Prognostic impact of family history in southern Chinese patients with undifferentiated nasopharyngeal carcinoma

Background:

Family history of cancer is associated with developing nasopharyngeal carcinoma (NPC); however, the impact of it on survival among established NPC patients remains unknown.

Methods:

We retrospectively analysed 1773 southern Chinese patients. Associations between a first-degree family history of NPC and overall survival (OS), locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS) were estimated by Cox regression.

Results:

Among 1773 patients, 207 (11.7%) reported a first-degree family history of NPC. Compared with patients without a family history, the adjusted hazard ratios among those with it were 0.60 (95% confidence interval (CI), 0.37–0.98; P=0.040) for OS, 0.52 (95% CI, 0.24–1.12; P=0.096) for LRFS and 0.51 (95% CI, 0.27–0.97; P=0.040) for DMFS. There were trends for improving OS, LRFS and DMFS with increasing number of affected relatives (P_trend: 0.050, 0.114 and 0.044, respectively). But no significant benefits of family history in second- or third-degree relatives were observed. In subgroup analysis, we observed the effects of family history with restriction to male patients and those of advanced stage and treated with conventional radiotherapy and addition of chemotherapy.

Conclusion:

A first-degree family history of NPC is associated with improved survival of patients.     

Serum apolipoprotein A-I is a novel prognostic indicator for non-metastatic nasopharyngeal carcinoma

Background

We investigated the value of pretreatment serum apolipoprotein A-I (ApoA-I) in complementing TNM staging in the prognosis of non-metastatic nasopharyngeal carcinoma (NPC).

Patients and methods

We retrospectively reviewed 1196 newly diagnosed patients with non-metastatic NPC. Disease-specific survival (DSS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS) rates were compared according to serum ApoA-I level. Multivariate analysis was performed to assess the prognostic value of serum ApoA-I.

Results

The 5-year DSS, DMFS, and LRFS rates for patients with elevated or decreased serum ApoA-I were 81.3% versus 69.3% (P < 0.001), 83.4% versus 67.4% (P < 0.001), and 80.9% versus 67.3% (P < 0.001), respectively. ApoA-I ≥ 1.025 g/L was an independent prognostic factor for superior DSS, DMFS, and LRFS in multivariate analysis. After stratification by clinical stage, serum ApoA-I remained a clinically and statistically significant predictor of prognosis.

Conclusion

Our data suggest that the level of ApoA-I at diagnosis is a novel independent prognostic marker that could complement clinical staging for risk definition in non-metastatic NPC.     

Risk factors for recurrence amongst high intermediate risk patients with endometrioid adenocarcinoma

Objective

To determine risk factors associated with recurrence in patients with high intermediate risk (HIR) endometrioid adenocarcinoma.

Methods

A retrospective analysis of patients with HIR endometrioid adenocarcinoma who underwent hysterectomy, bilateral salpingo-oophorectomy, with or without pelvic/para-aortic lymphadenectomy at the University of Pennsylvania between 1990 and 2009 was performed.

Results

A total of 103 women with HIR endometrial cancer were identified. Multivariable analysis revealed that ≥2/3 myometrial invasion (HR, 4.79; p=0.010) and grade 3 disease (HR, 3.04; p=0.045) were independently predictive of distant metastases. The 5-year distant metastases free survival (DMFS) for patients with neither or one of these risk factors was 89%, and the 5-year DMFS for patients with both risk factors was 48% (p<0.001).

Conclusion

Patients with both grade 3 disease and deep third myometrial invasion have a high risk of distant metastases. Identifying these patients may be important in rationally selecting patients for systemic therapy.     

Prognostic value of ABO blood group in southern Chinese patients with established nasopharyngeal carcinoma

Background:

ABO blood group is associated with aetiology of nasopharyngeal carcinoma (NPC); however, the effect of it on survival of patients diagnosed with NPC has not been explored.

Methods:

We retrospectively analysed two cohorts of southern Chinese patients with WHO histological type III: intensity-modulated radiotherapy (IMRT) cohort, 924 patients; and conventional radiotherapy (CRT) cohort, 1193 patients. Associations of ABO blood group with survival were estimated using Cox regression.

