Head and neck MRI-based T stage and [18F]FDG PET/CT-based N/M stage improved prognostic stratification in primary nasopharyngeal carcinoma.

OBJECTIVES: To evaluate whether MRI-based T stage (TMRI), [18F]FDG PET/CT-based N (NPET/CT), and M stage (MPET/CT) are superior in NPC patients' prognostic stratification based on long-term survival evidences, and whether TNM staging method involving TMRI + NPET/CT + MPET/CT could improve NPC patients' prognostic stratification. METHODS: From April 2007 to December 2013, 1013 consecutive untreated NPC patients with complete imaging data were enrolled. All patients' initial stages were repeated based on (1) the NCCN guideline recommended "TMRI + NMRI + MPET/CT" ("MMP") staging method; (2) the traditional "TMRI + NMRI + Mconventional work-up (CWU)" ("MMC") staging method; (3) the single-step "TPET/CT + NPET/CT + MPET/CT" ("PPP") staging method; or (4) the "TMRI + NPET/CT + MPET/CT" ("MPP") staging method recommended in present research. Survival curve, ROC curve, and net reclassification improvement (NRI) analysis were used to evaluate the prognosis predicting ability of different staging methods. RESULTS: [18F]FDG PET/CT performed worse on T stage (NRI = - 0.174, p < 0.001) but better on N (NRI = 0.135, p = 0.004) and M stage (NRI = 0.126, p = 0.001). The patients whose N stage upgraded by [18F]FDG PET/CT had worse survival (p = 0.011). The "TMRI + NPET/CT + MPET/CT" ("MPP") method performed better on survival prediction when compared with "MMP" (NRI = 0.079, p = 0.007), "MMC" (NRI = 0.190, p < 0.001), or "PPP" method (NRI = 0.107, p < 0.001). The "TMRI + NPET/CT + MPET/CT" ("MPP") method could reclassify patients' TNM stage to a more appropriate stage. The improvement is significant in patients with more than 2.5-years follow-up according to the time-dependent NRI values. CONCLUSIONS: The MRI is superior to [18F]FDG PET/CT in T stage, and [18F]FDG PET/CT is superior to CWU in N/M stage. The "TMRI + NPET/CT + MPET/CT" ("MPP") staging method could significantly improve NPC patients' long-term prognostic stratification. CLINICAL RELEVANCE STATEMENT: The present research provided long-term follow-up evidence for benefits of MRI and [18F]FDG PET/CT in TNM staging for nasopharyngeal carcinoma, and proposes a new imaging procedure for TNM staging incorporating MRI-based T stage and [18F]FDG PET/CT-based N and M stage, which significantly improves long-term prognostic stratification for patients with NPC. KEY POINTS: • The long-term follow-up evidence of a large-scale cohort was provided to evaluate the advantages of MRI, [18F]FDG PET/CT, and CWU in the TNM staging of nasopharyngeal carcinoma. • A new imaging procedure for TNM stage of nasopharyngeal carcinoma was proposed.

Comparing three induction chemotherapy regimens for patients with locoregionally advanced nasopharyngeal carcinoma based on TNM stage and plasma Epstein-Barr virus DNA level.

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 < 1500 copies) and high-risk group (pre-EBV DNA ≥ 1500 copies). Progression free survival (PFS), overall survival (OS), locoregional relapse free survival (LRFS), distant metastasis free survival (DMFS) and grade 3-4 toxicities were compared among different IC regimens. The survival rates were compared using log-rank test and a Cox proportional hazards model was used to perform multivariate analyses. RESULTS: A multivariate analysis revealed TPF to be more effective than TP. Among stage III patients, no significant difference in clinical outcome between the different IC regimens was showed, while TPF was associated with significantly better survival conditions in the stage IV patients. A further subgroup analysis revealed that only patients with pre-EBV DNA ≥ 1500 copies could benefit from the application of TPF among stage IV NPC. In terms of acute toxicities, PF was associated with fewer grade 3/4 acute toxicities. CONCLUSIONS: In low-risk NPC patients, PF-based IC showed similar efficacy as TPF and TP but was associated with fewer grade 3/4 acute toxicities. In high-risk patients, however, the TPF regimen was superior to PF and TP, although grade 3/4 toxicities were more common with the TPF regimen.

