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Background: Post-radiation nasopharyngeal necrosis (PRNN) is a severe adverse event following re-radiotherapy for patients with locally recurrent nasopharyngeal carcinoma (LRNPC) and associated with decreased survival. Biological heterogeneity in recurrent tumors contributes to the different risks of PRNN. Radiomics can be used to mine high-throughput non-invasive image features to predict clinical outcomes and capture underlying biological functions. We aimed to develop a radiogenomic signature for the pre-treatment prediction of PRNN to guide re-radiotherapy in patients with LRNPC. Methods: This multicenter study included 761 re-irradiated patients with LRNPC at four centers in NPC endemic area and divided them into training, internal validation, and external validation cohorts. We built a machine learning (random forest) radiomic signature based on the pre-treatment multiparametric magnetic resonance images for predicting PRNN following re-radiotherapy. We comprehensively assessed the performance of the radiomic signature. Transcriptomic sequencing and gene set enrichment analyses were conducted to identify the associated biological processes. Results: The radiomic signature showed discrimination of 1-year PRNN in the training, internal validation, and external validation cohorts (area under the curve (AUC) 0.713–0.756). Stratified by a cutoff score of 0.735, patients with high-risk signature had higher incidences of PRNN than patients with low-risk signature (1-year PRNN rates 42.2–62.5% vs. 16.3–18.8%, P < 0.001). The signature significantly outperformed the clinical model (P < 0.05) and was generalizable across different centers, imaging parameters, and patient subgroups. The radiomic signature had prognostic value concerning its correlation with PRNN-related deaths (hazard ratio (HR) 3.07–6.75, P < 0.001) and all causes of deaths (HR 1.53–2.30, P < 0.01). Radiogenomics analyses revealed associations between the radiomic signature and signaling pathways involved in tissue fibrosis and vascularity. Conclusions: We present a radiomic signature for the individualized risk assessment of PRNN following re-radiotherapy, which may serve as a noninvasive radio-biomarker of radiation injury-associated processes and a useful clinical tool to personalize treatment recommendations for patients with LANPC. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to compare the metastatic patterns of synchronous bone metastasis (SBM) and metachronous bone metastasis (MBM) in nasopharyngeal carcinoma (NPC). Methods: This study included bone metastases in NPC patients from 2005 to 2016 in a Chinese hospital. Cohort 1 was collected from 2005 to 2010 for discovery, and Cohort 2 from 2011 to 2016 for validation. The chi‐squared test, Wilcoxon rank sum test, and Kaplan–Meier technique were used to compare site, time, and survival between cohorts 1 and 2. Prognostic factors were analyzed using univariate or multivariate Cox regression. Results: Cohort 1 had 112 individuals with SBM and 394 with MBM, and cohort 2 had 328 with SBM and 307 with MBM. The thoracic vertebra was the most frequently affected site of metastasis. Patients with SBM more often had metastasis to the cervical vertebrae compared with patients with MBM (34.5% vs. 22.3%, p < 0.05). Patients with SBM had better overall survival (42.2 months, 95% CI: 33.9–50.7) than patients with MBM (24.9 months, 95% CI: 22.2–28.7). Age at bone metastasis detection, metastasis to other organs, and more bone metastasis locations were associated with worse prognosis. The majority of MBMs occurred at 7 to 18 months after NPC diagnosis. Conclusion: Radiotherapy does not modify the metastatic patterns of NPC bone metastases. Patients with SBM tend to have metastasis to the cervical vertebra, which is close to the nasopharynx. Paying more attention to bone metastases during follow‐up in the first 2 years after an NPC diagnosis. [ABSTRACT FROM AUTHOR]

Immunotherapy combined with antiangiogenic targeted therapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for refractory recurrent/metastatic nasopharyngeal carcinoma (RM-NPC). We conducted a phase 2 trial to evaluate the safety and activity of camrelizumab plus apatinib in platinum-resistant (cohort 1, NCT04547088) and PD-1 inhibitor resistant NPC (cohort 2, NCT04548271). Here we report on the primary outcome of objective response rate (ORR) and secondary endpoints of safety, duration of response, disease control rate, progression-free survival, and overall survival. The primary endpoint of ORR was met for cohort 1 (65%, 95% CI, 49.6–80.4, n = 40) and cohort 2 (34.3%; 95% CI, 17.0–51.8, n = 32). Grade ≥ 3 treatment-related adverse events (TRAE) were reported in 47 (65.3%) of 72 patients. Results of our predefined exploratory investigation of predictive biomarkers show: B cell markers are the most differentially expressed genes in the tumors of responders versus non-responders in cohort 1 and that tertiary lymphoid structure is associated with higher ORR; Angiogenesis gene expression signatures are strongly associated with ORR in cohort 2. Camrelizumab plus apatinib combination effectiveness is associated with high expression of PD-L1, VEGF Receptor 2 and B-cell-related genes signatures. Camrelizumab plus apatinib shows promising efficacy with a measurable safety profile in RM-NPC patients. Combination of immune checkpoint inhibitors with anti-angiogenic targeted therapy has shown efficacy in some solid tumours. Here the authors report the results of a phase 2 trial of camrelizumab (anti-PD1) plus apatinib as a second-line or later-line treatment regimen in platinum-resistant (cohort 1) or PD-1 inhibitor-resistant (cohort 2) Recurrent/Metastatic Nasopharyngeal Carcinoma patients. [ABSTRACT FROM AUTHOR]

