Balancing the risks and benefits of concurrent reirradiation and chemotherapy for recurrent head and neck cancers is difficult for physicians at even the most experienced centers. Research recently published in Cancer, however, suggests that selection of patients who may benefit from this therapy should be based on the patient’s previous treatment and the amount of time that has elapsed since initial treatment (Choe KS, Haraf DJ, Solanki A. [Published online ahead of print June 13, 2011.]
Explore this issue:September 2011
Patients being considered for reirradiation start with a poor prognosis, said Douglas Frank, MD, chief of the division of head and neck surgery at Long Island Jewish Medical Center and associate professor in the department of otolaryngology-head and neck surgery at Albert Einstein College of Medicine in New York. “What we struggle with as clinicians is that we know that there is somewhat of a desperation to it,” he said. “We have to be very judicious in offering this type of treatment, knowing which patients are least likely to benefit and who will have the most complications.”
The retrospective study, conducted at the University of Chicago, included data from nine consecutive phase 1 and 2 protocols with 166 patients who had recurrent or second primary squamous cell carcinoma in a region that had previously been irradiated. Eighty-one of the patients had had surgical resection or de-bulking before enrollment. All patients received reirradiation as well as concurrent chemotherapy, which generally comprised 5-fluorouracil, hydroxyurea and a third agent. After a median follow-up of 53 months, median overall survival (OS) was 10.3 months. The two-year OS rate was 24.8 percent.
A subgroup analysis found that four prognostic factors were significantly linked with survival: surgical resection before protocol, reirradiation dose ≥ 60 Gy, an interval ≥ 36 months since prior radiation therapy and no previous chemoradiation therapy. The OS rate was 63.6 percent for the 11 patients in the study who had all of those variables.
Survival was lower in the patients who had previously been treated with concurrent chemoradiotherapy, however. For those initially treated with chemoradiotherapy, the two-year OS rate was 10.8, compared with 28.4 percent for those who had not received that concurrent therapy. In a subgroup analysis of the 11 patients who had undergone previous chemoradiation therapy and had a reirradiation dose < 60 Gy, the median survival was only 1.2 months, and none of those patients survived for two years.
Combining chemotherapy with reirradiation for treatment of recurrent or second cancer, although beneficial for some patients, carries with it significant risk. The mortality rate from treatment-related toxicities was 19.9 percent in the retrospective study. Among the 40 patients who had previously been treated with chemoradiotherapy, 30 percent experienced grade 5 toxicity. More than 66 percent of all patients at the last follow-up required a gastrostomy tube for feeding. Other adverse events included 15 episodes of carotid hemorrhage, with 10 of those fatal, and 18 patients who developed osteoradionecrosis requiring surgical intervention.