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Objectives: To evaluate the patterns of failure and survival trends of patients with stage I nasopharyngeal carcinoma (NPC) treated with radiotherapy alone over the last 20 years. Materials and Methods: A retrospective cohort study was conducted on 720 patients with stage I NPC who were treated with curative two-dimensional radiotherapy (2DRT), three-dimensional conformal radiotherapy (3DRT), or intensity-modulated radiotherapy (IMRT) between January 1990 and December 2012. The patients were categorized into four calendar periods (1990-1996, 1997-2002, 2003-2007, and 2008-2012) and four age subgroups (18-39, 40-49, 50-59, and >60). We computed overall survival (OS), progression free survival (PFS), locoregional relapse free survival (LRFS) and distant metastasis free survival (DMFS) as measures of patient survival. Results: After a median follow-up period of 105 months (range 1-280 months), we observed the increasing trends in survival and disease control. The 3-, 5-, and 7-year OS rates increased from 97.0%, 86.7%, and 81.7% in the first calendar period (1990-1996) to 100%, 99.3%, and 98.0% in the last calendar period (2008-2012), respectively (P

The goal of this study was to explore the value of adding neoadjuvant chemotherapy (NACT) or adjuvant chemotherapy (ACT) to concurrent chemoradiotherapy (CCRT) in patients with nasopharyngeal carcinoma (NPC) with different risks of treatment failure.A total of 2,263 eligible patients with stage III-IVb NPC treated with CCRT ± NACT or ACT were included in this retrospective study. Distant metastasis-free survival (DMFS), overall survival, and progression-free survival were calculated using the Kaplan-Meier method and differences were compared using the log-rank test.Patients in the low-risk group (stage N0-1 disease and Epstein-Barr virus [EBV] DNA4,000 copies/mL) who received NACT followed by CCRT achieved significantly better 5-year DMFS than those treated with CCRT alone (96.2% vs 91.3%; P= .008). Multivariate analyses also demonstrated that additional NACT was the only independent prognostic factor for DMFS (hazard ratio, 0.42; 95% CI, 0.22-0.80; P=.009). In both the intermediate-risk group (stage N0-1 disease and EBV DNA ≥4,000 copies/mL and stage N2-3 disease and EBV DNA4,000 copies/mL) and the high-risk group (stage N2-3 disease and EBV DNA ≥4,000 copies/mL), comparison of NACT or ACT + CCRT versus CCRT alone indicated no significantly better survival for all end points.The addition of NACT to CCRT could reduce distant failure in patients with low risk of treatment failure.

The goal of this study was to explore the benefits of S-1/capecitabine as maintenance therapy in locoregionally advanced nasopharyngeal carcinoma (NPC) patients with different risks of treatment failure.A total of 2205 eligible, locoregionally advanced NPC patients were recruited for this retrospective study. Multivariate Cox regression analysis was performed to identify optimal predictors of overall survival (OS) and distant metastasis-free survival (DMFS) for constructing the nomograms. Patients were stratified into high-risk or low-risk groups based on the total score of the nomograms. Propensity score matching (PSM) was performed to match the maintenance and non-maintenance cohorts in different risk groups. A log-rank test was performed to evaluate correlations between maintenance therapy and survival.A nomogram for OS was established (C-index, 0.664; 95% confidence interval, 0.635-0.693). The 5-year OS rate was significantly higher in the low-risk group than in the high-risk group (83.5% vs. 67.2%, P 0.001). Patients in the high-risk group who received S-1/capecitabine maintenance therapy achieved significant improvement in the 5-year OS rate (82.8% vs. 67.1%, p = 0.034), whereas patients in the low-risk group did not (86.7% vs. 80.9%, P = 0.081). There was no significant difference in OS, DMFS, progression-free survival (PFS), or toxicities between the S-1 and capecitabine groups (all P 0.05), and overall treatment-related adverse events (AEs) were not severe (grade 1-2).S-1/capecitabine maintenance therapy could prolong OS for locoregionally advanced NPC patients in the high-risk group. The toxicities of S-1/capecitabine maintenance therapy were mild and tolerable. Our findings can help guide maintenance therapy in locoregionally advanced NPC.

Purpose To evaluate the prognostic value of the restaging system after neoadjuvant chemotherapy (NACT) in patients with advanced-stage nasopharyngeal carcinoma (NPC). Materials and Methods This study was approved by the clinical research committee and a written informed consent was required before enrolling in the study. Prospectively enrolled were 412 consecutive patients with stage III-IVb NPC treated with NACT followed by concurrent chemotherapy and radiation therapy. Patients were staged before NACT and restaged after NACT. The progression-free survival (PFS) and distant metastasis-free survival (DMFS) were calculated with the Kaplan-Meier method, and differences were compared by using the log-rank test. Results Post-NACT T classification (PFS, P = .001) and N classification (PFS, P < .001; DMFS, P = .001) resulted in better survival curve separations than pre-NACT T classification and N classification. Patients downstaged from N2-N3 to N0-N1 disease had a better prognosis than did patients who continued to have N2-N3 diseases (3-year PFS, 83.8% vs 66.6%, P = .001; 3-year DMFS, 88.0% vs 78.4%, P = .026). Multivariate analysis revealed that post-NACT T classification (hazard ratio [HR] = 1.67; 95% confidence interval [CI]: 1.18, 2.36; P = .003) and post-NACT N classification (HR = 1.54; 95% CI: 1.17, 2.03; P = .002) were independent prognostic factors for PFS; also, post-NACT N classification (HR = 1.48; 95% CI: 1.05, 2.07; P = .025) was an independent prognostic factor for DMFS. Multivariate analysis in patients with N2-N3 disease demonstrated that the N downstaging effects of NACT was the only independent prognostic factor for PFS (HR = 0.48; 95% CI: 0.29, 0.81; P = .006) and DMFS (HR = 0.52; 95% CI: 0.28, 0.97; P = .039). Conclusion The post-NACT stage is more representative of prognosis than the pre-NACT stage in advanced-stage NPC patients, which suggests that major clinical decisions should be based on the post-NACT stage. © RSNA, 2016 Online supplemental material is available for this article.

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), 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.

Nasopharyngeal carcinoma (NPC) is a malignancy with unique clinical biological profiles such as associated Epstein-Barr virus infection and high radiosensitivity. Radiotherapy has long been recognized as the mainstay for the treatment of NPC. However, the further efficacy brought by radical radiotherapy has reached the bottleneck in advanced patients, who are prone to develop recurrence and distant metastasis after treatment. The application of photon therapy makes it possible for radiation dose escalation in refractory cases and may provide second chance for recurrent patients with less unrecoverable tissue damage. The concept of adaptive radiotherapy is put forward in consideration of target volume shrinkage during treatment. The replanning procedure offers better protection for the organ at risk. However, the best timing and candidates for adaptive radiotherapy is still under debate. The current tendency of artificial intelligence in NPC mainly focuses on image recognition, auto-segmentation and dose prediction. Although artificial intelligence is still in developmental stage, the future of it is promising. To further improve the efficacy of NPC, multimodality treatment is encouraged. In-depth studies on genetic and epigenetic variations help to explain the great heterogeneity among patients, and could further be applied to precise screening and prediction, personalized radiotherapy and the evolution of targeted drugs. Given the clinical benefit of immunotherapy in other cancers, the application of immunotherapy, especially immune checkpoint inhibitor, in NPC is also of great potential. Results from ongoing clinical trials combining immunotherapy with radiotherapy in NPC are expected.

Objective We aimed to investigate whether zoledronic acid (ZA) can prevent skeletal-related events (SREs) and offer survival benefits for nasopharyngeal carcinoma (NPC) patients with bone-only metastasis at diagnosis. Materials and Methods A total of 228 newly diagnosed NPC cases with bone-only metastasis were eligible for this retrospective study. Using the propensity score method (PSM) method, a well-balanced cohort was created for further analysis. Overall survival (OS) was the primary endpoint. The difference in survival was evaluated using the log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) for all­cause mortality were derived from a Cox regression model. Cumulative incidence competing risk analyses using Fine and Gray’s method was used to test the cumulative incidence of SREs between the different treatment groups. Result In the PSM cohorts, patients in the platinum-based palliative chemotherapy (PCT) + ZA group and PCT alone group achieved similar 3-year OS (57.3% vs. 46.4%; log rank P = 0.188). Multivariate analysis indicated that ZA administration was not an independent prognostic factor (HR, 0.783; 95% CI, 0.267–2.300; P = 0.657). There was no significant difference in acute treatment toxicity between the 2 treatment groups, although the cumulative incidence of bone-related events (SREs) was significantly lower in the PCT + ZA group (Fine-Gray P = 0.026). Conclusion ZA combined with PCT could not improve OS in NPC patients with bone-only metastasis at diagnosis. However, the incidence of SREs could be effectively prevented via ZA application.

