Reirradiation for Cancers of the Rectum and Anal Canal

S352

International Journal of Radiation Oncology  Biology  Physics

2356

previously defined for several pathologies including anal canal carcinomas. Treatment indications were locally advanced squamous cell anal carcinoma T2 > 4 cm or N positive, protocols and evaluation criteria were planned for prospective evaluation. Prescribed dose to the pelvis including inguinal nodes was 45 Gy. The primary site and involved nodes were boosted to 59.4 Gy, 1.8 Gy per fraction per day, 5 days a week. A positional MVCT was systematically performed before each treatment session. All acute and late toxicities were scored according to CTCAE V3. Survival analysis was performed using Kaplan-Meier method. With a median follow up of 24 months, no patient was lost for follow up. Analysis was completed at February 2012. Results: From June 2007 to December 2011, 69 consecutive patients (median age: 65 years, 12 males, 57 females) were treated with helicoidal tomotherapy for locally advanced anal squamous cells carcinoma. Twenty three patients (33.3%) had T2 tumors, 19 patients (27.6%) T3 and 27 patients (39.1%) T4. Forty three patients (62.3%) had nodal involvement and four patients presented with metastatic disease. Mean size of tumors was 49 mm [range 20-110]. Seven patients had a colostomy before the beginning of the treatment. All patients except seven received concomitant chemotherapy (5FU-cisplatinum or 5 FU mitomycin based). Fifty (72.4%) patients experienced a complete response. Fifteen patients experienced a partial response or local recurrence, and 12 had salvage surgery; among them 6 are in complete remission. Four patients experienced distant failure only. The 2 year overall survival, recurrence free survival, local recurrence free survival and colostomy free survival were 87%, 69%, 76% and 79%, respectively. Acute grade 3 toxicity included: 20.3% gastrointestinal, 45% dermatological and 13% hematological. Acute grade 4 hematological toxicity occurred in one patient. No grade 5 was observed. Conclusion: Tomotherapy in locally advanced anal cancer is feasible. In our three centers of expertise in anal carcinoma this technique seems to reduce acute GI toxicity; nevertheless high rates of dermatological toxicities remain observed. The therapeutic efficacy is in the range of expectation and similar to previous techniques according to the high rates of locally advanced tumors and nodal involvement. Author Disclosure: V. Vendrely: None. E. Rio: None. B. Henriques: None. J. Benech: None. A. Lisbona: None. S. Belhomme: None. J.P. Maire: None. M.A. Mahe´: None. G. Kantor: None.

A Comparative Study of Conventional Radiation Therapy Versus Intensity Modulated Radiation Therapy in the Management of Patients With Anal Canal Cancer O.M. Mahmoud, S. Zia, D. Kwon, M. Abramowitz, B. Lally, and L. Portelance; University of Miami, Miami, FL Background: In a recently published collaborative group trial, intensity modulated radiation therapy (IMRT) for the treatment of anal canal squamous cell carcinoma (SCCA) was found to be associated with an excellent disease control and low treatment toxicity. In order to investigate further the potential benefit of IMRT in the management of anal canal cancer, we conducted a retrospective study on the treatment toxicity and outcome in patients with SCCA who were treated with definitive chemoradiation therapy by either IMRT or conventional radiation therapy (CRT) in our institution. Methods: Eighty-four patients who received definitive chemoradiation therapy from January 2001 to December 2011 were included. All patients received 5-fluorouracil with Mitomycin C on week one and five. Thirtynine patients (46%) were treated with CRT and 45 (54%) with IMRT. The median dose was 54 Gy in both groups (21.6-59.4 CRT; 45-59.4: IMRT). Median follow-up was 26.5 months for CRT and 9.3 months for IMRT. Results: The T3-T4 stage patients were similar between the two groups (35.9% in CRT and 44.5% in IMRT). However, lymph node-positive disease was higher in the IMRT group (20.6% in CRT vs. 47.7% in IMRT (p Z 0.012). Seventeen patients (20%) tested positive for Human immunodeficiency virus (HIV). The treatment was delivered without interruptions in only 28.2% of the patients treated with CRT vs. 66.7%, of the patients treated with IMRT. In addition treatment breaks in the IMRT group were statistically shorter (p Z 0.005). Nineteen (22%) patients in the CRT group experienced grade >2 skin toxicity compared with 5 (5%) patients in the IMRT group (p Z 0.0005). There was no statistical difference in the gastrointestinal toxicity. The hematologic toxicity, using the weekly blood counts, was not statistically different between the two treatment groups. There was no correlation between weekly blood count and the bone marrow volume receiving 10 Gy (V10) and 20 Gy (V20). The locoregional control (LRC) and disease free survival (DFS) were 86.5%, 65.9% for the IMRT group and 88.1%, 78.1% for the CRT group. There was no statistical difference between both groups in terms of LRC and DFS (p Z 0.374). In addition, no difference was found in DFS by HIV status (p Z 0.757). Conclusions: In our institution experience, the use of pelvic IMRT for the treatment of patients with SCCA of the anal canal is associated with less treatment toxicity, reduced need for treatment breaks and similar disease control when compared with CRT. Even if IMRT allows for the delivery of lower bone marrow dose (in terms of V10 and V20) when compared to CRT, this finding was not associated with a better hematologic toxicity profile. Thus suggesting that in a patient population receiving 5-FU and Mitomycin C different strategy might have to be used to decrease the hematologic toxicity. Author Disclosure: O.M. Mahmoud: None. S. Zia: None. D. Kwon: None. M. Abramowitz: None. B. Lally: None. L. Portelance: None.

