Endobronchial brachytherapy is an evolving treatment modality. Although standard clinical indications and dosage schedules have not yet been established, the wide range of individual experience overwhelmingly demonstrates its efficacy in palliating lung cancer patients who generally have limited treatment options. Although the exact complication rate is not known, it appears to be low and the potential benefits far outweigh the risks. The role of endobronchial brachytherapy for cure is less clear. For most instances "prolonged palliation" would be a more suitable term than "cure." Further data is needed to clarify the proper place of endobronchial brachytherapy as a boost to external beam radiation therapy. The dose, fractionation scheme, and timing relative to external beam radiation therapy are based on institutional preference at this time. The historical evolution, treatment technique, results, and complications of endobronchial brachytherapy are reviewed here.

Total lymphoid irradiation (TLI) is effective in the immunosuppressive treatment of human and experimental autoimmune disorders, including experimental autoimmune myasthenia gravis (EAMG). Under certain circumstances. TLI may facilitate the induction of specific tolerance to antigens present during or shortly after the TLI treatment. This study was designed to determine whether TLI could induce or enhance tolerance to acetylcholine receptor (AChR), the antigen in myasthenia gravis, or to other antigens. We presented the antigens in various potentially tolerogenic forms to rats that were first pre-treated with TLI, or controls treated with sham irradiation. Injection of deaggregated human gamma globulin (HGG), a classical tolerogen, was most effective; it produced antigen-specific tolerance, which was significantly enhanced by pre-treatment with TLI. Injection of HGG coupled to rat peritoneal cells induced a moderate degree of specific tolerance; in this case, pre-treatment with TLI added only nonspecific suppression. In contrast, AChR, either in solubilized form with no adjuvant, or coupled to syngeneic rat peritoneal cells, failed to induce tolerance, and actually primed the immune system, when given alone or in conjunction with TLI. Subsequent challenge with AChR resulted in an enhanced (secondary) anti-AChR antibody response. These results show that the nature of the antigen itself may predispose to tolerance or to immune stimulation. AChR appears to be highly immunogenic. However, if a tolerogenic fragment or form of AChR can be identified, its use in combination with TLI may result in specific tolerance. If such specific tolerance can be induced during an ongoing autoimmune reaction to AChR, it would be an effective treatment for myasthenia gravis.

Total Lymphoid Irradiation (TLI) has been successful in inducing immunosuppression in experimental and clinical applications. However, both the experimental and clinical utility of TLI are hampered by the prolonged treatment courses required (23 days in rats and 30-60 days in humans). Low-dose-rate TLI has the potential of reducing overall treatment time while achieving comparable immunosuppression. This study examines the immunosuppressive activity and treatment toxicity of conventional-dose-rate (23 days) vs low-dose-rate (2-7 days) TLI. Seven groups of Lewis rats were given TLI with 60Co. One group was treated at conventional-dose-rates (80-110 cGy/min) and received 3400 cGy in 17 fractions over 23 days. Six groups were treated at low-dose-rate (7 cGy/min) and received total doses of 800, 1200, 1800, 2400, 3000, and 3400 cGy over 2-7 days. Rats treated at conventional-dose-rates over 23 days and at low-dose-rate over 2-7 days tolerated radiation with minimal toxicity. The level of immunosuppression was tested using allogeneic (Brown-Norway) skin graft survival. Control animals retained allogeneic skin grafts for a mean of 14 days (range 8-21 days). Conventional-dose-rate treated animals (3400 cGy in 23 days) kept their grafts 60 days (range 50-66 days) (p less than .001). Low-dose-rate treated rats (800 to 3400 cGy total dose over 2-7 days) also had prolongation of allogeneic graft survival times following TLI with a dose-response curve established. The graft survival time for the 3400 cGy low-dose-rate group (66 days, range 52-78 days) was not significantly different from the 3400 cGy conventional-dose-rate group (p less than 0.10). When the total dose given was equivalent, low-dose-rate TLI demonstrated an advantage of reduced overall treatment time compared to conventional-dose-rate TLI (7 days vs. 23 days) with no increase in toxicity. This was accomplished without compromise of the immunosuppressant activity of TLI as demonstrated by comparable allogeneic skin graft survival times between the two 3400 cGy treatment groups. This clinical advantage would prove to be beneficial where immediate suppression of the immune system is desirable.

Total lymphoid irradiation (TLI) has been reported to be effective in the immunosuppressive treatment of certain human and experimental autoimmune disorders. We have investigated the effects of TLI in Lewis rats with experimental autoimmune myasthenia gravis (EAMG) produced by immunization with purified torpedo acetylcholine receptor (AChR). The radiation is given in 17 divided fractions of 200 rad each, and nonlymphoid tissues are protected by lead shielding. This technique suppresses the immune system, while minimizing side effects, and permits the repopulation of the immune system by the patient's own bone marrow cells. Our results show that TLI treatment completely prevented the primary antibody response to immunization with torpedo AChR, it rapidly abolished the ongoing antibody response in established EAMG, and it suppressed the secondary (anamnestic) response to a boost of AChR. No EAMG animals died during TLI treatment, compared with six control animals that died of EAMG. TLI produces powerful and prompt immunosuppression and may eventually prove useful in the treatment of refractory human myasthenia gravis.