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Abstract Background To compare the differences in long-term quality of life (QoL) between survivors of paediatric and adult patients with nasopharyngeal carcinoma (NPC) and assess the clinical factors that predict long-term QoL. Methods We enrolled 420 long-term NPC survivors who were alive for at least 8 years after treatment, including 195 paediatric and 225 adult patients diagnosed and treated with intensity-modulated radiotherapy (IMRT) at Sun Yat-sen University Cancer Centre (SYSUCC) between 2011 and 2015. Data on clinical factors and EORTC QLQ-C30 were collected from all participants. The QoL of paediatric and adult NPC survivors was compared. Results The paediatric group had significantly better outcomes in global health status (paediatric: 80.2 ± 12.7; adult: 77.2 ± 11.5; P = 0.027), physical function (paediatric: 98.5 ± 4.6; adult: 95.1 ± 7.0; P

Abstract Background To investigate the prognosis of longitudinal health-related quality of life (HRQOL) during concurrent chemoradiotherapy (CCRT) on survival outcomes in patients with advanced nasopharyngeal carcinoma (NPC). Methods During 2012–2014, 145 adult NPC patients with stage II-IVb NPC were investigated weekly using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30 (EORCT QLQ-C30) during their CCRT period. The effects of longitudinal trends of HRQOL on survival outcomes were estimated using joint modeling, and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were reported as a 10-point increase in HRQOL scores. Results After a median follow-up of 83.4 months, the multivariable models showed significant associations of longitudinal increasing scores in fatigue and appetite loss during the CCRT period with distant metastasis-free survival: 10-point increases in scores of fatigue and appetite loss domains during CCRT period were significantly associated with 75% (HR: 1.75, 95% CI: 1.01, 3.02; p = 0.047) and 59% (HR: 1.59, 95% CI: 1.09, 2.59; p = 0.018) increase in the risk of distant metastasis, respectively. The prognostic effects of the longitudinal HRQOL trend on overall survival and progress-free survival were statistically non-significant. Conclusion Increases in fatigue and appetite loss of HRQOL during the CCRT period are significantly associated with high risks of distant metastasis in advanced NPC patients. Nutritional support and psychological intervention are warranted for NPC patients during the treatment period.

Abstract Patients with residual nasopharyngeal carcinoma after receiving definitive treatment have poor prognoses. Although immune checkpoint therapies have achieved breakthroughs for treating recurrent and metastatic nasopharyngeal carcinoma, none of these strategies have been assessed for treating residual nasopharyngeal carcinoma. In this single-arm, phase 2 trial, we aimed to evaluate the antitumor efficacy and safety of toripalimab (anti-PD1 antibody) plus capecitabine in patients with residual nasopharyngeal carcinoma after definitive treatment (ChiCTR1900023710). Primary endpoint of this trial was the objective response rate assessed according to RECIST (version 1.1). Secondary endpoints included complete response rate, disease control rate, duration of response, progression-free survival, safety profile, and treatment compliance. Between June 1, 2020, and May 31, 2021, 23 patients were recruited and received six cycles of toripalimab plus capecitabine every 3 weeks. In efficacy analyses, 13 patients (56.5%) had complete response, and 9 patients (39.1%) had partial response, with an objective response rate of 95.7% (95% CI 78.1-99.9). The trial met its prespecified primary endpoint. In safety analyses, 21 of (91.3%) 23 patients had treatment-related adverse events. The most frequently reported adverse event was hand-foot syndrome (11 patients [47.8%]). The most common grade 3 adverse event was hand-foot syndrome (two patients [8.7%]). No grades 4-5 treatment-related adverse events were recorded. This phase 2 trial shows that combining toripalimab with capecitabine has promising antitumour activity and a manageable safety profile for patients with residual nasopharyngeal carcinoma.

Abstract Background Post-radiation nasopharyngeal necrosis (PRNN) is a severe adverse event following re-radiotherapy for patients with locally recurrent nasopharyngeal carcinoma (LRNPC) and associated with decreased survival. Biological heterogeneity in recurrent tumors contributes to the different risks of PRNN. Radiomics can be used to mine high-throughput non-invasive image features to predict clinical outcomes and capture underlying biological functions. We aimed to develop a radiogenomic signature for the pre-treatment prediction of PRNN to guide re-radiotherapy in patients with LRNPC. Methods This multicenter study included 761 re-irradiated patients with LRNPC at four centers in NPC endemic area and divided them into training, internal validation, and external validation cohorts. We built a machine learning (random forest) radiomic signature based on the pre-treatment multiparametric magnetic resonance images for predicting PRNN following re-radiotherapy. We comprehensively assessed the performance of the radiomic signature. Transcriptomic sequencing and gene set enrichment analyses were conducted to identify the associated biological processes. Results The radiomic signature showed discrimination of 1-year PRNN in the training, internal validation, and external validation cohorts (area under the curve (AUC) 0.713–0.756). Stratified by a cutoff score of 0.735, patients with high-risk signature had higher incidences of PRNN than patients with low-risk signature (1-year PRNN rates 42.2–62.5% vs. 16.3–18.8%, P

Abstract Immunotherapy combined with antiangiogenic targeted therapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for refractory recurrent/metastatic nasopharyngeal carcinoma (RM-NPC). We conducted a phase 2 trial to evaluate the safety and activity of camrelizumab plus apatinib in platinum-resistant (cohort 1, NCT04547088) and PD-1 inhibitor resistant NPC (cohort 2, NCT04548271). Here we report on the primary outcome of objective response rate (ORR) and secondary endpoints of safety, duration of response, disease control rate, progression-free survival, and overall survival. The primary endpoint of ORR was met for cohort 1 (65%, 95% CI, 49.6–80.4, n = 40) and cohort 2 (34.3%; 95% CI, 17.0–51.8, n = 32). Grade ≥ 3 treatment-related adverse events (TRAE) were reported in 47 (65.3%) of 72 patients. Results of our predefined exploratory investigation of predictive biomarkers show: B cell markers are the most differentially expressed genes in the tumors of responders versus non-responders in cohort 1 and that tertiary lymphoid structure is associated with higher ORR; Angiogenesis gene expression signatures are strongly associated with ORR in cohort 2. Camrelizumab plus apatinib combination effectiveness is associated with high expression of PD-L1, VEGF Receptor 2 and B-cell-related genes signatures. Camrelizumab plus apatinib shows promising efficacy with a measurable safety profile in RM-NPC patients.

