Journal of Cancer Research and Clinical Oncology最新文献

{"title":"Exceptional long-term responses from OCEAN and HORIZON trials: melflufen-dexamethasone as an expansion of treatment options for relapsed/refractory multiple myeloma in the era of new immunotherapies?","authors":"M Talarico, S Barbato, V Maisnar, S Delimpasi, M Puppi, I Rizzello, L Pantani, P Tacchetti, M Martello, I Vigliotta, C Terragna, M Cavo, Elena Zamagni, K Mancuso","doi":"10.1007/s00432-025-06326-3","DOIUrl":"https://doi.org/10.1007/s00432-025-06326-3","url":null,"abstract":"<p><p>Alkylating agents have represented the first effective drug class in multiple myeloma (MM) but, since the introduction of novel effective drugs, their use has progressively decreased and is currently relegated to autologous stem cell transplant (ASCT) and few other settings. Nevertheless, the combination of melflufen (a peptide-drug conjugate pro-drug of melphalan) and dexamethasone was approved by the U.S. Food & Drug Administration (FDA) for triple-class refractory (TCR) patients after ≥ 4 prior lines of therapy (LOT) following results of HORIZON clinical trial (NCT02963493). This combination was subsequently withdrawn as it was not associated with improved overall survival (OS) as compared to pomalidomide-dexamethasone (OCEAN clinical trial, NCT03151811). However, since a post-hoc analysis showed a benefit in OS for patients without prior ASCT or with a time to progression (TTP) > 36 months after ASCT, the European Medicines Agency (EMA) has approved melflufen-dexamethasone for TCR patients after ≥ 3 LOT, including specification that TTP must be ≥ 3 years in patients with prior ASCT. In this paper, we report three cases of patients receiving the combination melflufen-dexamethasone in the aforementioned clinical trials in three hematologic centers across Europe and achieving exceptionally long responses as compared to the overall enrolled populations, with good tolerability. Further, we discuss the potential use of this chemotherapy-based regimen in the era of novel immunotherapies.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"151 11","pages":"288"},"PeriodicalIF":2.8,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"\"Life gives you a lemon, you make lemonade\": a qualitative study of identity among young male adult cancer survivors.","authors":"Glenn F Flecther, May Aa Hauken","doi":"10.1007/s00432-025-06317-4","DOIUrl":"https://doi.org/10.1007/s00432-025-06317-4","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to explore how male young adult cancer survivors (YACSs), aged 18-39, reconstruct and make sense of their identity following the completion of cancer treatment by answering the research question: \"How do male YACS perceive and interpret changes in their identity following cancer treatment?</p><p><strong>Methods: </strong>A qualitative approach with an interpretive descriptive design was employed. Drawing on the theoretical framework of Agency and Communion, individual semi-structured interviews were conducted with 12 male YACS. The transcribed interviews were analyzed using Systematic Text Condensation.</p><p><strong>Results: </strong>The findings indicate that the identities of male YACS underwent significantly transformation following cancer treatment. The overarching theme \"A changed and matured identity\" was identified and elaborated by three main themes (1) \"I feel like an old man\", (2) \"My values and perspectives have changed\", and (3) \"I have some advice to share\". Participants reported impaired physical, cognitive and social capacities, which contributed to shift in their sense of self. These changes required them to adapt to new life circumstances, often affecting their ability to pursue age-normative goals critical to identity development.</p><p><strong>Conclusion: </strong>The findings indicate that the participants' pre-cancer identities, which emphasized agentic qualities over communal ones, were significantly altered. Post-treatment, they experienced a reorientation of values and priorities, shifting from an agentic to more communal self-perception contributing to the development of a more mature identity and a revised outlook on life. These findings may serve as a foundational basis for future research and to inform the development of clinical practices.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"151 11","pages":"287"},"PeriodicalIF":2.8,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptional regulation of nucleotide metabolism in medulloblastoma subtypes and prognostic implications analyzed by RNA-Seq.","authors":"Rong Huang, Xiaoxu Lu, Xueming Sun, Hui Wu","doi":"10.1007/s00432-025-06327-2","DOIUrl":"https://doi.org/10.1007/s00432-025-06327-2","url":null,"abstract":"<p><strong>Objective: </strong>Subtypes of medulloblastoma (MB), WNT, SHH, Group 3 and Group 4, have different prognoses and the impact of abnormal nucleotide metabolism remains unclear. Multi-omics data was integrated to analyze the effect of nucleotide metabolism genes on MB molecular characteristics, prognosis and drug sensitivity. The aim was to identify subtype-specific therapeutic targets to inform treatment.