Plasma Epstein–Barr viral DNA load at midpoint of radiotherapy course predicts outcome in advanced-stage nasopharyngeal carcinoma

BackgroundTo test the hypothesis that prognostication of treatment outcome is feasible by biomarker response at midcourse of chemoradiotherapy (CRT)/radiotherapy (RT), with respect to the plasma load of Epstein–Barr viral (EBV) DNA in nasopharyngeal carcinoma (NPC).Patients and methodsOne hundred seven patients with stage IIB–IV NPC were prospectively studied. Plasma EBV DNA load was measured by quantitative PCR before therapy (pre-DNA), at completion of 4 weeks of CRT/RT (mid-DNA), and within 3 months of completion of therapy (post-DNA). The end points are post-DNA load, a recognized surrogate of survival, and clinical outcome.ResultsNinety-three percent of patients had detectable EBV DNA before therapy (median load = 972 copies/ml). EBV DNA became undetectable in 55 (51%) patients at the end of week 4 of therapy. Detectable mid-DNA was associated with worse clinical outcome (median follow-up time, 6.2 years), for distant failure [hazard ratio (HR) 12.02, 95% confidence interval (CI) 2.78–51.93; P < 0.0001], progression-free survival (PFS; HR 4.05, 95% CI 1.89–8.67, P < 0.0001), and overall survival (OS; HR 3.29, 95% CI 1.37–7.90, P = 0.0077). Seventy-four percent of all failures were associated with detectable mid-DNA, whereas 34% of all failures were associated with detectable post-DNA. Stratification by tumor stage (IIB, III, IV) has no significant prognostic effect.ConclusionsUnfavorable EBV DNA response at midcourse of RT/CRT is an adverse prognosticator for treatment outcome, is linked to majority of all failures, and discriminates outcome better than tumor stage. The data could provide a basis for trial design that addresses alteration of therapy intensity during the latter phase of CRT, and adjuvant therapy. Validation studies are awaited.     

Prognostic significance of a combined and controlled nutritional status score and EBV-DNA in patients with advanced nasopharyngeal carcinoma: a long-term follow-up study

Objective: Several studies have reported that the controlling nutritional status(CONUT) score is a prognostic predictor for survival among patients with different types of cancer. We assessed the prognostic value of changes in the CONUT score during treatment and the ΔCONUT-EBV DNA score in patients with advanced nasopharyngeal carcinoma(NPC).Methods: We retrospectively analyzed 433 patients with advanced NPC having no evidence of metastasis from January 2007 to June 2011; the patients underwent...     

The impact of plasma epstein–barr virus DNA and fibrinogen on nasopharyngeal carcinoma prognosis: an observational study

Background:

The impact of combining plasma fibrinogen levels with Epstein–Barr Virus DNA (EBV DNA) levels on the prognosis for patients with nasopharyngeal carcinoma (NPC) was evaluated.

Methods:

In this observational study, 2563 patients with non-metastatic NPC were evaluated for the effects of circulating plasma fibrinogen and EBV DNA levels on disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival (OS).

Results:

Compared with the bottom biomarker tertiles, TNM stage-adjusted hazard ratios (HR, 95% confidence intervals (CIs)) for predicting DFS in fibrinogen tertiles 2 to 3 were 1.26 (1.00 to 1.60) and 1.81 (1.45 to 2.26), respectively; HR for EBV DNA tertiles 2 to 3 were 1.49 (1.12 to 1.98) and 4.24 (3.27 to 5.49), respectively. After additional adjustment for established risk factors, both biomarkers were still associated (P for trend <0.001) with reduced DFS (HR: 1.79, 95% CI, 1.43 to 2.25 for top fibrinogen tertiles; HR: 4.04, 95% CI: 3.10 to 5.27 for top EBV DNA tertiles compared with the bottom tertiles). For patients with advanced-stage disease, those with high fibrinogen levels (⩾3.34 g l⁻¹) presented with worse DFS, regardless of EBV DNA ⩾4000 or <4000 copies ml⁻¹ subgroup. Similar findings were observed for DMFS and OS.

Conclusions:

Circulating fibrinogen and EBV DNA significantly correlate with NPC patients survival. Combined fibrinogen and EBV DNA data lead to improved prognostic prediction in advanced-stage disease.     

