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Wei-Xiong Xia,1,2,* Hu Liang,1,2,* Xing Lv,1,2 Lin Wang,1,2 Yan-Fang Ye,3 Liang-Ru Ke,1,2 Lin-Hao Xu,4 Xiang Guo,1,2 Yan-Qun Xiang1,2 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, People’s Republic of China; 2Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 3Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 4IBM Research China, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiang Guo; Yan-Qun XiangDepartment of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, People’s Republic of ChinaTel +86 208 734 3392; +86 208 734 3379Email guoxiang@sysucc.org.cn; xiangyq@sysucc.org.cnPurpose: This large population-based analysis aims to investigate whether the additional induction chemotherapy to concurrent chemoradiotherapy improved overall survival (OS) and disease-free survival (DFS) for locoregionally advanced nasopharyngeal carcinoma (LRANPC).Patients and Methods: The study group comprised 3,980 patients who were treated either with IC+CCRT (1,888 patients) or CCRT alone (2,092 patients) between January 1998 and June 2013. Survival outcomes were compared using Cox proportional hazards regression models with adjustments for confounding provided by propensity score methods. Primary outcome variables included OS and DFS.Results: Kaplan–Meier analysis showed that CCRT and IC+CCRT were of similar benefit to OS (P=0.099), whereas there was a marginal benefit of CCRT to DFS (P=0.063) in the overall cohort, which showed no differences between the two treatment regimens using multivariate Cox analysis and propensity score. Interestingly, for patients with 2D radiationtherapy (2DRT), CCRT had OS and DFS benefits for stage III, with 5-year and 10-year OS for CCRT vs IC+CCRT being 88% and 75% vs 81% and 67%, respectively (P=0.002); 5-year and 10-year DFS for CCRT vs IC+CCRT being 84% and 74% vs 76% and 66%, respectively (P=0.002). In contrast, IC + CCRT had OS and DFS benefits for stage IVa-b, with 5-year and 10-year OS for CCRT vs IC+CCRT being 71% and 55% vs 76% and 60%, respectively (P=0.037, HR=0.786); 5-year and 10-year DFS for CCRT vs IC+CCRT were 64% and 50% vs 69% and 58%, respectively (P=0.038, HR=0.801). No difference was found in intensity-modulated radiotherapy (IMRT) subgroup.Conclusion: Our study indicates that CCRT and IC+CCRT may have similar OS and DFS benefits for overall LRANPC. Stage-specific chemoradiotherapy may be administered based on the greatest benefit of IC+CCRT for stage IVa-b patients and CCRT alone for stage III patients received 2DRT. The optimal chemotherapy pattern in combination with IMRT needs further investigation.Trial registration: ClinicalTrials.gov ID: NCT02604472Keywords: nasopharyngeal carcinoma, concurrent chemotherapy, radiation therapy, induction chemotherapy, prognosis, stage specific

Objective: To compare the effectiveness and safety of nab-paclitaxel, cisplatin, and capecitabine (nab-TPC) with gemcitabine and cisplatin as an alternative first line treatment option for recurrent or metastatic nasopharyngeal carcinoma., Design: Phase 3, open label, multicentre, randomised trial., Setting: Four hospitals located in China between September 2019 and August 2022., Participants: Adults (≥18 years) with recurrent or metastatic nasopharyngeal carcinoma., Interventions: Patients were randomised in a 1:1 ratio to treatment with either nab-paclitaxel (200 g/m 2 on day 1), cisplatin (60 mg/m 2 on day 1), and capecitabine (1000 mg/m 2 twice on days 1-14) or gemcitabine (1 g/m 2 on days 1 and 8) and cisplatin (80 mg/m 2 on day 1)., Main Outcome Measures: Progression-free survival was evaluated by the independent review committee as the primary endpoint in the intention-to-treat population., Results: The median follow-up was 15.8 months in the prespecified interim analysis (31 October 2022). As assessed by the independent review committee, the median progression-free survival was 11.3 (95% confidence interval 9.7 to 12.9) months in the nab-TPC cohort compared with 7.7 (6.5 to 9.0) months in the gemcitabine and cisplatin cohort. The hazard ratio was 0.43 (95% confidence interval 0.25 to 0.73; P=0.002). The objective response rate in the nab-TPC cohort was 83% (34/41) versus 63% (25/40) in the gemcitabine and cisplatin cohort (P=0.05), and the duration of response was 10.8 months in the nab-TPC cohort compared with 6.9 months in the gemcitabine and cisplatin cohort (P=0.009). Treatment related grade 3 or 4 adverse events, including leukopenia (4/41 (10%) v 13/40 (33%); P=0.02), neutropenia (6/41 (15%) v 16/40 (40%); P=0.01), and anaemia (1/41 (2%) v 8/40 (20%); P=0.01), were higher in the gemcitabine and cisplatin cohort than in the nab-TPC cohort. No deaths related to treatment occurred in either treatment group. Survival and long term toxicity are still being evaluated with longer follow-up., Conclusion: The nab-TPC regimen showed a superior antitumoural efficacy and favourable safety profile compared with gemcitabine and cisplatin for recurrent or metastatic nasopharyngeal carcinoma. Nab-TPC should be considered the standard first line treatment for recurrent or metastatic nasopharyngeal carcinoma. Longer follow-up is needed to confirm the benefits for overall survival., Trial Registration: Chinese Clinical Trial Registry ChiCTR1900027112., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the Guangdong Basic and Applied Basic Research Foundation, National Natural Science Foundation of China, CPSF, and Postdoctoral Fellowship Program of CPSF for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The data of 115 patients with nasopharyngeal masses (78 males and 37 females) aged between 12 and 78 years at the Sun Yat-sen University Cancer Center from May 2022 to July 2023 were retrospectively reviewed, including 70 cases of nasopharyngeal carcinoma and 45 cases of benign hyperplasia. The mean, median, and percentiles (10 th , 25 th , 75 th , and 90 th ) of the apparent diffusion coefficient (ADC) histogram derived from multiplexed sensitivity encoding diffusion-weighted imaging (MUSE-DWI) of the benign hyperplasia group were significantly higher than those of the nasopharyngeal carcinoma group (all P <0.05). Conversely, the kurtosis and skewness of benign hyperplasia group were significantly lower than those of the nasopharyngeal carcinoma group (both P <0.05). The area under receiver operating characteristic (ROC) curve of the combined ADC histogram parameters was 0.812 (95% CI : 0.732-0.892), and the sensitivity, specificity and accuracy were 92.86%, 57.78% and 79.13%, respectively. The current study indicates ADC histogram parameters derived MUSE-DWI exhibit significant discriminatory value between nasopharyngeal carcinoma and benign hyperplasia.

