Goal-Based Nutrition Support May Not Limit Muscle Loss in Esophageal Cancer

A goal-directed nutritional support (GDNS) protocol built around indirect calorimetry, structured dietitian follow-up, and proactive nutritional supplementation did not significantly reduce loss of appendicular skeletal muscle index (ASMI) compared with usual care in patients with esophageal cancer (OEC) undergoing neoadjuvant chemoradiotherapy (CRT) and esophagectomy, according to results from a prospective, nonrandomized cluster trial (NL6179/NTR6326) published in Supportive Care in Cancer.

Between baseline and CRT completion, ASMI declined (–2.53% ± 3.43%) with GDNS and with usual care (–3.20% ± 6.92%; P = .559). ASMI partially recovered between CRT completion and surgery, more so with usual care (2.51% ± 7.95%) than GDNS (0.95% ± 4.33%; P = .368), and by 12 months after esophagectomy had fallen a further –5.75% ± 4.75% with GDNS and –7.09% ± 7.38% with usual care relative to the presurgical visit (P = .598), for an overall decline from baseline of –6.92% ± 4.50% with GDNS vs –6.91% ± 4.82% with usual care (P = .996).

The only statistically significant between-group difference occurred in the immediate perioperative period, from the presurgical visit to hospital discharge, when ASMI fell by –0.93% ± 4.42% with GDNS vs –4.88% ± 5.75% with usual care (P = .038). After adjustment for confounders including blood loss, length of stay, duration of surgery, and sepsis, and in mixed-effects models incorporating a group-by-time interaction, no significant intervention effect on ASMI remained across the full treatment course. Prevalence of low ASMI did not differ between arms at any time point.

CT-derived skeletal muscle index (SMI), assessed only in the GDNS group, correlated significantly with bioelectrical impedance analysis (BIA)–derived ASMI at baseline (r = 0.48; P = .003), presurgery (r = 0.81; P = .002), and at 12 months (r = 0.96; P <.001). SMI did not change significantly through the presurgical visit but declined by –6.21% (95% CI, −11.8% to −0.63%) from the presurgical visit to 12 months postoperatively (P = .032). Low SMI was prevalent, at 56% incidence or greater, at every time point, while low psoas muscle index occurred in 16.0% to 40.0% of assessments and declined further, though not significantly, after surgery.

The 1-year overall survival (OS) rate from CRT initiation was 88.0% (95% CI, 79.4%-97.5%) with GDNS vs 84.0% (95% CI, 74.4%-95.0%) with usual care; the 1-year disease-free survival (DFS) rate was 66.0% (95% CI, 54.1%-80.5%) vs 69.7% (95% CI, 58.0%-83.8%), respectively. Measured from surgery, the postoperative 1-year OS rate was 75.0% (95% CI, 62.1%-90.6%) with GDNS vs 82.1% (95% CI, 70.8%-95.0%) with usual care, with 1-year DFS rates of 58.3% (95% CI, 44.3%-76.9%) vs 58.9% (95% CI, 45.4%-76.6%); none of these differences reached significance by log-rank test. Overall postoperative complication rates were similar between groups, but sepsis was more common with GDNS (19.4% vs 2.6%; P = .022).

“GDNS is associated with more favorable outcomes in nutritional intake, body composition, and quality of life, but a higher sepsis rate and no survival benefit compared [with] usual care,” lead author Iris Barth, PhD candidate and research dietitian in the Department of Gastroenterology & Hepatology at University Medical Centre Groningen, wrote in the publication with study coinvestigators. “Our findings underscore the need for personalized, integrated interventions to optimize recovery, particularly postoperatively.”

The trial enrolled 100 patients with histologically confirmed, previously untreated OEC scheduled for neoadjuvant CRT and curative-intent surgery across 2 Dutch hospitals between July 2018 and June 2023. To limit cross-contamination between protocols, GDNS was delivered only at University Medical Centre Groningen (n = 50), while usual care was delivered at Hospital Group Twente (n = 50). Under GDNS, a dedicated case-manager dietitian used indirect calorimetry and the Patient-Generated Subjective Global Assessment to individualize energy targets and proactively initiate oral, enteral, or parenteral nutritional support; usual care involved dietitians across multiple sites and research nurses who monitored weight and intake and initiated support as needed. Esophagectomy was ultimately performed in 36 patients with GDNS and 39 with usual care; 16 and 21 patients, respectively, completed 12-month follow-up.

The primary end point was the between-group difference in relative ASMI, measured by BIA, at CRT completion, after CRT/presurgery, and 12 months after esophagectomy. Secondary end points included 1-year OS and DFS, postoperative complications, CT-derived SMI and psoas muscle index, nutritional status and intake, and quality-of-life outcomes.

The authors noted several limitations, including a reduced sample size from patient dropout and disruptions during the COVID-19 pandemic, and incomplete nutritional data collection in usual care because dietary care was delivered across multiple, decentralized sites. Dietitians were not blinded to group allocation, raising the possibility of performance bias favoring the intervention hospital, and physical activity was not tracked, precluding evaluation of its confounding effect on muscle outcomes. Because usual care was enrolled later, it may have evolved to more closely resemble GDNS over time, and CT-based muscle assessment was available only in the GDNS group, precluding direct between-group comparison.

Reference

Barth I, Stelwagen I, Weerink LBM, et al. Goal-directed nutritional support in preserving muscle mass and optimising recovery in treatment of oesophageal cancer: results of a prospective non-randomised cluster trial. Support Care Cancer. 2026;34(10):929. doi:10.1007/s00520-026-11153-4