Objective We aimed to investigate the efficacy and safety of cetuximab (CTX) or nimotuzumab (NTZ) on the addition of palliative chemotherapy (PCT) in patients with de novo metastatic nasopharyngeal carcinoma (NPC). Materials and methods From 2007 to 2016, 451 eligible patients with de novo metastatic NPC were enrolled in the study. With propensity score matching technique, we created a well-balanced cohort by matching patients who received CTX/NTZ plus PCT (62 patients) with those receiving PCT alone (248 patients) in a ratio of 1:4. The primary endpoint was overall survival (OS). All potential prognostic factors were involved in the multivariate analysis with the Cox regression hazards model. Kaplan–Meier curves were used to compare the survival status, and log-rank test to measure the significance. Results The median follow-up time was 27.7 months (range, 1–126 months). No significant difference in survival was observed between the CTX/NTZ plus PCT group and PCT group. (3-year OS: 63.0% vs 58.1%; P=0.485). The administration of CTX/NTZ was not found to be an independent prognostic factor in multivariate analysis. With regard to toxicity, the development of a G3-4 skin reaction and mucositis was more common in patients receiving CTX plus PCT. Interaction effects analysis did not show any significant interaction effects on OS between the treatment regimen and prognostic factors (P>0.05). Conclusion The efficacy of CTX/NTZ and PCT is comparable to single PCT treatment in terms of survival outcomes among de novo metastatic NPC patients. Moreover, the application of CTX exacerbated skin reactions and mucositis.

Background This study aimed to evaluate the prognostic value of maximal standard uptake values (SUVmax) of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (PET) comparing with Epstein-Barr virus (EBV) DNA levels in de novo metastatic nasopharyngeal carcinoma (NPC) patients. Methods From December 2006 to December 2016, 253 de novo metastatic NPC patients assessed by PET/ computed tomography were involved in current study. SUVmax-T, SUVmax-N, and SUVmax-M referred to the SUVmax at the primary tumor, cervical lymph nodes, and metastatic lesions respectively. Overall survival (OS) was the primary endpoint. Result Patients who died during the follow-up had significantly higher SUVmax-N, SUVmax-M, and EBV DNA level than those in the patients who were alive. SUVmax-N and SUVmax-M were positively correlated with EBV DNA level. The cut-off values of SUVmax-T, SUVmax-N, SUVmax-M, and EBV DNA were 17.0, 12.7, and 6.9, and 13,800 copies/mL respectively, which were determined by receiver operating characteristic (ROC) curve analysis. Patients with elevated SUVmax-N, SUVmax-M, and EBV DNA levels had a lower 3-year OS rate. In multivariate analysis, the independent prognostic factors of OS included EBV DNA, metastatic site, and locoregional radiotherapy application, while SUVmax was not an independent prognostic factor. Conclusion In de novo metastatic NPC patients, higher SUVmax-N and SUVmax-M were associated with worse prognosis. However, the predictive ability of SUVmax-N and SUVmax-M was poorer than that of EBV DNA. Electronic supplementary material The online version of this article (10.1186/s12885-019-6106-2) contains supplementary material, which is available to authorized users.

Background Currently, the diagnosis and treatment of nasopharyngeal carcinoma (NPC) patients with residual cervical lymphadenopathy following radical radiotherapy with or without chemotherapy are challenging. We investigated the prognosis of NPC patients with residual cervical lymphadenopathy and assessed the diagnostic and prognostic values of Epstein-Barr virus (EBV) DNA in these patients. Methods This study included 82 NPC patients who were diagnosed with suspected residual cervical lymphadenopathy following completion of antitumor therapy. Their plasma EBV DNA levels were measured using quantitative polymerase chain reaction (qPCR) before the initiation of treatment and before neck dissection. Fine needle aspiration cytology (FNAC) was performed in 21 patients. All patients had undergone neck dissection and postoperative pathological examination to identify the nature of residual cervical lymphadenopathy. The overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) were calculated using the Kaplan–Meier method and compared using the log-rank test. The Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Multivariable analysis was used to estimate the effect of potential prognostic factors on survival. Results Following a median follow-up of 52.6 months, compared with patients with negative postoperative pathological findings for residual cervical lymphadenopathy, the patients with positive findings had a significantly lower 3-year PFS rate (49.9% vs. 83.3%, P = 0.008). Among NPC patients with residual cervical lymphadenopathy, the patients with preoperative plasma EBV DNA > 0 copy/mL had a lower 3-year PFS rate than did those with no detectable EBV DNA (43.7% vs. 61.1%, P = 0.031). In addition, combining FNAC with preoperative EBV DNA detection improved the diagnostic sensitivity. Multivariable analysis demonstrated that residual cervical lymphadenopathy with positive postoperative pathological result was an independent prognostic factor for PFS and that detectable preoperative plasma EBV DNA was an independent prognostic factor for OS. Conclusions Using FNAC combined with preoperative EBV DNA detection improves the sensitivity in diagnosing NPC with residual cervical lymphadenopathy. Compared with patients with undetectable EBV DNA, patients with detectable preoperative plasma EBV DNA have worse prognosis and may require a more aggressive treatment strategy.

Background Initial 3-year results from our clinical trial in locoregionally advanced nasopharyngeal carcinoma (NPC) patients showed that induction chemotherapy (IC) with cisplatin and fluorouracil resulted in improved disease-free survival (DFS) with a marginally significant effect on distant metastasis-free survival (DMFS), but the effect of IC on locoregional relapse-free survival and overall survival (OS) did not differ significantly. Here, we present 5-year follow-up results. Patients and methods Our trial was a randomised, open-label phase III trial comparing IC followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in patients with stage III-IVB (except T3N0-1) NPC. The IC followed by CCRT group received cisplatin (80 mg/m2 d1) and fluorouracil (800 mg/m2 d1-5) every 3 weeks for two cycles before CCRT. Both groups were treated with 80 mg/m2 cisplatin every 3 weeks concurrently with radiotherapy. The primary end-points were DFS and DMFS. We did efficacy analyses in the 476 randomised patients (intention-to-treat population). Results After a median follow-up of 82.6 months, the 5-year DFS rate was 73.4% (95% confidence interval [CI] 67.7–79.1) in the IC followed by CCRT group and 63.1% (95% CI 56.8–69.4) in the CCRT alone group (p = 0.007). The 5-year DMFS rate was also significantly higher in the IC followed by CCRT group (82.8%, 95% CI 77.9–87.7) than in the CCRT alone group (73.1%, 95% CI 67.2–79.0, p = 0.014). Our updated analysis revealed an OS benefit of IC: the 5-year OS rate was 80.8% in the IC followed by CCRT group versus 76.8% in the CCRT alone group (p = 0.040). The proportion of patients with eye damage was significantly higher in the CCRT alone group than the IC followed by CCRT group (16.4% [39/238] versus 9.7% [23/238], p = 0.029). Conclusion IC followed by CCRT provides long-term DFS, DMFS and OS benefits compared with CCRT alone in locoregionally advanced NPC and, therefore, can be recommended for these patients.