The antiangiogenic agent apatinib has been shown to clinically improve responses to immune checkpoint inhibitors in several cancer types. Patients with N3 nasopharyngeal carcinoma have a high risk of distant metastasis, however, if the addition of immunotherapy to standard treatment could improve efficacy is unclear. In this phase II clinical trial (ChiCTR2000032317), 49 patients with stage T any N3M0 nasopharyngeal carcinoma were enrolled and received the combination of three cycles of induction chemotherapy, camrelizumab and apatinib followed by chemoradiotherapy. Here we report on the primary outcome of distant metastasis-free survival and secondary end points of objective response rate, failure-free survival, locoregional recurrence-free survival, overall survival and toxicity profile. After induction therapy, all patients had objective response, including 13 patients (26.5%) with complete response. After a median follow-up of 28.7 months, the primary endpoint of 1-year distant metastasis-free survival was met for the cohort (1-year DMFS rate: 98%). Grade≥3 toxicity appeared in 32 (65.3%) patients, with the most common being mucositis (14[28.6%]) and nausea/vomiting (9[18.4%]). In this work, camrelizumab and apatinib in combination with induction chemotherapy show promising distant metastasis control with acceptable safety profile in patients with stage T any N3M0 nasopharyngeal carcinoma., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

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 < 0.001] vs. 0.3% [p = 0.302]; workload reduction, 79.3% vs. 76.2%). The workflow also yielded a triaging performance of 83.6%, with increases of 1.5% in sensitivity (p = 1.000) and 0.6%-1.3% (all p < 0.05) in specificity compared to three radiologists in the reader study. The semiautomated workflow shows its unique superiority in reducing radiologist's workload by eliminating negative scans while retaining the diagnostic performance of radiologists., Competing Interests: The authors declare no competing interests., (© 2023.)

Background: There are limited treatment options for patients with metastatic nasopharyngeal carcinoma (mNPC) after failure of platinum-based chemotherapy. In this trial, we assessed the efficacy and safety of sintilimab plus bevacizumab in patients with mNPC where platinum-based chemotherapy has been ineffective., Methods: This was a single-centre, open-label, single-arm, phase 2 trial in Guangzhou, China for patients with mNPC progressed after at least one line of systemic therapy. Eligible patients were between 18 and 75 years old, were histologically confirmed differentiated or undifferentiated non-keratinized NPC, were ineffective after platinum-based chemotherapy, and they had at least one measurable metastatic lesion assessed with Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST V.1.1) by investigators and unsuitable for local surgery or radiotherapy. Key exclusion criterion was previous treatment with anti-PD-1/PD-L1 antibodies plus anti-VEGF antibodies and high risk of hemorrhage or nasopharyngeal necrosis. Patients were enrolled and received sintilimab (200 mg) plus bevacizumab (7.5 mg/kg) intravenously every 3 weeks. Intention-to-treat population was included in primary endpoint analyses and safety analyses. The primary endpoint was objective response rate (ORR) assessed by investigators following the guidelines of RECIST V1.1. Key secondary endpoints were progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety. This trial is registered with ClinicalTrials.gov (NCT04872582)., Findings: Between July 29, 2021 and August 16, 2022, 33 patients were enrolled. Median age was 46 years (range, 18-64 years), and 63.6% of patients had previously received two or more lines of chemotherapy for metastatic disease. Median follow-up was 7.6 months (range, 4.1-17.5 months). ORR was 54.5% (95% CI, 36.4-71.9%) with 3 complete responses (9.1%) and 15 partial responses (45.5%). Median PFS was 6.8 months (95% CI, 5.2 months to not estimable). Median DOR was 7.2 months (95% CI, 4.4 months to not estimable). Median OS was not reached. The most common potential immune-related adverse event (AE) was Grade 1-2 hypothyroidism (42.4%). Treatment-related grade 3 or 4 AEs occurred in 7 patients (21.2%), including nasal necrosis (3/33), hypertension (1/33), pruritus (1/33), total bilirubin increased (1/33) and anaphylactic shock (1/33). No treatment-related deaths and severe epistaxis occurred., Interpretation: This phase 2 trial showed that sintilimab plus bevacizumab demonstrated promising antitumour activity and manageable toxicities in patients with mNPC after failure of platinum-based chemotherapy. Further trials are warranted, and the detailed mechanisms need to be elucidated., Funding: The Guangdong Basic and Applied Basic Research Foundation, the National Natural Science Foundation of China, the Natural Science Foundation of Guangdong Province, and the Science and Technology Planning Project of International Cooperation of Guangdong Province., Competing Interests: We declare no competing interests., (© 2023 The Author(s).)

Background: Dysregulation of lipid metabolism is closely associated with cancer progression. The study aimed to establish a prognostic model to predict distant metastasis-free survival (DMFS) in patients with nasopharyngeal carcinoma (NPC), based on lipidomics., Methods: The plasma lipid profiles of 179 patients with locoregionally advanced NPC (LANPC) were measured and quantified using widely targeted quantitative lipidomics. Then, patients were randomly split into the training (125 patients, 69.8%) and validation (54 patients, 30.2%) sets. To identify distant metastasis-associated lipids, univariate Cox regression was applied to the training set (P < 0.05). A deep survival method called DeepSurv was employed to develop a proposed model based on significant lipid species (P < 0.01) and clinical biomarkers to predict DMFS. Concordance index and receiver operating curve analyses were performed to assess model effectiveness. The study also explored the potential role of lipid alterations in the prognosis of NPC., Results: Forty lipids were recognized as distant metastasis-associated (P < 0.05) by univariate Cox regression. The concordance indices of the proposed model were 0.764 (95% confidence interval (CI), 0.682-0.846) and 0.760 (95% CI, 0.649-0.871) in the training and validation sets, respectively. High-risk patients had poorer 5-year DMFS compared with low-risk patients (Hazard ratio, 26.18; 95% CI, 3.52-194.80; P < 0.0001). Moreover, the six lipids were significantly correlated with immunity- and inflammation-associated biomarkers and were mainly enriched in metabolic pathways., Conclusions: Widely targeted quantitative lipidomics reveals plasma lipid predictors for LANPC, the prognostic model based on that demonstrated superior performance in predicting metastasis in LANPC patients., (© 2023. The Author(s).)

