Dataset Information

Significant benefits of adding neoadjuvant chemotherapy before concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: a meta-analysis of randomized controlled trials.

ABSTRACT:

Purpose

We did a meta-analysis to compare the efficacy and safety of neoadjuvant chemotherapy (NACT) followed by concurrent chemoradiotherapy (CCRT) versus CCRT with or without adjuvant chemotherapy (AC) for patients with locoregionally advanced nasopharyngeal carcinoma based on randomized controlled trials.

Methods

We searched PubMed, Embase, Web of Science, ClinicalTrials.gov, Chinese National Knowledge Infrastructure, and meeting proceedings of major relevant conferences to identify published and unpublished randomized controlled trials. Progression-free survival (PFS) was the primary endpoint.

Results

This meta-analysis included 9 randomized clinical trials with 2215 patients. NACT followed by CCRT significantly improved PFS (HR=0.68, 95% CI 0.56 - 0.81, P < 0.001) compared versus CCRT with or without AC, and no heterogeneity was observed (I2 = 0.0%, P = 0.975). NACT was associated with a significant improvement in overall survival (HR = 0.64, 95% CI 0.49 - 0.84, P = 0.001; I2 = 0.0%, P = 0.467) and distant failure-free survival (HR = 0.72, 95% CI 0.53 - 0.97, P = 0.031; I2 = 0.0%, P = 0.744). No significant benefit was shown by NACT for locoregional control. NACT with CCRT increased risks of grade 3 - 4 anemia, thrombocytopenia, leukopenia, and fatigue, compared versus CCRT with or without AC.

Conclusions

Our meta-analysis confirmed that the addition of NACT to CCRT significantly improved PFS and OS versus CCRT with or without AC for locoregionally advanced nasopharyngeal carcinoma. These results may alter the standard of care - CCRT with or without AC, for locoregionally advanced nasopharyngeal carcinoma.

SUBMITTER: Wang M

PROVIDER: S-EPMC5217024 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Publications

Significant benefits of adding neoadjuvant chemotherapy before concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: a meta-analysis of randomized controlled trials.

Wang Mengmeng M Tian Huimin H Li Gang G Ge Tingwen T Liu Yudi Y Cui Jiuwei J Han Fujun F

Oncotarget 20160701 30

<h4>Purpose</h4>We did a meta-analysis to compare the efficacy and safety of neoadjuvant chemotherapy (NACT) followed by concurrent chemoradiotherapy (CCRT) versus CCRT with or without adjuvant chemotherapy (AC) for patients with locoregionally advanced nasopharyngeal carcinoma based on randomized controlled trials.<h4>Methods</h4>We searched PubMed, Embase, Web of Science, ClinicalTrials.gov, Chinese National Knowledge Infrastructure, and meeting proceedings of major relevant conferences to ide ...[more]