Results:

In IMRT cohort, we observed significant associations of blood type A with overall survival (OS) and distant metastasis-free survival (DMFS), compared with type O, after adjusting for prognostic factors. Compared with non-A blood types (B, AB, and O), type A patients had significantly lower OS and DMFS (adjusted hazard ratio (HR)=1.49, 95% CI 1.03–2.17, P=0.036; HR=1.68, 95% CI 1.13–2.51, P=0.011, respectively); similar results were obtained in CRT cohort. Subgroup analyses of the entire population showed that lower OS conferred by blood type A was not significantly modified by age, smoking status, drinking status, immunoglobulin A against Epstein–Barr virus viral capsid antigen (VCA-IgA) titre, or chemotherapy; however, lower OS was not observed in female patients or patients with early clinical stage disease.

Conclusion:

ABO blood group is associated with survival in NPC; patients with blood type A had significantly lower OS and DMFS than patients with non-A blood types.     

Prognostic Factors for Distant Metastasis in Patients with Locoregional Recurrence after Mastectomy

Purpose

The purpose of this study was to identify patients with high risk of distant metastasis (DM) after salvage treatment for postmastectomy locoregional recurrence (LRR).

Methods

We retrospectively reviewed 142 patients who received salvage radiotherapy with or without wide excision for isolated LRR after mastectomy between January 1999 and December 2012. Distant metastasis-free survival (DMFS) was estimated from the date of diagnosis of isolated LRR to the date of DM or last follow-up using the Kaplan-Meier method, and Cox regression analysis was performed to identify prognostic factors for DM.

Results

The median follow-up period was 54 months. The major failure pattern was DM (56%) and the 5-year DMFS was 43%. In multivariate analysis, initial N (iN) stage, recurrent N (rN) stage, and hormone receptor (HR) status were significant prognostic factors for DM (5-year DMFS: iN0 vs. iN1-3, 73% vs. 25%, p<0.001; rN0 vs. rN1-3, 61% vs. 29%, p<0.001; HR+ vs. HR-, 49% vs. 21%, p<0.001).

Conclusion

Patients with lymph node involvement and/or HR- specimens seem to experience more DM than patients with chest wall-only recurrence and HR+ specimens. Further studies are needed to investigate the role of chemotherapy in these patients.     

Propensity score matching analysis of cisplatin-based concurrent chemotherapy in low risk nasopharyngeal carcinoma in the intensity-modulated radiotherapy era

Background

Patients with stage II nasopharyngeal carcinoma were reported to benefit from adding cisplatin-based concurrent chemotherapy to two-dimensional conventional radiotherapy. But this benefit becomes uncertain in the intensity-modulated radiotherapy (IMRT) era, owing to its significant advantage.

Methods

We enrolled 661 low risk (T1N1M0, T2N0-1M0 or T3N0M0, the 2010 UICC/AJCC staging system) patients who underwent IMRT with or without concurrent chemotherapy. Particularly, patients with IMRT alone or IMRT plus cisplatin-based concurrent chemotherapy were equally matched using propensity-score matching method. Overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRFS) were assessed with Kaplan-Meier method, log-rank test and Cox regression.

Results

Among 661 patients, IMRT alone achieved parallel OS (P = 0.379), DMFS (P = 0.169) and LRFS (P = 0.849) to IMRT plus concurrent chemotherapy. In the propensity-matched cohort of 482 patients, similar survival were observed between both arms (4-years OS 97.4% vs 96.1%, P = 0.134; DMFS 96.5% vs 95.1%, P = 0.763; LRFS 93.8% vs 91.5%, P = 0.715). In multivariate analysis, cisplatin-based concurrent chemotherapy did not lower the risk of death, distant metastasis or locoregional relapse. And this association remained unchanged in subgroups by age, sex, histology and stage.

Conclusions

In this study, low risk nasopharyngeal carcinoma patients who underwent IMRT could not benefit from cisplatin-based concurrent chemotherapy.     

Concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: Treatment outcomes of a prospective,multicentric clinical study

Background and purpose

To evaluate long-term outcome in locoregionally advanced nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy.