Summary: It is imperative to optimally utilize virtues and obviate defects of fully automated analysis and expert knowledge in new paradigms of healthcare. We present a deep learning-based semiautomated workflow (RAINMAN) with 12,809 follow-up scans among 2,172 patients with treated nasopharyngeal carcinoma from three centers (ChiCTR.org.cn, Chi-CTR2200056595). A boost of diagnostic performance and reduced workload was observed in RAINMAN compared with the original manual interpretations (internal vs. external: sensitivity, 2.5% [p = 0.500] vs. 3.2% [p = 0.031]; specificity, 2.9% [p

Abstract Background Previous studies have shown that monotherapy with apatinib, an oral tyrosine kinase inhibitor, has promising efficacy for treating recurrent or metastatic (RM) nasopharyngeal carcinoma (NPC) patients. In this study, we aimed to assess the efficacy and safety of apatinib combined with capecitabine as a second-line therapy or beyond for treating RM-NPC patients who failed the first-line platinum-based chemotherapy. Methods In this single-arm, phase II study, we enrolled RM-NPC patients who had at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1). The sample size was determined using Simon’s two-stage design. All patients were administered with apatinib 500 mg once daily and capecitabine 1000 mg/m2 twice per day on days 1–14 of each 21-day cycle. The primary endpoint was the objective response rate (ORR), and the secondary endpoints comprised disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. Results We enrolled 64 patients from September 2018 to August 2020. The ORR and DCR were 39.1% (95% CI, 27.1–52.1) and 85.9% (95% CI, 75.0–93.4), respectively. The median DoR was 14.4 months (95% CI, 7.8–21.0). As of April 20, 2021, the median follow-up duration was 12.0 months. The median PFS was 7.5 months (95% CI, 5.0–10.0) and the median OS was 15.7 months (95% CI, 11.3–20.1). The most common toxicities of any grade were anemia (75.0%), hand-foot syndrome (65.6%), and proteinuria (64.0%). Grade 3–4 toxicities were observed in 36 (56.3%) patients, with hypertension (14.1%), mucositis (12.4%), and fatigue (10.9%) most commonly observed. Conclusions Apatinib plus capecitabine shows promising efficacy as a second-line treatment option in pretreated platinum-refractory RM-NPC patients. Dose selection of this combination needs further investigation considering the toxicity. Trial registration Chi-CTR1800017229.

Summary: Background: Previous studies demonstrated that induction chemotherapy (IC) followed by de-escalated chemoradiotherapy adapted to tumor response was effective in treating childhood nasopharyngeal carcinoma (NPC), but the toxicity profile of this treatment strategy, and whether childhood patients with advanced stages can obtain enough benefits from it requires further investigation. Methods: We conducted a single-center phase II trial (NCT03020329). All participants received 3 cycles of paclitaxel liposome, cisplatin and 5-fluorouracil (TPF)-based IC. Patients who showed complete or partial response received de-escalated radiotherapy of 60 Gy with 3 cycles of concurrent cisplatin, and those who showed stable or progressive disease received standard-dose radiotherapy of 70 Gy with concurrent cisplatin. The primary endpoint was the complete response (CR) rate at the end of concurrent chemoradiotherapy (CCRT). Findings: From November 2016 to March 2021, 44 patients were recruited in the cohort. The CR rate was 80% (35/44, 95% CI, 65–90) of the whole cohort. All patients achieved CR 3 months after CCRT. By the last follow-up, the 3-year progression-free survival and overall survival were 91% (95% CI, 82–99) and 100% respectively. Dry mouth was the most common late toxicity, with an incidence of 41% (18/44), followed by skin fibrosis and hearing impairment. No patient suffered from severe late toxicity and growth retardation. Interpretation: Our results proved the efficacy and safety of TPF regimen followed by de-escalated radiotherapy with concurrent cisplatin in treating stage IVa-b childhood NPC patients. Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Abstract Purpose To analyze the clinical outcomes of patients with regional persistent/recurrent nasopharyngeal carcinoma (NPC) who received neck dissection, and to evaluate the clinical benefit of postoperative adjuvant therapy (PAT) based on patients’ positive lymph node counts (PLNs), extracapsular spread (ECS) and preoperative plasma EBV DNA levels. Methods From 2003 to 2017, 342 patients with regional persistent/recurrent NPC were included in this study. All patients were treated with neck dissection and 76 patients received PAT. Progression-free survival (PFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRFS) were compared between groups using propensity score matching (PSM). Results 152 patients without PAT treatment and 76 patients with PAT treatment were selected by the PSM. There was no significant difference in 2-year PFS (52.4% vs. 61.3%, P = 0.371), 2-year OS (91.9% vs. 90.5%, P = 0.097) or 2-year LRFS (66.3% vs. 67.9%, P = 0.872) between the two groups. However, the application of PAT brought survival benefits to patients in terms of 2-year DMFS (76.5% vs. 84.7%, P = 0.020). PLN, ECS and preoperative EBV DNA level remained independent risk factors for poorer PFS. Accordingly, patients were divided into low-risk and high-risk groups using receiver operating characteristic (ROC) curve; the 2-year PFS rates for two risk groups were 73.4% and 59.1% (P

