Role of Hypofractionated Radiation Therapy Before, During or after Chemotherapy in Patients with NSCLC Stage IIIA-IIIB: Analysis of LC, OS and Toxicities

Abstract

Currently, the therapeutic strategy for locally advanced lung cancer is based on the use of chemotherapy for treat primitive tumor and control metastatic spread and use of radiotherapy to consolidate thoracic disease. For integrated approaches, conventional radiotherapy requires sequential use of the same to avoid excessive toxicities. In this study, we used SBRT alone or with different temporal association with chemotherapy and analyzed the results in terms of LC, OS and toxicities. Between 2011 and 2017, 67 pts were treated with SBRT for locally advanced lung tumor NSCLC stage IIIa-IIIb. Median age was 68 ys, KPS >70. 25 pts underwent sequential SBRT after chemotherapy, 22 pts SBRT between one cycle and another, in 9 pts SBRT was delivered before chemotherapy and 11 pts were treated with only SBRT. Histology was Adenocarcinoma and Squamous Carcinoma in 60% and 40% of pts. In pts who have integrated treatment, SBRT was performed no earlier than two weeks before or after chemotherapy. Target was contoured using CT, co-registration with PET images was performed for 26 pts. Median volume GTV was 82,6 cc (range 36 -192). Median delivered dose was 40 Gy/5fx (median BED 10 of 100 Gy). The dose was prescribed to 80% isodose line. Dose Constraints used were: Single lung V10<20%, Dmax bronchus 38 Gy, Dmax esophagus 35 Gy, Dmax Spinal cord 22.5 Gy, Dmax Heart 38 Gy. The IGRT-VMAT treatment was delivered by 6MeV beam modulator Linac with 4 mm MLC and in breath hold using ABC (Active Breathing Coordinator) device for 28 pts. Patient set-up at isocenter position was checked before each fraction by CBCT. Toxicities were assessed by CTCAE 4.3 criteria and the results were evaluated two months after the end of SABR and every four month successively using CT and PET/CT. Median follow-up was 16 months. Treated lesions of 40/67 pts show complete response and 22/67 partial response. LC was 90% at 12 months and 75% at 18 months for pts that underwent SBRT between or after cycles of chemotherapy, for pts that underwent SBRT only or SBRT before chemotherapy LC was 85% at 12 months and 72% at 18 months. OS was 86% at 12 months and 74% at 18 months for pts that underwent SBRT between or after cycles of chemotherapy, for pts that underwent SBRT only or SBRT before chemotherapy OS was 83% at 12 months and 70% at 18 months. The most common Grade 2 early toxicity was disphagia, that occurred in 10 pts. Late toxicity G3 was observed in 3 pts (esophageal stenosis in 1 case and bronco-esophageal fistula in 2 pts), but endoscopy showed local recurrence in all cases. In our experience SBRT for locally advanced NSCLC are safe and effective. Treatments with BED 10 values of 100 Gy or more are effective leading to mean LC rate of 88% and 74% at 12 and 18 month respectlively. SABR in association with chemotherapy increases statistically LC and OS with few and acceptable toxicities.