{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T05:08:11Z","timestamp":1780463291748,"version":"3.54.1"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"\n Objective<\/jats:title>\n In the age of intensity-modulated radiotherapy (IMRT), the best cumulative cisplatin dose (CCD) for concurrent chemoradiotherapy for locally advanced nasopharyngeal cancer (LA-NPC) is still up for debate. In order to guide clinical dose decisions, this meta-analysis sought to examine the effects of various CCD on survival outcomes.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n A thorough search was conducted in PubMed, Embase, Web of Science, and Cochrane Library through December 2025. Randomized controlled trials or observational studies comparing CCD thresholds (\u2265200\u202fmg\/m\n 2<\/jats:sup>\n vs. &lt;200\u202fmg\/m\n 2<\/jats:sup>\n ) in IMRT-treated patients were included. Overall survival (OS) and progression-free survival (PFS) were the main results. Treatment-related toxicities and distant metastasis-free survival (DMFS) were secondary outcomes. Random-effects models were used to pool hazard ratios (HRs) with 95% confidence intervals (CIs) for survival outcomes. Relative risks (RRs) with 95% CIs were computed for toxicities (\u22652 trials). To investigate the robustness of the results, subgroup and sensitivity analyses were carried out.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Included were 10 retrospective cohort studies with 11,220 individuals. OS displayed a favorable trend approaching statistical significance (HR\u202f=\u202f0.65, 95% CI: 0.51\u20130.82). Moderate heterogeneity was observed (I\n 2<\/jats:sup>\n =\u202f50.4%,\n P<\/jats:italic>\n for heterogeneity\u202f=\u202f0.060). PFS showed no significant difference between dose groups (HR\u202f=\u202f0.81, 95% CI: 0.54\u20131.22), with substantial heterogeneity (I\n 2<\/jats:sup>\n =\u202f81.0%,\n P<\/jats:italic>\n for heterogeneity &lt;0.001). Higher CCD was associated with significantly improved DMFS (HR\u202f=\u202f0.54, 95% CI: 0.40\u20130.74), with moderate heterogeneity (I\n 2<\/jats:sup>\n =\u202f61.4%,\n P<\/jats:italic>\n for heterogeneity\u202f=\u202f0.011). Subgroup analysis revealed that the OS and DMFS benefit was consistent across treatment modalities, while the PFS effect differed significantly by treatment modality (\n p<\/jats:italic>\n \u202f&lt;\u202f0.001). For toxicity, the lower-dose group demonstrated significantly reduced risks of any-grade leukopenia (RR\u202f=\u202f0.91, 95% CI: 0.86\u20130.97,\n p<\/jats:italic>\n \u202f=\u202f0.002), any-grade ALT elevation (RR\u202f=\u202f0.69, 95% CI: 0.58\u20130.82,\n p<\/jats:italic>\n \u202f&lt;\u202f0.001), any-grade creatinine elevation (RR\u202f=\u202f0.73, 95% CI: 0.60\u20130.88,\n p<\/jats:italic>\n \u202f=\u202f0.001), any-grade hearing impairment (RR\u202f=\u202f0.81, 95% CI: 0.70\u20130.94,\n p<\/jats:italic>\n \u202f=\u202f0.005), and any-grade skin fibrosis (RR\u202f=\u202f0.77, 95% CI: 0.64\u20130.92,\n p<\/jats:italic>\n \u202f=\u202f0.004), suggesting a more favorable safety profile.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Higher CCD improves DMFS in LA-NPC patients with IMRT, with a near-significant OS trend. However, this survival benefit must be balanced against increased risks of certain acute and late toxicities associated with higher doses. These findings support risk-adapted dose intensification strategies while emphasizing individualized decision-making that integrates efficacy, toxicity, and patient characteristics.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fmed.2026.1829699","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T04:48:21Z","timestamp":1780462101000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparing the effectiveness of various cumulative doses of cisplatin in treating locally advanced nasopharyngeal cancer during the period of intensity-modulated radiotherapy: a meta-analysis"],"prefix":"10.3389","volume":"13","author":[{"given":"Tao","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Otolaryngology, The Third People\u2019s Hospital of Yibin","place":["Yibin, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyi","family":"Lin","sequence":"additional","affiliation":[{"name":"Jiangxi Medical College, Nanchang University","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunqiu","family":"Zheng","sequence":"additional","affiliation":[{"name":"Gaoxian Center for Disease Control and Prevention","place":["Yibin, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1114652","DOI":"10.3389\/fonc.2023.1114652","article-title":"Effect of radiotherapy interruption on nasopharyngeal cancer","volume":"13","author":"Zhao","year":"2023","journal-title":"Front Oncol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1186\/s12885-020-07024-8","article-title":"Optimal cumulative dose of cisplatin for concurrent chemoradiotherapy among patients with non-metastatic nasopharyngeal carcinoma: a multicenter analysis in Thailand","volume":"20","author":"Ngamphaiboon","year":"2020","journal-title":"BMC Cancer"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1522","DOI":"10.3389\/fonc.2019.01522","article-title":"Treating patients with locally advanced squamous cell carcinoma of the head and neck unsuitable to receive cisplatin-based therapy","volume":"9","author":"Porceddu","year":"2019","journal-title":"Front Oncol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"104666","DOI":"10.1016\/j.oraloncology.2020.104666","article-title":"Impact of cumulative cisplatin dose and adjuvant chemotherapy in locally-advanced