Material and methods

Between January 2006 and August 2008, 249 patients with stage III–IVb NPC were treated by IMRT plus concurrent chemotherapy in this multicenter prospective study.

Results

With a mean follow-up of 54.1 months, the 5-year actuarial rates of overall survival (OS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), and distant metastasis-free survival (DMFS) were 78.4%, 86.8%, 88.4%, 78.0%, respectively. There were 29 local recurrences, 25 regional recurrences and 52 distant metastases, respectively. Distant metastasis is the main cause of treatment failure. N-stage was an independent prognostic factor for LRFS, RRFS, DMFS and OS. Acute toxicity ?grade III mainly consisted of mucositis (34.9%), neutropenia (11.2%), xerostomia (5.6%), and dermatitis (5.2%). The main documented late toxicity was xerostomia, and the severity of xerostomia decreased over time. At 24 months after treatment, 13.2% of patients had grade 2 xerostomia, and none had grade 3 or 4 xerostomia.

Conclusions

IMRT with concurrent cisplatin chemotherapy resulted in encouraging rates of local and distant control and overall survival with acceptable rates of acute and limited rates of late toxicity in patients with locoregionally advanced NPC. Distant metastasis remained the main cause of failure. More effective systemic therapy should be explored for patients with advanced N-stage.     

Prediction of 2 years-survival in patients with stage I and II non-small cell lung cancer utilizing 18F-FDG PET/CT SUV quantification

Background

The purpose of the study was to evaluate the correlation between the maximum standardized uptake value (SUVmax), size of primary lung lesion, disease-free survival (DFS) and overall survival (OS) in patients with stage I and II non-small cell lung cancer (NSCLC) in 2 years follow-up.

Patients and methods.

Forty-nine patients with stage I–II NSCLC were included in this study. Pre-surgical 2-deoxy-2-[18F]fluoro-D-glucose positron-emission tomography (¹⁸F-FDG PET/CT) study was performed for all patients. The relationship between SUVmax, tumour size and clinical outcome was measured. The cut-off value for SUVmax and tumour size with the best prognostic significance, probability of DFS and the correlation between SUVmax and the response to therapy were calculated.

Results

There was a statistically significant correlation between SUVmax and DFS (p = 0.029). The optimal cut-offs were 9.00 for SUVmax (p = 0.0013) and 30mm for tumour size (p = 0.0028). Patients with SUVmax > 9 and primary lesion size > 30 mm had an expected 2years-DFS of 37.5%, while this rose to 90% if the tumour was <30 mm and/or SUVmax was <9.

Conclusions

In stage I-II, SUVmax and tumour size might be helpful to identify the subgroup of patients with high chance for recurrence.     

Epstein-Barr Virus latent membrane protein 1 induces Snail and epithelial-mesenchymal transition in metastatic nasopharyngeal carcinoma

Background:

Epstein-Barr Virus (EBV)-associated nasopharyngeal carcinoma (NPC) is distinctive among head-and-neck cancers in its undifferentiated histopathology and highly metastatic character. We have recently investigated the involvement of epithelial–mesenchymal transition (EMT) in NPC. In a previous study, we found a close association of expression of LMP1, the principal EBV oncoprotein, with expression of Twist and induction of EMT.

Methods:

We analysed expression of Snail in 41 NPC tissues by immunohistochemistry. The role of Twist as well as Snail in EMT of NPC was investigated by using NP69SV40T human nasopharyngeal cells.

Results:

In NPC tissues, overexpression of Snail is associated with expression of LMP1 in carcinomatous cells. In addition, expression of Snail positively correlated with metastasis and independently correlated inversely with expression of E-cadherin. Expression of Twist had no association with expression of E-cadherin. Further, in a human nasopharyngeal cell line, LMP1 induces EMT and its associated cellular motility and invasiveness. Expression of Snail is induced by LMP1 in these cells, and small hairpin RNA (shRNA) to Snail reversed the cellular changes. By contrast, Twist did not produce EMT in these nasopharyngeal cells.

