Prognostic Impact of Plasma Epstein-Barr Virus DNA in Patients with Nasopharyngeal Carcinoma Treated using Intensity-Modulated Radiation Therapy.
ABSTRACT: The prognostic value of plasma Epstein-Barr virus (EBV) DNA remains unknown in nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). We retrospectively reviewed medical records of 584 newly diagnosed patients with nonmetastatic and biopsy-proven NPC treated using IMRT. Plasma EBV DNA concentration was measured before therapy (pre-DNA) and within 1 month of completing therapy (post-DNA) using real-time quantitative polymerase chain reaction. Receiver operating characteristic (ROC) curves were generated to identify pre-DNA and post-DNA cut-off values. Prognostic value was assessed using a multivariate Cox proportional hazards model .Three-year disease-free survival (DFS), overall survival (OS), loco-regional relapse-free survival (LRRFS) and distant metastasis-free (DMFS) for pre-DNA >2010 vs.?2010 were 78.1% vs. 93.6% (P?0 vs.?=?0 were 49.9% vs. 88.5% (P?
Project description:The main aim of this study is to analyze the prognostic differences in nasopharyngeal carcinoma (NPC) patients who are positive and negative for Epstein-Barr virus (EBV).Of the 1106 patients, 248 (22.4%) had undetectable pre-treatment plasma EBV DNA levels. The total distant metastasis rate for EBV-negative group vs. EBV-positive group were 3.6% (9/248) vs. 15.0% (128/858) (P < 0.001). The estimated 4-year disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) for EBV-negative group vs. EBV-positive group were 88.9% vs. 76.9% (P < 0.001), 93.6% vs. 85.9% (P = 0.001), 96.7% vs. 84.8% (P < 0.001) and 94.1% vs. 90.0% (P = 0.1), respectively. Multivariate analysis revealed that the EBV status was an independent prognostic factor for DFS (HR, 1.813; 95% CI, 1.219-2.695; P = 0.003), OS (HR, 1.828; 95% CI, 1.075-3.107; P = 0.026) and DMFS (HR, 3.678; 95% CI, 1.859-7.277; P <0.001), and overall stage still remained the most important prognostic factor in patients with stage III-IVB NPC.Data on 1106 patients with non-metastatic, histologically proven advanced-stage (III-IVB) NPC who underwent intensity-modulated radiotherapy (IMRT) were retrospectively reviewed. Patient survival between different EBV status groups were compared.EBV status was an independent prognostic factor for patients with stage III-IVB NPC. Neoadjuvant chemotherapy (NCT) plus concurrent chemoradiotherapy (CCRT) should be better treatment regimen for EBV-positive patients since distant metastasis was the main failure pattern, and CCRT may be enough for EBV-negative patients.
Project description:Background: Plasma Epstein-Barr virus (EBV) DNA has been determined as a prognostic factor in adult nasopharyngeal carcinoma (NPC) patients. This study was designed to evaluate the prognostic value of plasma pretreatment EBV DNA in children and adolescent NPC patients receiving intensity-modulated radiotherapy (IMRT). Methods: Pretreatment EBV DNA was retrospectively assessed in 147 children with newly diagnosed, non-metastatic NPC. All patients were treated using IMRT. Receiver operating characteristic (ROC) curve was used to identify the optimal EBV DNA cutoff point. Prognostic value was examined using a multivariate Cox proportional hazards model. Results: The median follow-up for the entire cohort was 58 months (range, 10-119 months), and the 5-year survival rates for all patients were as follows: overall survival (OS), 88.7%; locoregional relapse-free survival, 95.2%; distant metastasis-free survival (DMFS), 84.8%; and disease-free survival (DFS), 81.5%. For ROC curve analysis, the optimal cutoff value of pretreatment EBV DNA load for DFS was 40,000 copies/mL. High plasma EBV DNA was significantly associated with poorer 5-year DMFS (70.6 vs. 89.1%, P = 0.003) and DFS (63.9 vs. 86.9%, P < 0.001). In multivariate analysis, high plasma EBV DNA was an independent predictor for DMFS and DFS. Conclusions: Pretreatment EBV DNA level was a powerful prognostic discriminator for DMFS and DFS in children and adolescent NPC patients treated with IMRT.