2357 French Multicentric Clinical Evaluation of Helicoidal Tomotherapy for Anal Cancer in a Cohort of 69 Consecutive Patients V. Vendrely,1 E. Rio,2 B. Henriques,3 J. Benech,1 A. Lisbona,2 S. Belhomme,3 J.P. Maire,1 M.A. Mahe´,2 and G. Kantor3; 1Department of Radiation Oncology, University Hospital, Bordeaux, France, 2Department of Radiation Oncology, Centre Rene´ Gauducheau, Nantes, France, 3 Department of Radiation Oncology, Institut Bergonie´, Bordeaux, France Purpose/Objectives: To assess feasibility and toxicity of helicoidal tomotherapy for treating anal cancer patients. Materials/Methods: Three tomotherapy units were installed in 2007 in France as part of the French National Cancer Institute project (INCa) on implementing new technology. Medical and economic impact was

2358 Reirradiation for Cancers of the Rectum and Anal Canal S. Hanasoge,1 P.S. Sullivan,2 J. Kauh,3 C. Staley,2 R. Prabhu,1 and J. Landry1; 1Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA, 2Department of Surgery, Emory University School of Medicine, Atlanta, GA, 3Department of Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA Purpose: The purpose of this study is to retrospectively determine freedom from progression, overall survival and toxicity in patients with a prior history of pelvic radiation who were treated with re-irradiation for rectal and anal cancers. Materials/Methods: Nineteen patients with history of previous pelvic radiation (RT) and treated with re-irradiation for colorectal or anal cancers from 1990 to 2011 were reviewed. These included primary (n Z 4) and persistent/ recurrent (n Z 7) colorectal cancers, and primary (n Z 1) and persistent/recurrent (n Z 7) anal canal cancers. A total of 5 patients underwent resection first and received adjuvant radiation for close/positive surgical margins; these patients were included in toxicity analysis but not in outcomes analysis. Median initial RT dose was 50.4 Gy (range, 36 - 70 Gy) and the median interval between the 2 RT courses was 4.13 years (range, 0.5 to 40 years). All patients received hyperfractionated RT at 1.2 Gy per fraction, 2 fractions per day, with median total dose of 39.6 Gy (range, 31.2 - 50.4 Gy). All but 1 patient received concurrent chemotherapy with 5FU, mitomycin C or platinum based regimens. The median follow- up period was 12.2 months (range, 0.5 - 49.4 months). Time to event was defined from the end of re-irradiation for all outcomes. Results: One patient was lost to follow up after completion of treatment and was excluded from analysis. Median overall survival time was 18.1