Objectives: This study focused on developing and validating a nomogram to predict the overall survival (OS) of patients with nasopharyngeal carcinoma (NPC) without distant metastasis based on their clinical characteristics, serum biomarkers, and presence of nasopharyngeal (NP) necrosis. Methods: This study included 9298 patients with NPC. Patients from January 2009 to December 2014 were randomly categorized into the training cohort and validation cohort A. Validation cohort B, whose data were collected from January 2015 to December 2017, was also included. OS was the primary endpoint of this study. Cox regression analysis was used to detect independent risk variables. Decision curve analysis, calibration curve, time-dependent receiver operating characteristic (ROC) curve, and concordance index (C-index) were used to evaluate the performance of the nomogram model. Results: A total of 267 patients developed NP necrosis after the first routine radiotherapy. After radiotherapy, patients with NP necrosis had significantly lower OS than other patients in all three cohorts (p < 0.001). Eleven factors, including NP necrosis, were involved in the nomogram, which had favorable discrimination and calibration with a C-index of 0.768 in the training cohort, 0.749 in validation cohort A, and 0.739 in validation cohort B. The nomogram exhibited a significantly larger area under the ROC curve for predicting OS than the TNM stage and Epstein-Barr virus (EBV) DNA (p < 0.001). Conclusion: Compared with the TNM system and EBV DNA, we established a nomogram model with an accurate prognostic prediction for patients with NPC, which might help with patient management in NPC. Key Points: • This study included 9298 patients with NPC, and 11 factors were involved in the final model. • The nomogram had a significantly higher C-index and area under the ROC curve than the TNM stage and EBV DNA. • We established the first nomogram model for NPC involving the occurrence of NP necrosis, which was valuable for providing individual counseling and clinical assessments. [ABSTRACT FROM AUTHOR]

Purpose: Radiotherapy is the most important primary treatment for patients with nasopharyngeal carcinoma. Generally, the treatment duration of radiotherapy takes six or six and half weeks with 30 to 33 fractions. The current study was conducted to evaluate the association between prognosis and the duration of radiotherapy in nasopharyngeal carcinoma patients. Methods: Patients with primary nasopharyngeal carcinoma who were treated with intensity-modulated radiotherapy and concurrent cisplatin-based chemotherapy, with or without induction chemotherapy between January, 2008 and December, 2013 at a single institution were retrospectively reviewed. Results: In total, 1292 patients were included. At a median follow-up of 71.0 months (range 2.0–126.0 months), locoregional recurrence, distant failure and death were observed in 8.8%, 12.2% and 15.6% of all patients, respectively. Estimated 5-year locoregional relapse–free survival, distant metastasis–free survival, progression-free survival and overall survival in patients with radiation ≤ 7 weeks versus patients with radiation >7 weeks were: 93.2% versus 87.0% (P < 0.001), 89.4% versus 84.4% (P = 0.016), 79.8% versus 70.6% (P < 0.001) and 87.2% versus 78.4% (P < 0.001), respectively. Conclusions: Prolonged duration of radiotherapy with a significantly higher risk of distant metastasis and death in nasopharyngeal carcinoma patients. Understanding this point, healthcare providers should make efforts to avoid prolonged duration of radiotherapy to minimize the risk of treatment failure. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to establish an effective nomogram to predict primary distant metastasis (DM) in patients with nasopharyngeal carcinoma (NPC) to guide the application of PET/CT. Methods: In total, 3591 patients with pathologically confirmed NPC were consecutively enrolled. The nomogram was constructed based on 1922 patients treated between 2007 and 2014. Multivariate logistical regression was applied to identify the independent risk factors of DM. The predictive value of the nomogram was evaluated using the concordance index (C-index), calibration curve, probability density functions (PDFs), and clinical utility curve (CUC). The results were validated in 1669 patients enrolled from 2015 to 2016. Net reclassification improvement (NRI) was applied to compare performances of the nomogram with other clinical factors. The best cut-off value of the nomogram chosen for clinical application was analyzed. Results: A total of 355 patients showed primary DM among 3591 patients, yielding an incidence rate of 9.9%. Sex, N stage, EBV DNA level, lactate dehydrogenase level, and hemoglobin level were independent predictive factors for primary DM. C-indices in the training and validation cohort were 0.796 (95% CI, 0.76–0.83) and 0.779 (95% CI, 0.74–0.81), respectively. The NRI indices demonstrated that this model had better predictive performance than plasma EBV DNA level and N stage. We advocate for a threshold probability of 3.5% for guiding the application of PET/CT depending on the clinical utility analyses. Conclusion: This nomogram is a useful tool to predict primary DM of NPC and guide the clinical application of PET/CT individually at the initial staging. [ABSTRACT FROM AUTHOR]

