling short in effectiveness and lacking an integrated work-health approach. In response, iCanWork—a theoretically informed, multidisciplinary RTW intervention integrating vocational rehabilitation (VR) and occupational therapy (OT)—was conceptualized and developed to address the gap identified in recent reviews for robust, work-health-focused RTW interventions. Methods: A pilot randomized controlled trial was conducted to explore the feasibility, acceptability, and preliminary work-related outcomes of the iCanWork intervention among 23 ITBC participants randomized to either the intervention or control group. Feasibility was assessed through recruitment, retention, and engagement benchmarks; acceptability was measured using a participant satisfaction survey. Preliminary work-health-related outcomes included RTW status, work ability index (WAI) scores, and health-related quality of life (QoL) domains. Results: Feasibility benchmarks were achieved, with 92% recruitment, 83% retention, and 100% completing at least one VR session. Adherence to the session delivery benchmarks was met by 75% of participants before RTW and 41.7% after RTW. Participants rated the intervention highly for its tailored and supportive approach. Compared to the control group, the iCanWork group showed modest improvements in RTW status, WAI scores (mean change: +2.54), and QoL domains, including fatigue, social roles, and pain interference. Given the small sample size, these exploratory findings should be interpreted as preliminary signals to inform outcome selection for a future trial. Conclusions: iCanWork is a feasible and acceptable RTW intervention for ITBC with early indications of benefit. These findings inform the design and outcome selection for a future, larger trial aimed at evaluating the intervention’s potential to improve RTW outcomes for ITBC. Full article

(This article belongs to the Special Issue Self-Management/Patient Activation and Self-Management Support Interventions for Cancer Survivors)

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16 pages, 243 KiB

Open AccessSystematic Review

Patient-Reported Outcome Measures (PROMS) in Lymphoma

by Neha Akkad and Christopher R. Flowers

Curr. Oncol. 2025, 32(5), 265; https://doi.org/10.3390/curroncol32050265 - 1 May 2025

Abstract

Patient-reported outcome measures (PROMs) are often used to evaluate the impact of treatment and clinical decisions on the patient experience for patients with lymphoma. Regulatory agencies have provided guidance on the use of PROMs for patient-focused drug development. Though PROMs are increasingly utilized, [...] Read more.

Patient-reported outcome measures (PROMs) are often used to evaluate the impact of treatment and clinical decisions on the patient experience for patients with lymphoma. Regulatory agencies have provided guidance on the use of PROMs for patient-focused drug development. Though PROMs are increasingly utilized, the way in which they are used, analyzed, and reported is heterogeneous. This systematic evidence-based review will focus on how PROMs are currently used for patients with lymphoma, what domains PROMs measure, their clinical significance, links to clinical outcomes, and what gaps need to be filled to better incorporate PROMs as endpoints in clinical trials and clinical decision-making. Full article

(This article belongs to the Section Hematology)

15 pages, 522 KiB

Open AccessReview

Role of Immunotherapy in the Treatment of Hepatocellular Carcinoma

by Irina Y. Dobrosotskaya, Rashmi Kumar and Timothy L. Frankel

Curr. Oncol. 2025, 32(5), 264; https://doi.org/10.3390/curroncol32050264 - 30 Apr 2025

Abstract

Hepatocellular carcinoma is the most common primary liver tumor and is strongly related to underlying liver cirrhosis. Common etiologies include viral hepatitis, elevated alcohol consumption and metabolic diseases, all of which result in liver inflammation and scarring. Previously, systemic therapies for locally advanced [...] Read more.

Hepatocellular carcinoma is the most common primary liver tumor and is strongly related to underlying liver cirrhosis. Common etiologies include viral hepatitis, elevated alcohol consumption and metabolic diseases, all of which result in liver inflammation and scarring. Previously, systemic therapies for locally advanced or metastatic disease were limited to tyrosine kinase inhibitors with poor efficacy and rare cures. Recent advances have harnessed the power of the immune system to combat disease, resulting in improved outcomes and occasional cures. Here, we describe the recent clinical trials in immunotherapies for the treatment of hepatocellular carcinoma as first- and second-line therapies and in combination with other drug classes. Full article

(This article belongs to the Special Issue Innovative Therapeutic Strategies, Biomarkers, and Molecular Pathways in Gastrointestinal and Hepatobiliary Cancers)