PMID: 27356743

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Project description:BackgroundConcurrent chemoradiotherapy followed by adjuvant chemotherapy (CCRT-AC) is currently recommended as the standard treatment for locally advanced nasopharyngeal carcinoma (LA-NPC). Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy (NAC-CCRT) is an alternative strategy for decreasing tumor size and controlling micrometastases before main treatment. The aim of this study was to investigate and compare survival outcomes between LA-NPC patients treated with CCRT-AC and those treated with NAC-CCRT.MethodsThis retrospective cohort study included consecutive histologically confirmed LA-NPC patients that were treated with NAC-CCRT or CCRT-AC at Siriraj Hospital during the March 2010 to October 2014 study period. CCRT in both protocols consisted of 3-week cycles of cisplatin 100 mg/m2 with concurrent radiotherapy. Either NAC or AC consisted of 3-week cycles of cisplatin on day 1 and fluorouracil/leucovorin on days 1-4 for a maximum three cycles. The primary endpoint was 5-year overall survival (OS). Flexible parametric survival analysis was used, because the proportional hazards assumption of Cox regression was violated.ResultsOf the 266 LA-NPC patients that received treatment during the study period, 79 received NAC-CCRT and 187 received CCRT-AC. Median follow-up was 37 months. Significantly more patients with advanced clinical stage (stage IVA-IVB) received NAC-CCRT (86% in NAC-CCRT vs. 29% in CCRT-AC; p < 0.001). Compared to CCRT-AC in crude analysis, 3-year and 5-year OS of NAC-CCRT were 72% vs. 86% and 62% vs. 75% respectively (p = 0.059). Interestingly, the 3-year and 5-year post-estimation adjusted OS was 84% and 74% for NAC-CCRT and 81% and 70% for CCRT-AC, respectively (HR: 0.83, 95% confidence interval (CI): 0.45-1.56; p = 0.571). Also, adjusted analysis of distant-metastasis survival, NAC-CCRT showed HR was 0.79 (95% CI:0.37-1.72, p = 0.557). Conversely, adjusted analysis of locoregional relapse (LLR)-free survival revealed NAC-CCRT to have a significantly higher risk of LRR (HR: 2.18, 95% CI: 0.98-4.87; p = 0.057).ConclusionsThe results suggested that prognosis in the NAC-CCRT treated patients was not superior to that of the CCRT-AC treated individuals. In patients that receive neoadjuvant chemotherapy, locoregional relapse should be of concern. High-risk distant metastasis patients (N3 stage) that could achieve survival advantage from NAC-CCRT is an interesting and important topic for further study.

Project description:BackgroundStudies on several malignancies have suggested that the time to commencement of adjuvant chemotherapy (AC) is associated with survival outcomes. There have, however, been no relevant reports of nasopharyngeal carcinoma (NPC).Patients and methodsThis clinical study examined newly diagnosed patients between April 2017 and December 2020. The primary endpoint was progression-free survival (PFS). Inverse probability of treatment weighting was used to control for confounding factors. Cox models with restricted cubic splines, Kaplan-Meier method and log-rank tests were used to evaluate the relationship between AC timing and survival.ResultsA total of 551 patients were identified [median age, 45 years (interquartile range 36-52 years); 383 (69.5%) male]. Restricted cubic splines demonstrated that the timing of AC initiation had a U-shaped association with PFS. The risk of disease progression decreased within 37 days and subsequently increased. From 37 to 90 days, each additional 7-day delay conferred worse PFS of 1.32 months {hazard ratio (HR): 1.14 [95% confidence interval (CI) 1.01-1.28], P = 0.04}. The cut-off value of the receiver operating characteristic curve for initiation was 69.5 days. At a median follow-up of 48 months, the PFS was significantly better in patients initiated within 69.5 days [HR: 2.18 (95% CI 1.17-4.06), log-rank P = 0.009], with a higher 3-year rate [78.8% (95% CI 75.1% to 82.7%) versus 59.0% (95% CI 42.2% to 82.5%)] than beyond 69.5 days. Positive results were also observed in secondary endpoints. The initiation group was an independent prognostic factor [HR: 2.28 (95% CI 1.42-3.66), P < 0.001].ConclusionsThe optimal timing of AC initiation is ∼37 days after concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. A delay beyond 69.5 days is associated with compromised survival. Efforts should be made to address the reasons for delays and ensure the timely initiation of AC.

