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      Radiotherapy with neoadjuvant chemotherapy versus concurrent chemoradiotherapy for ascending-type nasopharyngeal carcinoma: a retrospective comparison of toxicity and prognosis

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          Abstract

          Background

          In the era of intensity-modulated radiotherapy (IMRT), the role of neoadjuvant chemotherapy (NACT) in treating ascending-type nasopharyngeal carcinoma (NPC) is under-evaluated. This study was to compare the efficacy of NACT followed by IMRT (NACT + RT) with the efficacy of concurrent chemoradiotherapy (CCRT) on ascending-type NPC.

          Methods

          Clinical data of 214 patients with ascending-type NPC treated with NACT + RT or CCRT between December 2009 and July 2011 were analyzed. Of the 214 patients, 98 were treated with NACT followed by IMRT, and 116 were treated with CCRT. The survival rates were assessed using Kaplan–Meier analysis, and the survival curves were compared using a log-rank test.

          Results

          The 4-year overall survival, locoregional failure-free survival, distant failure-free survival, and failure-free survival rates were not significantly different between the two groups (all P > 0.05). However, patients in the CCRT group exhibited more severe acute adverse events than did patients in the NACT + RT group during radiotherapy, including leukopenia (30.2% vs. 15.3%, P = 0.016), neutropenia (25.9% vs. 11.2%, P = 0.011), and mucositis (57.8% vs. 40.8%, P = 0.028). After radiotherapy, patients in the CCRT group exhibited significantly higher rates of xerostomia (21.6% vs. 10.2%, P = 0.041) and hearing loss (17.2% vs. 6.1%, P = 0.023).

          Conclusions

          The treatment outcomes of the NACT + RT and CCRT groups were similar; however, CCRT led to higher rates of acute and late toxicities. NACT + RT may therefore be a better treatment strategy for ascending-type NPC.

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          Most cited references26

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          How does intensity-modulated radiotherapy versus conventional two-dimensional radiotherapy influence the treatment results in nasopharyngeal carcinoma patients?

          To compare the results of intensity-modulated radiotherapy (IMRT) with those of two-dimensional conventional radiotherapy (2D-CRT) in the treatment of patients with nasopharyngeal carcinoma (NPC). A retrospective review of data from 1,276 patients with biopsy-proven, nonmetastatic NPC was performed. All patients had undergone magnetic resonance imaging and were staged according to the sixth edition of the American Joint Committee on Cancer staging criteria. Radiotherapy was the primary treatment for all patients. Of the 1,276 patients, 512 were treated with IMRT and 764 with 2D-CRT. The 5-year actuarial local relapse-free survival (LRFS), the nodal relapse-free survival (NRFS), the distant metastasis-free survival (DMFS), and the disease-free survival (DFS) rates were 92.7%, 97.0%, 84.0%, and 75.9%, respectively, for the IMRT group, and 86.8%, 95.5%, 82.6%, and 71.4%, respectively, for the 2D-CRT group. In stage T1 patients, improvement of LRFS in the IMRT group was even significantly higher than in the 2D-CRT group (100% vs. 94.4%; p = 0.016). A trend of improvement of DFS was observed in the IMRT group compared with the 2D-CRT group but without reaching statistical significance. NRFS and DMFS rates were similar in the two groups. A greater improvement of treatment results with IMRT than with 2D-CRT was demonstrated primarily by achieving a higher local tumor control rate in NPC patients, especially in the early T stage patients. The goal of better control of both local failure in advanced, nonmetastatic NPC patients and of distant failure should be addressed in future studies. Copyright © 2011 Elsevier Inc. All rights reserved.
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            Phase III study of concurrent chemoradiotherapy versus radiotherapy alone for advanced nasopharyngeal carcinoma: positive effect on overall and progression-free survival.

            Nasopharyngeal carcinoma (NPC) is a radiosensitive and chemosensitive tumor. This randomized phase III trial compared concurrent chemoradiotherapy (CCRT) versus radiotherapy (RT) alone in patients with advanced NPC. From December 1993 to April 1999, 284 patients with 1992 American Joint Committee on Cancer stage III to IV (M0) NPC were randomly allocated into two arms. Similar dosage and fractionation of RT was administered in both arms. The investigational arm received two cycles of concurrent chemotherapy with cisplatin 20 mg/m(2)/d plus fluorouracil 400 mg/m(2)/d by 96-hour continuous infusion during the weeks 1 and 5 of RT. Survival analysis was estimated by the Kaplan-Meier method and compared by the log-rank test. Baseline patient characteristics were comparable in both arms. After a median follow-up of 65 months, 26.2% (37 of 141) and 46.2% (66 of 143) of patients developed tumor relapse in the CCRT and RT-alone groups, respectively. The 5-year overall survival rates were 72.3% for the CCRT arm and 54.2% for the RT-only arm (P =.0022). The 5-year progression-free survival rates were 71.6% for the CCRT group compared with 53.0% for the RT-only group (P =.0012). Although significantly more toxicity was noted in the CCRT arm, including leukopenia and emesis, compliance with the combined treatment was good. The second cycle of concurrent chemotherapy was refused by nine patients and was delayed for > or = 1 week for another nine patients. There were no treatment-related deaths in either arm. We conclude that CCRT is superior to RT alone for patients with advanced NPC in endemic areas.
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              Randomized trial of radiotherapy versus concurrent chemoradiotherapy followed by adjuvant chemotherapy in patients with American Joint Committee on Cancer/International Union against cancer stage III and IV nasopharyngeal cancer of the endemic variety.