Post-treatment plasma EBV-DNA positivity predicts early relapse and poor prognosis for patients with extranodal NK/T cell lymphoma in the era of asparaginase

Circulating Epstein-Barr virus (EBV) DNA is a biomarker of EBV-associated malignancies. Its prognostic value in early stage NK/T-cell lymphoma (NKTCL) in the era of asparaginase was investigated. 68 patients were treated with a median of 4 cycles of asparaginase-based chemotherapy followed by a median of 54.6Gy (range 50–60Gy) radiation. The amount of EBV-DNA was prospectively measured in both pretreatment and post-treatment plasma samples by real-time quantitative PCR. At the end of treatment, complete response (CR) rate was 79.4%, and overall response rate (ORR) was 88.2%. Patients with negative pretreatment EBV-DNA had a higher CR rate (96.0% vs. 69.8%, p = 0.023). The 3-year progression-free survival (PFS) rate and overall survival (OS) rate was 71% and 83%, respectively. In multivariate survival analysis, post-treatment EBV-DNA positivity and treatment response (non-CR) were prognostic factors for both worse PFS and OS (p < 0.05). Local tumor invasion was also a prognostic factor for worse OS (p = 0.010). In patients with CR, post-treatment EBV-DNA positivity correlated with inferior PFS and OS (both p < 0.0001). In patients with positive pretreatment EBV-DNA, negative post-treatment EBV-DNA correlated with better PFS and OS (both p < 0.0001). These findings indicate that post-treatment EBV-DNA positivity can predict early relapse and poor prognosis for patients with early stage NKTCL in the era of asparaginase, and may be used as an indicator of minimal residual disease.     

Comparison of Epstein-Barr virus DNA level in plasma, peripheral blood cell and tumor tissue in nasopharyngeal carcinoma

BACKGROUND: The plasma Epstein-Barr virus DNA (EBV-DNA) level has been found to be an indicator for staging and prognosis of nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: The EBV-DNA level in plasma, peripheral blood cells (PBC) and neoplastic tissues was quantitatively analyzed and potential associations with clinical parameters of NPC were investigated. RESULTS: The plasma EBV-DNA detecting rate and level in NPC (92%, 82,500 copies/ml) was significantly higher than that in NPC after treatment (19%, 0 copy/ml) and in controls (12%, 0 copy/ml) (p < 0.001); while there was no significance of the PBC EBV-DNA detecting rate and EBV-DNA load in NPC before (24%, 0 copy/actin) and after treatment (14%, 0 copy/actin), and in controls (16%, 0 copy/actin). The plasma EBV-DNA level was not correlated to the PBC EBV-DNA load in NPC before (p = 0.92) and after treatment (p = 0.267), and in controls (p = 0.735). The EBV-DNA level in NPC tumor (27.8 copies/actin) was significantly higher than that in nasopharyngitis and was positively correlated to the ratio of EBER1-positive cells on the NPC section (p = 0.001). The plasma EBV-DNA level was significantly increased in TNM stages I, II, III and IV NPC, whereas there was no significant difference of PBC EBV-DNA load in different stage NPC. CONCLUSION: Our results indicate that plasma EBV-DNA is a more sensitive and reliable biomarker than PBC EBV-DNA for diagnosis, staging and therapeutic effect evaluation at a molecular level in NPC clinical practice. Plasma EBV-DNA may derive from the cancer cells and PBC EBV-DNA from circulating mononuclear cells in NPC patients.     

Plasma Epstein-Barr Virus MicroRNA BART8-3p as a Diagnostic and Prognostic Biomarker in Nasopharyngeal Carcinoma

