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      Nodal failure patterns and utility of elective nodal irradiation in submandibular gland carcinoma treated with postoperative radiotherapy - a multicenter experience

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          Abstract

          Background

          The patterns of nodal relapse in submandibular gland carcinoma (SMGC) patients treated with postoperative radiotherapy (PORT) remain unclear. This study aims to investigate the nodal failure patterns and the utility of elective nodal irradiation (ENI) in SMGC patients undergoing PORT.

          Methods

          We retrospectively enrolled 65 SMGC patients who underwent PORT between 2000 and 2014. The nodal failure sites in relation to irradiation fields and pathological parameters were analyzed. ENI regions were categorized into three bilateral echelons (first, levels I–II; second, level III; and third, levels IV–V). Extended ENI was defined as coverage of at least the immediately adjacent uninvolved echelons bilaterally; otherwise, limited ENI was administered.

          Results

          Thirty patients (46%) were stage III–IV, and 18 (28%) were pN+. Neck irradiation included limited (72%) and extended ENI (28%). With a median follow-up of 79 months, 11 patients (17%) developed nodal failures (ipsilateral, N = 6; contralateral, N = 7), 7 (64%) of whom relapsed in the adjacent uninvolved echelons. We identified pN+ ( P = 0.030), extranodal extension (ENE, P = 0.002), pT3–4 ( P = 0.021), and lymphovascular invasion (LVI, P = 0.004) as significant predictors of contralateral neck recurrence. Extended ENI significantly improved regional control (RC) in patients with pN+ ( P = 0.003), ENE ( P = 0.022), pT3–4 ( P = 0.044), and LVI ( P = 0.014), and improved disease-free survival (DFS) in patients with pN+ ( P = 0.034). For patients with ≥2 coincident adverse factors, extended ENI significantly increased RC ( P < 0.001), distant metastasis-free survival ( P = 0.019), and DFS ( P = 0.007); conversely, no nodal recurrence was observed in patients without these adverse factors, even when only the involved echelon was irradiated.

          Conclusions

          Nodal failure is not uncommon in SMGC patients treated with PORT if pN+, ENE, pT3–4, and LVI are present. Extended ENI should be considered, particularly in patients with multiple pathological adverse factors.

          Electronic supplementary material

          The online version of this article (10.1186/s13014-018-1130-y) contains supplementary material, which is available to authorized users.

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          Most cited references33

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          Salivary neoplasms: Overview of a 35-year experience with 2,807 patients

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            Salivary gland carcinoma: independent prognostic factors for locoregional control, distant metastases, and overall survival: results of the Dutch head and neck oncology cooperative group.

            We analyzed the records of patients with malignant salivary gland tumors, as diagnosed in centers of the Dutch Head and Neck Oncology Cooperative Group, in search of independent prognostic factors for locoregional control, distant metastases, and overall survival. In 565 patients, we analyzed general results and looked for the potential prognostic variables of age, sex, delay, clinical and pathologic T and N stage, site (332 parotid, 76 submandibular, 129 oral cavity, 28 pharynx/larynx), pain, facial weakness, clinical and pathologic skin involvement, histologic type (WHO 1972 classification), treatment, resection margins, spill, perineural and vascular invasion, number of neck nodes, and extranodal disease. The median follow-up period was 74 months; it was 99 months for patients who were alive on the last follow-up. The rates of local control, regional control, distant metastasis-free and overall survival after 10 years were, respectively, 78%, 87%, 67%, and 50%. In multivariable analysis, local control was predicted by clinical T-stage, bone invasion, site, resection margin, and treatment. Regional control depended on N stage, facial nerve paralysis, and treatment. The relative risk with surgery alone, compared to surgery plus postoperative radiotherapy, was 9.7 for local recurrence and 2.3 for regional recurrence. Distant metastases were independently correlated with T and N stage, sex, perineural invasion, histologic type, and clinical skin involvement. Overall survival depended on age, sex, T and pN stage, site, skin and bone invasion. Several prognostic factors for locoregional control, distant metastases, and overall survival were found. Postoperative radiotherapy was found to improve locoregional control. Copyright 2004 Wiley Periodicals, Inc.
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              The role of radiotherapy in the treatment of malignant salivary gland tumors.

              We analyzed the role of primary and postoperative low linear energy transfer radiotherapy in 538 patients treated for salivary gland cancer in centers of the Dutch Head and Neck Oncology Cooperative Group, in search for prognostic factors and dose response. The tumor was located in the parotid gland in 59%, submandibular gland in 14%, oral cavity in 23%, and elsewhere in 5%. In 386 of 498 patients surgery was combined with radiotherapy, with a median dose of 62 Gy. Median delay between surgery and radiotherapy was 6 weeks. In the postoperative radiotherapy group, adverse prognostic factors prevailed. Elective radiotherapy to the neck was given in 40%, with a median dose of 50 Gy. Primary radiotherapy (n = 40) was given for unresectable disease or M(1), with a dose range of 28-74 Gy. Postoperative radiotherapy improved 10-year local control significantly compared with surgery alone in T(3-4) tumors (84% vs. 18%), in patients with close (95% vs. 55%) and incomplete resection (82% vs. 44%), in bone invasion (86% vs. 54%), and perineural invasion (88% vs. 60%). Local control was not correlated with interval between surgery and radiotherapy. No dose-response relationship was shown. Postoperative radiotherapy significantly improved regional control in the pN(+) neck (86% vs. 62% for surgery alone). A rating scale for different sites, T stage, and histologic type may be applied to calculate the risk of disease in the neck at presentation, and so indicate the need for elective neck treatment. A marginal dose-response was seen, in favor of a dose > or =46 Gy. A clear dose-response relationship was shown for patients treated with primary radiotherapy. Five-year local control was 50% with a dose of 66-70 Gy. Postoperative radiotherapy with a dose of at least 60 Gy is indicated for patients with T(3-4) tumors, incomplete or close resection, bone invasion, perineural invasion, and pN(+). In unresectable tumors, a dose of at least 66 Gy is advisable.
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                Author and article information

