Study of Interest of Personalized Radiotherapy Dose Redistribution in Patients With Stage III NSCLC

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).

Sex

All

Minimum age

18 Years

Maximum age

75 Years

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.).

• DERIVEDVera P, Giraud P, Hapdey S, Gouel P, Jan O, Le Roux P, Langlais A, Leveque E, Le Tinier F, Olivier A, Martin E, Berriolo-Riedinger A, Pourel N, Broglia JM, Boisselier P, Guillemard S, Salem N, Brenot-Rossi I, Garcia C, Berthold C, Giroux-Leprieur E, Moreau D, Guillerm S, Benali K, Tessonnier L, Audigier-Valette C, Lerouge D, Quak E, Massabeau C, Courbon F, Loo M, Larrouy A, Ghazzar N, Chaumet-Riffaud P, Amour E, Zalcman G, Modzelewski R, Thureau S. Prognostic Value of FDG PET Metabolic Parameters Before and After 42 Gy of Radiochemotherapy in Patients with Inoperable Stage III Nonsmall Cell Lung Cancer. J Nucl Med. 2025 Apr 1;66(4):516-524. doi: 10.2967/jnumed.124.268499. PMID 40015915
• DERIVEDVera P, Thureau S, Le Tinier F, Chaumet-Riffaud P, Hapdey S, Kolesnikov-Gauthier H, Martin E, Berriolo-Riedinger A, Pourel N, Broglia JM, Boissellier P, Guillemard S, Salem N, Brenot-Rossi I, Le Pechoux C, Berthold C, Giroux-Leprieur E, Moreau D, Guillerm S, Benali K, Tessonnier L, Audigier-Valette C, Lerouge D, Quak E, Massabeau C, Courbon F, Moisson P, Larrouy A, Modzelewski R, Gouel P, Ghazzar N, Langlais A, Amour E, Zalcman G, Giraud P. Adaptive radiotherapy (up to 74 Gy) or standard radiotherapy (66 Gy) for patients with stage III non-small-cell lung cancer, according to [18F]FDG-PET tumour residual uptake at 42 Gy (RTEP7-IFCT-1402): a multicentre, randomised, controlled phase 2 trial. Lancet Oncol. 2024 Sep;25(9):1176-1187. doi: 10.1016/S1470-2045(24)00320-6. Epub 2024 Aug 9. PMID 39134086