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20 pages, 3116 KiB

Open AccessArticle

Risk Factors for Recurrence in Serous Borderline Ovarian Tumors and Early-Stage Low-Grade Serous Ovarian Carcinoma

by Jingjing Zhang, Ming Wang and Yumei Wu

Curr. Oncol. 2025, 32(5), 263; https://doi.org/10.3390/curroncol32050263 - 30 Apr 2025

Abstract

Background: Tumor recurrence significantly impacts the quality of life and fertility of patients with serous borderline ovarian tumors (SBOT) and early-stage low-grade serous ovarian carcinoma (LGSOC). This study aims to characterize recurrence patterns, identify independent risk factors for recurrence, and develop a nomogram [...] Read more.

Background: Tumor recurrence significantly impacts the quality of life and fertility of patients with serous borderline ovarian tumors (SBOT) and early-stage low-grade serous ovarian carcinoma (LGSOC). This study aims to characterize recurrence patterns, identify independent risk factors for recurrence, and develop a nomogram to predict recurrence-free survival (RFS). Methods: We conducted a retrospective case-control study to investigate recurrence in patients undergoing fertility-sparing surgery (FSS) and radical surgery (RS). Logistic regression and Cox regression were used to identify risk factors. Kaplan–Meier analysis was applied to evaluate RFS. A nomogram was developed based on identified variables to predict RFS. Results: Tumor capsule disruption and micropapillary were associated with higher recurrence risk in the FSS group. Non-invasive implants were associated with higher recurrence risk in the RS group. The nomogram prediction model was developed based on identified risk factors. The area under the curve (AUC) for RFS predictions was 0.74 (95% CI: 0.62–0.85) at 3 years and 0.78 (95% CI: 0.67–0.89) at 5 years for the FSS group and 0.87 (95% CI: 0.76–0.98) at 3 years and 0.81 (95% CI: 0.65–0.97) at 5 years for the RS group. Conclusions: We identified the risk factors for recurrence of SBOT and early-stage LGSOC following FSS and RS procedures and developed a predictive model for forecasting RFS. This model provides valuable guidance for patients and clinicians in predicting recurrence risk for patients. Full article

(This article belongs to the Section Gynecologic Oncology)

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18 pages, 7056 KiB

Open AccessArticle

The Spatial Proximity of CD8⁺ FoxP3⁺PD-1⁺ Cells to Tumor Cells: A More Accurate Predictor of Immunotherapy Outcomes in Advanced Non-Small-Cell Lung Cancer

by Zijuan Hu, Zhihuang Hu, Keji Chen, Huixia Huang, Xinyang Zhong, Yaxian Wang, Jiayu Chen, Xuefeng He, Di Shi, Yupeng Zeng, Jiwei Li, Xiaoyan Zhou and Ping Wei

Curr. Oncol. 2025, 32(5), 262; https://doi.org/10.3390/curroncol32050262 - 30 Apr 2025

Abstract

Background: To optimize precision immunotherapy for advanced NSCLC, comprehensive tumor immune microenvironment (TIME) characterization is crucial for efficacy prediction. Methods: Pretreatment tumor samples from 46 advanced NSCLC patients treated with PD-1/PD-L1 inhibitors were analyzed. The subregional abundance and spatial proximity scores of TIME [...] Read more.

Background: To optimize precision immunotherapy for advanced NSCLC, comprehensive tumor immune microenvironment (TIME) characterization is crucial for efficacy prediction. Methods: Pretreatment tumor samples from 46 advanced NSCLC patients treated with PD-1/PD-L1 inhibitors were analyzed. The subregional abundance and spatial proximity scores of TIME cell subpopulations in 27 samples were assessed via multiplex immunohistochemistry (mIHC) targeting pan-CK, CD163, CD8, FoxP3, PD-1, and PD-L1. Correlations between the TIME features, clinicopathologic factors, treatment response, and prognosis were evaluated. Results: CD8⁺FoxP3⁺ cells were identified in NSCLC tissues, predominantly expressing PD-1/PD-L1. The PD-L1 TPS subgroups showed significant immune cell density/proximity differences, but CD8⁺FoxP3⁺PD-1⁺ infiltration was PD-L1 TPS-independent. Responders had higher CD8⁺FoxP3⁺PD-1^high density (p = 0.0497) and proximity scores (p = 0.0099) than non-responders. The CD8⁺FoxP3⁺PD-1⁺ presence and tumor proximity were essential for favorable outcomes. In low-PD-L1 TPS patients, the CD8⁺FoxP3⁺PD-1⁺ abundance and proximity scores strongly predicted the response (AUC: 0.79 and 0.75 vs. PD-L1 TPS AUC = 0.58). A survival analysis linked the presence and proximity score of CD8⁺FoxP3⁺PD-1⁺ cells to prolonged overall survival (OS) and progression-free survival (PFS). Notably, a low proximity score of CD8⁺FoxP3⁺PD-1⁺ cells emerged as an independent risk factor for a shorter PFS (HR = 6.16, 95% CI: 2.12–17.93, p = 0.001). Conclusion: The CD8⁺FoxP3⁺PD-1⁺ spatial proximity to tumor cells robustly predicts improved immunotherapy outcomes in advanced NSCLC. Full article

