Background Carcinoma of the anal canal accounts for 1.5% of all digestive system malignancies in the United States. 1 The annual incidence continues to rise resulting in increased recognition of this rare malignancy. Eighty-five percent of all anal cancers are squamous cell carcinomas. 1 Risk factors for anal carcinoma include a history of HPV infection, chronic immunosuppression, i.e., organ transplantation, or HIV infection. Notably, the use of anti-retroviral therapy has not reduced the incidence of anal carcinoma among HIV+ patients. 2 Greater than 90% of patients will present with locoregional disease treated with chemoradiation therapy with curative intent reserving abdominal perineal resection with colostomy (APR) for salvage surgery. For greater than 3 decades the treatment paradigm for locally advanced anal carcinoma has remained unchanged and consists of 5-FU with mitomycin C (MMC) and concurrent radiation therapy. 5-FU with MMC is associated with dose-limiting myelosuppression which may be particularly challenging for immunocompromised or elderly patients. Alternatively, 5-FU with concurrent cisplatin(C) results in less myelosuppresssion. 4 Efficacy of cisplatin and non-inferiority of cisplatin when compared to MMC 3 has been demonstrated in phase III studies. However, cisplatin for induction 4 or adjuvant 3 chemotherapy has shown no benefit. Results 184 pts were evaluable for response; 4 were lost to follow up. Patient and tumor characteristics at baseline are shown in Table 1. Median XRT dose: 55 Gy in 30 fractions (range 34 Gy to 69.9 Gy). Chemotherapy regimens are shown in Table 2. Treatment response (Tables 3-4): CCR in 172 pts (93%) Partial response in 12 pts (7%). Salvage surgery was completed in 6 patients. Higher T-stage correlated with need for salvage surgery (p= 0.01). Survival outcomes (Table 5, Figures 1-7): Median follow up: 8.6 years Local recurrence in 15 pts (8%) Distant metastasis (DM) in 16 pts (9%) Salvage surgery performed in 13 pts (7%) 5-yr DFS = 81%; 5-yr OS = 86%; and 5-yr CFS =88%. By univariate analysis, N-stage was a poor prognostic indicator for 5-yr DFS (p=0.02, 95% CI: ) and DM (p=0.04, 95% CI: ), but not for OS (p=0.59, 95% CI: ) or CFS (p=0.17, 95% CI: ). Table 3. Overall Clinical Response Table 1. Demographics Conclusions Cisplatin based chemoradiation for locally advanced SCCA of the anal canal resulted in favorable DFS, OS, and CFS compared to historical data and prior Phase III studies. Platinum based chemoradiation therapy is an acceptable alternative to the currently accepted standard, MMC, and should be considered as an option for locally advanced carcinoma of the anal canal. By univariate analysis higher N-stage was a poor prognostic indicator for 5-yr DFS and DM but not for OS or CFS. Additionally, higher T-stage correlated with need for salvage surgery. References 1. Johnson et al: Cancer Jul 15;101(2): Silverberg et al: Curr Opin HIV AIDS Jan;4(1): James et al: J Clin Oncol 27:18s, 2009 (suppl; abstr LBA4009) 4. Ajani et al: JAMA Apr 23;299(16): Cisplatin based chemoradiation for locally advanced squamous cell carcinoma of the anal canal: A 20-year perspective. Cathy Eng 1, Yan Xing 2, Y. Nancy You 2, George J. Chang 2, Prajnan Das 3, Jonathan Phillips 1, Robert A. Wolff 1, Miguel A. Rodriguez-Bigas 2, Aki Ohinata 1, Christopher H. Crane 3 The Department of Gastrointestinal Medical