Abstract Background Distinguishing patients at a greater risk of recurrence is essential for treating locoregional advanced nasopharyngeal carcinoma (NPC). This study aimed to explore the potential of aldo–keto reductase 1C4 (AKR1C4) in stratifying patients at high risk of locoregional relapse. Methods A total of 179 patients with locoregionally advanced NPC were grouped by different strategies; they were: (a) divided into two groups according to AKR1C4 expression level, and (b) classified into three clusters by integrating AKR1C4 and Epstein-Barr virus (EBV) DNA. The Kaplan–Meier method was used to calculate locoregional relapse-free survival (LRFS), overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS). The Cox proportional hazards model was used to determine potential prognostic factors, and a nomogram was generated to predict 3-year and 5-year LRFS. Results A significant difference in the 5-year LRFS was observed between the high and low AKR1C4 expression groups (83.3% vs. 92.7%, respectively; p = 0.009). After integrating AKR1C4 expression and EBV DNA, the LRFS (84.7%, 84.5%, 96.9%, p = 0.014) of high-, intermediate-, and low- AKR1C4 and EBV DNA was also significant. Multivariate analysis indicated that AKR1C4 expression (p = 0.006) was an independent prognostic factor for LRFS. The prognostic factors incorporated into the nomogram were AKR1C4 expression, T stage, and EBV DNA, and the concordance index of the nomogram for locoregional relapse was 0.718. Conclusions In conclusion, high AKR1C4 expression was associated with a high possibility of relapse in NPC patients, and integrating EBV DNA and AKR1C4 can stratify high-risk patients with locoregional recurrence.

Purpose: Chemotherapy, when added to radiotherapy, improves survival in locally advanced nasopharyngeal carcinoma (NPC). This article presents the second update of the Meta-Analysis of Chemotherapy in NPC. Methods: Published or unpublished randomized trials assessing radiotherapy (±a second chemotherapy timing) with/without chemotherapy in non-metastatic NPC patients were identified. Updated data were sought for studies included in the previous rounds of the meta-analysis. The primary endpoint was overall survival. All trials were analyzed following the intent-to-treat principle using a fixed-effects model. Treatments were classified in five subsets according to chemotherapy timing. The statistical analysis plan was pre-specified. Results: Eighteen new trials were identified. Individual patient data were available for seven. In total, the meta-analysis now included 26 trials and 7,080 patients. The addition of chemotherapy reduced the risk of death, with a hazard ratio (HR) of 0.79 (95% confidence interval (CI) [0.73; 0.85]), and an absolute survival increase at 5 and 10 years of 6.1% [+3.9; +8.3] and + 8.4% [+5.7; +11.1], respectively. The largest effect was observed for concomitant + adjuvant, induction (with concomitant in both arms) and concomitant chemotherapy, with respective HR [95%CI] of 0.68 [0.59; 0.79] (absolute survival increase at 5 years: 12.3% (7.0%;17.6%)), 0.73 [0.63; 0.86] (6.0% (2.5%;9.5%)) and 0.81 [0.70; 0.92] (5.2% (0.8%;9.6%)). The benefit of chemotherapy was also demonstrated by improvement in progression-free survival, cancer mortality, locoregional control and distant control. There was a significant interaction between patient age and chemotherapy effect. Conclusion: This updated meta-analysis confirms the benefit of concomitant chemotherapy and concomitant + adjuvant chemotherapy, and suggests that addition of induction or adjuvant chemotherapy to concomitant chemotherapy improves tumor control and survival. The benefit of chemotherapy decreases with increasing patient age.

Abstract Background To evaluate the prognostic value of the apparent diffusion coefficient (ADC) derived from diffusion-weighted magnetic resonance imaging (MRI) and monitor the early treatment response to induction chemotherapy (IC) with plasma EBV DNA in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Results A total of 307 stage III-IVb NPC patients were prospectively enrolled. All patients underwent MRI examinations to calculate ADC and plasma EBV DNA measurements pretreatment and post-IC. The participants’ ADC value of 92.5% (284/307) increased post-IC. A higher percent change in ADC value (ΔADC%high group) post-IC was associated with a higher 5-year OS rate (90.7% vs 74.9%, p

Purpose: To establish a risk classification of de novo metastatic nasopharyngeal carcinoma (mNPC) patients based on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET-CT) radiomics parameters to identify suitable candidates for locoregional radiotherapy (LRRT). Methods: In all, 586 de novo mNPC patients who underwent 18 F-FDG PET-CT prior to palliative chemotherapy (PCT) were involved. A Cox regression model was performed to identify prognostic factors for overall survival (OS). Candidate PET-CT parameters were incorporated into the PET-CT parameter score (PPS). Recursive partitioning analysis (RPA) was applied to construct a risk stratification system. Results: Multivariate Cox regression analyses revealed that total lesion glycolysis of locoregional lesions (LRL-TLG), the number of bone metastases (BMs), metabolic tumor volume of distant soft tissue metastases (DSTM-MTV), pretreatment Epstein–Barr virus DNA (EBV DNA), and liver involvement were independent prognosticators for OS. The number of BMs, LRL-TLG, and DSTM-MTV were incorporated as the PPS. Eligible patients were divided into three stages by the RPA-risk stratification model: M1a (low risk, PPS low + no liver involvement), M1b (intermediate risk, PPS low + liver involvement, PPS high + low EBV DNA), and M1c (high risk, PPS high + high EBV DNA). PCT followed by LRRT displayed favorable OS rates compared to PCT alone in M1a patients ( p 0.05). Conclusions: The PPS-based RPA stratification model could identify suitable candidates for LRRT. Patients with stage M1a disease could benefit from LRRT.

