Journal Of Cancer Research And Clinical Oncology[JOURNAL]
Sun
200 papers
Social inequalities in cancer in Germany: a call to action.
Sibert NT, Wellbrock M, Bedir A … +16 more , Grundmann N, Herrmann M, Hoebel J, Jansen L, Popova V, Schwettmann L, Arndt V, Brand T, Gude AC, Hoe C, Hübner J, Lückemeyer M, Mons U, Dalton SO, Voigtländer S, Erdmann F
J Cancer Res Clin Oncol · 2026 Mar · PMID 41806187 · Full text
BACKGROUND: Social inequalities in cancer constitute a major public health challenge. A lower socioeconomic position (SEP) is consistently associated with higher exposure to cancer risk factors, lower participation in sc...
BACKGROUND: Social inequalities in cancer constitute a major public health challenge. A lower socioeconomic position (SEP) is consistently associated with higher exposure to cancer risk factors, lower participation in screening, more advanced stage at diagnosis, poorer survival, and adverse survivorship outcomes. In Germany, these inequalities remain insufficiently addressed in research and health policy. METHODS: This paper synthesises evidence and expert perspectives derived from a national workshop organised by the Cancer Epidemiology Working Group of the German Society for Epidemiology (DGEpi) in collaboration with the German Cancer Research Center. More than 30 experts in cancer epidemiology and social inequality research, together with international contributors, reviewed-based on existing conceptual frameworks-the German data landscape, and empirical evidence across the cancer continuum. Structural, methodological, and ethical barriers were identified, and implications for research, policy, and practice were discussed. An international comparison with Denmark was used to contextualise findings. RESULTS: Available evidence demonstrates pronounced socioeconomic inequalities across nearly all stages of the cancer continuum in Germany, including prevention, screening, incidence, diagnosis, survival, and survivorship. However, major research gaps persist. Key barriers include limited availability of individual-level SEP data, reliance on area-based deprivation indices, restricted data linkage, fragmented healthcare structures, and limited integration of equity considerations into national cancer strategies. International experience shows that comprehensive registries, data linkage, and targeted interventions can reduce inequalities. CONCLUSIONS: Reducing social inequalities in cancer in Germany requires coordinated and evidence-based action. Priorities include improving SEP data availability and linkage, embedding equity objectives into the National Cancer Plan, implementing targeted interventions for vulnerable groups, and strengthening intersectoral collaboration. Ethical and patient perspectives strongly support responsible use of health data to address avoidable inequalities.
RBM15B promotes hepatocellular carcinoma progression via IGF2BP1-mediated ITSN2 mRNA stabilization.
Xu Y, Xiong M, Chen W … +6 more , Yao C, Chen Y, Man D, Xie H, Ye X, Jia C
J Cancer Res Clin Oncol · 2026 Mar · PMID 41795047 · Full text
BACKGROUND: N6-methyladenosine (m6A) is a chemical modification of adenosine in RNA that plays a crucial role in the regulation of gene expression. As the most abundant form of RNA chemical methylation, m6A is aberrantly...
BACKGROUND: N6-methyladenosine (m6A) is a chemical modification of adenosine in RNA that plays a crucial role in the regulation of gene expression. As the most abundant form of RNA chemical methylation, m6A is aberrantly expressed in hepatocellular carcinoma (HCC), where it affects multiple biological processes including targeted RNA splicing, transport, degradation, stabilization, and translation. RBM15B (RNA-binding motif protein 15B), is a gene that encodes a protein involved in RNA processing and regulation. RBM15B is a member of the RNA-binding motif (RBM) protein family, which plays diverse roles in post-transcriptional gene regulation. RBM15B is proven to be involved in mRNA processing, including pre-mRNA splicing, mRNA transport, and mRNA stability. It may also participate in other RNA-related processes such as mRNA translation and RNA decay. METHOD: We investigated the phenotypes of RBM15B in HCC using the TCGA database, in-vitro, and in vivo assays. m6A dot blot was used to assess RNA methylation levels and Merip-seq/RNA-seq were employed to explore the biological effects and potential mechanisms of RBM15B in HCC. We hypothesized that RBM15B may regulate ITSN2 expression in HCC. To test this, RNA immunoprecipitation (RIP) followed by qRT-PCR was applied for the identification and characterization of target ITSN2 mRNA that interacted with RNA binding protein IGF2BP1, which may mediate the effects of RBM15B. To further elucidate the functional relationship between RBM15B and ITSN2, we performed rescue assays of cell proliferation and migration to determine whether RBM15B over-expression is able to restore the loss of function induced by ITSN2 knockdown to an extent. RESULTS: High levels of RBM15B were verified by both TCGA data and our cohort. High levels of RBM15B predicted a poor prognosis. RBM15B promotes HCC propagation and invasion in vitro and in vivo. RBM15B regulates the m6A of intersectin2 (ITSN2) mRNA via insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1)-facilitated stabilization of ITSN2 mRNA. ITSN2 depletion rescued the tumor-promoting phenotype induced by RBM15B overexpression. CONCLUSION: In summary, RBM15B-regulated m6A in ITSN2 mRNA facilitates HCC progression via IGF2BP1-guided stabilization of ITSN2 mRNA. Our study illustrates the importance of the RBM15B-IGF2BP1-ITSN2 regulatory axis based on m6A activity and provides new insights into epi-transcriptomic maladjustments of initiation and metastasis in HCC.