Background: To develop and validate a predictive nomogram for tumor residue 3-6 months after treatment based on postradiotherapy plasma Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA), clinical stage, and radiotherapy (RT) dose in patients with stage II-IVA nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT)., Methods: In this retrospective study, 1050 eligible patients with stage II-IVA NPC, who completed curative IMRT and underwent pretreatment and postradiotherapy (-7 to +28 days after IMRT) EBV DNA testing, were enrolled from 2012 to 2017. The prognostic value of the residue was explored using Cox regression analysis in patients (n=1050). A nomogram for predicting tumor residues after 3-6 months was developed using logistic regression analyses in the development cohort (n=736) and validated in an internal cohort (n=314)., Results: Tumor residue was an independent inferior prognostic factor for 5-year overall survival, progression-free survival, locoregional recurrence-free survival and distant metastasis-free survival (all P<0.001). A prediction nomogram based on postradiotherapy plasma EBV DNA level (0 vs. 1-499 vs. ≥500 copies/ml), clinical stage (II vs. III vs. IVA), and RT dose (68.00-69.96 vs. 70.00-74.00 Gy) estimated the probability of residue development. The nomogram showed better discrimination (area under the curve (AUC): 0.752) than either the clinical stage (0.659) or postradiotherapy EBV DNA level (0.627) alone in the development and validation cohorts (AUC: 0.728)., Conclusions: We developed and validated a nomogram model integrating clinical characteristics at the end of IMRT for predicting whether tumor will residue or not after 3-6 months. Thus, high-risk NPC patients who might benefit from immediate additional intervention could be identified by the model, and the probability of residue can be reduced in the future., (© 2023. The Author(s).)

Importance: Induction chemotherapy added to concurrent chemoradiotherapy significantly improves survival for patients with locoregionally advanced nasopharyngeal carcinoma, but the optimal induction regimen remains unclear., Objective: To determine whether induction chemotherapy with paclitaxel, cisplatin, and capecitabine (TPC) improves survival vs cisplatin and fluorouracil (PF) prior to chemoradiotherapy for patients with stage IVA to IVB nasopharyngeal carcinoma., Design, Setting, and Participants: This randomized, open-label, phase 3 clinical trial recruited 238 patients at 4 hospitals in China from October 20, 2016, to August 29, 2019. Patients were 18 to 65 years of age with treatment-naive, nonkeratinizing stage IVA to IVB nasopharyngeal carcinoma and an Eastern Cooperative Oncology Group performance status of 0 to 1., Interventions: Patients were randomly assigned (1:1) to receive induction chemotherapy with two 21-day cycles of TPC (intravenous paclitaxel [150 mg/m2, day 1], intravenous cisplatin [60 mg/m2, day 1], and oral capecitabine [1000 mg/m2 orally twice daily, days 1-14]) or PF (intravenous cisplatin [100 mg/m2, day 1] and fluorouracil [800 mg/m2 daily, days 1-5]), followed by chemoradiotherapy., Main Outcomes and Measures: The primary end point was failure-free survival in the intention-to-treat population. Secondary end points included distant metastasis-free survival, locoregional relapse-free survival, overall survival, tumor response, and safety., Results: Overall, 238 eligible patients (187 men [78.6%]; median age, 45 years [range, 18-65 years]) were randomly assigned to receive TPC (n = 118) or PF (n = 120). The median follow-up duration was 48.4 months (IQR, 39.6-53.3 months). Failure-free survival at 3 years was 83.5% (95% CI, 77.0%-90.6%) in the TPC group and 68.9% (95% CI, 61.1%-77.8%) in the PF group (stratified hazard ratio [HR] for recurrence or death, 0.47; 95% CI, 0.28-0.79; P = .004). Induction with the TPC regimen resulted in a significant reduction in the risk of distant metastases (stratified HR, 0.49 [95% CI, 0.24-0.98]; P = .04) and locoregional recurrence (stratified HR, 0.40 [95% CI, 0.18-0.93]; P = .03) compared with the PF regimen. However, there was no effect on early overall survival (stratified HR, 0.45 [95% CI, 0.17-1.18]; P = .10). The incidences of grade 3 to 4 acute adverse events and late-onset toxicities were 57.6% (n = 68) and 13.6% (16 of 118), respectively, in the TPC group and 65.8% (n = 79) and 17.9% (21 of 117), respectively, in the PF group. One treatment-related death occurred in the PF group., Conclusions and Relevance: This randomized clinical trial found that induction chemotherapy with 2 cycles of TPC for patients with stage IVA to IVB nasopharyngeal carcinoma improved failure-free survival compared with 2 cycles of PF, with no increase in the toxicity profile., Trial Registration: ClinicalTrials.gov Identifier: NCT02940925.

