Assessment of pulmonary outcomes, exercise capacity, and longitudinal changes in lung function in pediatric survivors of high-risk neuroblastoma.

BACKGROUND/OBJECTIVES: Survivors of high-risk neuroblastoma (NB) are exposed to multimodality therapies early in life and confront late therapy-related toxicities. This study assessed respiratory symptoms, exercise capacity, and longitudinal changes in pulmonary function tests (PFTs) among survivors. DESIGN/METHODS: Survivors of high-risk NB followed in the long-term follow-up clinic at Memorial Sloan Kettering Cancer Center were enrolled. Symptom and physical activity questionnaires were completed. Medical records were reviewed for treatments and comorbidities. Participants completed spirometry, plethysmography, diffusion capacity of the lung for carbon monoxide, 6-minute walk tests (6MWTs), and cardiopulmonary exercise testing. Questionnaires and PFTs were repeated at least one year after enrollment. RESULTS: Sixty-two survivors participated (median age at study: 10.92 years; median age at diagnosis: 2.75 years; median time since completion of therapy: 5.29 years). Thirty-two percent had chronic respiratory symptoms. Seventy-seven percent had PFT abnormalities, mostly mild to moderate severity. Thirty-three completed 6MWTs (median, 634.3 meters); eight completed cardiopulmonary exercise tests (mean VO2 max: 63% predicted); 23 completed a second PFT revealing declines over a median 2.97 years (mean percent predicted forced vital capacity: 79.9 to 70.0; mean forced expiratory volume in 1 second: 81.6 to 69.9). Risks for abnormalities included thoracic surgery, chest radiation therapy (RT), thoracic surgery plus chest RT, and hematopoietic stem cell transplant. CONCLUSIONS: In this cohort of survivors of high-risk NB, PFT abnormalities were common but mostly mild or moderate. Maximal exercise capacity may be affected by respiratory limitations and declines in lung function may occur over time. Continued pulmonary surveillance of this at-risk population is warranted.

Assessment of Organ Dosimetry for Planning Repeat Treatments of High-Dose 131I-MIBG Therapy: 123I-MIBG Versus Posttherapy 131I-MIBG Imaging.

PURPOSE: To evaluate detailed organ-based radiation-absorbed dose for planning double high-dose treatment with I-MIBG. METHODS: In a prospective study, 33 patients with high-risk refractory or recurrent neuroblastoma were treated with high-dose I-MIBG. Organ dosimetry was estimated from the first I-MIBG posttherapy imaging and from subsequent I-MIBG imaging prior to the planned second administration. Three serial whole-body scans were performed per patient 2 to 6 days after I-MIBG therapy (666 MBq/kg or 18 mCi/kg) and approximately 0.5, 24, and 48 hours after the diagnostic I-MIBG dose (370 MBq/kg or 10 mCi/1.73 m). Organ radiation doses were calculated using OLINDA. I-MIBG scan dosimetry estimations were used to predict doses for the second I-MIBG therapy and compared with I-MIBG posttherapy estimates. RESULTS: Mean ± SD whole-body doses from I-MIBG and I-MIBG scans were 0.162 ± 112 and 0.141 ± 0.068 mGy/MBq, respectively. I-MIBG and I-MIBG organ doses were variable-generally higher for I-MIBG-projected doses than those projected using posttherapy I-MIBG scans. Mean ± SD doses to liver, heart wall, and lungs were 0.487 ± 0.28, 0.225 ± 0.20, and 0.40 ± 0.26, respectively, for I-MIBG and 0.885 ± 0.56, 0.618 ± 0.37, and 0.458 ± 0.56, respectively, for I-MIBG. Mean ratio of I-MIBG to I-MIBG estimated radiation dose was 1.81 ± 1.95 for the liver, 2.75 ± 1.84 for the heart, and 1.13 ± 0.93 for the lungs. No unexpected toxicities were noted based on I-MIBG-projected doses and cumulative dose limits of 30, 20, and 15 Gy to liver, kidneys, and lungs, respectively. CONCLUSIONS: For repeat I-MIBG treatment planning, both I-MIBG and I-MIBG imaging yielded variable organ doses. However, I-MIBG-based dosimetry yielded a more conservative estimate of maximum allowable activity and would be suitable for planning and limiting organ toxicity with repeat high-dose therapies.