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The European Organisation for Research and Treatment of Cancer (EORTC) phase II single-arm prospective multicentre Lungtech trial 22113-08113 assessed safety and efficacy of stereotactic body radiotherapy (SBRT) in inoperable patients with centrally located NSCLC.

Patients with inoperable non-metastatic NSCLC (T1-T3 N0, ≤7cm), located within 2 cm or touching the proximal bronchial tree or immediately adjacent to the mediastinal or pericardial pleura, were included. After prospective imaging review and radiation therapy quality assurance (RTQA), patients were treated with SBRT (8x7.5Gy, ICRU 83). Follow-up was performed 6 weeks after treatment, then 3-monthly for 3 years, 6-monthly in year 4 and 5, including assessment of adverse events (AEs, acute < and late ≥ 90 days; CTCAE 4.0), CT, FDG-PET and/or biopsy in case of suspected progression. The primary endpoint was freedom from local progression rate at three years after the start of SBRT.

In 2017, the trial was closed early, due to poor accrual caused by repeated safety-related halt in recruitment. Between 08/15 and 12/17, 39 patients from 13 sites in 6 European countries were included; 33 cases passed review; 31 were treated per protocol and analysed. Patients were mainly male (58%) with a median age of 75 (61-89) years. Median tumor was 2.6 (1.2-5.5) cm, median PTV 42.9 (14.1-133.5) ml. Most cancers were T1 (52%) or T2a (39%) and squamous cell carcinomas (48%). Baseline comorbidities were mainly respiratory (68%, including 4 cases with grade 3 AEs and 6 cases with COPD reported) and cardiac (48%; including 3 patients with grade 3 AEs). The majority of patients had a performance status of 0/1 (68%) and were medically inoperable according to a multimodality tumor board (87%). The statistical analysis was conducted with a median follow-up of 3.6 years. Freedom from local progression at 3 years was 78.6% (90% CI: 60.2–89.2) (figure 1) with a cumulative incidence rate of local, regional and distant progression of 10.0% (90%CI: 3.2-21.5%), 3.3%, (90%CI: 0.3-12.5%) and 26.5% (90%CI: 14.2-40.5%), respectively.  48.4 % of the patients died, mainly due to disease progression (46.7%). Median OS was 46 months; 3 year OS was 61% (90%CI: 44-74%). As previously reported, in 2 patients, death due to treatment related toxicity could not be excluded. SBRT-related acute AEs ≥Grade 3 were reported in 6.5%, which were 2 cases with pneumonitis (G3 and G5). SBRT related late AEs ≥Grade 3 were reported in 19.4 %, including atrial fibrillation (G3), aggravated COPD (both G3), lung infection (G3), dyspnea (both G3), and haemoptysis (G5).

SBRT with 8X7.5Gy in inoperable patients with central lung tumours is associated with high rate of local control; however, as far as can be judged from this small cohort with a high load of baseline cardiac and pulmonary comorbidities, the risk of severe late toxicity is clinically significant.