Annals of Oncology 19 (Supplement 4): iv47–iv50, 2008 doi:10.1093/annonc/mdn195 Radiotherapy in non-Hodgkin lymphomas M. Gospodarowicz 1 1 Princess Margaret Hospital, Ontario Cancer Institute, Toronto, Ontario, Canada Most patients with localized non-Hodgkin lymphoma (NHL) who receive radiotherapy (RT) are treated with the intent of achieving local control of disease [1]. A palliative approach is used only when, due to the condition of the patient and/or the extent or location of the disease, a radical course of treatment carries no chance of local control. Knowledge of histology, extent and pattern of disease is essential to select the appropriate therapeutic strategy. Involved field RT is routinely used, whether for cure or local control. The recognition of the high risk for occult distant disease mandates the use of chemotherapy in all cases of diffuse large cell lymphoma or similar histologies. For localized disease, the initial decision for patients treated with curative intent is the use of a combined modality approach—chemotherapy and RT, or a local treatment alone with RT. The choice is predicated upon the inherent risk of occult distant disease, availability of curative chemotherapy and the potential need for local control. Patients with stage III and IV are routinely treated with chemotherapy alone. The aim of RT is to deliver an adequate dose of radiation to the target volume to ensure local control. The design for a proper course of RT must take into account the extent of disease, the appropriate margins, routes of lymphatic and possible extranodal spread, and the radiation tolerance of normal tissues and organs. Dose fractionation parameters must assure local control with acceptable acute and late toxicity. The technique should guarantee reproducibility of treatment on a daily basis. Custom-designed fields should be used to conform to the target volume while keeping the volume of irradiated normal tissues to a minimum. The use of CT simulation with delineation of target volumes including the gross tumour volume (GTV), the clinical target volume (CTV), which includes the microscopic disease extent, and planning target volume (PTV), which takes into account variation in the location of the GTV and CTV. Three dimensional conformal RT (3D CRT) or intensity modulated RT (IMRT) may be used to shape the dose distribution. It is important to note that when RT follows chemotherapy in CMT protocols, RT is usually started 4–6 weeks following the last course of chemotherapy to minimize the drug–radiation sensitization effect. follicular and MALT Lymphomas The standard approach to RT in follicular lymphomas [2, 3] is involved field (IF) RT. With moderate doses of radiation (30–35 Gy in daily fractions in 4 weeks), the local control rate is >95%. Because of occult systemic disease, relapse in unirradiated sites occurs in >50% of patients within the next 5–15 years. Treatment at the time of recurrence requires chemotherapy, although RT is also very useful in selected cases. In palliative approaches in patients with disseminated or recurrent follicular lymphomas, high response rates are observed even with a low dose of 4 Gy (2 · 2 Gy). Because of the indolent nature of follicular lymphomas, long-term follow- up is required to test the effects on survival of any new treatment approaches. The relative rarity of localized disease, the long follow-up required and competing mortality from unrelated causes, form significant barriers to the conduct of clinical trials in this disease. MALT lymphomas, indolent B-cell tumors, present with stage I–II disease in 70–90% of cases. MALT lymphomas arise most commonly in the stomach, orbit, thyroid, salivary glands, breast, lung, skin and bladder. When applied, IF RT to 25–35 Gy results in a >95% local control rate with a significant proportion of patients being cured. Although MALT lymphomas are usually indolent, transformation into aggressive large cell lymphomas occurs. Current experience with MALT lymphomas shows cure with local therapy in a significant proportion of patients [4]. large cell lymphomas (diffuse large B-cell lymphoma) The treatment of localized large cell lymphomas [5, 6] has evolved from the use of RT alone to the routine use of combined modality therapy (CMT). The best results with RT alone were obtained in small trials that included meticulously staged patients with favorable prognostic factors. Pathologic stage I patients have 10-year relapse-free rates of 90% with RT alone. Similarly stage IA or IIA patients with favorable clinical attributes treated with RT alone to a dose of 35 Gy achieved a 77% relapse-free rate at 10 years. In the early 1980s, several phase III trials showed the superiority of chemotherapy and radiation. CMT became the standard approach, with the administration of three to eight courses of doxorubicin- containing chemotherapy followed by IF RT. Brief chemotherapy with three courses of CHOP followed by radiation (30 Gy or equivalent) produces excellent results in patients with non-bulky (<10 cm) stage I–II with 10-year PFS of 74% and overall survival (OS) of 63% after a median follow up of 7.3 years. With the success of chemotherapy in advanced NHL, the role of routine RT in localized disease was questioned The author reports no relationships with companies whose products or services are mentioned in this manuscript. ª The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org