(This article belongs to the Section Thoracic Oncology)

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15 pages, 1197 KiB

Open AccessReview

ADCs and TCE in SCLC Therapy: The Beginning of a New Era?

by Paola Muscolino, Fausto Omero, Desirèe Speranza, Carla Infurna, Silvana Parisi, Vincenzo Cianci, Massimiliano Berretta, Alessandro Russo and Mariacarmela Santarpia

Curr. Oncol. 2025, 32(5), 261; https://doi.org/10.3390/curroncol32050261 - 30 Apr 2025

Abstract

The therapeutic landscape for small cell lung cancer (SCLC) has remained stationary for decades, with chemotherapy representing the sole treatment strategy, with a modest survival benefit. The addition of immune checkpoint inhibitors (ICIs) to standard first-line chemotherapy for SCLC was a considerable milestone. [...] Read more.

The therapeutic landscape for small cell lung cancer (SCLC) has remained stationary for decades, with chemotherapy representing the sole treatment strategy, with a modest survival benefit. The addition of immune checkpoint inhibitors (ICIs) to standard first-line chemotherapy for SCLC was a considerable milestone. However, despite high overall response rates, this strategy failed to deliver long-term benefits for most patients, who continue to face a poor prognosis. Over the last few years, a deeper knowledge of the molecular biology of SCLC and the impressive advancements in drug development, have led to the generation of novel classes of systemic therapies that promise to revolutionize the current therapeutic scenario. Among the various therapeutic approaches in development, T-cell Engagers (TCE) and antibody-drug conjugates (ADCs) stand out due to their unique structural characteristics and mechanisms of action. These therapies represent a paradigm shift from traditional monoclonal antibody (mAb) and chemotherapy regimens, allowing direct engagement of multiple targets associated with tumor progression. In this review, we provide an overview of current drug development in SCLC, specifically focusing on these new agents, summarizing available evidence, and tracking future directions. Full article

(This article belongs to the Special Issue Hype or Hope—Combination Therapies for Lung Cancer)

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10 pages, 1280 KiB

Open AccessCase Report

Spontaneous Dramatic Regression of Clear Cell Renal Cell Carcinoma After Pazopanib-Induced Severe Systemic Inflammatory Syndrome: A Case Report and Literature Review

by Chi Hyuk Oh and Hong Jun Kim

Curr. Oncol. 2025, 32(5), 260; https://doi.org/10.3390/curroncol32050260 - 30 Apr 2025

Abstract

Renal cell carcinoma (RCC) is the most common type of kidney cancer, accounting for a significant proportion of all cancer cases in Korea. This case report presents a unique instance of spontaneous dramatic tumor regression in a 42-year-old Korean male diagnosed with clear [...] Read more.

Renal cell carcinoma (RCC) is the most common type of kidney cancer, accounting for a significant proportion of all cancer cases in Korea. This case report presents a unique instance of spontaneous dramatic tumor regression in a 42-year-old Korean male diagnosed with clear cell RCC. The patient initially presented with right lower back pain, weight loss, and a loss of appetite. Following systemic immunotherapy with nivolumab and ipilimumab, and right radical nephrectomy, the patient was diagnosed with metastatic clear cell RCC, with new metastatic lesions detected in the liver, and on the chest wall on follow-up imaging. Second-line systemic treatment with pazopanib was initiated. Shortly thereafter, the patient developed severe systemic inflammatory syndrome, resulting in a mental stupor and acute kidney failure. Intensive care, including continuous renal replacement therapy and high-dose immunosuppressants, was administered. The patient’s condition improved significantly with the intensive care regimen, leading to unintended tumor regression. These potentially fatal side effects occurred without infection, as confirmed by negative blood and urine cultures, and were attributed to the recent introduction of pazopanib. Follow-up imaging showed a significant reduction in hepatic metastatic lesions and the disappearance of chest wall nodules. This is the first reported case of RCC tumor regression following the side effects of pazopanib, underscoring the need for further studies into the immune mechanisms involved in RCC treatment and highlighting potential therapeutic strategies that leverage innate immune responses. Full article

