Predictive Factors for Response to Adaptive Therapy in Thoracic Stereotactic Ablative Radiotherapy

Abstract

Online adaptive radiotherapy (ART) has been increasingly adopted for clinical use. However, ART for thoracic malignancies has lagged beyond its implementation for other primary cancers. Efforts are needed to identify optimal patients for ART by finding trends for changes in tumor position, shape, or proximity to OARs are needed. We hypothesized tumor size, histology, pre-RT SUV value, and intrathoracic location could influence how tumors change during cone beam computed tomography (CBCT)-based ART Stereotactic Ablative Radiotherapy (SAbR) for thoracic disease. Data was collected from a prospective registry of patients who received CBCT-ART and SAbR for primary and secondary lung tumors. Dosimetry data was obtained from the simulation planning and the daily adaptive workflow. Central lung tumors were defined as those located within 2 cm of the bronchial tree. Plans were either delivered as per simulation or through the online adaptive workflow delivery (AD). Change in planning tumor volumes (PTV) were calculated between initial and final fractions (ΔPTV). A total of 42 patients with a median age of 67 (range 17-90) and median 8.3 months follow up, treated between June 2021 and December 2022 were included. Most patients had NSCLC or presumed NSCLC (73.85%, 31/42), and most lesions were peripheral (61.9%, 26/42) versus central (31%, 13/42) or apical (7.1%, 3/42). Mean dose and median fractions were 52.5 Gy (SD 8.07) and 5 (range 3-5) while median initial (i) PTV was 31.75 cm3 (IQR 42.3 cm3). On average, ΔPTV decreased by 4.9% (SD 21) and volume shrunk by 5 cm3 (SD 14.5). AD improved per fraction PTV coverage and conformality while esophageal, cardiac, and spinal cord dose were significantly decreased (all p < 0.05), and most fractions were delivered with AD (73.4%, 138/188). AD was aborted most often for small iPTVs. ΔPTV grew >10% for two lesions though their iPTV were < 10 cm3. 12/42 ΔPTV were >10% smaller by the end of RT and corresponded to larger iPTVs. Age, lung primary, metastatic disease, smoking status, and tumor location were not predictive for >10% decrease in ΔPTV. Among 24 biopsy-proven NSCLC ΔPTV was >10% smaller in 6/12 patients (50%) with adenocarcinoma and only in 2/12 (16.7%) with SCC, although this was not significant on χ2 testing (p = 0.08). There were no differences in local, regional, distant failure or death comparing those with a ΔPTV of >10% vs <10% (all p > 0.1). Comparing pre-treatment PET SUV and tumor response, lower SUVs appear to be associated with more PTV shrinkage, with no significant PTV change plateauing at SUV 20. However, this analysis was limited by the number of patients with high SUV values. CBCT-ART SAbR is associated with improved PTV coverage, target conformality, and reduced OAR dose. Large iPTV and adenocarcinomas were more likely to decrease >10%. High metabolic activity appeared predictive for a lack of significant ΔPTV. Further clinical and radiographic features should be explored to predict response to ART.