Hormonal management after risk-reducing surgery in BRCA-mutated triple-negative breast cancer survivors.
Jörg I, Chronas D
J Cancer Res Clin Oncol · 2026 Mar · PMID 41793502 · Full text
Premenopausal women carrying a BRCA1 or BRCA2 mutation are frequently advised to undergo risk-reducing bilateral salpingo-oophorectomy (BSO) to lower their significantly increased lifetime risk of ovarian cancer. However...
Premenopausal women carrying a BRCA1 or BRCA2 mutation are frequently advised to undergo risk-reducing bilateral salpingo-oophorectomy (BSO) to lower their significantly increased lifetime risk of ovarian cancer. However, this procedure induces abrupt estrogen deprivation, resulting in premature menopause with well-documented consequences including vasomotor symptoms (e.g., hot flashes, night sweats), urogenital atrophy, and long-term risks such as osteoporosis, cardiovascular disease, and cognitive decline (Nelson in Lancet 371(9614):760-770, 2008; Shuster et al. in Maturitas 65(2):161-166, 2010). To alleviate symptoms and prevent sequelae, hormone replacement therapy (HRT) remains the most effective intervention. However, the issue becomes complex when the patient has a personal history of triple-negative breast cancer (TNBC). Although TNBC lacks hormone receptor expression, systemic HRT has traditionally been contraindicated in breast cancer survivors, as early studies indicated an increased risk of recurrence with hormone therapy, even in receptor-negative subtypes (Kenemans et al. Lancet Oncol 10(2):135-146, 2009a). This leads to a critical question: Is HRT appropriate in BRCA mutation carriers with a history of TNBC following BSO, and if so, under what clinical conditions? What do current international guidelines, evidence, and expert recommendations suggest?
Targeting SLC6A8 suppresses tumor growth and enhances ferroptosis in hepatocellular carcinoma.
Bao W, Yu Y, Yu G … +3 more , Chen J, Li Y, Hai Y
J Cancer Res Clin Oncol · 2026 Mar · PMID 41787198 · Full text
BACKGROUND: Hepatocellular carcinoma (HCC) persists as a therapeutic challenge owing to restricted treatment alternatives and the dearth of effective biomarkers. The creatine transporter SLC6A8 has been documented to par...
BACKGROUND: Hepatocellular carcinoma (HCC) persists as a therapeutic challenge owing to restricted treatment alternatives and the dearth of effective biomarkers. The creatine transporter SLC6A8 has been documented to participate in the progression of various malignancies. However, the role that SLC6A8 plays in HCC remains poorly characterized. Hence, this study aimed to investigate the function of the SLC6A8 in HCC and evaluate its candidacy as a therapeutic target. METHODS: Bioinformatics analysis, qPCR on tissue specimens, and immunohistochemistry on tissue microarrays were utilized to assess the expression and clinical significance of SLC6A8 in HCC. In vitro assays including cell viability, colony formation, and cell migration, as well as an in vivo subcutaneous xenograft model, were employed to explore the impacts of both genetic silencing of SLC6A8 and pharmacological blockade of SLC6A8 on HCC tumor growth. The anti-tumor effect of SLC6A8 inhibition in combination with the ferroptosis inducer RSL3 in HCC was also examined in cellular and animal models. RESULTS: Our findings revealed that SLC6A8 is notably upregulated in HCC tissues and is associated with a poor prognosis. SLC6A8 knockdown suppressed cell proliferation and migration of HCC cells. RGX-202 also demonstrated potent antitumor efficacy in HCC cells both in vitro and in vivo. Moreover, SLC6A8 inhibition augmented cellular susceptibility to ferroptosis and significantly enhanced the anti-tumor efficacy of the ferroptosis inducer RSL3 in xenograft models of HCC. CONCLUSION: These findings underscore SLC6A8 as a promising therapeutic target, and its inhibitor combined with ferroptosis inducers may serve as an innovative treatment strategy for improving the therapeutic effect in HCC.
From mechanism to clinic: a panoramic perspective on targeting HMOX1 to overcome drug resistance.
Huang D, Ma Y, Gao W … +1 more , Xie Q
J Cancer Res Clin Oncol · 2026 Mar · PMID 41786997 · Full text
Drug resistance is a pivotal factor leading to the failure of cancer therapy, within which heme oxygenase-1 (HMOX1) plays a complex and paradoxical dual role. On one hand, HMOX1 protects cancer cells from oxidative damag...