Table S1. Follow-up durations of different subgroups (DOCX 51 kb)

Table S1. Relationship between EBV DNA levels after PCT and tumor response to PCT. (DOCX 49 kb)

PURPOSE The purpose of this study was to investigate the survival trends and patterns of failure in patients with stage II nasopharyngeal carcinoma (NPC) treated with radiotherapy (RT) and chemotherapy over the last 20 years. Materials and Methods Thirty-eight hundred and eight patients diagnosed with stage II NPC between January 1990 and December 2012 were involved in this retrospective cohort study. All patients were treated with RT. According to the main imaging techniques and RT technology, we categorized these patients into four calendar periods: 1990-1996, 1997-2002, 2003-2007, and 2008-2012. Overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were served as the clinical outcome. RESULTS After a median follow-up period of 84.7 months, we observed increasing trends in survival and disease control. The 3- and 5-year OS rates increased from 87.1% and 78.7% in the first calendar period to 97.4% and 94.5% in the last calendar period, respectively (p

Background We wished to evaluate the efficacy and safety of liposomal paclitaxel and docetaxel for induction chemotherapy (IC) for nasopharyngeal carcinoma (NPC). Methods A total of 1498 patients with newly-diagnosed NPC between 2009 and 2017 treated with IC plus concurrent chemotherapy were included in our observational study. Overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and grade-3–4 toxicities were compared between groups using propensity score matching (PSM). Results In total, 767 patients were eligible for this study, with 104 (13.6%) and 663 (86.4%) receiving a liposomal paclitaxel-based and docetaxel-based taxanes, cisplatin and 5-fluorouracil (TPF) regimen, respectively. PSM identified 103 patients in the liposomal-paclitaxel group and 287 patients in the docetaxel group. There was no significant difference at 3 years for OS (92.2% vs. 93.9%, P = 0.942), PFS (82.6% vs. 81.7%, P = 0.394), LRFS (94.7% vs. 93.3%, P = 0.981) or DMFS (84.6% vs. 87.4%, P = 0.371) between the two groups after PSM. Significant interactions were not observed between the effect of chemotherapy regimen and sex, age, T stage, N stage, overall stage, or Epstein–Barr virus DNA level in the subgroup multivariate analysis. The prevalence of grade-3–4 leukopenia and neutropenia in the liposomal-paclitaxel group was significantly lower than that of the docetaxel group (P

6005 Background: We conducted a multicenter, randomized controlled phase III clinical trial (NCT02143388) to investigate the efficacy and toxicity of adjuvant capecitabine (AC) in addition to concurrent cisplatin and radiotherapy (CCRT) compared to CCRT alone in high-risk locoregionally advanced nasopharyngeal carcinoma (LANPC) patients. Methods: Eligibility criteria included AJCC/UICC 7th ed TNM stage III-IVb and one of the following features: T3-4N2 or T1-4N3 or pre-treatment plasma EBV DNA concentration of >20,000 copy/ml or gross primary tumor volume (GTVnx) of >30 cm3 or a maximum standard uptake value (SUVmax) of >10.0 by 18FDG PET-CT within the primary tumor or multiple neck node metastases, with any larger than 4 cm. All patients were randomly assigned in a 1:1 ratio to receive CCRT (3-weekly cisplatin at 100 mg/m2 for 2-3 cycles) followed by AC (1000 mg/m2 bi-daily for 14 days every 21-day cycle for 8 cycles), or CCRT alone. The prescribed radiation doses were 68-72 Gy/30-32 fractions to the PTVnx, 60-68 Gy/30-32 fractions to PTVnd, 60-64Gy/30-32 fractions to PTVhigh-risk, 54-58Gy/30-32 fractions to PTVlow-risk. Primary end point was failure-free survival (FFS). Results: Between Mar 2014 to Jul 2018, 180 patients were recruited (90 patients in CCRT+AC arm and 90 in CCRT alone arm). All patients completed RT and ≥2 cycles of concurrent cisplatin in both treatment arms (cumulative dose intensities for cisplatin were 200 mg/m2 in both arms). 85 (94.4%) patients went on to receive AC, with 71 (78.9%) patients completing 8 cycles; 19 (22.4%) patients had dose reduction of AC. With a median follow-up of 44.8 mo, the 3-y FFS was significantly superior in the CCRT+AC arm than the CCRT arm for the intention-to-treat cohort (87.7% vs 73.3%; HR: 0.52 [95% CI: 0.29-0.77], P = 0.037). 3-year overall, distant metastasis-free and locoregional relapse-free survival were 92.6% vs 88.9% (HR [95% CI]: 0.66 [0.28-1.59]), 88.8% vs. 81.1% (HR: 0.67 [0.33-1.33]) and 91.5% vs 80.0% (HR: 0.50 [0.25-1.00]), respectively. Incidences of G3-4 acute toxicities were 57.8% (52 of 90) in CCRT+AC arm and 51.1% (46 of 90) in CCRT alone arm, with a higher incidence of hand foot syndrome (3.5% vs 0%), xerostomia (11.1% vs 3.3%), mucositis (23.3% vs 16.7%), and anemia (5.6% vs 2.2%) in the CCRT+AC arm. G3-4 late toxicities occurred in 13.3% (12 of 90) and 9.0% (8 of 89), respectively. Conclusions: The addition of capecitabine to CCRT conferred a superior disease control than CCRT alone in high-risk LANPC. Survivals in ITT and PP set. Clinical trial information: NCT02143388. [Table: see text]

10575 Background: Epstein-Barr virus (EBV) infection was highly prevalent, as was found in more than 90% of the adults globally. EBV infection has been found to be related with several types of cancer and classified as group 1 carcinogen by the International Agency for Research on Cancer. The association between EBV infection and malignancy was observed in Burkitt lymphoma (BL), Hodgkin lymphoma (HL), extranodal natural killer (NK)/T-cell lymphoma (NNKTL), gastric cancer (GC) and nasopharyngeal cancer (NPC). In this study, we aimed to analyze the incidence and the trend of incidence of these virus-related cancer and to identify whether the trend was similar between them. Methods: This was a retrospective analysis based on the data from Surveillance, Epidemiology, and End Results (18 registries, 2000-2017), which totally included 71,415 patients. EBV-related cancers were defined as BL, HL, NNKTL, GC and NPC. Age-adjusted incidence rates were displayed as per 100,000 persons. In terms of incidence trend, we calculated the average annual percent change (AAPC). AAPC was considered significantly different from 0 when the P-value was smaller than 0.05. The impact of the epidemiological and clinical characteristics on the incidence trend was estimated, with cancer type, histology, age, sex and race considered. Results: Incidence rates of EBV-related cancers were 6.68 per 100,000 persons in 2000 and 5.80 in 2017, of which the AAPC was -0.8 (95%CI, -1.1 - -0.5, P-value < 0.001). (Table) Similar with EBV-related cancer as a whole, the APCCs of BL, HL and GC were statistically significantly smaller than 0, except that the APCCs of NNKTL and NPC were statistically significantly larger than 0 and not statistically significantly different from 0 respectively. The incidence of EBV-related cancer also decreased in mixed cellularity classical HL, nodular sclerosis classical HL, adenocarcinoma of GC, signet ring cell carcinoma in GC, undifferentiated carcinoma of NPC, squamous cell carcinoma of NPC, patients diagnosed at the age of 20-39 years old and 60-79 years old, male patients and race as white, black or Asian, but increased in classical HL, NOS, nodular lymphocyte predominant HL and non-keratinizing carcinoma of NPC. Conclusions: Incidence of EBV-related cancer decreased during 2000 and 2017, which was consistent in BL, HL and GC.[Table: see text]

110 Background: The cisplatin-based chemoradiotherapy (CCRT), given at a dose of 100 mg/m2 for 3 cycles during radiotherapy, is the major treatment for locoregionally advanced nasopharyngeal carcinoma (NPC). As several retrospective studies showed that receiving a cumulative cisplatin dose of 200 mg/m2 can bring survival benefits to NPC patients, we sought to test the non-inferiority of 2-cycle concurrent cisplatin over 3-cycle in locoregionally advanced NPC with Epstein-barr virus (EBV) DNA levels < 4000 copies/ml. Methods: We did a non-inferiority, phase 2, randomised controlled trial. Patients were enrolled with stage III–IVB NPC, EBV DNA levels < 4000 copies/ml, aged 18–70 and adequate haematological, renal, and hepatic function. Eligible patients were randomly assigned (1:1) to receive 2 or 3 cycles of cisplatin-based CCRT. Patients in the 2-cycle group were scheduled to receive 100 mg/m2 cisplatin given every 3 weeks concurrently with radiotherapy, and patients in the 3-cycle group received 100 mg/m2 cisplatin given every 3 weeks for 3 cycles. Randomization was done by a computer-generated random number code with a block size of six, stratified by clinical stage III or IV. The primary endpoint was 3-year progression-free survival (PFS), with a non-inferiority margin of 10%. This study was registered with ClinicalTrials.gov, ID. NCT02871518. Results: Between September 2016 and October 2018, 342 patients were enrolled, of whom 332 were randomly assigned to receive 2 or 3 cycles of cisplatin. 314 (94.6%) patients completed protocol-defined cycles of chemotherapy. After median follow-up of 33.6 months, 20 (12.0%) patients in the 2-cycle group and 17 (10.2%) patients in the 3-cycle group had tumor progression, and the 3-year PFS rates were 88.0% and 90.4% respectively, with a difference of 2.4% (95%CI -4.3 to 9.1, Pnon-inferiority < 0.001). In the per-protocol analysis, 3-year PFS was 88.5% in the 2-cycle group and 90.6% in the 3-cycle group, with a difference of 2.1% (95% CI –4.7 to 8.9; Pnon-inferiority= 0.001). No significant difference was observed concerning OS, LRRFS and DMFS. The grade 3 or 4 acute adverse events were recorded in 113 (68.1%) patients in the 2-cycle group and 116 (69.9%) patients in the 3-cycle group. Patients in the 3-cycle group was observed to have significantly more hyponatremia. Besides, patients in the 3-cycle group presented with more grade 1 or 2 dry mouth, dysphagia, weight loss, fatigue, constipation, fever, mucositis and dermatitis. More grade 3 or 4 anorexia, mucositis and dermatitis were also recorded in the 3-cycle group. No patients died from treatment-related toxicities. Conclusions: IMRT plus 2 cycles of concurrent 100 mg/m2 cisplatin could be an alternative option for patients with low-risk locoregionally advanced NPC. Further phase III studies are needed to validate the findings of this study. Clinical trial information: NCT02871518.

