CHICAGOA study of 129 patients with
intermediate-grade and large-cell immunoblastic lymphomas shows that the
radiotherapy dose should be adjusted to the initial size of the tumor, said
Richard Wilder, MD, assistant professor of radiation oncology, M.D. Anderson
Cancer Center. The study constitutes the largest series of these patients in
the modern era of chemoradiation, he said.
"Others have reported that a complete response to
chemotherapy represented 5.0 to 8.5 logs of tumor cell killing. As a result,
there may be greater residual tumor burden after bulky tumors have completely
responded to chemotherapy," Dr. Wilder said at the annual meeting of the
Radiological Society of North America.
Radiation oncologists at M.D. Anderson consequently have
adjusted radiotherapy fractionation schemes based on initial tumor size.
"The hypothesis of this study was that the prechemotherapy size of Working
Formulation intermediate-grade or large-cell immunoblastic lymphomas affects
the dose of irradiation that should be delivered," Dr. Wilder said.
Based on data from the study and a review of the literature,
physicians at M.D. Anderson administer a total dose of 30.6 Gy to small tumors
that measure less than 3.5 cm. The dose increases to 39.6 Gy in 22 fractions
for tumors between 3.5 and 10 cm. Bulky tumors greater than 10 cm receive a 45
Gy dose of irradiation.
A total of 294 patients with newly diagnosed clinical stage
I-IV intermediate- grade or large-cell immunoblastic lymphomas were enrolled in
two prospective treatment protocols at M.D. Anderson between 1988 and 1996. Of
these, 172 patients with 265 sites of disease as defined by the Ann Arbor
staging system achieved a complete response to two to six cycles of induction
chemotherapy involving cyclophosphamide, doxorubicin, vincristine, and
A total of 129 patients who had a complete response to
chemotherapy then underwent radiotherapy at 180 nodal sites. The total
radiation dose delivered to these patients ranged from 30.0 to 50.4 Gy, which
was given over a period of 23 to 49 days in daily fractions of 1.5 to 2.0 Gy.
Because of the differences in prescribed fractions, the
researchers used a linear quadratic model to convert the total dose to a
biologically equivalent dose of 1.8 Gy per fraction (D1.8). Patients were
followed for a median of 62 months.
Local Control Rates
Local control depended on the tumor size at the start of
treatment as well as the D1.8, Dr. Wilder said. Local control was analyzed for
three groups of patients: those with tumors 10 cm or less who received a D1.8
of 26.8 to 39 Gy; those with tumors 10 cm or less who received a D1.8 of 39.2
to 52.9 Gy; and those with tumors greater than 10 cm.
"This is the first study to treat tumor size as a
continuous variable. All other studies in the literature have arbitrarily
grouped patients according to tumor size without an explanation about how those
tumor sizes were arrived at. In this study, 10 cm was the cutoff point for
local control," Dr. Wilder said.
In patients who received D1.8 less than 39.2 Gy, local control
was significantly better (P = .003) when lymphomas were less than 3.5 cm at the
start of chemotherapy. Five-year local control rates were 95% in these
patients. "There was no significant difference in local control for nodal
sites vs non-nodal or extranodal sites, and lower doses of radiotherapy
sufficed for lymphomas smaller than 3.5 cm," he said. Higher doses of
radiotherapy were necessary, however, for patients with larger lymphomas, he
Lymphomas that initially measured between 3.5 and 10 cm
required radiotherapy doses ranging from 39.2 to 50.8 Gy after three to six
cycles of induction chemotherapy. The 5-year local control rate was 97%.
Local control was worse in patients whose lymphomas were
greater than 10 cm at the start of chemotherapy (P = .009). There were,
however, only five lymphomas larger than 10 cm, and the radiotherapy dose range
Dr. Wilder concluded the following:
D1.8 between 29.8 and 39.1 Gy provided excellent local
control when lymphomas were less than 3.5 cm at the start of five cycles of
CHOP-based chemotherapy in patients who completely responded to cytotoxic
A D1.8 between 39.2 and 52.9 Gy also produced excellent
local control when lymphomas were between 3.5 and 10 cm before chemotherapy.
Treatment of lymphomas larger than 10 cm with a D1.8
radiotherapy dose ranging from 39.6 to 42.3 Gy did not produce adequate local
control, which suggests higher doses are needed.
[The research was published in the January 2001 issue of the
International Journal of Radiation Oncology, Biology, Physics.]