Hypofractionated accelerated high-dose radiotherapy (RT) in non-small cell lung cancer (NSCLC).

7527 Background: Dose escalation and RT intensification may improve local control in NSCLC but may potentially increase late toxicity. We postulated that accelerated hypofractionated RT is safe and efficacious with use of 3D-CRT and application of strict dose volume constraints (DVC).,50 patients with stage I-III medically inoperable/unresectable NSCLC, with weight loss less than 10% and KPS >70% were enrolled on a phase 1/11 clinical trial (ICORG 99-09) with a schedule of 72 Gy in 24 fractions, once daily, five fractions per week, over 32 days. Median age = 65 years (Range: 45-82 yrs). 39 patients were male and 11 female. 31 patients had induction chemotherapy. No elective lymph node irradiation was used. Primary endpoints were acute and late esophageal (RTOG/EORTC scale) and pulmonary toxicity (SWOG). Secondary endpoints were response rate at 3 months, time to tumor progression (TTP), time to tumor local progression (TTLP), time to distant progression (TTDP), progression-free survival (PFS) and overall survival (OS).,45 patients were treated with median f/u =11 months (range 3-73 mos). Acute toxicity was as follows: acute pneumonitis (20 pts: Grade (Gr) 1=19 pts, Gr2=1 pt); acute esophagitis (20 pts: Gr1=14pts, Gr2=3 pts, Gr3=3 pts) with one 4 day treatment interruption. 12 pts had late pneumonitis (Gr1=10 pts, Gr2=2 pts). A previous analysis presented at ASCO 2004 reported 2 pts with Gr 5 late esophagitis. Therefore, we introduced an additional esophageal DVC where <1 cm of circumferential esophagus was within the 98% isodose. Since then 8 patients were treated with no grade 5 toxicity and Gr1 = 1pt, Gr2 = 1pt, Gr3=1pt, with median f/u = 9 mos. Tumor response rate at 3 mos: (18% CR, 29% PR, 15% SD, 17% PD and 20 % non-evaluable). Median TTP = 12 mos, median TTLP =21 mos, and median TTDP = 11 mos. 1 yr PFS=81%, 3 yr PFS=28%. Median OS=17 mos with 1 yr OS=81%, 3 yr OS=25%.,The toxicity profile is favorable apart from initial unexpected esophageal late toxicity. We continue to evaluate the safety of our esophageal DVC. The median survival and TTLP results are encouraging as 40% pts had Stage III disease. No significant financial relationships to disclose.