// Shan-Shan Guo 1, 2, * , Lin-Quan Tang 1, 2, * , Qiu-Yan Chen 1, 2 , Lu Zhang 1, 2 , Li-Ting Liu 1, 2 , Ling Guo 1, 2 , Hao-Yuan Mo 1, 2 , Dong-Hua Luo 1, 2 , Pei-Yu Huang 1, 2 , Yan-Qun Xiang 1, 2 , Rui Sun 1, 2 , Ming-Yuan Chen 1, 2 , Lin Wang 1, 2 , Xing Lv 1, 2 , Chong Zhao 1, 2 , Xiang Guo 1, 2 , Ka-Jia Cao 1, 2 , Chao-Nan Qian 1, 2 , Mu-Shen Zeng 1 , Jin-Xin Bei 1 , Ming-Huang Hong 1, 3 , Jian-Yong Shao 1, 4 , Ying Sun 1, 5 , Jun Ma 1, 5 , Hai-Qiang Mai 1, 2 1 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China 2 Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou 510060, China 3 Good Clinical Practice center, Sun Yat-sen University Cancer Center, Guangzhou 510060, China 4 Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou 510060, China 5 Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China * These authors have contributed equally to this work Correspondence to: Hai-Qiang Mai, e-mail: maihq@sysucc.org.cn Keywords: nasopharyngeal carcinoma, induction chemotherapy, concurrent chemotherapy, IMRT, EBV DNA Received: November 22, 2015 Accepted: March 28, 2016 Published: April 18, 2016 ABSTRACT Background: 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. Methods: 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). Results: 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). Conclusions : 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.

// Lu Zhang 1, 2, * , Huai Liu 4, 5, 6, * , Lin-Quan Tang 1, 2 , Qiu-Yan Chen 1, 2 , Shan-Shan Guo 1, 2 , Li-Ting Liu 1, 2 , Ling Guo 1, 2 , Hao-Yuan Mo 1, 2 , Chong Zhao 1, 2 , Xiang Guo 1, 2 , Ka-Jia Cao 1, 2 , Chao-Nan Qian 1, 2 , Mu-Sheng Zeng 1 , Jian-Yong Shao 1, 7 , Ying Sun 1, 8 , Jun Ma 1, 8 , Ming-Huang Hong 1, 3 , Hai-Qiang Mai 1, 2 1 Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China 2 Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China 3 GCP center, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China 4 Department of Radiotherapy, Hunan Cancer Hospital, Changsha, P. R. China 5 Department of Radiotherapy, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, P. R. China 6 Key Laboratory of Translational Radiation Oncology, Changsha, P. R. China 7 Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China 8 Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China * These authors contributed equally to this work Correspondence to: Ming-Huang Hong, e-mail: hongmh@sysucc.org.cn Hai-Qiang Mai, e-mail: maihq@sysucc.org.cn Keywords: nasopharyngeal carcinoma, pregnancy, prognosis, survival Received: December 10, 2015 Accepted: February 21, 2016 Published: March 09, 2016 ABSTRACT Objectives: We aimed to evaluate the prognosis of pregnancy-associated patients with nasopharyngeal carcinoma (NPC) in a young population. Methods: From June 1999 to December 2010, 51 patients aged ≤ 35 years who were diagnosed with NPC during pregnancy or within one year after delivery were admitted into the pregnancy-associated group in our institution. An additional 51 patients who were not pregnant at diagnosis were selected from 451 patients based on the matching criteria to match the pregnancy-associated female patients. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS) and distant-metastasis failure-free survival (DMFS) and locoregional failure-free survival (LRFS). Results: The advanced stage was not different between the pregnant and the non-pregnant group before matching (69.8% vs. 70.3%, P = 0.690). No difference in OS at the median follow-up time of 92 months was observed between the pregnancy-associated and the non-pregnant group (85.4% vs. 92.2%, P = 0.478); likewise, no differences were observed regarding PFS and DMFS. However, the pregnancy-associated group had worse LRFS than the non-pregnant group (84.8% vs. 95.9%, P = 0.033). When the pregnancy-associated patients were dichotomized into an early pregnancy group and a late pregnancy group, our data showed that pregnancy interval did not seem to impact the risk of death or relapse. Conclusion: Our results show that patients in the pregnant group did not seem to have more advanced stage or inferior survival than that in the non-pregnant group.

// Rui-Chen Li 1,2,5,* , Yong Du 2,* , Qiu-Yao Zeng 3,* , Lin-Quan Tang 2,4 , Hua Zhang 2 , Yan Li 2 , Wan-Li Liu 3 , Qian Zhong 2 , Mu-Sheng Zeng 2 and Xiao-Ming Huang 1 1 Department of Otorhinolaryngology Head and Neck Surgery, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, P. R. China 2 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China 3 Department of Clinical Laboratory, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China 4 Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China 5 Department of Otorhinolaryngology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, P. R. China * These authors have contributed equally to this work Correspondence to: Mu-Sheng Zeng, email: // Xiao-Ming Huang, email: // Keywords : nasopharyngeal carcinoma, Epstein-Barr virus, biomarker, gH/gL, viral capsid antigen Received : July 19, 2015 Accepted : February 05, 2016 Published : February 24, 2016 Abstract To determine whether measuring antibodies against Epstein-Barr virus (EBV) glycoprotein gH/gL in serum could improve diagnostic accuracy in nasopharyngeal carcinoma (NPC) cases, gH/gL expressed in a recombinant baculovirus system was used in an enzyme-linked immunosorbent assay (ELISA) to detect antibodies in two independent cohorts. Binary logistic regression analyses were performed using results from a training cohort ( n = 406) to establish diagnostic mathematical models, which were validated in a second independent cohort ( n = 279). Levels of serum gH/gL antibodies were higher in NPC patients than in healthy controls ( p < 0.001). In the training cohort, the IgA-gH/gL ELISA had a sensitivity of 83.7%, specificity of 82.3% and area under the curve (AUC) of 0.893 (95% CI, 0.862-0.924) for NPC diagnosis. Furthermore, gH/gL maintained diagnostic capacity in IgA-VCA negative NPC patients (sensitivity = 78.1%, specificity = 82.3%, AUC = 0.879 [95% CI, 0.820 - 0.937]). Combining gH/gL and viral capsid antigen (VCA) detection improved diagnostic capacity as compared to individual tests alone in both the training cohort (sensitivity = 88.5%, specificity = 97%, AUC = 0.98 [95% CI, 0.97 - 0.991]), and validation cohort (sensitivity = 91.2%, specificity = 96.5%, AUC = 0.97 [95% CI, 0.951-0.988]). These findings suggest that EBV gH/gL detection complements VCA detection in the diagnosis of NPC and aids in the identification of patients with VCA-negative NPC.