(This article belongs to the Section Genitourinary Oncology)

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8 pages, 209 KiB

Open AccessArticle

Does Pre-Existing Chronic Obstructive Pulmonary Disease Increase the Risk of Checkpoint Inhibitor Pneumonitis in Advanced/Metastatic Non-Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors?

by David Spillane, Carmela Pepe, Goulnar Kasymjanova, Diane Cruiziat, Sara Cohen, Jeremy Naimer and Jason Agulnik

Curr. Oncol. 2025, 32(5), 259; https://doi.org/10.3390/curroncol32050259 - 29 Apr 2025

Abstract

Objective: Immune checkpoint inhibitors (ICIs) are front-line treatment options for NSCLC. ICI therapy is associated with a risk of immune-related adverse events (irAEs). Checkpoint inhibitor pneumonitis (CIP) is a potentially life-threatening irAE. Previous studies have demonstrated that asthma and interstitial lung disease are [...] Read more.

Objective: Immune checkpoint inhibitors (ICIs) are front-line treatment options for NSCLC. ICI therapy is associated with a risk of immune-related adverse events (irAEs). Checkpoint inhibitor pneumonitis (CIP) is a potentially life-threatening irAE. Previous studies have demonstrated that asthma and interstitial lung disease are associated with an increased risk of CIP. We sought to determine whether chronic obstructive pulmonary disease (COPD) is associated with CIP. Methods: This retrospective study examines a cohort of ICI-treated NSCLC patients either with or without chemotherapy at the Anna and Peter Brojde Lung Cancer Centre, Jewish General Hospital in Montreal, Canada between 2014 and 2023. We explored associations between risk factors and CIP using the Mann–Whitney U test or Fisher’s exact test. Analysis of prognostic factors was performed using a logistic regression model. All statistical analyses were carried out using SPSS software, version 24.0 (SPSS, Chicago, IL, USA). p-values of 0.05 or less were considered significant. Results: Of the 327 selected patients on ICIs, 23 experienced an acute respiratory deterioration that was attributed to CIP, 87/327(26.6%) patients had a pre-existing diagnosis of COPD, and 11/87 (12.6%) COPD patients experienced CIP compared to 13/240 (5.5%) non-COPD patients (p = 0.061). There was no statistical or clinically meaningful correlation between COPD severity and CIP. The only variable significantly associated with CIP was a poor ECOG performance status. Among ECOG 1 patients, 18/91 (19.8%) experienced CIP compared to 5/226 (2.2%) of those with an ECOG of 0. A multivariate assessment involving all 327 patients revealed no significant factors affecting CIP development. Conclusions: Our single-institution study revealed that although there was a trend, the presence of COPD was not statistically associated with an increased risk of CIP. Additionally, neither FEV1 nor DLCO had a meaningful impact on the development of CIP in COPD patients. Given these findings, we emphasize the need for larger prospective studies to confirm these observations before drawing definitive clinical recommendations. Full article

(This article belongs to the Section Thoracic Oncology)

18 pages, 932 KiB

Open AccessArticle

A Population Survival Kinetics Assessment of Extensive Small Cell Lung Cancer and Rationale for Maintenance Therapy

by David J. Stewart, Katherine Cole and Stephanie Brule

Curr. Oncol. 2025, 32(5), 258; https://doi.org/10.3390/curroncol32050258 - 29 Apr 2025

Abstract

Progression-free survival (PFS) and overall survival (OS) curves generally approximate first-order kinetics. On log-linear plots, convex curves with downward inflection (indicating late acceleration of progression/death) might arise from stopping effective therapies. We digitized published PFS/OS curves for etoposide/platinum-treated extensive small-cell lung cancer (SCLC) [...] Read more.