Drug resistance is a pivotal factor leading to the failure of cancer therapy, within which heme oxygenase-1 (HMOX1) plays a complex and paradoxical dual role. On one hand, HMOX1 protects cancer cells from oxidative damage induced by chemotherapeutic drugs through its antioxidant properties. Concurrently, its catalytic downstream product, carbon monoxide (CO), inhibits cancer cell apoptosis, thereby mediating acquired drug resistance. On the other hand, HMOX1 is a key source of intracellular free iron. When its activity is excessively induced, it leads to the accumulation of excessive free iron, triggering the buildup of lipid peroxides and ferroptosis, which presents a novel opportunity to overcome drug resistance. This demonstrates that the function of HMOX1 can switch depending on its degree of activation. Therefore, a thorough analysis of its regulatory network and the mechanisms of its functional switch within different microenvironments is crucial for developing novel therapeutic strategies that target HMOX1 to overcome drug resistance. This review systematically summarizes the multiple mechanisms of HMOX1 in drug resistance, with a focus on HMOX1 inducers and inhibitors, as well as synergistic sensitization strategies in combination with other therapies. It aims to provide a comprehensive theoretical foundation and a forward-looking perspective for translating HMOX1-targeted therapy from basic research to clinical practice.
Real-world monitoring strategies and predictors guiding the transition from active surveillance to treatment in ISUP 1 prostate cancer.
Giannini G, Mousa A, Steiner E … +3 more , Artamonova N, Kafka M, Heidegger I
J Cancer Res Clin Oncol · 2026 Mar · PMID 41779210 · Full text
PURPOSE: Active surveillance (AS) is the standard approach for managing ISUP 1 prostate cancer (PCa), ensuring oncological safety while minimizing overtreatment. However, AS protocols vary significantly. This study asses...
PURPOSE: Active surveillance (AS) is the standard approach for managing ISUP 1 prostate cancer (PCa), ensuring oncological safety while minimizing overtreatment. However, AS protocols vary significantly. This study assessed a structured AS protocol incorporating PSA kinetics, multiparametric MRI (mpMRI), and targeted biopsies to identify predictors of treatment transition. METHODS: We retrospectively reviewed 89 patients with ISUP 1 PCa managed with AS between 2010 and 2024. Inclusion criteria were PSA < 10 ng/mL and ≤ 2 positive biopsy cores with ≤ 50% tumor involvement per core. Patients underwent regular PSA testing, mpMRI, and risk-adapted biopsies. Outcomes included treatment conversion, progression predictors, and the role of mpMRI. RESULTS: Median follow-up was 52.8 months. PSA was monitored at a median interval of 4.8 months, and mpMRI every 15.7 months (median). At diagnosis, 68.5% underwent mpMRI, with PIRADS 4 as the most frequent. During AS, 66.3% underwent at least one re-biopsy, most commonly triggered by PSA progression (73%). Treatment was initiated in 37.1% after a median of 37.9 months due to PSA progression (54.5%), mpMRI changes (21.2%), combined PSA/mpMRI findings (6.1%), histological upgrading (9.1%), or patient preference (3%). Treatments included radical prostatectomy, EBRT or LDR brachytherapy. Among these patients, no PSA persistence was observed; biochemical recurrence occurred in 6.1%, metastases in 4.0%, and overall mortality in 4.5%, with no PCa-specific deaths. CONCLUSION: A structured, risk-adapted AS protocol using PSA kinetics and mpMRI enabled personalized management and timely detection of progression. These findings support the standardization of AS protocols, which should be validated in larger cohorts.
Modified clear cell likelihood score and a new CAT score in the assessment of indeterminate small renal masses.
Blachura T, Matusik PS, Kowal A … +5 more , Radzikowska J, Jarczewski JD, Skiba Ł, Popiela TJ, Chrzan R
J Cancer Res Clin Oncol · 2026 Mar · PMID 41774259 · Full text
PURPOSE: In recent decades, small renal masses (SRMs) have become common incidental findings in cross-sectional studies; however, a widely implemented approach for the characterization of SRMs is still lacking. Thus, in...
PURPOSE: In recent decades, small renal masses (SRMs) have become common incidental findings in cross-sectional studies; however, a widely implemented approach for the characterization of SRMs is still lacking. Thus, in this study, we aimed to explore the diagnostic performance of existing algorithms and to propose - as a conceptual framework rather than a clinically verified tool - a new simple radiological scale for estimating the probability of malignancy in SRMs. METHODS: Patients with indeterminate solid SRMs (N = 50), discovered using magnetic resonance imaging (MRI) between 2012 and 2023 were included. In 38 cases, the final diagnosis was based on histopathology, while in 12 cases it relied on regression or lack of progression during follow-up. Modified versions of the clear cell likelihood score (ccLS) were calculated, and its diagnostic performance was assessed. Moreover, we analyzed the newly created score, which consisted of selected MRI and clinical features. All of our modified scales used a Likert score for the likelihood of clear cell renal cell carcinoma (ccRCC). RESULTS: Based on the results of our statistical analyses, we modified the ccLS by adding T1 SI ratio < 0.73, arterial to delayed ratio (ADER) > 0.99, and smoking as independent predictors of ccRCC. We created a new scale, the CAT score, which combined hyperintensity in the Corticomedullary phase, ADER > 0.99, and TI SI ratio < 0.73 (with 1 point being assigned to each of the above-mentioned MRI parameters). In our results, the best diagnostic accuracy was observed for a CAT score ≥ 2, with a sensitivity of 73.9% (51.6-89.8%), a specificity of 77.8% (57.7-91.4%), and an accuracy of 76.0% (61.8-86.9%). Univariate logistic regression analyses demonstrated that all scales created by our group were significant predictors of ccRCC. Importantly, they showed a better predictive ability than the standard ccLS score. CONCLUSIONS: The CAT score appears to improve the prediction of ccRCC compared with both standard and modified versions of the ccLS and may serve as a potential aid in the routine assessment of indeterminate SRMs. Nonetheless, this study should be regarded as a preliminary, proof-of-concept analysis rather than a definitive model-development study. The main limitation of our study is its small, single-center cohort, which limits the statistical power and robustness of model development. Moreover, a substantial proportion of benign diagnoses based only on radiological follow-up rather than histopathology. Therefore, before clinical implementation, the CAT score requires prospective validation in larger, independent, multicenter cohorts.
