Daniel M Green1, Thomas E Merchant2, Catherine A Billups3, Dennis C Stokes4, Alberto Broniscer5, Ute Bartels6, Murali Chintagumpala7, Timothy E Hassall8, Sridharan Gururangan9, Geoffrey B McCowage10, John A Heath11, Richard J Cohn12, Michael J Fisher13, Ashok Srinivasan14, Giles W Robinson5, Amar Gajjar5. 1. Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee. Electronic address: daniel.green@stjude.org. 2. Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee. 3. Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee. 4. Department of Pediatrics, University of Tennessee School of Medicine, Memphis, Tennessee. 5. Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee. 6. Department of Haematology and Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada. 7. Department of Pediatric Medicine, Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, Texas. 8. Department of Haematology and Oncology, Royal Children's Hospital, Brisbane, Australia. 9. Department of Pediatrics, Duke University Medical Center, Durham, North Carolina. 10. Department of Pediatrics, Children's Hospital at Westmead, Sydney, Australia. 11. Children's Cancer Center, Royal Children's Hospital Melbourne, Melbourne, Australia. 12. Department of Clinical Oncology, Sydney Children's Hospital, Sydney, Australia. 13. Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. 14. Department of Bone Marrow Transplantation & Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee.
Abstract
PURPOSE: The treatment of children with embryonal brain tumors (EBT) includes craniospinal irradiation (CSI). There are limited data regarding the effect of CSI on pulmonary function. METHODS: Protocol SJMB03 enrolled patients 3 to 21 years of age with EBT. Pulmonary function tests (PFTs) (forced expiratory volume in 1 second [FEV1] and forced vital capacity [FVC] by spirometry, total lung capacity [TLC] by nitrogen washout or plethysmography, and diffusing capacity of the lung for carbon monoxide corrected for hemoglobin [DLCO(corr)]) were obtained. Differences between PFTs obtained immediately after the completion of CSI and 24 or 60 months after the completion of treatment (ACT) were compared using exact Wilcoxon signed-rank tests and repeated-measures models. RESULTS: Between June 24, 2003, and March 1, 2010, 303 eligible patients (spine dose: ≤ 2345 cGy, 201; >2345 cGy, 102; proton beam, 20) were enrolled, 260 of whom had at least 1 PFT. The median age at diagnosis was 8.9 years (range, 3.1-20.4 years). The median thoracic spinal radiation dose was 23.4 Gy (interquartile range [IQR], 23.4-36.0 Gy). The median cyclophosphamide dose was 16.0 g/m(2) (IQR, 15.7-16.0 g/m(2)). At 24 and 60 months ACT, DLCO(corr) was <75% predicted in 23% (27/118) and 25% (21/84) of patients, FEV1 was <80% predicted in 20% (34/170) and 29% (32/109) of patients, FVC was <80% predicted in 27% (46/172) and 28% (30/108) of patients, and TLC was <75% predicted in 9% (13/138) and 11% (10/92) of patients. DLCO(corr) was significantly decreased 24 months ACT (median difference [MD] in % predicted, 3.00%; P = .028) and 60 months ACT (MD in % predicted, 6.00%; P = .033) compared with the end of radiation therapy. These significant decreases in DLCO(corr) were also observed in repeated-measures models (P = .011 and P = .032 at 24 and 60 months ACT, respectively). CONCLUSIONS: A significant minority of EBT survivors experience PFT deficits after CSI. Continued monitoring of this cohort is planned.
PURPOSE: The treatment of children with embryonal brain tumors (EBT) includes craniospinal irradiation (CSI). There are limited data regarding the effect of CSI on pulmonary function. METHODS: Protocol SJMB03 enrolled patients 3 to 21 years of age with EBT. Pulmonary function tests (PFTs) (forced expiratory volume in 1 second [FEV1] and forced vital capacity [FVC] by spirometry, total lung capacity [TLC] by nitrogen washout or plethysmography, and diffusing capacity of the lung for carbon monoxide corrected for hemoglobin [DLCO(corr)]) were obtained. Differences between PFTs obtained immediately after the completion of CSI and 24 or 60 months after the completion of treatment (ACT) were compared using exact Wilcoxon signed-rank tests and repeated-measures models. RESULTS: Between June 24, 2003, and March 1, 2010, 303 eligible patients (spine dose: ≤ 2345 cGy, 201; >2345 cGy, 102; proton beam, 20) were enrolled, 260 of whom had at least 1 PFT. The median age at diagnosis was 8.9 years (range, 3.1-20.4 years). The median thoracic spinal radiation dose was 23.4 Gy (interquartile range [IQR], 23.4-36.0 Gy). The median cyclophosphamide dose was 16.0 g/m(2) (IQR, 15.7-16.0 g/m(2)). At 24 and 60 months ACT, DLCO(corr) was <75% predicted in 23% (27/118) and 25% (21/84) of patients, FEV1 was <80% predicted in 20% (34/170) and 29% (32/109) of patients, FVC was <80% predicted in 27% (46/172) and 28% (30/108) of patients, and TLC was <75% predicted in 9% (13/138) and 11% (10/92) of patients. DLCO(corr) was significantly decreased 24 months ACT (median difference [MD] in % predicted, 3.00%; P = .028) and 60 months ACT (MD in % predicted, 6.00%; P = .033) compared with the end of radiation therapy. These significant decreases in DLCO(corr) were also observed in repeated-measures models (P = .011 and P = .032 at 24 and 60 months ACT, respectively). CONCLUSIONS: A significant minority of EBT survivors experience PFT deficits after CSI. Continued monitoring of this cohort is planned.
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