              The Intergroup 00-99 Trial for nasopharyngeal cancer (NPC) showed a benefit of adding chemotherapy to radiotherapy. However, there were controversies regarding the applicability of the results to patients in endemic regions. This study aims to confirm the findings of the 00-99 Trial and its applicability to patients with endemic NPC. Between September 1997 and May 2003, 221 patients were randomly assigned to receive radiotherapy (RT) alone (n = 110) or chemoradiotherapy (CRT; n = 111). Patients in both arms received 70 Gy in 7 weeks using standard RT portals and techniques. Patients on CRT received concurrent cisplatin (25 mg/m2 on days 1 to 4) on weeks 1, 4, and 7 of RT and adjuvant cisplatin (20 mg/m2 on days 1 to 4) and fluorouracil (1,000 mg/m2 on days 1 to 4) every 4 weeks (weeks 11, 15, and 19) for three cycles after completion of RT. All patients were analyzed by intent-to-treat analysis. The median follow-up time was 3.2 years. Distant metastasis occurred in 38 patients on RT alone and 18 patients on CRT. The difference in 2-year cumulative incidence was 17% (95% CI, 14% to 20%; P = .0029). The hazard ratio (HR) for disease-free survival was 0.57 (95% CI, 0.38 to 0.87; P = .0093). The 2- and 3-year overall survival (OS) rates were 78% and 85% and 65% and 80% for RT alone and CRT, respectively. The HR for OS was 0.51 (95% CI, 0.31 to 0.81; P = .0061). This report confirms the findings of the Intergroup 00-99 Trial and demonstrates its applicability to endemic NPC. This study also confirms that chemotherapy improves the distant metastasis control rate in NPC.
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                Author and article information

                Contributors
                yaojj@sysucc.org.cn
                522157666@qq.com
                zhangfan@sysucc.org.cn
                zhangwj35@mail2.sysu.edu.cn
                zhougq@sysucc.org.cn
                tangll@sysucc.org.cn
                maoyp@sysucc.org.cn
                chenlei@sysucc.org.cn
                majun2@mail.sysu.edu.cn
                +86-20-87342253 , sunying@sysucc.org.cn
                Journal
                Chin J Cancer
                Chin J Cancer
                Chinese Journal of Cancer
                BioMed Central (London )
                1000-467X
                1944-446X
                6 March 2017
                6 March 2017
                2017
                : 36
                : 26
                Affiliations
                [1 ]ISNI 0000 0001 2360 039X, GRID grid.12981.33, Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, , Sun Yat-sen University Cancer Center, ; 651 Dongfeng Road East, Guangzhou, 510060 Guangdong P. R. China
                [2 ]GRID grid.452859.7, Department of Radiation Oncology, , The Fifth Affiliated Hospital of Sun Yat-sen University, ; Zhuhai, 519001 Guangdong P. R. China
                [3 ]ISNI 0000 0001 2360 039X, GRID grid.12981.33, Department of Radiation Oncology, Sun Yat-sen Memorial Hospital, , Sun Yat-sen University, ; Guangzhou, 510120 Guangdong P. R. China
                [4 ]ISNI 0000 0001 2360 039X, GRID grid.12981.33, Department of Medical Statistics and Epidemiology & Health Information Research Center & Guangdong Key Laboratory of Medicine, School of Public Health, , Sun Yat-sen University, ; Guangzhou, 510080 Guangdong P. R. China
                Article
                195
                10.1186/s40880-017-0195-6
                5338080
                28264724
                d8904bea-a69b-4f23-b945-e7818e06a1e9
                © The Author(s) 2017

                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
                : 6 March 2016
                : 21 June 2016
                Funding
                Funded by: the Science and Technology Project of Guangzhou City, China
                Award ID: No. 14570006
                Award Recipient :
                Funded by: the National Natural Science Foundation of China
                Award ID: No.81372409
                Award ID: No. 81402532
                Award Recipient :
                Funded by: the Sun Yat-sen University Clinical Research 5010 Program
                Award ID: No.2012011
                Award Recipient :
                Categories
                Original Article
                Custom metadata
                © The Author(s) 2017

                nasopharyngeal carcinoma,ascending-type,intensity-modulated radiotherapy,neoadjuvant chemotherapy,concurrent chemoradiotherapy

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