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Purpose: The aims of the study were to monitor circulating lymphocyte subset counts before and after therapy for nasopharyngeal carcinoma (NPC), and investigate their relationships with patient outcomes. Patients and Methods: Subjects comprised patients with TNM stage I–IVA NPC who underwent radiotherapy. Peripheral venous blood samples were collected before and after treatment. Lymphocyte subset counts were analyzed by flow cytometry. Differences between post-treatment and baseline counts were calculated to determine Δ values. Patients were divided into high and low groups, based on median lymphocyte subset counts; propensity score matching was applied to balance groups. Progression-free survival (PFS) and overall survival (OS) were plotted using Kaplan-Meier curves and compared using a Log rank test. Relationships between lymphocyte subset counts and patient survival were subjected to Cox regression analysis. Results: Patients with NPC (n=746) were enrolled from 2012– 2022. Higher CD8+ and total T cell baseline counts were associated with better 5-year PFS (73.7% vs 63.1%, P=0.002 and 73.8% vs 64.1%, P=0.005, respectively). Similarly, higher Δ values of CD4+ and total T cells were associated with higher 5-year PFS (76.2% vs 63.5%, P=0.001; 74.3% vs 65.4%, P=0.010) and OS (89.8% vs 81.6%, P=0.005; 88.6% vs 82.5%, P=0.009). Multivariate Cox regression revealed that CD8+ (hazard ratio (HR) 0.651, P=0.002) and total T (HR 0.600, P< 0.001) cells were significantly associated with PFS. CD4+ (HR 0.708, P=0.038) and total T (HR 0.639, P=0.031) cells were independent prognostic factors for OS. Conclusion: NPC patients with low total or CD8+ T cell counts before treatment had worse prognosis; however, those with more significant decreases in total or CD4+ T cells possibly had better outcomes. T cell counts can be reliable indicators to predict prognosis. [ABSTRACT FROM AUTHOR]

Background: The optimal number of cycles of induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LANPC) is unclear. We aimed to combine the tumor response during IC and tumor stage to individualize the number of IC cycles. Methods: Totally, 498 LANPC patients who received IC plus CCRT between 2014 and 2018 were reviewed. Tumor response during IC was used to stratify patients with different risks. All patients were classified into those who received two cycles of IC and those who were treated with three cycles. Propensity score matching methods were performed to compare the treatment efficiency. Results: After two cycles of IC, 340/498 (68.3%) cases showed complete tumor response (CR)/partial response (PR) and 158 (31.7%) achieved stable disease (SD)/disease progression (PD). Unfavorable responders (SD/PD) exhibited poor survival outcomes. The three‐cycle IC regimen was correlated with better OS and PFS than the two‐cycle regimen for N2‐3 patients in the CR/PR group. However, the use of different IC cycle strategies achieved similar survival outcomes for SD/PD or N0‐1 patients. The incidences of acute toxicities were higher in the IC = 3 group. Conclusions: Tumor response during IC could be a powerful predictor of LANPC and could be used to guide the individualized number of IC cycles. A three‐cycle IC regimen seemed to be preferable for N2‐3 patients who received CR/PR during IC. However, an additional cycle of IC could not benefit N0‐1 or SD/PD patients, and the optimal treatment strategies for these patients require further consideration. [ABSTRACT FROM AUTHOR]

Background: Nomograms specifically used to predict the prognosis of ascending type nasopharyngeal carcinoma (NPC) have not been constructed. Methods: Data of ascending type (T3‐4N0‐1M0) NPC from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015 were extracted. Results: Altogether 862 patients with ascending type NPC were enrolled, including 603 in training cohort and 259 in validation cohort. Age, marital status, pathology, grade, tumor size, T classification, and chemotherapy were the independent prognostic factors for overall survival (OS). Age, marital status, pathology, grade, and chemotherapy were the independent prognostic factors for cancer‐specific survival (CSS). In training cohort, the concordance index of the OS and CSS nomograms were 0.694 (95% confidence interval [CI], 0.677–0.711) and 0.678 (95%CI, 0.659–0.697), respectively, while those in validation cohort were 0.740 (95%CI, 0.715–0.765) and 0.708 (95%CI, 0.679–0.737), separately. Conclusion: The as‐constructed nomograms for ascending type NPC could provide accurate prognostic predictions of OS and CSS. [ABSTRACT FROM AUTHOR]