                Contributors
                rodney445@gmail.com
                r22068@cgmh.org.tw
                khs.fan@gmail.com
                vstsang@adm.cgmh.org.tw
                cgmhnog@gmail.com
                whm526@adm.cgmh.org.tw
                shuhangng@gmail.com
                liaoct@adm.cgmh.org.tw
                yentc1110@gmail.com
                b8401085@adm.cgmh.org.tw
                +886-3-3281200 , qqvirus1022@gmail.com
                Journal
                Radiat Oncol
                Radiat Oncol
                Radiation Oncology (London, England)
                BioMed Central (London )
                1748-717X
                21 September 2018
                21 September 2018
                2018
                : 13
                : 184
                Affiliations
                [1 ]ISNI 0000 0004 1756 1461, GRID grid.454210.6, Radiation Oncology, , Chang Gung Memorial Hospital at Linkou and Chang Gung University, ; No. 5, Fuxing St., Guishan Dist, Taoyuan City, 33305 Taiwan, Republic of China
                [2 ]ISNI 0000 0004 1756 1461, GRID grid.454210.6, Pathology, , Chang Gung Memorial Hospital at Linkou and Chang Gung University, ; Taoyuan City, Taiwan, Republic of China
                [3 ]ISNI 0000 0004 1756 1461, GRID grid.454210.6, Medical Oncology, , Chang Gung Memorial Hospital at Linkou and Chang Gung University, ; Taoyuan City, Taiwan, Republic of China
                [4 ]ISNI 0000 0004 1756 1461, GRID grid.454210.6, Diagnostic Radiology, , Chang Gung Memorial Hospital at Linkou and Chang Gung University, ; Taoyuan City, Taiwan, Republic of China
                [5 ]ISNI 0000 0004 1756 1461, GRID grid.454210.6, Otorhinolaryngology, Head and Neck Surgery, , Chang Gung Memorial Hospital at Linkou and Chang Gung University, ; Taoyuan City, Taiwan, Republic of China
                [6 ]ISNI 0000 0004 1756 1461, GRID grid.454210.6, Nuclear Medicine and Molecular Imaging Center, , Chang Gung Memorial Hospital at Linkou and Chang Gung University, ; Taoyuan City, Taiwan, Republic of China
                [7 ]ISNI 0000 0004 1756 1461, GRID grid.454210.6, Head and Neck Oncology Group, , Chang Gung Memorial Hospital at Linkou and Chang Gung University, ; Taoyuan City, Taiwan, Republic of China
                [8 ]GRID grid.145695.a, Graduate Institute of Clinical Medical Science, , Chang Gung University, ; Taoyuan City, Taiwan, Republic of China
                [9 ]GRID grid.145695.a, School of Traditional Chinese Medicine, , Chang Gung University, ; Taoyuan City, Taiwan, Republic of China
                [10 ]Radiation Oncology, Xiamen Chang Gung Hospital, Xiamen City, Fujian Province China
                [11 ]ISNI 0000 0001 2291 4776, GRID grid.240145.6, Departments of Experimental Radiation Oncology, Division of Radiation Oncology, , The University of Texas MD Anderson Cancer Center, ; Houston, Texas USA
                [12 ]ISNI 0000 0001 2291 4776, GRID grid.240145.6, The University of Texas MD Anderson Cancer Center-UT Health Graduate School of Biomedical Sciences, ; Houston, Texas USA
                [13 ]ISNI 0000 0004 1756 1461, GRID grid.454210.6, Particle Physics and Beam Delivery Core Laboratory, Institute for Radiological Research, , Chang Gung Memorial Hospital at Linkou and Chang Gung University, ; Taoyuan City, Taiwan, Republic of China
                Author information
                http://orcid.org/0000-0002-0972-9397
                Article
                1130
                10.1186/s13014-018-1130-y
                6151022
                30241545
                5e321b69-dc17-450d-866c-6b5807650bb2
                © The Author(s). 2018

                Open AccessThis 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
                : 8 September 2017
                : 12 September 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100005795, Chang Gung Memorial Hospital, Linkou;
                Award ID: CORPG3G0961
                Award ID: CMRPG3F0061
                Award ID: CMRPG3F0861
                Award ID: CMRPG3F0061-2
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2018

                Oncology & Radiotherapy
                submandibular gland cancer,postoperative radiotherapy,elective nodal irradiation,nodal failure pattern

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