Volume 84  Number 3S  Supplement 2012 months (range, 1.7 - 125.4 months). Median freedom from local progression time was 11.4 months for the entire group, and 18.7 months for patients with anal cancer. Four of 7 patients (57%) with anal canal cancer and 2 of 6 patients (33%) with rectal cancer underwent surgery after reirradiation, respectively. In the anal cancer group, 2 patients already had colostomies at the time of re-irradiation. Of those who did not, colostomy was avoided in 3 of 5 patients (60%). Acute toxicity rate was low, with only one grade 3 (Gastrointestinal/dehydration, 5.5%) and no grade 4 acute toxicities. Grade 3-4 late toxicity was seen in 5 patients (27.8%). Late toxicities included avascular necrosis of the femoral head (1), lumbosacral radiculopathy (2), non-healing ulcer (1), rectovesical fistula (1), and hydronephrosis from possible radiation-induced stricture (1). Conclusion: Pelvic re-irradiation for rectal and anal cancers is feasible and associated with moderate late toxicity. Our outcomes are comparable to other published reports of rectal re-irradiation. Re-irradiation of anal canal cancer was able to preserve normal organ function in 3 out of 5 patients. With the caveat of small patient numbers and a short follow-up period, our findings indicate that further research in this area is warranted to provide an organ-sparing alternative to patients with recurrent anal cancers. Author Disclosure: S. Hanasoge: None. P.S. Sullivan: None. J. Kauh: None. C. Staley: None. R. Prabhu: None. J. Landry: None.

2359 Inguinal Node Recurrence to the Untreated Groin in Patients With Anal Carcinoma J. Nuyttens, S.E. Blinde, and M. Olofsen; Erasmus MC, Rotterdam, Netherlands Purpose: To examine the inguinal recurrence rates in 119 patients with anal carcinoma (T1-4, N0-1) who did not receive elective radiation therapy to the inguinal regions and to determine the prognostic factors of the inguinal recurrence. Methods and Materials: From 1987 to the end of 2004, 160 patients with an anal carcinoma were treated at our department with (chemo)radiation. After exclusion of patients with lymphogenic metastasis in the iliac and/or inguinal regions or patients with distance metastasis at the time of diagnosis or patients with prophylactic irradiation to groin, 119 patients remained. Twenty one patients had a T1 tumor (18%), 57 patients had a T2 tumor (49%), 28 patients a T3 tumor (23%) and 13 patients a T4 tumor (11%). The median tumor size was 3.5 cm (range: 1-13). Fifty four percent of the tumors were localized in the anal canal, 29% in the perianal skin and 17% in both locations. A dose of 40 Gy was delivered to the target volume being the pelvis from S1-2 including the primary tumor and perirectal tissue followed by 2 weeks rest and then a boost of 20 Gy to the primary tumor and perirectal tissue. The concomitant chemotherapy consisted of infusional continuous 5-fluorouracil during four days and mitomycin-C on one day in weeks 1 and 7. Eleven patients were treated without chemotherapy, mainly due to comorbidity. The median follow up was 60 months (range: 1-248). The median age was 59 years (range: 34-95), and 57% of the patients were female and 43% male. Results: The 5-year inguinal failure was 0% for T1, 12% for T2, 17% for T3 and 18% for T4 tumors. T2 tumors of the perianal skin, anal canal and both locations had a 5-years inguinal failure of 25%, 8%, and 0%, resp. T3 tumors of the anal canal and both locations had a 5-years inguinal failure of 15% and 33%, resp. The 5-years inguinal failure was 19% for tumors  4 cm compared to 4% for tumors < 4 cm (p Z 0.02). The 5-years local control at the anus was 90% for T1, 69% for T2, 76% for T3 and 63% for T4 tumors. The 5- and 10-years overall survival rates were 95% and 69% for T1, 60% and 37% for T2, 34% and 34% for T3 and 60% and 20% for T4 (p Z 0.001). Conclusion: The 5-years inguinal failure was 0% for T1, 12% for T2, 17% for T3 and 18% for T4 tumors. T2 tumors of the perianal skin had a 5years inguinal failure of 25%. The 5-years inguinal failure was 19% for tumors  4 cm. The inguinal nodes must be treated elective in patients with T2 tumors of the perianal skin, and in patients with tumors larger than 4 cm.

