Abstract

Line CLAUDE¹, Vanina ISNARDI², Camille SCHIFFLER³, Séverine METZGER⁴, Isabelle MARTEL-LAFAY⁵, Simon RIT⁶, David SARRUT⁶, Thomas BAUDIER⁶, Myriam AYADI⁵

¹Centre Léon Bérard, Radiation Oncology department, Lyon , France; ²Centre Léon Bérard, Nuclear Medicine department , Lyon, France; ³Centre Léon Bérard , Innovation and clinical research department, Lyon, France; ⁴Centre Léon Bérard, Innovation and clinical research department, Lyon, France; ⁵Centre Léon Bérard, Radiation Oncology department, Lyon, France; ⁶Centre Léon Bérard, CREATIS, UMR CNRS 5220, Inserm U1294 , Lyon, France

The overall survival (OS) of patients (pts) with non-resectable locally advanced non-small cell lung carcinoma (LA-NSCLC) is poor, in part due to insufficient local control (LC) using conformal irradiation techniques (RT). The personalization of the RT margins may impact the LC and the outcome. Internal Target Volume strategy (ITV) versus "Mid-position" strategy (Mid-p), was compared in a prospective non-comparative randomized monocentric phase II trial in NSCLC patients treated by definitive radiotherapy. Planning Target volumes and mean lung dose were previously reported as significantly reduced using the Mid-p strategy (DOI: 10.1259/bjr.20190692). We report here the clinical results. 

Eligible patients were randomized (2:1) to be treated with Mid-p or ITV strategies. Patients with proven LA-NSCLC, non-resected, non-metastatic treated by definitive RT could be included. The main objective was to evaluate the 1-year progression-free-survival (PFS) rate in the two arms. 36 pts were planned in the Mid-p arm, Fleming single-stage design (1-sided a=0.1, 80% power, P0=30%, P1=50%). Secondary objectives were to evaluate 1-y and 2-y LC, OS and acute/middle term toxicity (NCI-CTCAE v4).

54 pts were randomized from 09/12 to 05/18. 3 patients finally did not receive radiotherapy and were excluded from the analysis. Median age was 65.2 y, 2/3 of the patients were male and had IIIA NSCLC stages, 31% received concomitant chemotherapy. 34 pts and 17 pts were included in the analysis in the Mid-p arm and ITV arm respectively. Median RT dose was 66 Gy in the Mid-p arm and 62 Gy in the ITV arm. Median PFS were 9.3 months and 10.3 months in the Mid-p arm and ITV arms respectively. 1-year PFS rate were 38% (1-sided CI95% = [25-[) and 47% (CI95% = [27;[) in the Mid-p/ITV arm respectively. Efficacy in Mid-p arm is below that expected (starting hypothesis p0=30%, p1=50%). 2-year PFS rates were 15% (Mid-p) and 12% (ITV).

2-years LC rates were 65% (CI95% [48;81]) and 76% (CI95% [53;94]) in the Mid-p/ITV arms respectively (see Figure). The analysis of the type of local failures (in field versus border of fields) is under analysis and will be available for the congress.

No grade 4 or toxic deaths related to RT were reported. Grade 3 acute lung toxicity were reported in 12% and 23% in Mid-p and in ITV arms respectively. Grade 2 and Grade 3 late radiation fibrosis were reported in 29% and 15% respectively in the Mid-p arm, versus 23% and 29% using ITV strategy.

Two-year LC and PFS in LA-NSCLC seems similar in this non comparative Phase II randomized study using Mid-p or ITV strategies. The details of local relapses regarding RT fields and margins are under analysis and will be presented during the congress.