Conclusions:

This study strengthens the association of EMT with the metastatic behaviour of NPC. These results suggest that induction of Snail by the EBV oncoprotein LMP1 has a pivotal role in EMT in NPC.     

Familial nasopharyngeal carcinomas possess distinguished clinical characteristics in southern China

Objective： To compare clinical characteristics between familial nasopharyngeal carcinomas（NPCs） and sporadic NPCs in Guangdong province, China, a high-risk area.
Methods： Between 1991 and 2001, 993 NPC patients treated at the Cancer Center of Sun Yat-Sen University in Guangdong were randomly selected as probands. Information about NPC among the probands＇ relatives and other information were obtained from a retrospective review of the patients＇ medical records. The patients were divided into sporadic NPC, low-frequency familial NPC（one NPC patient in addition to the proband in three generations）, and high-frequency familial NPC（2 or more additional NPC patients in three generations） groups. Pathological and clinical characteristics were compared among these groups.
Results： Of the 993 patients, 131（13.2%） had a familial history of NPC. The average age at diagnosis was the lowest in the high-frequency familial NPC group（39 years; P=0.048）. Although the overall survival（OS）, distant metastasis-free survival（DMFS）, and disease-free survival（DFS） rates did not differ between familial and sporadic NPCs, the locoregional recurrence-free survival（LRFS） rate increased in the order sporadic NPCs, low-frequency familial NPCs, and high-frequency familial NPCs（P=0.009）, with 5-year rates of 70%, 83%, and 87%, respectively. Multivariate analysis showed that family history of NPC was an independent favorable prognostic factor for LRFS, with adjusted hazard ratio（a HR） of 0.548, 95% CI（0.342-0.878）. The high LRFS for familial NPCs was mainly noted among young, advanced-stage patients who received continuous radiation treatment.
Conclusions： Genetic factors may play an important role in the etiology of high-frequency familial NPC and underlie the early age of onset and sensitivity to radiotherapy.     

Efficacy of intensity-modulated radiotherapy with concurrent carboplatin in nasopharyngeal carcinoma

Background.

The aim of the prospective phase II study was to evaluate the efficacy and toxicities of concurrent carboplatin with intensity-modulated radiotherapy (IMRT) in the treatment of nasopharyngeal carcinoma (NPC).

Patients and methods.

Between October 2005 and November 2011, 73 stage II–IVB NPC patients received IMRT 70 Gy concurrently with three cycles of carboplatin (AUC 5) every three weeks, followed by three cycles of adjuvant carboplatin (AUC 5) and 5-FU (1,000 mg/m²/day for four days) every four weeks. All patients were evaluated for tumour response using response evaluation criteria in solid tumour (RECIST) criteria, survival analysis using Kaplan-Meier methods, and toxicities according to common terminology criteria for adverse events (CTCAE) version 4.0.

Results.

At three months after chemoradiation, 82.2% and 17.8% of patients achieved complete and partial response, respectively. With a median follow-up of 48.1 months (1.3–97.8 months), 9.6% and 17.8% had local recurrence and distant metastasis, respectively. The median survival was not reached. A three-year overall survival was 83.6% and a progression-free survival was 65.3%. Regarding treatment compliance, 97.2%, 68.5% and 69.8% completed radiation treatment, concurrent carboplatin and adjuvant chemotherapy, respectively. Grade 3–4 acute toxicities were oral mucositis (16.4%), dysphagia (16.4%), xerostomia (15.1%) and haematotoxicity (6.8%).

Conclusions.

Carboplatin concurrently with IMRT provided excellent tumour response, manageable toxicities and good compliance. This should be considered as an alternative treatment for NPC patients.     