BackgroundNasopharyngeal carcinoma is an Epstein-Barr virus (EBV)-associated tumor that is highly common in southern China. Our previous sequencing data demonstrated that the EBV-encoded microRNA BART8-3p was most upregulated in nasopharyngeal carcinoma (NPC) and was closely associated with the metastasis of NPC. However, the values of plasma BART8-3p in NPC patients have not yet been well characterized.Material and MethodsWe quantified plasma BART8-3p expression by quantitative real-time PCR in 205 newly diagnosed NPC patients. Kaplan-Meier analysis was used to compare overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) between the groups.ResultsPlasma pretreatment BART8-3p was highly expressed in NPC patients compared with healthy controls. Pretreatment BART8-3p yielded a 92% predictive value for detecting NPC. Importantly, BART8-3p decreased dramatically after therapy relative to pretreatment levels. High levels of pretreatment or post-treatment BART8-3p were associated with worse OS, DMFS, and LRRFS. Multivariate analysis showed that high pretreatment or post-treatment BART8-3p was an independent unfavorable prognostic marker for OS (HR 3.82, 95% CI 1.77-8.24, P = .001 or HR 2.74, 95% CI 1.27-5.91, P = .010), DMFS (HR 2.82, 95% CI 1.36-5.85, P = .005 or HR 3.27, 95% CI 1.57-6.81, P = .002), and LRRFS (HR 1.94, 95% CI 1.12-3.35, P = .018 or HR 2.03, 95% CI 1.14-3.62, P = .016) in NPC. Subgroup analysis revealed that for patients with locally advanced NPC with high levels of pretreatment BART8-3p (n = 58), more cycles of chemotherapy (≥6 cycles) tended to prolong OS (P = .070). Over 50% (6/11) patients with high levels of post-treatment BART8-3p presented distant metastasis.ConclusionPlasma BART8-3p is a promising biomarker for the detection and prognosis of NPC.     

鼻咽癌患者血浆EBV-DNA检测的临床价值

目的 EB病毒与鼻咽癌的发生发展明确相关,多个研究显示血浆EBV-DNA对于鼻咽癌的诊断分期及预后判断有重要意义,因此对我院患者进行了血浆EBV-DNA的检测并分析其临床价值。方法 2013—2016年连续性鼻咽癌患者471例,分析其治疗前EBV-DNA水平与分期、肿瘤负荷的相关性,并对治疗前、治疗末EBV-DNA进行生存相关分析。结果 患者治疗前血浆EBV-DNA中位数137 copies/ml (0~494000),与T分期、N分期、M分期、总的临床分期、肿瘤负荷均有明显统计学相关性。生存分析显示治疗前血浆EBV-DNA拷贝数≤1300组比>1300组的患者有更好OS (P=0.007)、PFS (P=0.011)、DMFS (P=0.003)。治疗末血浆EBV-DNA不可检测到的患者有更好OS (P=0.016)、PFS (P=0.000)、DMFS (P=0.000)。Cox多因素分析T分期、治疗末是否可检测到EBV-DNA为OS (P=0.030、0.012)的预后因素,N分期(P=0.037、0.017)、放疗末是否可检测到EBV-DNA (P=0.006、0.001)为PFS及DMFS的预后因素。结论 鼻咽癌患者治疗前血浆EBV-DNA水平与分期及肿瘤负荷有明显相关性,治疗前EBV-DNA水平更高的患者可能治疗后的预后更差。治疗末血浆EBV-DNA是否可检测到对于OS、PFS、DMFS有较好的预测价值。     

Detection of Epstein-Barr virus DNA in the peripheral-blood cells of patients with nasopharyngeal carcinoma: relationship to distant metastasis and survival.

PURPOSE: Nasopharyngeal carcinoma (NPC) has been proved to be an Epstein-Barr virus (EBV)-associated cancer. By use of nested polymerase chain reactions (PCRs), we examined whether the presence of EBV DNA in the peripheral-blood cells (PBC) can serve as a prognostic indicator for NPC. PATIENTS AND METHODS: Peripheral blood from 124 patients with NPC who had no evidence of distant metastasis and 114 healthy volunteers with serologically positive findings for EBV infection was collected prospectively. Plasma and erythrocytes were separated. DNA was extracted from PBCs and analyzed by a nested PCR using primers specific to Epstein-Barr virus nuclear antigen 1 (EBNA-1). All patients were treated by radiotherapy with or without chemotherapy. Clinical parameters and status of EBNA-1 in PBCs were used for survival analysis using the Kaplan-Meier method and the Cox proportional hazards model. RESULTS: Positive rates of EBNA-1 DNA in PBCs of NPC patients and healthy volunteers are 71% and 14%, respectively (P =.001). No significant difference was observed with regard to the clinical characteristics of patients who were EBNA-1-positive (n = 88) and those who were EBNA-1-negative (n = 36). After a median follow-up period of 38 months (range, 24 to 56 months), 29 of 88 EBNA-1-positive patients and only one of 36 EBNA-1-negative patients developed distant metastases (P =.00015). Kaplan-Meier estimates of overall survival (P =.0010), metastasis-free survival (P =.0004), and progression-free survival (P =.0004) were significantly lower for the patients in the EBNA-1-positive group than for those in the EBNA-1-negative group. Multivariate Cox analysis confirmed the same results. CONCLUSION: The presence of EBNA-1 DNA in PBCs is a novel, important risk factor for patients with NPC that indicates a significantly higher risk of developing distant metastasis as well as a lower survival rate.     