// Pei-Yu Huang 1, 2, * , Shan-Shan Guo 1, 2, * , Yu Zhang 1, 3, * , Jia-Bin Lu 1, 3 , Qiu-Yan Chen 1, 2 , Lin-Quan Tang 1, 2 , Lu Zhang 1, 2 , Li-Ting Liu 1, 2 , Li Zhang 1, 4 , Hai-Qiang Mai 1, 2 1 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China 2 Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, China 3 Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, China 4 Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China * These authors contributed equally to this work Correspondence to: Li Zhang, e-mail: zhangli@sysucc.org.cn Hai-Qiang Mai, e-mail: maihq@sysucc.org.cn Keywords: CTLA-4, CD28, nasopharyngeal carcinoma, immunohistochemistry, prognostic factor Received: July 05, 2015 Accepted: January 26, 2016 Published: February 16, 2016 ABSTRACT The expression levels of CTLA-4 and CD28 were analyzed in 191 nasopharyngeal carcinoma (NPC) patients diagnosed and treated at our hospital between January 2010 and November 2011. The 3-year overall survival (OS) rate (91.4% vs. 81.2%, p = 0.043), failure-free survival (FFS) rate (82.8% vs. 68.0%, p = 0.009) and distant failure-free survival (D-FFS) rate (85.8% vs. 72.3%, p = 0.006) in the low tumor CTLA-4 expression group was higher than in the high tumor CTLA-4 group. There were no differences between the locoregional failure-free survival (LR-FFS) rates in the high and low tumor CTLA-4 expression groups. Moreover, no differences in the OS, FFS, D-FFS, or LR-FFS were observed between the groups with high and low lymphocyte CTLA-4 levels, high and low tumor CD28 levels, or high and low lymphocyte CD28 levels. Cox regression analysis confirmed the prognostic value of tumor CTLA-4 expression, particularly for D-FFS, in NPC patients ( p = 0.044). NPC patients with high tumor CTLA-4 expression had a poorer prognosis than those with low expression.

Importance The role of locoregional radiotherapy in patients with de novo metastatic nasopharyngeal carcinoma (mNPC) is unclear. Objective To investigate the efficacy and safety of locoregional radiotherapy in de novo mNPC. Design, Setting, and Participants Patients with biopsy-proven mNPC, who demonstrated complete or partial response (RECIST v1.1) following 3 cycles of cisplatin and fluorouracil chemotherapy, were enrolled. Eligible patients were randomly assigned (1:1) to receive either chemotherapy plus radiotherapy or chemotherapy alone. Overall, 126 of 173 patients screened were eligible to the study, and randomized to chemotherapy plus radiotherapy (n = 63) or chemotherapy alone (n = 63). Median (IQR) follow-up duration was 26.7 (17.2-33.5) months. Interventions The chemotherapy regimens were fluorouracil continuous intravenous infusion at 5 g/m2over 120 hours and 100 mg/m2intravenous cisplatin on day 1, administered every 3 weeks for 6 cycles. Patients assigned to the chemotherapy plus radiotherapy group received intensity-modulated radiotherapy (IMRT) after chemotherapy. Main Outcomes and Measures The primary end point of the study was overall survival (OS). The secondary end point was progression-free survival (PFS) and safety. Results Overall, 126 patients were enrolled (105 men [83.3%] and 21 women [16.7%]; median [IQR] age, 46 [39-52] years). The 24-month OS was 76.4% (95% CI, 64.4%-88.4%) in the chemotherapy plus radiotherapy group, compared with 54.5% (95% CI, 41.0%-68.0%) in the chemotherapy-alone group. The study met its primary end point of improved OS (stratified hazard ratio [HR], 0.42; 95% CI, 0.23-0.77;P = .004) in favor of chemotherapy plus radiotherapy. Progression-free survival was also improved in the chemotherapy plus radiotherapy group compared with the chemotherapy-alone group (stratified HR, 0.36; 95% CI, 0.23-0.57). No significant differences in acute hematological or gastrointestinal toxic effects were observed between the treatment arms. The frequency of acute grade 3 or higher dermatitis, mucositis, and xerostomia was 8.1%, 33.9%, and 6.5%, respectively, in the chemotherapy plus radiotherapy group. The frequency of late severe grade 3 or higher hearing loss and trismus was 5.2% and 3.4%, respectively, in the chemotherapy plus radiotherapy group. Conclusions and Relevance In this randomized clinical trial, radiotherapy added to chemotherapy significantly improved OS in chemotherapy-sensitive patients with mNPC. Trial Registration ClinicalTrials.gov Identifier:NCT02111460

BackgroundThe tumor immune microenvironment has clinicopathological significance in predicting prognosis and therapeutic efficacy. We aimed to develop an immune signature to predict distant metastasis in patients with nasopharyngeal carcinoma (NPC).MethodsUsing multiplexed quantitative fluorescence, we detected 17 immune biomarkers in a primary screening cohort of 54 NPC tissues presenting with/without distant metastasis following radical therapy. The LASSO (least absolute shrinkage and selection operator) logistic regression model used statistically significant survival markers in the training cohort (n=194) to build an immune signature. The prognostic and predictive accuracy of it was validated in an external independent group of 304 patients.ResultsEight statistically significant markers were identified in the screening cohort. The immune signature consisting of four immune markers (PD-L1+ CD163+, CXCR5, CD117) in intratumor was adopted to classify patients into high and low risk in the training cohort and it showed a high level of reproducibility between different batches of samples (r=0.988 for intratumor; pConclusionsThe immune signature provided a reliable estimate of distant metastasis risk in patients with NPC and might be applied to identify the cohort which benefit from IC+CCRT.

Germline polymorphisms are linked with differential survival outcomes in cancers but are not well studied in nasopharyngeal carcinoma (NPC). Here, a two‐phase association study is conducted to discover germline polymorphisms that are associated with the prognosis of NPC. The discovery phase includes two consecutive hospital cohorts of patients with NPC from Southern China. Exome‐wide genotypes at 246 173 single nucleotide polymorphisms (SNPs) are determined, followed by survival analysis for each SNP under Cox proportional hazard regression model. Candidate SNP is replicated in another two independent cohorts from Southern China and Singapore. Meta‐analysis of all samples (n = 5553) confirms that the presence of rs1131636‐T, located in the 3′‐UTR of RPA1, confers an inferior overall survival (HR = 1.33, 95% CI = 1.20–1.47, P = 6.31 × 10−8). Bioinformatics and biological assays show that rs1131636 has regulatory effects on upstream RPA1. Functional studies further demonstrate that RPA1 promotes the growth, invasion, migration, and radioresistance of NPC cells. Additionally, miR‐1253 is identified as a suppressor for RPA1 expression, likely through regulation of its binding affinity to rs1131636 locus. Collectively, these findings provide a promising biomarker aiding in stratifying patients with poor survival, as well as a potential drug target for NPC., This study reveals a functional germline polymorphism at RPA1 to be associated with survival outcome of patients with nasopharyngeal carcinoma (NPC). The study also shows that RPA1 is able to regulate tumor progression and radioresistance in NPC cells. Together, the study proposes the genetic variation of RPA1 as a promising germline biomarker for precise treatment planning and prognosis of NPC.

Background and Purpose Our previous phase III randomized trial demonstrated that the addition of concurrent chemotherapy to radiotherapy (RT) could improve survival in stage II nasopharyngeal carcinoma (NPC). Based on the study, we sought to develop a nomogram for predicting the 5-year and 10-year survival of patients with stage II NPC and estimating the benefit of concurrent chemoradiotherapy (CCRT) for individual patients. Materials and methods Data of 199 enrolled patients from the original trial was analyzed to build a nomogram. Overall survival (OS) was the primary endpoint. The discrimination and calibration capacities were evaluated using Harrell Concordance Index (C-index) and calibration curves, respectively. Internal validation of the nomogram was performed by a separate cohort of 306 patients from the same cancer center. Result In training cohort, patients in CCRT group achieved higher 5-year and 10-year OS compared with patients in RT group. Three independent prognostic factors, which were age, N stage and treatment method from multivariable analysis were extracted to enter the nomogram. T stage was also included due to its importance in clinical decisions. The Harrell C-index of the nomogram in training and validation cohort was 0.748 and 0.653 respectively. The calibration curves showed an acceptable agreement between prediction and observed probability. Conclusion We developed and validated a nomogram to predict the 5-year and 10-year OS in stage II NPC patients. The nomogram could serve as a pragmatic tool in clinical decisions to estimate the individual risk of stage II patients and identify those who could benefit from chemotherapy.

