Risks of Spinal Abnormalities and Growth Impairment After Radiation to the Spine in Childhood Cancer Survivors: A PENTEC Comprehensive Review

Ronica H Nanda; Chia-Ho Hua; Stella Flampouri; Bree Eaton; Sue Kaste; Tushar Patni; Cecile Ronckers; Louis S Constine; Lawrence B Marks; Natia Esiashvili

doi:10.1016/j.ijrobp.2023.10.039

Risks of Spinal Abnormalities and Growth Impairment After Radiation to the Spine in Childhood Cancer Survivors: A PENTEC Comprehensive Review

Int J Radiat Oncol Biol Phys. 2023 Dec 8:S0360-3016(23)08044-6. doi: 10.1016/j.ijrobp.2023.10.039. Online ahead of print.

Authors

Affiliations

¹ Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida. Electronic address: ronica.nanda@moffitt.org.
² Department of Radiation Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
³ Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.
⁴ Departments of Diagnostic Imaging and Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
⁵ Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee.
⁶ Division of Childhood Cancer Epidemiology / German Childhood Cancer Registry, Institute for Medical Biostatistics, Epidemiology and Informatics, University Medicin at the Johannes Gutenberg University Mainz, Mainz, Germany.
⁷ Department of Radiation Oncology, University of Rochester Medical Center, Rochester, New York.
⁸ Department of Radiation Oncology, Lineberger Cancer Center, University of North Carolina, Chapel Hill, North Carolina.

PMID: 38069918
DOI: 10.1016/j.ijrobp.2023.10.039

Abstract

Purpose: A PENTEC (Pediatric Normal Tissue Effects in the Clinic) review was performed to estimate the dose-volume effects of radiation therapy on spine deformities and growth impairment for patients who underwent radiation therapy as children.

Methods and materials: A systematic literature search was performed to identify published data for spine deformities and growth stunting. Data were extracted from 12 reports of children irradiated to the spine (N = 603 patients). The extracted data were analyzed to find associations between complication risks and the radiation dose (conventional fractionation throughout) as impacted by exposed volumes and age using the mixed-effects logistic regression model. When appropriate, corrections were made for radiation modality, namely orthovoltage beams.

Results: In the regression analysis, the association between vertebral dose and scoliosis rate was highly significant (P < .001). Additionally, young age at time of radiation was highly predictive of adverse outcomes. Clinically significant scoliosis can occur with doses ≥15 Gy to vertebrae during infancy (<2 years of age). For children irradiated at 2 to 6 years of age, overall scoliosis rates of any grade were >30% with doses >20 Gy; grade 2 or higher scoliosis was correlated with doses ≥30 Gy. Children >6 years of age remain at risk for scoliosis with doses >30 Gy; however, most cases will be mild. There are limited data regarding the effect of dose gradients across the spine on degree of scoliosis. The risk of clinically meaningful height loss was minimal when irradiating small volumes of the spine up to 20 Gy (eg, flank irradiation), except in infants who are more vulnerable to lower doses. Growth stunting was more frequent when larger segments of the spine (eg, the entire spine or craniospinal irradiation) were irradiated before puberty to doses >20 Gy. The effect was modest when patients were irradiated after puberty to doses >20 Gy.

Conclusions: To reduce the risk of kyphoscoliosis and growth impairment, the dose to the spine should be kept to <20 Gy for children <6 years of age and to <10 to 15 Gy in infants. The number of vertebral bodies irradiated and dose gradients across the spine should also be limited when possible.