Gündüz Karaoğlan

Background and Objectives: Evidence regarding predictors of pathological response and long-term outcomes in older patients receiving perioperative FLOT chemotherapy for resectable gastric or gastroesophageal junction cancer remains limited. We aimed to identify factors associated with pathological response and survival in patients aged ≥65 years treated with neoadjuvant FLOT. Materials and Methods: This retrospective single-center study included 86 consecutive patients (median age, 69 years; 72.1% male) aged ≥65 years with resectable gastric or gastroesophageal junction adenocarcinoma who underwent neoadjuvant FLOT chemotherapy followed by curative-intent gastrectomy. Major pathological response was defined as College of American Pathologists tumor regression grade (CAP TRG) 0–1. Logistic regression analyses were performed to identify predictors of pathological response. Disease-free survival (DFS) and overall survival (OS) were analyzed using the Kaplan–Meier method and Cox proportional hazards regression analyses. Results: Overall, 14 patients (16.3%) achieved a major pathological response. Body mass index (BMI) ≥ 25 kg/m² (OR 5.13, p = 0.04) was independently associated with a major pathological response. During a median follow-up of 29.2 months, 39 patients (45.3%) developed recurrence and 35 (40.7%) died. ECOG performance status (ECOG PS) ≥ 1 was independently associated with both inferior DFS (HR = 2.76, p = 0.02) and OS (HR = 2.52, p = 0.045). In addition, ypN stage 2–3 (HR = 2.58, p = 0.008) was independently associated with worse DFS, whereas positive surgical margins were independently associated with worse OS (HR = 2.62, p = 0.02). Conclusions: In older patients with resectable gastric or gastroesophageal junction adenocarcinoma treated with perioperative FLOT chemotherapy, baseline BMI was independently associated with major pathological response, whereas ECOG PS and postoperative pathological factors were independently associated with survival. These findings highlight the importance of careful patient selection and individualized multimodal treatment in this population.

Background: Age- and cancer-related sarcopenia and malnutrition are common in older patients with colorectal cancer (CRC) and may negatively influence treatment tolerance and prognosis. However, the comparative prognostic value of post-chemotherapy changes in CT-based body composition parameters at the third lumbar vertebra (L3) and the twelfth thoracic vertebra (T12) levels, and their associations with nutritional indices, remain unclear. This study aimed to examine and compare the prognostic relevance of post-chemotherapy body composition changes at L3 and T12 and to assess their relationship with nutritional indices in older patients with metastatic CRC (mCRC). Methods: This retrospective study included 87 older patients with mCRC. Baseline and ~3-month follow-up CT scans were analyzed at L3 and T12 using 3D Slicer to quantify skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI), visceral adipose tissue index (VATI), visceral-to-subcutaneous fat ratio (VSR), and intramuscular adipose tissue index (IMATI). Changes (Δ) in CT-derived body composition after chemotherapy were calculated as percentage change using ((follow-up − baseline)/baseline) × 100. Prognostic Nutritional Index (PNI) and Geriatric Nutritional Index (GNRI), which are established nutritional assessment tools, were calculated from baseline laboratory/anthropometric data. Agreement between T12 and L3 was assessed, and associations with grade ≥ 3 toxicity, progression-free survival (PFS), and overall survival (OS) were evaluated using multivariable models and ROC analyses. Results: Mean age was 69.0 ± 4.5 years (59 male/28 female), and 26.4% developed grade ≥ 3 adverse events. Over 3 months, mean SMI declined significantly at both L3 (46.7 ± 8.8 → 42.8 ± 9.8 cm²/m²) and T12 (34.6 ± 8.2 → 31.6 ± 8.1 cm²/m²) (p < 0.001 for both), accompanied by decreases in VATI and VSR; T12-IMATI increased significantly. Baseline PNI showed a weak positive correlation with L3-SMI (r = 0.302, p = 0.033), whereas GNRI showed moderate correlations with SMI at L3 (r = 0.502, p < 0.001) and T12 (r = 0.317, p = 0.025) and was associated with longitudinal changes in muscle metrics. T12-SMI consistently yielded lower values than L3-SMI, and agreement varied by compartment (best for SATI; weakest for VSR). Lower GNRI and greater L3-SMI loss were independently associated with grade ≥ 3 toxicity; ΔL3-SMI showed the highest discrimination (AUC = 0.79, 95% CI = 0.69–0.87, p < 0.001; cut-off >5.1% loss). All patients progressed (median PFS 7.6 months); mortality was 82.8% (median follow-up: 25 months). In multivariable analysis, PFS, CRP, GNRI, and ΔL3-SMI remained independently associated with OS. ΔL3-SMI provided the strongest mortality discrimination (AUC = 0.85, 95% CI = 0.74–0.94, p < 0.001; cut-off >10.4% loss), while ΔIMATI was also informative (AUC = 0.71, 95% CI = 0.59–0.82, p = 0.023). Conclusions: In older patients with mCRC, early post-chemotherapy skeletal muscle loss—particularly at the L3 level—showed the strongest prognostic association with severe toxicity and mortality. GNRI provided complementary prognostic information as a marker of baseline immunonutritional reserve. Although T12-derived measurements were correlated with L3-derived values, systematic bias suggests that they should not be interpreted interchangeably for longitudinal risk stratification.