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Risk stratification for nasopharyngeal carcinoma: a real-world study based on locoregional extension patterns and Epstein-Barr virus DNA load.

ABSTRACT: Aim:The present study aimed to evaluate the combined value of locoregional extension patterns (LEPs) and circulating cell-free Epstein-Barr virus (cf EBV) DNA for risk stratification of locoregionally advanced nasopharyngeal carcinoma (LA-NPC) to better guide therapeutic strategies. Methods:A total of 7227 cases of LA-NPC were reviewed retrospectively and classified into six groups according to their LEP (ascending, descending, or mixed type) and pre-treatment cf EBV-DNA load (? versus <4000 copy/ml). Using a supervised statistical clustering approach, patients in the six groups were clustered into low, intermediate, and high-risk clusters. Progression-free survival (PFS), overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) were calculated using the Kaplan-Meier method and differences were compared using the log-rank test. Results:Survival curves for the low, intermediate, and high-risk clusters were significantly different for all endpoints. The 5-year survival rate for the low, intermediate, and high-risk clusters, respectively, were: PFS (83.5%, 73.2%, 62.6%, p?

SUBMITTER: Zhang LL

PROVIDER: S-EPMC7294474 | BioStudies | 2020-01-01

REPOSITORIES: biostudies

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Comparing treatment outcomes of concurrent chemoradiotherapy with or without nimotuzumab in patients with locoregionally advanced nasopharyngeal carcinoma.

Project description:Purpose: The benefits of additional use of nimotuzumab (NTZ) in the treatment of locoregionally advanced nasopharyngeal carcinoma (LA-NPC) is largely unclear. We aim to compare LA-NPC treatment outcomes in patients that received CCRT with nimotuzumab (NTZ) to patients that received CCRT only. Materials and Methods: Between October 2009 and January 2012, 31 previously untreated and newly diagnosed LA-NPC patients were administered CCRT (3 cycles of 100 mg/m2 cisplatin every third week with intensity-modulated radiotherapy) plus NTZ according to an IRB-approved institutional research protocol. A well-balanced cohort of 62 patients who received CCRT alone was created by matching each patient who received CCRT plus NTZ via propensity-matched analysis in a 2:1 ratio. Results: Compared with CCRT only, CCRT plus NTZ was significantly associated with superior overall survival (5-year OS; 96.8% vs. 82.3%; P = 0.001), superior distant metastasis-free survival (5-year DMFS; 90.3% vs. 80.6%, P = 0.012) and superior progression-free survival (5-year PFS; 83.9% vs. 71.0%, P = 0.006). In multivariate analysis, the inclusion of NTZ to CCRT was confirmed to be a favorable factor for OS (HR, 0.31; 95% CI, 0.02-0.71; P = 0.027), DMFS (HR, 0.45; 95% CI, 0.13-0.77; P = 0.034), and PFS (HR, 0.38; 95% CI, 0.11-0.89; P = 0.041). In addition, no significant differences in hematology parameters, dermatitis, nausea, vomiting, xerostomia, nephrotoxicity or neurotoxicity were found between the two arms (all P > 0.05). Conclusion: The inclusion of NTZ to CCRT is more effective for long-term survival among LA-NPC patients than CCRT only.

2018-01-01 | S-EPMC6301798 | BioStudies

The role of concurrent chemotherapy for stage II nasopharyngeal carcinoma in the intensity-modulated radiotherapy era: A systematic review and meta-analysis.