Project description:BackgroundNasopharyngeal carcinoma (NPC) is a prevalent form of head and neck cancer, particularly in specific regions with a higher incidence. The optimal treatment strategy for locally advanced NPC (stage III and IVA, LA-NPC) involves various combinations of induction chemotherapy (IC), concurrent chemoradiotherapy (CCRT), and adjuvant chemotherapy (AC), each with distinct advantages. This one institutional study aims to retrospectively analysis the efficacy and clinical outcomes of IC with CCRT (IC+CCRT), CCRT with AC (CCRT+AC), and the comprehensive approach of IC followed by CCRT and subsequently AC (IC+CCRT+AC) in the management of LA-NPC.Materials and methodsA total of 352 LA-NPC patients were included: 173 accepted IC+CCRT, 60 received CCRT+AC, and 119 underwent IC+CCRT+AC. The primary endpoints including overall survival (OS) and progression-free survival (PFS), were assessed using the Kaplan-Meier method and log-rank test.ResultsThe median follow-up was 61.2 months (1-216 months). There was no significant difference in 5-year OS and PFS between IC group and no IC group, extending the observation time to 90 months, the OS and PFS were significantly better in IC group than no IC group (OS: 76% vs. 70%,P<0.05; PFS: 76% vs. 71%, P<0.05). Patients with 1, 2, or 3 cycles of IC had higher 5-year OS and PFS than those with more than 3 cycles (1-4 cycles IC OS: 89% vs. 87% vs. 88% vs. 79%, P<0.05; 1-4 cycles IC PFS: 87% vs. 85% vs. 85% vs. 70%, P<0.05). NP regimen demonstrated higher OS and PFS than TP, PF, and TPF regimens (OS: 95% vs. 82% vs. 85% vs. 71%, P<0.05; PFS: 93% vs. 83% vs. 81% vs. 80%, P<0.05). The 5-year OS and PFS were significantly better in AC group than no AC group (OS: 82% vs. 72%, P<0.05; PFS: 81% vs. 69%, P<0.05). In the AC group, there was no differential effect of chemotherapy cycles and chemotherapy regimens on patients' OS and PFS. In the ThNh group, patients receiving IC+CCRT+AC had higher OS and PFS compared to those receiving IC+CCRT, with no significant difference in the rest (OS: 85% VS 66% P<0.05; PFS: 78% VS 62%, P<0.05).ConclusionCCRT combined with IC or AC could benefit LA-NPC patients. The IC+CCRT +AC regimen was most beneficial for NPC patients with later T and N stages.

Project description:BackgroundDespite the success of PD-1 blockade in recurrent/metastatic nasopharyngeal carcinoma (NPC), its effect for locoregionally advanced NPC (LANPC) remains unclear. This study aimed to evaluate the benefit of adding PD-1 blockade to the current standard treatment (gemcitabine and cisplatin IC <induction chemotherapy> plus cisplatin CCRT <concurrent chemoradiotherapy>) for LANPC patients.MethodsFrom January 2020 to November 2022, 347 patients with non-metastatic high-risk LANPC (stage III-IVA, excluding T3-4N0) were included. Of the 347 patients, 268 patients were treated with standard treatment (IC-CCRT), and 79 received PD-1 blockade plus IC-CCRT (PD-1 group). For the PD-1 group, PD-1 blockade was given intravenously once every 3 weeks for up to 9 cycles (3 induction and 6 adjuvant). The primary endpoint was disease-free survival (DFS) (i.e. freedom from local/regional/distant failure or death). The propensity score matching (PSM) with the ratio of 1:2 was performed to control confounding factors.ResultsAfter PSM analysis, 150 patients receiving standard treatment and 75 patients receiving additional PD-1 blockade remained in the current analysis. After three cycles of IC, the PD-1 group had significantly higher rates of complete response (defined as disappearance of all target lesions; 24% vs. 9%; P = 0.006) and complete biological response (defined as undetectable cell-free Epstein-Barr virus DNA, cfEBV DNA; 79% vs. 65%; P = 0.046) than that in the standard group. And the incidence of grade 3-4 toxicity during IC was 47% in the PD-1 group and 41% in the standard group, with no significant difference (P = 0.396). During follow-up period, additional PD-1 blockade to standard treatment improved 3-year DFS from 84 to 95%, with marginal statistical significance (HR, 0.28; 95%CI, 0.06-1.19; P = 0.064).ConclusionAdditiaonl PD-1 blockade to gemcitabine and cisplatin IC and adjuvant treatment results in significant improvement in tumor regression, cfEBV DNA clearance, superior DFS, and comparable toxicity profiles in high-risk LANPC patients.

Dataset Information

Significant benefits of adding neoadjuvant chemotherapy before concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: a meta-analysis of randomized controlled trials.

Purpose

Methods

Results

Conclusions

Publications

Significant benefits of adding neoadjuvant chemotherapy before concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: a meta-analysis of randomized controlled trials.

Similar Datasets

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