Background and purpose Nasopharyngeal carcinoma (NPC) patients can be separated into two risk subgroups according to tumor responses to induction chemotherapy (IC). We aimed to elucidate the optimal cumulative cisplatin dose (CCD) of concurrent chemoradiotherapy (CCRT) for different NPC patient subgroups. Participants and methods A total of 990 patients with incident NPC diagnosed between 2008 and 2017 treated with IC plus CCRT were included in our observational study. The clinicopathological features of patients with different tumor responses were compared using the Chi-square test or Fisher’s exact test. Prognosis was assessed using a multivariate Cox proportional hazards model. In addition, acute and late toxicities were compared between different CCD groups. Results After IC, 761/990 (76.9%) patients had a complete tumor response (CR)/partial response (PR) and 229 (23.1%) had stable disease (SD)/disease progression (PD). An unsatisfactory tumor response (SD/PD) after IC correlated with poor clinical outcome (3-year PFS 61.4% vs. 83.2%, P 200 mg/m2 and showed higher 3-year PFS and DMFS rates than those receiving a CCD Conclusions Tumor response to IC was an independent prognostic factor for patients with NPC. For the patients who achieved CR/PR after IC, patients receiving high CCD showed significantly improved 3-year PFS and DMFS compared with patients receiving low CCD. Balancing toxicity and efficacy, 200 mg/m2 seemed to be the optimal dose in the CR/PR groups. However, enhancement of CCD did not provide survival benefit for patients who achieved SD/PD after IC, and treatment options for these patients require further consideration.

Background and purpose No nomogram has been established for de novo metastatic NPC patients previously. Thus, we retrospectively involved 502 de novo NPC patients to develop a practical clinical tool by combining prognostic biomarkers to estimate individual risk. Methods The nomogram was based on a primary cohort involving 353 patients from 2007 to 2013; all independent prognostic factors were integrated for inclusion in the model. The predictive accuracy of the model was evaluated by concordance index (C-index). A calibration curve was used to compare predicted and observed survival. We confirmed the results using a validation cohort study on 149 patients enrolled from 2014 to 2016. Results Five independent prognostic factors derived from multivariable analysis were entered into the nomogram. The C-index of the nomogram was 0.724. The calibration curves for probability of 3- and 5-year overall survival (OS) showed satisfactory agreement between predicted survival and actual observed survival. The Kaplan–Meier survival curves showed a significant difference in survival among different risk groups according to the total score. All results were confirmed in the validation cohort. Conclusion We established a convenient nomogram that provides individual prediction of OS for patients with de novo metastatic NPC.

Background Famitinib is a tyrosine kinase inhibitor against multiple targets, including vascular endothelial growth factor receptor 2/3, platelet-derived growth factor receptor, and stem cell factor receptor (c-kit). Previous studies have demonstrated anti-tumour activities of famitinib against a wide variety of advanced-stage solid cancers. We aimed to determine the safety and efficacy of famitinib with concurrent chemoradiotherapy (CCRT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). We also evaluated the feasibility of contrast-enhanced ultrasound (D-CEUS) as a predictor of early tumour response to famitinib and to correlate functional parameters with clinical efficacy. Methods The trial was conducted in subjects with stage III or IVa-b NPC using a 3 + 3 design of escalating famitinib doses. Briefly, subjects received 2 weeks of famitinib monotherapy followed by 7 weeks of famitinib plus CCRT. D-CEUS of the neck lymph nodes was performed at day 0, 8 and 15 after famitinib was administered before starting concurrent chemoradiotherapy. End points included safety, tolerability and anti-tumour activity. Results Twenty patients were enrolled (six each for 12.5, 16.5 and 20 mg and two for 25 mg). Two patients in the 25 mg cohort developed dose-limiting toxicities, including grade 4 thrombocytopenia and grade 3 hypertension. The most common grade 3/4 adverse events were leukopenia, neutropenia and radiation mucositis. D-CEUS tests showed that more than 60% of patients achieved a perfusion parameter response after 2 weeks taking famitinib alone, and the parameter response was associated with disease improvement. In the famitinib monotherapy stage, three patients (15%) showed partial responses. The complete response rate was 65% at the completion of treatment and 95% 3 months after the treatment ended. After a median follow-up of 44 months, the 3-year progression-free survival (PFS) and distant metastasis-free survival were 70% and 75%, respectively. Subjects with a decrease of perfusion parameter response, such as peak intensity decreased at least 30% after 1 week of famitinib treatment, had higher 3-year PFS (90.9% vs. 44.4%, 95% CI 73.7%–100% vs. 11.9%–76.9%, P

Survival analyses of populations and the establishment of prognoses for individual patients are important activities in the practice of medicine. Standard survival models, such as the Cox proportional hazards model, require extensive feature engineering or prior knowledge to model at an individual level. Some survival analysis models can avoid these problems by using machine learning extended the CPH model, and higher performance has been reported. In this paper, we propose an innovative loss function that is defined as the sum of an extended mean squared error loss and a pairwise ranking loss based on ranking information on survival data. We apply this loss function to optimize a deep feed-forward neural network (RankDeepSurv), which can be used to model survival data. We demonstrate that the performance of our model, RankDeepSurv, is superior to that of other state-of-the-art survival models based on an analysis of 4 public medical clinical datasets. When modelling the prognosis of nasopharyngeal carcinoma (NPC), RankDeepSurv achieved better prognostic accuracy than the CPH established by clinical experts. The difference between high and low risk groups in the RankDeepSurv model is greater than the difference in the CPH. The results show that our method has considerable potential to model survival data in medical settings.

Purpose Our previous results showed survival benefits of concurrent chemoradiotherapy (CCRT) in treating stage II nasopharyngeal carcinoma (NPC) compared with radiotherapy (RT) alone. Here, we present the updated 10-year survival results and late toxicity profile to assess the ultimate effectiveness of concurrent chemotherapy. Methods Patients with stage II NPC were randomly assigned to RT arm (n = 114) or to CCRT arm (n = 116) with a concurrent weekly cisplatin regimen. The primary end-point was overall survival (OS). Results With a median follow-up of 125 months, significant improvements in OS (83.6% vs 65.8%, P = 0.001), progression-free survival (76.7% vs 64.0%, P = 0.014), cancer-specific survival (86.2% vs 71.9%, P = 0.002), distant-metastasis free survival (94.0% vs 83.3%, P = 0.007) were observed in CCRT arm. In point of locoregional-relapse free survival, the impact of CCRT was not remarkable. The findings were in accordance with our previous report. The survival benefits earned by CCRT mainly reflected in T2N1 population. Although CCRT brought more acute toxic effects (P = 0.001), as presented in previous report, the late toxicities and treatment-associated deaths events were comparable between two arms. Conclusions Ten-year outcomes confirmed that CCRT could improve the OS of stage II patients without adding late toxicities compared with conventional RT.

Table S1. PICC-VTE vs non PICC-VTE: Risk of primary and secondary outcomes in the PSM cohort and the entire cohort. (DOCX 19 kb)

// Wen-Hui Chen 1, * , Lin-Quan Tang 1,2, * , Lu Zhang 1, 2, * , Qiu-Yan Chen 1, 2 , Shan-Shan Guo 1, 2 , Li-Ting Liu 1, 2 , Wei Fan 1, 3 , Xu Zhang 1, 3 , Ling Guo 1, 2 , Chong Zhao 1, 2 , Ka-Jia Cao 1, 2 , Chao-Nan Qian 1, 2 , Xiang Guo 1, 2 , Dan Xie 1 , Mu-Sheng Zeng 1 , Hai-Qiang Mai 1, 2 1 Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China 2 Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou 510060, China 3 Department of Nuclear Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China * These authors have contributed equally to this work. Correspondence to: Hai-Qiang Mai, e-mail: maihq@sysucc.org.cn Keywords: nasopharyngeal carcinoma, EBV DNA, SUVmax, survival Received: June 25, 2015 Accepted: September 30, 2015 Published: October 13, 2015 ABSTRACT 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.

Recurrent tumour, node and metastasis (rTNM) stage system does not have an outstanding prognostic value for survival outcome of patients with recurrent nasopharyngeal carcinoma (rNPC) and it cannot aid the clinicians to choose the most suitable treatment for these patients.In total, 894 rNPC patients were consecutively enroled. All recurrent (r) tumour (T) stages (rT) and node (N) stages (rN) were stratified as resectable and unresectable based on the imaging data of the head and neck. These stages were re-subdivided into surgical T stages (sT) and surgical N stages (sN) with similar clinical characteristics and death risks and were re-integrated into a new 'surgical' stage using a Cox proportional hazards model.The 5-year overall survival (OS) was 72.0%, 55.1%, 21.1% and 10.1% in 'surgical' stages I, II, III and IV, respectively (P0.001). The 'surgical' stage was a significant independent prognostic factor for OS (hazard ratio [HR] 1.78, P0.001) and exhibited enhanced prognostic value compared with the rTNM staging system (area under receiver operating characteristics 0.68 versus 0.63, P0.001). Endoscopic nasopharyngectomy and intensity-modulated radiation therapy were significant independent positive prognostic factors for the OS of patients with primary lesions in 'surgical' stage I/II and 'surgical' stage III, respectively (P0.05). A combination of aggressive treatments for loco-regional lesions exhibited a beneficial trend for OS of patients with 'surgical' stage IV (P0.05).Compared with the rTNM stage system, the 'surgical' staging system exhibited enhanced prognostic value for rNPC patient survival and could aid clinicians in choosing the most suitable treatment for rNPC patients.