Oncology 1, Surgical Oncology 2, and Radiation Oncology 3, The University of Texas M. D. Anderson Cancer Center, Houston, Texas. Methods Study Design and Population (Tables 1 & 2) Retrospective consecutive cohort study of patients with SCCA of the anal canal treated with concurrent 5-FU/C/XRT over a 20-year period, Records were reviewed for patient demographics, tumor factors, and clinical outcomes including: History of STD’s or chronic immunosuppression, Stage, XRT dose, toxicity Clinical complete response (CCR), recurrence, colostomy-free survival (CFS), and OS. Initial clinical response was evaluated 6-12 weeks after the completion of chemoradiation therapy. Clinical complete response (CCR) identified at any time point during physician follow-up was considered (some patients required > 12 weeks) for CCR. Patients were followed by physical examination including a digital rectal exam and proctoscopy every 3-4 months, and annual CT scan. Statistical Analysis OS, DFS, and CFS were determined using the Kaplan-Meier method. The log-rank test was used for univariate comparisons. [j1] This is out of 184 (4 not evaluable, lost to followup 3M, 1F)[j1] N=12 (%) Partial Response Salvage APR Unresectable Other 6 (50) 4 (33) 2 (17) Table 4. Outcomes for Partial Response Table 5. Recurrence and Metastasis Total N (%) Salvage Surgery / XRT N (%) Metastasectomy N (%) Systemic Chemo N (%) Other / Unknown N (%) Local Recurrence15 (8)13 (87)N/A-2 (13) Distant Metastasis16 (9)N/A4 (25)5 (31)7 (44) Liver10 Lung1 Pelvis2 Distant LN2 Bone2 Figure 1. Figure 2. Figure 3. Figure 4. Figure 5. Figure 6. Figure 7. [j1] This is out of 184 (4 not evaluable, lost to followup 3M, 1F)[j1] *Fisher’s Exact Test N=188 (%)Regimen 5FU/Cisplatin Capecitabine /Cisplatin 165 (88) 23 (12) IV 5-FU (300 mg/m2) + cis 4mg/m2/day, M-F OR IV 5-FU (300 mg/m2) + cis 20 mg/m2, day 1 only of each week, M-F Capecitabine (825 mg/m2 BID) + cis 4mg/m2/day, M-F OR Capecitabine (825 mg/m2 BID) + cis 20 mg/m2, day 1 only of each week, M-F Table 2. Chemotherapy Regimens Aim To evaluate the efficacy of cisplatin and 5-FU based chemoradiation for patients with locally advanced squamous cell carcinoma of the anal canal treated at a single institution over the past 20 years. CCR N (%) PR N (%) P Total172 (93)12 (7) Sex : Male45 (94)3 (6)1.000* Female127 (93)9(7) AJCC Stage0.114* Stage I24 (100)0 (0) Stage II74 (96)3 (4) Stage IIIA31 (86)5 (14) Stage IIIB43 (91)4 (9) AJCC Primary Tumor0.459* T129 (97)1 (3) T277 (94)5 (6) T346 (94)3 (6) T4 Unknown 17 (85) 3 (100) 3 (15) 0 (0) AJCC Lymph Nodes0.070* N0111 (96)5 (4) N124 (89)3 (11) N227 (96)1 (4) N314 (82)3 (18) Histologic Grade0.157* Well14 (100)0 (0) Moderate to Well3 (75)1 (25) Moderate57 (97)4 (3) Moderate to Poor6 (75)2 (25) Poor Unknown 46 (92) 46 (98) 4 (8) 1 (2) Concurrent Chemo0.176* 5-FU/cisplatin Capecitabine/cisplatin 152 (94) 20 (87) 9 (6) 3 (13) N=188 (%) Age (Mean)56 Standard Deviation11 Sex: Male51 (27) Female137 (73) History of STD/Immunosuppression HIV5 (3) HPV2 (1) Hepatitis C1 (<1) Unknown180 (96) AJCC Stage (v7) Stage I25 (13) Stage II78 (41) Stage IIIA37 (20) Stage IIIB48 (26) AJCC Primary Tumor T131 (16) T283 (44) T350 (27) T421 (11) Unknown3 (2) AJCC Lymph Nodes N0118 (63) N124 (13) N228 (15) N318 (9) Histologic Grade Well14 (7) Well-moderate5 (3) Moderate64 (34) Moderate to Poor8 (4) Poor50 (27) Unknown47 (25) Basaloid/cloacogenic5 (11)