In patients with locally advanced stage III non-small cell lung cancer, the probability of local control remains low (about 17% at 1 year). Concomitant radio-chemotherapy is the standard treatment. An increase in total radiotherapy dose (from 66 to 74 Gray) has been proposed to improve local control, with contradictory results.

Relevant FDG-PET scan images can be acquired during radio-chemotherapy, with a demonstrated prognostic impact and recently in a multicentre prospective study. A significant reduction in FDG uptake / volume (metabolic response) suggests that the radiotherapy target volume could be reduced during radiotherapy possibly improving organs at risk tolerance. Conversely, a lack of metabolic response may justify treatment intensification before the end of radiotherapy. The investigators hypothesis is to investigate the individual tumour heterogeneity on FDG-PET during radio-chemotherapy to reduce the volume to a biological target that could receive a higher total dose (personalized dose redistribution).

The investigators objective is to determine whether tumour radiotherapy dose escalated up to 74 Gy in 6.6 weeks can improve the disease Local Regional Control rate at 15 months (1 year after completion of RCT) by adapting radiotherapy target volume to the metabolic response as assessed on FDG-PET/CT performed at 42 Gy of concomitant radio-chemotherapy in stage III non-small cells lung cancer and warrant more extensive phase III study.

Eligible patients will be allocated to one of 2 treatment groups:

• Arm A: Patients in the experimental arm will receive an individualized radiotherapy prescription up to a total dose of 74 Gy given in 6.6 weeks if they have a positive FDG-PET at 42Gy.
• 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 chemotherapy (based platinum salts) and a curative radio-chemotherapy. In both arms all fields must be treated daily.

Inclusion Criteria:

• Male or female patients,
• Age over 18 years and below 75-year-old,
• Good general condition: WHO performance status ≤ 1,
• Histological evidence of non-small cell lung cancer,
• Measureable tumour according to RECIST 1.1 evaluation criteria,
• Mediastinoscopy or endobronchial ultrasound to prove the histological stage N2/N3,
• Patient eligible to curative-intent radio-chemotherapy,
• Absence of pleural involvement, of pulmonary or extra-thoracic metastatic localisation,
• Absence of co-morbidity contra-indicating radio-chemotherapy,
• Lung function: FEV1 ≥ 40% of theoretical value and DLCO/VA ≥ 60% of theoretical value and PaO2 ≥ 60 mm Hg,
• Tumour FDG uptake higher than mediastinal background noise on baseline PET/CT,
• Haematological parameters:
• Neutrophil count ≥ 1.5x109/L and platelet count ≥ 100x109/L,
• Haemoglobin ≥ 9 g/dL,
• Provisional RT plan confirming that the dose objectives (minimal dose of 62.7 Gy (95% of the prescribed dose) in 98% of target volumes and 70.3 Gy for the "boosted" volume at 74 Gy) and constraints (lungs, spinal cord) are met (ICRU83),
• Estimated creatinine clearance ≥ 60 mL/min,
• Signed informed consent
• Affiliated or beneficiary of a social benefit system

Exclusion Criteria:

• Histology other than non-small cell lung cancer,
• Absence of FDG uptake on FDG-PET/CT scan before induction chemotherapy,
• Patients for whom curative radiotherapy is not indicated (tumour extension, metastases, general condition, co-morbidities),
• Significant interstitial disease on CT scan,
• Previous neoplastic disease of less than 5 years duration or progressive (without basal cell carcinoma of the skin, in situ carcinoma of the cervix),
• Previous thoracic radiotherapy,
• Patient enrolled in another therapeutic trial,
• Pregnant women or women of child-bearing potential or breast feeding mothers,
• Adult subjects who are under protective custody or guardianship,
• Patient unable to comply with the specific obligations of the study (geographic, social or physical reasons),
• Uncontrolled diabetes with blood glucose ≥10 mmol/L,
• Hypersensitivity to the active substance (FDG) or to any of the excipients,
• Patients unable to understand the purpose of the study (language, etc.).