OA09.07 Individual Isotoxic RT Dose Escalation Based on V20 and Advanced Technologies Benefit Stage III NSCLC Treated with CCRT

RTOG 0617 recommended 60Gy as the standard dose for unresectable stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy (CCRT) Is the conclusion true? The phase I/II trial to determine the feasibility and effects of individual isotoxic radiation dose escalation in unresectable stage III NSCLC treated with CCRT based on bilateral lung V20 and advanced technologies was studied. Consecutive patients with unresectable stage III NSCLC were entered in cohorts of eight from March 2006 to May 2009. Patients were assigned to receive concurrent administration of late course accelerated hyperfrationation (LCAHF) intensity modulated radiotherapy (IMRT) and chemotherapy. Isotoxic dose escalation was based on V20 and advanced technologies including PET-CT, single-photon emission computed tomography (SPECT) and LCAHF IMRT. PET-CT was used to delineate the gross tumor volume. SPECT lung perfusion was applied to define different functional lung regions, which was used to optimize the IMRT plans. Patients with a V20 of 27% as a base level were enrolled into the first cohort. From the second cohort, the V20 further increased to 30%, 33%, 35%, 37%, and so on. The criteria for cessation of dose escalation was defined as more than 25% of patients in the cohort experienced dose limiting toxicity (DLT). To test the power of escalation dose, patients with total radiation dose over 66Gy would be assigned to the higher dose group (HD), while the other patients would be assigned to the standard dose one (SD). Forty patients were enrolled. The maximum tolerated value of V20 was 37% in this study. Nineteen patients entered SD group, while twenty-one in HD. The overall response rate was as high as 80%. Follow-up for all patients ranged from 1 to 112 months with survival patients from 101 to 112 months. The median overall and progression free survivals were 25.0 and 13.0 months, respectively. 1-, 3-, 5- and 8-year overall survival (OS) rates were 72.5%, 22.5%, 17.5%, and 10.0%, respectively. Patients with stage IIIa achieved a longer median OS than those of stage IIIb (31 vs. 21 months, P=0.029). Especially, patients received HD radiotherapy got a significant better OS and local recurrence free survival than those in SD (27, 23 vs. 16, 19 months, P = 0.053, 0.037) without increasing severe toxicity. The protocol is feasible and effective. In the future, the radiation dose escalation for unresectable stage III NSCLC treated with CCRT should be focused on toxicity control and advanced technology application.