Radiation Therapy for Stage I-II Follicular Lymphoma

Richard T. Hoppe, MD
Editor of Radiation Oncology
MDvista Journal of MedicineTM

Professor of Radiation Oncology
Stanford University School of Medicine
Stanford, California, USA

Follicular lymphoma accounts for 40% of lymphomas diagnosed in the US. Histologically, these lymphomas are characterized by effacement of the normal lymph node architecture by neoplastic B cells that form variable size follicles. The subtypes of follicular lymphoma in the Working Formulation include follicular small-cleaved cell, follicular mixed small-cleaved and large cell, and follicular large cell lymphoma. In the new WHO Classification, follicular lymphomas are defined as Grade 1, 2, or 3 depending upon the proportion of large cells. Genetically, the cells of follicular lymphoma usually display a translocation between chromosomes 14 and 18, which results in overproduction of the bcl-2 protein and inhibition of apoptosis with continued cell proliferation. The disease generally arises in people 50-70 years old and in the majority (about 75%) presents as stage IV, with generalized lymphadenopathy and bone marrow involvement. Although often presenting in advanced stages of disease, these lymphomas may behave in an indolent fashion, requiring only symptomatic management. It is difficult to achieve cure in advanced disease with contemporary therapies.

Stage I-II disease (involvement of a single lymph node region or multiple lymph node regions on the same side of the diaphragm) is uncommon, and accounts for only 15-20% of patients with low grade lymphoma. However, since this lymphoma is quite radiosensitive, there is a possibility to treat patients who present with stage I-II disease with radiation therapy with curative intent. The treatment of choice is to use localized (involved or slightly extended field) irradiation with doses adequate to eradicate and achieve long term local control of disease. Involved field irradiation implies treatment to all of the involved lymph node regions, not simply the specifically involved lymph nodes. In addition, slight extension of the radiation fields to adjacent, uninvolved lymph node regions often can be accomplished with little added toxicity, and this may decrease the likelihood of relapse.

The specific design of the radiation fields requires adequate imaging evaluation. Initial radiographic staging generally includes a computed tomographic scan of the chest, abdomen, and pelvis. Intrathoracic lymphadenopathy is unusual, but there may be involvement of high axillary nodes not appreciated by physical examination. If facility is available to perform and interpret a lymphogram, this may be helpful for both staging and design of radiation fields.

Common supradiaphragmatic sites of presentation and reasonable radiation fields are as follows: axilla - ipsilateral axilla and supraclavicular (optional extension to cervical and contralateral cervical/supraclavicular and axillary areas); supraclavicular - ipsilateral supraclavicular/cervical and axilla (optional extension to superior mediastinum, contralateral cervical/supraclavicular and axillary areas). Common subdiaphragmatic sites of presentation and radiation fields are as follows: inguinal-femoral - ipsilateral inguinal-femoral and iliac; iliac - ipsilateral inguinal-femoral, iliac and paraortic (optional extension to contralateral iliac and inguinal-femoral). CT scans and/or lymphograms are especially helpful in the design of subdiaphragmatic radiation fields.

Patients should undergo careful simulation and field design using a dedicated conventional or CT simulator. Treatment is generally via opposed field technique. The dose that is required for long term local control is 30-40 Gy. Larger or more slowly responding masses may be treated to the higher doses. Daily fraction size should be 1.5-2.0 Gy, depending upon the field size.

Regions of concern with respect to potential toxicity include: axillary breast tissue (primarily a concern for women under thirty, who will have an increased risk of breast cancer); mediastinum (increased risk of cardiovascular disease if the coronary arteries are within the radiation fields); ovaries (function will be ablated if the iliac region is treated); and testes (can generally be protected adequately with specialized testicular shielding).

Employing treatment with radiation therapy alone, the expected ten-year survival is 60-70% and ten-year freedom-from-relapse 45-55% for stages I-II combined. Results for treatment of stage I are slightly better than for stage II. When patients relapse, it is generally in lymph node regions not included in the initial radiation treatment fields. However, although more extensive radiation fields (e.g., total lymphoid irradiation) may decrease the relapse risk, there is no improvement in survival, due to greater toxicity among patients who receive more extensive treatments.Likewise, although non-randomized studies suggest an improvement in freedom-from-relapse, randomized clinical trials have failed to demonstrate a superiority in either survival or freedom-from-relapse for combined modality therapy (radiation followed by adjuvant chemotherapy) compared to treatment with radiation alone.

Published March 2000