Background: The optimal cumulative cisplatin dose (CCD) during radiation therapy for locoregionally advanced nasopharyngeal carcinoma (LA‐NPC) patients receiving induction chemotherapy (IC) plus CCRT remains controversial. This study aimed to explore the treatment efficiency of CCD for high‐and low‐risk patients with LA‐NPC. Methods: Data from 472 LA‐NPC patients diagnosed from 2014 to 2018 and treated with IC plus CCRT were reviewed. After propensity score matching, the therapeutic effects of a CCD > 200 and CCD ≤ 200 mg/m2 were evaluated comparatively. Five factors selected by multivariate analysis were incorporated to develop a nomogram. Subgroup analysis was conducted to explore the role of different CCDs in nomogram‐defined high‐ and low‐risk groups. Additionally, acute toxicities were evaluated comparatively between the high‐ and low‐CCD groups. Results: After matching, there was no difference between different CCD groups for all patients in terms of 3‐year overall survival (OS), distant metastasis‐free survival (DMFS), locoregional recurrence‐free survival (LRRFS), or progression‐free survival (PFS). A nomogram was built by integrating pretreatment EBV DNA, clinical stage, and post‐IC EBV DNA, post‐IC primary gross tumor and lymph node volumes obtained a C‐index of 0.674. The high‐risk group determined by the nomogram had poorer 3‐year PFS, OS, DMFS, and LRRFS than the low‐risk group. A total of CCD > 200 mg/m2 increased the survival rates of 3‐year PFS and DMFS (PFS: 72.5% vs. 54.4%, p = 0.012; DMFS: 81.9% vs. 61.5%, p = 0.014) in the high‐risk group but not in the low‐risk group. Moreover, the high CCD increased treatment‐related acute toxicities. Conclusions: A high CCD was associated with better 3‐year PFS and DMFS rates than a low dose for high‐risk patients but could not produce a survival benefit for low‐risk patients. [ABSTRACT FROM AUTHOR]

Purpose: We set out to explore the prognostic value of circulating lymphocyte subsets in patients with nasopharyngeal carcinoma (NPC) before treatment and to investigate changes in lymphocyte subsets resulting from chemoradiotherapy. Patients and Methods: This retrospective study included 677 patients with non-metastatic NPC. The cutoff value of lymphocyte subsets was determined by the receiver operating characteristic curve (ROC), and the prognostic significance of lymphocyte subsets was evaluated by the Log rank test and Cox proportional hazards model. The endpoints were overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS). Differences in lymphocyte subsets before and after chemoradiotherapy were analyzed by Wilcoxon signed rank test. Results: NPC patients with high levels of CD19+ B cells (> 9.55%) had better 5-year OS (90.4% VS 76.8%, P < 0.001), 5-year PFS (85.3% VS 71.6%, P < 0.001) and 5-year DMFS (94% VS 86.8%, P = 0.002) than patients with low levels of CD19+ B cells. Patients with high levels of CD4+ T cells (> 37.05%) had better 5-year PFS (83% VS 74.2%, P = 0.015) and better 5-year DMFS (95.8% VS 86.7%, P < 0.001) than those with low levels of CD4+ T cells. Multivariate analyses indicated that CD19+ B cell was an independent prognostic factor for OS, PFS and DMFS in NPC. And CD4+ T cell was an independent prognostic factor for PFS and DMFS. Within 1 month after chemoradiotherapy, the percentages of CD4+ T cells, CD19+ B cells, and the CD4/CD8 ratio decreased significantly, while the percentages of CD8+ T cells increased significantly. Conclusion: NPC patients with low levels of CD19+ B cells or CD4+ T cells before treatment have a poor prognosis. In addition, chemoradiotherapy may reduce the body's immune function in NPC patients. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to construct of a nomogram to predict progression-free survival (PFS) in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) with risk stratification using computed tomography (CT) radiomics features and clinical factors. Patients and Methods: A total of 311 patients diagnosed with LA-NPC (stage III–IVa) at our hospital between 2010 and 2014 were included. The region of interest (ROI) of the primary nasopharyngeal mass was manually outlined. Independent sample t-test and LASSO-logistic regression were used for selecting the most predictive radiomics features of PFS, and to generate a radiomics signature. A nomogram was built with clinical factors and radiomics features, and the risk stratification model was tested accordingly. Results: In total, 20 radiomics features most associated with prognosis were selected. The radiomics nomogram, which integrated the radiomics signature and significant clinical factors, showed excellent performance in predicting PFS, with C-index of 0.873 (95% CI: 0.803∼ 0.943), which was better than that of the clinical nomogram (C-index, 0.729, 95% CI: 0.620∼ 0.838) as well as of the TNM staging system (C-index, 0.689, 95% CI: 0.592– 0.787) in validation cohort. The calibration curves and the decision curve analysis (DCA) plot obtained suggested satisfying accuracy and clinical utility of the model. The risk stratification tool was able to predict differences in prognosis of patients in different risk categories (p< 0.001). Conclusion: CT-based radiomics features, an in particular, radiomics nomograms, have the potential to become an accurate and reliable tool for assisting with prognosis prediction of LA-NPC. [ABSTRACT FROM AUTHOR]

