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      Impact of radiation dose on local control and survival in extramedullary head and neck plasmacytoma

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          Abstract

          Background

          Patients with plasma-cell neoplasia usually suffer from systemic disease, although a minority (< 5%) may present with solitary involvement of bone or soft tissue (extramedullary plasmacytoma (EMP)). Radiotherapy (RT) is a state-of-the-art treatment for these tumors offering long term curation.

          Methods and materials

          Between January 2005 and January 2017, twenty-seven patients underwent RT at our institution. The aim of this study was to analyse the effectiveness of various RT doses for different forms of EMP.

          Results

          A total of 33 radiation courses were administered to 27 patients with a median age of 56 years. The median RT dose was 45 Gy (range: 12–55.8). The local control rate was 76% (93% for primary EMP vs. 61% for the secondary EMP lesions; P < 0.05). A complete response (CR) rate to local RT was achieved for 42% lesions (67% for primary EMP vs. 22% for the secondary EMP lesions; P < 0.01). The overall response rate (ORR) for the EMP lesions treated with high-dose regimens (> 45 Gy) versus low-dose regimens (≤ 45 Gy) was 87% versus 67%, respectively ( P = 0.2). The median survival with high-dose RT group was significantly longer ( P = 0.02). In subgroups analysis, primary EMP patients treated with high-dose RT had a non-significant higher ORR (100% vs. 80%, respectively; P = 0.3,) longer duration of LC ( P = 0.3) with a longer survival ( P = 0.05) than patients in low-dose group. No significant difference has been detected in secondary EMP patients treated with high-dose RT regarding ORR (60% vs. 62%, respectively; P = 1), and survival ( P = 0.4).

          Conclusion

          RT is an efficacious treatment modality in the treatment of EMP. A radiation dose ≤45 Gy confer a comparable CR rate to high-dose regimens and appears to be an effective treatment for controlling local EMP progression. Radiation dose-escalation may be beneficial for particular subgroups of patients.

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          Most cited references26

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          Extramedullary plasmacytoma: tumor occurrence and therapeutic concepts.

          Extramedullary plasmacytoma (EMP) is a rare entity belonging to the category of non-Hodgkin lymphoma. EMPs make up 4% of all plasma cell tumors and occur mainly in the upper aerodigestive tract (UAD). Seven patients with EMP included in this evaluation were under the authors' care and have been clinically followed since 1990. Because there are no general guidelines for the treatment of patients with EMP, the authors tried to obtain detailed data about the occurrence of this disease and also reviewed the therapies that have been used. To do so, they evaluated all EMP cases published in the medical literature until now and included their own experience. Based on the clinical course and follow-up of their own EMP patients, the authors evaluated and reinvestigated all EMP cases cited in MEDLINE, Index Medicus, DIMDI (Deutsches Institut fur medizinische Dokumentation und Information, Cologne, Germany), and the reference lists of the publications found through these sources. In a detailed literature search, more than 400 publications between 1905 and 1997 were found, and these revealed that EMP mainly occurs between the fourth and seventh decades of life. Seven hundred fourteen cases (82.2%) were found in the UAD, and 155 cases (17.8%) were found in other body regions. The following therapeutic strategies were used to treat patients with EMP of the UAD: radiation therapy alone in 44.3%, combined therapy (surgery and radiation) in 26.9%, and surgery alone in 21.9%. The median overall survival or recurrence free survival was longer than 300 months for patients who underwent combined intervention (surgery and radiation). This result was statistically highly significant (P = 0.0027, log rank test) compared with the results for patients who underwent surgical intervention alone (median survival time, 156 months) or radiation therapy alone (median survival time, 144 months). In most cases of non-UAD EMP, surgery was performed (surgery alone, 55.6%; surgery and radiation combined, 19.8%; radiation alone, 11.1%), but there were no statistical differences in survival (P = 0.62). Overall, after treatment for EMP in the UAD, 61.1% of all patients had no recurrence or conversion to systemic involvement (i.e., multiple myeloma, MM); however, 22.0% had recurrence of EMP, and 16.1% had conversion to MM. After treatment for EMP in non-UAD areas, 64.7% of all patients had no recurrence or MM, 21.2% had recurrence, and 14.1% had conversion to MM. The current investigation provides evidence that surgery alone gives the best results in cases of EMP of the UAD when resectability is good. However, if complete surgical tumor resection is doubtful or impossible and/or if lymph node areas are affected, then combined therapy (surgery and radiation) is recommended. These results, which were obtained from retrospective studies, should be confirmed in randomized trials comparing surgery with combined radiation therapy and surgery.
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            Molecular pathogenesis of multiple myeloma: basic and clinical updates.