Tumor Volume Is Better Than Diameter for Predicting the Prognosis of Patients with Early-Stage Non-small Cell Lung Cancer.

BACKGROUND: This study aimed to investigate whether tumor volume (TV) is better than diameter for predicting the prognosis of patients with early-stage non-small cell lung cancer (NSCLC) after complete resection. METHODS: This study retrospectively reviewed the clinicopathologic characteristics of 274 patients with early-stage NSCLC who had received pretreatment computed tomography (CT) scans and complete resection. TV was semi-automatically measured from CT scans using an imaging software program. The optimal cutoff of TV was determined by X-tile software. Disease-free survival (DFS) and overall survival (OS) were assessed by the Kaplan-Meier method. The prognostic significance of TV and other variables was assessed by Cox proportional hazards regression analysis. RESULTS: Using 3.046 cm3 and 8.078 cm3 as optimal cutoff values of TV, the patients were separated into three groups. A larger TV was significantly associated with poor DFS and OS in the multivariable analysis. Kaplan-Meier curves of DFS and OS showed significant differences on the basis of TV among patients with stage 1a disease, greatest tumor diameter (GTD) of 2 cm or smaller, and GTD of 2-3 cm, respectively. Using two TV cutoff points, three categories of TV were created. In 54 cases (19.7%), patients migrated from the GTD categories of 2 cm or smaller, 2-3 cm, and larger than 3 cm into the TV categories of 3.046 cm3 or smaller, 3.046-8.078 cm3, and larger than 8.078 cm3. CONCLUSION: TV is an independent prognostic factor of DFS and OS for early-stage NSCLC. The findings show that TV is better than GTD for predicting the prognosis of patients with early-stage NSCLC.

Maximal standard uptake values of 18F-fluoro-2-deoxy-D-glucose positron emission tomography compared with Epstein-Barr virus DNA as prognostic indicators in de novo metastatic nasopharyngeal carcinoma patients.

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.

Identifying optimal candidates for local treatment of the primary tumor among patients with de novo metastatic nasopharyngeal carcinoma: a retrospective cohort study based on Epstein-Barr virus DNA level and tumor response to palliative chemotherapy.

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 < 0.001). Multivariate analyses demonstrated that LRRT was an independent prognostic factor of OS in the low-risk patients (P < 0.001). However, among the high-risk patients (patients with detectable EBV DNA and/or unsatisfactory response after PCT), no statistically significant survival differences were observed between the LRRT and non-LRRT groups. CONCLUSIONS: EBV DNA level and tumor response after PCT both correlate with the prognosis of de novo metastatic NPC. In such cases, LRRT may benefit the patients with undetectable EBV DNA levels and satisfactory tumor response after PCT.

Concurrent chemoradiotherapy with nedaplatin versus cisplatin in stage II-IVB nasopharyngeal carcinoma: an open-label, non-inferiority, randomised phase 3 trial.