Abstract Background Nasopharyngeal carcinoma (NPC) is a malignancy predominantly associated with infection by the Epstein-Barr virus (EBV). Approximately 12,900 new cases of NPC occur each year, with more than 70% of cases occurring in the east and southeast Asia. NPC is different from ordinary head and neck squamous cell carcinoma due to its particular biological properties and it is highly sensitive to radiotherapy. With the development of RT technology, the 3-year local control rate and survival rates of non-metastatic NPC reached 80–90% in the intensity-modulated RT (IMRT) era. However, whether distant metastatic NPC (de novo mNPC, dmNPC) should receive locoregional RT (LRRT) needs to be clarified. Results Multivariate analysis identified three independent prognostic factors: Epstein-Barr virus (EBV) DNA, number of metastatic lesions, and number of metastatic organs. Through these factors, all patients were successfully divided into 3 subgroups: low-risk (single metastatic organ, EBV DNA ≤ 25,000 copies/ml, and ≤ 5 metastatic lesions), intermediate-risk (single metastatic organ, EBV DNA > 25,000 copies/ml, and ≤ 5 metastatic lesions), and high-risk (multiple metastatic organs or > 5 metastatic lesions or both). By comparing LRRT and non-LRRT groups, statistical differences were found in OS in the low-risk and intermediate-risk subgroups (p = 0.039 and p = 0.010, respectively) but no significant difference was found in OS in the high-risk subgroup (p = 0.076). Further multivariate analysis of different risk stratifications revealed that LRRT can improve OS of low- and intermediate-risk subgroups. Conclusions The risk stratification of dmNPC may be used as a new prognostic factor to help clinicians organize individualized LRRT treatment to improve the survival outcomes of dmNPC patients.

Purpose: Our purpose was to investigate the prognostic role of plasma Epstein-Barr virus (EBV) DNA levels in the middle of intensity modulated radiation therapy (IMRT). Methods and Materials: In total, 1881 patients with stage III-IVa tumors were included. The overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method, and the differences were compared using the log-rank test. Receiver operating characteristic curve analysis was performed to analyze the diagnostic value of EBV DNA levels for tumor progression or death. Multivariate analyses using the Cox model were used to evaluate potential prognostic factors. Results: The positive predict value and negative predict value of plasma EBV DNA > 0 copies/mL in the middle of IMRT in predicting nasopharyngeal carcinoma progression was 37.4% and 85.5%, respectively. In patients with plasma EBV DNA level = 0 copies/mL, no significant differences in OS were observed between patients treated with 200 mg/m² cisplatin and those treated with >200 mg/m² cisplatin (5-year OS, 94.9% vs 94.4%; PFS, 81.5% vs 87.6%). However, those treated with >200 mg/m² cisplatin had higher PFS. In patients with plasma EBV DNA level > 0 copies/mL, patients treated with >200 mg/m² cisplatin displayed a favorable 5-year OS (84.6% vs 73.9%) and PFS (72.3% vs 54.8%) compared with those treated with 200 mg/m² cisplatin. Additionally, higher incidences of grade 3 and 4 adverse events were recorded in patients treated with >200 mg/m² cisplatin than in those treated with 200 mg/m² cisplatin. Conclusions: Plasma EBV DNA > 0 copies/mL in the middle of IMRT suggests that higher doses of chemotherapy should be used. For concurrent chemoradiation therapy, >200 mg/m² cisplatin is recommended for patients with plasma EBV DNA level > 0 copies/mL in the middle of IMRT but not for patients with plasma EBV DNA level = 0 copies/mL considering the similar OS rates.

Abstract Metabolic reprogramming plays important roles in development and progression of nasopharyngeal carcinoma (NPC), but the underlying mechanism has not been completely defined. In this work, we found INSL5 was elevated in NPC tumor tissue and the plasma of NPC patients. Plasma INSL5 could serve as a novel diagnostic marker for NPC, especially for serum VCA‐IgA‐negative patients. Moreover, higher plasma INSL5 level was associated with poor disease outcome. Functionally, INSL5 overexpression increased, whereas knockdown of its receptor GPCR142 or inhibition of INSL5 reduced cell proliferation, colony formation, and cell invasion in vitro and tumorigenicity in vivo. Mechanistically, INSL5 enhanced phosphorylation and nuclear translocation of STAT5 and promoted glycolytic gene expression, leading to induced glycolysis in cancer cells. Pharmaceutical inhibition of glycolysis by 2‐DG or blockade of INSL5 by a neutralizing antibody reversed INSL5‐induced proliferation and invasion, indicating that INSL5 can be a potential therapeutic target in NPC. In conclusion, INSL5 enhances NPC progression by regulating cancer cell metabolic reprogramming and is a potential diagnostic and prognostic marker as well as a therapeutic target for NPC.

Abstract Objective We aimed to establish and validate two nomograms that predict progression‐free survival (PFS) and overall survival (OS) in patients with stage II–IVa nasopharyngeal carcinoma (NPC) while evaluating the benefit of concurrent chemotherapy. Patients and Methods We randomly divided 3412 patients newly diagnosed with stage II‐IVa NPC between 2008 and 2013 into training and validation ‘A’ cohorts (n = 1706 each). Another set of patients diagnosed between 2014 and 2016 served as validation cohort ‘B’ (n = 1503). A Cox multivariate model using the backward stepwise approach was applied to develop the nomograms, which were assessed for accuracy (Harrel C index) and calibration. Results The 3‐ and 5‐year PFS rates in the training cohort were 86.8% (95% confidence interval [CI] 85.0%‐88.6%) and 82.3% (95% CI 80.1%‐84.5%), respectively. For the PFS nomogram, 5 variables were selected based on a backward procedure in the multivariate Cox model (gender, T stage, N stage, Epstein‐Barr virus DNA, and treatment method). The same variables plus patient age and diabetes mellitus were used for the OS nomogram. The Harrell C indices of the training, validation A, and validation B cohorts were 0.711, 0.700, and 0.703, respectively, for PFS, and 0.775, 0.743, and 0.727, respectively, for OS. Both nomograms performed well in terms of calibration in the training and validation cohorts. Conclusions Our nomograms are reliable prognostic predictors of PFS and OS in patients with stage II‐IVa NPC. These nomograms could robustly estimate an individual's benefit from concurrent chemotherapy, which assists in treatment decision‐making.

