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      Endocrine Deficiency as a Function of Radiation Dose to the Hypothalamus and Pituitary in Pediatric and Young Adult Patients With Brain Tumors

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          Abstract

          <div class="section"> <a class="named-anchor" id="d4806281e227"> <!-- named anchor --> </a> <h5 class="section-title" id="d4806281e228">Purpose</h5> <p id="d4806281e230">There are sparse data defining the dose response of radiation therapy (RT) to the hypothalamus and pituitary in pediatric and young adult patients with brain tumors. We examined the correlation between RT dose to these structures and development of endocrine dysfunction in this population. </p> </div><div class="section"> <a class="named-anchor" id="d4806281e232"> <!-- named anchor --> </a> <h5 class="section-title" id="d4806281e233">Materials and Methods</h5> <p id="d4806281e235">Dosimetric and clinical data were collected from children and young adults (&lt; 26 years of age) with brain tumors treated with proton RT on three prospective studies (2003 to 2016). Deficiencies of growth hormone (GH), thyroid hormone, adrenocorticotropic hormone, and gonadotropins were determined clinically and serologically. Incidence of deficiency was estimated using the Kaplan-Meier method. Multivariate models were constructed accounting for radiation dose and age. </p> </div><div class="section"> <a class="named-anchor" id="d4806281e237"> <!-- named anchor --> </a> <h5 class="section-title" id="d4806281e238">Results</h5> <p id="d4806281e240">Of 222 patients in the study, 189 were evaluable by actuarial analysis, with a median follow-up of 4.4 years (range, 0.1 to 13.3 years), with 31 patients (14%) excluded from actuarial analysis for having baseline hormone deficiency and two patients (0.9%) because of lack of follow-up. One hundred thirty patients (68.8%) with medulloblastoma were treated with craniospinal irradiation (CSI) and boost; most of the remaining patients (n = 56) received involved field RT, most commonly for ependymoma (13.8%; n = 26) and low-grade glioma (7.4%; n = 14). The 4-year actuarial rate of any hormone deficiency, growth hormone, thyroid hormone, adrenocorticotropic hormone, and gonadotropin deficiencies were 48.8%, 37.4%, 20.5%, 6.9%, and 4.1%, respectively. Age at start of RT, time interval since treatment, and median dose to the combined hypothalamus and pituitary were correlated with increased incidence of deficiency. </p> </div><div class="section"> <a class="named-anchor" id="d4806281e242"> <!-- named anchor --> </a> <h5 class="section-title" id="d4806281e243">Conclusion</h5> <p id="d4806281e245">Median hypothalamic and pituitary radiation dose, younger age, and longer follow-up time were associated with increased rates of endocrinopathy in children and young adults treated with radiotherapy for brain tumors. </p> </div>

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          Most cited references37

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          Chronic disease in the Childhood Cancer Survivor Study cohort: a review of published findings.

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            Long-term toxic effects of proton radiotherapy for paediatric medulloblastoma: a phase 2 single-arm study

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              Advantage of protons compared to conventional X-ray or IMRT in the treatment of a pediatric patient with medulloblastoma.

              To compare treatment plans from standard photon therapy to intensity modulated X-rays (IMRT) and protons for craniospinal axis irradiation and posterior fossa boost in a patient with medulloblastoma. Proton planning was accomplished using an in-house 3D planning system. IMRT plans were developed using the KonRad treatment planning system with 6-MV photons. Substantial normal-tissue dose sparing was realized with IMRT and proton treatment of the posterior fossa and spinal column. For example, the dose to 90% of the cochlea was reduced from 101.2% of the prescribed posterior fossa boost dose from conventional X-rays to 33.4% and 2.4% from IMRT and protons, respectively. Dose to 50% of the heart volume was reduced from 72.2% for conventional X-rays to 29.5% for IMRT and 0.5% for protons. Long-term toxicity with emphasis on hearing and endocrine and cardiac function should be substantially improved secondary to nontarget tissue sparing achieved with protons. The present study clearly demonstrates the advantage of conformal radiation methods for the treatment of posterior fossa and spinal column in children with medulloblastoma, when compared to conventional X-rays. Of the two conformal treatment methods evaluated, protons were found to be superior to IMRT.
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                Author and article information

                Journal
                Journal of Clinical Oncology
                JCO
                American Society of Clinical Oncology (ASCO)
                0732-183X
                1527-7755
                July 17 2018
                August 17 2018
                : JCO.2018.78.149
                Affiliations
                [1 ]Ralph E. Vatner, Andrzej Niemierko, Madhusmita Misra, Elizabeth A. Weyman, Claire P. Goebel, David H. Ebb, Robin M. Jones, Mary S. Huang, Takara Stanley, Shannon M. MacDonald, Nancy J. Tarbell, and Torunn I. Yock, Massachusetts General Hospital, Boston, MA; Ralph E. Vatner, University of Cincinnati College of Medicine and Cincinnati Children’s Hospital Medical Center, Cincinnati, OH; Anita Mahajan, Mayo Clinic, Rochester, MN; and David R. Grosshans and Arnold C. Paulino, MD Anderson Cancer Center,...
                Article
                10.1200/JCO.2018.78.1492
                6161835
                30118397
                9c196229-c018-4773-b363-80a215c0b4f2
                © 2018
                History

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