BACKGROUND: Cisplatin-based concurrent chemoradiotherapy is currently considered to be the standard treatment regimen for patients with advanced nasopharyngeal carcinoma, but has well known side-effects such as gastrointestinal reactions, nephrotoxicity, and ototoxicity. Nedaplatin was developed to decrease the toxic effects induced by cisplatin, and in this trial we assessed whether a nedaplatin-based concurrent chemoradiotherapy regimen was non-inferior to a cisplatin-based regimen in patients with locoregional, stage II-IVB nasopharyngeal carcinoma. METHODS: We did an open-label, non-inferiority, phase 3, randomised, controlled trial at two centres in China. Patients aged 18-65 years with non-keratinising stage II-IVB (T1-4N1-3 or T3-4N0) nasopharyngeal carcinoma, a Karnofsky score of at least 70, and adequate haematological, renal, and hepatic function were randomly assigned (1:1) to receive intravenously either nedaplatin 100 mg/m2 or cisplatin 100 mg/m2 on days 1, 22, and 43 for three cycles concurrently with intensity-modulated radiotherapy. Randomisation was done manually using a computer-generated random number code and patients were stratified by treatment centre and clinical stage. Patients and clinicians were not masked to treatment allocation. The primary endpoint was progression-free survival at 2 years; non-inferiority was shown if the upper limit of the 95% CI for the difference in 2-year progression-free survival between the two groups did not exceed 10%. Analyses were by both intention to treat and per protocol, including all patients who received at least one complete cycle of chemotherapy. This trial is registered with ClinicalTrials.gov, number NCT01540136, and is currently in follow-up. FINDINGS: Between Jan 16, 2012, and July 16, 2014, we randomly assigned 402 patients to nedaplatin-based (n=201) or cisplatin-based (n=201) concurrent chemoradiotherapy. In the intention-to-treat population, 2-year progression-free survival was 89·9% (95% CI 85·8-94·0) in the cisplatin group and 88·0% (83·5-94·5) in the nedaplatin group, with a difference of 1·9% (95% CI -4·2 to 8·0; pnon-inferiority=0·0048). In the per-protocol analysis (cisplatin group, n=197; nedaplatin group, n=196), 2-year progression-free survival was 89·7% (95% CI 85·4-94·0) in the cisplatin group and 88·7% (84·2-94·5) in the nedaplatin group, with a difference of 1·0% (95% CI -5·2 to 7·0; pnon-inferiority=0·0020). A significantly higher frequency of grade 3 or 4 vomiting (35 [18%] of 198 in the cisplatin group vs 12 [6%] of 200 in the nedaplatin group, p<0·0001), nausea (18 [9%] vs four [2%], p=0·0021), and anorexia (53 [27%] vs 26 [13%], p=0·00070) was observed in the cisplatin group compared with the nedaplatin group. 11 (6%) patients in the nedaplatin group had grade 3 or 4 thrombocytopenia compared with four (2%) in the cisplatin group (p=0·065). Patients in the cisplatin group had a higher frequency of any grade or grade 3 or 4 late auditory or hearing toxicities than did patients in the nedaplatin group (grade 3 or 4: three [2%] in the nedaplatin group vs 11 [6%] in the cisplatin group, p=0·030). No patients died from treatment-related causes. INTERPRETATION: Our findings show that nedaplatin-based concurrent chemoradiotherapy represents an alternative doublet treatment strategy to cisplatin-based concurrent chemoradiotherapy for patients with locoregional, advanced nasopharyngeal carcinoma. Further investigations are needed to explore the potential use of this treatment as induction or adjuvant chemotherapy or in combination with other agents. FUNDING: National Key R&D Program of China, National Natural Science Foundation of China, Sun Yat-sen University Clinical Research 5010 Program, Sci-Tech Project Foundation of Guangzhou City, National Key Basic Research Program of China, Special Support Plan of Guangdong Province, Sci-Tech Project Foundation of Guangdong Province, Health & Medical Collaborative Innovation Project of Guangzhou City, National Science & Technology Pillar Program during the Twelfth Five-year Plan Period, PhD Start-up Fund of Natural Science Foundation of Guangdong Province, Cultivation Foundation for the Junior Teachers in Sun Yat-sen University, and Fundamental Research Funds for the Central Universities.

Symptomatic venous thromboembolism associated with peripherally inserted central catheters predicts a worse survival in nasopharyngeal carcinoma: results of a large cohort, propensity score-matched analysis.

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 < 0.001), DMFS (85.0% vs 91.2%, p < 0.001), LRRFS (93.9% vs 97.7%, p < 0.001) and OS (85.4% vs 87.6%, p < 0.001). Subgroup analyses indicated that no significant survival difference was found between PICC-related superficial venous thrombosis and deep vein thrombosis, nor did different anticoagulant treatment methods. CONCLUSIONS: PICC-VTE was associated with a worse survival outcome in nonmetastatic NPC patients. A prospective randomized clinical trial is required to verify the results.

Liposomal paclitaxel versus docetaxel in induction chemotherapy using Taxanes, cisplatin and 5-fluorouracil for locally advanced nasopharyngeal carcinoma.

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 < 0.05 for all). CONCLUSIONS: Compared with docetaxel, liposomal paclitaxel has identical anti-tumor efficacy, but causes fewer and milder adverse reactions in IC for NPC.