Objectives: The value of using PET/CT for staging of stage I–II NPC remains unclear. Hence, we aimed to investigate the survival benefit of PET/CT for staging of early-stage NPC before radical therapy. Methods: A total of 1003 patients with pathologically confirmed NPC of stages I–II were consecutively enrolled. Among them, 218 patients underwent both PET/CT and conventional workup ([CWU], head-and-neck MRI, chest radiograph, liver ultrasound, bone scintigraphy) before treatment. The remaining 785 patients only underwent CWU. The standard of truth (SOT) for lymph node metastasis was defined by the change of size according to follow-up MRI. The diagnostic efficacies were compared in 218 patients who underwent both PET/CT and CWU. After covariate adjustment using propensity scoring, a cohort of 872 patients (218 with and 654 without pre-treatment PET/CT) was included. The primary outcome was overall survival based on intention to treat. Results: Retropharyngeal lymph nodes were metastatic based on follow-up MRI in 79 cases. PET/CT was significantly less sensitive than MRI in detecting retropharyngeal lymph node lesions (72.2% [62.3–82.1] vs. 91.1% [84.8–97.4], p = 0.004). Neck lymph nodes were metastatic in 89 cases and PET/CT was more sensitive than MRI (96.6% [92.8–100.0] vs. 76.4% [67.6–85.2], p < 0.001). In the survival analyses, there was no association between pre-treatment PET/CT use and improved overall survival, progression-free survival, local relapse-free survival, regional relapse-free survival, and distant metastasis-free survival. Conclusions: This study showed PET/CT is of little value for staging of stage I–II NPC patients at initial imaging. Key Points: • PET/CT was more sensitive than MRI in detecting neck lymph node lesions whereas it was significantly less sensitive than MRI in detecting retropharyngeal lymph node lesions. • No association existed between pre-treatment PET/CT use and improved survival in stage I–II NPC patients. [ABSTRACT FROM AUTHOR]

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 [18F]‐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. [ABSTRACT FROM AUTHOR]

Background Endoscopic nasopharyngectomy is a new salvage treatment for locally recurrent nasopharyngeal carcinoma (NPC). However, how to resurface the nasopharyngeal defects in endoscopic endonasal approaches to avoid persistent postoperative headache, to the best of our knowledge, has not been reported. Methods From September 2009 to August 2010, we used a modified posterior pedicle nasal septum and floor mucoperiosteum flap (nasal septum and floor flap, NSFF) after endoscopic nasopharyngectomy in 12 patients with locally recurrent NPC. Most of the nasal septum and floor mucoperiosteum, except for the posterior pedicle, was harvested to cover the nasopharyngeal defects. Results All NSFFs successfully covered the entire nasopharyngeal defects and relined the nasopharynx with good functional recovery. The nasopharyngeal wounds recovered in 28 days (range, 14 to 56 days), and the donor-site wounds recovered in 46.5 days (range, 24-84 days). No reconstruction-related complications or disease recurrences were observed. Conclusion The NSFF is a safe and promising reconstructive option to resurface the nasopharyngeal defect after endoscopic nasopharyngectomy in patients with locally recurrent NPC. © 2011 Wiley Periodicals, Inc. Head Neck, 2011 [ABSTRACT FROM AUTHOR]