Project description:The objective of this study is to verify the prognostic value of pretreatment plasma Epstein-Barr viral deoxyribonucleic acid (pEBV DNA) levels in nasopharyngeal carcinoma (NPC) patients to complement TNM classification based on the application of the intensity-modulated radiotherapy (IMRT) technique.In total, 1467 patients staged at I-IVa-b (M0) and treated with IMRT were retrospectively analyzed at our cancer center from January 2007 to December 2010. Patient survival among different stages and EBV DNA levels were compared.Outcome analyses of different stages and EBV DNA levels revealed that patients in stages II-III with low EBV DNA levels had similar survival as that of patients in stages IVa-b with low EBV DNA (5-yr overall survival (OS), 94.7% vs. 92.9% (P = 0.141), progression failure-free survival (PFS), 87.2% vs. 89.0% (P = 0.685), distant metastasis failure-free survival (DMFS), 93.5% vs. 92.4% (P = 0.394) and locoregional failure-free survival (LRFS), 93.8% vs. 96.3% (P = 0.523)). Conversely, patients in stages II-III with high EBV DNA had better survival than patients in stages IVa-b with high EBV DNA (5-yr OS, 82.7% vs. 71.7% (P = 0.001), PFS, 70.7% vs. 66.2% (P = 0.047), DMFS, 79.6% vs. 74.8% (P = 0.066) and LRFS, 89.3% vs. 87.6% (P = 0.425)) but poorer survival than patients in stages IVa-b with low EBV DNA (5-yr OS, 82.7% vs. 92.9% (P = 0.025), PFS, 70.7% vs. 89.0, (P < 0.001), DMFS, 79.6% vs. 92.4%, (P = 0.001), LRFS, 89.3% vs. 96.3%, (P = 0.022)).pEBV DNA is a strong prognostic factor for patients with NPC when complemented with TNM staging in the era of IMRT application.
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.
Project description:PURPOSE:This study aimed to clarify the prognostic utility of high-sensitivity C-reactive protein (hs-CRP) in nasopharyngeal carcinoma (NPC) patients in the Intensity-Modulated Radiotherapy (IMRT) era. PATIENTS AND METHODS:In this observational study, 1,589 non-metastatic NPC patients treated with IMRT were recruited. Blood samples were collected before treatment for examination of hs-CRP levels. We evaluated the association of pretreatment hs-CRP levels with overall survival rate (OS), progression free survival rate (PFS), locoregional relapse free survival rate (LRFS) and distant metastasis free survival rate (DMFS). RESULTS:Baseline hs-CRP levels were correlated with sex, clinical stage, body mass index, smoking status, and EBV DNA level. Multivariate analysis showed that hs-CRP had significant association with OS (HR:1.723; 95%CI:1.238-2.398; p = 0.001), PFS (HR:1.621; 95%CI:1.273-2.064; p<0.001) and DMFS (HR:1.879; 95%CI:1.394-2.531; p<0.001). In subgroups such as advanced-stage group, low EBV DNA group and high EBV DNA group, elevated hs-CRP levels still predicted poor clinical outcomes. Furthermore, in patients with chronic HBV infection, decreased 4-year survival was observed in the cohort of high hs-CRP levels, with 87.4% vs. 94.9% (p = 0.023) for OS, 65.2% vs. 90.8% (p<0.001) for PFS, and 67.6% vs. 95.0% (p<0.001) for DMFS. A similar finding was observed for patients with cardiovascular disease, with 79.1% vs. 90.2% (p = 0.020) for PFS, and 71.4% vs. 97.6% (p = 0.002) for DMFS. CONCLUSION:Elevated serum hs-CRP levels were correlated with poor survival for NPC patients in the IMRT era, playing a complementary role to TNM stage and EBV DNA. In addition, elevated hs-CRP level was still an effective indicator for patients with chronic HBV infection and cardiovascular disease.
