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    Individualized cumulative cisplatin dose for locoregionally-advanced nasopharyngeal carcinoma patients receiving induction chemotherapy and concurrent chemoradiotherapy. Wen Dan-Wan,Li Zhi-Xuan,Chen Fo-Ping,Lin Li,Peng Bin-Ying,Kou Jia,Zheng Wei-Hong,Yang Xing-Li,Xu Si-Si,Sun Ying,Zhou Guan-Qun Oral oncology OBJECTIVES:To screen subgroup potentially benefiting from cumulative cisplatin dose (CCD) ≥ 200 mg/m during concurrent chemoradiotherapy (CCRT) of patients with locoregionally-advanced nasopharyngeal carcinoma (LA-NPC) receiving induction chemotherapy (IC) and CCRT. MATERIALS AND METHODS:In total, 2 063 patients with non-disseminated LA-NPC diagnosed from 2009 to 2015 receiving IC plus CCRT were enrolled. Patients were restaged based on proposed stage groupings and risk groupings was established. After propensity score matching, survival outcomes were compared within different risk groupings with 200 mg/m CCD. Post-IC gross primary tumor (GTVp) and lymph node (GTVnd) volumes were calculated from planning computed tomography. The role of risk groupings and post-IC tumor volume to CCD was explored. RESULTS:Compared with the low-risk group, the high-risk group showed poor survival outcomes in terms of 5-year progression-free survival (PFS), overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS). CCD ≥ 200 mg/m improved survival in terms of 5-year PFS, OS and DMFS in the high-risk group but not in the low-risk group. High-risk patients with unfavorable response to IC benefited from CCD ≥ 200 mg/m with respect to PFS and DMFS; while those in low-risk group or with favorable response to IC didn't. CONCLUSIONS:Risk groupings was effective for risk stratification. Combining risk groupings and post-IC tumor volume is a simple and useful method to guide individualized CCD treatment of CCRT for patients with LA-NPC receiving IC and CCRT. CCD ≥ 200 mg/m may be indicated for high-risk patients with unfavorable response to IC. 10.1016/j.oraloncology.2020.104675
    Optimal cumulative cisplatin dose in nasopharyngeal carcinoma patients based on plasma Epstein-Barr virus DNA level after induction chemotherapy. Liu Sai-Lan,Sun Xue-Song,Liu Li-Ting,Sun Rui,Luo Dong-Hua,Chen Qiu-Yan,Lin Huan-Xin,Yuan Li,Tang Lin-Quan,Guo Ling,Mai Hai-Qiang Aging PURPOSE:This study aimed to elucidate the optimal cumulative cisplatin dose (CCD) for concurrent chemoradiotherapy (CCRT) according to the post-induction chemotherapy (IC) plasma Epstein-Barr virus (EBV) DNA level. RESULTS:EBV DNA was detected and undetected in 179 and 370 patients, respectively. Of the entire cohort, 73/549 (13.3%) patients received a total CCD ≥ 160 mg/m and 476/549 (86.7%) patients, <160 mg/m. CCD enhancement was not associated with a survival benefit in patients with undetected EBV DNA after IC. However, among patients with post-IC detectable EBV DNA, higher 3-year PFS and locoregional relapse-free survival (LRFS) rates were observed in those who received a CCD ≥ 160 mg/m. Multivariate analysis also showed CCD was an independent prognostic factor for PFS and LRFS in patients with post-IC detectable EBV DNA. CONCLUSIONS:CCD enhancement was not associated with a survival benefit in patients with undetected EBV DNA after IC. However, among patients with post-IC detectable EBV DNA, those receiving ≥160 mg/m CCD showed significantly improved 3-year PFS and LRFS. METHODS:NPC patients (549) treated with IC and CCRT were included. Prognosis was assessed using a multivariate Cox proportional hazards model. Furthermore, grade 1-4 toxicities were compared between different CCD groups. 10.18632/aging.102920