Abstract Background We compared the efficacy and toxicity of three IC regimens (TPF: taxanes, cisplatin, and 5-fluorouracil; TP: taxanes and cisplatin; and PF: cisplatin and 5-fluorouracil) followed by CCRT in locoregionally advanced NPC. Methods The retrospective study involved 1354 patients with newly diagnosed stage III-IVA NPC treated with IC and CCRT. The median follow-up time in our cohort was 50 months. Based on EBV DNA level, all the patients with stage IV were divided into low- (pre-EBV DNA

Alpha-fetoprotein hardly increased due to nasopharyngeal cancer. In this article, we reported a 57-year-old male nasopharyngeal carcinoma patient who had posttreatment subscapular metastasis with high serum alpha-fetoprotein but negative plasma Epstein–Barr virus DNA. Pathology results indicated that the scapular mass was undifferentiated non-keratinizing carcinoma originated in the nasopharynx. Moreover, no liver lesion was detected by imaging examination. In view of the positive alpha-fetoprotein and alpha-fetoprotein messenger RNA staining result in the right scapular mass fine needle aspiration biopsy sample, we considered the diagnosis of alpha-fetoprotein-producing nasopharyngeal carcinoma that had never been reported before.

Background: Despite the development of such multiple therapeutic approaches, approximately 20% patients experience recurrence. Identification of molecular markers for stratifying the different risks of tumour recurrence and progression is considered imperative.Methods: We used a RayBio Human Cytokine Antibody Array that simultaneously detected the levels of 297 proteins and profiled the conditioned medium of HONE1 cells and the radioresistant NPC cells HONE1-IR. We found Angiogenin(ANG) expression to be significantly increased in HONE1-IR and HONE1-IR cells exposed to 4-Gy X-ray radiation.Results: We investigated the expression of ANG in NPC tissues and explored its prognostic significance in patients with NPC. We found that ANG expression was increased in recurrent NPC tissues. Elevated expression of ANG induced radio-resistance in NPC cells, in addition to being significantly associated with shorter PFS, OS, and LRFS in patients with NPC. Multivariate analysis results revealed that ANG was an independent prognostic factor that predicted PFS, OS, and LRFS. Furthermore, a nomogram model was generated to predict OS in terms of ANG expression.Conclusion: Our results found the radioresistant function of ANG and proved the clinical prognostic significance of ANG, and the results could help predict radio-sensitivity and stratify high-risk patients or tumour recurrence.

Abstract This study aimed to evaluate the prognostic value of combining pretreatment Epstein‐Barr virus (EBV) DNA level and cervical node necrosis (CNN) for patients with nasopharyngeal carcinoma (NPC) receiving intensity‐modulated radiotherapy (IMRT). A total of 607 incident nonmetastatic NPC patients treated with IMRT ± chemotherapy were reviewed. Patients were divided into four groups based on EBV DNA level and CNN status. The primary endpoint was progression‐free survival (PFS). Kaplan‐Meier curves with log‐rank test were applied to compare survival outcomes and the Cox proportional model was used to identify independent prognostic factors. Pretreatment EBV DNA level and CNN status were independent prognostic factors. Patients in the low‐level EBV DNA group or non‐CNN group had significantly better 5‐year PFS. Multivariate analyses demonstrated that CNN was an independent prognostic factor for overall survival (OS) (HR = 1.927, 95% CI: 1.129‐3.290, P = .016), PFS (HR = 1.492, 95% CI: 1.005‐2.214, P = .047), distant metastasis‐free survival (DMFS) (HR = 1.661, 95% CI: 1.044‐2.644, P = .032), but not locoregional relapse‐free survival. EBV DNA levels correlated significantly with CNN with a correlation coefficient of .324 (P

Abstract 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.

Abstract Object To ascertain the treatment effect of concurrent chemotherapy (CCT) in stage II‐III nasopharyngeal carcinoma (NPC) patients with different Epstein‐Barr virus (EBV) DNA level in intensity‐modulated radiotherapy (IMRT) era. Methods A total of 2742 patients diagnosed with stage II‐III NPC were involved in this study. Patients received IMRT with/without CCT. Overall survival (OS) was the primary endpoint. Receiver operating characteristics curve was used to determine the cut‐off value of pre‐DNA based on OS. After propensity score matching, the role of CCT was explored in patients with different EBV DNA level. Results In our cohort, the cut‐off value of pre EBV DNA was 1460 copies/mL (area under curve [AUC], 0.695‐0.769; sensitivity, 0.766; specificity, 0.599). Patients with high EBV DNA level showed poor survival in OS, progression free survival (PFS), locoregional relapse‐free survival (LRFS) and distant metastasis‐free survival (DMFS). In patients with EBV DNA level >1460 copies/mL, the concurrent chemoradiotherapy (CCRT) group achieved higher 3‐year OS compared with IMRT groups. However, the CCRT and IMRT groups showed comparable OS in patients with EBV DNA ≤1460 copies/mL. In multivariate analyses, CCT was a protective factor for OS, PFS, and LRFS in high‐risk patients (EBV DNA level >1460 copies/mL), while not an independent prognostic factor among the low‐risk patients (EBV DNA level ≤1460 copies/mL). Conclusion Pre‐EBV DNA could be a useful tool to guide individualized treatment for stage II‐III NPC patients. Additional CCT to IMRT improved the survival for patients with high pre‐EBV DNA, while those with low pre‐EBV DNA could not.

Abstract 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.

