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      Secondary Malignancy Risk Following Proton Radiation Therapy

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          Abstract

          Radiation-induced secondary malignancies are a significant, yet uncommon cause of morbidity and mortality among cancer survivors. Secondary malignancy risk is dependent upon multiple factors including patient age, the biological and genetic predisposition of the individual, the volume and location of tissue irradiated, and the dose of radiation received. Proton therapy (PRT) is an advanced particle therapy with unique dosimetric properties resulting in reduced entrance dose and minimal to no exit dose when compared with standard photon radiation therapy. Multiple dosimetric studies in varying cancer subtypes have demonstrated that PRT enables the delivery of adequate target volume coverage with reduced integral dose delivered to surrounding tissues, and modeling studies taking into account dosimetry and radiation cell biology have estimated a significantly reduced risk of radiation-induced secondary malignancy with PRT. Clinical data are emerging supporting the lower incidence of secondary malignancies after PRT compared with historical photon data, though longer follow-up in proton treated cohorts is awaited. This article reviews the current dosimetric and clinical literature evaluating the incidence of and risk factors associated with radiation-induced secondary malignancy following PRT.

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          Most cited references 33

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          Intensity-modulated radiation therapy, protons, and the risk of second cancers.

           Eric Hall (2006)
          Intensity-modulated radiation therapy (IMRT) allows dose to be concentrated in the tumor volume while sparing normal tissues. However, the downside to IMRT is the potential to increase the number of radiation-induced second cancers. The reasons for this potential are more monitor units and, therefore, a larger total-body dose because of leakage radiation and, because IMRT involves more fields, a bigger volume of normal tissue is exposed to lower radiation doses. Intensity-modulated radiation therapy may double the incidence of solid cancers in long-term survivors. This outcome may be acceptable in older patients if balanced by an improvement in local tumor control and reduced acute toxicity. On the other hand, the incidence of second cancers is much higher in children, so that doubling it may not be acceptable. IMRT represents a special case for children for three reasons. First, children are more sensitive to radiation-induced cancer than are adults. Second, radiation scattered from the treatment volume is more important in the small body of the child. Third, the question of genetic susceptibility arises because many childhood cancers involve a germline mutation. The levels of leakage radiation in current Linacs are not inevitable. Leakage can be reduced but at substantial cost. An alternative strategy is to replace X-rays with protons. However, this change is only an advantage if the proton machine employs a pencil scanning beam. Many proton facilities use passive modulation to produce a field of sufficient size, but the use of a scattering foil produces neutrons, which results in an effective dose to the patient higher than that characteristic of IMRT. The benefit of protons is only achieved if a scanning beam is used in which the doses are 10 times lower than with IMRT.
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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

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                26 November 2015
                2015
                : 5
                Affiliations
                1Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School , Boston, MA, USA
                Author notes

                Edited by: Marco Durante, GSI, Germany

                Reviewed by: Dalong Pang, Georgetown University Hospital, USA; Uwe Schneider, University of Zurich and Radiotherapy Hirslanden, Switzerland; Wayne D. Newhauser, Louisiana State University, USA

                *Correspondence: Bree R. Eaton, brupper@ 123456emory.edu

                Present address: Bree R. Eaton, Winship Cancer Institute of Emory University, Atlanta, GA, USA

                Specialty section: This article was submitted to Radiation Oncology, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2015.00261
                4659915
                Copyright © 2015 Eaton, MacDonald, Yock and Tarbell.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 37, Pages: 6, Words: 4249
                Categories
                Oncology
                Mini Review

                Oncology & Radiotherapy

                proton, radiotherapy, radiation, second malignancy

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