Poster Viewing Abstracts S353 Author Disclosure: J. Nuyttens: None. S.E. Blinde: None. M. Olofsen: None.

2360 Dose-painted Intensity Modulated Radiation Therapy for Anal Cancer: No Differences in Treatment Toxicity and Early Outcomes Between Human Immunodeficiency Virus Positive and Negative Patients L.A. Kachnic,1 P. Romesser,1 J.D. Mancias,2 M.M. Qureshi,1 K.L. Hartshorn,1 J.D. Willins,1 and T.S. Hong3; 1Boston Medical Center, Boston, MA, 2Harvard Radiation Oncology Program, Boston, MA, 3 Massachusetts General Hospital, Boston, MA Purpose/Objective(s): HIV infected patients are reported to experience increased treatment toxicity with non-conformal radiation and concurrent chemotherapy for anal cancer. We report our multi-institutional analysis of toxicity and two-year outcomes utilizing dose-painted intensity-modulated radiation therapy (DP-IMRT) in HIV positive (HIV+) patients on highly active antiretroviral therapy (HAART). Materials/Methods: From August 2005 to December 2010, 63 patients with squamous cell cancer of the anal canal, (10 HIV+), received DPIMRT and concurrent chemotherapy at two academic medical centers. The patient cohort consisted of 13 (20.6%) T1, 24 (38.1%) T2, 19 (30.2%) T3, and 7 (11.1%) T4, with 33 (52.4%) N0, 12 (19.0%) N1, 13 (20.6%) N2, and 5 (7.9%) N3. Three patients had metastatic disease. Acute and late toxicities were recorded using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, and the Radiation Therapy Oncology Group scoring system, respectively. Toxicity comparisons between HIV+ and HIV- patients utilized Chi-square or Fisher’s exact test. Two-year actuarial outcomes used Kaplan-Meier methodology. Results: HIV+ and HIV- patients received a median DP-IMRT dose of 50.4 Gy over 43.5 and 42.0 days, respectively. No significant differences were noted in acute grade 3+ toxicity in HIV+ versus HIV- patients: dermatologic 10.0% vs. 13.21%, P Z 1.0; genitourinary 10.0% vs. 3.77%, P Z 0.410; gastrointestinal 20.0% vs. 15.09%, P Z 0.653; and hematologic 80.0% vs. 64.15%, P Z 0.474. Multivariate analysis confirmed that HIV infection was not predictive of acute grade 3/4 toxicity. The median follow-up was 29.3 and 24.3 months for HIV+ and HIV- patients, respectively. No significant differences were noted in two-year local control (90.0% vs. 95.0%), distant control (90.0% vs. 89.7%), overall survival (90.0% vs. 89.2%), and colostomy-free survival (90.0% vs. 83.7%) rates among HIV+ vs. HIV- patients. There was also no significant difference in late effects: colostomies for post-IMRT anorectal dysfunction were necessary in 0% of HIV+ and 3.8% of HIVe patients. Conclusions: Dose-painted IMRT as part of definitive chemoradiation for HIV+ patients on HAART with anal cancer allows for comparable toxicity rates and two-year outcomes to non-HIV patients. As such, HIV+ patients with anal cancer should be considered eligible for all national trials in which IMRT is employed. Author Disclosure: L.A. Kachnic: None. P. Romesser: None. J.D. Mancias: None. M.M. Qureshi: None. K.L. Hartshorn: None. J.D. Willins: None. T.S. Hong: None.

2361 Analysis of HIV Negative and Positive Patients With Anal Squamous Cell Carcinoma Treated With Definitive Chemoradiation Therapy: An Update S.M. Schuman, A. Melamed, and P.G. Pagnini; University of Southern California, Los Angeles, CA Purpose/Objectives: The goal was to summarize the experience treating anal squamous cell carcinoma (SCC) with attention to differences in chemotherapy, local control, colostomy rate and survival between HIV negative and positive patients. Materials/Methods: Cases were identified from 6/2000 through 12/2010. Inclusion criteria included biopsy proven anal SCC, definitive chemoradiation therapy and documented HIV status. Continuous variables, which