Spontaneous remission of residual post-therapy plasma Epstein–Barr virus DNA and its prognostic implication in nasopharyngeal carcinoma: A large-scale,big-data intelligence platform-based analysis

Detectable post-therapy plasma Epstein–Barr virus (EBV) DNA predicts poor survival in non-metastatic nasopharyngeal carcinoma (NPC). However, some patients subsequently experience spontaneous remission of residual EBV DNA during follow-up and it was unclear whether these patients were still at high risk of disease failure. Using the NPC database from an established big-data intelligence platform, 3269 NPC patients who had the plasma EBV DNA load measured at the end of therapy (± 1 week) were identified. In total, 93.0% (3031/3269) and 7.0% (238/3269) of patients had undetectable and detectable (> 0 copy/ml) plasma EBV DNA at the end of therapy (EBV DNA_end), respectively. Detectable EBV DNA_end was a prognostic factor for poorer 3-year disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS), and loco-regional recurrence-free survival (LRRFS) in both univariate and multivariate analyses. Of 238 patients with residual EBV DNA_end, 192 underwent EBV DNA assay 3 months after and s pontaneous remission occurred in 72.4% (139/192). However, these patients still had poorer 3-year DFS (55.1% vs. 89.8%), OS (79.1% vs. 96.2%), DMFS (68.4% vs. 94.1%) and LRRFS (84.5% vs. 95.0%) than patients with undetectable EBV DNA_end (all p < 0.001). And patients with persistent detectable post-therapy EBV DNA had the worst outcomes. These results were confirmed in multivariate analysis. In conclusion, residual EBV DNA post therapy was a robust biomarker for NPC prognosis. Although residual post-therapy EBV DNA could spontaneous remit during follow-up, these patients were still at high risk of disease failure and such patients may benefit from adjuvant therapy.     

Comparison of the prognostic impact of serum anti-EBV antibody and plasma EBV DNA assays in nasopharyngeal carcinoma

PURPOSE: Nasopharyngeal carcinoma (NPC) has been proven as an Epstein-Barr virus (EBV)-associated cancer. Serum anti-EBV antibodies and plasma EBV DNA have been investigated as surrogate markers for NPC. A comparison of the prognostic impacts of both assays has never been reported. METHODS AND MATERIALS: Paired serum and plasma samples from 114 previously untreated NPC patients were collected and subjected to an immunofluorescence assay for immunoglobulin (Ig)A and IgG antibodies against the viral capsid antigen (VCA) and a real-time quantitative polymerase chain reaction assay for EBV DNA measurement. The effects of both assays on patient prognosis were thoroughly investigated. RESULTS: Relapsed patients had significantly higher pretreatment EBV DNA concentration than patients without relapse (p = 0.0006). No associations of VCA-IgA (p = 0.9669) or VCA-IgG (p = 0.6125) were observed between patients with and without relapse. The 4-year overall survival (60.3% vs. 93.1%, p < 0.0001) and relapse-free survival rates (54.4% vs. 77.9%, p = 0.0009) were significantly lower in patients with higher pretreatment EBV DNA load than in those with lower EBV DNA load. Patients with persistently detectable EBV DNA after treatment had significantly worse 4-year overall (30.8% vs. 84.6%, p < 0.0001) and relapse-free survival rates (15.4% vs. 74.0%, p < 0.0001) than those with undetectable EBV DNA. The VCA-IgA and VCA-IgG titer could not predict survivals (all p > 0.1). Cox multivariate analyses also showed the same results. CONCLUSION: Plasma EBV DNA is superior to serum EBV VCA antibodies in prognostic predictions for NPC.     

