The clinician treating a patient with limited-stage Hodgkin lymphoma has two very important but competing responsibilities: First, the treatment chosen must have the highest likelihood of curing the lymphoma. Second, it should have the least probability of inducing major permanent toxicity such as infertility, cardiac injury, or induction of a secondary neoplasm. Stated simply, the goal is cure with the least harm.

Historically, limited-stage Hodgkin lymphoma was first reliably cured with wide-field radiation. However, once multiagent chemotherapy had been shown to cure advanced-stage disease it became logical to explore its role in limited-stage disease. At first the role of chemotherapy was to eliminate highly invasive staging with laparotomy and later to reduce the size of the field of radiation. Thus, combined brief chemotherapy plus involved-field radiation became the treatment of choice and has been repeatedly demonstrated to be able to cure at least 90% of patients with limited-stage Hodgkin lymphoma.¹

The success of this approach and the demonstration that the radiation field can be reduced to a very small size² opened the question as to whether any radiation is needed at all if highly effective chemotherapy is employed. False starts with older chemotherapy such as MOPP (mechlorethamine, vincristine, procarbazine, prednisone) or newer but inferior regimens like EVE (etoposide, vincristine, epirubicin) and EBVP (epirubicin, bleomycin, vinblastine, prednisone) demonstrated that one must be careful to use the most effective chemotherapy, which is currently ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). In the pivotal trial addressing this issue, the experimental arm-ABVD alone-demonstrated that at least 80% of patients can be cured with just chemotherapy.³

The final task, then, became how to recognize the small minority of patients whose lymphoma required radiation. The current leading contender for that role is functional imaging, namely FDG-PET scanning, and the definitive trials to test that question are in progress.

Success Bar Raised Higher

As the treatment of limited-stage Hodgkin lymphoma evolves, the success bar is raised higher and higher. Today we expect to cure at least 95% of patients, and death from lymphoma should be rare.1 With almost all patients being cured, minimization of late major toxicity becomes essential. Undoubtedly, reduction of field size and greater sophistication of dosimetry have reduced cardiac injury and second neoplasms. However, no dose of radiation is completely safe, and it should be eliminated if excellent disease control can be maintained without it.

Guided by PET scanning, since 2004 we have offered all patients with limited-stage Hodgkin lymphoma in British Columbia treatment with an initial two cycles of ABVD. If the PET scan is negative after those two cycles, treatment continues with two more (for a total of four). We switch to radiation instead of ABVD if that PET scan is positive. Following this algorithm, 80% of patients avoid radiation. With 120 patients treated and more than 80% followed for longer than the maximum time to relapse, we have seen a progression-free survival of 95%, and no patient has died from Hodgkin lymphoma.

With optimal chemotherapy (presently ABVD), the large majority of patients with limited-stage Hodgkin lymphoma can be cured using brief chemotherapy alone. Radiation should be reserved for a carefully chosen small minority-no more than 20% of patients. In this way, we can meet our responsibility to achieve cure with the least harm. Most patients with limited-stage Hodgkin lymphoma do not require radiotherapy. ■

Dr. Connors is Clinical Director, Centre for Lymphoid Cancer, BC Cancer Agency, and Clinical Professor, University of British Columbia, Vancouver.

References

1. Engert A, Diehl V, Pluetschow A, et al: Two cycles of ABVD followed by involved field radiotherapy with 20 gray (Gy) is the new standard of care in the treatment of patients with early-stage Hodgkin lymphoma: Final analysis of the randomized German Hodgkin Study Group (GHSG) HD10. Study supported by the Deutsche Krebshilfe and in part by the Competence Network Malignant Lymphoma. American Society of Hematology Annual Meeting. Abstract 716. Presented December 7, 2009.

2. Campbell BA, Voss N, Pickles T, et al: Involved-nodal radiation therapy as a component of combination therapy for limited-stage Hodgkin's lymphoma: A question of field size. J Clin Oncol 26:5170-5174, 2008.

3. Meyer RM, Gospodarowicz MK, Connors JM, et al: Randomized comparison of ABVD chemotherapy with a strategy that includes radiation therapy in patients with limited-stage Hodgkin's lymphoma: National Cancer Institute of Canada Clinical Trials Group and the Eastern Cooperative Oncology Group. J Clin Oncol 23:4634-4642, 2005.