</p><p><strong>Methods: </strong>A total of 132 MB samples datasets were accessed, UMAP and hierarchical clustering analysis were performed using the expression profiles of 1804 nucleotide metabolism genes and association with molecular subtype was evaluated. Genes were screened and prognostic signatures constructed by univariate Cox regression, cross-validation and LASSO-Cox regression and predictive efficacy was verified in training and independent validation sets. Pharmacogenomic data were combined to predict differences in drug sensitivity between high- and low-risk groups.</p><p><strong>Results: </strong>Nucleotide metabolism gene expression profiles were distinct among the four major MB subtypes, indicating coupling of metabolic reprogramming and tumor lineage. 51 prognostic genes were screened and were involved in RNA splicing, anatomical structure maintenance and purine compound metabolism. A signature was constructed from 17 nucleotide metabolism genes which distinguished high from low-risk (p < 0.001) groups and gave an independent prognosis in multivariate analysis. Drug sensitivity analysis showed the high-risk group to be more sensitive to MEK/ERK inhibitors and the low-risk group to PLK1, IGF1R/IR, ROCK and mTORC1/2 inhibitors.</p><p><strong>Conclusion: </strong>Nucleotide metabolism-transcription coupling endows MB subtypes with heterogeneity and affects prognosis. The signature is a quantitative tool for individualized risk assessment and metabolism targeted therapy.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"151 11","pages":"281"},"PeriodicalIF":2.8,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative effectiveness and safety of enzalutamide versus abiraterone in patients with metastatic castration-resistant prostate cancer: a nationwide registry-based cohort study from Taiwan.","authors":"Wen-Kuan Huang, Po-Jung Su, Chun-Chi Chen, Ching-Fu Chang, Shao-Ming Yu, Ming-Jer Hsieh, Ming-Lung Tsai, Tien-Hsing Chen, Pao-Hsien Chu, I-Chang Hsieh, See-Tong Pang, Dong-Yi Chen","doi":"10.1007/s00432-025-06335-2","DOIUrl":"https://doi.org/10.1007/s00432-025-06335-2","url":null,"abstract":"<p><strong>Purpose: </strong>The real-world effectiveness and safety of abiraterone or enzalutamide in the Asian population with metastatic castration-resistant prostate cancer (mCRPC) remains unclear.</p><p><strong>Methods: </strong>Using the Taiwan National Health Insurance Research Database, we identified a cohort of 3056 patients diagnosed with mCRPC receiving abiraterone or enzalutamide from January 1, 2017 through April 30, 2020, followed until December 31, 2021. We applied inverse probability of treatment weighting (IPTW) to balance the treatment groups and compare outcomes between the two treatment groups. Effectiveness outcomes included all-cause death, prostate cancer-related death, and treatment failure. Safety outcomes included major adverse CV events (MACE), fractures, and venous thromboembolism (VTE).</p><p><strong>Results: </strong>Enzalutamide use was associated with superior overall survival (hazard ratio 0.88, 95% confidence interval [CI] 0.82-0.96) compared with abiraterone use, which was majorly contributed from pre-docetaxel use (HR 0.89, 95% CI 0.81-0.98) but not post-docetaxel use (HR = 0.93, 95% CI 0.80-1.07). The median overall survival of pre-docetaxel abiraterone and enzalutamide was 36.1 and 39.9 months, respectively. In contrast, the median overall survival of post-docetaxel abiraterone and enzalutamide was 22.5 and 24.2 months, respectively. In terms of safety outcomes, enzalutamide use was significantly associated with lower VTE events compared with abiraterone use, but there was no difference in MACE or fracture risk between enzalutamide and abiraterone.</p><p><strong>Conclusions: </strong>We demonstrated the survival of enzalutamide and abiraterone use in Taiwanese patients with mCRPC is consistent with pivotal trials. The higher VTE risk with abiraterone use should be monitored.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"151 11","pages":"284"},"PeriodicalIF":2.8,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deficient DNA mismatch repair and Nectin-4 expression in upper tract urothelial carcinoma (UTUC).","authors":"Peichen Duan, Le Yu, Yichang Hao, Shaohui Deng, Peng Hong, Min Lu, Shudong Zhang","doi":"10.1007/s00432-025-06312-9","DOIUrl":"https://doi.org/10.1007/s00432-025-06312-9","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the prevalence of deficient DNA mismatch repair (dMMR) status in upper tract urothelial carcinoma (UTUC) and its association with clinicopathological characteristics as well as Nectin-4 immunohistochemical expression.