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Sarcopenia influences toxicity and survival in non-small cell lung cancer, and sarcopenia assessment can guide personalized treatment planning.

Sarcopenia was associated with both poorer survival outcomes and greater high-grade toxicity in patients with non-small cell lung cancer (NSCLC) as measured by an AI deep-learning system, indicating that the technology may help clinicians use sarcopenia in making personalized treatment decisions, the researchers reported in Clinical Lung Cancer.

“Sarcopenia, characterized by loss of skeletal muscle mass and strength, is a surrogate for frailty and has been associated with worse survival outcomes in [patients with NSCLC]. Furthermore, sarcopenia has been identified as a predictor of chemotherapy toxicity in NSCLC patients,” Anurag Saraf, MD, and colleagues wrote. “However, the interplay between sarcopenia, toxicity, and survival remains understudied, as previous findings have been associated with less robust associations and confounding variables.”

Furthermore, the researchers added, that previous studies have undertaken the labor-intensive process of quantifying sarcopenia manually, making it difficult to implement in the clinic. “Deep learning-based methods for sarcopenia assessment may be able to overcome these limitations,” Dr. Saraf and colleagues wrote.

The researchers performed a retrospective study of 318 patients at one institution with NSCLC who received chemotherapy and radiation, as well as an external validation cohort of 108 patients from another institution who were treated with surgery and chemotherapy. They used a deep-learning pipeline to evaluate CT scans of pre-treatment skeletal muscle (SM) area, defining sarcopenia by dichotomizing patients’ SM indices and adjusting for sex and height.

Grade 3 to 5 toxicity within 3 weeks of the first cycle of chemotherapy served as the main outcome. Other outcomes included changes to chemotherapy, defined as an unplanned treatment delay, early cessation of treatment, dose reduction, or drug change in response to toxicity at any time during treatment, and hospital use, defined as unplanned emergency department visits or hospital admissions related to toxicity from chemotherapy.

Sarcopenia Linked to Worse Toxicity

The median age of patients in the chemoradiotherapy group was 65 and included more men (52%) than women. In the chemo-surgery group, the median age was 63, and 58% of patients were women. In both groups, patients with sarcopenia tended to be older than those without.

Sarcopenia occurred in 36.5% of the chemoradiation and 36% of the chemo-surgery cohort, the researchers reported. Multivariate analysis showed that sarcopenia was linked with worse grade 3 to 5 toxicities in both the chemoradiotherapy group and chemo-surgery group, doubling in comparison to those without sarcopenia (hazard ratio [HR]=2; P<0.01) in the radiation therapy group, and nearly tripling in comparison to patients without sarcopenia in the chemo-surgery group (HR=2.95, P=0.02).

Chemoradiotherapy Vs Chemotherapy & Surgery

More than half of patients in the chemoradiotherapy group (n=184; 58%) experienced a grade 3 to 5 adverse event (AE), Dr. Saraf and colleagues found. The most common of these AEs were lymphopenia, which occurred in 50% of the cohort, neutropenia (14%), infection (4%), and febrile neutropenia (3%). Sarcopenia appeared significantly associated with an increased risk for high-grade toxicity (OR=2.0, 95% CI: 1.24-3.24, P<0.01), and 52 patients (16%) in this cohort had their chemotherapy changed after the first cycle due to toxicity. In total, clinicians changed chemotherapy for 22% of patients who had sarcopenia and 13% of patients who did not. The rate of hospital use due to toxicity in this cohort was 40%, occurring in 47% of those with sarcopenia and 37% of those without sarcopenia.

In the chemotherapy with surgery cohort, 25 patients (23%) experienced grade 3 to 5 toxicity. Neutropenia was the most frequent type, occurring in 19% of patients, followed by lymphopenia (10%) and febrile neutropenia (5%). Once again, sarcopenia was associated with an increased risk for high-grade toxicity (OR=2.66, 95% CI: 1.08-6.67, P = 0.03). The rate of hospital use for toxicity in this cohort was 24%, including 26% of patients with sarcopenia and 23% without sarcopenia.

Poorer overall survival was linked with grade 3 to 5 toxicities in multivariable analyses (HR=1.42, P=0.02), but was not associated with sarcopenia in the chemoradiation therapy cohort, the researchers found. However, in the chemo-surgery cohort, multivariable analyses showed worse OS was associated with sarcopenia (HR 2.03, P=0.02), and not associated with grade 3 to 5 toxicity.

Incorporating Sarcopenia in Survival Predictions 

“Our study is the first to suggest an association of sarcopenia with survival in different clinical scenarios,” Dr. Saraf and colleagues wrote. “Sarcopenia may predict toxicity and tolerance to therapy in advanced-stage patients where disease-specific factors impact survival, while sarcopenia predicts non-disease specific survival in patients with early-stage cancer with favorable risk factors. In either scenario, sarcopenia is an important risk factor for the management of cancer.”

Further, sarcopenia is “a notable predictor of overall survival,” the researchers noted.

“These findings underscore the clinical utility of using deep learning-based, imaging-assessed sarcopenia assessment to guide personalized treatment strategies,” Dr. Saraf and colleagues wrote.