Initial Size of Aggressive Lymphoma Guides RT Dose

CHICAGO—A 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 prednisone (CHOP).

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 said.

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 was narrow.

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 drugs.

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.]