ATLANTA, GeorgiaChildren with low-risk Hodgkin’s disease
(HD) who have a complete remission after chemotherapy can forego radiation
therapy without an increased risk of recurrence, according to a trial presented
at the 46th Annual Meeting of the American Society for Therapeutic Radiology
and Oncology (abstract 3).
In contrast, the multicenter study showed that children with
intermediate-risk or high-risk disease who have a complete remission still need
radiation therapy to prevent a recurrence, although a lower radiation dose and
volume appear to be sufficient.
"Treatment results in pediatric Hodgkin’s disease are
excellent nowadays and can hardly be improved with respect to tumor control and
overall survival," said lead author Ursula Rühl, MD, director of radiation
oncology, Moabit Hospital, Berlin, Germany. "However, there have been concerns
in the past with regard to the very intensive treatment using chemotherapy and
radiation; this treatment can cause late effects, such as functional impairment
of vital organs, male infertility, infections, and, especially, the induction
of second malignancies."
These concerns have prompted a series of trials aimed at
reducing the intensity of treatment without compromising clinical outcomes, she
Children younger than age 18 with Hodgkin’s disease were
enrolled in the German Multinational trial GPOH-HD 95, and divided into three
risk groups according to the stage of their disease, B symptoms, and extranodal
extension. Those in the low-, intermediate-, and high-risk groups were treated
with two, four, and six cycles, respectively, of intensive combination
All of the children then underwent restaging. Those with a
complete remission (more than 95% tumor volume reduction and residual disease
measuring no more than 2 mL) did not receive radiation therapy. Those with a
good partial remission (more than 75% tumor volume reduction) were treated with
20 Gy to initially involved areas, while those with a poor partial remission
(less than 75% tumor volume reduction) were treated with 30 Gy to such areas;
residual disease of more than 50 mL was given a local boost to 35 Gy.
A total of 1,018 patients from seven European countries were
enrolled in the trial. After chemotherapy, 21% of patients had a complete
remission (and therefore did not receive radiation therapy), 66% had a good
partial remission, and 12% had a poor partial remission.
At a median follow-up of 58 months, 90% of patients were in
a complete continuous first remission, she said. There were 94 treatment
failures (57 relapses after complete remission and 37 cases of progressive
disease), as well as 5 second tumors and 5 deaths from other causes.
The 6-year rate of overall survival was 97% for the entire
study population, with no substantial differences between the low-,
intermediate-, and high-risk groups (99%, 97%, and 93%, respectively), and no
difference between irradiated and nonirradiated patients. "The good message is
that the overall survival for both groups [nonirradiated and irradiated] is
absolutely identical because we have a very potent salvage treatment at hand,"
Dr. Rühl noted.
The 6-year rate of event-free survival was 90%, but in
contrast, this rate was significantly higher in the low-risk group (94%) than
in the intermediate-risk group (86%) and the high-risk group (85%).
Stage IV disease, B symptoms, extra-nodal extension, nodular
sclerosis type II, and male sex were all risk factors for treatment failure,
she said. Omission of radiation therapy was associated with failure as well,
but only among patients with intermediate- or high-risk disease.
Specifically, in the low-risk group, rates of disease-free
survival did not differ between patients with a complete remission (who did not
receive radiation therapy) and patients with a partial remission (who received
radiation therapy) (95% vs 97%, respectively). But among patients with
intermediate-risk and high-risk disease, the rate of disease-free survival was
significantly lower among those with a complete remission and no radiation (77%
Longer Follow-up Needed
"Our trial turned out to have favorable resultshigh cure
rates and few treatment failures, and nearly 20% of the children were spared
radiotherapy and its potential late effects," she said. "The risk-adapted
treatment was successful; response-adjusted low-dose radiotherapy seems to be
safe, and also the reduced involved-field treatment seems to be safe. Not
safe is the omission of radiotherapy for advanced cases."
Dr. Rühl added that longer follow-up will be needed to
determine if the tailored treatment strategy succeeds in reducing late sequelae
and second cancers. "A further reduction of treatment intensity might be
possible, while intensified treatment might be necessary for some cases," she