Project description:OBJECTIVES:To compare clinical outcomes of concurrent chemoradiotherapy (CCRT) with those of radiotherapy alone for stage II nasopharyngeal carcinoma in the intensity-modulated radiotherapy (IMRT) era. MATERIALS AND METHODS:We comprehensively searched PubMed, Embase, and the Cochrane Library to identify eligible studies. Overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), locoregional recurrence-free survival (LRRFS) with hazard ratios (HRs), and toxicities with odd ratios (ORs) were analyzed. RESULTS:A total of seven studies met the criteria, with 1302 patients who were treated with IMRT alone or IMRT plus concurrent chemotherapy. No significant survival benefit was shown by CCRT regardless of OS (HR = 1.17, 95% CI 0.73-1.89, P = 0.508), PFS (HR = 0.76, 95% CI 0.38-1.50, P = 0.430), DMFS (HR = 0.89, 95% CI 0.33-2.41, P = 0.816), or LRRFS (HR = 1.03, 95% CI 0.95-1.12, P = 0.498). Additionally, CCRT notably increased the risk of acute grade 3-4 leukopenia (OR = 4.432, 95% CI 2.195-8.952, P < 0.001), compared to IMRT alone. CONCLUSION:Adding concurrent chemotherapy to IMRT led to no survival benefit and increased acute toxicity reactions for stage II nasopharyngeal carcinoma.

2018-01-01 | S-EPMC5864049 | BioStudies

Nomogram Predicting the Benefits of Adding Concurrent Chemotherapy to Intensity-Modulated Radiotherapy After Induction Chemotherapy in Stages II-IVb Nasopharyngeal Carcinoma.

Project description:Background:To compare the efficacy of induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) versus induction chemotherapy plus radiotherapy (IC+RT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Patients and Methods:One thousand three hundred twenty four patients with newly-diagnosed NPC treated with IC+CCRT or IC+RT were enrolled. Progression-free survival (PFS), distant metastasis-free survival (DMFS), overall survival (OS), locoregional relapse-free survival (LRFS), and acute toxicities during radiotherapy were compared using propensity score matching (PSM). A nomogram was developed to predict the 3- and 5-year PFS with or without concurrent chemotherapy (CC). Results:PSM assigned 387 patients to the IC+CCRT group and IC+RT group, respectively. After 3 years, no significant difference in PFS (84.7 vs. 87.5%, P = 0.080), OS (95.5 vs. 97.6%, P = 0.123), DMFS (89.7 vs. 92.8%, P = 0.134), or LRFS (94.0 vs. 94.1%, P = 0.557) was noted between the groups. Subgroup analysis indicated comparable survival outcomes in low-risk NPC patients (II-III with EBV DNA <4,000 copies/ml) between the groups, although IC+RT alone was associated with fewer acute toxicities. However, IC+CCRT was associated with significantly higher 3-year PFS, OS, DMFS, and LRFS rates, relative to IC+RT alone, in high-risk NPC patients (IVa-b or EBV DNA ?4,000 copies/ml). Multivariate analysis showed that T category, N category, EBV DNA level, and treatment group were predictive of PFS, and were hence incorporated into the nomogram. The nomogram predicted that the magnitude of benefit from CC could vary significantly. Conclusions:IC+RT had similar efficacy as IC+CCRT in low-risk NPC patients, but was associated with fewer acute toxicities. However, in high-risk patients, IC+CCRT was superior to IC+RT.

2020-01-01 | S-EPMC7681000 | BioStudies

Prognostic value of Diabetes in Patients with Nasopharyngeal Carcinoma Treated with Intensity-Modulated Radiation Therapy.