Progression-free survival (PFS) and overall survival (OS) curves generally approximate first-order kinetics. On log-linear plots, convex curves with downward inflection (indicating late acceleration of progression/death) might arise from stopping effective therapies. We digitized published PFS/OS curves for etoposide/platinum-treated extensive small-cell lung cancer (SCLC) and other malignancies and replotted the curves log-linearly. Of 26 SCLC PFS curves, 21 (81%) were highly convex (with a marked late down-turn), and 26 (100%) were moderately or highly convex vs. 35/888 (4%) highly convex and 186 (21%) moderately/highly convex curves for other cancers (p < 0.0001). For SCLC, all 32 OS curves were moderately or highly convex vs. 87/363 (24%) that were moderately/highly convex for other cancers (p < 0.0001). The SCLC PFS curves had an initial downward inflection at a median of 3.1 months (around the completion of first-line chemotherapy), then a second inflection at 5.4 months, with further acceleration of progression. The median PFS half-life was 11.9 months while receiving treatment vs. 1.7 months after the second inflection point. Immunotherapy benefit appeared to be limited to 6–10% of the population. SCLC PFS/OS curves are more often convex than for other cancers, reflecting SCLC chemotherapy sensitivity but rapid progression following the completion of first-line chemotherapy. Effective maintenance strategies are needed. Full article

(This article belongs to the Section Thoracic Oncology)

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13 pages, 891 KiB

Open AccessArticle

The Role of [¹⁸F]FDG PET/CT Prior to and During Neoadjuvant Chemotherapy for Soft Tissue Sarcomas

by Stijn J.C. van der Burg, Bernies van der Hiel, Lotte Heimans, J. Martijn Kerst, Michel W.J.M. Wouters, Petur Snaebjornsson, Yvonne M. Schrage, Winette T.A. van der Graaf and Winan J. van Houdt

Curr. Oncol. 2025, 32(5), 257; https://doi.org/10.3390/curroncol32050257 - 28 Apr 2025

Abstract

This retrospective, single-center study investigates the association between PET parameters and pathological response or disease recurrence in patients with soft tissue sarcoma (STS) treated with neoadjuvant chemotherapy (NACT). The maximum standardized uptake value (SUVmax_BL), metabolic tumor volume (MTV_BL), and [...] Read more.

This retrospective, single-center study investigates the association between PET parameters and pathological response or disease recurrence in patients with soft tissue sarcoma (STS) treated with neoadjuvant chemotherapy (NACT). The maximum standardized uptake value (SUVmax_BL), metabolic tumor volume (MTV_BL), and total lesion glycolysis (TLG_BL) were measured at baseline [¹⁸F]FDG PET/CT and the change in percentage (ΔSUVmax, ΔMTV, ΔTLG) from baseline to early evaluation [¹⁸F]FDG PET/CT was calculated. The optimal cutoff values of the different PET parameters for pathological response, defined as <10% residual viable tumor (RVT) or >15% fibrosis/hyalinization, and recurrence-free survival were obtained for analysis. Forty-two patients who underwent baseline [¹⁸F]FDG PET/CT and NACT followed by surgery were included between January 2015 and January 2023. The primary diagnoses were angiosarcoma (n = 15), leiomyosarcoma (n = 15), sarcoma not otherwise specified (n = 9) and synovial sarcoma (n = 3). Twenty-eight (66.6%) patients underwent an early evaluation PET/CT. MTV_BL, TLG_BL, and ΔSUVmax (p = 0.024; p = 0.042, p = 0.009, respectively) values above the cutoff were associated with a pathological response based on RVT. ΔSUVmax, ΔMTV, and ΔTLG (p = 0.002; p = 0.019; p = 0.039, respectively) values above the cutoff were positively related to >15% fibrosis/hyalinization. MTV_BL, TLG_BL, and ΔMTV (p = 0.014; p = 0.022; p = 0.034, respectively) values above the cutoff were prognostic for the recurrence of disease. [¹⁸F]FDG PET/CT has a promising role in STS patients treated with NACT. Full article

(This article belongs to the Special Issue Sarcoma Surgeries: Oncological Outcomes and Prognostic Factors)

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26 pages, 6801 KiB

Open AccessSystematic Review

Minimally Invasive Surgical Techniques for Renal Cell Carcinoma with Intravenous Tumor Thrombus: A Systematic Review of Laparoscopic and Robotic-Assisted Approaches

by Yiting Wu, Shuyang Feng and Ping Fu

Curr. Oncol. 2025, 32(5), 256; https://doi.org/10.3390/curroncol32050256 - 28 Apr 2025

Abstract

Introduction: Locally advanced renal cell carcinoma (RCC) with intravenous tumor thrombus (IVTT) represents 4–10% of renal tumors. This review assesses the safety and outcomes of minimally invasive techniques, specifically laparoscopic (LAP) and robotic-assisted (RA) methods, for treating RCC with IVTT. Methods: A literature [...] Read more.