Associations between tumor necrosis factor alpha gene polymorphism and sarcoidosis: a meta-analysis.

Published studies regarding the association between tumor necrosis factor alpha (TNF-α) gene polymorphism and sarcoidosis risk are inconsistent. In order to clarify this association, we performed a meta-analysis of case-control studies with available data. PubMed, EMBASE and BIOSIS Previews were comprehensively searched to identify relevant studies. Twelve case-control studies in 11 articles involving 3,218 participants were included in the meta-analysis to assess the association between TNF-α gene polymorphism and susceptibility to sarcoidosis. We estimated the pooled odds ratio (OR) with its 95% confidence intervals (95% CI) to explore the potential association. Our meta-analysis results suggested that TNF-α-308G/A AA/AG genotype increased sarcoidosis risk, in Asian and Caucasian ethnicity, and in sarcoidosis with Löfgren syndrome. No association was found between TNF-α-238G/A, TNF-α-857C/T polymorphism and sarcoidosis risk. In conclusion, our meta-analysis indicated that AG/GG genotype of TNF-α-308G/A are associated with increased sarcoidosis risk.

rac-(S,S)-Bis(1-ferrocenylbut-3-en-yl) ether.

The title complex, [Fe2(C5H5)2(C18H20O)], formed by dehydration of 1-ferrocenylbut-3-en-1-ol, crystallizes as a racemic compound. The central C-O-C fragment, in which the C atoms are the chiral centers, is characterized by an angle of 116.26 (10)° at the O atom. One ferrocene group shows a staggered conformation whereas the other shows an eclipsed conformation.

Efficacy of Transnasal Endoscopic Fine-Needle Aspiration Biopsy in Diagnosing Submucosal Nasopharyngeal Carcinoma.

OBJECTIVES/HYPOTHESIS: The routine practices of examining submucosal lesions are not suitable for deep lesions. Therefore, we evaluated the efficacy of non-real-time image-guided transnasal endoscopic fine-needle aspiration biopsy (FNAB) in diagnosing nasopharyngeal carcinoma (NPC) with submucosal lesions. STUDY DESIGN: The effectiveness evaluation of diagnostic methods. METHODS: Fifty suspected NPC patients who failed in conventional biopsies were enrolled in this study. The efficacy, maneuverability, and safety of FNAB in diagnosing these intractable cases were evaluated. RESULTS: The definitive diagnostic results of these 50 patients were NPC (34/50, 68.0%), nasopharyngeal necrosis (1/50, 2.0%), nasopharyngeal mucositis (12/50, 24.0%), and other cancers (3/50, 6.0%), respectively. The results of the diagnostic efficacy of FNAB were sensitivity, 89.2%; specificity, 100.0%; positive predictive value, 100.0%; negative predictive value, 76.5%; and accuracy, 92.0%, respectively. The area under the receiver operating characteristic curves was 0.946 (95% confidence interval = 0.884-1.00, P < .001). No severe complications occurred after FNAB. CONCLUSIONS: FNAB can improve the diagnostic efficiency of NPC occurring in the submucosal space. It can be an additional option for routine nasopharyngeal biopsy and is worthy of clinical application. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1798-1804, 2021.

Geriatric nutritional risk index as an independent prognostic factor in locally advanced nasopharyngeal carcinoma treated using radical concurrent chemoradiotherapy: a retrospective cohort study.

