Are Advanced Radiation Techniques Safe to Use in Locally Advanced Non-Small Cell Lung Cancer (LA-NSCLC)? Analysis Based on Pathologic Regression and Local Recurrence

Abstract

VMAT, deep inspiratory breath hold (DIBH) and adaptive replanning (ART), are increasingly used for LA-NSCLC to improve conformality and reduce treatment toxicity. Yet, impact of these advanced techniques on pathologic response (PR) and local recurrence (LR) is lacking. We evaluated VMAT, DIBH and ART compared to 3D-conformal radiation therapy (3DCRT) and free breathing (FB), hypothesizing that PR and LR would be unaffected.Retrospective analysis of PR and LR in patients with LA-NSCLC treated in a single academic center between 2012-2021 with platinum based chemoradiation (CRT) followed by completion resection. Radiation techniques assessed: VMAT, DIBH and ART (due to tumor shrinkage during treatment).gender, smoking, stage, GTV, tumor histology, tumor location, dose (Gy), chemotherapy, and time interval between CRT and surgery.PR and LR. PR was converted to a binary variable: Major pathologic regression (MPR) (complete response or ≤10% residual tumor cells) vs. residual tumor (> 10% residual tumor cells). Pathological assessment was blinded to radiation technique. LR was determined by CT or PET-CT. Statistical analysis was by logistic regression.Characteristics of patients (n = 106) with LA-NSCLC were: median age: 63 (range 43-79), males: 73/106 (69%), mean radiation dose: 60.7 Gy (SD 4.6 Gy), median GTV: 115cc (range 19-448), and median time interval (CRT-surgery): 65d (range 28-424d). Radiation techniques were: 3DCRT-FB (n = 51, 48 %), VMAT-FB (n = 40, 38%), VMAT-DIBH (n = 15, 14%), and ART (n = 24, 22.6%). Overall MPR was 73/106 (68.9%). MPR was not significant for VMAT (40/55, 73%) vs. 3DCRT (33/51, 64.7%) (OR 0.7, NS) or DIBH (11/15, 73%) vs. FB (62/91, 68%) (OR-1.1, NS). MPR was significant for ART (20/24, 83%) vs. no-ART (53/82, 64.6%) (OR 3.2, P = 0.037), never smokers (6/18, 33%) vs. smokers (65/86, 75%) (OR-0.49, P = 0.007), GTV > 115cc (45/55, 81%) vs. GTV ≤115 cc (28/51, 55%) (OR-0.27, P = 0.007), and time interval between CRT and surgery > 66 d (44/53, 83%) vs. time interval ≤ 65 d (29/53, 55%) (OR-0.2, P = 0.002). The following variables did not corelate with MPR: age, gender, histology, stage, lower lobe location, chemotherapy type and dose > 60 Gy. LR occurred in 17/106 patients. LR trended lower with: ART (1/24, 4%) vs. no ART (16/81, 20%) (HR 1.25 P = 0.7), DIBH (1/15, 6.7%) vs. FB (16/90, 17.8%) (HR-0.86, P = 0.7), and VMAT (6/54, 11%) vs. 3D CRT (11/51, 21%) (HR 0.7, P = 0.6).Pathologic and radiographic comparisons show use of VMAT, DIBH and ART in LA-NSCLC did not adversely influence pathologic regression or LR. Use of ART was associated with increased MPR and reduced LR. GTV, smoking status and time interval between CRT and surgery were associated with MPR. Further investigation of these variables is planned.