Locally advanced NSCLC: a plea for sparing the ipsilateral normal lung-prospective, clinical trial with DART-bid (dose-differentiated accelerated radiation therapy, 1.8 Gy twice daily) by VMAT

Abstract

Background: In radiation treatment of locally advanced non-small cell lung cancer (LA-NSCLC), 'margins' from internal target volumes to planning target volumes in the range of 12 to 23 mm are reported, and avoiding exposure of the contralateral lung is common practice. We investigated prospectively an approach with tight margins (7 mm) and maximal sparing of the ipsilateral normal lung. Mature results for the first endpoint (pneumonitis) and further toxicities are reported.

Methods: Primary tumors were treated by VMAT with 73.8-90.0 Gy in positive correlation to tumor volumes, nodes with 61.2 Gy, a restricted volume of nodes electively with 45 Gy. Fractional doses of 1.8 Gy bid, interval 8 h. Before radiotherapy, two cycles platin-based chemotherapy were given. 12 patients finished maintenance therapy with Durvalumab. Median follow up time for all patients is 19.4 months, for patients alive 27.0 months (3.4-66.5 months).

Results: 100 consecutive, unselected patients with LA-NSCLC in stages II through IVA were enrolled (UICC/AJCC, 8th edition). No acute grade 4/5 toxicity occurred. Pneumonitis grade 2 and 3 was observed in 12% and 2% of patients, respectively; lowering the risk of pneumonitis grade ≥ 2 in comparison to the largest study in the literature investigating pneumonitis in LA-NSCLC, is significant (p < 0.0006). Acute esophageal toxicity grade 1, 2 and 3 occurred in 12%, 57% and 3% of patients, respectively. Two patients showed late bronchial stricture/atelectasis grade 2. In two patients with lethal pulmonary haemorrhages a treatment correlation cannot be excluded. Median overall survival for all stage III patients, and for those with 'RTOG 0617 inclusion criteria' is 46.6 and 50.0 months, respectively.

Conclusions: Overall toxicity is low. In comparison to results in the literature, maximal sparing the ipsilateral normal lung lowers the risk for pneumonitis significantly.

Trial registration: Ethics committee of Vorarlberg, Austria; EK-0.04-105, Registered 04/09/2017-Retrospectively registered. http://www.ethikkommission-vorarlberg.at.

Keywords: DART-bid; Locally advanced NSCLC; Lung cancer; Margins; Planning; QUANTEC; Radiation dose intensification; VMAT.