The radiation doses required to secure local control in lymphomas are in the range of 30 Gy to 40 Gy, modest in comparison to those required for local control in carcinomas or sarcomas.¹, ², ³ These doses have produced only a few immediate normal tissue toxicities, and have therefore been generally regarded as safe and tolerable. However, with increasing survivorship in lymphomas, late effects of radiation have emerged in tissues receiving doses previously regarded as below the threshold for normal tissue injury.⁴ In some cases, it appears that the injury is related to substantial cell loss in tissues receiving moderate radiation doses, whereas in other cases, the injury appears to be related to cell damage from low radiation doses manifested as second malignancies many years after the radiation exposure. Because of the perception of a high therapeutic ratio with radiation therapy in lymphomas, lymphomas have not been considered as a high priority for proton therapy. In addition, the wide variety of presentations and complex patterns of tumor involvement make the technical aspects of proton delivery for lymphomas challenging. Consequently, to date there is little experience in using proton therapy for lymphomas.

There have been several case reports of the use of protons in the management of lymphomas. Kirsch et al.⁵ from the Massachusetts General Hospital reported on proton treatment a young patient with Hodgkin’s disease involving the sacrum who was treated with combined modality chemoradiation. Protons were used in lieu of photons to minimize the radiation dose to the remainder of the pelvis in a female adolescent in an attempt to minimize the late effects of radiation therapy. The group from Loma Linda reported on the treatment a 53-year-old patient with a large B-cell lymphoma of the cavernous sinus with sphenoid sinus and clival extension, treated with partial resection, CHOP-R chemotherapy, and proton beam irradiation.⁶ Conformal protons were utilized to minimize the volume of normal brain receiving radiation. Conformal proton beam radiotherapy to a moderate dose proved valuable in this case because it minimized the volume of normal brain receiving low to moderate doses of radiation.

Probably the presentation offering the most potential for an increased therapeutic ratio with proton therapy is the large mediastinal mass in Hodgkin’s lymphoma, because of the well described late cardiopulmonary risks of radiation therapy⁷ for lymphoma that might be decreased with the use of protons.⁸ The emergence of increasing problems related to both high and low radiation doses to normal tissues in lymphoma survivors presents an opportunity for
improved outcomes accruing from the improved radiation dose distributions possible with proton therapy.