Sandrasegaran, Kumar

Background Sarcopenia is associated with worse outcomes in pancreatic cancer patients, but longitudinal body composition changes during neoadjuvant therapy remain poorly understood. Methods A retrospective review identified patients who underwent pancreatectomy, either upfront or after neoadjuvant therapy, for pancreatic adenocarcinoma between 2011 and 2021. Skeletal muscle area, index, and mean attenuation were calculated from CT images throughout the treatment course to assess sarcopenia. Multivariable generalized linear and logistic regression models were used to assess associations between sarcopenia, neoadjuvant therapy, and postoperative outcomes. Results A total of 72 patients were included: 32 who underwent neoadjuvant therapy and 40 who underwent upfront surgery. Forty-one (57%) patients had sarcopenia at diagnosis (65% upfront surgery vs 47% neoadjuvant, P = 0.154). Post-neoadjuvant therapy, 15.6% developed and 18.8% resolved sarcopenia. Median skeletal muscle mean attenuation increased by 2.4 HU after neoadjuvant therapy ( P = 0.02). Patients receiving neoadjuvant therapy were more likely to undergo nutrition consultation prior to surgery (61% vs 7%, P = 0.003). Neoadjuvant therapy was also associated with higher postoperative albumin levels (β = 0.244; 95% CI 0.041-0.446). Baseline sarcopenia diagnosed by skeletal muscle area was associated with increased postoperative complications (OR 13.696; 95% CI 2.537-73.921), while neoadjuvant therapy did not significantly impact complications (OR 0.384; 95% CI 0.12-1.226). Conclusions Patients who completed neoadjuvant therapy and underwent resection did not have increased rates of sarcopenia and were more likely to receive preoperative nutrition consultation and have higher postoperative albumin levels. The neoadjuvant period may represent an opportunity for sarcopenia assessment, nutritional optimization, and multimodal prehabilitation prior to pancreatectomy.

Abstract VEGF blockade does not uniformly result in clinical benefit. We evaluated safety, dose-limiting toxicities (DLT), recommended phase II dose (RP2D), antitumor efficacy, and exploratory biomarkers including pharmacogenomics and pharmacokinetics with sorafenib, bevacizumab, and paclitaxel in patients with refractory cancers. The study had a “3 + 3” design, using paclitaxel 80 mg/m2 every week for 3 weeks, in every 4 week cycles, bevacizumab 5 mg/kg every 2 weeks, and sorafenib 200 or 400 mg twice a day, 5 or 7 days/week (5/7, 7/7). The MTD cohort was expanded. Twenty-seven patients enrolled in 3 cohorts: sorafenib 200 mg twice a day 5/7, 200 mg twice a day 7/7, and 400 mg twice a day 5/7. DLTs were grade 3 neutropenia >7 days (cohort 1, 1), grade 3 hypertension (cohort 2, 1), grade 3 hand–foot skin reaction (HFSR; cohort 3, 2). MTD was sorafenib 200 mg twice a day 7/7. Six DLTs occurred in cohort 2 expansion: grade 3 HFSR (2), grade 2 HFSR with sorafenib delay >7 days (2), grade 4 cerebrovascular accident (1), grade 3 neutropenia >7 days (1). RP2D was sorafenib 200 mg twice a day 5/7. Most patients (62%) dose reduced sorafenib to 200 mg daily 5/7 after a median 3 (range, 2–17) cycles. Response rates were 48% overall (27) and 64% for ovarian cancers (14). VEGF-A-1154AA and -7TT recessive homozygous genotypes conferred worse overall survival versus alternative genotypes (7 vs. 22 months). Intermittent, low-dose sorafenib (200 mg twice a day 5/7) combined with bevacizumab and paclitaxel was tolerable and had high antitumor efficacy in patients with refractory cancer (NCT00572078).