Background Concurrent chemoradiotherapy (CCRT) has been shown to improve outcomes for stage III–IV nasopharyngeal carcinoma (NPC) patients compared with radiotherapy (RT) alone, but the effectiveness of the combined therapy for stage II NPC patients is unknown. Methods Patients with Chinese 1992 stage II NPC were randomly assigned to receive either RT alone (n = 114) or CCRT (n = 116). The CCRT patients were given concurrent cisplatin (30 mg/m2 on day 1) weekly during RT. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), distant metastasis-free survival, and locoregional relapse-free survival. All patients were analyzed by the intent-to-treat principle. The Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) and in multivariable analyses to test the independent statistical significance of treatment intervention. Toxic effects and the response to treatment were analyzed using the χ2 test. All statistical tests were two-sided. Results With a median follow-up of 60 months, adding chemotherapy statistically significantly improved the 5-year OS rate (94.5% vs 85.8%; HR of death = 0.30, 95% CI = 0.12 to 0.76; P = .007), PFS (87.9% vs 77.8%; HR of progression = 0.45, 95% CI = 0.23 to 0.88; P = .017), and distant metastasis-free survival (94.8% vs 83.9%; HR of distant relapse = 0.27, 95% CI = 0.10 to 0.74; P = .007); however, there was no statistically significant difference in the 5-year locoregional relapse-free survival rate (93.0% vs 91.1%; HR of locoregional relapse = 0.61, 95% CI = 0.25 to 1.51; P = .29). Multivariable analysis showed that the number of chemotherapy cycles was the only independent factor that was associated with OS, PFS, and distant control in stage II NPC. The CCRT arm experienced statistically significantly more acute toxic effects (P = .001), although the rate of late toxic effects did not increase statistically significantly. Conclusion Concurrent chemotherapy and radiotherapy is associated with a considerable survival benefit for patients with stage II NPC. [ABSTRACT FROM PUBLISHER]

• From 1990 to 2016, the smoking rate of patients showed a downward trend, while the overall survival improved over time. • The 5-year OS rates in the entire cohort were 76.4%, 68.9%, and 79.8% in the former, current, and never smokers. • In the multivariate analysis of the IMRT cohort, the risk of death and metastasis was higher in the current smokers. • Heavy smoking increases the risk of death and metastasis. We aimed to compare the survival outcomes of patients with nasopharyngeal carcinoma (NPC) who had different smoking behaviors and were treated with two- or three-dimensional radiotherapy (2D/3DRT) or intensity-modulated radiotherapy (IMRT) with a long-term follow up. From 1990 to 2016, 23,325 patients with NPC were included. The primary endpoint of this study was overall survival (OS). The log-rank test and Cox proportional hazards regression model were used to assess the patients' survival outcomes. The 5-year OS rates in the entire cohort were 76.4%, 68.9%, and 79.8% in the former, current, and never smokers, respectively. In the IMRT cohort, the OS rates showed the same trend. Compared with the never smokers, the 5-year distant metastasis-free survival (DMFS) was lower in the former (P = 0.004) and current smokers (P < 0.001). In the multivariate analysis of the IMRT cohort, the risk of death (P = 0.003) and recurrence (P = 0.027) was higher in the current smokers, while the risk of metastasis was higher in the former and current smokers (P = 0.031 and P = 0.019, respectively) than the never smokers. A total of 53.9% of the effect of smoking status on OS was through sex, age, and Epstein-Barr virus DNA, which were significant mediators. In the IMRT era, being a former smoker or current smoker was an independent risk factor for DMFS. The difference in OS and locoregional relapse-free survival was significant only between the current smokers and never smokers. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy of induction chemotherapy in the treatment of stage II nasopharyngeal carcinoma (NPC) in era of intensity modulated radiotherapy (IMRT).Methods and Materials: A total of 173 patients with American Joint Committee on Cancer (AJCC) 7th stage II NPC from two institutions were included. All patients were divided into two groups: induction chemotherapy + concurrent chemoradiotherapy group (ICRT) group and concurrent chemoradiotherapy group (CCRT). Induction chemotherapy was consisted of one to three cycles of cisplatin plus fluorouracil (PF) or paclitaxel plus cisplatin (TP). Concurrent chemotherapy included one to three cycles of cisplatin. We retrospectively assessed overall survival (OS), progression-free survival (PFS), locoregional failure free survival (LRFFS) and distant metastasis free survival (DMFS) in patients of both groups. T-test, Chi-square test, Kaplan-Meier methodology and Cox proportional hazards model were used to analyze.Results: With a median follow up of 64.7 months, no significant difference was found in grade 3-4 hematologic toxicity, liver dysfunction and renal impairment between ICRT and CCRT group. Univariable analyses shown adding induction chemotherapy to CCRT significantly decreased 5-year OS (87.9% vs 95.5%, P = 0.033), 5-year PFS (74.0% vs 86.1%, P = 0.035), 5-year LRFFS (80.0% vs 91.2%, P = 0.016), but there was no statistically significant difference in 5-year DMFS (87.1% vs 94.7%, P = 0.095). In multivariable analyses, we found the consistent results that induction chemotherapy was a negative factor associated with OS (HR of death = 3.768, 95% CI = 1.117-12.709; P = 0.032), PFS (HR of progression = 2.156, 95% CI = 1.060-4.386; P = 0.034), LRFFS (HR of locoregional relapse = 2.435, 95% CI = 1.009-5.874; P = 0.048) and also DMFS (HR of metastasis = 2.873, 95% CI = 1.005-8.211; P = 0.049), in stage II NPC patients.Conclusion: In present study, we found that induction chemotherapy caused deleterious effect on stage II NPC patients. However, this is a retrospective study and the adverse effects of induction chemotherapy has not been previously reported. It warrants further investigation. [ABSTRACT FROM AUTHOR]

