Body composition dynamics and impact on clinical outcome in gastric and gastro-esophageal junction cancer patients undergoing perioperative chemotherapy with the FLOT protocol

Abstract

Purpose Perioperative chemotherapy with FLOT constitutes a standard of care approach for locally advanced, resectable gastric or gastro-esophageal junction (GEJ) cancer. We aimed at investigating anthropometric, CT-based and FDG-PET-based body composition parameters and dynamics during this multidisciplinary approach and the impact on clinical outcomes. Methods This retrospective, single-center study was based on medical records and (FDG-PET)-CT images among gastric/GEJ cancer patients undergoing perioperative FLOT chemotherapy. Results Between 2016 and 2021, 46 gastric/GEJ cancer patients started perioperative FLOT at our tertiary cancer center (Salzburg, Austria). At a median follow-up of 32 months median PFS was 47.4 months and median OS was not reached. The skeletal muscle index (SMI, cm2/m2) turned out to be the only body composition parameter with a statistically significant decrease during pre-operative FLOT (51.3 versus 48.8 cm2/m2, p = 0.02). Neither pre-FLOT body mass index (BMI), nor SMI had an impact on the duration of pre-operative FLOT, the time interval from pre-operative FLOT initiation to surgery, the necessity of pre-operative or post-operative FLOT de-escalation or the likelihood of the start of postoperative chemotherapy. Pre-FLOT BMI (overweight versus normal, HR: 0.11, 95% CI: 0.02–0.65, p = 0.02) and pre-FLOT SMI (sarcopenia versus no sarcopenia, HR: 5.08, 95% CI: 1.27–20.31, p = 0.02) were statistically significantly associated with PFS in the multivariable analysis. Conclusion The statistically significant SMI loss during pre-operative FLOT and the meaningful impact of baseline SMI and BMI on PFS argue for the implementation of a nutritional screening and support program prior to the initiation of pre-operative FLOT in clinical routine.

Impact of neoadjuvant FLOT treatment of advanced gastric and gastroesophageal junction cancer following surgical therapy

“…Interestingly, while modifying the neoadjuvant treatment protocols, the addition of oxaliplatin (FLOT) resulted in a higher rate of pCR—as expected—, but neither improved survival or increased locoregional control can be reported yet ( 25 ).…”

Dynamic changes in body composition during XELOX/SOX chemotherapy in patients with gastric cancer

“…The aforementioned studies investigated the correlation between changes in L3SMI over time and survival rates. In all of these investigations, baseline sarcopenia ( P = 0.021) and a decrease in SMI during chemotherapy ( P = 0.032) were significant negative predictors for survival ( 5 , 27 ). In this investigation, the decrease in L3SMI before and after chemotherapy in patients with gastric cancer (-2.60 ± 11.50%) was similar to the decrease observed during chemotherapy for gastrointestinal tumors in our previous research (-2.05 ± 9.21%) ( 10 ).…”

“…Similarly, Florian Huemer et al. (2023) reported a statistically significant decrease in body composition parameters during perioperative FLOT chemotherapy for gastric cancer (51.3 vs. 48.8 cm 2 /m 2 , P = 0.02) ( 27 ). The aforementioned studies investigated the correlation between changes in L3SMI over time and survival rates.…”

Adverse effects of systemic cancer therapy on skeletal muscle: myotoxicity comes out of the closet

“…Earlier meta-analyses [8,9] identified that male sex is associated with higher rates of muscle loss. Here, male colorectal cancer patients with metastatic disease showed muscle loss of À8.3%/100 days [25], testicular cancer patients showed muscle loss up to À11.9%/100 days [20,21], and four new studies in neoadjuvant chemotherapy for esophageal/esophagogastric cancer, which has a high proportion of male individuals [16][17][18][19], showed relatively high intensity of muscle change (À7.2% to À9%/100 days). Muscle loss in the intermediate range were seen in a series of single reports, including Hodgkin's Lymphoma (À5.6%/ 100 days) [22], neoadjuvant chemotherapy for advanced ovarian cancer (6%/100 d) [15], curative intent chemoradiotherapy for head and neck cancer (À3.8%/100 days) [26] and targeted therapy cabozantinib in renal cell carcinoma (À4.6%/100 days) [27].…”

“…The rate of muscle loss on postoperative day 7 in both ghrelin groups was lower than that in the placebo group (high dose vs. placebo: 2.8 vs. 8.5%, P < 0.001; low dose vs. placebo: 4.9 vs. 8.5%, P ¼ 0.028). The interest of this study is that substantial muscle losses have been described during the neoadjuvant chemotherapy that precedes esophagectomy [8,[16][17][18][19]. Although the efficacy of ghrelin intervention postoperatively could assist in restoring some of these losses, earlier intervention during neoadjuvant treatment could also be considered.…”