Objectives: To establish and validate an effective nomogram to predict clinical outcomes for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Materials and Methods: The clinicopathological parameters and follow-up information of 402 locoregionally advanced NPC patients (training cohort, n = 302; validation cohort, n = 100) were retrospectively enrolled. The nomogram was built with the important prognostic variables identified by Cox regression analysis. Overall survival (OS) and progression-free survival (PFS) were the primary and secondary endpoints, respectively. The predictive power and clinical utility of the nomogram were assessed using the Harrell concordance index (C-index), calibration curve, and decision curve analysis. We compared the eighth staging system model with the nomogram to analyze whether the model could improve the accuracy of prognosis Results: Epstein–Barr virus (EBV) DNA load, the gross tumor volume (GTVnx), and cervical lymph node tumor volume (GTVnd) after induction chemotherapy were the independent predictors of OS and PFS. The calibration curves indicated superb agreement between the nomogram-predicted probabilities and observed actual probabilities of survival. The C-index and area under the receiver operator characteristic curve (AUC) of the nomogram integrating these significant factors and N stage, and TNM stage were higher than those of the eighth TNM system alone. In addition, the decision curve analyses demonstrated the clinical value and higher overall net benefit of the nomogram. High-risk groups identified by the nomogram had significantly poorer OS and PFS than the low-risk group (p < 0.05). Conclusions: The multidimensional nomogram incorporating TNM stage, EBV DNA load, and tumor volume after induction chemotherapy led to a more precise prognostic prediction and could be helpful for stratifying risk and guiding treatment decisions in locoregionally advanced NPC patients who have undergone induction chemotherapy and concurrent chemoradiation. [ABSTRACT FROM AUTHOR]

aimed to investigate the predictive value of some inflammatory indexes, such as the ratio of C-reactive protein-to-albumin (CAR), high-sensitivity C-reactive protein-to-albumin (HCAR), C-reactive protein-to-lymphocyte (CLR), and high-sensitivity C-reactive protein-to-lymphocyte (HCLR) in the survival and toxicity of nasopharyngeal carcinoma and provide reference for the development of treatment. Methods: A retrospective analysis was conducted on 162 patients from 2013 to 2018. The value of the indexes before the treatment was calculated. SPSS 25.0 software was used for the analysis, and the cutoff values of the indexes were determined by the receiver operating characteristic curve (ROC). The prognostic value of the indexes was evaluated according to the overall survival rate (OS), progression-free survival rate (PFS), and the incidence of toxic side effects. Results: The index CLR was found to be the predictor of mortality of nasopharyngeal carcinoma but not the indicator for toxicity. Conclusion: The index CLR can be used for risk-stratification. However, whether the risk-stratification treatment based on these indicators can improve the prognosis subsequently needs further prospective study. [ABSTRACT FROM AUTHOR]

