182 I. J. Radiation Oncology 0 Biology 0 Physics Volume 36, Number I, Supplement, 1996 47 Treatment-Related Cardiac Toxicity From Doxorubicin (DOX) and Radiation Therapy (RT) in Patients Treated with Breast-Conserving Therapy Patricia M. Harrigant, Abram Rechtt, Smitha G. Payne 1, Steven E. Comez, Daniel F. Hayes3, Lawrence N. Shulman4, Anne O’NeiBs, Rebecca S. Gelman’ls, Barbara Silver’, Jay R. Harris’ 1) Joint Center for Radiation Therapy; Harvard Medical School, 2) the Department of Medicine, Beth Israel Hospital, 3) the Breast Evaluation Center, Dana-Farber Cancer Institute, 4) the Department of Medicine, Brigham and Women’s Hospital, 5) the Department of Biostatistics, Dana. Farber Cancer Institute and Harvard School of Public Health, Boston, MA. Purpose: There is anecdotal evidence that breast cancer patients treated with left-sided RT and DOX may have an increased risk of early cardiac toxicity. We reviewed patients treated on a randomized trial testing sequencing of chemotherapy and RT to determine if there is an increase in cardiac events in patients treated with a moderate dose of DOX (total dose: 180 mg/mz) and radiation therapy to the left breast as compared to the right breast. Materials and Methods: From June 1984 to December 1992,244 patients with clinical stage I or II breast cancer were randomized following conservative surgery to receive chemotherapy ( 4 cycles of CAMFP at 3 wk intervals) either before or after RT (45 Gy to the entire breast, followed by a boost of 16 Gy; nodal radiation therapy was optional. No patient received a hockey stick field for treatment of the IMNs.) Pts with a prior history of radiation or chemotherapy or co-morbid illnesses were excluded from entry onto the protocol. The median age at diagnosis was 45 yrs (range 20-68). The median time for follow-up is 4.5 yrs. Chemotherapy doses and schedule included: doxorubicin given in 45 mp/m2 IV bolus, dl; methotrexate 200 mg/m2 IV, dl and 15; leucovorin 10 mg/m* p,o. q 6 hr for 12 doses; 5-flourouricil 500 mg/m2 IV, dl; cyclophosphnmide 500 mg/m2 IV, dl; prednisone 40 mg p.o., dl-5. Eight pts were excluded because they were not treated per protocol. An additional 5 pts were lost to cardiac follow-up. For each pt, medical records were reviewed for evidence of a cardiac event. A cardiac event was defined as a Ml or clinical evidence of CHF. Pts were excluded from review and further analysis at the time of additional treatment for recurrent cancer or a contralateral breast cancer. Age adjusted rates were calculated within each pt group using the number of expected cardiac events per 1000 women-yn of follow-up, based on findings from the Framingham Heart Study. Results: * One pt had a MI 4 months after start of treatment for a contralateral breast cancer. Anglography showed a lesion in the LAD which appears to be outside the RT field. Conclusions: Among these pts treated with moderate-dose DOX and tangential breast RT in either sequence there is no evidence of an increase in cardiac toxicity at a median follow-up of 4.5 yrs. More follow-up and detailed cardiac evaluation is needed to confirm this finding. 48 LONG TERM RESULTS OF TOTAL LYMPHOlD IRRADIATION IN THE TRBATMBNT OF CARDIAC -RAFI. REJBCI’ION Suzanne L. Walden, M.D.,’ David J. Tate, M.D.,’ Sharon A. Hunt, M.D.: Samuel Stmber, MD.2 and Richard T. Hoppc, M.D.’ Pwpuse: To evalute the short and long term effec@ of total Iymphoid inadiation (TLI) in the treatment of allogmft rejection in cardiac naosplant patients. Materials & Methods: From 1986 to 1995.48 courses of TLI wex delivered to 47 patients who had received cardiac transplants at Stanford University. In 38 cases, TLI was adminis@& for chronic, intractable allo@ rejection despite conventional anti-rejection therapy, including con&steroids, azathioprine, cyclosporine, OKT3. DHPG, RATG, and methotrexate. Ten patients received TLI prophylactically, beginning radiation between 5 snd 16 days after heart tnmsplantation. ?he prescribed radiation dose was 800 ffiy given in 80 cGy fractions twice weekly to all major lymph node regions using mantle and inverted Y fields. Patients continued to receive all medications except azathioprine which was held during TLI to prevent severe marrow suppressicn. All patients WQC closely monitored for episodes of rejection, infection, prcdnisone requirements, blood counts, and complications of treatment. Post-irradiation follow up ranged fmm 6 months to 9.1 years with a mean of 3.1 years. Results: The actual mean dose of radiation was 730 cGy delivered over a mean of 39 calendar days. Fifty six pacent of patients required ueatment delay or abtueviation because of thrombocytopenia, leukopenia, infection, or unrelated problems. In patients treated fm intractable rejection, the ftcquency of Ejection dropped from 0.46 epimdcs,$atient/roonth before radiation to 0.14 episodes/patient/month during TLI (p c O.ooOl) and 0.06 episodes/patient/month after TLI@ < O.ooOl). Rejection rates remained consistently low with up to 9.1 years of follow up. Prednisone requirements dd from 0.41 mg&g before treatment to 0.21 mg/kg afterward (p c 0.0001). For patients aeatai prophylactically, the rcjeclion rate was 0.45 @odes&atient/month dtig irradiation, but dccrcastd to 0.01 episodes/patient/month following TLI (p < O.ooOl). Transient thrombocytopenia occurred in 54% and anemia in 48% of all patients. AU patients had a substantial decrrase in white blood cell count which rctumed to normal 2-4 months after treatment. Mean CD4+ lymphocyte counts demascd from 309.5 to 58.7 cells/mm’ during TLI @ = 0.01) and nzmained low at 167.6 cell&m’ 2-4 months after treatment @ = 0.05). CDB+ lymphocytes also dccnased during treatment from 233.2 to 65.8 cells/mm3 (p = 0.003) but rose siguiticantly above normal to 381.3 cells/mm3 2-4 months after TLI (p = 0.05). Thus, the ratio of helper/suppresser T-cells was chronically decreased. Infection rates were not significantly different before, during or after radiation. Two malignancies were repaid during the follow-up period. One was prostate cancer in a 57 year old man which was probably utuelated to treamnmt. The other was a non-Hodgkin’s lymphoma in a 7 year old boy who had also received multiple courses of OKT3. h year actuarial survival after irradiation was 60% and 70% for the intractable rejection cohort and pmphylactic groups respectively. Most deaths occurred within 2 years of TLI and were caused in equal proportions by rejection, b&ction and other urdical pmblems. Conclusion: TLI is an effective and durable ueatment for control of chronic, intractable cardiac rejection as demonstrated in long-term follow up of up to 9.1 years. A possible mechanii of action is long term alteration in T-lymphocyte subsets. Patients ex ‘once transient bone marrow F suppression but no increase in infection or bleeding. They may be permanently maintained on lower doses 0 steroids and the risk of radiation induced malignancy is low. TLI is not recumnended as induction therapy because of the high risk of rejection when azathio@e is withheld dming inadiation in the immediate post-transplant period.