Patients with N2–3 nasopharyngeal carcinoma have a high risk of treatment being unsuccessful despite the current practice of using a concurrent adjuvant cisplatin–fluorouracil regimen. We aimed to compare the efficacy and safety of concurrent adjuvant cisplatin–gemcitabine with cisplatin–fluorouracil in N2–3 nasopharyngeal carcinoma. We conducted an open-label, randomised, controlled, phase 3 trial at four cancer centres in China. Eligible patients were aged 18–65 years with untreated, non-keratinising, stage T1–4 N2–3 M0 nasopharyngeal carcinoma, an Eastern Cooperative Oncology Group performance status score of 0–1, and adequate bone marrow, liver, and renal function. Eligible patients were randomly assigned (1:1) to receive concurrent cisplatin (100 mg/m2 intravenously) on days 1, 22, and 43 of intensity-modulated radiotherapy followed by either gemcitabine (1 g/m2 intravenously on days 1 and 8) and cisplatin (80 mg/m2 intravenously for 4 h on day 1) once every 3 weeks or fluorouracil (4 g/m2 in continuous intravenous infusion for 96 h) and cisplatin (80 mg/m2 intravenously for 4 h on day 1) once every 4 weeks, for three cycles. Randomisation was done using a computer-generated random number code with a block size of six, stratified by treatment centre and nodal category. The primary endpoint was 3-year progression-free survival in the intention-to-treat population (ie, all patients randomly assigned to treatment). Safety was assessed in all participants who received at least one dose of chemoradiotherapy. This study was registered at ClinicalTrials.gov , NCT03321539 , and patients are currently under follow-up. From Oct 30, 2017, to July 9, 2020, 240 patients (median age 44 years [IQR 36–52]; 175 [73%] male and 65 [27%] female) were randomly assigned to the cisplatin–fluorouracil group (n=120) or cisplatin–gemcitabine group (n=120). As of data cutoff (Dec 25, 2022), median follow-up was 40 months (IQR 32–48). 3-year progression-free survival was 83·9% (95% CI 75·9–89·4; 19 disease progressions and 11 deaths) in the cisplatin–gemcitabine group and 71·5% (62·5–78·7; 34 disease progressions and seven deaths) in the cisplatin–fluorouracil group (stratified hazard ratio 0·54 [95% CI 0·32–0·93]; log rank p=0·023). The most common grade 3 or worse adverse events that occurred during treatment were leukopenia (61 [52%] of 117 in the cisplatin–gemcitabine group vs 34 [29%] of 116 in the cisplatin–fluorouracil group; p=0·00039), neutropenia (37 [32%] vs 19 [16%]; p=0·010), and mucositis (27 [23%] vs 32 [28%]; p=0·43). The most common grade 3 or worse late adverse event (occurring from 3 months after completion of radiotherapy) was auditory or hearing loss (six [5%] vs ten [9%]). One (1%) patient in the cisplatin–gemcitabine group died due to treatment-related complications (septic shock caused by neutropenic infection). No patients in the cisplatin–fluorouracil group had treatment-related deaths. Our findings suggest that concurrent adjuvant cisplatin–gemcitabine could be used as an adjuvant therapy in the treatment of patients with N2–3 nasopharyngeal carcinoma, although long-term follow-up is required to confirm the optimal therapeutic ratio. National Key Research and Development Program of China, National Natural Science Foundation of China, Guangdong Major Project of Basic and Applied Basic Research, Sci-Tech Project Foundation of Guangzhou City, Sun Yat-sen University Clinical Research 5010 Program, Innovative Research Team of High-level Local Universities in Shanghai, Natural Science Foundation of Guangdong Province for Distinguished Young Scholar, Natural Science Foundation of Guangdong Province, Postdoctoral Innovative Talent Support Program, Pearl River S&T Nova Program of Guangzhou, Planned Science and Technology Project of Guangdong Province, Key Youth Teacher Cultivating Program of Sun Yat-sen University, the Rural Science and Technology Commissioner Program of Guangdong Province, and Fundamental Research Funds for the Central Universities. [ABSTRACT FROM AUTHOR]

