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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
158
Patients 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. 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.
Patients 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-PET2 result).
Centre Henri Becquerel
Rouen, France
Local regional control rate
LCR rate (responders or stable disease) at 1 year after completion of RCT (M15 visit). Disease progression will be assessed by RECIST 1.1 criteria
Time frame: one year
Percentage of local regional control with RECIST 1.1 criteria
Disease progression will be assessed by RECIST 1.1 criteria
Time frame: assessed at 9 months, 15 months, 27 months and 39 months
interval from the date of registration to date of local or regional progression
the interval from the date of registration to date of local or regional progression
Time frame: 3 years
Percentage of severe (grade 3+ CTCAE, v4) radiation-induced toxicity affecting lung and oesophagus at M9 visit (early toxicity) and M15, M27, M39 visits (late toxicity),
Percentage of severe (grade 3+ CTCAE, v4) radiation-induced toxicity affecting lung and oesophagus at M9 visit (early toxicity) and M15, M27, M39 visits (late toxicity),
Time frame: assessed at 9 months, 15 months, 27 months and 39 months
Percentage of patients in arm A for whom the radiotherapy dose could be increased
Percentage of patients in arm A for whom the RT dose could be increased
Time frame: 6.6 weeks
correlation of progression free survival with PET measure
standardized uptake value max and metabolic tumor volume of FDG -PET2 will be correlated with progression free survival at M15 visit
Time frame: one year
correlation of overall survival with PET measure
standardized uptake value max and metabolic tumor volume of FDG -PET2 will be correlated with overall survival at M15 visit
Time frame: one year
Change in standardized uptake value max
Measurements of the relative change in SUVmax from the 18F-FDG -PET1 (baseline) to the FDG -PET2 at 42 Gy defined as \[(PET2- PET1) / PET1\] x 100%
Time frame: weeks 12
Change in metabolic volume
Measurements of the relative change metabolic tumour volume from the 18F-FDG -PET1 (baseline) to the FDG -PET2 at 42 Gy defined as \[(PET2- PET1) / PET1\] x 100%
Time frame: weeks 12
Overall Survival
overall survival after M9, M15, M27, M39 follow-up visits
Time frame: assessed at 9 months, 15 months, 27 months and 39 months
progression-free survival
progression-free survival after M9, M15, M27, M39 follow-up visits
Time frame: assessed at 9 months, 15 months, 27 months and 39 months
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