Crosstalk between mitophagy and breast cancer: mechanisms of action and clinical applications.
Rui K, Qiu J, Li M … +3 more , Huang J, Wang T, Yin K
J Cancer Res Clin Oncol · 2026 Feb · PMID 41764124 · Full text
Mitophagy, a key mechanism of selective autophagy, maintains cellular homeostasis by removing dysfunctional mitochondria, and its dysregulation is closely associated with tumor initiation and progression. As breast cance...
Mitophagy, a key mechanism of selective autophagy, maintains cellular homeostasis by removing dysfunctional mitochondria, and its dysregulation is closely associated with tumor initiation and progression. As breast cancer remains one of the most prevalent malignancies among women worldwide, its heterogeneity and therapeutic resistance have prompted growing interest in identifying novel molecular targets. Emerging evidence indicates that mitophagy plays a dual role in breast cancer development, metastasis, and treatment resistance by regulating energy metabolism, oxidative stress, and cell-fate decisions. This review systematically summarizes the molecular mechanisms of mitophagy and its dynamic regulatory networks in breast cancer. Further, it discusses emerging mitophagy-targeted therapeutic strategies, aiming to provide a theoretical foundation for the precision treatment of breast cancer.
Comparative cross-methodological analysis of the IDH-wildtype glioblastoma tumor microenvironment.
Cakmak P, Lun JH, Köhler M … +7 more , Burger MC, Macas J, Starzetz T, Schulz MH, Reiss Y, Plate KH, Weber KJ
J Cancer Res Clin Oncol · 2026 Feb · PMID 41762316 · Full text
PURPOSE: Glioblastoma, IDH-wildtype is a highly aggressive and often recurrent brain malignancy characterized by a profoundly immunosuppressive and heterogeneous tumor microenvironment. In this study, we aimed to systema...
PURPOSE: Glioblastoma, IDH-wildtype is a highly aggressive and often recurrent brain malignancy characterized by a profoundly immunosuppressive and heterogeneous tumor microenvironment. In this study, we aimed to systematically compare commonly used immune profiling methodologies. METHODS: We conducted a cross-platform comparison using matched primary and recurrent tumor samples analyzed by immunohistochemistry, multiplex immunofluorescence, AI-driven image analysis, DNA methylation profiling, and bulk RNA sequencing. A total of 72 samples from 36 patients were evaluated to assess cross-method concordance, cell-type resolution, and each platform’s ability to capture TME dynamics throughout disease progression. RESULTS: Across modalities, monocyte/macrophage-lineage cells were the most consistently identified and quantifiable population. Image-based techniques, including immunohistochemistry, multiplex immunofluorescence, and AI-driven quantification, demonstrated strong concordance for B cell and macrophage detection, whereas T cell quantification showed greater inter-method variability, particularly in recurrent tumors. RNA sequencing-based deconvolution captured broader spectrum of immune and neoplastic states, including microglial enrichment, but aligned only moderately with protein-level measurements. DNA methylation-based approaches performed robustly for myeloid cell estimation but limited accuracy for lymphocyte populations. CONCLUSION: This study highlights the complementary strengths and limitations of current immune profiling modalities in GB. An integrative, method-aware framework facilitates more accurate immune cell quantification and deeper biological insights into TME evolution, ultimately informing the development of precision immunotherapeutic strategies for recurrent GB.
Personalizing cancer risk: a systematic review of risk communication strategies.
Anandarajah A, Roy R, Cross G … +5 more , Stoll C, Hardi A, Jiang S, Colditz GA, Housten AJ
J Cancer Res Clin Oncol · 2026 Feb · PMID 41762298 · Full text
Purpose: Personalized risk communication (PRCom) can help individuals make informed decisions about electing to undergo cancer screening based on their specific risk. In this systematic review, we examined existing risk...
