A retrospective analysis of 116 primary cases of stage I, II and III-A Hodgkin's disease demonstrated 27 failures, fourteen confirmed by biopsy. Twenty of the 27 (74%) were in lymph node areas only and seven had extranodal extensions. The most frequent site of failure was the hilar nodes and contiguous lung. The majority of failures (78%) occurred within 30 months of treatment and the cause of failure determined in 23 (85%), sixteen of which were due to technical errors of irradiation. Analysis of the dosimetry in the mediastinal, hilar nodes and contiguous lung failures revealed three factors which may have contributed to a low dose. These factors are: 1) the equivalent square, 2) off-axis beam diminution, and 3) the anteroposterior dose profile. Combined radiation therapy and chemotherapy was more effective than either modality alone in the treatment of these failures.

Using an experimental model with a transplanted murine lymphosarcoma, several observations strongly suggest that following tumor transplantation, there is a selective transient accumulation of tumor cells in the regional lymph nodes. Furthermore, the surgical removal of these lymph nodes immediately prior to or within a week following implantation of the tumor cells significantly impairs the cure of the tumor by a dose of local irradiation which in control animals cures 83%. Local irradiation of the regional lymph nodes (3000 rads single dose) produced a moderate decrease in cure rates, not as severe as that observed in the lymphadenectomized animals. It is postulated that there is a critical period of time during which an immune response is initiated in the regional lymph nodes, following antigen injection. If tumor cells have reached the regional lymph nodes and the immune response has been initiated by the time a tumor becomes clinically apparent, then prophylactic irradiation or dissection of these lymph nodes should not interfere with tumor control by the usual therapeutic methods. However, if this is not the case, and the body has not recognized the tumor antigens, then lymphadenectomy and to a much lesser degree, irradiation, may result in less effective therapeutic results. Further understanding of the processes involved in tumor dissemination in patients is necessary to correlate these experimental observations with the clinical management of cancer.