Importance: Capecitabine maintenance therapy improves survival outcomes in various cancer types, but data are limited on the efficacy and safety of capecitabine maintenance therapy in metastatic nasopharyngeal carcinoma (NPC)., Objective: To investigate the efficacy and safety of capecitabine maintenance therapy in metastatic NPC., Design, Setting, and Participants: This randomized phase 3 clinical trial was conducted at Sun Yat-sen University Cancer Center from May 16, 2015, to January 9, 2020, among 104 patients with newly diagnosed metastatic NPC who had achieved disease control after 4 to 6 cycles of induction chemotherapy with paclitaxel, cisplatin, and capecitabine. The final follow-up date was May 30, 2021. All efficacy analyses were conducted in the intention-to-treat population., Interventions: Eligible patients were randomly assigned (1:1) to receive either capecitabine maintenance therapy (1000 mg/m2 orally twice daily on days 1-14) every 3 weeks plus best supportive care (BSC) (capecitabine maintenance group) or BSC alone after 4 to 6 cycles of induction chemotherapy., Main Outcomes and Measures: Progression-free survival (PFS). Secondary end points were objective response rate, duration of response, overall survival, and safety., Results: This study included 104 patients (84 men [80.8%]; median age, 47 years [IQR, 38-54 years]), with 52 assigned to the capecitabine maintenance group and 52 assigned to the BSC group. After a median follow-up of 33.8 months (IQR, 22.9-50.7 months), there were 23 events (44.2%) of progression or death in the capecitabine maintenance group and 37 events (71.2%) of progression or death in the BSC group. Median PFS survival was significantly higher in the capecitabine maintenance group (35.9 months [95% CI, 20.5 months-not reached]) than in the BSC group (8.2 months [95% CI, 6.4-10.0 months]), with a hazard ratio of 0.44 (95% CI, 0.26-0.74; P = .002). Higher objective response rates and longer median duration of response were observed in the capecitabine maintenance group (25.0%; 40.0 months) compared with the BSC group (objective response rate, 25.0% [n = 13] vs 11.5% [n = 6]; and median duration of response, 40.0 months [95% CI, not reached-not reached] vs 13.2 months [95% CI, 9.9-16.5 months]). The most common grade 3 or 4 adverse events during maintenance therapy were anemia (6 of 50 [12.0%]), hand-foot syndrome (5 of 50 [10.0%]), nausea and vomiting (3 of 50 [6.0%]), fatigue (2 of 50 [4.0%]), and mucositis (2 of 50 [4.0%]). No deaths in the maintenance group were deemed treatment-related., Conclusions and Relevance: In this phase 3 randomized clinical trial, capecitabine maintenance therapy significantly improved PFS for patients with newly diagnosed metastatic NPC who achieved disease control after capecitabine-containing induction chemotherapy. Capecitabine exhibited manageable toxic effects., Trial Registration: ClinicalTrials.gov Identifier: NCT02460419.

Purpose: Previous studies suggest that a cumulative cisplatin dose of 200 mg/m 2 might be adequate in the intensity-modulated radiation therapy (IMRT) era for locoregionally advanced nasopharyngeal carcinoma (LANPC). However, two cycles of once-every-3-weeks cisplatin at 100 mg/m 2 has never been prospectively compared with standard once-a-week cisplatin regimen., Patients and Methods: This trial was conducted at three hospitals from 2011 to 2016. Patients who met the eligibility criteria were recruited (ChiCTR-TRC-12001979) and randomly assigned (1:1) via a computer-generated sequence to receive once-every-3-weeks cisplatin at 100 mg/m 2 for two cycles or once-a-week cisplatin at 40 mg/m 2 for six cycles concurrently with IMRT. Primary endpoint was failure-free survival and between-group absolute difference of 10% as the noninferiority margin., Results: A total of 510 patients were enrolled. Median follow-up time was 58.3 months with 85.4% of 3-year failure-free survival in the once-every-3-weeks group and 85.6% in the once-a-week group. An absolute difference of -0.2% (95% confidence interval, -6.3 to 5.9; P noninferiority = 0.0016). Acute toxicities of grade 3 or higher occurred in 55.8% in the once-every-3-weeks group and 66.3% in the once-a-week group ( P = 0.015). The most common acute toxicities were hematologic abnormalities, including leukopenia (16% vs. 27%; P = 0.0022) and thrombocytopenia (1% vs. 5%; P = 0.015). The late grade 3-4 auditory loss rate was significantly lower in the once-every-3-weeks group than the once-a-week group (6% vs. 13%; P = 0.0039)., Conclusions: Once-every-3-weeks cisplatin as concurrent chemoradiotherapy is noninferior to once-a-week cisplatin in the treatment efficacy in the LANPC. Although both regimens are well tolerated, severe acute toxicities and late-onset auditory loss are higher in the once-a-week group., (©2021 The Authors; Published by the American Association for Cancer Research.)