nasopharyngeal carcinoma treated with definitive chemoradiotherapy","volume":"105","author":"Oliva","year":"2020","journal-title":"Oral Oncol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"957","DOI":"10.2147\/CMAR.S239729","article-title":"Management of Chemotherapy for stage II nasopharyngeal carcinoma in the intensity-modulated radiotherapy era: a review","volume":"12","author":"Wu","year":"2020","journal-title":"Cancer Manag Res"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"101324","DOI":"10.1016\/j.tranon.2021.101324","article-title":"Local control and failure patterns after intensity modulated radiotherapy with reduced target volume delineation after induction chemotherapy for patients with T4 nasopharyngeal carcinoma","volume":"16","author":"Kong","year":"2022","journal-title":"Transl Oncol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"101008","DOI":"10.1016\/j.jrras.2024.101008","article-title":"Short course irradiation in rectal cancer: dosimetry study comparing 3D conformal radiotherapy versus intensity-modulated radiotherapy versus volumetric modulated arc therapy","volume":"17","author":"Algaoud","year":"2024","journal-title":"J Radiat Res Appl Sci"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/j.adro.2019.11.003","article-title":"IMRT reduces acute toxicity in patients treated with preoperative chemoradiation for gastric Cancer","volume":"5","author":"Moningi","year":"2020","journal-title":"Adv Radiat Oncol"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"10527","DOI":"10.2147\/IJGM.S343644","article-title":"Correlation between higher cumulative dose of cisplatin for concurrent chemoradiation and acute kidney disease incidence among nasopharyngeal carcinoma patients: a comparative study","volume":"14","author":"Rachman","year":"2021","journal-title":"Int J Gen Med"},{"key":"ref10","volume-title":"The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses","author":"Wells","year":"2000"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1186\/s12885-015-1964-8","article-title":"The impact of the cumulative dose of cisplatin during concurrent chemoradiotherapy on the clinical outcomes of patients with advanced-stage nasopharyngeal carcinoma in an era of intensity-modulated radiotherapy","volume":"15","author":"Guo","year":"2015","journal-title":"BMC Cancer"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1111\/cas.13474","article-title":"Optimal cumulative cisplatin dose in nasopharyngeal carcinoma patients receiving additional induction chemotherapy","volume":"109","author":"Lv","year":"2018","journal-title":"Cancer Sci"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.radonc.2019.04.020","article-title":"Optimal cumulative cisplatin dose in nasopharyngeal carcinoma patients based on induction chemotherapy response","volume":"137","author":"Liu","year":"2019","journal-title":"Radiother Oncol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1016\/j.bjorl.2019.04.008","article-title":"A comparison of cisplatin cumulative dose and cisplatin schedule in patients treated with concurrent chemo-radiotherapy in nasopharyngeal carcinoma","volume":"86","author":"Gundog","year":"2020","journal-title":"Braz J Otorhinolaryngol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1758835920937424","DOI":"10.1177\/1758835920937424","article-title":"Treatment effects of cumulative cisplatin dose during radiotherapy following induction chemotherapy in nasopharyngeal carcinoma: propensity score analyses","volume":"12","author":"Peng","year":"2020","journal-title":"Ther Adv Med Oncol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"104675","DOI":"10.1016\/j.oraloncology.2020.104675","article-title":"Individualized cumulative cisplatin dose for locoregionally-advanced nasopharyngeal carcinoma patients receiving induction chemotherapy and concurrent chemoradiotherapy","volume":"107","author":"Wen","year":"2020","journal-title":"Oral Oncol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1186\/s12885-022-10237-8","article-title":"Cisplatin-based concurrent chemoradiotherapy improved the survival of locoregionally advanced nasopharyngeal carcinoma after induction chemotherapy by reducing early treatment failure","volume":"22","author":"Yang","year":"2022","journal-title":"BMC Cancer"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1002\/cam4.4477","article-title":"Efficiency of high cumulative cisplatin dose in high-and low-risk patients with locoregionally advanced nasopharyngeal carcinoma","volume":"11","author":"Jiang","year":"2022","journal-title":"Cancer Med"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"17588359241286222","DOI":"10.1177\/17588359241286222","article-title":"Individualised cumulative cisplatin dose for locoregionally advanced nasopharyngeal carcinoma patients based on induction chemotherapy response and tumour volume","volume":"16","author":"Lin","year":"2024","journal-title":"Ther Adv Med Oncol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"17588359231221343","DOI":"10.1177\/17588359231221343","article-title":"Combined pre-treatment and middle-treatment Epstein-Barr virus DNA load contributes to prognostication and treatment modification in nasopharyngeal carcinoma patients","volume":"16","author":"Lan","year":"2024","journal-title":"Ther Adv Med Oncol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1515\/hsz-2021-0321","article-title":"EGFR binding fc domain-drug conjugates: stable and highly potent cytotoxic molecules mediate selective cell killing","volume":"403","author":"Jager","year":"2022","journal-title":"Biol