Background and Purpose:Treatment outcomes vary greatly in patients with nasopharyngeal carcinoma (NPC). The purpose of this study is to evaluate the influence of radiation and chemotherapy drug action pathway gene polymorphisms on the survival of patients with locoregionally advanced NPC treated with cisplatin- and fluorouracil-based chemoradiotherapy. Material and Methods:Four hundred twenty-one consecutive patients with locoregionally advanced NPC were prospectively recruited. We utilized a pathway approach and examined 18 polymorphisms in 13 major genes. Polymorphisms were detected using the LDR-PCR technique. Multifactor dimensionality reduction (MDR) analysis was performed to detect potential gene-gene interaction. Results:After adjustment for clinicopathological characteristics, overall survival was significantly decreased in patients with the MPO rs2243828 CT/CC genotype (HR=2.453, 95% CI, 1.687-3.566, P<0.001). The ERCC1 rs3212986 CC (HR=1.711, 95% CI, 1.135-2.579, P=0.010), MDM2 rs2279744 GT/GG (HR=1.743, 95% CI, 1.086-2.798, P=0.021), MPO rs2243828 CT/CC (HR=3.184, 95% CI, 2.261-4.483, P<0.001) and ABCB1 rs2032582 AT/AA (HR=1.997, 95% CI, 1.086-3.670, P=0.026) genotypes were associated with poor progression-free survival. Prognostic score models based on independent prognostic factors successfully classified patients into low-, intermediate-, and high-risk groups. Furthermore, MDR analysis showed no significant interaction between polymorphisms. Conclusions:Four single nucleotide polymorphisms were associated with survival in patients with locoregionally advanced NPC treated with cisplatin- and fluorouracil-based chemoradiotherapy. Combining clinical prognostic factors with genetic information was valuable in identifying patients with different risk. [ABSTRACT FROM AUTHOR]

• A total of 531 patients with local recurrence nasopharyngeal carcinoma (lrNPC) were retrospectively reviewed. • We established and validated an integrated prognostic model for lrNPC patients. • Three risk groups were derived from an RPA model that combined rT stage and EBV DNA. • Re-radiotherapy could benefit patients in the low and intermediate-risk subgroups. • No association between re-RT and survival benefit was found in the high-risk. subgroup. In this study, we aimed to establish and validate an integrated prognostic model for locally recurrent nasopharyngeal carcinoma (lrNPC) patients, and evaluate the benefit of re-radiotherapy (re-RT) in patients with different risk levels. In total, 531 patients with lrNPC were retrospectively reviewed in this study, including 271 patients from 2006 to 2012 as the training cohort and 260 patients from 2013 to 2016 as the validation cohort. Overall survival (OS) was the primary endpoint. Multivariate analysis was performed to select the significant prognostic factors (P < 0.05). A prognostic model for OS was derived by recursive partitioning analysis (RPA) combining independent predictors using the algorithm of optimized binary partition. Three independent prognostic factors (age, relapsed T [rT] stage, and Epstein-Barr virus [EBV] DNA) were identified from multivariate analysis. Five prognostic groups were derived from an RPA model that combined rT stage and EBV DNA. After further pair-wise comparisons of survival outcome in each group, three risk groups were generated. We investigated the role of re-RT in different risk groups, and found that re-RT could benefit patients in the low (P < 0.001) and intermediate-risk subgroups (P = 0.017), while no association between re-RT and survival benefit was found in the high-risk subgroup (P = 0.328). The results of risk stratification and re-RT efficacy were verified in the validation cohort. Age, rT stage and EBV DNA were identified as independent predictors for lrNPC. We established an integrated RPA-based prognostic model for OS incorporating rT stage and EBV DNA, which could guide individual treatment for lrNPC. [ABSTRACT FROM AUTHOR]

