Oxygen uptake efficiency slope predicts response to concurrent chemoradiotherapy in patients with esophageal cancer – a pilot study

Concurrent chemoradiotherapy (CCRT) is a cornerstone treatment for esophageal cancer, yet response rates vary widely, and treatment can cause adverse effects. This study investigated the predictive value of physical fitness for CCRT outcomes, including cardiorespiratory fitness (CRF), body composition, and muscle strength. This prospective observational study included 84 patients with esophageal cancer undergoing curative-intent CCRT. Pre-treatment assessments comprised cardiopulmonary exercise testing (CPET), bioelectrical impedance analysis, and handgrip strength (HGS). CCRT response was determined by institutional multidisciplinary tumor board consensus based on RECIST 1.1 measurements, endoscopy, and positron emission tomography, and patients were classified as responder or non-responder. Candidate predictors were analyzed using least absolute shrinkage and selection operator (LASSO)-penalized logistic regression with 10-fold cross-validation and bootstrap validation (1,000 iterations). Subgroup and sensitivity analyses addressed potential confounding by sex and treatment intent. Among 84 patients, 13 (15.5%) were non-responders. Non-responders demonstrated lower CRF, muscle mass, and HGS. LASSO retained oxygen uptake efficiency slope (OUES), a submaximal CPET parameter, and female sex (standardized odds ratios 0.745 and 1.191, respectively), with bootstrap selection frequencies of 75.3% and 76.5%. OUES alone showed an area under the curve (AUC) of 0.860, with 84.6% sensitivity and 74.6% specificity at an optimal cutoff of 1.27 ((L/min)/log(L/min)), nearly identical to the model combining OUES and sex (apparent AUC 0.862; optimism-corrected AUC 0.814). The association between OUES and non-response persisted after adjustment for sex, in male patients only, and within both neoadjuvant and definitive CCRT subgroups. OUES emerged as a novel predictor of CCRT non-response in esophageal cancer, suggesting a potential promising role for CRF and other physical fitness measures in guiding subsequent individualized treatment strategies. Prospective validation in larger and more diverse cohorts is needed to confirm its predictive value and clinical applicability.