BACKGROUND: Nutritional status is a key factor influencing the prognosis of patients with cancer. The Geriatric Nutritional Risk Index (GNRI) has been used to predict mortality risk and long-term outcomes. In this study, we aimed to evaluate the predictive value of pretreatment GNRI in patients with nasopharyngeal carcinoma (NPC). METHODS: A total of 1,065 patients with biopsy-proven non-disseminated nasopharyngeal carcinoma were included. Based on a cutoff value of pretreatment GNRI, patients were divided into two groups (low ≤107.7 and high >107.7). Combining GNRI and baseline Epstein-Barr virus (EBV) DNA, all patients were further stratified into three risk groups, namely, high-risk (high EBV DNA and low GNRI), low-risk (low EBV DNA and high GNRI), and medium-risk (except the above) groups. Multivariate analyses were performed using the Cox proportional hazards model to assess the predictive value of the GNRI. RESULTS: Among the 1,065 patients, 527 (49.5%) and 538 (50.5%) were divided into low and high GNRI groups, respectively. Within a median follow-up of 83 months, patients with a high GNRI score exhibited significantly higher overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) compared to those with low GNRI scores (P<0.05). Multivariate analyses revealed that high GNRI is an independent prognostic factor for OS and PFS (hazard ratio, HR, 0.471, 95% CI, 0.270-0.822, P=0.008; HR 0.638, 95% CI, 0.433-0.941, P=0.023, respectively). Using a combination of baseline GNRI and EBV DNA, a satisfying separation of survival curves between different risk groups for OS, PFS, DMFS was observed. The survival rates of patients in the high-risk group were significantly lower than those in the low- and medium-risk groups (all P<0.001). The combined classification was demonstrated to be an independent prognostic factor for OS and PFS after adjustment using multivariate analysis. CONCLUSIONS: Pretreatment GNRI is an independent prognostic factor for NPC patients. The combination of baseline GNRI score and EBV DNA level improved the prognostic stratification of NPC patients.

Identifying optimal candidates for induction chemotherapy among stage II-IVa nasopharyngeal carcinoma based on pretreatment Epstein-Barr virus DNA and nodal maximal standard uptake values of [18 F]-fluorodeoxyglucose positron emission tomography.

OBJECTIVE: This study aimed to select optimal candidates benefiting from the addition of induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in stage II-IVa nasopharyngeal carcinoma (NPC) based on Epstein-Barr virus (EBV) DNA and nodal maximal standardized uptake values (SUVmax-N) of [18 F]-fluorodeoxyglucose positron emission tomography. PATIENTS AND MATERIALS: A total of 679 patients diagnosed with stage II-IVa (except N0) NPC were retrospectively included in this study. Overall survival was the primary endpoint. Survival differences between different groups were compared using the log-rank test. The hazard ratio (HR) and 95% confidence interval (CI) were calculated using a multivariable Cox proportional hazards model. RESULTS: Both high levels of EBV DNA (>1500 copies/mL) and SUVmax-N (>12.3) indicated worse survival conditions. All patients were divided into low- and high-risk groups based on these two biomarkers. The risk group was an independent prognostic factor in OS, progression-free survival (PFS), and distant metastasis-free survival (DMFS) (all p-values<0.05). The addition of IC to CCRT was associated with survival improvement in OS, PFS, and DMFS in high-risk patients, while no survival difference was found between CCRT and IC+CCRT in low-risk patients. CONCLUSIONS: Our study can help clinicians select stage II-IVa NPC patients who benefit from IC, which is important in guiding individual treatment.

Induction chemotherapy followed by radiotherapy versus concurrent chemoradiotherapy in the treatment of different risk locoregionally advanced nasopharyngeal carcinoma.

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.

Effect of local treatment for metastasis and its sequence with chemotherapy on prognosis of post-treatment metastatic nasopharyngeal carcinoma patients.

BACKGROUND: Distant metastasis after chemoradiotherapy remains the leading cause of death in NPC patients. But the effect of local treatment for metastatic sites and its sequence with chemotherapy on prognosis of them are poorly documented. METHODS: 448 post-treatment metastatic NPC patients were included in our retrospective study. And Cox regression and log-rank tests were applied to investigate the association between topical treatment and its sequence with chemotherapy and survival using the propensity score method (PSM) to adjust for gender, age, Tumor stage, Node stage, metastatic sites, diabetes and smoking with a 1:2 matching protocol. RESULTS: The 3-year OS was significantly higher in patients who received local treatment of distant metastasis compared with patients who did not (48.8% vs 33.8%, P = 0.001) in primary cohort. PSM identified 120 patients in the cohort with local treatment and 240 in that without and similar survival benefits were observed for the local treatment (3-year OS: 36.2% versus 48.8%, P = 0.011). Subgroup analyses indicated that there was no significant survival difference in patients with different treatment sequence. CONCLUSIONS: In conclusion, post-treatment metastatic NPC patients could be beneficial from local treatment for metastasis but its sequence with palliative chemotherapy does not affect overall survival.