Purpose: Personalized risk communication (PRCom) can help individuals make informed decisions about electing to undergo cancer screening based on their specific risk. In this systematic review, we examined existing risk communication strategies used in the presentation of PRCom and how they may impact screening-related cognitive and behavioral outcomes. Methods: We searched Embase.com, Ovid-Medline All, Scopus, CINAHL Complete, and CENTRAL Trials (via Cochrane Library) for randomized controlled trials addressing interventions with an element of “personalized” cancer risk communication based on the individual’s risk factors. Results: Eighteen unique studies were included. From these 18 studies, we extracted data on PRCom presentation methods and outcome measures such as knowledge and screening completion. Text was used in the majority of PRCom (56%, n = 10), followed by graphs (39%, n = 7), icon arrays (17%, n = 3), charts (17%, n = 3), graphics (17%, n = 3), and video (6%, n = 1). None of these studies included direct format comparisons. We found that knowledge of risk increased in scenarios where PRCom: 1) combined visual (e.g., videos) and text-based communication; and 2) used verbatim (4/5), rather than gist communication (2/7). Screening completion also increased for PRCom with both visual and text-based communication (3/4). However, knowledge of risk and screening completion were minimally impacted if PRCom used only text/verbal communication (1/3 for knowledge of risk, 0/2 for screening completion) or only visual aids (1/3 for knowledge of risk, 2/5 for screening completion). Conclusion: Future research examining the translation of communication strategies to screening-related cognitive and behavioral outcomes is warranted.
When AI joins the table: evaluating large language model performance in soft tissue sarcoma tumor board decisions.
Dehdab R, Afat S, Mankertz F … +11 more , Brendel JM, Maalouf N, Werner S, Brendlin A, Herrmann J, Nikolaou K, Kloker LD, Calukovic B, Benzler K, Zender L, Deinzer CKW
J Cancer Res Clin Oncol · 2026 Feb · PMID 41758476 · Full text
OBJECTIVES: Multidisciplinary tumor boards (MDTs) are critical for the personalized management of soft tissue sarcomas (STS), but they are limited by time, costs, and resource demands. With recent advances in large langu...
OBJECTIVES: Multidisciplinary tumor boards (MDTs) are critical for the personalized management of soft tissue sarcomas (STS), but they are limited by time, costs, and resource demands. With recent advances in large language models (LLMs) like ChatGPT, there is growing interest in evaluating their potential role in augmenting MDT workflows. This study aimed to assess the clinical performance of ChatGPT-4o in real-world STS cases using predefined evaluation criteria, comparing its treatment suggestions with expert MDT decisions. MATERIALS AND METHODS: This retrospective study included 152 patients presented to the multidisciplinary sarcoma tumor board. ChatGPT-4o was prompted to generate guideline-based treatment recommendations based on anonymized tumor board registration letters. Outputs were scored by blinded expert reviewers using a five-domain framework: diagnostic modalities, therapeutic modalities, treatment sequencing/timing, chemotherapy regimen, and clinical contextualization. Descriptive statistics and non-parametric ANOVA with post hoc tests assessed performance, including subgroup analysis by sarcoma subtype. RESULTS: ChatGPT-4o scores were significantly lower than the maximum achievable value of 1.0 across all five criteria (all p < 0.0001). Among individual domains, clinical contextualization significantly outperformed all other criteria in pairwise comparisons (all p < 0.05). No significant performance differences were observed across sarcoma subtypes (H = 19.74, p = 0.138). CONCLUSIONS: ChatGPT-4o demonstrated substantial expert-rated performance in generating tumor board recommendations for soft tissue sarcoma cases, particularly excelling in personalized contextualization. Discrepancies in treatment sequencing and chemotherapy selection highlight the need for expert oversight. These findings support the feasibility of LLM integration into oncology workflows, warranting further refinement toward safe, supportive clinical use.
Racial/ethnic and sex disparities in mortality among US cancer survivors.
Xiong Q, Luo Y, Han K … +8 more , Pan Y, Wang J, He J, Li J, Xu W, Xiang T, Su S, Wei C
J Cancer Res Clin Oncol · 2026 Feb · PMID 41748965 · Full text
BACKGROND: Cancer survivors in the United States face significant disparities in mortality influenced by race and sex. Despite advances in cancer treatment, the disparities of social determinants, behavioral health, and...
BACKGROND: Cancer survivors in the United States face significant disparities in mortality influenced by race and sex. Despite advances in cancer treatment, the disparities of social determinants, behavioral health, and metabolic risk factors remain underexplored. METHODS: Analysis was based on the data from the National Health and Nutrition Examination Survey (NHANES) linked to the National Death Index and the follow-up data up to December 31, 2019. Survey-weighted multiple Cox regression was employed to assess the relationships of multiple risk factors and all-cause mortality. Analyses were informed by a conceptual causal framework (Directed Acyclic Graph). We performed an explanatory decomposition analysis to quantify the collective explanatory role of social determinants of health (SDoH) in the observed racial disparity. RESULTS: During median follow-up of 8.5 years, 2269 cancer survivors out of 6028 participants experienced all-cause mortality. In weighted analyses, we observed Black survivors had highest mortality rates (32.4%), followed by White (26.8%). Before covariables adjustment, Black had a higher all-cause mortality (HR 1.40, 95% CI 1.24-1.59) compared to the Whites. After adjustment of all covariables, there was no significant difference in mortality. Female cancer survivors had lower mortality rate (21.7%) and lower hazard ratio (HR 0.72, 95% CI 0.63-0.81). The analysis identified independent risk factors for increased mortality, including unemployment, lower family income, lack of private health insurance, current smoking, poor diet, physical inactivity, suboptimal sleep, hypertension, and diabetes. Central obesity was associated with lower mortality (HR 0.74, 95% CI 0.64-0.86), a finding that requires cautious interpretation due to potential reverse causation and confounding. Exploratory decomposition analysis suggested SDoH collectively explained a substantial portion of the unadjusted Black-White mortality difference. CONCLUSION: In this mixed population of cancer survivors, a higher burden of social and behavioral risk factors was associated with increased mortality. The findings underscore the critical need to integrate SDoH assessment and mitigation into long-term survivorship care to address social determinants and health behaviors to promote equity in survivorship outcomes. Future research with detailed clinical data is needed to disentangle the effects of cancer type and stage from post-diagnostic factors.