Clinicopathological and prognostic differences between mucinous gastric carcinoma and signet-ring cell carcinoma

Objective: To analyze the differences in clinicopathologic characteristics and prognosis between mucinous gastric carcinoma (MGC) and signet-ring cell carcinoma (SRCC). Methods: Clinicopathologic and prognostic data of 1,637 patients with histologically confirmed MGC or SRCC who received surgical operations in the Department of Gastroenterological Surgery, Beijing Cancer Hospital between December 2004 and December 2009 were retrospectively collected and analyzed. The clinicopathological features were analyzed statistically using χ 2 test. Survival was analyzed using the Kaplan-Meier method and multivariate analysis of Cox proportional hazards regression model (backward, stepwise). Results: A total of 181 patients with gastric cancer (74 MGC, 107 SRCC) were included. MGC, when compared with SRCC, was featured by senile patients, stage III and IV, upper third stomach, large tumor size, positive lymph node metastasis, and positive lymphatic vascular invasion (P<0.05). The overall 5-year survival rate showed no difference between the two groups (48.8% vs. 44.8%, P>0.05). However, the survival rate for MGC patients was significant lower than that for SRCC patients when compared among the age <60 years, negative distant metastasis, and tumor localized at upper third stomach (P<0.05). Multivariate Cox proportional hazards models revealed that distant metastasis was a significant independent prognostic indicator in MGC group, and lymph node metastasis and distant metastasis was significant independent prognostic indicators in SRCC group. Conclusions: While compared with SRCC, MGC is associated with a more aggressive tumor biologic behavior. There is no statistically significant difference in distant metastasis, an independent prognostic indicator for both MGC and SRCC, which might be the reason for no significant difference of the overall survival rate between the patients with MGC and SRCC.     

Prognostic significance of PET assessment of metabolic response to therapy in oesophageal squamous cell carcinoma

Objectives:

The role of maximum standard uptake value (SUVmax) at baseline and after induction chemotherapy (CT) on positron emission tomography (PET) as an imaging biomarker has not been well established in oesophageal squamous cell carcinoma (SCC). In this retrospective analysis, we investigated the prognostic significance of various PET metrics in oesophageal SCC patients treated with induction chemotherapy followed by concurrent chemoradiotherapy (CRT).

Methods:

A total of 57 patients were treated with CRT; 52 patients received induction chemotherapy and 10 patients underwent surgery following CRT. Scans were independently analysed by a nuclear medicine physician blinded to patient outcome. Using region of interest analysis, SUVmax and metabolic tumour volume (MTV) were calculated for the index lesion and lymph node metastases in each patient. Kaplan–Meier analysis was used to evaluate overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS). Cox proportional hazards regression was used to assess correlation between outcomes and PET metrics.

Results:

Median follow-up for those who are alive was 4.4 years, with a median survival for all patients of 2.9 years. The 3-year OS, DFS, DMFS and LRFS rates were 47, 40, 44 and 36%, respectively. Using a pre-established cutoff of a 35% decrease in SUVmax from baseline to post-induction PET, 3-year OS for responders (⩾35% decrease from baseline) was 64%, whereas non-responders (<35% decrease from baseline) had a 3-year OS of 15% (P=0.004).

Conclusions:

The pre-specified 35% decrease in SUVmax after induction chemotherapy was prognostic for OS. Baseline and post-induction PET metrics provide prognostic information for oesophageal SCC.     

Survival analyses correlate stanniocalcin 2 overexpression to poor prognosis of nasopharyngeal carcinomas

Background

Stanniocalcin 2 (STC2) is overexpressed in several types of human cancers, and its overexpression positively correlates to tumor progression and poor prognosis. However, the clinical significance of STC2 overexpression in nasopharyngeal carcinomas (NPC) has not been investigated. This study examined STC2 expression in a cohort of 94 NPC samples, and explored its value in clinical diagnosis and prognosis.

Methods

Tumor samples from 94 patients diagnosed in 2008 were studied. All samples were obtained prior to treatment start. All cases were clinically diagnosed and pathologically confirmed to be poorly differentiated or undifferentiated NPC without distant metastasis, and have been treated with radical radiation therapy and followed-up for five years. Survival analyses were performed.

Results

Of the 94 NPC samples, STC2 overexpression (STC2+) was detected in 65 samples (69.1%). Overall survival rate of STC2 (+) patients is significantly lower than that of patients with normal STC2 levels (72.2% vs. 96.4%, respectively, P = 0.049). Moreover, STC2 (+) is also strongly predictive of a low progression-free survival and distant metastasis-free survival (63.0% vs 92.9%. P = 0.007; and 77.0% vs 96.4%. P = 0.028). Of the 54 patients treated with IMRT, residual tumors were found in 54.8% of STC2 positive patients (17/31), but only in 17.4% of STC2 negative ones (4/23), suggesting STC2 overexpression predicts a higher risk of residual tumors after IMRT.

