2066 - Circulating miRNA Profiling Distinguishes Radiation-Induced Fibrosis from Locoregional Recurrence in Patients Who Received Radiotherapy for Lung Cancer

J. E. Juarez Casillas¹, E. Kyubwa², C. J. Rogers², J. Axtelle², N. Menon², and D. L. Gage³; ¹Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, ²Chromologic LLC, Pasadena, CA, ³Greater Los Angeles VA Medical Center, Los Angeles, CA

Purpose/Objective(s): Early and late fibrotic changes in pulmonary tissue is commonly observed after radiotherapy (RT) for thoracic malignancies, which makes it difficult to distinguish benign post-radiation changes from local recurrence. It is critical to identify tumor recurrence early while salvage therapy remains an option. We investigate, as proof of concept, whether a circulating microRNA (miRNA)-based assay could be utilized as a molecular biomarker to distinguish radiation-induced fibrosis from local recurrence in patients who received thoracic RT. Materials/

Methods: Plasma samples for miRNA-seq analysis were collected at multiple timepoints ranging from 20 days before to 200 days after RT. Pulmonary fibrosis was assessed up to 20 months post-RT using the computer tomography (CT) component of the positron emission tomography /computer tomography (PET/CT) reports, as interpreted by a board-certified radiologist. A fibrosis risk score was calculated using relative levels of a panel of miRNAs, and the performance of the biomarker panel was assessed by area under the ROC curve (AUC) analysis.
Results: The cohort included 17 veterans (15 Males, 2 Females), age range 61-87 years. 16 patients received RT for a primary lung malignancy (10 adenocarcinoma, 5 squamous cell carcinoma, and 1 small cell carcinoma histology). One patient was treated for a lung metastasis from renal cell carcinoma primary. 4 patients had a history of prior RT, these sites included the contralateral lung, whole brain, lumbar spine or prostate. The treatment regimens included concurrent chemoRT in 8 patients, stereotactic body radiotherapy in 7 patients, and conventionally fractionated RT in 2 patients. Patients with fibrotic lesions (11/17 patients) had a higher average risk score [0.57 vs 0.39, p=0.28] compared to patients with no radiographic evidence of fibrosis. The biomarker panel had an AUC of 0.68 for predicting fibrosis. Following completion of RT, the average duration for a positive biomarker score compared to the appearance of radiographic evidence of fibrosis was 10 vs 296 days, respectively. During the follow-up period, one patient experienced local recurrence, with the post-RT average fibrotic risk score of 0.32.
Conclusion: These data suggests the proposed miRNA biomarker exhibits potential to differentiate between fibrotic lesions and local recurrence in lung cancer patients post-RT. Radiographic changes on surveillance imaging alongside negative biomarker scores for fibrosis may suggest a need for earlier intervention. Limitations to the biomarker includes patients with underlying fibrotic disease, connective tissue disorders, or medication toxicity, and further research is needed to enhance the biomarkers accuracy.