Chemotherapy and Radiotherapy should be standard treatment for Localized Hodgkin's Lymphoma

A combination of chemotherapy and radiotherapy, rather than radiotherapy alone, should now be considered standard treatment for all patients with localized Hodgkin's lymphoma where the tumor is situated above the diaphragm, according to the results of a randomized controlled trial. Furthermore, the trial results suggest that radiotherapy need only target areas directly involved in the cancer, sparing more extensive treatment of surrounding tissue.

This finding adds clarity to speculation about the appropriate treatment of this cancer, after previous results from trials done during the late 1980s and early 1990s showed that clinical staging is sufficient for stratifying early stages of the disease; that chemotherapy followed by involved-field radiotherapy (limited to the areas of cancer, rather than extensive surrounding tissue) should be the standard treatment; and that duration of chemotherapy should be adapted to the severity of the disease.

Dr. Christophe Fermé and colleagues at the European Organization for Research and Treatment of Cancer and the Groupe d'Études des Lymphomes de l'Adulte initiated the trial to further elucidate treatment options that might improve event-free survival in patients with Hodgkin's lymphoma. By use of a set of prognostic factors previously published by the EORTC to stratify patients by severity of disease, the researchers compared subtotal nodal radiotherapy alone with a combination of chemotherapy and radiotherapy in patients pre-classified as have good or poor prognosis.

A total of 1538 patients between the ages of 15 and 70 years were enrolled in the trial. All had untreated clinical stage I or II supradiaphragmatic Hodgkin's disease and were being treated at any of 91 centers in Belgium, France, Italy, the Netherlands, Poland, Portugal, Slovenia, and Spain. Of the total patient population, 542 (35%) were categorized as having a favorable prognostic factors and 996 (65%) were categorized as having an unfavorable prognostic factors.

Patients in the favorable prognostic factor arm were randomly assigned to receive either subtotal nodal radiotherapy or combination therapy consisting of three cycles of chemotherapy plus involved-field radiotherapy. Patients in the unfavorable prognostic factor arm were randomly assigned to one of three regimens: six or four cycles of chemotherapy plus involved-field radiotherapy or four cycles of drugs plus subtotal nodal radiotherapy. The chemotherapy regimen used for all the groups was mechlorethamine, vincristine, procarbazine, and prednisone in combination with doxorubicin, bleomycin, and vinblastine.

Taking event-free survival as a primary endpoint, the researchers found that, in the group with favorable prognostic features, response rates to the two treatment regimens were similar. However, among the 446 patients from both groups who had a complete remission there was a significant different in rates between the combination group and the radiotherapy alone group: five had a relapse after combination therapy and 61 after subtotal nodal radiotherapy. This equated to a difference in the estimated 5-year event-free survival rate of 24%, favoring the combination-therapy group.

For patients with unfavorable prognostic factors, complete-remission rates were 83% in the group receiving six cycles of chemotherapy plus involved-field radiotherapy, 85% in the group receiving four cycles plus involved-field radiotherapy, and 86% in the group receiving four cycles plus subtotal nodal radiotherapy. However, there were no significant differences in the 5-year event-free survival estimates or in estimated overall survival.

The researchers conclude from their findings that four courses of a doxorubicin-containing regimen and involved-field radiotherapy should be the standard treatment for this tumor type. Furthermore, they note, in patients with risk factors, four cycles of a doxorubicin-containing regimen are as effective as six cycles and involved-field radiotherapy yields a disease-control rate similar to that with subtotal nodal radiotherapy.

"Our study showed that a combination of chemotherapy and radiotherapy should now be considered the standard treatment for all patients with localized stage supradiaphragmatic Hodgkin's disease and that subtotal nodal radiotherapy alone can no longer be recommended," summarize the authors.

"The results of our trial show that it is possible to tailor the duration of chemotherapy according to risk factors. Moreover, our findings point to a new role for adjuvant radiotherapy with smaller radiation fields, allowing for the reduction of toxic effects associated with large fields. A remaining question now under investigation is whether patients with early-stage Hodgkin's disease can be cured with chemotherapy alone," they conclude.

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