Conclusions

STC2 overexpression correlates to poor prognosis for NPC and may be useful as a novel biomarker to predict NPC responses to radiation. Whether STC2 promotes NPC progression and metastasis remains to be investigated.     

Serum CCL2 and serum TNF-α--two new biomarkers predict bone invasion, post-treatment distant metastasis and poor overall survival in nasopharyngeal carcinoma

Purpose

To evaluate the prognostic potential of serum CCL2 (sCCL2) and serum TNF-α (sTNF-α) in nasopharyngeal carcinoma (NPC) before treatment by analysing the expression of these two markers.

Experimental design

Both sCCL2 and sTNF-α were prospectively detected in 297 NPC patients with enzyme-linked immunosorbent assay (ELISA) before treatment. The correlations between sCCL2 level or sTNF-α level and patient’s survival were evaluated.

Results

For sCCL2, the 5-year overall survival (OS) and 5-year distant metastasis-free survival (DMFS) of high expression group and low expression group were 64% versus 81% and 67% versus 84% (P < 0.05), respectively. For sTNF-α, the 5-year OS and 5-year DMFS of high expression group and low expression group were 62% versus 79% and 66% versus 82% (P < 0.05), respectively. The 5-year OS and 5-year DMFS for both positive patients, one marker positive patient and both negative patients were 53% versus 77% versus 85% and 58% versus 80% versus 86% (P < 0.05), respectively. Concentrations of sCCL2 and sTNF-α in patients with large skull base invasion were higher than those without or with small skull invasion (P < 0.05). Patients who developed bone metastasis alone after radical treatment had higher pre-treatment concentrations of sCCL2 and sTNF-α than those without metastasis (P < 0.001). Multifactorial Cox regression analyses demonstrated that T/N/M classification, chemotherapy, sCCL2 level and sTNF-α level were independent predictors of OS and DMFS of NPC patients.

Conclusion

High expression levels of sCCL2 and sTNF-α predict bone invasion, post-treatment distant metastasis and poor overall survival in NPC patients.     

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.     

Prognostic score models for survival of nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy and chemotherapy

Purpose

To establish accurate prognostic score models to predict survival for patients with nasopharyngeal carcinoma (NPC), treated with intensity-modulated radiotherapy (IMRT) and chemotherapy.

Materials and methods

Six hundred and seventy-five patients with newly diagnosed, nonmetastatic and histologically proven NPC who were treated with IMRT and chemotherapy were analyzed retrospectively. Samples were split randomly into a training set (n = 338) and a test set (n = 337) to analyze. All data from the training set were used to perform an extensive survival analysis and to develop multivariate nomograms based on Cox regression. Data from the test set was used as an external validation set. Risk group stratification was proposed for the nomograms.

Results

The nomograms are able to predict survival with a C-index for external validation of local recurrence-free survival (LRFS; 0.66, 95% CI: 0.58-0.74), distant metastasis-free survival (DMFS; 0.73, 95% CI: 0.66-0.79), and disease-specific survival (DSS; 0.73, 95% CI: 0.67-0.79). The calibration curve for probability of survival showed good agreement between prediction by nomogram and actual observation. The C-index of the nomogram for LRFS, DMFS and DSS were statistically higher than the C-index values of the AJCC seventh edition (P < 0.001). In the test set, the nomogram discrimination was also superior to the AJCC Staging systems (P < 0.001). The stratification in risk groups allows significant distinction between Kaplan-Meier curves for outcome.

Conclusions

Prognostic score models were successfully established and validated to predict LRFS, DMFS, and DSS over a 5-year period after IMRT and chemotherapy, which will be useful for individual treatment.     

Correlates of anti-EBV EBNA1 IgA positivity among unaffected relatives from nasopharyngeal carcinoma multiplex families

Background:

To determine whether non-viral nasopharyngeal carcinoma (NPC) risk factors might be associated with (and mediated through) Epstein–Barr virus (EBV) serological responses linked to NPC risk, we evaluated predictors of risk of anti-EBNA1 IgA seropositivity and other markers among unaffected relatives from a large NPC family study in Taiwan.