Purpose: To explore acute toxicities and prognosis of elderly NPC patients after IMRT; to identify predictors regarding age, chemotherapy, comorbidities, nutrition status, and psychological condition; and to establish a nomogram for the prediction of prognosis. Patients and Methods: Elderly NPC patients were divided into three groups (age of 60– 65, age of 66– 70, and age over 70) and were retrospectively analyzed. The acute toxicities, prognosis, and potential predictors were analyzed. Then, a nomogram for PFS was established, and the performance of nomogram was compared with the performance of TNM system. Results: A total of 214 elderly patients (214/1981, 10.8%) were involved. Patients of Stage III and IV accounted for 73.4%. The 3-year, 5-year PFS and OS were 77.9%, 66.3%, 79.3% and 66.8%, respectively. Elder patients had a worse prognosis (P=0.002). The main cause of death remained in recurrence and metastasis; few died from comorbidities, and some died from nutrition status and psychological condition. Age (HR=1.10, 95% CI=1.05– 1.15, P< 0.001), ALB level (HR=0.93, 95% CI=0.88– 0.99, P=0.019), and T stage (HR=1.85, 95% CI=1.10– 3.13, P=0.022) were critical for PFS, but chemotherapy or comorbidities were not. Acute toxicities were mainly at or under grade II. N stage (OR=2.50, 95% CI=1.28– 4.88, P=0.007) and chemotherapy (OR=6.01, 95% CI=3.11– 11.63, P< 0.001) were risk factors for hematological toxicity; while age (OR=0.59, 95% CI=0.37– 0.92, P=0.020) and chemotherapy (OR=225.14, 95% CI=61.91– 818.64, P< 0.001) influenced emesis; ALB (OR=1.11, 95% CI=1.04– 1.19, P=0.002) affected mucositis. Comorbidities were not influential in acute toxicities. The nomogram for PFS (C-index=0.682, 95% CI=0.617– 0.747) performed better than the TNM system (C-index=0.604, 95% CI=0.532– 0.674, P< 0.001). Conclusion: Elderly NPC patients sustained poor prognosis. The easily applied nomogram is hopeful to benefit the clinical decision-making. [ABSTRACT FROM AUTHOR]

Background: Skeletal muscle loss is a novel imaging biomarker that is considered to be predictive of survival outcomes and toxicity in a variety of solid tumors. This study explored to investigate whether skeletal muscle loss after chemoradiotherapy (CRT) in nasopharyngeal carcinoma (NPC) patients can predict survival. Methods: A total of 394 non‐metastatic NPC patients were enrolled. The cross‐sectional area of the third lumbar skeletal muscle based on computed tomography (CT) scan was measured and the skeletal muscle index (SMI) was calculated. A cut‐off value suitable for the Chinese population was used to define sarcopenia, and relative changes in skeletal muscle after treatment were analyzed for the confirmation of skeletal muscle tissue loss during treatment and its impact on overall survival (OS). Results: The median follow‐up was 22.7 (range, 2.5‐46.4) months. One hundred and thirty patients (33.0%) were defined sarcopenia at baseline. Two hundred and forty one patients (61.2%) had posttreatment sarcopenia. The mean SMI before and after treatment was 42.8 and 38.1 cm2/m2 (P < .001), and the average SMA loss was 13.1 cm2. While sarcopenia before or after treatment was not associated with OS, severe muscle loss after CRT was an independent predictor of survival prognosis for NPC (hazard ratio 2.79, 95% confidence interval 1.47‐5.28, P = .002) when adjusted for gender and cancer stage. Conclusions: During CRT, patients with NPC often experience different levels of muscle loss, and severe skeletal muscle loss may shorten OS. [ABSTRACT FROM AUTHOR]

Purpose: To assess the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in stage II nasopharyngeal carcinoma (NPC). Methods: Stage II (2010 UICC/AJCC staging system) NPC patients treated between January 2007 and December 2014 were retrospectively analyzed. The NLR was calculated from peripheral blood cell counts before treatment. The optimal cut-off value of NLR was determined by receiver operating characteristic curve analysis. Survival rates were compared according to the NLR value. Multivariable Cox regression analyses were performed to assess the association between the NLR and overall survival (OS), locoregional-free survival (LRFS), and distant metastasis-free survival (DMFS). Results: Two hundred and fifty-one stage II NPC patients were included in this study. The NLR was correlated with T stage (r=0.158, p=0.012). An NLR ≥2.92 was associated with poor 5-year OS (84.3% vs 97.4%, p=0.001) and LRFS (91.4% vs 98.4%, p=0.003). An NLR ≥2.82 was associated with poor 5-year DMFS (92.6% vs 98.2%, p=0.033). The multivariate Cox regression analysis showed that an NLR ≥2.92 was an independent prognostic biomarker in stage II NPC. Conclusion: The NLR is an independent prognostic factor in stage II NPC. [ABSTRACT FROM AUTHOR]