Project description:The prognostic value of the tumour response to induction chemotherapy (IC) for long-term survival outcomes after intensity-modulated radiation therapy in nasopharyngeal carcinoma (NPC) remains unknown. We retrospectively reviewed 1811 consecutive patients with newly diagnosed NPC treated using IMRT, and 399 eligible patients with pre- and post-induction chemotherapy magnetic resonance images were recruited. The clinicopathological features of patients with different tumour responses were compared using the Chi-square test or Fisher's exact test. Prognostic value was assessed using a multivariate Cox proportional hazards model. After IC, 101/399 (25.3%) patients had a complete tumour response overall (CR), 262 (65.7%) had a partial response (PR) and 36 (9.0%) had stable disease (SD). The 4-year disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) rates for CR vs. PR vs. SD were 90.0% vs. 79.0% vs. 58.2% (CR vs. PR: P1 = 0.007; CR vs. SD: P2 < 0.001; PR vs. SD: P3 = 0.004), 95.7% vs. 88.7% vs. 70.2% (P1 = 0.017, P2 < 0.001, P3 = 0.005), 92.0% vs. 87.4% vs. 74.3% (P1 = 0.162, P2 = 0.005, P3 = 0.029) and 95.9% vs. 88.8% vs. 81.8% (P1 = 0.024, P2 = 0.006, P3 = 0.268), respectively. Multivariate analysis identified that the tumour response to IC was an independent prognostic factor for DFS, OS and LRRFS.
Project description: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?<?0.001), OS (91.0%, 82.7%, 73.2%, p?<?0.001), DMFS (92.3%, 83.0%, 73.4%, p?<?0.001), and LRRFS (91.0%, 88.0%, 83.3%, p?<?0.001). The risk clusters acted as independent prognostic factors for all endpoints. Among the patients in the high-risk cluster, neoadjuvant chemotherapy combined with concurrent chemoradiotherapy (CCRT) significantly improved the patients 5-year PFS (66.4% versus 57.9%, p?=?0.014), OS (77.6% versus 68.6%; p?<?0.002), and DMFS (76.6% versus 70.6%; p?=?0.028) compared with those treated with CCRT. Conclusion:Our results could facilitate the development of risk-stratification and risk-adapted therapeutic strategies for patients with LA-NPC.
Project description:<b><i>Purpose</i></b> : To evaluate the prognostic value of magnetic resonance imaging (MRI)-detected tumor residue after intensity-modulated radiation therapy (IMRT) and its association with post-treatment plasma Epstein-Barr virus deoxyribonucleic acid (EBV DNA) in nasopharyngeal carcinoma (NPC). <b><i>Methods and materials</i></b> : A prospective database of patients with histologically-proven NPC was used to retrospectively analyze 664 cases. Pre- and post-treatment MRI scans were independently reviewed by two senior radiologists who were blinded to clinical findings. Factors significantly associated with MRI-detected tumor residue were identified and included in the following multivariate logistic regression model. Residual risk model were established. Receiver operating characteristic (ROC) identify the optimal cut-off risk score for tumor residue. <b><i>Results</i></b> : MRI-detected residual tumor at three months after IMRT was associated with poor prognosis. The 5-year survival rates for the non-residual and residual groups were: OS (93.8% vs. 76.6%, <i>P</i><0.001), PFS (84.7% vs. 67.9%, <i>P</i>=0.006), LRFS (93.4% vs. 80.4%, <i>P</i>=0.002), and DMFS (90.3% vs. 87.9%, <i>P</i>=0.305), respectively. Three-month post-treatment EBV DNA was significantly associated with tumor residue (<i>P</i><0.001). A residual risk score model was established, consisting of T and N categories and post-treatment EBV DNA. ROC identified 22.74 as the optimal cut-off risk score for tumor residue. High-risk score was independently associated with poor treatment outcomes. <b><i>Conclusions</i></b> : MRI-detected tumor residue was an independent adverse prognostic factor in NPC; and significantly associated with three-month post-treatment EBV DNA. As limited resources in some endemic areas prevent patients from undergoing routine post-treatment imaging, our study identifies a selection risk-model, providing a cost-effective reference for the selection of follow-up strategies and clinical decision-making.