Purpose To evaluate the effects of combining the assessment of circulating high-sensitivity C-reactive protein (hs-CRP) with that of Epstein-Barr virus DNA (EBV DNA) in the pretherapy prognostication of nasopharyngeal carcinoma (NPC). Patients and Methods Three independent cohorts of NPC patients (training set of n=3113, internal validation set of n=1556, and prospective validation set of n=1668) were studied. Determinants of disease-free survival, distant metastasis–free survival, and overall survival were assessed by multivariate analysis. Hazard ratios and survival probabilities of the patient groups, segregated by clinical stage (T1-2N0-1M0, T3-4N0-1M0, T1-2N2-3M0, and T3-4N2-3M0) and EBV DNA load (low or high) alone, and also according to hs-CRP level (low or high), were compared. Results Elevated hs-CRP and EBV DNA levels were significantly correlated with poor disease-free survival, distant metastasis–free survival, and overall survival in both the training and validation sets. Associations were similar and remained significant after excluding patients with cardiovascular disease, diabetes, and chronic hepatitis B. Patients with advanced-stage disease were segregated by high EBV DNA levels and high hs-CRP level into a poorest-risk group, and participants with either high EBV DNA but low hs-CRP level or high hs-CRP but low EBV DNA values had poorer survival compared with the bottom values for both biomarkers. These findings demonstrate a significant improvement in the prognostic ability of conventional advanced NPC staging. Conclusion Baseline plasma EBV DNA and serum hs-CRP levels were significantly correlated with survival in NPC patients. The combined interpretation of EBV DNA with hs-CRP levels led to refinement of the risks for the patient subsets, with improved risk discrimination in patients with advanced-stage disease.

It has been suggested that formin-like protein 1 (FMNL1) plays an important role in the pathogenic process of several hematopoietic malignancies. In this study, we performed a series of in vivo and in vitro assays to elucidate the biological functions of FMNL1 and underlying mechanisms in human nasopharyngeal carcinoma (NPC) pathogenesis. Herein, we report that high expression of FMNL1 in NPC is positively associated with an aggressive disease and/or poor patient survival. Ectopic overexpression of FMNL1 in NPC cells substantially promoted cell invadopodia formation, epithelial-mesenchymal transition (EMT) and invasiveness, whereas depletion of FMNL1 potently suppressed NPC cells invadopodia formation, EMT, and invasive/metastatic capacities. We further show that FMNL1 could enhance NPC cell aggressiveness by increasing a key downstream target, the metastasis-associated protein 1 (MTA1) gene. Importantly, ectopic overexpression of FMNL1 in NPC cells markedly improved the binding of HDAC1 with Profilin2 in the cytoplasm and suppressed the enrichment of HDAC1 on the promoter of MTA1 and thereby, leading to an increased MTA1 transcription and expression. Furthermore, in addition to the amplification of FMNL1 gene, decreased level of miR-16 in NPCs is another critical mechanism to upregulate FMNL1 expression. These results, collectively, provide first-line of evidences that high expression of FMNL1, resulted from decreased miR-16 and/or MTA1 amplification, has a potent oncogenic role to drive the development and aggressive process of NPC by upregulating MTA1, and FMNL1 might be employed as a new prognostic biomarker and therapeutic target for human NPC.

Summary Background Cisplatin-based concurrent chemoradiotherapy is currently considered to be the standard treatment regimen for patients with advanced nasopharyngeal carcinoma, but has well known side-effects such as gastrointestinal reactions, nephrotoxicity, and ototoxicity. Nedaplatin was developed to decrease the toxic effects induced by cisplatin, and in this trial we assessed whether a nedaplatin-based concurrent chemoradiotherapy regimen was non-inferior to a cisplatin-based regimen in patients with locoregional, stage II–IVB nasopharyngeal carcinoma. Methods We did an open-label, non-inferiority, phase 3, randomised, controlled trial at two centres in China. Patients aged 18–65 years with non-keratinising stage II–IVB (T1–4N1–3 or T3–4N0) nasopharyngeal carcinoma, a Karnofsky score of at least 70, and adequate haematological, renal, and hepatic function were randomly assigned (1:1) to receive intravenously either nedaplatin 100 mg/m 2 or cisplatin 100 mg/m 2 on days 1, 22, and 43 for three cycles concurrently with intensity-modulated radiotherapy. Randomisation was done manually using a computer-generated random number code and patients were stratified by treatment centre and clinical stage. Patients and clinicians were not masked to treatment allocation. The primary endpoint was progression-free survival at 2 years; non-inferiority was shown if the upper limit of the 95% CI for the difference in 2-year progression-free survival between the two groups did not exceed 10%. Analyses were by both intention to treat and per protocol, including all patients who received at least one complete cycle of chemotherapy. This trial is registered with ClinicalTrials.gov, number NCT01540136, and is currently in follow-up. Findings Between Jan 16, 2012, and July 16, 2014, we randomly assigned 402 patients to nedaplatin-based (n=201) or cisplatin-based (n=201) concurrent chemoradiotherapy. In the intention-to-treat population, 2-year progression-free survival was 89·9% (95% CI 85·8–94·0) in the cisplatin group and 88·0% (83·5–94·5) in the nedaplatin group, with a difference of 1·9% (95% CI −4·2 to 8·0; p non-inferiority =0·0048). In the per-protocol analysis (cisplatin group, n=197; nedaplatin group, n=196), 2-year progression-free survival was 89·7% (95% CI 85·4–94·0) in the cisplatin group and 88·7% (84·2–94·5) in the nedaplatin group, with a difference of 1·0% (95% CI −5·2 to 7·0; p non-inferiority =0·0020). A significantly higher frequency of grade 3 or 4 vomiting (35 [18%] of 198 in the cisplatin group vs 12 [6%] of 200 in the nedaplatin group, p vs four [2%], p=0·0021), and anorexia (53 [27%] vs 26 [13%], p=0·00070) was observed in the cisplatin group compared with the nedaplatin group. 11 (6%) patients in the nedaplatin group had grade 3 or 4 thrombocytopenia compared with four (2%) in the cisplatin group (p=0·065). Patients in the cisplatin group had a higher frequency of any grade or grade 3 or 4 late auditory or hearing toxicities than did patients in the nedaplatin group (grade 3 or 4: three [2%] in the nedaplatin group vs 11 [6%] in the cisplatin group, p=0·030). No patients died from treatment-related causes. Interpretation Our findings show that nedaplatin-based concurrent chemoradiotherapy represents an alternative doublet treatment strategy to cisplatin-based concurrent chemoradiotherapy for patients with locoregional, advanced nasopharyngeal carcinoma. Further investigations are needed to explore the potential use of this treatment as induction or adjuvant chemotherapy or in combination with other agents. Funding National Key R&D Program of China, National Natural Science Foundation of China, Sun Yat-sen University Clinical Research 5010 Program, Sci-Tech Project Foundation of Guangzhou City, National Key Basic Research Program of China, Special Support Plan of Guangdong Province, Sci-Tech Project Foundation of Guangdong Province, Health & Medical Collaborative Innovation Project of Guangzhou City, National Science & Technology Pillar Program during the Twelfth Five-year Plan Period, PhD Start-up Fund of Natural Science Foundation of Guangdong Province, Cultivation Foundation for the Junior Teachers in Sun Yat-sen University, and Fundamental Research Funds for the Central Universities.