• Pretreatment plasma EBV DNA, N stage, LDH, ALP, BMI, and sex were independent predictive factors of EM. • Our nomogram had good accuracy in predicting EM incidence, and a 5.0% threshold was appropriate for clinical decision-making, which could distinguish about 85% and 48% of non-EM and EM patients, respectively. • C-index of the nomogram was significantly superior to any one of independent factors. This study aimed to establish an effective prognostic nomogram to predict the risk of early metastasis (EM) in nasopharyngeal carcinoma (NPC) patients, as a guide for intensive treatment. A total of 9021 patients with biopsy-confirmed NPC at our institute were enrolled in this study between December 2006 to December 2016. We randomized these patients using a proportion of 2/3 and 1/3 and selected 6044 and 2977 patients as the training and validation cohorts, respectively. All patients received radiotherapy with or without chemotherapy. Univariate and multivariate logistical regressions were used to identify independent risk factors. The nomogram's predictive value was evaluated by concordance indexes (C-indexes), calibration curves, probability density functions (PDFs), and clinical utility curves (CUCs). ROC analysis using Delong test was used to compare efficiency between the nomogram and other risk factors. In total, 174 (2.9%) and 81 (2.7%) patients in training and validation cohorts, respectively, had EM. Pretreatment plasma EBV DNA, N stage, LDH, ALP, BMI, and sex were independent predictive factors of EM. The C-indexes of nomogram were 0.756 (95% CI = 0.719–0.793) and 0.766 (95% CI = 0.720–0.813), in the training and validation cohorts, respectively. The C-index of the nomogram was significantly superior to any one of independent factors. According to the PDFs and CUCs and considering the balance of the true positive EM patients and true positive non-EM patients, we chose 5.0% as a threshold probability for clinical decision-making, which could distinguish about 85% and 48% of non-EM and EM patients, respectively. Our nomogram had good accuracy in predicting EM incidence, and a 5.0% threshold was appropriate for clinical decision-making. [ABSTRACT FROM AUTHOR]

• The combination of nab-paclitaxel, cisplatin and capecitabin (TPC) as induction chemotherapy followed by cisplatin concurrent chemoradiotherpay showed good tolarance and anti-tumor effecacy in patients with advanced nasopharyngeal carcinoma. • The MTD of nab-paclitaxel is 225 mg/m2, that combined with cisplatin and capecitabine as induction chemotherapy, followed by concurrent chemoradiotherapy. • The RP2D of nab-paclitaxel is 200 mg/m2. Nab-paclitaxel is a promising albumin-bound paclitaxel with a therapeutic index superior to that of docetaxel, but the optimal dose of nab-paclitaxel combined with cisplatin and capecitabine as induction chemotherapy followed by concurrent chemoradiotherapy for patients with locally advanced nasopharyngeal carcinoma remains unknown. This was an open-label, single-arm study investigating the safety and efficacy of nab-paclitaxel + cisplatin + capecitabin as IC for three cycles, followed by cisplatin CCRT, conducted by using the standard "3 + 3" design in LA-NPC. If more than one-third of the patients in a cohort experienced dose-limiting toxicity (DLT), the dose used in the previous cohort was designated the maximum tolerated dose (MTD). The recommended phase 2 dose (RP2D) was defined as one level below the MTD. From 29 May 2021 to 17 March 2022, 19 patients with LA-NPC were enrolled, one patient withdrew informed consent. Two DLTs occurred in cohort 4 (grade 4 febrile neutropenia and grade 3 peripheral neuropathy), and an MTD was established as 225 mg/m2. The most frequent grade 3 or 4 adverse events were neutropenia (16.7 %), hypertriglyceridemia (16.7 %), leukopenia (5.6 %) and peripheral neuropathy (5.6 %) during IC. The RP2D is nab-paclitaxel 200 mg/m2 on day 1, combined with cisplatin 75 mg/mg2 on day 1 and capecitabin1000 mg/m2 on days 1–14, twice a day, every 3 weeks, for three cycles as an IC regimen prior to CCRT. Trial registration: ClinicalTrials.gov Identifier: NCT04850235. [ABSTRACT FROM AUTHOR]

