Kachnic study: Dose-painted IMRT shows fewer significant side effects

A phase II Radiation Therapy Oncology Group (RTOG) trial showed that combining chemotherapy with intensity-modulated radiation therapy (IMRT) is just as effective after two years in treating anal cancer as chemotherapy and conventionally delivered radiation therapy, but with fewer significant side effects.

Radiation therapy with concurrent 5-fluorouracil and mitomycin-C chemotherapy is the standard of care for patients with non-metastatic squamous cell cancer of the anal canal but is associated with high rates of acute morbidity due in part to the large radiation fields. In contrast to two or three-dimensional conventional radiation fields, which indiscriminately treat normal organs, IMRT conforms the radiation dose to the tumor and lymph node regions, while sparing healthy surrounding tissues. Improvements in treatment-related toxicity have already been described in patients with breast, head and neck and prostate cancers treated with IMRT, as compared to conventionally delivered radiation therapy.

In the RTOG 0529 trial, lead researcher Dr. Lisa Kachnic, chair of radiation oncology at BUSM and RTOG co-investigators analyzed the outcome of 52 among 63 accrued patients with stage II and III anal cancer treated with IMRT and 5-fluorouracil/mitomycin-C chemotherapy. After a median follow-up of 26.7 months, the two-year disease-free survival was 77%, and overall survival was 86%. These results were very similar to the 325-patient, 5-fluorouracil/mitomycin-C arm of the RTOG 9811 trial, which used conventionally delivered radiation: 75% disease-free survival and 91% overall survival at two years. The causes of death for the 7 patients that died in RTOG 0529 study are: anal cancer in 5, morbidity in one and second primary cancer outside the radiation field in one.

Based on RTOG 0529, IMRT with 5-fluorouracil and mitomycin-C is associated with significant sparing of grade 3 and higher dermatologic and gastrointestinal acute toxicity as compared to the 5-fluorouracil/mitomycin-C and conventionally delivered radiation arm of RTOG 9811, without compromising two year outcomes. Because of the associated acute toxicity sparing and possibility to escalate radiation doses, IMRT will be used as the standard radiation technique in future RTOG anal cancer trials assessing novel agents in combination with radiation.

The study was presented at the eighth annual Gastrointestinal Cancers Symposium (January 20-22, 2011, San Francisco). The 2011 Gastrointestinal Cancers Symposium was co-sponsored by the American Gastroenterological Association (AGA) Institute, the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO), and the Society of Surgical Oncology (SSO).