Project description:Our objective was to examine whether adding induction chemotherapy to concurrent chemoradiotherapy improved survival in stage III nasopharyngeal carcinoma (NPC) patients, especially in low-risk patients at stage T3N0-1.We retrospectively analyzed 687 patients with stage T3N0-1 NPC treated with intensity-modulated radiation therapy (IMRT) plus concurrent chemotherapy (CC) with or without induction chemotherapy (IC). Propensity score matching (PSM) method was used to select 237 pairs of patients from two cohorts. Overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS) were assessed by using the Kaplan-Meier method, log-rank test, and Cox regression analysis.No significant survival differences were observed between IC plus CC and CC cohorts with similar 4-year OS (91.7% vs 92.6%, P=0.794), LRFS, (92.7% vs 96.8%, P=0.138), DMFS (93.5% vs 94.3%, P=0.582), and PFS (87.5% vs 91.1%, P=0.223). In a univariate analysis, lower Epstein-Barr virus deoxyribonucleic acid (EBV DNA; <4,000 copies/mL) significantly improved 4-year DMFS (95.5% vs 91.6%, P=0.044) compared with higher EBV DNA (≥4,000 copies/mL). No factors were associated with 4-year OS, LRFS, DMFS, and PFS in a multivariate analysis. IC plus CC group experienced higher rates of grade 3-4 leucopenia (P<0.001) and neutropenia (P<0.001).The addition of IC to CC in stage T3N0-1 NPC patients treated with IMRT did not significantly improve their survival. The IC group experienced higher rates of grade 3-4 hematological toxicities. Therefore, further investigation is required.
Project description:Little is known about combination of the circulating Epstein-Barr viral (EBV) DNA and tumor volume in prognosis of stage II nasopharyngeal carcinoma (NPC) patients in the intensity modulated radiotherapy (IMRT) era. We conducted this cohort study to evaluate the prognostic values of combining these two factors.By Kaplan-Meier, we compare the differences of survival curves between 385 patients with different EBV DNA or tumor volume levels, or with the combination of two biomarkers mentioned above.Gross tumor volume of cervical lymph nodes (GTVnd, p < 0.001) and total tumor volume (GTVtotal, p < 0.001) were both closely related to pretreatment EBV DNA, while gross tumor volume of nasopharynx (GTVnx, p=0.047) was weakly related to EBV DNA. EBV DNA was significantly correlated with progress-free survival (PFS, p=0.005), locoregional-free survival (LRFS, p=0.039), and distant metastasis-free survival (DMFS, p=0.017), while GTVtotal, regardless of GTVnx and GTVnd, had a significant correlation with PFS and LRFS. The p-values of GTVtotal for PFS and LRFS were 0.008 and 0.001, respectively. According to GTVtotal and pretreatment EBV DNA level, patients were divided into a low-risk group (EBV DNA 0 copy/mL, GTVtotal < 30 cm3; EBV DNA 0 copy/mL, GTVtotal ? 30 cm3; or EBV DNA > 0 copy/mL, GTVtotal < 30 cm3) and a high-risk group (EBV DNA > 0 copy/mL, GTVtotal ? 30 cm3). When patients in the low-risk group were compared with those in the high-risk group, 3-year PFS (p=0.003), LRFS (p=0.010), and DMFS (p=0.031) rates were statistically significant.Pretreatment plasma EBV DNA and tumor volume were both closely correlated with prognosis of stage II NPC patients in the IMRT era. Combination of EBV DNA and tumor volume can refine prognosis and indicate for clinical therapy.