Background: Cisplatin-based induction chemotherapy plus concurrent chemoradiotherapy in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma has been recommended in the National Comprehensive Cancer Network Guidelines. However, cisplatin is associated with poor patient compliance and has notable side-effects. Lobaplatin, a third-generation platinum drug, has shown promising antitumour activity against several malignancies with less toxicity. In this study, we aimed to evaluate the efficacy of lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy over a cisplatin-based regimen in patients with locoregional, advanced nasopharyngeal carcinoma., Methods: In this open-label, non-inferiority, randomised, controlled, phase 3 trial done at five hospitals in China, patients aged 18-60 years with previously untreated, non-keratinising stage III-IVB nasopharyngeal carcinoma; Karnofsky performance-status score of at least 70; and adequate haematological, renal, and hepatic function were randomly assigned (1:1) to receive intravenously either lobaplatin-based (lobaplatin 30 mg/m 2 on days 1 and 22, and fluorouracil 800 mg/m 2 on days 1-5 and 22-26 for two cycles) or cisplatin-based (cisplatin 100 mg/m 2 on days 1 and 22, and fluorouracil 800 mg/m 2 on days 1-5 and 22-26 for two cycles) induction chemotherapy, followed by concurrent lobaplatin-based (two cycles of intravenous lobaplatin 30 mg/m 2 every 3 weeks plus intensity-modulated radiotherapy) or cisplatin-based (two cycles of intravenous cisplatin 100 mg/m 2 every 3 weeks plus intensity-modulated radiotherapy) chemoradiotherapy. Total radiation doses of 68-70 Gy (for the sum of the volumes of the primary tumour and enlarged retropharyngeal nodes), 62-68 Gy (for the volume of clinically involved gross cervical lymph nodes), 60 Gy (for the high-risk target volume), and 54 Gy (for the low-risk target volume), were administered in 30-32 fractions, 5 days per week. Randomisation was done centrally at the clinical trial centre of Sun Yat-sen University Cancer Centre by means of computer-generated random number allocation with a block design (block size of four) stratified according to disease stage and treatment centre. Treatment assignment was known to both clinicians and patients. The primary endpoint was 5-year progression-free survival, analysed in both the intention-to-treat and per-protocol populations. If the upper limit of the 95% CI for the difference in 5-year progression-free survival between the lobaplatin-based and cisplatin-based groups did not exceed 10%, non-inferiority was met. Adverse events were analysed in all patients who received at least one cycle of induction chemotherapy. This trial is registered with the Chinese Clinical Trial Registry, ChiCTR-TRC-13003285 and is closed., Findings: From June 7, 2013, to June 16, 2015, 515 patients were assessed for eligibility and 502 patients were enrolled: 252 were randomly assigned to the lobaplatin-based group and 250 to the cisplatin-based group. After a median follow-up of 75·3 months (IQR 69·9-81·1) in the intention-to-treat population, 5-year progression-free survival was 75·0% (95% CI 69·7-80·3) in the lobaplatin-based group and 75·5% (70·0 to 81·0) in the cisplatin-based group (hazard ratio [HR] 0·98, 95% CI 0·69-1·39; log-rank p=0·92), with a difference of 0·5% (95% CI -7·1 to 8·1; p non-inferiority =0·0070). In the per-protocol population, the 5-year progression-free survival was 74·8% (95% CI 69·3 to 80·3) in the lobaplatin-based group and 76·4% (70·9 to 81·9) in the cisplatin-based group (HR 1·04, 95% CI 0·73 to 1·49; log-rank p=0·83), with a difference of 1·6% (-6·1 to 9·3; p non-inferiority =0·016). 63 (25%) of 252 patients in the lobaplatin-based group and 63 (25%) of 250 patients in the cisplatin-based group had a progression-free survival event in the intention-to-treat population; 62 (25%) of 246 patients in the lobaplatin-based group and 58 (25%) of 237 patients in the cisplatin-based group had a progression-free survival event in the per-protocol population. The most common grade 3-4 adverse events were mucositis (102 [41%] of 252 in the lobaplatin-based group vs 99 [40%] of 249 in the cisplatin-based group), leucopenia (39 [16%] vs 56 [23%]), and neutropenia (25 [10%] vs 59 [24%]). No treatment-related deaths were reported., Interpretation: Lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy resulted in non-inferior survival and fewer toxic effects than cisplatin-based therapy. The results of our trial indicate that lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy might be a promising alternative regimen to cisplatin-based treatment in patients with locoregional, advanced nasopharyngeal carcinoma., Funding: National Science and Technology Pillar Program, International Cooperation Project of Science and Technology Program of Guangdong Province, Planned Science and Technology Project of Guangdong Province, and Cultivation Foundation for the Junior Teachers at Sun Yat-sen University., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background and Purpose: To evaluate the prognostic value of MRI-detected residual retropharyngeal lymph node (RRLN) at three months after intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC) and second, to establish a nomogram for the pretherapy prediction of RRLN., Materials and Methods: We included 1103 patients with NPC from two hospitals (Sun Yat-Sen University Cancer Center [SYSUCC, n = 901] and Dongguan People's Hospital [DGPH, n = 202]). We evaluated the prognostic value of RRLN using Cox regression model in SYSUCC cohort. We developed a nomogram for the pretherapy prediction of RRLN using logistic regression model in SYSUCC training cohort (n = 645). We assessed the performance of this nomogram in an internal validation cohort (SYSUCC validation cohort, n = 256) and an external independent cohort (DGPH validation cohort, n = 202)., Results: RRLN was an independent prognostic factor for OS (HR 2.08, 95% CI 1.32-3.29), DFS (HR 2.45, 95% CI 1.75-3.42), DMFS (HR 3.31, 95% CI 2.15-5.09), and LRRFS (HR 3.04, 95% CI 1.70-5.42). We developed a nomogram based on baseline Epstein-Barr virus DNA level and three RLN status-related features (including minimum axial diameter, extracapsular nodal spread, and laterality) that predicted an individual's risk of RRLN. Our nomogram showed good discrimination in the training cohort (C-index = 0.763). The favorable performance of this nomogram was confirmed in the internal and external validation cohorts., Conclusion: MRI-detected RRLN at three months after IMRT was an unfavorable prognostic factor for patients with NPC. We developed and validated an easy-to-use nomogram for the pretherapy prediction of RRLN., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: To explore the prognostic value of early radiological response (ERR) to first-line platinum-containing chemotherapy in patients with metastatic nasopharyngeal carcinoma (mNPC), as well as its correlation with the best radiological response (BRR)., Patients and Methods: A total of 756 mNPC patients with measurable lesions who received first-line platinum-containing chemotherapy were enrolled in this study. ERR was defined as complete or partial response after 6 weeks of chemotherapy according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. We performed survival analyses according to the radiological response after repeated chemotherapy. Log-rank test and Cox regression were used to analyze the survival data., Results: About 470 patients achieved ERR and 78 patients achieved subsequent response (objective response after repeated chemotherapy). ERR patients had better OS (P < .001, median OS: 34.3 vs 22.2 months) and PFS (P < .001, median PFS: 10.2 vs 7.4 months) than non-ERR ones. ERR (OS: HR = 0.591, 95% CI, 0.495-0.705, P < .001, PFS: HR = 0.586, 95% CI, 0.500-0.686, P < .001) was independently prolonged survival compared with non-ERR ones. Besides, ERR was significantly correlated with the BRR (Kappa: 0.73; Pearson: 0.74, P < .001), and had significantly longer OS and PFS than patients with subsequent response, respectively., Conclusion: ERR is an independent prognostic factor in determining survival in mNPC patients received first-line platinum-containing chemotherapy, which may be a more sensitive predictor to assess overall efficacy of systemic treatment than BRR in mNPC. Prospective validation studies are needed., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: To date, no guidelines exist for elderly nasopharyngeal carcinoma (NPC) patients (60 years of age or older) due to a lack of prospective clinical trials. This study evaluated the efficacy of concurrent chemotherapy (CCRT) for NPC in elderly patients treated with intensity-modulated radiotherapy (IMRT). Methods: Patients were identified from a prospectively maintained database. A total of 198 consecutive cases of elderly patients with NPC receiving IMRT, including 103 patients treated with IMRT plus CCRT and 95 patients treated with IMRT alone, were analysed from January 2002 to December 2013. Multivariate analysis (MVA) using the Cox proportional hazards model and propensity score analysis (PSA) were performed for overall survival (OS) and disease-free survival (DFS). Finally, sensitivity analysis was performed. Results: The median follow-up time was 55.3 months (range, 3-135.6 months). In the entire cohort, both MVA and PSA models showed that compared with IMRT alone, IMRT plus CCRT significantly improved survival (hazard ratio [HR] 2.143, 95% confidence interval [95% CI] 1.180-3.890; HR 1.961, 95% CI, 1.117-3.443, for OS and DFS, respectively). Similar results were found in the subgroups with high levels of Epstein-Barr virus (EBV) DNA, except in the low-EBV-DNA cohort. The total rates of severe acute toxicity, including leukopenia, neutropenia, stomatitis, and emesis, were significantly higher in the IMRT+CCRT group than in the IMRT-alone group (P < 0.001) but were similar to the rates of severe late toxicity (P = 0.818). Sensitivity analysis confirmed the robustness of our analysis. Conclusions: In the era of IMRT, CCRT retained survival benefits at high EBV DNA levels but not at low EBV DNA levels for elderly NPC patients. Randomized clinical trials are needed to confirm our findings., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background: In the intensity-modulated radiotherapy (IMRT) era, the survival benefit of concurrent chemotherapy for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) remains undetermined. This study aimed to evaluate the benefits of IMRT with concurrent chemotherapy compared with IMRT alone for LA-NPC patients with different plasma Epstein-Barr virus (EBV) DNA levels., Methods: Patients were identified from a prospectively maintained database in an endemic area between November 2002 and December 2013. Cox proportional hazards models, propensity score matching, and inverse probability weighting models were established for survival analysis. Stratification analysis was performed based on interaction effects analysis. Finally, sensitivity analysis was performed considering unmeasured confounders., Results: A total of 1357 eligible patients were enrolled (median follow up 62.4 months; range 3.5-155.8 months). No significant survival differences were observed between groups in the entire cohort. Notably, a significant interaction effect was observed between treatment regimens and EBV DNA levels. In patients with high EBV DNA levels (>4000 copies/ml), all three models showed that IMRT with concurrent chemotherapy significantly improved overall survival [hazard ratio (HR) 2.521, 95% confidence interval (CI) 1.218-5.216], disease-free survival (HR 2.168, 95% CI 1.349-3.483), and distant metastasis-free survival (HR 2.331, 95% CI 1.194-4.551) compared with IMRT alone. No differences were found in patients with low EBV DNA levels. Sensitivity analysis confirmed the robustness of the results., Conclusion: In the IMRT era, concurrent chemotherapy treatment of LA-NPC patients with high EBV DNA levels is reasonable. However, the optimal regimen for LA-NPC patients with low EBV DNA levels needs further validation in randomized clinical trials., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest.

