Dataset Information

Induction versus adjuvant chemotherapy combined with concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: a retrospective cohort study.

ABSTRACT:

Background

Currently available evidence favors the combination of chemotherapy with concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma (LANPC). However, the optimal timing for additional chemotherapy is unclear. This study was conducted to compare the efficacy and toxicity of induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) versus concurrent chemoradiotherapy plus adjuvant chemotherapy (CCRT+AC).

Methods

Two medical centers in China enrolled patients with LANPC (stage III-IVB) between January 2009 and May 2020. Through the use of propensity score matching (PSM), baseline characteristics were balanced. The primary endpoint was overall survival (OS), which was evaluated by the Kaplan-Meier method and log-rank test. Potential independent prognostic factors were identified using univariate and multivariate Cox proportional hazard analyses. Based on the chi-squared test, we compared the adverse events associated with treatment between the groups.

Results

After the implementation of PSM, 159 patients treated with IC+CCRT and 72 patients treated with CCRT+AC were eventually enrolled in this study. There was no significant difference between patients treated with IC+CCRT and CCRT+AC in terms of 3-year OS (94.7% versus 90.9%, p=0.816), progression-free survival (PFS) (91.2% versus 83.1%, p=0.588), locoregional recurrence-free survival (LRFS) (92.5% versus 81.8%, p=0.478), or distant metastasis-free survival (DMFS) (93.4% versus 88.2%, p=0.783). There was no prognostic significance of the treatment for OS, PFS, LRFS, or DMFS (all p > 0.05) in the univariate and multivariate analyses. Patients treated with CCRT+AC had a higher incidence of grade 3 to 4 leucopenia (p=0.001) and neutropenia (p=0.001) than those treated with IC+CCRT.

Conclusions

IC plus CCRT achieved comparable survival outcomes to CCRT plus AC and had a lower incidence of toxicity.

SUBMITTER: Mu X

PROVIDER: S-EPMC9467407 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Induction versus adjuvant chemotherapy combined with concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: a retrospective cohort study.

Mu Xiaoli X Liu Hongyan H Wu Juan J Chen Shi S Peng Xingchen X Wang Jingjing J Wei Zhigong Z He Ling L Liu Jiyan J Lu Zejun Z Su Yonglin Y

Aging 20220826 16

<h4>Background</h4>Currently available evidence favors the combination of chemotherapy with concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma (LANPC). However, the optimal timing for additional chemotherapy is unclear. This study was conducted to compare the efficacy and toxicity of induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) versus concurrent chemoradiotherapy plus adjuvant chemotherapy (CCRT+AC).<h4>Methods</h4>Two medical centers in China ...[more]

PMID: 36036759

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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:PurposeThis large population-based analysis aims to investigate whether the additional induction chemotherapy to concurrent chemoradiotherapy improved overall survival (OS) and disease-free survival (DFS) for locoregionally advanced nasopharyngeal carcinoma (LRANPC).Patients and methodsThe study group comprised 3,980 patients who were treated either with IC+CCRT (1,888 patients) or CCRT alone (2,092 patients) between January 1998 and June 2013. Survival outcomes were compared using Cox proportional hazards regression models with adjustments for confounding provided by propensity score methods. Primary outcome variables included OS and DFS.ResultsKaplan-Meier analysis showed that CCRT and IC+CCRT were of similar benefit to OS (P=0.099), whereas there was a marginal benefit of CCRT to DFS (P=0.063) in the overall cohort, which showed no differences between the two treatment regimens using multivariate Cox analysis and propensity score. Interestingly, for patients with 2D radiationtherapy (2DRT), CCRT had OS and DFS benefits for stage III, with 5-year and 10-year OS for CCRT vs IC+CCRT being 88% and 75% vs 81% and 67%, respectively (P=0.002); 5-year and 10-year DFS for CCRT vs IC+CCRT being 84% and 74% vs 76% and 66%, respectively (P=0.002). In contrast, IC + CCRT had OS and DFS benefits for stage IVa-b, with 5-year and 10-year OS for CCRT vs IC+CCRT being 71% and 55% vs 76% and 60%, respectively (P=0.037, HR=0.786); 5-year and 10-year DFS for CCRT vs IC+CCRT were 64% and 50% vs 69% and 58%, respectively (P=0.038, HR=0.801). No difference was found in intensity-modulated radiotherapy (IMRT) subgroup.ConclusionOur study indicates that CCRT and IC+CCRT may have similar OS and DFS benefits for overall LRANPC. Stage-specific chemoradiotherapy may be administered based on the greatest benefit of IC+CCRT for stage IVa-b patients and CCRT alone for stage III patients received 2DRT. The optimal chemotherapy pattern in combination with IMRT needs further investigation.Trial registration ClinicalTrials.gov ID: NCT02604472.