Background To evaluate the prognostic significance of pretreatment quality of life for patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy. Methods We performed a prospective, longitudinal study on 554 newly diagnosed patients with NPC from April 2011 to January 2015. A total of 501 consecutive NPC patients were included. Patients were asked to complete the EORTC QLQ-C30 (version 3.0) and QLQ-H&N35 questionnaires before treatment. Results Global health status among QLQ-C30 correlates with EBV DNA(P = 0.019). In addition, pretreatment appetite loss was significantly correlated with EBV DNA(P = 0.02). Pretreatment teeth, opening mouth, feeding tube was significantly correlated with EBV DNA, with P value of 0.003

Purpose 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. Materials and methods 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. Results Gross tumor volume of cervical lymph nodes (GTVnd, p l 0.001) and total tumor volume (GTVtotal, p l 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 l 30 cm3; EBV DNA 0 copy/mL, GTVtotal ≥ 30 cm3; or EBV DNA g 0 copy/mL, GTVtotal l 30 cm3) and a high-risk group (EBV DNA g 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. Conclusion 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.

Purpose The measuring Epstein-Barr virus (EBV) DNA is an important predictor of nasopharyngeal carcinoma (NPC). This study evaluated the predictive value of pretreatment serum amyloid A (SAA) and C-reactive protein (CRP) comparing with EBV DNA in patients with NPC. Materials and methods In an observational study of 419 non-metastatic NPC patients, we prospectively evaluated the prognostic effects of pretreatment SAA, CRP, and EBV DNA on survival. The primary endpoint was progress-free survival (PFS). Results The median level of SAA and CRP was 4.28 mg/L and 1.88 mg/L, respectively. For the highSAA group (g 4.28 mg/L) versus the low-SAA (≤ 4.28 mg/L) group and the high-CRP group (g 1.88 mg/L) versus the low-CRP (≤ 1.88 mg/L) group, the 5-year PFS was 64.5% versus 73.1% (p=0.013) and 65.2% versus 73.3% (p=0.064), respectively. EBV DNA detection showed a superior predictive result, the 5-year PFS in the EBV DNA ≥ 1,500 copies/mL group was obviously different than the EBV DNA l 1,500 copies/mL group (62.2% versus 77.8%, p l 0.001). Multifactorial Cox regression analysis confirmed that in the PFS, the independent prognostic factors were including EBV DNA (hazard ratio [HR], 1.788; p=0.009), tumour stage (HR, 1.903; p=0.021), and node stage (HR, 1.498; p=0.049), but the SAA and CRP were not included in the independent prognostic factors. Conclusion The results of SAA and CRP had a certain relationship with the prognosis of NPC, and the prognosis of patients with high level of SAA and CRP were poor. However, the predictive ability of SAA and CRP was lower than that of EBV DNA.

Background This study aimed to evaluate the long-term outcome and toxicities in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated by concurrent chemoradiotherapy (CCRT) with/without adding cetuximab. Methods A total of 62 patients treated with CCRT plus cetuximab were matched with 124 patients treated with CCRT alone by age, sex, pathological type, T category, N category, disease stage, radiotherapy (RT) technique, Epstein-Barr virus (EBV) DNA levels, and Eastern Cooperative Oncology Group (ECOG). Overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were assessed using the Kaplan–Meier method and log-rank test. Treatment toxicities were clarified and compared between two groups. Results A total of 186 well-balanced stage II to IV NPC patients were retrospectively analyzed (median follow-up, 76 months). Compared to CCRT alone, adding cetuximab resulted in more grade 3 to 4 radiation mucositis (51.6% vs. 23.4%; P

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

This abstract was not presented at the conference. Citation Format: Luo J, Chen Q, Tang L, Yang L, Han E, Chen Y, Yuan L. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-02-01.

To evaluate the prognostic value of serum endostatin levels in patients with advanced-stage nasopharyngeal carcinoma (NPC).Between August 2003 and March 2005, 218 patients with advanced-stage NPC were enrolled in this study, including 70 patients in the training cohort and 148 in the validation cohort. The pre-treatment serum endostatin and vascular endothelial growth factor (VEGF) levels were measured using competitive enzyme immunoassays. For the normal control, serums samples from 20 healthy individuals were also collected.Serum endostatin levels in the patients with advanced-stage NPC were significantly higher than those of controls, but VEGF levels were similar in the two groups. Univariate analysis revealed significant differences between the high and low endostatin level groups regarding 5 year overall survival (63.9% versus 90.5%; P = 0.003), progression-free survival (PFS) (50.2% versus 79.3%; P = 0.003) and distant metastasis-free survival (DMFS) (59.1% versus 85.3%; P = 0.01) in the training cohort. Using the same cut-off value generated from the training cohort, there were also significant unfavourable correlations between serum endostatin levels and overall survival (P = 0.001), PFS (P = 0.001) and DMFS (P = 0.002) in the second independent validation cohort. Multivariate analysis using the entire group (n = 218) revealed that the serum endostatin level was an independent unfavourable prognostic factor for overall survival (hazard ratio 4.8; 95% confidence interval 2.48-9.23; P0.0001), PFS (hazard ratio 3.44; 95% confidence interval 2.06-5.74; P0.0001) and DMFS (hazard ratio 3.65; 95% confidence interval 1.92-6.94; P0.0001) in patients with advanced-stage NPC. No associations were observed between the outcomes and the serum VEGF levels in patients with advanced-stage NPC.High endostatin levels are associated with poor survival and this knowledge may improve the risk stratification of patients with advanced-stage NPC.

Background The role of neoadjuvant chemotherapy (NACT) for locoregionally advanced nasopharyngeal carcinoma (NPC) is unclear. We aimed to evaluate the feasibility and efficacy of NACT followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in locoregionally advanced NPC. Methods Patients with stage III–IVB (excluding T3N0-1) NPC were randomly assigned to receive NACT followed by CCRT (investigational arm) or CCRT alone (control arm). Both arms were treated with 80 mg/m2 cisplatin every 3 weeks concurrently with radiotherapy. The investigational arm received cisplatin (80 mg/m2 d1) and fluorouracil (800 mg/m2 civ d1–5) every 3 weeks for two cycles before CCRT. The primary end-point was disease-free survival (DFS) and distant metastasis-free survival (DMFS). Secondary end-point was overall survival (OS). Survival curves for the time-to-event endpoints were analyzed by the Kaplan–Meier method and compared using the log-rank test. The P value was calculated using the 5-year endpoints. Results Four hundred seventy six patients were randomly assigned to the investigational (n = 238) and control arms (n = 238). The investigational arm achieved higher 3-year DFS rate (82.0%, 95% CI = 0.77–0.87) than the control arm (74.1%, 95% CI = 0.68–0.80, P = 0.028). The 3-year DMFS rate was 86.0% for the investigational arm versus 82.0% for the control arm, with marginal statistical significance (P = 0.056). However, there were no statistically significant differences in OS or locoregional relapse-free survival (LRRFS) rates between two arms (OS: 88.2% versus 88.5%, P = 0.815; LRRFS: 94.3% versus 90.8%, P = 0.430). The most common grade 3–4 toxicity during NACT was neutropenia (16.0%). During CCRT, the investigational arm experienced statistically significantly more grade 3–4 toxicities (P Conclusion NACT improved tumour control compared with CCRT alone in locoregionally advanced NPC, particularly at distant sites. However, there was no early gain in OS. Longer follow-up is needed to determine the eventual therapeutic efficacy.

Background The study aimed to evaluate the long-term outcome in patients with advanced local recurrent nasopharyngeal carcinoma (NPC) treated with or without reirradiation. Methods A total of 44 patients treated without reirradiation (non-RT + chemotherapy) were matched with 44 patients treated with reirradiation (re-RT+/-chemtherapy) by age, sex, Karnosky performance score (KPS), rT stage, rN stage, and time interval between initial radiation and recurrence (TI). Overall survival (OS) rate and time to progression (TTP) rate were assessed using Kaplan–Meier method, log-rank test, and Cox regression analysis. Results From March 2008 to December 2013, a total of 88 well-balanced rT3–4 N0-1 NPC patients were retrospectively analyzed. After a median follow-up of 27 months (range: 6–85), the 5-year OS rate and TTP rate was 23.4 %, 39.0 % in the non-RT + chemotherapy group and 27.5 %, 49.8 % in the re-RT+/-chemtherapy group, respectively. Multivariate analysis showed that significant toxic effect was the only significant prognosticator correlated with OS (HR: 2.15, 95 % CI = 1.02–4.53, p = 0.044). No statistically significant survival differences were observed between the two treatment groups in either univariate or multivariate analyses. Conclusion Compared with reiradiation, treating advanced local recurrent NPC with chemotherapy alone warrants further validation in the view of its similar survival and more acceptable toxicities. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2803-2) contains supplementary material, which is available to authorized users.