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      Cisplatin-based concurrent chemoradiotherapy improved the survival of locoregionally advanced nasopharyngeal carcinoma after induction chemotherapy by reducing early treatment failure

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          Abstract

          Purpose

          The aims of this study focusing on Locoregionally advanced nasopharyngeal carcinoma (LANPC) were mainly two-fold: on the one hand, to establish a cut-off value to differentiate early and late failure based on prognosis after recurrence or metastasis; and on the other hand, to investigate the duration of concurrent cisplatin benefit over follow-up time. The results of our study have the potential to guide clinical practice and follow-up.

          Methods

          In total, 3123 patients with stage III-IVa NPC receiving Induction chemotherapy followed by concurrent cisplatin or not were analysed. The cut-off value of treatment failure was calculated using the minimum P-value approach. Random survival forest (RSF) model was to simulate the cumulative probabilities of treatment failure (locoregional recurrence and /or distant metastasis) over-time, as well as the monthly time-specific, event-occurring probabilities, for patients at different treatment groups.

          Results

          Based on subsequent prognosis, early locoregional failure (ELRF) should be defined as recurrence within 14 months ( P = 1.47 × 10 − 3), and early distant failure (EDF) should be defined as recurrence within 20 months ( P = 1.95 × 10 − 4). A cumulative cisplatin dose (CCD) > 200 mg/m 2 independently reduced the risk of EDF (hazard ratio, 0.351; 95% confidence interval (CI), 0.169–0.732; P = 0.005). Better failure-free survival (FFS) and overall survival (OS) were observed in concurrent chemotherapy settings ([0 mg/m 2 vs. 1-200 mg/m 2 vs. >200 mg/m 2]: FFS: 70.4% vs. 74.4% vs. 82.6%, all P < 0.03; OS: 79.5% vs. 83.8% vs. 90.8%, all P < 0.01). In the monthly analysis, treatment failure mainly occurred during the first 4 years, and the risk of distant failure in patients treated with concurrent chemotherapy never exceeded that of patients without concurrent chemotherapy.

          Conclusion

          Locoregional failure that developed within 14 months and/or distant failure within 20 months had poorer subsequent survival. Concurrent chemotherapy provides a significant FFS benefit, primarily by reducing EDF, translating into a long-term OS benefit.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12885-022-10237-8.

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          Most cited references36

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          Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

          This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.
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            Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma

            Platinum-based concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma. Additional gemcitabine and cisplatin induction chemotherapy has shown promising efficacy in phase 2 trials.
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              Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial.

              The value of adding cisplatin, fluorouracil, and docetaxel (TPF) induction chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is unclear. We aimed to compare TPF induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone in a suitably powered trial.
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                Author and article information

                Contributors
                sunying@sysucc.org.cn
                linli@sysucc.org.cn
                Journal
                BMC Cancer
                BMC Cancer
                BMC Cancer
                BioMed Central (London )
                1471-2407
                29 November 2022
                29 November 2022
                2022
                : 22
                : 1230
                Affiliations
                [1 ]GRID grid.12981.33, ISNI 0000 0001 2360 039X, Department of Radiation Oncology, The First Affiliated Hospital, , Sun Yat-sen University, ; 510060 Guangzhou, People’s Republic of China
                [2 ]GRID grid.488530.2, ISNI 0000 0004 1803 6191, Department of Molecular Diagnostics, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Collaborative Innovation Center for Cancer Medicine, , Sun Yat-sen University Cancer Center, ; 510060 Guangzhou, People’s Republic of China
                [3 ]GRID grid.488530.2, ISNI 0000 0004 1803 6191, Department of Anaesthesiology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Collaborative Innovation Center for Cancer Medicine, , Sun Yat-sen University Cancer Center, ; 510060 Guangzhou, People’s Republic of China
                [4 ]GRID grid.488530.2, ISNI 0000 0004 1803 6191, Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Collaborative Innovation Centre of Cancer Medicine, , Sun Yat-sen University Cancer Centre, ; 651 Dongfeng Road East, 510060 Guangzhou, People’s Republic of China
                Article
                10237
                10.1186/s12885-022-10237-8
                9706941
                36443685
                14dedcf0-e371-4851-85c9-9bf71cb1244c
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.

                History
                : 12 September 2021
                : 26 October 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 82002220
                Award ID: 12026601
                Award ID: 81902762
                Categories
                Research
                Custom metadata
                © The Author(s) 2022

                Oncology & Radiotherapy
                nasopharyngeal carcinoma,chemotherapy,cisplatin dose,failure,survival
                Oncology & Radiotherapy
                nasopharyngeal carcinoma, chemotherapy, cisplatin dose, failure, survival

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