            Multiple myeloma is divided into two distinct genetic subtypes based on chromosome content. Hyperdiploid myeloma is characterized by multiple trisomies of chromosomes 3, 5, 7, 9 11, 15, 19 and 21, and lacks recurrent immunoglobulin gene translocations. Non-hyperdiploid myeloma in contrast is characterized by chromosome translocations t(4;14), t(14;16), t(14;20), t(6;14) and t(11;14). A unifying event in the pathogenesis of multiple myeloma is the dysregulated expression of a cyclin D gene, either directly by juxtaposition to an immunoglobulin enhancer, as a result of ectopic expression of a MAF family transcription factor, or indirectly by as yet unidentified mechanisms. Secondary genetic events include rearrangements of MYC, activating mutations of NRAS, KRAS or BRAF, a promiscuous array of mutations that activate NFkB and deletions of 17p. Among the poor-risk genetic features are t(4;14), t(14;16), t(14;20), del 17p and gains of 1q. Available evidence supports the use of a risk-stratified approach to the treatment of patients with multiple myeloma, with the early and prolonged use of bortezomib particularly in patients with t(4;14) and del 17p.
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              Guidelines on the diagnosis and management of solitary plasmacytoma of bone and solitary extramedullary plasmacytoma.

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                Author and article information

                Contributors
                michael.oertel@ukmuenster.de
                +49 0251 83 47384 , Khaled.elsayad@uni-muenster.de
                kai.kroeger@ukmuenster.de
                uwe.haverkamp@ukmuenster.de
                claudia.rudack@ukmuenster.de
                georg.lenz@ukmuenster.de
                hans.eich@ukmuenster.de
                Journal
                Radiat Oncol
                Radiat Oncol
                Radiation Oncology (London, England)
                BioMed Central (London )
                1748-717X
                15 April 2019
                15 April 2019
                2019
                : 14
                : 63
                Affiliations
                [1 ]ISNI 0000 0004 0551 4246, GRID grid.16149.3b, Department of Radiation Oncology, , University Hospital of Muenster, ; Albert-Schweitzer-Campus 1, Building A1, 48149 Muenster, Germany
                [2 ]ISNI 0000 0004 0551 4246, GRID grid.16149.3b, Department of Otorhinolaryngology, Head and Neck Surgery, , University Hospital of Muenster, ; Muenster, Germany
                [3 ]ISNI 0000 0004 0551 4246, GRID grid.16149.3b, Department of Internal Medicine-A (Hematology, Oncology, Hemostaseology and Pulmonology), , University Hospital Muenster, ; Muenster, Germany
                Author information
                http://orcid.org/0000-0001-9303-7336
                Article
                1265
                10.1186/s13014-019-1265-5
                6466654
                30987659
                a9284a0f-a401-4c3d-a517-c927ed7521d1
                © The Author(s). 2019

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 19 November 2018
                : 28 March 2019
                Categories
                Research
                Custom metadata
                © The Author(s) 2019

                Oncology & Radiotherapy
                extramedullary,plasmocytoma,radiotherapy,imrt,local control,prognosis
                Oncology & Radiotherapy
                extramedullary, plasmocytoma, radiotherapy, imrt, local control, prognosis

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