Long-term results of a prospective phase II trial of medically inoperable stage I NSCLC treated with SBRT – the Nordic experience

Abstract

Background. Presentation of long term results of a phase II multicenter Nordic trial of medically inoperable stage I non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT). Material and methods. We report the extended outcome, focusing on long-term effects, of a prospective cohort of 57 evaluable patients with peripherally located T1N0M0 (72%) and T2N0M0 (28%) NSCLC, treated with SBRT 15 Gy ϫ 3, prescribed to the 67% isodose line encompassing the PTV. The patients were inoperable due to chronic obstructive pulmonary disease (65%), cardiovascular disease (25%) or other illnesses (3%) or refused surgery (7%). Median Karnofsky score pre-treatment was 80% (70 -100%). Late effects were defi ned as occurring Ͼ 36 months. Results. Thirty-eight patients (67%) were relapse free during their entire follow-up. Local control rate at four and fi ve years were 79% (CI 95% 64 -95%) and local relapses occurred at 10 -76 months post-treatment. Seven local failures were noted, four occurring Յ 36 months (all T2a-tumors; two isolated and two in combination with out-of-fi eld relapses) and three occurring Ͼ 36 months (T1b-tumors n ϭ 3). Thirteen patients had out-of-fi eld failure only as fi rst presentation of recurrence. Overall survival rate and lung cancer-specifi c survival rate at fi ve years were 30% and 74%, respectively. Toxicity throughout the entire observation period was acceptable without any grade 5 toxicities. Seventeen grade 3 -4 toxicities were noted, three presenting Ͼ 36 months (rib fracture, dyspnea and ventricle tachycardia). Median follow-up was 41.5 months (3.4 -113.0) for the entire cohort and 59.3 months (36.4 -113.0) for the 34 patients (60%) with a follow-up of Ͼ 36 months. Conclusion. Throughout the observation period local control was excellent and toxicity limited with no increase in late presenting local relapses or late treatment-related morbidity. This further supports SBRT as an effi cient local treatment modality even in a medically impaired patient cohort.

ESTRO ACROP consensus guideline on implementation and practice of stereotactic body radiotherapy for peripherally located early stage non-small cell lung cancer

“…6/57 items were recommended for best practice, but the majority of 32/57 technologies and work-flows were considered as optional. This recommendation is in agreement with the excellent outcome of all prospective phase II trials of SBRT for early stage NSCLC: local tumor control was high with a favorable toxicity profile despite the relatively undemanding requirements on the technological aspects of SBRT from a 2016 perspective [22][23][24][25][26][27]. Consequently, the high investment costs associated with dedicated SBRT technology should not be a barrier to starting a lung SBRT program.…”

Predicting risk factors for radiation pneumonitis after stereotactic body radiation therapy for primary or metastatic lung tumours

“…No Grade 5 toxicities were reported. In the Nordic Phase II study of SBRT, 19 Grade 3 toxicities were observed in 12 (21%) of the 57 patients, but no Grade 4 or 5 toxicities were reported. According to the protocol of the Japan Clinical Oncology Group 0403 study, 16 the only patients restricted from participation are pregnant females.…”

“…1 Several trials have confirmed the safety of SBRT for patients with lung tumours. [16][17][18][19] In the Radiation Therapy Oncology Group Trial 0236, 17 Grade 3 and Grade 4 toxicities related to SBRT occurred in 12.7% (7/59) and 3.6% (2/59) of cases, respectively. No Grade 5 toxicities were reported.…”

“…With regard to conventional radiotherapy, many clinical and dosimetric factors have frequently been analyzed and reported to be significantly associated with RP. 14,15,22,23 Recently, the risk factors of RP after SBRT in patients with lung tumours have been investigated, 19,[22][23][24][25][26][27][28][29] and some studies reported about the clinical and dosimetric risk factors of RP. 21,[29][30][31][32][33][34][35][36][37][38][39][40][41][42] Table 7 summarizes published reports of the clinical and dosimetric risk factors associated with Grade 2 or worse RP after SBRT.…”

The American Society of Clinical Oncology–endorsed American Society for Radiation Oncology Evidence-Based Guideline of stereotactic body radiotherapy for early-stage non–small cell lung cancer: An expert opinion

“…We agree that data on the long-term outcomes of SBRT are still limited; however, several prospective phase II trials of SBRT reported outcome with follow-up greater than 3 to 5 years, and all did not observe an increased risk of late recurrences or risk of death. [24][25][26][27] It should also be pointed out that response assessment after SBRT is more difficult because of fibrotic changes in the high-dose volumes, and in most reports local control after SBRT is defined as ''absence of progressive disease'' in contrast to surgery where no tumor remains after complete R0 resection. 28 However, computed tomography-based criteria for differentiation of fibrotic changes and true local progression recently have been developed and validated.…”