Effectiveness of Platinum-Based Treatment for Triple Negative Metastatic Breast Cancer: a Meta-Analysis

Background: Triple-negative breast cancer (TNBC) is a sub-group of breast cancers with a particularly poorprognosis. The results of studies investigating the role of platinum-based chemotherapy (PBC) in metastatic TNBC(mTNBC) have been conflicting. In this meta-analysis, our aim was to assess the effectiveness of PBCs for mTNBCs.Methods: The PubMed, Cochrane Controlled Trials Register Databases, and EBSCOhost databases were accessed.The English language was used as the search language and only human studies were included. The Newcastle–OttawaQuality Assessment Scale and the Jadad scoring system were used to evaluate the quality of the included randomizedcontrolled studies. Results: Seven studies and 1,571 patients were included in this meta-analysis. The pooled hazardratio (HR) for overall survival (OS), evaluated on the basis of six studies, showed the use of PBC regimes to be relatedto OS in mTNBCs (HR 0.620; 95% CI 0.513-0.749; p:<0.001). Four studies containing HR and abstract statisticsused for HR calculation were included in the meta-analysis for progression-free survival (PFS). The pooled HR againindicated a significant relation (HR, 0.628; 95% CI, 0.501-0.786; p:<0.001). Conclusions: In this meta-analysis, weconfirmed that PBC regimes provide OS and PFS advantages compared to non-PBC regimes. The use of PBC regimescould be a good choice in mTNBC patients for better quality of life and survival.     

Treatment of Metastatic Urothelial Carcinoma After Previous Cisplatin-based Chemotherapy for Localized Disease: A Retrospective Comparison of Different Chemotherapy Regimens

BackgroundOptimal chemotherapy for patients who received cisplatin for localized urothelial carcinoma (UC) and develop metastatic disease is unclear. We compared the efficacy of platinum-based (PBC) versus non–platinum-based (NPBC) first-line chemotherapy for metastasis.Patients and MethodsData were collected from the Retrospective International Study of Cancers of the Urothelial Tract (RISC), a database of 3024 patients from 28 international academic centers from 2005 to 2012. Patient inclusion criteria included: (1) predominant UC; (2) any primary tumor site; (3) cT2-4, cN0-N2, cM0; (4) prior receipt of perioperative/radiation cisplatin-containing chemotherapy; and (5) receipt of cytotoxic chemotherapy in the first-line metastatic setting. Multivariate Cox proportional hazards models were used to show progression-free survival (PFS) and overall survival (OS) from the first day of chemotherapy for metastatic disease to date of censor.ResultsEligibility criteria was met by 132 patients (n = 74 PBC; n = 58 NPBC). The median OS was 8.13 months (interquartile range, 4.87-16.64 months) and 8.77 months (interquartile range, 4.01-13.49 months) for PBC and NPBC, respectively. Neither OS (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.64-1.69; P = .87) nor PFS (HR, 0.86; 95% CI, 0.56-1.31; P = .48) differed for PBC versus NPBC. However, for patients who received chemotherapy more than a year after perioperative/radiation chemotherapy, OS was superior for PBC over NPBC (HR, 0.31; 95% CI, 0.10-0.92; P = .03).ConclusionsThere is no significant outcome difference between PBC and NPBC in patients with metastatic UC who previously received cisplatin-based chemotherapy for localized disease. However, if over a year has elapsed, return to PBC is associated with superior OS.     

A seven-Gene Signature assay improves prognostic risk stratification of perioperative chemotherapy treated gastroesophageal cancer patients from the MAGIC trial

BackgroundFollowing neoadjuvant chemotherapy for operable gastroesophageal cancer, lymph node metastasis is the only validated prognostic variable; however, within lymph node groups there is still heterogeneity with risk of relapse. We hypothesized that gene profiles from neoadjuvant chemotherapy treated resection specimens from gastroesophageal cancer patients can be used to define prognostic risk groups to identify patients at risk for relapse.Patients and methodsThe Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial (n = 202 with high quality RNA) samples treated with perioperative chemotherapy were profiled for a custom gastric cancer gene panel using the NanoString platform. Genes associated with overall survival (OS) were identified using penalized and standard Cox regression, followed by generation of risk scores and development of a NanoString biomarker assay to stratify patients into risk groups associated with OS. An independent dataset served as a validation cohort.ResultsRegression and clustering analysis of MAGIC patients defined a seven-Gene Signature and two risk groups with different OS [hazard ratio (HR) 5.1; P < 0.0001]. The median OS of high- and low-risk groups were 10.2 [95% confidence interval (CI) of 6.5 and 13.2 months] and 80.9 months (CI: 43.0 months and not assessable), respectively. Risk groups were independently prognostic of lymph node metastasis by multivariate analysis (HR 3.6 in node positive group, P = 0.02; HR 3.6 in high-risk group, P = 0.0002), and not prognostic in surgery only patients (n = 118; log rank P = 0.2). A validation cohort independently confirmed these findings.ConclusionsThese results suggest that gene-based risk groups can independently predict prognosis in gastroesophageal cancer patients treated with neoadjuvant chemotherapy. This signature and associated assay may help risk stratify these patients for post-surgery chemotherapy in future perioperative chemotherapy-based clinical trials.     