</p><p><strong>Methods: </strong>We retrospectively identified histologically confirmed UTUC cases treated at Peking University Third Hospital between December 2016 and September 2023. Eligible participants were required to also possess complete clinicopathological records and available formalin-fixed, paraffin-embedded (FFPE) tumor specimens suitable for immunohistochemical evaluation. MMR protein expression was categorized as either dMMR or proficient mismatch repair (pMMR), while Nectin-4 expression was quantitatively assessed using the H-score system. Samples were then classified as negative (H-score 0-14), low (H-score 15-99), medium (H-score 100-199), and high (H-score 200-300). Statistical significance was established at P < 0.05 using two-tailed tests.</p><p><strong>Results: </strong>A total of 339 patients were deemed eligible, with specimens successfully evaluated. 25 patients (7.4%) demonstrated dMMR status. High Nectin-4 expression was observed in 124 patients (36.7%). A statistically significant association was identified between dMMR status and elevated Nectin-4 expression (P = 0.044). No significant differences were detected between dMMR and pMMR groups regarding clinical parameters, including gender, age, tumor grade, or immunophenotypic characteristics.</p><p><strong>Conclusion: </strong>Our study revealed that 7.4% of UTUC patients exhibited dMMR status, with heterogeneous Nectin-4 expression observed across the cohort. Notably, we demonstrated a statistically significant correlation between dMMR status and elevated Nectin-4 expression, suggesting potential biological interplay. The combined biomarker profile warrants further investigation as a predictive tool for therapeutic strategies involving antibody-drug conjugates (e.g., enfortumab vedotin) and immune checkpoint inhibitors.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"151 11","pages":"280"},"PeriodicalIF":2.8,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From pathogenesis to the patient's bedside: a comprehensive review of extraskeletal myxoid chondrosarcoma.","authors":"Piotr Remiszewski, Sławomir Falkowski, Anna Szumera-Ciećkiewicz, Mateusz J Spałek, Piotr Rutkowski, Anna M Czarnecka","doi":"10.1007/s00432-025-06316-5","DOIUrl":"https://doi.org/10.1007/s00432-025-06316-5","url":null,"abstract":"<p><p>Extraskeletal myxoid chondrosarcoma (EMC) is characterised by recurrent NR4A3 gene rearrangements, most commonly EWSR1::NR4A3, and accounts for approximately 1-3% of soft-tissue sarcomas (STS). It typically arises in the deep soft tissues of the proximal lower limb, particularly the thigh. Diagnosis is best established by integrating morphology and immunophenotype with molecular confirmation; in particular, NR4A3 break-apart fluorescence in situ hybridisation (FISH) provides a practical single-assay solution. For localised disease, complete surgical excision remains the cornerstone of treatment. Radiotherapy (RT) improves local control when margins are close or tumours are large. Recurrence-free survival (RFS) varies: local recurrence (LR) rates range from 13 to 42% across studies, and distant metastases develop in around 35-45% of patients, primarily in the lungs. The median time to metastasis is approximately 28 months. Overall survival (OS) reflects the typically indolent yet metastatic course: 5-year OS 66-88%, and 10-year disease-specific survival approximately 85%. In advanced disease, anthracycline-based chemotherapy yields a low objective response rate (ORR), although occasional partial responses occur. By contrast, the anti-angiogenic tyrosine kinase inhibitor pazopanib produced an ORR of 18% and a median progression-free survival (PFS) of 19 months in a multicentre phase 2 study (NCT02066285). No clinically validated agents directly target NR4A3. This review summarises contemporary diagnostics and treatment, emphasising high-quality surgery, selective RT, and consideration of anti-angiogenic tyrosine kinase inhibitors in advanced disease.