1. Complete pathologic responses in the primary of rectal or colon cancer treated with FOLFOX without radiation A. Cercek, M. R. Weiser, K. A. Goodman, D. L. Reidy, W. D. Wong, J. G. Guillem, L. K. F. Temple, D. Schrag, P. Paty, L. Saltz Memorial Sloan-Kettering Cancer Center Abstract Results Background Methods Patient Characteristics Conclusions Pathologic complete response rate to FOLFOX-based chemotherapy is substantial and suggests clinically relevant biologic differences between the responsiveness of the primary vs. metastases These data support the hypothesis that routine use of pelvic radiation in all patients with rectal cancer may not be necessary for local control Further prospective trials of FOLFOX without radiation therapy in locally advanced rectal cancer patients are warranted Background: Stage II/III rectal cancer is treated with chemotherapy (chemo) plus radiation therapy (RT) followed by surgery, and then post-op chemo. Pelvic RT reduces local recurrence, but most studies don’t show a survival benefit. We retrospectively reviewed patients who received pre-op FOLFOX without RT as initial management of locally advanced rectal cancer, either because they had suspected metastatic disease, had relative contraindications to RT, or had refused RT. We also reviewed preoperative FOLFOX-based chemo in patients with known synchronous metastatic disease who ultimately underwent resection of the primary. Methods: Six pts with stage II/III rectal ca (see table) who received pre-op FOLFOX without RT, and 14 pts with synchronous metastatic colon or rectal cancer treated with pre-op FOLFOX + bevacizumab (bev) followed by resection of the primary were identified. Path reports were reviewed to assess the pathological complete response (path CR) and near-complete (>90% treatment effect) rates. Electronic records were reviewed for local and distant recurrence. Results: Of the 6 pts who received pre-op FOLFOX for localized rectal cancer, 2 had path CR, and 3 others had 99%, 95%, and 90% treatment effect. These 5 remain free of disease at time of last f/u. The sixth patient had minimal (10%) treatment effect in the primary: he failed in liver and lung one year post-resection without local failure. Of the 14 pts who had metastatic colon or rectal ca, 4 received FOLFOX and 10 received FOLFOX-bev. Of these 14 pts, 5 had path CR in the primary (4 with FOLFOX-bev, 1 with FOLFOX). Overall, of these 20 pts, 7 (35%) achieved a path CR to FOLFOX without RT. Conclusion: Even considering possible recall bias, the path CR rate to FOLFOX seen in these primaries appears much higher than seen in metastases (path CR rate less than 0.5% in metastatic disease). This warrants further study, and supports our prospective trial of pre-op FOLFOX-bev, without RT, in selected patients with locally advanced rectal cancer. 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 synchronous, stage IV colon (n=6) or rectal (n=8) cancer, or local-regional rectal cancer (n=6) treated with pre-operative FOLFOX without radiation therapy b)Treated between Jan 1, 2000 and Dec 31, 2006 c)No prior primary tumor-directed surgery, stenting or RT. d)Received neoadjuvant chemotherapy with FOLFOX (5FU, leucovorin and irinotecan) +/- bevacizumab Pathology reports were reviewed to assess complete and partial response rates. Locally Advanced Rectal Cancer (N=6) Age, median51 (38-85) ERUS StageT2N1 (1) T3N1 (5) ChemotherapyFOLFOX (6) Metastatic Rectal Cancer (N=8) Age, median53 (38-74) ChemotherapyFOLFOX-bev (7) FOLFOX (1) Metastatic Colon Cancer (N=6) Age, median61 (57-72) ChemotherapyFOLFOX-bev (4) FOLFOX (2) RESPONSE IN PRIMARY OF LOCALLY ADVANCED RECTAL CARCINOMA (N=6) PatientERUS Stage at Diagnosis Pathologic Stage Treatment Effect (%) RFS (mo) OS (mo) 85 FT3N1T0N0 (pCR) 100%21+ 48MT3N1T0N0 (pCR) 100%20+ 45FT3N1T1N099%16+ 59MT2N1 95%7+ 36FT3N1T2N090%20+ 53MT3N1 10%1224+ Combined modality therapy with 5FU-based chemotherapy plus radiation therapy, followed by surgical resection and further chemotherapy, is standard for locally advanced rectal cancer (NIH consensus JAMA 1990; 264(11):1444-50). Pelvic radiation has been shown to decrease local recurrence, while systemic chemotherapy further decreases local recurrence and can improve overall survival (NEJM 1985;312(23):1465-72, J Natl Cancer Inst 1988; 80(1): 21-29, NEJM 1991; 324(11):709-15, J Clin Oncol 1997; 15(5);2030-9, J Clin Oncol 1993; 11(10): 1879-87). Improvements in systemic chemotherapy (FOLFOX) have led to improved outcomes in the adjuvant setting in colon cancer (NEJM 2004; 350(23):2406-8). The effect of systemic chemotherapy alone (without radiation) on primary tumor response and local recurrence has not been well studied. Results RESPONSE IN PRIMARY OF METASTATIC COLON OR RECTAL CARCINOMA (N=14) Complete Pathologic Response >80%79-50%<50% 5 (36%)4(29%) 1 (7%) Overall 7 of 20 patients (35%) analyzed achieved a complete pathologic response to FOLFOX-based chemotherapy All patients achieved an R0 resection None have developed local recurrence thus far One of 6 patients from the locally advanced cohort developed metastases in the liver and lung; the rest remain disease free The toxicity profile was in accordance with the reported FOLFOX +/- bevacizumab toxicities