Background: Available data in the literature comparing different induction chemotherapy (IC) regimens on locoregionally advanced nasopharyngeal carcinoma (NPC) are scarce. The purpose of the present study was to evaluate the outcomes of locoregionally advanced NPC patients who were treated with taxane, cisplatin and 5-fluorouracil (TPF) or cisplatin and 5-fluorouracil (PF) as IC followed by concurrent chemoradiotherapy (CCRT)., Methods: In total, 1879 patients with locoregionally advanced NPC treated with IC and CCRT from a prospectively maintained database were included in the present observational study. We compared overall survival (OS), disease-specific survival (DSS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival, using the propensity score method., Results: In total, 1256 patients received TPF or PF as IC backbone. The TPF group showed significantly better OS (hazard ratio [HR], 0.660; 95% confidence interval [CI] 0.442-0.986; P = 0.042), DSS (HR, 0.624; 95% CI 0.411-0.947; P = 0.027) and DMFS (HR, 0.589; 95% CI 0.406-0.855; P = 0.005) compared with the PF group in multivariable analyses. Propensity score matching identified 294 patients in each cohort and confirmed that TPF was associated with significantly improved 5-year OS (88.1% vs. 80.7%; P = 0.042), DSS (88.5% vs. 80.7%; P = 0.021) and DMFS (87.9% vs. 78.6%; P = 0.012) rates compared with the PF group. There were no significant differences in locoregional relapse-free survival before or after matching., Conclusions: In our study, IC with the TPF regimen combined with CCRT showed improved long-term survival for the patients with locoregionally advanced NPC compared with the PF regimen. However, a prospective randomized clinical trial to validate these findings is necessary.

Background: Distant metastasis is the major cause of treatment failure in patients with nasopharyngeal carcinoma (NPC). Although several biomarkers correlate with metastasis and prognosis, the molecular mechanisms of NPC development and progression remain unclear., Methods: Quantitative RT-PCR (qRT-PCR), western blotting, cell growth, foci formation, migration and invasion assays, and xenograft mouse models were utilized to examine the expression levels and functions of the CXCL5/CXCR2 axis in NPC. A luciferase reporter assay, western blotting, immunofluorescence, and migration and invasion assays were used to identify and verify the ERK/GSK-3β/Snail signalling pathway., Results: CXCL5 was significantly increased in the sera of NPC patients, and high expression levels of CXCL5/CXCR2 in NPC primary tissues indicated poor survival. CXCL5 and CXCR2 were upregulated in NPC cell lines. Ectopic expression of the CXCL5/CXCR2 axis promoted NPC cell migration and invasion in vitro and the formation of lung metastases in vivo. Mechanistically, the dual overexpression of CXCL5 and CXCR2 promoted cell spreading by inducing the epithelial-mesenchymal transition (EMT) through the activation of the ERK/GSK-3β/Snail signalling pathway., Conclusion: The CXCL5/CXCR2 axis contributes to the EMT of NPC cells by activating ERK/GSK-3β/Snail signalling, and this axis may be a potential diagnostic marker and therapeutic target for patients with NPC.