Methods:

Multivariate logistic regression conditioned on family was used to examine the associations between sociodemographic, dietary, lifestyle, and occupational variables and risk of anti-EBV EBNA1 IgA positivity, anti-VCA IgA, and anti-DNase positivity.

Results:

Among 2393 unaffected relatives from 319 multiplex families, 1180 (49.3%) were anti-EBV EBNA1 IgA seropositive. None of the associations with anti-EBNA1 IgA were statistically significant, except for being 31–50 years of age (vs <30, adjusted ORs 0.51–0.57). For one or more EBV serological markers, there were suggestive associations for older age, GuangDong firm salted fish, betel use, current alcohol use, and male gender.

Conclusion:

Overall, we found little evidence to suggest that non-viral NPC risk factors significantly alter EBV serological patterns, suggesting that non-viral NPC risk factors act through pathways independent of EBV serological responses.     

Predictive value of miR-9 as a potential biomarker for nasopharyngeal carcinoma metastasis

Background:

Nasopharyngeal carcinoma (NPC) has a distinctive geographic distribution and is characterised by its strong tendency of metastasis. We aimed to examine the microRNA (miRNA) expression profiles in plasma samples of NPC patients to explore their clinical significance in disease development and progression.

Methods:

This study was divided into four steps: (1) confirmation of differentially expressed miRNAs using microarray analysis and quantitative PCR validation; (2) comparison of plasma miR-9 levels during NPC progression; (3) evaluation of the predictive performance of plasma miR-9 as a biomarker for NPC metastasis; and (4) comparison of plasma miR-9 levels between pre- and post-treatment samples.

Results:

Plasma microarray profiling identified 33 differentially expressed miRNAs between NPC patients and healthy volunteers. The significantly declined level of miR-9 in NPC patients was confirmed through two-stage validation. The low level of plasma miR-9 was significantly correlated with worse lymphatic invasion and advanced TNM stage. The plasma miR-9 could distinguish locoregional from metastatic NPC cases with a high sensitivity and specificity. Furthermore, the plasma miR-9 level was significantly elevated in post-treatment plasma compared with those pre-treatment samples.

Conclusion:

Our study reports that plasma miR-9 may serve as a useful biomarker to predict NPC metastasis and to monitor tumour dynamics.     

Effect of adaptive replanning in patients with locally advanced nasopharyngeal carcinoma treated by intensity-modulated radiotherapy: a propensity score matched analysis

Purpose

Limited data have been published regarding the effect of adaptive radiotherapy (ART) on clinical outcome in patients with nasopharyngeal carcinoma (NPC). We compared the long-term outcomes in patients with locally advanced NPC treated by adaptive intensity-modulated radiotherapy (IMRT) replanning versus IMRT.

Methods

200 NPC patients with stage T3/T4 were included between October 2004 and November 2010. Patients in both treatment groups were matched using propensity score matching method at the ratio of 1:1. Clinical outcomes were analyzed with Kaplan–Meier method, log-rank test and Cox regression.

Results

After matching, 132 patients (66 patients in each group) were included for analysis. The median follow-up for the IMRT replanning group was 70 months, while the IMRT group was 69 months. The 5-year local–regional recurrence-free survival (LRFS) rate was higher in IMRT replanning group (96.7 vs. 88.1 %, P = 0.022). No significant differences in distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS) were observed between the two groups. 21.2 % patients in IMRT replanning group and 28.8 % patients in IMRT group had distant metastasis. In multivariable analysis, IMRT replanning was identified as an independent prognostic factor for LRFS (hazard ratio 0.229; 95 % CI 0.062–0.854; P = 0.028), but not for DMFS, PFS and OS.

Conclusions

IMRT replanning provides an improved LRFS for stage T3/T4 NPC patients compared with IMRT. Distant metastasis remains the main pattern of treatment failure. No significant advantage was observed in DMFS, PFS and OS when adaptive replanning was used.