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"151 11","pages":"283"},"PeriodicalIF":2.8,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning-based hepatocellular carcinoma risk prediction model for patients with HBV-related compensated advanced chronic liver disease.","authors":"Yanqiu Li, Zihang Qiao, Yongqi Li, Ying Feng, Xianbo Wang","doi":"10.1007/s00432-025-06345-0","DOIUrl":"https://doi.org/10.1007/s00432-025-06345-0","url":null,"abstract":"","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"151 11","pages":"285"},"PeriodicalIF":2.8,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression and therapeutic potential of TROP2 in cisplatin-resistant germ cell tumors.","authors":"Laurenz Sperber, Melanie von Brandenstein, Carolina Kessler, Julian Heidenreich, Enno Storz, David Pfister, Pia Paffenholz, Yuri Tolkach, Marit Bernhardt, Ralph Wirtz, Markus Eckstein, Axel Heidenreich, Richard Weiten","doi":"10.1007/s00432-025-06325-4","DOIUrl":"https://doi.org/10.1007/s00432-025-06325-4","url":null,"abstract":"","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"151 11","pages":"279"},"PeriodicalIF":2.8,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of extracellular vesicles in the communication between endometrial cancer cells and tumour-associated macrophages: a review.","authors":"Feng Li, Wei Shi","doi":"10.1007/s00432-025-06318-3","DOIUrl":"https://doi.org/10.1007/s00432-025-06318-3","url":null,"abstract":"<p><p>Endometrial cancer is a significant threat to the health of women worldwide. Extracellular vesicles are essential for the proliferation, migration, and invasion of cancer cells, whereas tumour-associated macrophages (TAMs) are key regulators of cancer development. The interaction between macrophages and extracellular vesicles is also important in endometrial cancer. Extracellular vesicles from endometrial cancer cells can promote the polarization of macrophages towards an M2-like phenotype, and those from macrophages can also decrease the sensitivity of endometrial cancer cells to radiation. This paper presents a review of the various roles of extracellular vesicles in endometrial cancer and their potential as biomarkers and therapeutic targets. Research progress on the communication between endometrial cancer cells and tumour-associated macrophages mediated by extracellular vesicles is reviewed as well.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"151 11","pages":"286"},"PeriodicalIF":2.8,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic impact of lymph node count features in total laryngectomy for advanced laryngeal squamous cell carcinoma.","authors":"Mihnea Cristian Trache, Lisa Budelmann, Philippe Christophe Breda, Jördis Kristin Eden, Stefan Bartels, Sophia Marie Häußler, Christian Stephan Betz, Jacob Friedrich Clausen, Lukas Wittig, Arne Böttcher","doi":"10.1007/s00432-025-06320-9","DOIUrl":"https://doi.org/10.1007/s00432-025-06320-9","url":null,"abstract":"<p><strong>Introduction: </strong>The optimal surgical management in advanced laryngeal squamous cell carcinoma (ALSCC) is still under debate. The extent of neck dissection as well as the nodal involvement affect survival metrics in head and neck cancer (HNSCC) patients. Despite pN status, other parameters like nodal yield (NY) or lymph node ratio (LNR) have been investigated before. There are data showing that log odds of positive lymph nodes (LODDS) are a good survival prognosticator in HNSCC in general but specific data on ALSCC is missing. This study aims to assess the prognostic value of lymph node count features on survival in ALSCC.</p><p><strong>Methods: </strong>We conducted a retrospective patient chart review on curative intent laryngectomy and bilateral neck dissection for ALSCC between 2009 and 2024 at a tertiary care center. Investigated lymph node count features besides NY included lymph node burden (LNB = number of positive lymph nodes), LNR (= LNB/NY) and the LODDS = log ((LNB + 0.5) / (NY-LNB + 0.5)). Univariate survival analysis was performed using the log-rank testing and Kaplan-Meier curves. The R maxstat package was utilized for an optimized cut-off point determination for cohort risk stratification.</p><p><strong>Results: </strong>We included 56 patients who underwent laryngectomy and bilateral neck dissection in our department. Survival analysis revealed a 5-year OS of 51% and median OS of 60.7 months. The LODDS ranged from -2.48 to 0.37 with a mean value of -1.68 ± 0.50. The cut-off at -1.94 for LODDS showed a 5-year DSF of 33% vs. 61% with a HR of 0.27 (p = 0.005) and the optimized cut-off of -1.55 showed significant differences in 5-year OS (69 vs. 17%, HR: 0.29, p = 0.003). LODDS indicated the highest concordance indices for both DFS and OS compared to LNB and LNR.</p><p><strong>Conclusion: </strong>We propose LODDS to serve as a superior prognosticator compared to LNB and LNR concerning DFS and OS in TL for ALSCC. LODDS values of -1.94 for DFS and -1.55 for OS appear as suitable thresholds for risk stratification.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":"151 11","pages":"282"},"PeriodicalIF":2.8,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}