Radiotherapy-related toxicities of nasopharyngeal carcinoma (NPC) caused by a standard dose of 70 Gy remain a critical issue. Therefore, we assessed whether a radiotherapy dose of 60 Gy was non-inferior to the standard dose in patients with low-risk stage III NPC with a favourable response to induction chemotherapy (IC). We did a single-arm, single-centre, phase II clinical trial in China. Patients with low-risk (Epstein-Barr virus [EBV] DNA level <4000 copies/ml) stage III NPC were treated with two cycles IC. Patients with complete/partial response and undetectable EBV DNA level were assigned 60 Gy intensity-modulated radiotherapy concurrently with three cycles of cisplatin. The primary end-point was 2-year progression-free survival (PFS). This trial is registered with ClinicalTrials.gov , number NCT 03668730. One patient quit because of withdrawal of informed consent after IC. In total, 215 patients completed two cycles of IC, after which 116 (54.0%) and 99 (46.0%) patients were assigned 60 and 70 Gy radiotherapy, respectively. For 215 patients, the 2-year PFS was 90.7% (95% CI, 86.8%–94.6%) with a median follow-up of 43.9 months (interquartile range [IQR], 39.8–46.2). For patients treated with 60 Gy radiotherapy, the 2-year PFS rate was 94.8% (95%CI 90.7%–98.9%) with a median follow-up of 43.9 months (IQR 40.2–46.2). The most common late toxicity was grade 1–2 dry mouth (incidence rate: 54.3%). No grade 3+ long-term adverse event was observed, and most quality-of-life items, domains, and symptom scores returned to baseline by 6 months. Reduced-dose radiation (60 Gy) is associated with favourable survival outcomes and limited treatment-related toxicities in patients with low-risk stage III NPC sensitive to IC. • A total of 216 patients with low-risk stage III NPC were enroled in this study. • One hundred and sixteen patients had CR/PR and undetectable EBV DNA after IC. • Sixty Gy RT is non-inferior to the 70 Gy RT in low-risk stage III NPC. • No grade 3+ long-term adverse event was found in 60 Gy cohort. • The 2-year PFS rate of the whole cohort was 90.7%. [ABSTRACT FROM AUTHOR]

Background: To evaluate the cost-effectiveness of stage-based post-radiotherapy (PRT) nasopharyngeal carcinoma (NPC) surveillance strategies.Methods: Four post-radiotherapy surveillance strategies were established by a Markov model based on data from 1664 patients: 1) clinical follow-up (CFP) with biannual Epstein-Barr virus (EBV) DNA (EBV DNA strategy); 2) CFP with biannual EBV DNA, annual head and neck magnetic resonance imaging (HNMRI), chest X-ray, abdominal ultrasonography, bone scan (only for the first two years) for five years (MCWU strategy); 3) CFP with biannual EBV DNA, annual HNMRI, chest, abdomen, pelvic computerized tomography (CT) and bone scan for the first two years, followed by annual MCWU strategy (without bone scans) for the last three years (CT strategy); 4) CFP with biannual EBV DNA, annual whole-body positron emission/computerized tomography (PET/CT) for the first two years and biannual EBV DNA for the last three years (PET/CT strategy).Results: Compared with the EBV DNA strategy, the MCWU, CT, and PET/CT strategies gained 0.017, 0.047, and 0.082 quality-adjusted life years (QALY) for stage I-II patients. For stage III and IVa patients, the PET/CT strategy had a favorable incremental effectiveness (ICERs) of 0.277 and 0.385 QALY, respectively. The ICERs for the MCWU, CT, and PET/CT strategies were $74,037, $34,882, and $34,696 for stage III and $62,364, $27,981, and $28,340 for stage IVa, respectively.Conclusion: EBV DNA strategy was cost-effective for the long-term surveillance of stage I-II NPC patients with CR. PET/CT strategy was recommeded for patients having IVa NPC. As for stage III NPC, PET/CT strategy was still acceptable with the development of economy in China. [ABSTRACT FROM AUTHOR]

Summary: The aim of this randomized study was to compare the efficacy of induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) versus induction chemotherapy plus radiotherapy (IC+RT) for patients with locoregionally advanced nasopharyngeal carcinoma. From August 2002 to April 2005, 408 patients were randomly divided into two groups: an IC+CCRT group and an IC+RT group. Patients in both groups received the same induction chemotherapy: two cycles of floxuridine (FuDR)+carboplatin (FuDR, 750mg/m2, d1-5; carboplatin, area under the curve [AUC]=6). The patients received radiotherapy 1week after they finished the induction chemotherapy. The patients in the IC+CCRT group also received carboplatin (AUC=6) on days 7, 28, and 49 of radiotherapy. Eight patients did not meet the inclusion criteria, and the remaining 400 cases were analyzed. Grade III or IV toxicity was found in 28.4% of the patients in the IC+CCRT group and 13.1% of those in the IC+RT group (P <.001). Five-year overall survival rates were 70.3% and 71.7% (P =0.734) in the IC+CCRT and IC+RT groups, respectively. No significant differences in failure-free survival, locoregional control, and distant control were found between the two groups. Compared with the IC+RT program, the IC+CCRT program used in the present study did not improve the overall survival and failure-free survival in patients with locoregionally advanced nasopharyngeal carcinoma. Using carboplatin in the concurrent chemoradiotherapy was not suitable for nasopharyngeal carcinoma. [Copyright &y& Elsevier]