Sleep disturbances and psychological distress are the most common adverse effects associated with cancer diagnosis and treatment. The aim of this study was to examine sleep and psychological characteristics in patients with local-advanced nasopharyngeal carcinoma (NPC) following completion of intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy, and to describe the predictors of post-test psychological symptoms after treatment. Sleep quality and psychological symptoms were measured using Pittsburgh sleep-quality index (PSQI) and symptom checklist-90 in 60 local-advanced NPC patients treated with IMRT and concurrent chemotherapy, respectively. After treatment, the subscores of subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction increased significantly compared with their pre-test scores. Similar results were observed for the mean PSQI global score. However, for psychological symptoms, only subscores of somatization and depression were higher than their baseline level. Multivariate analysis revealed that concurrent chemotherapy cycle was the only predictor of depression after treatment among all of the psychological symptoms assessed. These findings indicate that sleep disturbance and psychological distress are significant problems in NPC patients treated with IMRT and concurrent chemotherapy. Patients who receive many cycles of concurrent chemotherapy may be at an increased risk of depression after completion of IMRT. [ABSTRACT FROM AUTHOR]

Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population. This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18–65 years with newly diagnosed high-risk non-metastatic stage III–IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3–4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing. Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0–44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81–90] vs 76% [70–81]; stratified hazard ratio 0·59 [0·38–0·92]; p=0·019). Grade 3–4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3–4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group. Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma. National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. For the Chinese translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

• Contradictory results have been reported for the potential survival benefit of radiation therapy for metastases. • We investigated the efficacy of metastatic lesion radiotherapy (MLRT) in patients with metastatic nasopharyngeal carcinoma (mNPC). • We found that MLRT offers substantial survival advantages to patients with mNPC. • The recommended regimen for MLRT is to employ a minimum biologically effective dose (BED) of 56 Gy to achieve optimal outcomes. We investigated the efficacy of metastatic lesion radiotherapy (MLRT) in patients with metastatic nasopharyngeal carcinoma (mNPC). Patients with mNPC from three institutions were included in this study. Propensity score matching (PSM) was employed to ensure comparability between patient groups. Overall survival (OS) rates were assessed using the Kaplan–Meier method and compared using the log-rank test. Prognostic factors were identified using univariate and multivariate Cox hazard analyses. Subgroup analyses were conducted to assess the effects of MLRT on specific patient populations. We analyzed data from 1157 patients with mNPC. Patients who received MLRT had significantly better OS than those who did not, both in the original (28 vs. 21 months) and PSM cohorts (26 vs. 23 months). MLRT was identified as an independent favorable predictor of OS in multivariate analyses, with hazard ratios of 0.67. The subgroup analysis results indicated that radiotherapy effectively treated liver, lung, and bone metastatic lesions, particularly in patients with a limited tumor burden. Higher total radiation doses of MLRT (biologically effective dose (BED) ≥ 56 Gy) were associated with improved OS, while neither radiation technique nor dose fractionation independently influenced prognosis. MLRT offers survival advantages to patients diagnosed with mNPC. Patients with limited metastatic burden derive the most benefit from MLRT, and the recommended regimen for MLRT is a minimum BED of 56 Gy for optimal outcomes. [ABSTRACT FROM AUTHOR]

• We aimed to establish an M1 subdivision for personalized prognosis prediction and treatment planning for mNPC. • M1 subdivision demonstrated superior discrimination and clinical utility. • The novel M1 staging strategy provides a refined approach for prognostic prediction and treatment planning. To meet the demand for personalized treatment, effective stratification of patients with metastatic nasopharyngeal carcinoma (mNPC) is essential. Hence, our study aimed to establish an M1 subdivision for prognostic prediction and treatment planning in patients with mNPC. This study included 1239 patients with mNPC from three medical centers divided into the synchronous mNPC cohort (smNPC, n = 556) to establish an M1 stage subdivision and the metachronous mNPC cohort (mmNPC, n = 683) to validate this subdivision. The primary endpoint was overall survival. Univariate and multivariate Cox analyses identified covariates for the decision-tree model, proposing an M1 subdivision. Model performance was evaluated using time-dependent receiver operating characteristic curves, Harrell's concordance index, calibration plots, and decision curve analyses. The proposed M1 subdivisions were M1a (≤5 metastatic lesions), M1b (>5 metastatic lesions + absent liver metastases), and M1c (>5 metastatic lesions + existing liver metastases) with median OS of 34, 22, and 13 months, respectively (p < 0.001). This M1 subdivision demonstrated superior discrimination (C-index = 0.698; 3-year AUC = 0.707) and clinical utility over those of existing staging systems. Calibration curves exhibited satisfactory agreement between predictions and actual observations. Internal and mmNPC cohort validation confirmed the robustness. Survival benefits from local metastatic treatment were observed in M1a, while immunotherapy improved survival in patients with M1b and M1c disease. This novel M1 staging strategy provides a refined approach for prognostic prediction and treatment planning in patients with mNPC, emphasizing the potential benefits of local and immunotherapeutic interventions based on individualized risk stratification. [ABSTRACT FROM AUTHOR]