Introduction: Locally advanced renal cell carcinoma (RCC) with intravenous tumor thrombus (IVTT) represents 4–10% of renal tumors. This review assesses the safety and outcomes of minimally invasive techniques, specifically laparoscopic (LAP) and robotic-assisted (RA) methods, for treating RCC with IVTT. Methods: A literature search across several databases identified 54 studies (42 case series, 12 cohort studies) for analysis. Perioperative outcomes, including operative time, blood loss, transfusion rates, length of stay, and complications, were compared based on IVTT levels. Results: LAP and RA techniques were feasible for low-level IVTT, showing similar perioperative results. RA outperformed LAP in high-level IVTT with shorter operative times and lower blood loss and transfusion rates, despite managing more complex cases. RA maintained stable cancer-specific mortality (CSM) and metastasis rates, whereas LAP exhibited higher rates in high-level cases. Both techniques had low local recurrence rates. Conclusion: RA may be a superior option for RCC with IVTT, especially in high-level cases, but the data come mainly from specialized centers, signaling a need for multicenter validation and standardized criteria. Long-term outcomes require further study to assess RA’s non-inferiority to LAP. Full article

(This article belongs to the Section Genitourinary Oncology)

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11 pages, 8363 KiB

Open AccessArticle

Molecular and Pathological Heterogeneity of Synchronous Small and Large Duct Intrahepatic Cholangiocarcinoma—A Case Series

by Savelina Popovska, Vladislav Nankov, Boriana Ilcheva and George Dimitrov

Curr. Oncol. 2025, 32(5), 255; https://doi.org/10.3390/curroncol32050255 - 27 Apr 2025

Abstract

Background: Synchronous small- and large-duct intrahepatic cholangiocarcinoma (iCCA) represents a rare and heterogeneous entity, posing challenges for diagnosis, prognosis, and treatment selection. The pathological and molecular diversity between these subtypes influences tumor behavior and therapeutic response, necessitating a personalized approach. This study investigates [...] Read more.

Background: Synchronous small- and large-duct intrahepatic cholangiocarcinoma (iCCA) represents a rare and heterogeneous entity, posing challenges for diagnosis, prognosis, and treatment selection. The pathological and molecular diversity between these subtypes influences tumor behavior and therapeutic response, necessitating a personalized approach. This study investigates the molecular and pathological heterogeneity of synchronous iCCA and its clinical implications. Methods: This prospective case series included six patients diagnosed with synchronous small- and large-duct iCCA at the Military Medical Academy, Sofia, between January 2023 and January 2025, with a median follow-up of 15 months. Tumor classification was based on histopathological examination, immunohistochemical analysis, and next-generation sequencing (NGS)-based genomic profiling. Radiological and clinical data were analyzed to assess tumor growth patterns, treatment response, and progression-free survival (PFS). Results: Small-duct-predominant iCCA was associated with IDH1/2 mutations and FGFR2 fusions, a mass-forming growth pattern, and longer PFS. In contrast, large-duct-predominant iCCA exhibited KRAS, TP53, and NF1 mutations, an infiltrative periductal growth pattern, and a more aggressive clinical course with shorter PFS. Tumor mutational burden-high (TMB-H) and microsatellite instability-high (MSI-H) were observed in a subset of large-duct iCCA cases, suggesting potential benefit from immune checkpoint inhibitors (ICIs). Conclusions: Synchronous small- and large-duct iCCA demonstrates distinct molecular, histopathological, and clinical features, necessitating individualized treatment strategies. Targeted therapies for IDH1/2- and FGFR2-altered small-duct iCCA have shown efficacy, whereas large-duct iCCA remains more aggressive and treatment-resistant, requiring novel therapeutic approaches. Future research should focus on adaptive treatment strategies that account for tumor heterogeneity and dominant molecular drivers. Full article

(This article belongs to the Section Gastrointestinal Oncology)

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