Predictors of response and survival in cemiplimab-treated cutaneous squamous cell carcinoma: multicenter real-world evidence from Germany.
Gambichler T, Brune J, Rüth J … +7 more , Abu Rached N, Boms S, Weyer-Fahlbusch SS, Kreuter A, Hyun J, Becker JC, Susok L
J Cancer Res Clin Oncol · 2026 Feb · PMID 41739240 · Full text
PURPOSE: To assess the association of systemic immune-inflammation biomarkers (SIIBs) and other clinical parameters with objective response rate (ORR), progression-free survival (PFS), overall survival (OS), disease-spec...
PURPOSE: To assess the association of systemic immune-inflammation biomarkers (SIIBs) and other clinical parameters with objective response rate (ORR), progression-free survival (PFS), overall survival (OS), disease-specific survival (DSS), and immune-related adverse events (irAEs) in patients with advanced cSCC treated with cemiplimab, and to compare baseline SIIBs levels between early-stage and advanced-stage disease. METHODS: A retrospective multicenter cohort of 110 immunocompetent advanced cSCC patients treated with cemiplimab was analysed. ORR was assessed using logistic regression; PFS and OS were evaluated using Cox models, and DSS using cause-specific hazards. ROC analyses assessed biomarker discrimination. Baseline SIIBs (LMR, NLR, SIRI) were compared between early-stage (AJCC I/II, non-ICI cohort, n = 59) and advanced-stage disease. Tumor characteristics, body mass index (BMI), and Charlson comorbidity index were evaluated. RESULTS: Among 110 patients, 79 (71.8%) achieved an objective response. Baseline LMR showed modest discrimination for ORR (AUC 0.64, 95% CI 0.53-0.75; p = 0.015) but did not retain statistical significance after adjustment for baseline clinical covariates (OR 1.35, 95% CI 0.95-1.91; p = 0.096). Higher BMI was associated with improved PFS (HR 0.94 per kg/m, 95% CI 0.89-1.00; p = 0.035) and showed a borderline association with OS (HR 0.92 per kg/m, 95% CI 0.85-1.00; p = 0.051). AJCC stage IV strongly predicted DSS (HR 14.03, 95% CI 1.80-109.67; p = 0.012). Baseline LMR was higher in early-stage than in advanced-stage disease (Hodges-Lehmann difference 0.43; p = 0.011), whereas NLR did not differ significantly between stage groups; SIRI was modestly higher in advanced-stage disease (p = 0.029). CONCLUSIONS: In immunocompetent patients with advanced cSCC receiving PD-1 inhibition, BMI was prognostic for survival and AJCC stage remained the key driver of cSCC-specific mortality. Baseline LMR showed a modest association with response and differed between early- and advanced-stage disease, whereas other SIIBs were not consistently linked to tumor progression. Prospective validation is warranted.
Correction: Immunogenic dying cells elicit potent anti-tumor T cell immunity against lung metastasis and tumorigenesis.
Deng J, Hu M, Meng X … +21 more , Wang T, Wang Y, Chen X, Xu D, He W, Zhang H, Guo W, Jing B, Zhang S, Xu J, Sun B, Sun X, Liu T, Ni N, Zhang T, Cui W, Wu X, Xia L, Yao F, Zhang F, Du J
J Cancer Res Clin Oncol · 2026 Feb · PMID 41701369 · Full text
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Correction: Pain and overall quality of life in palliatively treated colorectal cancer patients 1 year after diagnosis- results from the EDIUM cohort.
Schellack SK, Breidenbach C, Kowalski C … +22 more , Wedding U, van Oorschot B, Seufferlein T, Benz S, Schnell M, Köninger J, Klein C, Ockenga J, Freitag B, Wittel UA, Wahba R, Kim M, Elhabash S, Piso P, Weyhe D, Bunse J, Riechmann M, von Strauss M, Petzoldt S, Neumann PA, Kolb V, Sibert NT
J Cancer Res Clin Oncol · 2026 Feb · PMID 41632296 · Full text
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High resolution genome-wide SNP array analyses on matched colorectal-based lung and brain metastases.
Brandt VP, Sander C, Holland L … +6 more , Koschny R, Müller WC, Bläker H, Nestler U, Güresir E, Holland H
J Cancer Res Clin Oncol · 2026 Jan · PMID 41615482 · Full text
PURPOSE: Colorectal-based brain metastasis formation is a rare and late event in colorectal cancer (CRC) patients and is associated with poor survival. Compared with other metastatic sites, the knowledge about copy numbe...