Background: Patients with locoregionally advanced nasopharyngeal carcinoma have a high risk of disease relapse, despite a high proportion of patients attaining complete clinical remission after receiving standard-of-care treatment (ie, definitive concurrent chemoradiotherapy with or without induction chemotherapy). Additional adjuvant therapies are needed to further reduce the risk of recurrence and death. However, the benefit of adjuvant chemotherapy for nasopharyngeal carcinoma remains controversial, highlighting the need for more effective adjuvant treatment options.Methods: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was done at 14 hospitals in China. Patients (aged 18-65 years) with histologically confirmed, high-risk locoregionally advanced nasopharyngeal carcinoma (stage III-IVA, excluding T3-4N0 and T3N1 disease), no locoregional disease or distant metastasis after definitive chemoradiotherapy, an Eastern Cooperative Oncology Group performance status of 0 or 1, sufficient haematological, renal, and hepatic function, and who had received their final radiotherapy dose 12-16 weeks before randomisation, were randomly assigned (1:1) to receive either oral metronomic capecitabine (650 mg/m2 body surface area twice daily for 1 year; metronomic capecitabine group) or observation (standard therapy group). Randomisation was done with a computer-generated sequence (block size of four), stratified by trial centre and receipt of induction chemotherapy (yes or no). The primary endpoint was failure-free survival, defined as the time from randomisation to disease recurrence (distant metastasis or locoregional recurrence) or death due to any cause, in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of capecitabine or who had commenced observation. This trial is registered with ClinicalTrials.gov, NCT02958111.Findings: Between Jan 25, 2017, and Oct 25, 2018, 675 patients were screened, of whom 406 were enrolled and randomly assigned to the metronomic capecitabine group (n=204) or to the standard therapy group (n=202). After a median follow-up of 38 months (IQR 33-42), there were 29 (14%) events of recurrence or death in the metronomic capecitabine group and 53 (26%) events of recurrence or death in the standard therapy group. Failure-free survival at 3 years was significantly higher in the metronomic capecitabine group (85·3% [95% CI 80·4-90·6]) than in the standard therapy group (75·7% [69·9-81·9]), with a stratified hazard ratio of 0·50 (95% CI 0·32-0·79; p=0·0023). Grade 3 adverse events were reported in 35 (17%) of 201 patients in the metronomic capecitabine group and in 11 (6%) of 200 patients in the standard therapy group; hand-foot syndrome was the most common adverse event related to capecitabine (18 [9%] patients had grade 3 hand-foot syndrome). One (<1%) patient in the metronomic capecitabine group had grade 4 neutropenia. No treatment-related deaths were reported in either group.Interpretation: The addition of metronomic adjuvant capecitabine to chemoradiotherapy significantly improved failure-free survival in patients with high-risk locoregionally advanced nasopharyngeal carcinoma, with a manageable safety profile. These results support a potential role for metronomic chemotherapy as an adjuvant therapy in the treatment of nasopharyngeal carcinoma.Funding: The National Natural Science Foundation of China, the Key-Area Research and Development Program of Guangdong Province, the Natural Science Foundation of Guangdong Province, the Innovation Team Development Plan of the Ministry of Education, and the Overseas Expertise Introduction Project for Discipline Innovation.Translation: For the Chinese translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

