Background: Pre-operative CRT is a standard-of-care for LA EA. We showed that PET scan after induction C prior to CRT and surgery predicts outcomes (Cancer 118:2820; 2012). PET responders (PET+, defined as > 35% decrease in mSUV of tumor) had superior pathologic complete response (pCR) rates and progression-free survival (PFS) vs. PET non-responders (PET-, < 35% decrease). Some Pts with progression (PD) on PET after induction C had long-term overall survival (OS) when changed to alternative C during RT. Methods: We retrospectively reviewed all Pts with LA EA who received induction C and chemoRT prior to planned surgery. All Pts had PET scan before and after induction C. Results: 201 Pts were treated between 2002 to 2013, median age 62, 76% with uN+ disease. Induction C regimens included cisplatin/irinotecan (± bevacizumab on study) in 63% and carboplatin/paclitaxel in 29%. 113 Pts (56%) were PET+ and 88 (44%) were PET-. All PET+ received same C during RT. Of PET-, 49 (56%) continued with same C during RT (PET-/no change) and 39 (44%) received different C with RT (PET-/change). 49 Pts (24%) did not undergo surgery because of PD (16%), medical inoperability (6%), or refusal given clinical CR (2%). Of 152 operated Pts, 13/86 PET+ (15%) achieved a pCR vs. 1/35 (3%) of PET-/no change (p = 0.046) vs. 3/31 (10%) of PET-/change (p = 0.26 for PET-/no change vs. PET-/change). Median PFS (23.4 vs. 10.1 mos, p = 0.003) and OS (38.7 vs. 25.3 mos, p = 0.017) for all Pts were significantly better for PET+ vs. PET-/no change. Median PFS for PET-/change was not reached and was superior to PET-/no change (p = 0.02) and not different from PET+ (p = 0.73). The 3-yr OS rates were 48% for PET-/change vs. 31% for PET-/no change (p = 0.18). Median OS for PET-/change was not different than for PET-/no change (25.8 vs. 25.3 mos, p = 0.22). Conclusions: PET scan after induction C predicts for outcomes in LA EA Pts who undergo CRT and surgery. Median PFS is improved, and trends toward improved pCR rate and OS appear possible in PET- who change C during RT. The ongoing CALGB 80803 study (NCT01333033) is evaluating this strategy.