Chem"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.1016\/j.ijrobp.2020.11.052","article-title":"Localized delivery of cisplatin to cervical Cancer improves its therapeutic efficacy and minimizes its side effect profile","volume":"109","author":"Federico","year":"2021","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1007\/s13246-021-01082-3","article-title":"Evaluation of target autocrop function in nasopharyngeal carcinoma SIB IMRT plan","volume":"45","author":"Duan","year":"2022","journal-title":"Australas Phys Eng Sci Med"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1186\/s13014-023-02287-4","article-title":"Simultaneous dose distribution and fluence prediction for nasopharyngeal carcinoma IMRT","volume":"18","author":"Li","year":"2023","journal-title":"Radiat Oncol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"e31187","DOI":"10.1097\/MD.0000000000031187","article-title":"Efficacy and toxicity of three concurrent chemoradiotherapy regimens in treating nasopharyngeal carcinoma: comparison among cisplatin, nedaplatin, and lobaplatin","volume":"101","author":"Liang","year":"2022","journal-title":"Medicine"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"2350","DOI":"10.1200\/JCO.22.00980","article-title":"Results of phase III randomized trial for use of docetaxel as a radiosensitizer in patients with head and neck cancer, unsuitable for cisplatin-based chemoradiation","volume":"41","author":"Patil","year":"2023","journal-title":"J Clin Oncol"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1002\/hon.3165","article-title":"POLATUZUMAB and the progression-free survival (PFS) predicament: a comparative analysis of health technology assessment agency (HTA) reviews","volume":"41","author":"Cliff","year":"2023","journal-title":"Hematol Oncol"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"105092","DOI":"10.1016\/j.critrevonc.2025.105092","article-title":"Correlation of ORR and PFS with OS outcomes in phase III trials of immunotherapy in advanced NSCLC: systematic review and meta-analysis","volume":"218","author":"Salomone","year":"2026","journal-title":"Crit Rev Oncol Hematol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"255","DOI":"10.3389\/fonc.2020.00255","article-title":"Stratification of candidates for induction chemotherapy in stage III-IV nasopharyngeal carcinoma: a large cohort study based on a comprehensive prognostic model","volume":"10","author":"Sun","year":"2020","journal-title":"Front Oncol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"109721","DOI":"10.1016\/j.radonc.2023.109721","article-title":"Prognostic value of circulating Epstein-Barr virus DNA level post-induction chemotherapy for patients with nasopharyngeal carcinoma: a recursive partitioning risk stratification analysis","volume":"185","author":"Kong","year":"2023","journal-title":"Radiother Oncol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"107404","DOI":"10.1016\/j.oraloncology.2025.107404","article-title":"Optimal induction chemotherapy courses in nasopharyngeal carcinoma in the IMRT era: a recursive partitioning risk stratification analysis based on EBV DNA and AJCC staging","volume":"167","author":"Liang","year":"2025","journal-title":"Oral Oncol"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1007\/s10157-024-02490-x","article-title":"An integrated view of cisplatin-induced nephrotoxicity, hepatotoxicity, and cardiotoxicity: characteristics, common molecular mechanisms, and current clinical management","volume":"28","author":"Oliveira","year":"2024","journal-title":"Clin Exp Nephrol"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2024\/1511216","article-title":"The renin-angiotensin system involvement in cisplatin-induced nephrotoxicity: an overview of physiological and pathological mechanisms-a systematic review","volume":"2024","author":"Vakilian","year":"2024","journal-title":"Int J Nephrol"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16183237","article-title":"Optimizing hearing outcomes in nasopharyngeal Cancer survivors in the era of modern radiotherapy and systemic therapy","volume":"16","author":"Ho","year":"2024","journal-title":"Cancers (Basel)"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1563","DOI":"10.1016\/S1470-2045(24)00504-7","article-title":"Neoadjuvant and adjuvant toripalimab for locoregionally advanced nasopharyngeal carcinoma: a randomised, single-Centre, double-blind, placebo-controlled, phase 2 trial","volume":"25","author":"Liu","year":"2024","journal-title":"Lancet Oncol"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1001\/jama.2025.1132","article-title":"Adjuvant PD-1 blockade with Camrelizumab for nasopharyngeal carcinoma: the DIPPER randomized clinical trial","volume":"333","author":"Liang","year":"2025","journal-title":"JAMA"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1186\/s12916-025-03964-9","article-title":"Induction chemotherapy plus camrelizumab combined with concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma in non-endemic areas: a phase 2 clinical trial in North China","volume":"23","author":"Wang","year":"2025","journal-title":"BMC Med"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1829699\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T04:48:37Z","timestamp":1780462117000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1829699\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,3]]},"references-count":37,"alternative-id":["10.3389\/fmed.2026.1829699"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1829699","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,3]]},"article-number":"1829699"}}