    Optimal cumulative dose of cisplatin for concurrent chemoradiotherapy among patients with non-metastatic nasopharyngeal carcinoma: a multicenter analysis in Thailand. Ngamphaiboon Nuttapong,Dechaphunkul Arunee,Setakornnukul Jiraporn,Dechaphunkul Tanadech,Jiratrachu Rungarun,Suktitipat Bhoom,Jiarpinitnun Chuleeporn,Pattaranutaporn Poompis,Danchaivijitr Pongwut BMC cancer BACKGROUND:Chemoradiotherapy (CRT) with high cumulative doses (CDs) of cisplatin has been considered the standard of care for non-metastatic nasopharyngeal carcinoma (NPC). However, given most patients' inability to tolerate high CDs due to cisplatin-related toxicities, the optimal CD of cisplatin during CRT remains undetermined. METHODS:Patients with non-metastatic NPC who received CRT with cisplatin between 2007 and 2017 were identified through the Thai head and neck cancer multicenter database and then categorized according to cisplatin CD (mg/m) received. All complications and cisplatin-related toxicities during CRT were recorded. RESULTS:We identified 779 non-metastatic NPC patients receiving low (≤150; n = 97), intermediate (151-250; n = 411), and high (> 250; n = 271) CDs of cisplatin. Low CD patients had significantly lower mean actual radiation dose (p < 0.001) and more radiotherapy delay (p = 0.010), while intermediate CD patients had the least hospitalization (p < 0.001). Overall, 39.3% of the patients experienced cisplatin-related toxicity, which was associated with poor overall survival (OS) (p = 0.001). Acute kidney injury was observed in 7% in all patients, which was highest among low CD patients (15.5%; p = 0.002). Intermediate CD patients had significantly longer median OS than the low and high groups (64 vs. 49.8 vs. 53.2, respectively; p = 0.015). Univariate, but not multivariate, analysis showed that CD of cisplatin was significantly associated with OS. CONCLUSION:CD of cisplatin during CRT was not an independent prognostic factor for OS. An intermediate CD induced minimal toxicity without compromising survival and should be considered the optimal CD. Nonetheless, a randomized phase 3 study evaluating the optimal CD of cisplatin is warranted. 10.1186/s12885-020-07024-8
    Optimal cumulative cisplatin dose in nasopharyngeal carcinoma patients based on induction chemotherapy response. Liu Sai-Lan,Sun Xue-Song,Yan Jin-Jie,Chen Qiu-Yan,Lin Huan-Xin,Wen Yue-Feng,Guo Shan-Shan,Liu Li-Ting,Xie Hao-Jun,Tang Qing-Nan,Liang Yu-Jing,Li Xiao-Yun,Lin Chao,Du Yu-Yun,Yang Zhen-Chong,Xiao Bei-Bei,Yang Jin-Hao,Tang Lin-Quan,Guo Ling,Mai Hai-Qiang Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology BACKGROUND AND PURPOSE:Nasopharyngeal carcinoma (NPC) patients can be separated into two risk subgroups according to tumor responses to induction chemotherapy (IC). We aimed to elucidate the optimal cumulative cisplatin dose (CCD) of concurrent chemoradiotherapy (CCRT) for different NPC patient subgroups. PARTICIPANTS AND METHODS:A total of 990 patients with incident NPC diagnosed between 2008 and 2017 treated with IC plus CCRT were included in our observational study. The clinicopathological features of patients with different tumor responses were compared using the Chi-square test or Fisher's exact test. Prognosis was assessed using a multivariate Cox proportional hazards model. In addition, acute and late toxicities were compared between different CCD groups. RESULTS:After IC, 761/990 (76.9%) patients had a complete tumor response (CR)/partial response (PR) and 229 (23.1%) had stable disease (SD)/disease progression (PD). An unsatisfactory tumor response (SD/PD) after IC correlated with poor clinical outcome (3-year PFS 61.4% vs. 83.2%, P < 0.001 and 3-year LRFS 80.9% vs. 94.5%, P < 0.001). Patients who achieved CR/PR after IC received a CCD >200 mg/m and showed higher 3-year PFS and DMFS rates than those receiving a CCD <100 mg/m (PFS: 85.4% vs. 77.9%, P = 0.045; DMFS: 89.4% vs. 77.9%, P = 0.015). Multivariate analysis also showed that CCD was an independent prognostic factor for PFS and DMFS in CR/PR subgroup. Moreover, the medium dose group showed similar efficacy as high dose group but was associated with fewer grade 1-4 acute toxicities. However, application