Effect of PTV and Collimator Margins on Tumor Control for Patients with Stage III Non-small Cell Lung Cancer in NRG Oncology RTOG-0617

Abstract

RTOG-0617, a randomized phase III cooperative group trial using 2 x 2 factorial design, with radiation dose as one factor and cetuximab as the other factor for locally advanced non-small cell lung cancer, reported that patients in the high dose arms (74-Gy) had poorer survival and local control than those in the low dose arms (60-Gy). We hypothesized that patients in the 74-Gy arm have tighter planning target volume (PTV) and collimator margins, which may have caused poorer local control due to marginal misses. A total of 461 eligible patients were included in this study, with 261 and 200 patients in the 60-Gy and 74-Gy groups respectively. Local tumor control was defined as local progression free survival (LPFS). To study the PTV margin effect, a standard PTV was generated by expanding the gross tumor volume (GTV) with a 10 mm margin. A margin deviation index (MDI) was calculated as the percentage change of equivalent uniform dose (EUD) between the original PTV and the new PTV. Similarly, another new PTV was generated by expanding the original PTV with 6 mm margin, and a dose gradient index (DGI) was calculated as the percentage change of EUD between the original PTV and the new PTV to study the effect of collimator margin. A Cox statistical model was used to determine the associations of MDI and DGI with LPFS. MDI was 1.1 ± 1.6 and 1.5 ± 1.7 for the 60-Gy and 74-Gy groups, respectively (T test: P > 0.05), and DGI was 5.8 ± 4.4 and 6.7 ± 4.3 correspondingly (P > 0.05). The number of patients with extremely tight MDI (>3) or DGI (>11) was 27/261 (10%) and 26/200 (13%), or 30/261 (11%), 26/200 (13%) for the 60-Gy and 74-Gy group, respectively (P > 0.05). Interestingly, a larger DGI (tighter collimator margin) showed significantly better LPFS (HR = 0.98, P = 0.04), and a larger MDI (tighter PTV margin) had a trend of better LPFS (HR = 0.95, P = 0.10) for the entire group of patients. Larger MDI and DGI tended to result in better local control, suggesting that deviation from the standard PTV margin or tight collimator margin was not the cause of unexpected result in RTOG-0617. Further studies are required to better understand this phenomenon.