INTRODUCTION:Tumor glucose metabolism, as assessed by fluorodeoxyglucose positron emission tomography (FDG-PET), can reflect both intrinsic tumor biology and the host systemic condition. Increased FDG uptake has been linked to aggressive tumor behavior, altered metabolic activity, and a distinct tumor microenvironment. However, its clinical relevance remains unclear in patients with unresectable or recurrent esophageal squamous cell carcinoma (ESCC) treated with chemoimmunotherapy. METHODS:We retrospectively analyzed 47 patients treated with fluorouracil plus cisplatin-based chemoimmunotherapy. FDG-PET was performed before treatment initiation, and maximum standardized uptake value (SUVmax) was used to assess tumor glucose metabolism. Treatment response was evaluated according to the Response Evaluation Criteria in Solid Tumors, and overall survival (OS) was calculated from the start of treatment. Patients were classified using an exploratory data-derived SUVmax cutoff value of 17.55, and treatment response, survival, and baseline characteristics were compared between groups. Continuous SUVmax was also analyzed using Cox models. RESULTS:Patients with high SUVmax showed a significantly higher response rate than those with low SUVmax (83.3% vs. 52.6%, p = 0.0462). Higher SUVmax was independently associated with shorter OS (adjusted HR per unit, 1.105; 95% CI, 1.008-1.213; p = 0.0320). CONCLUSION:Higher pretreatment SUVmax was associated with a higher response rate but poorer OSin patients with unresectable or recurrent ESCC receiving chemoimmunotherapy. SUVmax may reflect both treatment sensitivity and aggressive tumor biology and may provide clinically relevant information on treatment response and prognosis, although the cutoff-based findings require external validation.
Purpose In HER2-negative metastatic gastric cancer, immune checkpoint inhibitors (ICIs) and CLDN18.2-targeted antibody zolbetuximab, combined with chemotherapy (CT), have emerged as first line options. Treatment selection is relatively straightforward in microsatellite instability-high (MSI-H), PD-L1 combined positive score (CPS)-high/negative disease, but uncertainty persists in overlapping biomarkers-particularly CLDN18.2-positive tumors with low-to-intermediate PD-L1 CPS-where direct comparative evidence is lacking. Methods Individual patient data were reconstructed from published Kaplan-Meier curves of pivotal phase III trials (SPOTLIGHT/GLOW, CheckMate-649, KEYNOTE-859). Descriptive, unadjusted indirect comparisons of progression-free survival (PFS) and overall survival (OS) were performed using pooled CT as common reference. Findings were interpreted within a biomarker-oriented framework incorporating PD-L1 CPS, CLDN18.2 expression, MSI status and treatment mechanisms. Results PFS benefit versus pooled CT was marked with zolbetuximab plus CT (hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.53-0.68), but more modest with pooled ICI-based regimens (HR 0.81, 95% CI 0.75-0.88). Both strategies improved OS. CLDN18.2-positive tumors are predominantly PD-L1 CPS-low, a biological context where ICI benefit may be heterogeneous. Conversely, zolbetuximab demonstrated consistent efficacy in this selected population; leveraging its established mechanism of direct CLDN18.2-targeting and innate immune activation, it provides a biomarker-directed therapeutic option that addresses the clinical gap in PD-L1 CPS-low disease. Conclusions Population-level efficacy estimates should not be interpreted as therapeutic interchangeability between ICIs and CLDN18.2-targeted therapy. Without direct comparative data, treatment selection in CLDN18.2-positive, PD-L1 CPS-low disease requires integration of biomarker biology and clinical context. This biomarker-informed framework supports clinical decision-making under uncertainty.