Background: To evaluate the clinical characteristics, treatment-related toxicities and survival in patients with nasopharyngeal carcinoma (NPC) with or without oropharyngealcandidiasis (OPC) during radiotherapy., Methods: The current study was conducted with NPC patients undergoing radiotherapy at Sun Yat-Sen University Cancer Center between June 2011 and May 2012. A clinical diagnosis of candidiasis was determined on the basis of a positive potassium hydroxide (KOH) test and the presence of pseudomembranous (white) form of candidal overgrowth. The Cox proportional hazard regression model was used to test the association of OPC and related survival rates., Results: Compared with the non-OPC group, the OPC group had significantly increased occurrence rates of grade 3-4 mucositis (14.5% vs. 7.4%, P = 0.049), anaemia (11.3% vs. 4.4%, P = 0.020), hepatotoxicity (4.8% vs. 1.1%, P = 0.021) and critical weight loss (85.5% vs. 56.6%, P<0.001) during radiotherapy. The OPC group had a significantly lower disease-free survival (DFS) (70.9% vs. 82.6%, P = 0.012), mainly as a result of a reduction in locoregional relapse-free survival (LRFS) (87.0%vs. 94.9%, P = 0.025). After stratification by T stage, the 5-year DFS in T3-4 patients were 82.0% and 68.8% in non-OPC and OPC groups, respectively (P = 0.022). Multivariate analyses indicated that OPC was a prognostic factor for LRFS and DFS., Conclusions: OPC during radiotherapy may worsen the nutritional status of NPC patients according to weight loss and anaemia, leading to a negative impact on 5-year locoregional relapse-free survival and disease-specific survival. Further investigations are needed to explore whether prevention and treatment of OPC during radiotherapy will be useful.

Objectives: Nanoparticle albumin-bound paclitaxel (NAB-paclitaxel) was designed to avoid solvent-related toxicities, and improve anti-tumor efficacy via increasing paclitaxel's intratumoral concentration and its uptake by tumor cells. This trial aimed to determine the safety and efficacy of induction NAB-paclitaxel combined with cisplatin followed by concurrent chemoradiotherapy (CCRT) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC)., Patients and Methods: Patients with stage III-IVb NPC received NAB-paclitaxel (260mg/m 2 ) combined with cisplatin (80mg/m 2 ) intravenously on days 1 and 22, followed by cisplatin (80mg/m 2 ) on days 43 and 64, concomitant with intensity-modulated radiation therapy. This trial is registered with the Chinese Clinical Trials Registry, number ChiCTR-ONC-12002615., Results: From July 2010 to November 2013, 36 eligible patients with nonmetastatic stage III-IVb NPC were enrolled. The objective response rates were 97.2% (eight complete responses [CRs] and 27 partial responses [PRs]) and 100% (30 CRs and six PRs) after two cycles of induction chemotherapy (ICT) and CCRT, respectively. With a median follow-up time of 45months, the estimated 3-year progression-free survival and cancer-specific survival were 86.1% (95% confidence interval [CI], 69.8-99.8%) and 91.7% (95% CI, 68.9-100.0%), respectively. The most frequent grade 3-4 toxicities were neutropenia (8.6%) and nausea (8.6%) after ICT and thrombocytopenia (34.3%) and leukopenia (28.6%) after CCRT., Conclusion: NAB-paclitaxel combined with cisplatin as an ICT regimen showed encouraging anti-tumor effects and manageable toxicities in LA-NPC. Further randomized controlled trials in phase III of NAB-paclitaxel in patients with LA-NPC are warranted., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: To compare the effectiveness of concurrent cisplatin chemoradiotherapy plus cetuximab with that of concurrent chemoradiotherapy (CCRT) alone in locoregionally advanced nasopharyngeal carcinoma (LRANPC) patients., Materials and Methods: A total of 3257 LRANPC patients from a prospectively maintained database were included in this observational study to examine the effectiveness of adding cetuximab to CCRT. We compared overall survival (OS), disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) using the propensity score method., Results: In this cohort, 131 patients received CCRT plus cetuximab. Cetuximab-treated patients were more likely to receive intensity-modulated radiation therapy and were less likely to receive induction chemotherapy or adjuvant chemotherapy. The addition of cetuximab was associated with increased DMFS compared with CCRT alone based on univariable and multivariable analyses (5-year OS, 94.1% vs. 87.3%; P=0.044), but not with increased OS, DFS, or LRRFS. Propensity score matching identified 96 patients in each cohort and confirmed that a DMFS benefit was associated with the addition of cetuximab (HR, 0.38; 95% CI, 0.15-0.99, P=0.044). Subgroup analyses demonstrated a significant DMFS benefit with CCRT plus cetuximab in patients with N2-N3 stage disease compared with N2-N3 patients receiving CCRT alone (87.9% and 66.2%, respectively; P=0.045)., Conclusions: In conclusion, the addition of cetuximab to first-line chemoradiotherapy is associated with an improvement in DMFS in patients with LRANPC. A prospective randomized clinical trial will be necessary to validate this result., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Whether the waiting time for radical radiotherapy (WRT) detrimentally impacts nasopharyngeal carcinoma (NPC) prognosis is unclear. We estimated the influence of WRT on overall survival (OS) and disease-specific survival (DSS) of NPC., Patients and Methods: Patients were identified from prospectively maintained database. WRT was calculated from histological diagnosis to initiation of radiotherapy (RT). Survival analysis was estimated using Weibull parametric model and propensity score analysis (PSA). Recursive partitioning analysis (RPA) identified optimal WRT threshold via conditional inference trees to estimate the greatest survival differences based on randomly selected training and validation sets, and this process was repeated 1000 times to ensure threshold robustness. Sensitivity analysis estimated effects of potential unmeasured confounders., Results: A total of 9896 patients were included. In multivariate analysis, WRT of 31-60°d, of 61-90°d and of greater than 90°d independently increased mortality risk compared to less than 30°d. Upon RPA, ranges of 30-35°d with the peak of 30°d were confirmed with 89% of simulations validating optimal thresholds. In threshold-based groups, adjusted hazard ratios (HRs) for WRT of greater than 30°d by both Weibull model and PSA were significantly higher than for WRT of less than 30°d [OS: HR = 1.13, 95% confidence interval (CI) 1.04-1.23, P = 0.003; DSS: HR = 1.15, 95% CI 1.05-1.26, P = 0.002]. Sensitivity analysis revealed robustness of results., Conclusions: WRT independently affects survival. Increasing WRT beyond 30°d was most consistently detrimental to survival. WRT of NPC should be as short as reasonably achievable (ASARA)., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Due to improvements in imaging and radiological techniques as well as the use of chemotherapy, distant metastasis has become the predominant mode of treatment failure in patients with locally advanced nasopharyngeal carcinoma (LA-NPC). Platinum-based systemic chemotherapy has shown survival benefits and is now the standard strategy for systemic therapy in patients with LA-NPC. Notably, the third-generation platinum reagent lobaplatin has shown anti-tumor effects in several solid tumors with lower incidences of gastrointestinal, hepatic and renal toxicity relative to other platinum drugs. However, the safety and efficacy of lobaplatin as a first-line regimen in patients with LA-NPC are undetermined., Methods: Patients with stage III-IVa-b NPC received lobaplatin at a dose of 30 mg/m2 on days 1 and 22 combined with a continuous 120-h intravenous injection of 5-fluorouracil at a dose of 4 g/m2 followed by lobaplatin at a dose of 50 mg/m2 on days 43 and 64 concomitant with intensity-modulated radiation therapy. Objective response rates and acute toxicity were assessed based on RECIST (1.1) and CTCAE v.3.0, respectively. Kaplan-Meier analysis was used to calculate survival rates., Results: Fifty-nine patients were enrolled, and 44 patients (74.6%) received allocated cycles of chemotherapy. The objective response rates were 88.1% (95% confidence interval [CI], 0.77 to 0.95) and 100% after induction chemotherapy (ICT) and concurrent chemoradiotherapy (CRT), respectively. With a median follow-up period of 44 months, the 3-year estimated progression-free survival and overall survival were 86.4% (95% CI, 69.8 to 98.8) and 94.9% (95% CI, 89.5 to 100), respectively. The most common grade 3-4 toxicities were neutropenia (8.5%) and thrombocytopenia (40.7%) after ICT and CRT, respectively., Conclusion: Lobaplatin combined with 5-fluorouracil followed by lobaplatin-RT treatment showed encouraging anti-tumor effects with tolerable toxicities in patients with LA-NPC. Randomized controlled trials of lobaplatin in patients with LA-NPC are warranted., Trial Registration: This trial was registered with the Chinese Clinical Trials Registry and approved on March 31 st , 2012, number ChiCTR-ONC-12002060 .