PURPOSE: Colorectal-based brain metastasis formation is a rare and late event in colorectal cancer (CRC) patients and is associated with poor survival. Compared with other metastatic sites, the knowledge about copy number variation (CNV) in brain metastases is still very limited. To get more information about CNVs, we applied SNP array to analyze chromosomal regions with a higher density of SNP markers. METHODS: Genome-wide high resolution single nucleotide polymorphism (SNP) array (CytoScan™ HD) analyses were carried out in matched colorectal-based lung and brain metastases of two patients. RESULTS: Brain metastases harbored more CNVs (77 CNVs) than pulmonary metastases (24 CNVs). Not previously described specific CNVs were: gain of 1p36.33-p36.32, 4p16.3-p16.1, 6q27, 12q24.33, 16p13.3, as well as 16p12.1-p11.2 in lung metastases and gain of 1p36.33-p36.21, 5q11.1-q13.2, 21q22.2-q22.3, 22q11.21-q12.2, as well as 22q12.3-q13.33 in brain metastases. Furthermore, we found 20 copy-neutral loss of heterozygosity (cn-LOH) regions exclusively in brain metastases, of which 11 cn-LOH regions have not been previously described. CONCLUSION: Brain metastases of CRC showed more cn-LOH regions than lung metastases. Potentially affected genes within these regions could influence signaling pathways (e.g., PI3K/AKT signaling) as well as transcriptional processes. Perspectively, increased awareness of specific genetic characteristics can potentially increase the chance of early diagnosis of brain metastases, which could contribute to improved treatment options.
Paraneoplastic cerebellar degeneration from an isolated nodal clear cell carcinoma of suspected gynecologic origin: case report and literature review.
Kissinger CR, Gupta A, Aiad M … +2 more , Rothkopf Z, Wilson M
J Cancer Res Clin Oncol · 2026 Jan · PMID 41593408 · Full text
Paraneoplastic cerebellar degeneration (PCD) is a rare neurologic syndrome that often presents before an underlying malignancy is diagnosed. Patients typically develop subacute cerebellar symptoms—such as vertigo, dysmet...
Paraneoplastic cerebellar degeneration (PCD) is a rare neurologic syndrome that often presents before an underlying malignancy is diagnosed. Patients typically develop subacute cerebellar symptoms—such as vertigo, dysmetria, disconjugate gaze, and dysarthria—before any tumor is detected. Establishing the diagnosis involves ruling out metastatic disease, treatment toxicity, infection, and metabolic disturbances, and often hinges on finding antineuronal antibodies (most commonly anti-Yo, also called type-1 anti-Purkinje cell antibody or PCA-1) in blood or cerebrospinal fluid (CSF). Anti-Yo positivity is classically linked to breast or gynecologic cancers and carries a poor prognosis. We describe a 56-year-old woman with a remote history of parotid basal cell adenocarcinoma who developed gradually worsening cerebellar dysfunction over several months, despite negative initial imaging and routine laboratory tests. When more extensive antibody testing revealed high-titer anti-Yo antibodies in serum and CSF, our suspicion for a paraneoplastic process increased. Subsequent FDG-PET/CT identified FDG-avid pelvic lymph nodes, and surgical pathology confirmed metastatic clear cell carcinoma in two iliac nodes, although the uterus, ovaries, and fallopian tubes were entirely benign. The patient received plasma exchange, intravenous immunoglobulin (IVIG), high-dose steroids, and adjuvant carboplatin/paclitaxel. Although she experienced some improvement in speech and upper-limb coordination, she remains non-ambulatory with persistent cerebellar deficits, three years after initial presentation. This case illustrates how anti-Yo PCD can foreshadow an occult nodal gynecologic malignancy without an identifiable primary tumor, highlighting the need for an extensive workup—including advanced metabolic imaging and, sometimes, empiric surgical exploration—when initial evaluations are unrevealing. Early tumor localization and treatment of both the malignancy and autoimmune response remain crucial to optimizing neurologic outcomes.
Metastatic and recurrent salivary gland carcinoma: clinical characteristics and comprehensive molecular profiling at a tertiary care center.
Rordorf T, Balermpas P, Brezina T … +9 more , Broglie MA, Freiberger SN, Ikenberg K, Lorch A, Morand GB, Mueller SA, Zoche M, Beyer J, Rupp NJ
J Cancer Res Clin Oncol · 2026 Jan · PMID 41593390 · Full text
PURPOSE: Salivary gland carcinomas (SGC) are rare, heterogenous malignancies with limited treatment options in recurrent or metastatic (r/m) disease. We investigated the impact of immunohistochemical and molecular marker...