Abstract Background To evaluate the clinical outcome in patients with de novo metastatic nasopharyngeal carcinoma (NPC) treated or not treated with locoregional radiotherapy (LRRT) based on plasma Epstein–Barr virus (EBV) DNA level and tumor response after palliative chemotherapy (PCT). Methods From 2007 to 2016, 502 patients with de novo metastatic NPC were included in this study. All patients were treated with PCT and 315 patients received LRRT. Our primary study endpoint was overall survival (OS). Results EBV DNA was detected in 461 patients (91.8%) before treatment but was undetectable in 249 patients (49.6%) after PCT. Three hundred and seventeen patients (63.1%) achieved satisfactory response (complete response or partial response) to PCT. Both the post-PCT EBV DNA level and tumor response were independent prognostic factors. Among low-risk patients (patients with undetectable EBV DNA and satisfactory tumor response after PCT), the 3-year OS rate was 80.4% in LRRT-treated patients and 45.3% in patients not treated with LRRT (P

Abstract 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

Abstract Background Despite increasing use, symptomatic venous thromboembolism (VTE) associated with peripherally inserted central catheter (PICC) is a common complication in nonmetastatic nasopharyngeal carcinoma (NPC) patients. Methods A total of 3012 nonmetastatic NPC patients were enrolled in this retrospective study, and we applied Cox regression and log-rank tests to assess the association between PICC-VTE and survival using the propensity score method (PSM) to adjust for gender, age, radiotherapy technique, tumor stage, node stage, UICC clinical stage and pre-treatment EBV DNA. Results 217 patients developed PICC-VTE, with an incidence of 7.20%. PSM identified 213 patients in the cohort with VTE and 852 in that without. Patients who developed PICC-VTE had a shorter 5-year PFS (77.5% vs 87.6%, p

BackgroundTo compare the efficacy of induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) versus induction chemotherapy plus radiotherapy (IC+RT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC).Patients and MethodsOne thousand three hundred twenty four patients with newly-diagnosed NPC treated with IC+CCRT or IC+RT were enrolled. Progression-free survival (PFS), distant metastasis-free survival (DMFS), overall survival (OS), locoregional relapse-free survival (LRFS), and acute toxicities during radiotherapy were compared using propensity score matching (PSM). A nomogram was developed to predict the 3- and 5-year PFS with or without concurrent chemotherapy (CC).ResultsPSM assigned 387 patients to the IC+CCRT group and IC+RT group, respectively. After 3 years, no significant difference in PFS (84.7 vs. 87.5%, P = 0.080), OS (95.5 vs. 97.6%, P = 0.123), DMFS (89.7 vs. 92.8%, P = 0.134), or LRFS (94.0 vs. 94.1%, P = 0.557) was noted between the groups. Subgroup analysis indicated comparable survival outcomes in low-risk NPC patients (II–III with EBV DNA

Background and Aims: To investigate the longitudinal trend of health-related quality of life (HRQOL) from the start to the end of concurrent chemoradiotherapy and survival in patients with advanced nasopharyngeal carcinoma (NPC).Methods: A total of 145 patients with stage II–IVb NPC, who were a subsample of a randomized phase III clinical trial, were recruited in this study. HRQOL was measured weekly for a total of 6 weeks during concurrent chemoradiotherapy by the Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30. Longitudinal trends of HRQOL domains over time were analyzed using mixed models. Survival rates were estimated using Kaplan-Meier method.Results: During a median follow-up of 45 months, the 3-year progression-free survival rate, overall survival rate, and distant metastasis-free survival rate were highly at 86.8% (95% CI: 80.1%, 91.4%), 95.1% (95% CI: 90.1%, 97.6%), and 91.0% (95% CI: 84.9%, 94.6%), respectively. The average weekly declines of five functioning domains were 1.83–3.52 points during the treatment period, with role functioning having the largest decline rate (−2.52 points per week, 95% CI: −4.50, −2.55; p < 0.001). Loss of appetite is the most affected symptom, with severe appetite loss ranging from 35.9 to 61.1%. The average increases of symptoms were 0.63–5.16 points per week during treatment period (all p-values for time

ObjectivesTo investigate the optimal treatment pattern in patients with de novo metastatic nasopharyngeal carcinoma (NPC).MethodsWe assessed 502 consecutive and unselected de novo metastatic NPC patients in Sun Yat-sen University Cancer Center (SYSUCC) from November 2006 to October 2016 in our study. All patients were treated with palliative chemotherapy (PCT) and 308 patients received locoregional radiotherapy (LRRT) subsequently. Our primary study endpoint was overall survival (OS).ResultsThe patients treated with LRRT were associated with improved survival on univariate analysis (3-year OS rate 63.7% vs. 31.8%, P < 0.001) and multivariate analysis (HR 0.52, 95%CI 0.40–0.68, P < 0.001). The overall survival benefit of more than 4 PCT cycles was significant in female (HR 0.45, 95% CI 0.24–0.86, P = 0.016) and patients with multiple metastatic sites (HR 0.42, 95% CI 0.26–0.66, P < 0.001). The application of concurrent chemotherapy (CCT) was not associated with better survival among patients receiving LRRT (HR 1.31, 95% CI 0.92–1.86, P = 0.141).ConclusionLRRT prolonged survival in de novo metastatic NPC. For patients treated with multiple metastatic sites, more than 4 cycles of PCT is necessary. CCT does not improve survival in de novo metastatic NPC patients.

Objective: Our study aimed to compare the efficacy and toxicity of two chemotherapy regimens, gemcitabine plus cisplatin (GP) vs. docetaxel plus, fluorouracil plus cisplatin (TPF), in metastatic nasopharyngeal carcinoma (NPC) patients.Methods: We retrospectively enrolled metastatic NPC patients between July 2006 and December 2016 who were treated with TPF or GP palliative chemotherapy (PCT). The association between the PCT regimens and survival conditions was evaluated by log-rank tests and the Cox proportional hazards model. A cohort was created using propensity score matching with the ratio of 1:1 to clarify the results of the multivariable Cox regression analyses. Overall survival (OS) was the primary endpoint.Results: Of 266 eligible patients, 186 and 80 patients, respectively, received TPF and GP regimen. No significant difference was demonstrated in the survival rate between the GP and TPF groups (3-year OS: 52.6 vs. 50.3%; P = 0.929). However, multivariable analysis suggested receiving GP as an independent protective factor (hazard ratio, 0.864; 95% confidence interval, 0.753–0.992; P = 0.042). In the matched cohort, treatment with GP was also associated with a significantly higher OS (3-year OS: 52.6 vs. 35.6%, P = 0.042). Subgroup analysis indicated that the superiority of GP reflected in patients with secondary metastases rather than primary metastases. The incidence of grade 3 to 4 treatment-related toxicity was more common in the TPF group than in the GP group.Conclusion: Our study suggested that GP might be superior to TPF for metastatic NPC patients, especially those with secondary distant metastases. Further studies are necessary to validate our results.

