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      Prognostic value of total tumor volume in patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy

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          Abstract

          Background

          Few studies have evaluated the prognostic value of total tumor volume (TTV), which reflects both the primary tumor volume and nodal tumor volume, in NPC. Furthermore, the relationship between TTV and survival remains unknown. The purpose of this study was to evaluate the prognostic value of TTV in patients with NPC treated with intensity-modulated radiation therapy (IMRT).

          Methods

          TTV was retrospectively assessed in 455 patients with newly diagnosed, non-metastatic NPC. All patients were treated using IMRT; 91.1% (288/316) of patients with stage III-IVb also received cisplatin-based chemotherapy. Receiver operating characteristic (ROC) curves were used to identify the optimal TTV cut-off point and examine the prognostic value of combined TTV with current clinical stage.

          Results

          Mean TTV was 11.1 cm 3 (range, 0.3–27.9 cm 3) in stage I, 22.5 cm 3 (1.3–92.4 cm 3) in stage II, 40.6 cm 3 in stage III (3.2–129.2 cm 3), and 77.5 cm 3 in stage IVa-b (7.1–284.1 cm 3). For all patients, the 4-year estimated FFS, OS, DMFS, and LRRFS rates for patients with a TTV ≤ 28 vs. > 28 cm 3 were 93 vs. 71.4% ( P < 0.001), 95.1 vs. 75.4% ( P < 0.001), 94.5 vs. 79.4% ( P < 0.001), and 96.2 vs. 88% ( P = 0.001). TTV was an independent prognostic factor for FFS, OS, DMFS and LRRFS in all patients. In stage III-IVb, 4-year estimated FFS, OS, DMFS, and LRRFS for a TTV ≤28 vs. >28 cm 3 were 88.9 vs. 70.5% ( P = 0.001), 96.2 vs. 72.7% ( P < 0.001), 91.2 vs. 78.3% ( P = 0.008), and 93.8 vs. 87.6% ( P = 0.063). TTV was an independent prognostic factor for FFS, OS and DMFS in stage III-IVb. Receiver operating characteristic (ROC) curve analysis curves revealed adding TTV to clinical stage had superior prognostic value for treatment failure compared to clinical stage alone ( P = 0.016).

          Conclusions

          TTV is an important prognosticator for treatment outcome and significantly improves the prognostic value of the current staging system for patients with NPC treated with IMRT.

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          Most cited references20

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          Management of Nasopharyngeal Carcinoma: Current Practice and Future Perspective.

          Nasopharyngeal carcinoma of the undifferentiated subtype is endemic to southern China, and patient prognosis has improved significantly over the past three decades because of advances in disease management, diagnostic imaging, radiotherapy technology, and broader application of systemic therapy. Despite the excellent local control with modern radiotherapy, distant failure remains a key challenge. Advances in molecular technology have helped to decipher the molecular pathogenesis of nasopharyngeal carcinoma as well as its etiologic association with the Epstein-Barr virus. This in turn has led to the discovery of novel biomarkers and drug targets, rendering this cancer site a current focus for new drug development. This article reviews and appraises the key literature on the current management of nasopharyngeal carcinoma and future directions in clinical research.
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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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              A prospective, randomized study comparing outcomes and toxicities of intensity-modulated radiotherapy vs. conventional two-dimensional radiotherapy for the treatment of nasopharyngeal carcinoma.

              To compare clinical outcomes and toxicities of two-dimensional conventional radiation therapy (2D-CRT) and intensity modulated radiation therapy (IMRT) for the treatment of nasopharyngeal carcinoma (NPC). Between July 2003 and October 2008, 616 patients with non-metastatic stage I to IVb NPC were prospectively randomized to receive 2D-CRT (n=310; mean age, 44.8±13.6 years) or IMRT (n=306; mean age, 46.7±12.5 years). Clinical outcomes and acute and late toxicities were determined and compared. The 2 groups were comparable with respect to all parameters of demographics and disease characteristics (all, p>0.05). Median follow-up was 42 months (range, 1-83 months). The 5-year actuarial local control rate was 90.5% in the IMRT group and 84.7% in the 2D-CRT group. The local control rates were 91% for stage T3 and 81.5% for stage T4 disease in the IMRT group and 80% and 62.2% in the 2D-CRT group, respectively. The 5-year actuarial nodal relapse-free survival (NRFS) rate was 92.4% in the IMRT and 92.9% in the 2D-CRT group (p>0.05). The NRFS was 93.9% for N2 disease in the IMRT group and 91.4% in the 2D-CRT group (p=0.02). The 5-year overall survival (OS) rate was 79.6% for the IMRT group and 67.1% for the 2D-CRT group (p=0.001). When stratified for stage, a significant difference was only noted for stage III disease. In terms of radiation-induced toxicities, patients in IMRT group had significantly lower radiation-induced toxicities than those in 2D-CRT group. IMRT provides improved local-recurrence free survival, especially in late-stage NPC patients and is associated with a lower incidence of toxicities. Copyright © 2012. Published by Elsevier Ireland Ltd.
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                Author and article information

                Contributors
                liangshb@sysucc.org.cn
                deartjj@163.com
                hxfeng@fsyyy.com
                yangxingl@sysucc.org.cn
                luomin@sysucc.org.cn
                fangxn@sysucc.org.cn
                ldsheng@fsyyy.com
                +86-20-87343505 , chenyong@sysucc.org.cn
                +86-20-87343163 , Fulw@mail.sysu.edu.cn
                Journal
                BMC Cancer
                BMC Cancer
                BMC Cancer
                BioMed Central (London )
                1471-2407
                28 July 2017
                28 July 2017
                2017
                : 17
                : 506
                Affiliations
                [1 ]ISNI 0000 0001 2360 039X, GRID grid.12981.33, State Key Laboratory of Oncology in South China, , Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, ; Guangzhou, 510060 China
                [2 ]ISNI 0000 0004 0604 5998, GRID grid.452881.2, Department of Radiation Oncology, Cancer Center, , First People’s Hospital of Foshan Affiliated to Sun Yat-sen University, ; Foshan, China
                [3 ]ISNI 0000 0004 0604 5998, GRID grid.452881.2, Department of Medical Statistics, , First People’s Hospital of Foshan Affiliated to Sun Yat-sen University, ; Foshan, China
                [4 ]GRID grid.412615.5, Department of Radiation Oncology, , The First Affiliated Hospital of Sun Yat-Sen University, ; Guangzhou, China
                Article
                3480
                10.1186/s12885-017-3480-5
                5534070
                28754109
                ea9ae57c-fe49-4d62-b43b-8bfcf9380cce
                © 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
                : 28 December 2016
                : 11 July 2017
                Funding
                Funded by: the National Natural Science Foundation of China
                Award ID: 1473233
                Award Recipient :
                Funded by: the Science Foundation from the Sci-Tech Office of Guangdong Province, China
                Award ID: 2016A020215083
                Award Recipient :
                Funded by: the Science Foundation from the Sci-Tech Office of Foshan City, China
                Award ID: 2015AB00294
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2017

                Oncology & Radiotherapy
                nasopharyngeal carcinoma,intensity-modulated radiotherapy,tumor volume,treatment failure,staging system

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