BOSTONHyperfractionated 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
"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
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
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.
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.