Purpose To evaluate the prognostic factors, patterns of failure, and late toxicity in patients treated with chemoradiation (CRT) for anal cancer. Methods and Materials Consecutive patients with nonmetastatic squamous cell carcinoma of the anus treated by CRT with curative intent between February 1983 and March 2008 were identified through the institutional database. Chart review and telephone follow-up were undertaken to collect demographic data and outcome. Results Two hundred eighty-four patients (34% male; median age 62 years) were identified. The stages at diagnosis were 23% Stage I, 48% Stage II, 10% Stage IIIA, and 18% Stage IIIB. The median radiotherapy dose to the primary site was 54 Gy. A complete clinical response to CRT was achieved in 89% of patients. With a median follow-up time of 5.3 years, the 5-year rates of locoregional control, distant control, colostomy-free survival, and overall survival were 83% (95% confidence interval [CI] 78–88), 92% (95% CI, 89–96), 73% (95% CI, 68–79), and 82% (95% CI, 77–87), respectively. Higher T stage and male sex predicted for locoregional failure, and higher N stage predicted for distant metastases. Locoregional failure occurred most commonly at the primary site. Omission of elective inguinal irradiation resulted in inguinal failure rates of 1.9% and 12.5% in T1N0 and T2N0 patients, respectively. Pelvic nodal failures were very uncommon. Late vaginal and bone toxicity was observed in addition to gastrointestinal toxicity. Conclusions CRT is a highly effective approach in anal cancer. However, subgroups of patients fare relatively poorly, and novel approaches are needed. Elective inguinal irradiation can be safely omitted only in patients with Stage I disease. Vaginal toxicity and insufficiency fractures of the hip and pelvis are important late effects that require prospective evaluation.

Twenty-five-year experience with radical chemoradiation for anal cancer.

Anal cancer used to be a rare cancer traditionally associated with elderly women. There are approximately 5260 cases per year in the U.S. (1). The onslaught of the Human Immunodeficiency Virus (HIV) virus has led to a change in anal cancer demographics. Anal cancer is on the rise in the U.S and the number of anal cases documented has quadrupled in the past 20 yrs correlating with the rise of the HIV epidemic. The incidence of anal cancer is 40 to 80 fold higher in the HIV positive (HIV+) population when compared to the general population (2). With the advent of highly active antiretroviral therapy (HAART), HIV+ patients are living longer as less are progressing to AIDS. As a consequence non AIDS defining cancers such as anal cancer are on the rise. Factors implicated in the etiology of anal cancer in HIV+ patients include (Human papillomavirus) HPV virus status, sexual habits, and a history of smoking. HPV 16 and receptive anal intercourse (RAI) increase the risk of anal cancer by 33% over the general population. In the general population, the rate of anal cancer is approximately 0.9 cases per 100,000. In patients with a history of RAI, the rate approaches 35 cases per 100,000 which is equivalent to the prevalence of cervical cancer (3). Smokers are eight times more likely to develop anal cancer. There has been much discussion about tailoring treatment decisions in HIV+ patients with anal cancer. This review focuses on squamous cell carcinomas of the anal canal which comprise 80 to 90% of all anal cancers diagnosed and highlight key issues in the management of HIV+ anal cancer patients including recent clinical trials.

/pdf/hiv-positive-anal-cancer-an-update-for-the-clinician-25n3ibkz0m.pdf

HIV- positive anal cancer: an update for the clinician.

The Radiation Therapy Oncology Group 9811, ACCORD-03, and ACT II Phase III trials in anal cancer showed no benefit for cisplatin-based induction and maintenance chemotherapy, or radiation dose-escalation >59 Gy This review examines the efficacy and toxicity of chemoradiation (CRT) in anal cancer, and discusses potential alternative radiotherapy strategies The evidence for the review was compiled from randomized and nonrandomized trials of radiation therapy and CRT A total of 103 retrospective/observational studies, 4 Phase I/II studies, 16 Phase II prospective studies, 2 randomized Phase II studies, and 6 Phase III trials of radiotherapy or chemoradiation were identified There are no meta-analyses based on individual patient data A "one-size-fits-all" approach for all stages of anal cancer is inappropriate Early T1 tumors are probably currently overtreated, whereas T3/T4 lesions might merit escalation of treatment Intensity-modulated radiotherapy or the integration of biological therapy may play a role in future

Anal cancer: an examination of radiotherapy strategies.

Oesophageal cancer is the 8th most common cancer worldwide, and has significant mortality and morbidity rates. The two most common histological types, squamous cell carcinoma and adenocarcinoma, have different localizations, distinctive risk factors, and molecular mechanisms. Survival for patients with locoregional oesophageal cancer is poor when treated with surgery only, with 5-year survival less than 10–15%. Radiation therapy has limited efficacy when given alone. Concurrent chemoradiation improves local-regional control and facilitates margin-free resection when delivered preoperatively. Chemoradiation prolongs survival when given as definitive treatment or combined with surgery. Neoadjuvant chemoradiation also reduces risk of distant recurrence. To date, there is no data supporting the addition of targeted therapy to concurrent chemoradiation. Understanding molecular pathways regulating both radiosensitivity and tumorigenesis/invasion may lead to the discovery of new targeted agents, improving outcome of chemoradiation in terms of both locoregional and systemic control, ultimately resulting in prolonged survival.

Chemoradiation in oesophageal cancer.

Introduction The definitive treatment of anal cancer with chemoradiotherapy spares abdominoperineal resection for salvage treatment but carries a high burden of toxicity. Intensity-modulated radiat...

Toxicity and survival of anal cancer patients treated with intensity-modulated radiation therapy.

The Impact of Overall Treatment Time on Survival and Local Control in Anal Cancer Patients: A Pooled Data Analysis of RTOG Trials 8704 and 9811

Patient-Reported Outcomes (PROs) in NRG Oncology/RTOG 0436: A Phase 3 Trial Evaluating the Addition of Cetuximab to Paclitaxel, Cisplatin, and Radiation for Esophageal Cancer Treated Without Surgery

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The Impact of Overall Treatment Time on Survival and Local Control in Anal Cancer Patients: A Pooled Data Analysis of RTOG Trials 8704 and 9811

Patient-Reported Outcomes (PROs) in NRG Oncology/RTOG 0436: A Phase 3 Trial Evaluating the Addition of Cetuximab to Paclitaxel, Cisplatin, and Radiation for Esophageal Cancer Treated Without Surgery