Background: For patients with nasopharyngeal carcinoma (NPC) who undergo re-irradiation with intensity-modulated radiotherapy (IMRT), lethal nasopharyngeal necrosis (LNN) is a severe late adverse event. The purpose of this study was to identify risk factors for LNN and develop a model to predict LNN after radical re-irradiation with IMRT in patients with recurrent NPC., Methods: Patients who underwent radical re-irradiation with IMRT for locally recurrent NPC between March 2001 and December 2011 and who had no evidence of distant metastasis were included in this study. Clinical characteristics, including recurrent carcinoma conditions and dosimetric features, were evaluated as candidate risk factors for LNN. Logistic regression analysis was used to identify independent risk factors and construct the predictive scoring model., Results: Among 228 patients enrolled in this study, 204 were at risk of developing LNN based on risk analysis. Of the 204 patients treated, 31 (15.2%) developed LNN. Logistic regression analysis showed that female sex (P = 0.008), necrosis before re-irradiation (P = 0.008), accumulated total prescription dose to the gross tumor volume (GTV) ≥145.5 Gy (P = 0.043), and recurrent tumor volume ≥25.38 cm(3) (P = 0.009) were independent risk factors for LNN. A model to predict LNN was then constructed that included these four independent risk factors., Conclusions: A model that includes sex, necrosis before re-irradiation, accumulated total prescription dose to GTV, and recurrent tumor volume can effectively predict the risk of developing LNN in NPC patients who undergo radical re-irradiation with IMRT.

Cervical lymph node metastasis is common in patients with nasopharyngeal carcinoma (NPC), but occipital lymph node metastasis in NPC patients has not yet been reported. In this case report, we describe an NPC patient with occipital lymph node metastasis. The clinical presentation, diagnostic procedure, treatment, and outcome of this case were presented, with a review of the related literature.

Background: The aim of this study was to determine whether baseline C-reactive protein (CRP) levels and CRP kinetics predict the overall survival in metastatic nasopharyngeal carcinoma (mNPC) patients., Methods: A total of 116 mNPC patients from January 2006 to July 2011 were retrospectively reviewed. Serum CRP level was measured at baseline and thereafter at the start of each palliative chemotherapy cycle for all patients., Results: Patients with higher values of baseline CRP (≥ 3.4 mg/L) had significantly worse survival than those with lower baseline CRP values (< 3.4 mg/L). Patients were divided into four groups according to baseline CRP and CRP kinetics: (1) patients whose CRP < 3.4 mg/L and never elevated during treatment; (2) patients whose CRP < 3.4 mg/L and elevated at least one time during treatment; (3) patients whose CRP ≥ 3.4 mg/L and normalized at least one time during treatment; and (4) patients whose CRP ≥ 3.4 mg/L and never normalized during treatment. The patients were further assigned to non-elevated, elevated, normalized, and non-normalized CRP groups. Overall survival rates were significantly different among the four groups, with three-year survival rates of 68%, 41%, 33%, and 0.03% for non-elevated, elevated, normalized, and non-normalized CRP groups respectively. When compared with the non-elevated group, hazard ratios of death were 1.69, 2.57, and 10.34 in the normalized, elevated, and non-normalized groups (P < 0.001)., Conclusions: Baseline CRP and CRP kinetics may be useful to predict the prognosis of metastatic NPC patients treated with palliative chemotherapy and facilitate individualized treatment. A prospective study to validate this prognostic model is still needed however.