Study to Treat Relapsed Follicular Non-Hodgkin's Lymphoma With Radiation and Bexxar

Total dose delivered and tumor size are important predictors of local control in the treatment of low-grade Non-Hodgkin's Lymphoma (NHL). The basic principle is that larger nodal masses require increased doses of External Beam Radiotherapy (EBRT) to achieve local control. Radioimmunotherapy (RIT) seems to share this same characteristic. Review of the published literature on both Bexxar and Zevalin reveals that one of the most important predictors of treatment failure is nodal volume and its apparent relationship to dose delivered by RIT. The best tumor dosimetry for RIT is from Dr. Wiseman et al reporting on the dosimetry of Zevalin (PMID:11418315). He showed that tumors ≥15 cm\^3 received only 1082 cGy with Zevalin, whereas the average dose delivered in tumors \<15 cm\^3 was 4763 cGy. Recently, Gokhale et al (PMID:16111589) published their experience with Zevalin at Cleveland Clinic and showed a significant correlation with pretreatment tumor volume and response to therapy. In their experience, tumors ≥5 cm had an 83% rate of local recurrence versus 28% for tumors \<5 cm. This dosing paradox (bigger masses, which require more dose, receive less with RIT) may be diminished by the delivery of additional EBRT. This is the hypothesis that underlies the pilot study. The dosimetric data available for Bexxar is more heterogeneous but confirms the observations seen with Zevalin. In patients previously untreated for low-grade Non-Hodgkin's Lymphoma (NHL), Koral et al (PMID:12621015) showed an increased likelihood of achieving a complete response (CR) if tumor doses were \>650 cGy. Previous work by these same authors showed a trend for larger tumor volumes receiving less dose (PMID:10994741). The most compelling data for this relationship comes from the clinical trials done using Bexxar. Both in the pivotal trial (PMID:11579112) and the recently published trial treating naïve patients (PMID:15689582), tumor volume was a significant predictor of response to Bexxar. In the pivotal trial, smaller tumor burden was the only factor predicting longer duration of response. Whereas EBRT might be able to provide reliable radiation dose, the use of Bexxar may provide the therapeutic equivalent of central lymphatic irradiation, which would permit the use of true involved field radiotherapy. Investigators have previously noted that increased EBRT field size is associated with increased short-term and long-term toxicity. The toxicities associated with the treatment of radiotherapy are related to the site treated, but do not necessarily include the dose limiting toxicity of Bexxar, which is primarily hematologic and transient. As the toxicity of RT and Bexxar may not overlap, the combination of both may allow an increase in the therapeutic window for both radiotherapy and Bexxar therapy.