Long-term Pulmonary Outcomes in Pediatric Survivors of High-risk Neuroblastoma

Abstract

Background Children with high-risk neuroblastoma (NB) are exposed to multimodality therapies early in life and survivors confront late therapy-related toxicities. This study assessed respiratory symptoms, pulmonary function tests (PFTs), and risk factors for abnormalities among survivors. Methods High-risk NB survivors followed in the Long-term Follow-up clinic at Memorial Sloan Kettering Cancer Center were enrolled. Self-administered symptom questionnaires were completed. Medical records were reviewed for treatment information and co-morbidities. PFTs included spirometry, plethysmography, and diffusion capacity of the lung for carbon monoxide (DLCO). Results Thirty nine survivors participated (median age at study: 11.4 years; median age at diagnosis: 2.3 years; median time since completion of therapy: 5.5 years). Chronic respiratory symptoms were reported for 33%. PFT abnormalities were identified in 79% and included low forced expiratory volume in 1 second (FEV1) (38%), decreased total lung capacity (TLC) (44%), and abnormal DLCO (67%). PFT abnormalities were mostly mild to moderate. Mean forced vital capacity, forced expiratory volume in 1 second, and total lung capacity were normal and mean DLCO was mildly abnormal. Risks included thoracic surgery, chest radiation therapy (RT), thoracic surgery plus chest RT, and shorter time since completion of therapy (p<0.05). Conclusions While respiratory abnormalities were common, they were mostly mild or moderate. Continued pulmonary surveillance of this at-risk population is warranted.

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

“…Approximately one‐third of subjects reported chronic respiratory symptoms in the past year and the presence of a physician‐diagnosed respiratory condition ever. This aligns with our previous work and differs from an earlier cohort in which respiratory symptoms were described among two‐thirds of pediatric survivors of high‐risk NB, with three of 18 reporting severe respiratory symptoms . As we previously suggested, this difference is most likely a reflection of the change in treatments over time, including exposures to high‐dose chemotherapy, total body irradiation (TBI), and autologous HSCT in the cohort treated in the late 1980s .…”

“…As we previously suggested, this difference is most likely a reflection of the change in treatments over time, including exposures to high‐dose chemotherapy, total body irradiation (TBI), and autologous HSCT in the cohort treated in the late 1980s . No subjects in our cohort received TBI, and only one subject was treated with whole lung irradiation, both of which have been associated with late adverse pulmonary outcomes . Although 90% of adolescent subjects in our cohort reported respiratory symptoms in the past month, only 25% reported frequent symptoms (daily or several days of the week).…”

“…Pulmonary outcomes among survivors of high‐risk NB have not been well described, and results of pulmonary function testing (PFTs) in long‐term survivors of NB are limited . We previously described mostly mild to moderate PFT abnormalities among a cohort of pediatric survivors of high‐risk NB . The current study aimed to examine chronic respiratory symptoms, exercise capacity, and longitudinal changes in lung function among a larger group of survivors of high‐risk NB followed at a single institution over time.…”

“…Children with high‐risk neuroblastoma (NB) are exposed to multimodality therapies very early in life and may therefore have a higher risk for developing pulmonary complications, including subclinical abnormalities in lung function. Pulmonary outcomes among survivors of high‐risk NB have not been well described, and results of pulmonary function testing (PFTs) in long‐term survivors of NB are limited . We previously described mostly mild to moderate PFT abnormalities among a cohort of pediatric survivors of high‐risk NB .…”

Late Effects and Survivorship Issues in Patients with Neuroblastoma

“…Adverse pulmonary outcomes have been reported as a late effect of neuroblastoma therapy [ 74 ], particularly among those with high-risk disease [ 21 , 75 , 76 ], and are thought to be multifactorial in nature. One study of 39 high-risk neuroblastoma survivors who underwent pulmonary function testing (PFT) found that 33% reported chronic respiratory symptoms; however, PFT abnormalities were mostly mild to moderate in severity [ 77 ]. Another case series reported on six survivors of high-risk neuroblastoma who developed bronchiectasis; all six patients were treated with multimodality therapy including busulfan/melphalan prior to autologous transplant [ 78 ], which is known to induce pulmonary toxicity.…”