Schéma : Primary objective:
To determine whether tumour RT dose escalated up to 74 Gy in 6.6 weeks can improve the disease Local Regional Control (LRC) rate at 15 months (1 year after completion of RCT) by adapting RT target volume to the metabolic response as assessed on FDG-PET/CT performed at 42 Gy of concomitant RCT in stage III NSCLC and warrant more extensive phase III study.

Secondary objectives:
- Overall survival (OS) at M9, M15, M27, M39 visits (6 months, 1, 2 and 3 years post-RCT) primary objective of phase III (D1 is the inclusion/randomization date),
- Evaluation of LCR at M9, M27, M39 visits (6 months, 2 and 3 years post-RCT),
- Evaluation of immediate toxicity at M9 (6 months post-RCT) and long term toxicity at M15, M27, M39 visits (1, 2 and 3 years post-RCT),
- Progression-free survival at M15, M27, M39 visits (1, 2 and at 3 years post-RCT),
- Predictive value at M9, M15, M27, M39 visits (6 months, 1, 2 and 3 years post-RCT) of 18F-FDG PET performed at 42 Gy of RCT,
- Impact of the relative change in FDG uptake (SUVmax) and metabolic tumour volume between baseline and per-RT (42 Gy) in terms of LRC at M15, M27, M39 follow-up visits (1, 2 and 3-year post-RCT),
- Impact of 4D CT and 4D FDG-PET/CT on delineation of the Planning Target Volume (PTV).

Study design:
- Open, double arm, randomized phase II of a phase II-III study (phase II/III with accrual suspension after phase II patients accrued),
- Patients will be stratified by center (according to IMRT vs bifractionated RT),
- The registration date (D1) is the inclusion/randomization date. M9, M15, M27 and M39 follow-up visits correspond to 6 months, 1, 2 and 3 years after completion of RCT.
- Eligible patients will be allocated to one of 2 treatment groups:
· Arm A: Patients in the experimental arm will receive an individualized RT prescription up to a total dose of 74 Gy given in 6.6 weeks if they have a positive FDG-PET42Gy (about two thirds of pts are expected as positive ie 50/75; Vera, EJNMMI2014). An initial dose of 50 Gy will be delivered in 5 weeks (single daily fractions of 2 Gy), then an additional dose up to 24 Gy will be delivered over 1.6 week using a twice-a-day (BID) fractionated RT: 2.0 Gy in the initial Planning Target Volume (PTV) plus a 1.0 Gy fraction at least 6 hours later in the biological target volume (BTV). The BTV will be delineated on a FDG-PET scan acquired after an initial dose of 42 Gy ± 2 Gy (FDG-PET2), i.e. after 21 fractions. If IMRT is applied, a single daily Simultaneous Integrated Boost (SIB) will be allowed.
· Arm B: Patients in the standard arm will receive a single prescription of 66 Gy in 33 fractions in 6.6 weeks, with 2 Gy fractions given once daily, 5 days a week, without target volume reduction or adaptation (whatever the FDG-PET result).
- In both arms, all patients will undergo 2 cycles of induction CT (based platinum salts) and a curative RCT. In both arms all fields must be treated daily. The total
dose will be prescribed so that the total Mean Lung Dose (MLD) is ≤ 20 Gy and V20 < 30%, and doses to other organs at risk (oesophagus, heart and spine)
meet the standard limits. Respiratory gating and IMRT will be optional. A biological ancillary study (RTEP7 bio) will be performed.
This funding request concerns only the phase II of this trial, therefore we do not present the exact design of the phase III part of the study in this document. For Phase III, all the patients included in phase II remain evaluable for survival.