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; p

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

Abstract 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.

Objective: To compare the survival outcomes brought by different radiation dose schedules to bone lesions and different chemotherapy regimens in bone metastatic nasopharyngeal carcinoma (NPC).Background: The current treatment strategy for bone metastatic NPC patients was empirically given and poorly studied before. It is of necessity to optimize the treatment for bone metastasis to enhance the therapeutic effect and increase the proportion of long-term survived patients.Methods: Three hundred patients who received chemoradiotherapy from 2002 to 2018 were involved in the study. Demographics, laboratory results, and detailed treatment plans were recorded. Radiotherapy plans were classified into three categories based on the intensity, and the survival analysis was performed using log-rank test. Multivariable analysis was made by the Cox proportional regression model.Results: Patients who received 60–75 Gy/30–35 fractions of radiation to the metastatic bones had significantly longer bone relapse-free survival (BRFS) (HR, 0.53, 95% CI, 0.37–0.78, P = 0.003), overall survival (OS) (HR, 0.63, 95% CI, 0.46–0.84, P = 0.007), and progression-free survival (PFS) (HR, 0.80, 95% CI, 0.67–0.95, P = 0.041). The administration of paclitaxel, cisplatin and 5-fluorouracil regimen was also associated with better BRFS (HR, 0.27, 95% CI, 0.10–0.75, P = 0.007), PFS (HR, 0.60, 95% CI, 0.42–0.87, P = 0.007), and OS with borderline significance (HR, 0.54, 95% CI, 0.29–1.03, P = 0.058). In multivariable analysis, the post-treatment EBV DNA level and radical radiation dose were proved as independent prognostic factors for both BRFS and OS.Conclusions: Radiotherapy to metastatic bones with palliative dose prescription should not be considered in bone metastatic NPC patients. TPF chemotherapy regimen might help to improve the survivals in NPC patients but failed to be an independent protective factor.

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.

Abstract 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,

Abstract 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

PURPOSE:To evaluate and compare the prognostic value of Epstein-Barr virus (EBV) DNA and maximal standard uptake values (SUVmax ) of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG-PET) in subgroups of nasopharyngeal carcinoma (NPC) patients with locoregional or distant recurrence. PATIENTS AND METHODS:A total of 194 patients with recurrent NPC (locoregional recurrence: 107, distant recurrence: 87) were enrolled. Patients took evidence of recurrence performed with 18F-FDG-PET and an EBV DNA test before salvage treatment. Clinical parameters, the status of EBV DNA and the value of SUVmax were used for survival analysis using the Kaplan-Meier method and the Cox proportional hazards regression model. RESULTS:In the subgroup of patients with locoregional recurrence, patients with SUVmax

BACKGROUND:Hemoglobin (Hb) levels are regarded as an important determinant of outcome in a number of cancers treated with radiotherapy. However, for patients treated with intensity modulated radiotherapy (IMRT), information regarding the prognostic value of hemoglobin level is scarce. PATIENTS AND METHODS:A total of 650 patients with nasopharyngeal carcinoma (NPC), enrolled between May, 2005, and November, 2012, were included in this study. The prognostic significance of hemoglobin level (anemia or no-anemia) at three different time points was investigated, including before treatment, during treatment and at the last week of treatment. Univariate and multivariate analyses were conducted using the log-rank test and the Cox proportional hazards model, respectively. RESULTS:The 5-year OS (overall survival) rate of patients who were anemia and no-anemia before treatment were 89.1%, and 80.7% (P = 0.01), respectively. The 5-year DMFS (distant metastasis-free survival) rate of patients who were anemia and no-anemia before treatment were 88.9%, and 78.2% (P = 0.01), respectively. The 5-year OS rate of patients who were anemia and no-anemia during treatment were 91.7% and 83.3% (P = 0.004). According to multivariate analysis, the pre-treatment Hb level predicted a decreased DMFS (P = 0.007, HR = 2.555, 95% CI1.294-5.046). Besides, the mid-treatment Hb level predicted a decreased OS (P = 0.013, HR = 2.333, 95% CI1.199-4.541). CONCLUSIONS:Hemoglobin level is a useful prognostic factor in NPC patients receiving IMRT. It is important to control the level of hemoglobin both before and during chemoradiotherapy.

BACKGROUND AND PURPOSE:Treatment outcomes vary greatly in patients with nasopharyngeal carcinoma (NPC). The purpose of this study is to evaluate the influence of radiation and chemotherapy drug action pathway gene polymorphisms on the survival of patients with locoregionally advanced NPC treated with cisplatin- and fluorouracil-based chemoradiotherapy. MATERIAL AND METHODS:Four hundred twenty-one consecutive patients with locoregionally advanced NPC were prospectively recruited. We utilized a pathway approach and examined 18 polymorphisms in 13 major genes. Polymorphisms were detected using the LDR-PCR technique. Multifactor dimensionality reduction (MDR) analysis was performed to detect potential gene-gene interaction. RESULTS:After adjustment for clinicopathological characteristics, overall survival was significantly decreased in patients with the MPO rs2243828 CT/CC genotype (HR=2.453, 95% CI, 1.687-3.566, P