Factors affecting the outcome of patients with metastatic leiomyosarcoma treated with doxorubicin-containing chemotherapy

BackgroundTo determine whether pulmonary metastasectomy or the addition of ifosfamide/dacarbazine to a doxorubicin-containing regimen offers a survival benefit to adult patients with metastatic leiomyosarcoma.Patients and methodsWe retrospectively collected data from 147 patients treated with a doxorubicin-containing regimen from 1998 to 2008.ResultsProgression-free survival (PFS) was 6.5 months (range 1–141 months). We did not identify an independent prognostic factor for PFS. Planned dose of doxorubicin was the sole parameter improving PFS [hazard ratio (HR) = 0.13, P = 0.023]. Overall survival (OS) was 17 months (range 1–115 months). The sole identified prognostic factor for OS was the interval between initial diagnosis and metastatic relapse. After adjustment to this prognostic factor, metastasectomy improved OS (HR = 0.52, P = 0.012) and the addition of ifosfamide seemed to worsen OS (HR = 1.42, P = 0.028).ConclusionIn our analysis, combined regimens did not improve the outcome. Maintenance of the doxorubicin dose was associated with improved PFS. Metastasectomy favorably influenced OS.     

Combining plasma Epstein-Barr virus DNA and nodal maximal standard uptake values of 18F-fluoro-2-deoxy-D-glucose positron emission tomography improved prognostic stratification to predict distant metastasis for locoregionally advanced nasopharyngeal carcinoma

Background

This study aimed to evaluate the value of combining the nodal maximal standard uptake values (SUVmax) of ¹⁸ F-fluoro-2-deoxy-D-glucose positron emission tomography with Epstein-Barr virus DNA(EBV DNA) levels to predict distant metastasis for nasopharyngeal carcinoma (NPC) patients

Patients and Methods

Eight hundred seventy-four patients with stage III-IVa-b NPC were evaluated for the effects of combining SUVmax and EBV DNA levels on distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS).

Results

The optimal cutoff value was 6,220 copies/mL for EBV DNA and 7.5 for SUVmax-N. Patients with lower EBV DNA levels or SUVmax-N had a significantly better 3-year DMFS, DFS, and OS. Patients were divided into four groups based on EBV DNA and SUVmax-N, as follows: low EBV DNA and low SUVmax-N (LL), low EBV DNA and high SUVmax-N (LH), high EBV DNA and low SUVmax-N (HL), and high EBV DNA and high SUVmax-N (HH). There were significant differences between the four mentioned groups in 3-year DMFS: 95.7%, 92.2%, 92.3%, and 80.1%, respectively (P^trend < 0.001). When looking at the disease stage, the 3-year DMFS in group LL, LH, HL, HH were 94.2%, 92.9%, 95.0%, and 81.1%, respectively, in stage III patients (P^trend < 0.001) and 92.7%, 87.2%, 86.3%, and 77.0% in stage IVa–b patients (P^trend = 0.026).

Conclusion

Pretreatment EBV DNA and SUVmax of neck lymph nodes were independent prognostic factors for distant metastasis in NPC patients. Combining EBV DNA and SUVmax-N led to an improved risk stratification for distant metastasis in advanced-stage disease.     