Project description:The prognostic value of diabetes remains unknown in nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). We retrospectively reviewed medical records of 1489 patients with non-metastatic, histologically-proven NPC treated using IMRT. 81/1489 (5.4%) patients were diabetic, 168/1489 (11.3%) were prediabetic, and 1240/1489 (83.3%) were normoglycemic. The 4-year disease-free survival (DFS), overall survival (OS), loco-regional relapse-free survival (LRRFS) and distant metastasis-free survival (DMFS) rates were 77.1% vs. 82.4% (P = 0.358), 85.8% vs. 91.0% (P = 0.123), 90.9% vs. 91.7% (P = 0.884), and 85.5% vs. 89.2% (P = 0.445) for diabetic vs. normoglycemic patients, and 82.4% vs. 82.4% (P = 0.993), 88.7% vs. 91.0% (P = 0.285), 90.6% vs. 91.7% (P = 0.832) and 91.5% vs. 89.2% (P = 0.594) for preidabetic vs. normoglycemic patients. Multivariate analysis did not established diabetes as poor prognostic factors in NPC patients treated with IMRT (P = 0.332 for DFS, P = 0.944 for OS, P = 0.977 for LRRFS, P = 0.157 for DMFS), however, triglycerides and low density lipoprotein cholesterol were independent prognostic factors. In conclusion, diabetes does not appear to be a prognostic factor in NPC patients treated with IMRT, and attention should be paid to hyperglycemia-associated hyperlipaemia.

2016-01-01 | S-EPMC4772023 | BioStudies

Induction chemotherapy followed by radiotherapy versus concurrent chemoradiotherapy in the treatment of different risk locoregionally advanced nasopharyngeal carcinoma.

Project description:Background:This study aimed to investigate the efficiency and toxicities of concurrent chemoradiotherapy (CCRT) and induction chemotherapy (IC) followed by radiotherapy (RT) in different risk locoregionally advanced nasopharyngeal carcinoma (NPC).Methods:A total of 1814 eligible patients with stage II–IVB disease treated with CCRT or IC plus RT were included. The overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS) were calculated using the Kaplan–Meier method, and the differences were compared using the log-rank test.Results:Nomograms were developed to predict OS, PFS and DMFS (C-index: 0.71, 0.70 and 0.71, respectively). Patients were then divided into three different risk groups based on the scores calculated by the nomogram for OS. In the low and intermediate-risk group, no significant survival differences were observed between patients treated with IC plus RT alone and CCRT (5-year OS, 97.3% versus 95.6%, p?=?0.642 and 87.6% versus 89.7%, p?=?0.381, respectively; PFS, 95.9% versus 95.6%, p?=?0.325 and 87.6% versus 89.0%, p?=?0.160, respectively; DMFS, 97.2% versus 94.8%, p?=?0.339 and 87.2% versus 89.3%, p?=?0.628, respectively). However, in the high-risk group, IC plus RT displayed an unfavorable 5-year OS (71.0% versus 77.2%, p?=?0.022) and PFS (69.4.0% versus 75.4%, p?=?0.019) compared with CCRT. A significantly higher incidence of grade 3 and 4 adverse events was documented in patients treated with CCRT than in those treated with IC plus RT in all risk groups (p?=?0.040).Conclusion:IC followed by RT represents an alternative treatment strategy to CCRT for patients with low and intermediate-risk NPC, but it is not recommended for patients with high-risk NPC.

2020-01-01 | S-EPMC7268167 | BioStudies

Induction chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in stage III-IVb nasopharyngeal carcinoma patients with Epstein-Barr virus DNA ?4000 copies/ml: a matched study.

Project description:The effects of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) in high-risk (stage III-IVb with EBV DNA?4000 copies/ml) nasopharyngeal carcinoma (NPC) patients are unclear.A total of 325 high-risk NPC patients treated with IC+CCRT or CCRT alone who were treated with intensity-modulated radiation therapy (IMRT) between March 2007 and March 2013 were included. For each patient in the IC+CCRT group, a matched pair in the CCRT group was matching for: gender, age, T stage, N stage, clinical stage and WHO (World Health Organization) type. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRFS).There were no significant differences in OS, PFS, DMFS, and LRFS between the IC+CCRT (148 patients) and CCRT (177 patients) groups. After matching, 103 paired patients were analyzed, and there were no differences between the IC+CCRT and CCRT groups regarding clinical outcomes. Based on the subgroup analysis of 156 very-high-risk patients (stage N2-3 with EBV DNA ?4000 copies/ml), the 5-year OS of the IC+CCRT and CCRT groups was 84.3% and 67.5% (P =0.033), respectively. Based on our multivariate analysis, the treatment group was significantly associated with OS (P=0.034; HR0.451, 95%CI 0.216-0.941).IC+CCRT did not improve the clinical outcomes of high-risk NPC patients compared to CCRT alone. However, in very-high-risk patients, IC+CCRT treatment led to increased OS compared to patients received CCRT treatment alone.

