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      Treatment of pediatric patients and young adults with particle therapy at the Heidelberg Ion Therapy Center (HIT): establishment of workflow and initial clinical data

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          Abstract

          Background

          To report on establishment of workflow and clinical results of particle therapy at the Heidelberg Ion Therapy Center.

          Materials and methods

          We treated 36 pediatric patients (aged 21 or younger) with particle therapy at HIT. Median age was 12 years (range 2-21 years), five patients (14%) were younger than 5 years of age. Indications included pilocytic astrocytoma, parameningeal and orbital rhabdomyosarcoma, skull base and cervical chordoma, osteosarcoma and adenoid-cystic carcinoma (ACC), as well as one patient with an angiofibroma of the nasopharynx. For the treatment of small children, an anesthesia unit at HIT was established in cooperation with the Department of Anesthesiology.

          Results

          Treatment concepts depended on tumor type, staging, age of the patient, as well as availability of specific study protocols. In all patients, particle radiotherapy was well tolerated and no interruptions due to toxicity had to be undertaken. During follow-up, only mild toxicites were observed. Only one patient died of tumor progression: Carbon ion radiotherapy was performed as an individual treatment approach in a child with a skull base recurrence of the previously irradiated rhabdomyosarcoma. Besides this patient, tumor recurrence was observed in two additional patients.

          Conclusion

          Clinical protocols have been generated to evaluate the real potential of particle therapy, also with respect to carbon ions in distinct pediatric patient populations. The strong cooperation between the pediatric department and the department of radiation oncology enable an interdisciplinary treatment and stream-lined workflow and acceptance of the treatment for the patients and their parents.

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          Most cited references26

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          Effectiveness of carbon ion radiotherapy in the treatment of skull-base chordomas.

          The aim of this study was to evaluate the effectiveness and toxicity of carbon ion radiotherapy in chordomas of the skull base. Between November 1998 and July 2005, a total of 96 patients with chordomas of the skull base have been treated with carbon ion radiation therapy (RT) using the raster scan technique at the Gesellschaft für Schwerionenforschung (GSI) in Darmstadt, Germany. All patients had gross residual tumors. Median total dose was 60 CGE (range, 60-70 CGE) delivered in 20 fractions within 3 weeks. Local control and overall survival rates were calculated using the Kaplan-Meier method. Toxicity was assessed according to the Common Terminology Criteria (CTCAE v.3.0) and the Radiation Therapy Oncology Group (RTOG) / European Organization for Research and Treatment of Cancer (EORTC) score. Mean follow-up was 31 months (range, 3-91 months). Fifteen patients developed local recurrences after carbon ion RT. The actuarial local control rates were 80.6% and 70.0% at 3 and 5 years, respectively. Target doses in excess of 60 CGE and primary tumor status were associated with higher local control rates. Overall survival was 91.8% and 88.5% at 3 and 5 years, respectively. Late toxicity consisted of optic nerve neuropathy RTOG/EORTC Grade 3 in 4.1% of the patients and necrosis of a fat plomb in 1 patient. Minor temporal lobe injury (RTOG/EORTC Grade 1-2) occurred in 7 patients (7.2%). Carbon ion RT offers an effective treatment option for skull-base chordomas with acceptable toxicity. Doses in excess of 75 CGE with 2 CGE per fraction are likely to increase local control probability.
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            Proton-based radiotherapy for unresectable or incompletely resected osteosarcoma.

            A study was undertaken to assess clinical outcome and the role of proton therapy for local control of osteosarcoma (OSA). All patients who received proton therapy or mixed photon-proton radiotherapy from 1983 to 2009 at the Massachusetts General Hospital were reviewed. Criteria for proton therapy were the need for high dose in the context of highly conformal radiotherapy of unresected or partially resected OSA, positive postoperative margins, postoperative imaging studies with macroscopic disease, or incomplete resection as defined by the surgeon. The primary endpoint was local control of the site treated; secondary endpoints were disease-free survival (DFS), overall survival (OS), long-term toxicity, and prognostic factors associated with clinical outcome. Fifty-five patients with a median age of 29 years (range, 2-76 years) were offered proton therapy. The mean dose was 68.4 gray (Gy; standard deviation, 5.4 Gy). Of the total dose, 58.2% (range, 11%-100%) was delivered with protons. Local control after 3 and 5 years was 82% and 72%, respectively. The distant failure rate was 26% after 3 and 5 years. The 5-year DFS was 65%, and the 5-year OS was 67%. The extent of surgical resection did not correlate with outcome. Risk factors for local failure were ≥ 2 grade disease (P < .0001) and total treatment length (P = .008). Grade 3 to 4 late toxicity was seen in 30.1 % of patients. One patient died from treatment-associated acute lymphocytic leukemia, and 1 from secondary carcinoma of the maxilla. Proton therapy to deliver high radiotherapy doses allows locally curative treatment for some patients with unresectable or incompletely resected OSA. Copyright © 2011 American Cancer Society.
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              Potential reduction of the incidence of radiation-induced second cancers by using proton beams in the treatment of pediatric tumors.

              To assess the potential influence of improved dose distribution with proton beams compared to conventional or intensity-modulated (IM) X-ray beams on the incidence of treatment-induced secondary cancers in pediatric oncology. Two children, one with a parameningeal rhabdomyosarcoma (RMS) and a second with a medulloblastoma, were used as models for the purpose of this study. After defining the target and critical structures, treatment plans were calculated and optimized, four for the RMS case (conventional X-ray, IM X-rays, protons, and IM protons) and three for the irradiation of the spinal axis in medulloblastoma (conventional X-ray, IM X-rays, protons). Secondary cancer incidence was estimated using a model based on Publication No. 60 of the International Commission on Radiologic Protection. This model allowed estimation of absolute risks of secondary cancer for each treatment plan based on dose-volume distributions for the nontarget organs. Proton beams reduced the expected incidence of radiation-induced secondary cancers for the RMS patient by a factor of >or=2 and for the medulloblastoma case by a factor of 8 to 15 when compared with either IM or conventional X-ray plans. The potential for a significant reduction in secondary cancers with pediatric cancers after using proton beams (forward planned or IM) in the treatment of RMS and MBD in children and adolescents represents an additional argument supporting the development of proton therapy for most radiotherapy indications in pediatric oncology.
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                Author and article information

                Journal
                Radiat Oncol
                Radiat Oncol
                Radiation Oncology (London, England)
                BioMed Central
                1748-717X
                2012
                17 October 2012
                : 7
                : 170
                Affiliations
                [1 ]Department of Radiation Oncology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, Heidelberg, 69120, Germany
                [2 ]Department of Pediatric Hematology and Oncology, University Hospital of Heidelberg, Im Neuenheimer Feld 430, Heidelberg, 69120, Germany
                [3 ]Heidelberg Ion Therapy Center (HIT), Im Neuenheimer Feld 450, Heidelberg, 69120, Germany
                [4 ]Department of Anaesthesiology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, Heidelberg, 69120, Germany
                [5 ]CCU Pediatric Oncology, German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg, 69120, Germany
                Article
                1748-717X-7-170
                10.1186/1748-717X-7-170
                3504515
                23072718
                b440397e-7108-4f09-a922-affa8eb5c9ea
                Copyright ©2012 Combs et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 July 2012
                : 13 October 2012
                Categories
                Research

                Oncology & Radiotherapy
                children,proton radiation,carbon ion radiotherapy
                Oncology & Radiotherapy
                children, proton radiation, carbon ion radiotherapy

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