[j1]This is out of 184 (4 not evaluable, lost to followup 3M, 1F) [j1]This is out of 184 (4 not evaluable, lost to followup 3M, 1F) Cisplatin based chemoradiation for locally advanced squamous cell carcinoma of the anal canal: A 20-year perspective. Cathy Eng1, Yan Xing2, Y. Nancy You2, George J. Chang2, Prajnan Das3, Jonathan Phillips1, Robert A. Wolff1, Miguel A. Rodriguez-Bigas2, Aki Ohinata1, Christopher H. Crane3The Department of Gastrointestinal Medical Oncology1, Surgical Oncology2, and Radiation Oncology3, The University of Texas M. D. Anderson Cancer Center, Houston, Texas. Table 3. Overall Clinical Response • 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-fivepercent 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 immunocompromisedor 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 MMC3 has been demonstrated in phase III studies. However, cisplatinfor induction4 or adjuvant3 chemotherapy has shown no benefit. • 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, 1989-2009. • 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 chemoradiationtherapy. • 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 proctoscopyevery 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. Table 2. Chemotherapy Regimens Figure 2. Figure 6. • 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: 1.17-2.01) and DM (p=0.04, 95% CI: 1.09-2.13), but not for OS (p=0.59, 95% CI: 0.88-1.51) or CFS (p=0.17, 95% CI: 0.86-1.79). Figure 3. Figure 7. *Fisher’s Exact Test Table 4. Outcomes for Partial 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. Figure 4. Table 5. Recurrence and Metastasis Figure 1. Figure 5. 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. References 1. Johnson et al: Cancer. 2004 Jul 15;101(2):281-8. 2. Silverberg et al: Curr Opin HIV AIDS. 2009 Jan;4(1):42-51. 3. James et al: J Clin Oncol 27:18s, 2009 (suppl; abstr LBA4009) 4. Ajani et al: JAMA. 2008 Apr 23;299(16):1914-21.