1000-01-01 | S-EPMC5045429 | BioStudies

Stratification of Candidates for Induction Chemotherapy in Stage III-IV Nasopharyngeal Carcinoma: A Large Cohort Study Based on a Comprehensive Prognostic Model.

Project description:Objective: To establish a prognostic index (PI) for patients with stage III-IV nasopharyngeal carcinoma (NPC) patients to personalize recommendations for induction chemotherapy (IC) before intensity-modulated radiotherapy (IMRT). Patients and Methods: Patients received concurrent chemoradiotherapy (CCRT) with or without IC. Factors used to construct the PI were selected by a multivariate analysis of progression-free survival (PFS), which was the primary endpoint (P < 0.05). Five variables were selected based on a backward procedure in a Cox proportional hazards model: gender, T stage, N stage, lactate dehydrogenase (LDH), and Epstein-Barr virus (EBV) DNA. The cutoff value for the PI was determined by the receiver operating characteristic curve analysis. Results: The present study involved 3,586 patients diagnosed with stage III-IV NPC. The cutoff value for PI was 0.8. The high-risk subgroup showed worse outcomes than did the low-risk subgroup on all endpoints: PFS, overall survival (OS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS). In the low-risk subgroup (PI <0.8), patients showed comparable survival outcomes on all clinical endpoints regardless of IC application, whereas in the high-risk subgroup (PI > 0.8), the addition of IC significantly improved PFS, OS, and DMFS, but not LRFS. In multivariate analyses, IC was a protective factor for PFS, OS, and DMFS in the high-risk subgroup, while it had no significant benefit in the low-risk subgroup. Conclusion: The proposed prognostic model effectively stratifies patients with stage III-IV NPC. High-risk patients are candidates for IC before CCRT, while low-risk patients are unlikely to benefit from it.

2020-01-01 | S-EPMC7059214 | BioStudies

Effectiveness of Cetuximab in Combination with Concurrent Chemoradiotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma: A 1:2 Propensity Score-matched Analysis.

Project description:Background: This study aimed to compare concurrent chemoradiotherapy (CCRT) plus cetuximab (C) with CCRT alone in locoregionally advanced nasopharyngeal carcinoma(NPC). Methods: A total of 682 locoregionally advanced NPC patients who had undergone chemoradiotherapy with or without cetuximab were included. Propensity score-matching method was used to match patients. Progression-free survival (PFS), overall survival (OS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were compared between the two treatment arms. Results: After matching, 225 patients were identified for the analysis. Compared to CCRT, CCRT plus C was associated with significantly improved 3-year PFS (83.7% vs 71.9%, P = 0.036), LRFS (98.6% vs 90.2%, P = 0.034) but not OS (91.4% vs 85.4%, P = 0.117). Among patients with T4 and/or N3 category, CCRT plus C significantly prolonged 3-year PFS (81.0% vs 61.4%, P = 0.022) and increased 3-year OS (88.0% vs 77.9%, P = 0.086). No significant differences were observed between CCRT plus C and CCRT alone groups with regard to 3-year PFS, OS, LRFS and DMFS rates in stage III patients. Acute oral and oropharyngeal mucositis during radiotherapy were more common in the CCRT plus C than that in CCRT, but late toxicities were comparable. Conclusions: This study reveals that patients with locoregionally advanced NPC could benefit from the addition of cetuximab to CCRT, and this therapeutic gain mainly originated from T4 and/or N3 subgroup although suffering more acute moderate to severe toxicities.

