Background: Pre-operative or definitive chemoRT is accepted treatment for locally advanced (LA) ESCC. We have retrospectively shown that assessment by PET scan following induction chemo prior to chemoRT and surgery predicts outcomes in SCC Pts (Cancer 118:2820; 2012). Some Pts with progression on PET after induction chemo had long-term survival when changed to alternative chemo during RT. Methods: We retrospectively reviewed all Pts with LA ESCC who received induction chemo and chemoRT from 2002 to 2010; all Pts had PET scan before and after induction chemo. Results: 62 Pts were identified, median age 63, median Karnofsky performance status 80%, 75% with uN+ disease. 43 (69%) received induction chemo with platinum/irinotecan (CPT-11), 13 (21%) with platinum/paclitaxel and 6 (10%) with docetaxel/CPT-11 ± cisplatin. 38 Pts (61%) were PET responders (PETr; ≥35% decrease in mSUV of tumor) and 24 (39%) were PET non-responders (PETnr; <35% decrease). All PETr received same chemo during RT. Of PETnr, 9 continued with same chemo during RT and 15 were changed to a different chemo with RT. 33/38 PETr (87%) achieved a clinical complete response (cCR) vs. 4/9 (44%) of PETnr/no chemo change vs. 11/15 (73%) of PETnr/chemo change (p=0.01 for PETr vs. PETnr/no chemo change; p=0.25 for PETr vs. PETnr/chemo change). 17 Pts had resection, all R0; 5/12 PETr (42%) had pathologic CR (pCR) while 0/3 PETnr/no chemo change Pts had pCR. Median disease-specific survival (not reached vs. 19 mos, p=0.002) and overall survival (OS; 69.6 vs. 17.4 mos, p=0.0056) were significantly better for PETr vs. PETnr. Median OS for PETnr/chemo change was 19.6 mos vs. 13.3 mos for PETnr/no chemo change (p=0.50); 6/15 PET nr who had different chemo with RT have extended survival, including 4 who are without disease at 2.8 – 9+ years. Conclusions: PET scan after induction chemo appears to predict for outcomes in ESCC Pts who received chemoRT. Long-term survival is possible in PETnr who switch to different chemo during RT. Such a strategy should be prospectively evaluated in a clinical trial.