Purpose: The prognosis of nasopharyngeal carcinoma (NPC) patients with parotid lymph node (PLN) metastasis remains unclear. This study was performed to investigate the prognostic significance and optimal staging category of PLN metastasis and develop a nomogram for estimating individual risk. Materials and Methods: Clinical data of 7,084 non-metastatic NPC patients were retrospectively reviewed. Overall survival (OS) was the primary endpoint. A nomogram was established based on the Cox proportional hazards regression model. The accuracy and calibration ability of this nomogram was evaluated by C-index and calibration curves with bootstrap validation. Results: Totally, 164/7,084 NPC patients (2.3%) presented with PLNs. Multivariate analyses showed that PLN metastasis was a negative prognostic factor for OS, progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRFS). Patients with PLN metastasis had a worse prognosis than N3 disease. Five independent prognostic factors were included in the nomogram, which showed a C-index of 0.743. The calibration curves for probability of 3- and 5-year OS indicated satisfactory agreement between nomogram-based prediction and actual observation. All results were confirmed in the validation cohort. Conclusion: NPC patient with PLN metastasis had poorer survival outcome (OS, PFS, DMFS, and LRFS) than N3 disease. We developed a nomogram to provide individual prediction of OS for patients with PLN metastasis. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study was to subdivide M1 stage nasopharyngeal carcinoma (NPC) patients with bone-only metastases for prognosis prediction while identifying the treatment effect of locoregional radiotherapy (LRRT) and metastasis radiotherapy (MRT) among patients with different risk. Materials and Methods From November 2006 to October 2016, a total of 226 patients with bone-only metastasic NPC were retrospectively enrolled. All patients developed distant lesions before receiving treatment. All potential prognostic factors were considered and the correlation of the M1 subdivisions with overall survival (OS) was determined by Cox regression hazards model. Kaplan-Meier curves were used to appraise survival condition and log-rank testing was used to compare the differences. Results The median follow-up time was 33.9 months (range, 3 to 126 months). According to multivariate Cox proportional hazard analysis, the number of metastatic lesions and Epstein-Barr virus (EBV) DNA status after palliative chemotherapy (PCT) were independent prognostic factors for OS. Thus, we subdivided patients into three risk groups according to these two factors. Systemic chemotherapy combined with LRRT may benefit patients in low- and intermediate-risk groups but not in the high-risk group. Further aggressive MRT based on systemic chemotherapy showed no survival benefit in any risk group. Conclusion The stratification of NPC patients with bone-only metastasis based on EBV DNA after PCT and the number of metastatic lesions provided promising prognostic value and could aid clinicians in person-specific treatment. [ABSTRACT FROM AUTHOR]

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<0.001). Additionally, significant increasing trends could be seen in the PFS and LRFS during the four calendar periods. In the subgroup analysis, the LRFS in patients older than 50 years at diagnosis showed greater improvement than younger patients. However, the rate of distant metastasis was stable and relatively low, as the 5-year DMFS ranged from 90.5% to 94.7% among the four calendar periods. Conclusion The survival rates in patients with stage II NPC showed increasing trends from 1990 to 2012. The advance of RT provided excellent locoregional control and enhanced OS. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study was to evaluate the long-term clinical outcome and toxicity of induction chemotherapy (IC) followed by concomitant chemoradiotherapy (CCRT) compared with CCRT alone for the treatment of children and adolescent locoregionally advanced nasopharyngeal carcinoma (LACANPC). Materials and Methods A total of 194 locoregionally advanced nasopharyngeal carcinoma patients younger than 21 years who received CCRT with or without IC before were included in the study population. Overall survival (OS) rate, progression-free survival (PFS) rate, locoregional recurrence-free survival (LRFS) rate, and distant metastasis-free survival (DMFS) rate were assessed by the Kaplan-Meier method and a log-rank test. Treatment toxicities were clarified and compared between two groups. Results One hundred and thiry of 194 patients received IC+CCRT. Patients who were younger and with more advanced TNM stage were more likely to receive IC+CCRT and intensive modulated radiotherapy. The addition of IC before CCRT failed to improve survival significantly. The matched analysis identified 43 well-balanced patients in both two groups. With a median follow-up of 51.5 months, no differences were found between the IC+CCRT group and the CCRT group in 5-year OS (83.7% vs. 74.6%, p=0.153), PFS (79.2% vs. 73.4%, p=0.355), LRFS (97.7% vs. 88.2%, p=0.083), and DMFS (81.6% vs. 81.6%, p=0.860). N3 was an independent prognostic factor predicting poorer OS, PFS, and DMFS. The addition of IC was associated with increased rates of grade 3 to 4 neutropenia. Conclusion This study failed to demonstrate that adding IC before CCRT could provide a significant additional survival benefit for LACANPC patients. Further investigations are warranted. [ABSTRACT FROM AUTHOR]

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 < 0.001) and total tumor volume (GTVtotal, p < 0.001) were both closely related to pretreatment EBV DNA, while gross tumor volume of nasopharynx (GTVnx, p=0.047) was weakly related to EBV DNA. EBV DNA was significantly correlated with progress-free survival (PFS, p=0.005), locoregional-free survival (LRFS, p=0.039), and distant metastasis-free survival (DMFS, p=0.017), while GTVtotal, regardless of GTVnx and GTVnd, had a significant correlation with PFS and LRFS. The p-values of GTVtotal for PFS and LRFS were 0.008 and 0.001, respectively. According to GTVtotal and pretreatment EBV DNA level, patients were divided into a low-risk group (EBV DNA 0 copy/mL, GTVtotal < 30 cm³; EBV DNA 0 copy/mL, GTVtotal 30 cm³; or EBV DNA > 0 copy/mL, GTVtotal < 30 cm³) and a high-risk group (EBV DNA > 0 copy/mL, GTVtotal ≥ 30 cm³). When patients in the low-risk group were compared with those in the high-risk group, 3-year PFS (p=0.003), LRFS (p=0.010), and DMFS (p=0.031) rates were statistically significant. 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. [ABSTRACT FROM AUTHOR]

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 high- SAA group (> 4.28 mg/L) versus the low-SAA (≤ 4.28 mg/L) group and the high-CRP group (> 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 < 1,500 copies/mL group (62.2% versus 77.8%, p < 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. [ABSTRACT FROM AUTHOR]

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