Subdivision of Nasopharyngeal Carcinoma Patients with Bone-Only Metastasis at Diagnosis for Prediction of Survival and Treatment Guidance.

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.

The development of a nomogram to predict post-radiation necrosis in nasopharyngeal carcinoma patients: a large-scale cohort study.

Objective: This study aimed to establish a nomogram to predict the risk of post-radiation necrosis in nasopharyngeal carcinoma (NPC) patients. Background: This study was performed to identify influencing factors for developing post-radiation necrosis, and to establish an effective nomogram model to predict individual risks in NPC patients. Methods: 7144 NPC patients receiving radical radiotherapy from 2007 to 2012 were involved in the study, and 207 of them developed nasopharyngeal necrosis (NPN). The clinical characteristics and baseline laboratory results were collected and analyzed. Independent predictive factors were selected using the Cox proportional model and incorporated into the nomogram. The receiver operating characteristic curve and the calibration curve were used to verify discrimination and calibration. Results: The experience of re-irradiation contributed most to the occurrence of NPN (HR, 15.56, 95% CI 10.84-22.35, p<0.001). Clinical factors including age, pathology type, history of diabetes, and original T stage were independent predictors of NPN. Factors reflecting patients' baseline nutritional and inflammatory status such as hemoglobin, albumin, and C-reactive protein were also significantly associated with the development of NPN. With all independent predictive factors incorporated, a nomogram was generated, and it showed excellent discrimination and calibration. Conclusion: This study was the first large-scale cohort study focusing on the development of NPN and established a nomogram to predict its occurrence based on the clinical and laboratory indicators. The nomogram demonstrated good discriminative capacity and satisfactory agreement, which would offer valuable clues for clinicians to distinguish the high-risk NPN population and maintain close surveillance.

The Association Between the Development of Radiation Therapy, Image Technology, and Chemotherapy, and the Survival of Patients With Nasopharyngeal Carcinoma: A Cohort Study From 1990 to 2012.

PURPOSE: Previous studies demonstrated that the radiation therapy, image technology, and the application of chemotherapy have developed in the last 2 decades. This study explored the survival trends and treatment failure patterns of patients with nonmetastatic nasopharyngeal carcinoma (NPC) treated with radiation therapy. Furthermore, we evaluated the survival benefit brought by the development of radiation therapy, image technology, and chemotherapy based on a large cohort from 1990 to 2012. METHODS AND MATERIALS: Data from 20,305 patients with nonmetastatic NPC treated between 1990 and 2012 were analyzed. Patients were divided into 4 calendar periods (1990-1996, 1997-2002, 2003-2007, and 2008-2012). Overall survival (OS) was the primary endpoint. RESULTS: Magnetic resonance imaging has replaced computed tomography as the most important imaging technique since 2003. Conventional 2-dimensional radiation therapy, which was the main radiation therapy technique in our institution before 2008, was replaced by intensity modulated radiation therapy later. An increasing number of patients have undergone chemotherapy since 2003. The 5-year OS across the 4 calendar periods increased at each TNM stage with progression-free survival (PFS) and locoregional relapse-free survival (LRFS) showing a similar trend, whereas distant metastasis-free survival showed small differences. Multivariate analyses showed that the application of intensity modulated radiation therapy and magnetic resonance imaging were independent protective factors in OS, PFS, LRFS, and distant metastasis-free survival. Chemotherapy benefited patients in OS, PFS, and LRFS. The main pattern of treatment failure shifted from recurrence to distant metastasis. CONCLUSIONS: The development of radiation therapy, image technology, and chemotherapy increased survival rates among patients with NPC because of excellent locoregional control. Distant failure has become the greatest challenge for NPC treatment.

The diagnostic and prognostic values of plasma Epstein-Barr virus DNA for residual cervical lymphadenopathy in nasopharyngeal carcinoma patients: a retrospective study.

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.

Patterns of Failure and Survival Trends in 3,808 Patients with Stage II Nasopharyngeal Carcinoma Diagnosed from 1990 to 2012: A Large-Scale Retrospective Cohort Study.

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.