Journal of Cancer Research and Clinical Oncology最新文献

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.

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.

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/m², 95% CI 0.89-1.00; p = 0.035) and showed a borderline association with OS (HR 0.92 per kg/m², 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.

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.

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.

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.

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.