Long-term outcome after static intensity-modulated total body radiotherapy using compensators stratified by pediatric and adult cohorts.

PURPOSE: To report the long-term outcome after total body irradiation with intensity-modulating compensators and allogeneic/autologous transplantation, especially in terms of therapy-related toxicity in pediatric and adult cohorts. METHODS AND MATERIALS: A total of 257 consecutive patients (40 children and 217 adults) have been treated since 1983 with TBI using static intensity-modulated radiotherapy for hematologic malignancies. The total dose of 12 Gy was applied in six fractions within 3 days before allogeneic (n = 174) or autologous (n = 83) transplantation. The median follow-up was 9.2 years. RESULTS: The 5-year overall survival rate was 47.9% (49.8% for the adults and 37.5% for the children, p = 0.171). The 5-year tumor-related mortality rate was 23%, and the 5-year treatment-related mortality rate 29.2% (29.5% in the adults and 27.5% in the pediatric patients). Interstitial pneumonitis developed in 28 (10.9%) of 257 patients and in 12.5% of the pediatric cohort. The interstitial pneumonitis rate was 25% in pediatric patients treated with a 12-Gy lung dose compared with 4.2% for those treated to an 11-Gy lung dose. The overall survival rate stratified by lung dose was 26.7% for 12 Gy and 52.4% for 11 Gy (p = 0.001). The incidence of veno-occlusive disease and cataract was 5.8% and 6.6% in all patients and 12.5% and 15% in the pediatric patients, respectively (p < 0.05). Secondary malignancies were found in 4.3% of all patients, all in the adult cohort at transplantation. CONCLUSION: Static intensity-modulated total body irradiation with a total dose of 12 Gy before allogeneic/autologous transplantation is a successful treatment with good long-term outcome and acceptable therapy-related toxicities. Constraining the lung dose to 11 Gy substantially lowered the actuarial treatment-related mortality. This effect was especially striking in the pediatric patients.

20 years of experience in static intensity-modulated total-body irradiation and lung toxicity. Results in 257 consecutive patients.

PURPOSE: To analyze lung complications after allogeneic or autologous transplantation following total-body irradiation (TBI) with compensators, so-called sIMRT (static intensity-modulated radiotherapy). PATIENTS AND METHODS: Between 1983 and 1998, 257 patients with different hematologic malignancies underwent TBI in six fractions to a total dose of 12 Gy within 3 consecutive days (212 with 11 Gy lung dose) prior to allogeneic (n=174) or autologous (n=83) transplantation. 40 patients were <16 years of age. Minimum follow-up time was 5 years. Median follow-up period was 110 months (13-231 months). RESULTS: 5-year survival rate was 47.9%, 5-year tumor-related mortality 23%, 5-year treatment-related mortality 29.2% (12 Gy lung dose: 53.3%+/-14.6%, 11 Gy: 24.1%+/-5.7%). Interstitial pneumonitis (IP) developed in 28 of 257 patients (10.9% +/- 3.8%). IP incidences in the allogeneic and autologous groups were 14.4% (+/-5.6%) and 3.6% (0-7.6%), respectively. IP incidences with 12/11 Gy lung dose were 22% (+/-12%)/8.5% (+/-3.7%). IP mortality was 9.3% (+/-3.6%). 13 of 28 patients with IP had a cytomegalovirus infection, five an acute graft-versus-host disease grade IV of the lungs. IP incidences with 12/11 Gy lung dose were 25% (9-50%)/4.2% (0.2-19.1%) in patients <16 years, and 20.7% (9.4-37.4%) and 13.3% (+/-6.5%) in older patients after allogeneic transplantation. CONCLUSION: Compensator-generated static intensity-modulated TBI with a total dose of 12 Gy and a lung dose of 11 Gy is a modern and comfortable treatment with moderate lung toxicity, small dose inhomogeneities and little setup failure before transplantation. Especially patients <16 years of age benefit from lung dose reduction.