Role of circulating tumor cells as prognostic marker in resected stage III colorectal cancer

This is the first study that seeks to establish the prognostic value of circulating tumor cell (CTC) (determined by CellSearch system) in patients with stage III CRC.Our results suggest that given the low number of CTC in patients with localized CRC and the particular pattern of metastatic dissemination in patients with CRC, it is likely that CTC does not have a prognostic role in this setting.BackgroundThe prognostic role of circulating tumor cells (CTC) in early colorectal cancer (CRC) has not been determined yet. We evaluated the potential prognostic value of CTC in stage III CRC patients.Patients and methodsProspective multicenter study of 519 patients with stage III CRC recruited between January 2009 and June 2010. CTC were enumerated with the CellSearch System after primary tumor resection and before the start of adjuvant therapy. A total of 472 patients were included in the analysis.ResultsCTC ≥1, ≥2, ≥3 and ≥5 were detected in 166 (35%), 93 (20%), 57 (12%) and 34 (7%) patients, respectively. Median follow-up was 40 months. In the overall population, CTC ≥1 (disease-free survival (DFS): HR 0.97,P = 0.85; overall survival (OS): HR 1.03,P = 0.89), ≥2 (DFS: HR 1.07,P = 0.76; OS: HR 1.02,P = 0.95), ≥3 (DFS: HR 0.96,P = 0.87; OS: HR 0.74,P = 0.41) and ≥5 (DFS: HR 0.72,P = 0.39; OS: HR 0.48,P = 0.21) were not associated with worse DFS and OS. No clinicopathological characteristics were significantly associated with the presence of CTC. In patients with disease relapse, the proportion with CTC ≥1 was not significantly different between those with single versus multiple metastatic locations (37.9% versus 31.4%,P = 0.761). In the multivariate analysis, CTC ≥1 was not an independent prognostic factor for DFS (HR 0.97,P = 0.87) and OS (HR 0.96,P = 0.89).ConclusionCTC detection was not associated with worse DFS and OS in patients with stage III CRC. Given the scarcity of CTC in these patients, it is likely that CTC determined by CellSearch system does not have a prognostic role in this setting. However, a longer follow-up is needed.     

Effect of latent membrane protein 1 expression on overall survival in Epstein-Barr virus-associated cancers: a literature-based meta-analysis

Latent membrane protein 1 (LMP1) is identified as the main transforming oncoprotein of Epstein-Barr virus (EBV). LMP1 is frequently expressed in a variety of EBV-associated cancers, including nasopharyngeal carcinoma (NPC), non-Hodgkin lymphoma (NHL), Hodgkin disease (HD), and gastric cancer (GC). However, due to conflicting results, the prognostic value of LMP1 expression on clinical outcomes in EBV-associated cancers remains unclear. We performed a meta-analysis on 32 studies with a total of 3752 patients to explore the association between LMP1 expression and overall survival (OS) in EBV-associated cancers. Overall, LMP1 expression was significantly associated with poorer OS (hazard ratio, HR = 1.51, 95% confidence interval, CI, 1.13–2.03), irrespective of cancer type. Further analyses showed that LMP1 expression correlated with poorer OS in NPC (HR = 2.48, 95% CI, 1.77–3.47) and NHL patients (HR = 1.83, 95% CI, 1.07–3.15), but not in HD patients (HR = 0.98, 95% CI, 0.60–1.62) or GC patients (HR = 0.70, 95% CI, 0.44–1.12). Subgroup analyses indicated that the age and geographical factors seemed to have an effect on the clinical outcomes of HD patients with positive LMP1 expression. In conclusion, LMP1 expression can be used as a prognostic biomarker in NPC, NHL, and certain HD patients. This data suggests that novel therapies targeting LMP1 may improve clinical outcomes for EBV-associated cancer patients.     

Plasma Epstein-Barr virus DNA and residual disease after radiotherapy for undifferentiated nasopharyngeal carcinoma