AIM:The demographic and clinical factors influencing the decision between amputation and limb salvage surgery (LSS) in chondrosarcoma patients are compared. METHODS:Data from the Surveillance, Epidemiology, and End Results program were utilized. Individuals ≥ 18-year-old with primary chondrosarcoma located in the limbs and underwent cancer-directed surgery were included. Patients were divided into groups based on receiving LSS or amputation. Factors associated with amputation were determined by logistic regression. Overall survival (OS) and cancer-specific survival (CSS) were assessed by Cox proportional hazard regression analysis. RESULTS:The study included 746 patients (LSS:617; amputation: 129). Compared with patients who underwent LSS, those who underwent amputation had poorer OS (adjusted hazard ratio [aHR]: 1.44, 95% confidence intervals [CI]: 1.08-1.93) and CSS (aHR: 1.60, 95% CI: 1.15-2.21). Lower limb as the primary site (adjusted odds ratio[aOR]: 1.87; 95% CI: 1.21-2.89; p=0.005), and M1 stage (aOR: 2.29; 95% CI:1.31-4.01) were significantly associated with a higher likelihood of undergoing amputation. CONCLUSION:In this population-based real-world study, amputation was associated with poorer OS and CSS among adults with primary extremity chondrosarcoma. This association likely reflects the advanced or surgically complex disease characteristics of patients requiring amputation rather than a direct adverse effect of amputation itself. These findings provide epidemiologic evidence to characterize this high-risk subgroup and inform future risk-stratified studies.
Introduction: With the widespread use of human epidermal growth factor receptor 2 (HER2) inhibitors in cancer treatment, cardiovascular diseases induced by these agents have become a significant adverse event. Methods: We retrieved reports of HER2 inhibitor-induced cardiovascular adverse events (CVAEs) from the FDA Adverse Event Reporting System(FAERS) database, covering the period from the first quarter of 2004 to the fourth quarter of 2024. Disproportionality analyses were conducted using reporting odds ratios and proportional reporting ratios. The signals of HER2 inhibitor-related CVAEs were evaluated at both the standardized MedDRA query and preferred term levels. Results: A total of 12,698 reports associated with CVAEs were identified, with HER2 inhibitors listed as the primary suspected drug, involving 12,398 patients. Most cases were observed in individuals aged 45 years and older, with a notably higher proportion in women. The time to onset of HER2 inhibitor-induced CVAEs showed certain variability. Trastuzumab exhibited higher cardiovascular toxicity compared with other HER2 inhibitors. In general, monoclonal antibodies demonstrated greater cardiovascular toxicity, whereas antibody-drug conjugates and HER2-tyrosine kinase inhibitors displayed comparable and lower effects. Conclusion: This pharmacovigilance analysis reveals a strong association between HER2 inhibitors and CVAEs, providing valuable insights for their prevention and clinical management.
INTRODUCTION:The immune landscape of the tumor microenvironment significantly influences the development and prognosis of colorectal cancer (CRC). High intratumoral and stromal expressions of CD3+ and CD8+ T-lymphocytes have been associated with a better prognosis in CRC patients. However, the prognostic role of antigen-presenting cells, such as dendritic cells and macrophages, has less attention. METHODS:In this study, we assessed the impact of CD11c expression and the disease-specific survival (DSS) in CRC patients. Thus, we evaluated the CD11c expression on tissue microarray samples via immunohistochemistry from 516 patients who underwent surgery at Helsinki University Hospital between 2000 and 2005. Samples were categorized as low expression (<5% positive stromal area) and high expression (≥5% positive). Colon and rectal cancer patients were analyzed separately using Cox regression for survival analysis. RESULTS:A lower CD11c expression associated with a worse DSS among rectal cancer patients (p < 0.001) and right-sided colon cancer patients (p = 0.03), but not among left-sided colon cancer patients (p = 0.41). Among rectal cancer patients, results remained consistent regardless of whether the patient received preoperative radiation (p < 0.003 and p = 0.03, respectively). In the multivariable analysis after adjusting for age, sex, stage, grade, and a mismatch repair status, a lower CD11c expression remained an independent prognostic factor among rectal cancer patients (p = 0.009), but not among colon cancer patients (p = 0.15). These results suggest that stromal CD11c expression captures the distinct immunological characteristics of rectal cancer compared to colon cancer. CONCLUSIONS:We conclude that CD11c could serve as a prognostic marker for rectal cancer patients. However, the immunological mechanisms differentiating colon and rectal cancers warrant further research.