Background: The value of adding cisplatin, fluorouracil, and docetaxel (TPF) induction chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is unclear. We aimed to compare TPF induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone in a suitably powered trial.Methods: We did an open-label, phase 3, multicentre, randomised controlled trial at ten institutions in China. Patients with previously untreated, stage III-IVB (except T3-4N0) nasopharyngeal carcinoma, aged 18-59 years without severe comorbidities were enrolled. Eligible patients were randomly assigned (1:1) to receive induction chemotherapy plus concurrent chemoradiotherapy or concurrent chemoradiotherapy alone (three cycles of 100 mg/m2 cisplatin every 3 weeks, concurrently with intensity-modulated radiotherapy). Induction chemotherapy was three cycles of intravenous docetaxel (60 mg/m2 on day 1), intravenous cisplatin (60 mg/m2 on day 1), and continuous intravenous fluorouracil (600 mg/m2 per day from day 1 to day 5) every 3 weeks before concurrent chemoradiotherapy. Randomisation was by a computer-generated random number code with a block size of four, stratified by treatment centre and disease stage (III or IV). Treatment allocation was not masked. The primary endpoint was failure-free survival calculated from randomisation to locoregional failure, distant failure, or death from any cause; required sample size was 476 patients (238 per group). We did efficacy analyses in our intention-to-treat population. The follow-up is ongoing; in this report, we present the 3-year survival results and acute toxic effects. This trial is registered with ClinicalTrials.gov, number NCT01245959.Findings: Between March 1, 2011, and Aug 22, 2013, 241 patients were assigned to induction chemotherapy plus concurrent chemoradiotherapy and 239 to concurrent chemoradiotherapy alone. After a median follow-up of 45 months (IQR 38-49), 3-year failure-free survival was 80% (95% CI 75-85) in the induction chemotherapy plus concurrent chemoradiotherapy group and 72% (66-78) in the concurrent chemoradiotherapy alone group (hazard ratio 0·68, 95% CI 0·48-0·97; p=0·034). The most common grade 3 or 4 adverse events during treatment in the 239 patients in the induction chemotherapy plus concurrent chemoradiotherapy group versus the 238 patients in concurrent chemoradiotherapy alone group were neutropenia (101 [42%] vs 17 [7%]), leucopenia (98 [41%] vs 41 [17%]), and stomatitis (98 [41%] vs 84 [35%]).Interpretation: Addition of TPF induction chemotherapy to concurrent chemoradiotherapy significantly improved failure-free survival in locoregionally advanced nasopharyngeal carcinoma with acceptable toxicity. Long-term follow-up is required to determine long-term efficacy and toxicities.Funding: Shenzhen Main Luck Pharmaceuticals Inc, Sun Yat-sen University Clinical Research 5010 Program (2007037), National Science and Technology Pillar Program during the Twelfth Five-year Plan Period (2014BAI09B10), Health & Medical Collaborative Innovation Project of Guangzhou City (201400000001), Planned Science and Technology Project of Guangdong Province (2013B020400004), and The National Key Research and Development Program of China (2016YFC0902000). [ABSTRACT FROM AUTHOR]

Purpose: Chemotherapy use remains controversial for stage II nasopharyngeal carcinoma (NPC). This retrospective study was conducted to identify whether chemoradiotherapy was associated with better survival compared to radiotherapy.Materials and Methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried for stage II NPC patients between 2004 and 2015. Patients were divided into radiotherapy and chemoradiotherapy groups. Overall survival (OS) and cancer-specific survival (CSS) were examined using the Kaplan-Meier method, Cox proportional hazards models, and propensity score matching analyses.Results: This study examined 908 patients, including 102 receiving radiotherapy and 806 receiving chemoradiotherapy. Chemoradiotherapy was associated with 5-year OS (78.01% vs. 75.12%; p = 0.22) and CSS (78.92% vs. 78.26%; p = 0.40) rates comparable to those of radiotherapy. Propensity score matching analyses demonstrated similar OS (HR: 0.63, 95% CI: 0.36--1.10; p = 0.10) and CSS (HR: 0.77, 95% CI: 0.41-1.48; p = 0.44) rates with radiotherapy. Age >60 years and non-Asian patients were associated with worse survival.Conclusion: This study revealed that chemoradiotherapy showed similar survivals to stage II NPC patients compared with radiotherapy. Due to the limitations of SEER database, further studies should be performed to verify the results. [ABSTRACT FROM AUTHOR]