Abstract Neoadjuvant Chemotherapy First, Followed by Chemoradiation and Then Surgery, in the Management of Locally Advanced Rectal Cancer A. Cercek, K. A. Goodman, C. Hajj, E. Weisberger, N. H. Segal, D. L. Reidy-Lagunes, Z. K. Stadler, A. Wu,M. R. Weiser, P. B. Paty, J. G. Guillem, G.M. Nash, L. K. F. Temple, J. Garcia-Aguilar, L. B. Saltz Memorial Sloan-Kettering Cancer Center Abstract Results Methods Patient Characteristics Conclusions FOLFOX and CRT before planned TME leads to substantial tumor regression and rate of pathCRs The regimen is well tolerated and leads to a high rate of delivery of all planned therapy Our recommended treatment schema includes interim imaging with MRI and/or endorectal ultrasound to assess for response to therapy This treatment strategy of completing all chemotherapy and chemoradiotherapy before planned surgery offers the opportunity for selective non-surgical management of locally advanced rectal cancer. Background: Standard therapy for locally advanced rectal cancer (LARC) is pre-operative chemo-radiotherapy (CRT) and post-operative chemotherapy. To address earlier systemic chemotherapy to target micrometastases. while treating the primary tumor, we began offering FOLFOX as initial treatment for patients with high-risk LARC. Purpose: To report safety and efficacy of initial FOLFOX before CRT on tumor downsizing and pathologic complete response (pathCR) in LARC. Patients and Methods: IRB waiver was obtained to review records of stage II/III rectal cancer patients (pts) treated at our institution between 2007 and Of approximately 300 LARC pts treated with CRT, 61 received FOLFOX as initial therapy. Results: Of the 61 pts, 57 received induction FOLFOX (median 7 cycles) then CRT, 4 pts had an excellent response, declined CRT, and had TME. Twelve pts did not undergo TME; 9 had a complete clinical response (CCR) and were managed non-operatively; 1 declined despite persistent tumor, 1 due to comorbidities, and 1 developed metastatic disease. 22/61 patients (36%) had either pathCR (n=13) or CCR (n=9). Of the 49 pts who underwent TME, all had R0 resections, 23 (47%) had tumor response >90%, including 13 (27%) pathCR. 28 pts received all 8 cycles of FOLFOX, 8 had pathCR (29%) and 3 CCR (11%). There were no SAEs requiring delay in treatment during FOLFOX or CRT. Conclusion: FOLFOX and CRT before planned TME results in substantial tumor regression, a high rate of delivery of planned therapy, substantial rate of pathCRs and the potential for non-operative management in select patients. A waiver of authorization was obtained from the MSKCC IRB to review an institutional database of colorectal cancer patients. The electronic medical records were searched to identify patients who met the following criteria: a)presentation to Memorial Sloan-Kettering Cancer Center with clinical (either MRI or ERUS) stage II/III (T3/4, N1-2) rectal cancer between 2007 and 2012 b)No prior primary tumor-directed surgery, stenting or RT c)Received induction chemotherapy with FOLFOX (5FU, leucovorin and oxaliplatin) or CapeOx followed by CRT (total dose if 5040cGY) then TME d)Patients had interim imaging with either MRI or surgical evaluation e)Pathology reports were reviewed to assess complete and partial response rates. Results Baseline Characteristics Number of Patients Total = 61 % Sex Male Female % 46% Age, years Average Range Performance Status (ECOG) % 31% Initial Diagnosis Stage (MRI or ERUS) T3N0 T3N1 T3N2 T4N0 T4N1 T4N % 43% 39% 2% 6% 4% Response to treatment Total number of patients with TME N=49 Pathologic Complete Response 13 (27%) >90% treatment effect23 (47%) Node positive clinical diagnosis N=46 Node negative ypN0 30 (65%) All patients completed all planned chemo and CRT There were no grade 4 toxicities or SAE Toxicities were consistent with those previously reported for FOLFOX. Grade 3 toxicities from CRT included diarrhea (4%), fatigue (1%), nausea (1%) and neutropenia (1%). All patients achieved R0 resections No patients progressed in the primary on treatment Median follow up of 15.5 months (range 47.6mo mo) Of 61 patients 22 (36%) either had a pathCR (13) or complete clinical response (9) Of 49 patients who underwent TME 23 (47%) had tumor response > 90% 13 (27%) had pathCR Results