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:ImportanceInduction or adjuvant chemotherapy with concurrent chemoradiotherapy (CCRT) are first-line treatment options for treatment of locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Adjuvant platinum regimens are, however, poorly tolerated, highlighting the unmet need for an efficacious, tolerable adjuvant regimen.ObjectiveTo investigate the efficacy and safety of adjuvant capecitabine with CCRT for the treatment of patients with LA-NPC.Design, setting, and participantsThis open-label randomized clinical trial recruited patients from March 31, 2014, to July 27, 2018, at 3 institutions in China, with at least 3 years of follow-up. The data collection cutoff date was February 9, 2022. Eligibility included stage III-IVb nasopharyngeal carcinoma and at least 1 of the following: T3-4N2 or T1-4N3; plasma Epstein-Barr virus DNA titer higher than 20 000 copies/mL; primary gross tumor volume larger than 30.0 cm3; fluorodeoxyglucose F 18 positron emission tomography/computed tomography maximum standard uptake value of the primary gross tumor volume larger than 10.0; or multiple nodal metastases and any larger than 4.0 cm.InterventionsPatients were randomly assigned 1:1 to receive either capecitabine (1000 mg/m2 twice daily for 14 days every 3 weeks for 8 cycles) or observation following CCRT (100 mg/m2 cisplatin every 3 weeks for 2 to 3 cycles, depending on duration of radiotherapy).Main outcomes and measuresFailure-free survival in the intention-to-treat cohort was assessed using Kaplan-Meier survival curves compared with the log-rank test. Unstratified Cox proportional hazards regression models were used to estimate hazard ratios, with corresponding 95% CIs based on the Wald test.ResultsThere were 180 patients enrolled (median [IQR] age, 47 [40-55] years; 143 [79.4%] men). Among 90 patients in the capecitabine group, 76 (84.4%) had at least 2 high-risk factors; among 90 patients in the control group, 80 (88.9%) had at least 2 high-risk factors. All patients completed CCRT, except 1 patient in the capecitabine group who received 1 cycle of cisplatin. Of the 90 patients in the capecitabine group, 85 (94.4%) received capecitabine, with 71 (78.9%) completing 8 cycles. With a median (IQR) follow-up of 58.0 (49.5-80.1) months, 18 events were recorded in the capecitabine group vs 31 events in the control group. Failure-free survival was improved with adjuvant capecitabine (3 years, 83.3% vs 72.2%; 5 years, 78.5% vs 65.9%; hazard ratio, 0.53 [95% CI, 0.30-0.94]; P = .03). The incidence of grade 3 treatment-related adverse events (TRAEs) was higher in the capecitabine group than in the control group (54 of 90 patients [60.0%] vs 46 of 90 patients [51.1%]). Treatment-related adverse events included xerostomia (17 [18.9%] vs 9 [10.0%] patients), mucositis (21 [23.3%] vs 15 [16.7%] patients), and anorexia (8 [8.9%] vs 4 [4.4%] patients). The incidence of grade 3 delayed treatment-related adverse events was comparable in both groups (9 of 83 [10.8%] vs 7 of 81 [8.6%] patients).Conclusions and relevanceIn this randomized clinical trial, adjuvant capecitabine at the full dose following CCRT was well tolerated and improved failure-free survival among patients with LA-NPC and high-risk factors. Further investigations assessing optimal dose and duration are warranted.Trial registrationClinicalTrials.gov Identifier: NCT02143388.

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:PurposeThe 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.MethodsIn 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.ResultsBased 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/m2 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/m2 vs. 1-200 mg/m2 vs. >200 mg/m2]: 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.ConclusionLocoregional 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.

Dataset Information

Induction versus adjuvant chemotherapy combined with concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: a retrospective cohort study.

Background

Methods

Results

Conclusions

Publications

Induction versus adjuvant chemotherapy combined with concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: a retrospective cohort study.

Similar Datasets

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