Pilot Study of Metabolomic Biomarkers Associated with Outcomes in Patients with Lung Cancer Undergoing Radiation Therapy

Lung cancer stands as the leading cause of cancer-related death worldwide, impacting both men and women in the United States and beyond. Radiation therapy (RT) serves as a key treatment modality for various lung malignancies. Our study aims to systematically assess the prognosis and influence of RT on metabolic reprogramming in patients diagnosed with nonsmall-cell lung cancer (NSCLC) through longitudinal metabolic profiling. A cohort of 54 NSCLC patients underwent thoracic radiotherapy, with 96% receiving a total radiation dose ranging from 40 to 70 Gy, averaging 56.3 Gy. Blood biospecimens were collected before RT, during RT, and at the first follow-up after RT, with a total of 126 serum samples randomized for liquid chromatography-mass spectrometry (LC-MS) metabolomics analysis using a high-performance LC (HPLC)-Q-Exactive mass spectrometry system. Our results indicated that the serum metabolite coumarin derivatives prior to radiotherapy exhibited the strongest unfavorable outcome with overall survival in these NSCLC cases. The metabolites in the blood samples can reflect the responses during RT. Notably, over half of the metabolites (12/23) were found to be fatty acids in the longitudinal analysis. This pilot study indicated that metabolic profiling of biofluids from NSCLC patients undergoing RT has the potential to assess the patient outcomes during and after treatment.