of different CCD didn't result in significantly different survival outcomes in SD/PD subgroup. CONCLUSIONS:Tumor response to IC was an independent prognostic factor for patients with NPC. For the patients who achieved CR/PR after IC, patients receiving high CCD showed significantly improved 3-year PFS and DMFS compared with patients receiving low CCD. Balancing toxicity and efficacy, 200 mg/m seemed to be the optimal dose in the CR/PR groups. However, enhancement of CCD did not provide survival benefit for patients who achieved SD/PD after IC, and treatment options for these patients require further consideration. 10.1016/j.radonc.2019.04.020
    A comparison of cisplatin cumulative dose and cisplatin schedule in patients treated with concurrent chemo-radiotherapy in nasopharyngeal carcinoma. Gundog Mete,Basaran Hatice,Bozkurt Oktay,Eroglu Celalettin Brazilian journal of otorhinolaryngology INTRODUCTION:Three-weekly cisplatin dose is accepted for standard treatment for concurrent chemo-radiotherapy in nasopharyngeal carcinoma. However, different chemotherapy schedules are presented in the literature. OBJECTIVE:We intend to compare toxicity and outcomes of high dose 3-weekly cisplatin versus low dose weekly-cisplatin and cumulative dose of cisplatin in the patients with nasopharyngeal carcinoma. METHODS:98 patients were included in the study, between 2010 and 2018. Cumulative doses of cisplatin (≥200mg/m and <200mg/m) and different chemotherapy schedules (weekly and 3-weekly) were compared in terms of toxicity and survival. Besides prognostic factors including age, gender, T category, N category and radiotherapy technique were evaluated in uni-multivariate analysis. RESULTS:Median follow-up time 41.5 months (range: 2-93 months). Five year overall survival, local relapse-free survival, regional recurrence-free survival and distant metastasis-free survival rates were; 68.9% vs. 90.3% (p=0.11); 66.2% vs. 81.6% (p=0.15); 87.3% vs. 95.7% (p=0.18); 80.1% vs. 76.1% (p=0.74) for the group treated weekly and 3 weekly, respectively. There was no statistically significant difference between groups. Five year overall survival, local relapse-free survival, regional recurrence-free survival and distant metastasis-free survival rates were; 78.2% vs. 49.2% (p=0.003); 75.8% vs. 47.9% (p=0.055); 91% vs. 87.1% (p=0.46); 80% vs. 72.2% (p=0.46) for the group treated ≥200mg/m and <200mg/m cumulative dose cisplatin. There was statistically significant difference between groups for overall survival and there was close to being statistically significant difference between groups for local relapse-free survival. Age, gender, T category, N category, chemotherapy schedules were not associated with prognosis in the uni-variety analysis. Radiotherapy technique and cumulative dose of cisplatin was associated with prognosis in uni-variate analysis (HR=0.21; 95% CI: 0.071-0.628; p=0.005 and HR=0.29; 95% CI: 0.125-0.686; p=0.003, respectively). Only cumulative dose of cisplatin was found as an independent prognostic factor in multivariate analysis (HR=0.36; 95% CI: 0.146-0.912; p=0.03). When toxicities were evaluated, such as hematological toxicity, dermatitis, mucositis, nausea and vomiting, there were no statistically significant differences between cumulative dose of cisplatin groups (<200mg/m and ≥200mg/m) and chemotherapy schedules (3-weekly and weekly). But malnutrition was statistically significant higher in patients treated with 3-weekly cisplatin compared with patients treated with weekly cisplatin (p=0.001). CONCLUSION:A cisplatin dose with ≥200mg/m is an independent prognostic factor for overall survival. Chemotherapy schedules weekly and 3-weekly have similar outcomes and adverse effects. If patients achieve ≥200mg/m dose of cumulative cisplatin, weekly chemotherapy schedules may be used safely and effectively in nasopharyngeal carcinoma patients. 10.1016/j.bjorl.2019.04.008