Hyperfractionated RT Ups Pharynx Cancer Survival

BOSTON—Hyperfractionated radiation improved local control and survival rates for advanced pharyngeal and laryngeal cancer patients in a randomized Canadian study presented at the annual meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO).

Bernard Cummings, MD, chief of radiation oncology, Princess Margaret Hospital, Toronto, reported that a twice-daily hyperfractionated schedule boosted 5-year overall survival from 30% to 40% in the 331-patient trial. Patients in the hyperfractionated group also had better local control than their counterparts who received conventional daily treatment: 56% vs 45% at 5 years.

As a result, the pharynx could be preserved in more cases than is possible with conventional treatments currently used in the United States or Canada, Dr. Cummings said. US physicians most often order surgery before radiation treatments for patients with advanced tumors of the larynx or pharynx, he explained. In Canada, surgery is mostly used for salvage after radiation therapy.

"The message is, we have higher doses of radiation leading to higher levels of local tumor control, and these can be achieved without excessive toxicity," Dr. Cummings said. "That translates into our being able to preserve these organs in a greater number of patients."

The hyperfractionated regimen increased the overall dose by 14% over the conventional dose used at Princess Margaret Hospital, Dr. Cummings said. It produced more acute toxicity, primarily mucositis, but not more late toxicities.

While acute toxicity caused 27% of hyperfractionated patients to need more time than the allotted 30 days for treatment, Dr. Cummings said that most patients completed the regimen. Both groups were on a 4-week schedule, with the additional 2 days for weekends, holidays, and machine breakdowns.

All 331 patients were treated between 1988 and 1995 at the hospital. About 20% had cancer of the hypopharynx, 40% of the larynx, and 40% of the oropharynx. Biopsy-proven squamous cell carcinoma, T3 or T4, was required for participation, and a preponderance had stage IV tumors, Dr. Cummings said.

The conventional-therapy group received 2.55 Gy once a day, adding up to 51 Gy over 4 weeks. The hyperfractionated group received 1.45 Gy twice a day, adding up to 58 Gy over 4 weeks.

Dr. Cummings described the results as significant for each survival endpoint. Locoregional control improved from 39% for the conventional group to 48% for the hyperfractionated group.

"The improvement is almost entirely in local control. It is not in regional control," Dr. Cummings said, noting that this was consistent with other studies. Regional control was achieved by 65% of the conventional group and 61% of the hyperfractionated patients.

Disease-specific survival at 5 years was 50% for the hyperfractionated group vs 44% for the conventional group.

Researchers have begun preliminary work for a trial that will try to increase the total dose to 64 Gy in 4 weeks at a rate of 1.6 Gy twice a day. This will concentrate high doses on the primary tumor, he said, with just an adjuvant dose to the lymph nodes. Patients will have surgery for regional involvement. At this point, he said, the investigators do not plan to add chemotherapy. "We feel the main role for chemotherapy is likely to come when we put it together with the best radiation therapy," he said.