WASHINGTONContinuous, hyperfractionated, accelerated
radiotherapy, or CHART, has won over official British medicine for
the treatment of non-small-cell lung cancer (NSCLC).
In the United Kingdom, CHART is now the treatment of choice in
the National Health Service, Mahesh (Max) Parmar, MD, said at
the Fall Symposium of the American Society for Therapeutic Radiology
and Oncology (ASTRO). The meeting, on advances in NSCLC, was
co-sponsored by the American College of Radiology.
Dr. Parmar, of Mount Vernon Hospital, Northwood, Middlesex, England,
described the modality as it is used in the United Kingdom and
Europe, and presented updated statistics from a 13-center,
multinational trial known as the CHART study.
There is only one randomized trial of accelerated fractionation
in non-small-cell lung cancer, and that is the CHART trial, Dr.
Parmar said. He noted, however, that other accelerated fractionation
studies similar to the CHART study are now in progress in the United
States and Germany.
The CHART study compared CHART with conventional radiotherapy in 563
patients with locally advanced NSCLC. Between February 19, 1990, and
March 31, 1995, the researchers randomized 338 patients to the CHART
arm and 225 to the control group.
Males made up 77% of the study participants. Forty-three percent of
the patients were between 61 and 70 years of age. Another 26% were
age 71 or older. By T stage, 45% were T2, 25% were T3, and 21% were T4.
CHART patients received 54 Gy over 12 straight days, delivered at 1.5
Gy three times a dayat 8 am, 2 pm, and 8 pm. Those in the
conventional arm received 60 Gy, given at 2 Gy a day for 6 weeks with
no radiation treatments on Saturdays and Sundays.
The rationale for the CHART schedule was to prevent repopulation of
cancer cells during the treatment period and to try to get the
treatment over and done before any morbidity could kick in and delay
therapy, Dr. Parmar said.
The latter objective appeared to work. More than 90% of CHART
patients received treatment on time, compared with only 19% of the
conventional therapy group, he said.
Endpoints for the study were survival, local tumor control, and
disease-free and metastasis-free intervals.
Among the CHART patients, 55% achieved some degree of local tumor
control, compared with 45% in the conventional therapy arm.
Local tumor control in non-small-cell lung cancer is a
difficult endpoint to assess; its rather subjective, Dr.
Parmar said. But at least the subjectivity is similar in both
arms. So although I am not sure about the absolute results, the
difference between the two arms is probably important.
And, Dr. Parmar added, consistently, CHART seems to
provide better local tumor control than conventional
chemotherapy. The relative risk of local tumor progression
among CHART patients, compared with controls, was 0.79. So,
with CHART, we are reducing the relative risk of local tumor
progression by about 21%, Dr. Parmar said.
The relative risk of metastasis or death in the two arms was 0.89 in
favor of CHART, he added. This is an estimated 11% reduction in
relative risk with CHART, but it is certainly not convincing that
this is a real effect, he said. Comparing the two arms,
you get a hazard ratio of 1.86, representing a reduction in the
relative risk of metastatic disease or death of 14% with CHART.
Again, this is encouraging evidence, but nothing dramatic.
Improvement in Survival
What is dramatic, he said, is the percentage difference in overall
survival across 4 years of follow-up. The hazard ratio was 0.78,
representing a reduction in relative risk of death with CHART of 22%,
with a P value everybody would like to see (P = .008),
Dr. Parmar said.
Four-year overall survival data from the study show that 59% of the
CHART patients and 57% of the controls were alive at 1 year. At 2
years, the comparable figures were 31% and 20%; at 3 years, 17% and
10%; and at 4 years, 9% and 4%. The median survival at 2 years was
16.5 months on CHART and 12 months on conventional therapy.
CHART researchers also looked at various subgroups within the trial
population. There is no clear evidence that CHART is more or
less effective in T1, T2, T3, or T4 patients, Dr. Parmar
commented. All age groups seem to do equally well.
However, when grouped by histology, there is some suggestion that
CHART is more effective in squamous cell carcinoma, compared with
non-squamous-cell carcinoma, he said. But 85% of the patients
in this trial had squamous cell disease. So its no more than an
interesting exploratory result, he noted.
The need for analgesia among the two arms varied. Although 5% of
patients in both groups required analgesics at the end of the first
week after beginning treatment, 30% of CHART patients required them
at 2 weeks, compared with a much smaller number in the
conventional radiotherapy group, Dr. Parmar said. However,
conventional radiotherapy patients required analgesics for a longer
period of time.
Dysphagia occurred earlier and was more aggressive in the
CHART group than in the control arm, but, at 6 weeks, few or no
patients had moderate or severe dysphagia on CHART, Dr. Parma added.
Late morbidity requiring follow-up was 4% in the CHART patients and
6% in the controls. Quality of life studies found no major
differences between the two groups. We conclude that there was
no radiation myelitis, a low incidence of serious morbidity in both
arms, and no difference in the two arms in the proportion of patients
with late morbidity, he said. There was, however, a major
difference between the two arms in cost, with CHART costing about
$1,200 more per patient than conventional radio-therapy.