PURPOSE: Salivary gland carcinomas (SGC) are rare, heterogenous malignancies with limited treatment options in recurrent or metastatic (r/m) disease. We investigated the impact of immunohistochemical and molecular markers on treatment choice and patient outcomes. METHODS: We retrospectively investigated clinical, pathological and molecular characteristics of 51 patients (pts) with r/m SGC treated at the University Hospital Zurich between 2010 and 2024. Immunohistochemical and molecular profiles were evaluated in respect to treatment selection, response and survival. RESULTS: Salivary duct carcinoma (SDC) and adenoid-cystic carcinoma (AdCC) were the most common subtypes. In the SDC group, in 15/20 pts personalized first-line treatment based on immunohistochemical or molecular findings resulted in higher response rates and longer duration of response compared to chemotherapy. In 20 pts of the AdCC group, no actionable alterations were identified. Yet, pts in this group demonstrated the longest overall survival despite low response rates. Among 11 pts with other subtypes, one pt with secretory carcinoma and ETV6::NTRK3 fusion experienced a sustained response to larotrectinib. HER2 IHC2 + expression without gene amplification was observed in 15 pts. Two pts responded to trastuzumab deruxtecan (TDxd) after progression on first line therapy. CONCLUSIONS: The impact of immunohistochemical or molecular markers on treatment selection and response was most pronounced in SDC. HER2 IHC2 + expression was observed across multiple subtypes, indicating that TDxd may represent a potential treatment option for more pts than previously anticipated. The impact of comprehensive genomic profiling on targeted treatment options is currently still modest.
Not all information is equally important: informed consent to genetic testing for hereditary cancer.
Thomas P, Asmussen S, Klein K … +7 more , Straub N, Stegen S, Kowalski C, Schüürhuis S, Speiser D, Feufel MA, Kendel F
J Cancer Res Clin Oncol · 2026 Jan · PMID 41591469 · Full text
PURPOSE: Informed consent in medical care is supposed to guarantee patient autonomy. However, in practice, written consent is often inadequate for this purpose: In an effort to meet legal requirements, consent forms are...
PURPOSE: Informed consent in medical care is supposed to guarantee patient autonomy. However, in practice, written consent is often inadequate for this purpose: In an effort to meet legal requirements, consent forms are often comprehensive and complex. They cover all information that could potentially be relevant, possibly overwhelming patients rather than addressing their concerns. Thus, there is an urgent need for more patient-centered consent forms. As a first step toward this goal, this study assessed the importance of various aspects of consent to genetic testing from the patients' perspective. METHODS: A cross-sectional online study was conducted with 224 participants at elevated risk for hereditary breast and/or ovarian cancer. Participants rated the importance of 14 aspects typically covered on the consent form. Each aspect was compared with all other aspects using multiple contrast tests for repeated measures. Participants also provided hypothetical consent to each aspect. Voluntary comments to the consent aspects were analyzed using qualitative content analysis. RESULTS: Although the majority of consent aspects were rated important in absolute terms, we observed relative differences. Specifically, consent aspects reflecting a clinical benefit for the patient and her family were rated as more important relative to all other aspects. This included, for example, consent to receiving additional test results which could imply further clinical consequences. CONCLUSION: Our results may inform the communication between patients and their counseling physicians prior to genetic testing. They also provide an empirical basis for revising consent forms to better align with patients' needs while remaining legally sound.
A single-cell derived spheroid approach to dissect intratumoural heterogeneity in colorectal cancer: cell lines show changes in proteomes and therapeutic response to 5-FU.
Radloff HS, Kohl M, Sauer T … +4 more , Hartwig S, Geisler S, Lehr S, Gemoll T
J Cancer Res Clin Oncol · 2026 Jan · PMID 41580526 · Full text
PURPOSE: Colorectal cancer (CRC) stands as a significant contributor to cancer-related mortality. Owing to its prognostic and therapeutic implications, intratumoural heterogeneity (ITH) presents a considerable challenge....
PURPOSE: Colorectal cancer (CRC) stands as a significant contributor to cancer-related mortality. Owing to its prognostic and therapeutic implications, intratumoural heterogeneity (ITH) presents a considerable challenge. We have developed an experimental framework integrating single-cell derived spheroids with proteomic profiling to facilitate a molecular, proteomic, and therapeutic characterization of intratumoural heterogeneity during CRC progression. METHODS: Single cells from the commercially available colorectal cancer cell lines SW480 (primary colorectal adenocarcinoma) and SW620 (locoregional lymph node metastasis of the same donor) were isolated using fluorescence-activated cell sorting (FACS) and subsequently cultured forming spheroids. This platform allowed controlled interrogation of clonal diversity through proliferation and viability assays, alongside deep proteomic characterization using label-free liquid chromatography-mass spectrometry (LC-MS) with data-independent acquisition. To evaluate its utility for therapeutic testing, chemotherapy response was measured after 72 h of incubation with 5-fluorouracil (5-FU). RESULTS: The single-cell derived spheroid system demonstrated significant heterogeneity, as evidenced by variations in morphology, growth dynamics, viability, and proteomic signatures. Protein profiling identified ITH-associated proteins (WDR5, CKB, IPO11, ATP6V1F, DCXR and PCCB) and underscored pathway variations including tumour suppressor and proto-oncogenic signalling, vascularization and metabolic regulation. Furthermore, individual spheroids exhibited differential sensitivities to 5-fluorouracil, demonstrating the platform's capacity to resolve heterogeneous therapeutic responses. CONCLUSION: Our study establishes a robust and scalable method that integrates single-cell spheroids with proteomics to model and quantify ITH in CRC. By capturing clinically relevant diversity across morphology, viability, proteomic profiles and drug response, this approach provides a foundation for translating spheroid- and proteomics-based assays into personalized therapeutic testing.
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