1000-01-01 | S-EPMC5950594 | BioStudies

Identifying optimal candidates for induction chemotherapy among stage II-IVa nasopharyngeal carcinoma based on pretreatment Epstein-Barr virus DNA and nodal maximal standard uptake values of [18 F]-fluorodeoxyglucose positron emission tomography.

Project description:Objective: This study aimed to select optimal candidates benefiting from the addition of induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in stage II-IVa nasopharyngeal carcinoma (NPC) based on Epstein-Barr virus (EBV) DNA and nodal maximal standardized uptake values (SUVmax-N) of [18 F]-fluorodeoxyglucose positron emission tomography. Patients and materials: A total of 679 patients diagnosed with stage II-IVa (except N0) NPC were retrospectively included in this study. Overall survival was the primary endpoint. Survival differences between different groups were compared using the log-rank test. The hazard ratio (HR) and 95% confidence interval (CI) were calculated using a multivariable Cox proportional hazards model. Results: Both high levels of EBV DNA (>1500 copies/mL) and SUVmax-N (>12.3) indicated worse survival conditions. All patients were divided into low- and high-risk groups based on these two biomarkers. The risk group was an independent prognostic factor in OS, progression-free survival (PFS), and distant metastasis-free survival (DMFS) (all p-values<0.05). The addition of IC to CCRT was associated with survival improvement in OS, PFS, and DMFS in high-risk patients, while no survival difference was found between CCRT and IC+CCRT in low-risk patients. Conclusions: Our study can help clinicians select stage II-IVa NPC patients who benefit from IC, which is important in guiding individual treatment.

2020-01-01 | S-EPMC7724500 | BioStudies

The Prognostic Value of Treatment-Related Lymphopenia in Nasopharyngeal Carcinoma Patients.

Project description:This study was conducted to evaluate the prognostic value of treatment-related lymphopenia in patients with nasopharyngeal carcinoma (NPC).A total of 413 consecutive stage II-IVb NPC patients treated with concurrent chemoradiotherapy (CCRT) were enrolled. The overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) were calculated with the Kaplan-Meier method, and differences were compared using the log-rank test.A minimum (mini)-absolute lymphocyte counts (ALC) of < 390 cells/?L or ALC after 3 months of CCRT (post3m-ALC) < 705 cells/?L was significantly associated with worse outcome than mini-ALC ? 390 cells/?L (OS, p=0.002; PFS, p=0.005; DMFS, p=0.004) or post3m-ALC ? 705 cells/?L (OS, p < 0.001; PFS, p < 0.001; DMFS, p=0.001). Patients with lymphopenia (mini-ALC < 390 cells/?L and post3m-ALC < 705 cells/?L) had a worse prognosis than those without lymphopenia (mini-ALC ? 390 cells/?L and post3m-ALC ? 705 cells/?L) (OS, p < 0.001; PFS, p < 0.001; DMFS, p < 0.001). Multivariate analysis revealed that post3m-ALC was an independent prognostic factor for OS (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.12 to 2.78; p=0.015), PFS (HR, 1.86; 95% CI, 1.23 to 2.82; p=0.003), and DMFS (HR, 1.87; 95% CI, 1.13 to 3.08; p=0.014). Multivariate analysis also revealed that patients with lymphopenia had a high risk of death (HR, 3.79; 95% CI, 1.75 to 8.19; p=0.001), disease progression (HR, 2.93; 95% CI, 1.59 to 5.41; p=0.001), and distant metastasis (HR, 3.89; 95% CI, 1.67 to 9.10; p=0.002). Multivariate analysis performed with time dependent Cox regression demonstrated ALC was an independent prognostic factor for OS (HR, 0.995; 95% CI, 0.991 to 0.999; p=0.025) and PFS (HR, 0.993; 95% CI, 0.988 to 0.998; p=0.006).Treatment-related lymphopenia was a poor prognostic factor in NPC patients.

1000-01-01 | S-EPMC5784643 | BioStudies

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