SAN ANTONIOLocal-regional control significantly improved with
two radiotherapy fractionation variants delivering either increased
total dose or shorter treatment time, compared with standard
fractionation, in patients with locally advanced squamous cell
carcinoma of the head and neck, Karen Fu, MD, reported at the 41st
Annual Scientific Meeting of the American Society for Therapeutic
Radiology and Oncology (ASTRO).
Fractionation schedule is probably one of the most
important factors determining the outcome of radiation therapy,
said Dr. Fu, professor of radiation oncology, University of
California, San Francisco. The optimal fractionation schedule
has been controversial.
In this phase III Radiation Therapy Oncology Group trial (RTOG 9003),
patients received radiotherapy delivered using standard
fractionation, hyper-fractionation, accelerated fractionation with
split course, or accelerated fractionation with concomitant boost
The total dose with hyperfrac-tionation is 16.6% higher while
the overall treatment time is the same as that of standard
fractionation, Dr. Fu said. The overall treatment time
for the two accelerated fractionation schedules is 1 week shorter,
although the total radiation doses are similar to those with the
standard fractionation regimen.
More Than 1,000 Patients
The study was opened in September 1991 and closed in August 1997.
The number of patients entered was 1,113. Of these, 1,073
patients were analyzable and formed the basis of this report,
Dr. Fu said. The most common primary site was the oropharynx,
accounting for 60% of the patients, followed by supraglottic larynx,
hypopharynx, and oral cavity.
The primary disease was stage T1 in 6% of patients, T2 in 27%, T3 in
38%, and T4 in 29%. Thus, two thirds of the patients had a T3
or T4 lesion, she said. The node stage was N0 in 22% of
patients, N1 in 20%, N2 in 46%, and N3 in 12%. By overall stage, 4%
of the patients had stage II disease (base of tongue or
hypopharyngeal primaries only); 28% had stage III disease; and 68%
had stage IV disease. The median follow-up was 23 months for all
The 2-year local-regional control rate was 54.5% for accelerated
fractionation with concomitant boost and 54.4% for
hyperfractionation, significantly better than the 46% rate for
standard fractionation. Accelerated fractionation with split course
produced a local control rate of 47.5%, which was not significantly
different from standard fractionation.
The 2-year disease-free survival was 37.6% for hyperfractionation and
39.3% for accelerated fractionation with concomitant boost, compared
with 31.7% for standard fractionation. For accelerated fractionation
with split course, it was 33.2%, which was not significantly
different from standard fractionation.
The 2-year overall survival was 54.5% for hyperfractionation, 46.1%
for standard fractionation, 50.9% for accelerated fractionation with
concomitant boost, and 46.2% for accelerated fractionation with split course.
There was a trend toward improved disease-free survival for
hyperfraction-ation and accelerated fractionation with concomitant
boost. However, there was no significant difference in overall
survival, Dr. Fu said. As expected, acute toxicity
increased with hyperfractionation and accelerated fractionation, but
was tolerable, she added. Late toxicity was mostly
transient, and there was no significant difference in the incidence
of persistent late toxicity among the treatment arms.
The 2-year distant metastasis rate ranged from 16.6% to 18%, and
there was no significant difference among the treatment arms, Dr. Fu reported.
This was one of the largest randomized controlled trials of the
treatment of head and neck cancer mounted in the United States in the
past 20 years, Dr. Fu said. As such, it has great validity.
Based on the results of this trial, future RTOG phase III trials for
locally advanced head and neck cancer will use accelerated
fractionation with concomitant boost as the control arm.