BACKGROUND: Epstein-Barr virus (EBV) DNA can be detected and quantified in the plasma of patients with EBV-related tumors, such as nasopharyngeal carcinoma (NPC). Although NPC at early stages can be cured by radical radiotherapy, there is a high recurrence rate in patients with advanced NPC. The pretreatment level of circulating EBV DNA is a prognostic factor for NPC, but the prognostic value of post-treatment EBV DNA has not been studied. We designed a prospective study in Hong Kong, China, to investigate the value of plasma EBV DNA as a prognostic factor for NPC. METHODS: One hundred seventy NPC patients, without metastatic disease at presentation, were treated with a uniform radiotherapy protocol. Circulating EBV DNA was measured by real-time quantitative polymerase chain reaction before treatment and 6-8 weeks after radiotherapy was completed. Risk ratios (RRs) were determined with a Cox regression model, and associations of various factors with progression-free and overall survival and recurrence rates were determined with a stepwise Cox proportional hazards model. All statistical tests were two-sided. RESULTS: Ninety-nine percent of patients achieved complete clinical remission. Levels of post-treatment EBV DNA dominated the effect of levels of pretreatment EBV DNA for progression-free survival. The RR for NPC recurrence was 11.9 (95% confidence interval [CI] = 5.53 to 25.43) for patients with higher post-treatment EBV DNA and 2.5 (95% CI = 1.14 to 5.70) for patients with higher pretreatment EBV DNA. Higher levels of post-treatment EBV DNA were statistically significantly associated with overall survival (P<.001; RR for NPC recurrence = 8.6, 95% CI = 3.69 to 19.97). The positive and negative predictive values for NPC recurrence for a higher level of post-treatment EBV DNA were 87% (95% CI = 58% to 98%) and 83% (95% CI = 76% to 89%), respectively. CONCLUSION: Levels of post-treatment plasma EBV DNA in patients with NPC appear to strongly predict progression-free and overall survival and to accurately reflect the post-treatment residual tumor load.     

To build a prognostic score model containing indispensible tumour markers for metastatic nasopharyngeal carcinoma in an epidemic area

Background and objectiveThe survival outcomes of patients with metastatic nasopharyngeal carcinoma (NPC) differ significantly between individuals. The aim of this study is to build a prognostic score model (PSM) incorporating circulating tumour markers for metastatic NPC in an epidemic area.MethodsSeven hundred and ninety-nine patients with disseminated NPC were analysed retrospectively. Univariate and multivariable analyses were conducted using the Cox proportion hazards model. Factors analysed included patients^, characteristics (gender, age group, performance status), circulating tumour-marker characteristics (Epstein–Barr virus (EBV) DNA level, EBV VCA-IgA level, lactate dehydrogenase (LDH) level, alkaline phosphatase (ALP) level), basic laboratory characteristics (leucocyte count, haemoglobin level, albumin level), and disease characteristics (presence of metastasis at presentation, disease-free interval, number of metastatic sites, specific metastatic sites). The PSM was built according to numerical score derived from the regression coefficients of each independent prognostic variable. The prognostic score of each patient was calculated by totalling up the scores of each independent variable.ResultsIndependent prognostic factors included performance status, age, haemoglobin level, LDH level, ALP level and EBV DNA level. Three prognostic groups based on PSM were obtained: low risk (total score = 0–4); intermediate risk (5–8); high risk (9–12). Median survivals of the three groups were 25.5, 15.1 and 7 months, respectively, (P < 0.001).ConclusionClinical and laboratory characteristics can help guide the prognostication of patients with metastatic NPC in epidemic areas.     

Prognostic value of pretreatment and recovery duration of cranial nerve palsy in nasopharyngeal carcinoma

ABSTRACT: BACKGROUND: The purpose of this study was to evaluate the prognostic value of cranial nerve (CN) palsy in nasopharyngeal carcinoma (NPC) patients. METHODS: A retrospective analysis was performed on CN involvement using medical records of 178 consecutive patients with histologically diagnosed, non-disseminated NPC. RESULTS: In 178 NPC patients with CN palsy, the 5-year survival rates were as follows: overall survival (OS), 61.0%; disease-specific survival (DSS), 69.6%; local relapse-free survival (LRFS), 75.2%; distant metastasis-free survival (DMFS), 73.4%; and disease-free survival (DFS), 55.3%. Significant differences were observed in the 5-year OS rates between patients with single and multiple CN palsy (69.8% vs. 54.3%; P = 0.033) and the OS rates between patients with different pretreatment durations (68.7% vs. 43.3%, P = 0.007). However, no significant differences were observed in OS, DSS, LRFS and DFS rates between patients with upper and lower CN palsy (P = 0.581, P = 0.792, P = 0.729 and P = 0.212, respectively). The results showed that recovery duration was an independent prognostic factor for OS (HR = 2.485; P < 0.001), DSS (HR = 2.065; P = 0.016), LRFS (HR = 3.051; P = 0.001) and DFS (HR = 2.440; P < 0.001). CONCLUSIONS: Recovery duration is an independent prognostic factor for NPC patients with CN palsy and is related to recurrence, which leads to poor survival. Recovery duration requires close surveillance and different treatment regimens.