Non-metastatic Nasopharyngeal Carcinoma Patients Research Articles

Survival outcomes and toxicity profiles among patients with nonmetastatic nasopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT) versus IMRT + carbon-ion radiotherapy: A propensity score-matched analysis.

To compare survival outcomes and toxic effects among patients with newly diagnosed nonmetastatic nasopharyngeal carcinoma (NPC) when treated with intensity-modulated radiotherapy (IMRT) versus IMRT + carbon-ion radiotherapy (CIRT). We performed a retrospective propensity score matching analysis (1:1) of patients treated with IMRT and IMRT + CIRT. Descriptive statistics were used to examine the baseline characteristics of the patients. Survival was estimated using the Kaplan-Meier method. Univariate and multivariable logistic regression analysis were used to identify the independent predictors of survival. We examined the association between risk factors and adverse events (AEs) using chi-square tests. Cox model and logistic regression were used to analyze AEs. Hundred and nine patients who received IMRT + CIRT were included and the median follow-up time was 20.6 months (range: 4.6-82 months). There were no statistically significant differences in locoregional failure-free survival, distant metastasis-free survival, disease-free survival, or overall survival between the two groups, but potentially better in IMRT + CIRT group (p > 0.05, respectively). Nodal boost was the only significant factor associated with LRFS and DFS on multivariable analysis. Thirty-seven patients (34.0%) developed grade 3 acute OMs and no grade 4 acute OMs were observed in IMRT + CIRT group. All patients in IMRT + CIRT group developed grade 1 dermatitis; while in the match group, 76 patients developed grade 1 dermatitis, 27 patients developed grade 2 dermatitis, 5 patients developed grade 3 dermatitis, 1 patient developed grade 4 dermatitis. IMRT + CIRT treatment was associated with a significant trend of lower grades of OM and dermatitis (p < 0.05, respectively). Any severe (i.e., grade 3) chronic AEs, such as xerostomia, skin fibrosis, temporal lobe necrosis, osteoradionecrosis, or radiation-induced optic neuropathy, was not observed. In this study, IMRT + CIRT was associated with significantly reduced acute toxicity burden compared with full course of IMRT, with excellent survival outcomes. Patients with persistent disease after treatment and treated with nodal boost had a worse outcome. More accurate assessments of IMRT + CIRT to primary nonmetastatic NPC patients will be imperative.

Patterns of failure in patients with nasopharyngeal cancer of Northeastern region of India: a retrospective observational study.

We aimed to analyzepatterns of failure and disease volume-treatment outcomes in patients with Nasopharyngeal carcinoma (NPC) treated with definitive radiation with or without concurrent chemotherapy at a tertiary cancer centre in northeast India. From February 2018 to February 2022, 99 histopathologically proved non-metastatic NPC patients treated with curative-intent RT with or without chemotherapy were retrospectively analyzed. Locally advanced patients received neoadjuvant or adjuvant chemotherapy. The Cox proportional hazards model was used to investigate the impact of various prognostic factors on locoregional free survival (LRFS), distant metastasis free survival (DMFS), progression free survival (PFS) and overall survival (OS). The log-rank test and Kaplan-Meir curves compared outcome variables based on ROC analysis-classified tumor volume. During a median follow up of 25.4months (17.3-39.2), 35(35.4%) patients developed recurrence. Twenty-three patients developed locoregional failures, of which 11 were in-field; 12 patient showed an out-field failure. The 3-year LRFS, DMFS, PFS and OS was 71.10%, 70.90%, 64.10% and 74.10% respectively. There was statistically significant difference in LRFS according to T staging (p < 0.0001). Gross tumor volume (GTVp) and gross nodal volume (GTVn) were an independent prognostic factor for OS, PFS, LRFS and DMFS. The cut-off volumes for GTVp and GTVn for distant metastases and locoregional failure, respectively, were found to be 13 and 22.7mL and 3.7 and 39.2mL, respectively, by ROC curve analysis. Based on this, 99 patients were divided into three subgroups. OS demonstrated significant differences among patients in different volume subgroups for GTVp (p = 0.03) and GTVn (p = 0.00024). For NPC patients who undergo curative IMRT, primary tumour and nodal volumes are independent prognostic indicators. GTVp and GTVn are highly predictive of local control, distant metastases, disease-free survival, and overall survival. This justifies their use as quantitative prognostic indicator for NPC.

Serum ferritin predicted prognosis in patients with nasopharyngeal carcinoma

Elevated serum ferritin (SF) levels have been associated with poor prognosis in various cancer types, but its impact on nasopharyngeal carcinoma (NPC) remains unclear. This retrospective study analyzed clinical data from 252 non-metastatic NPC patients admitted to Hainan General Hospital between January 2014 and May 2016. SF levels were measured using the chemiluminescence method. Patients were categorized into low, medium, and high-level SF groups based on tertile median SF levels. Survival outcomes were assessed using Kaplan–Meier analysis and Cox regression models. The overall survival rates of the entire patient cohort at 1, 3, 5, and 8 years were 95.2%, 85.7%, 76.2%, and 68.9% respectively. The high-level SF group (SF > 164.00 ng/mL) had significantly worse overall survival (83.1 vs 96.3 months, P = 0.023) and progression-free survival (77.8 vs 93.3 months, P = 0.019) compared to the low-level SF group. Univariate and multivariate analyses confirmed that high SF levels, along with T3/T4 staging and N3 staging, were independent risk factors for poor prognosis. In conclusion, high SF levels are associated with shorter overall survival and progression-free survival in NPC patients.

A Novel Prognostic Model Predicts Outcomes in Non-Metastatic Nasopharyngeal Carcinoma Based on Inflammation, Nutrition, and Coagulation Signature.

This study aimed to assess the prognostic and predictive value of a circulating hematological signature (CHS) and to develop a CHS-based nomogram for predicting prognosis and guiding individualized chemotherapy in non-metastatic nasopharyngeal carcinoma (NPC) patients. NPC patients were recruited between January 2014 and December 2017 at the Jiangxi Cancer Hospital. The CHS was constructed based on a series of hematological indicators. The nomogram was developed by CHS and clinical factors. A total of 779 patients were included. Three biomarkers were selected by least absolute shrinkage and selection operator regression, including prognostic nutritional index, albumin-to-fibrinogen ratio, and prealbumin-to-fibrinogen ratio, were used to construct the CHS. The patients in the low-CHS group had better 5-year DMFS and OS than those in the high-CHS group in the training (DMFS: 85.0% vs 56.6%, p<0.001; OS: 90.3% vs 65.4%, p<0.001) and validation cohorts (DMFS: 92.3% vs 43.6%, p<0.001; OS: 92.1% vs 65.5%, p<0.001). The nomogram_CHS showed better performance than clinical stage in predicting distant metastasis (concordance index: 0.728 vs 0.646). In the low-TRS (total risk scores) group, the patients received RT alone, CCRT and IC plus CCRT had similar 5-year DMFS and OS (p>0.05). In the middle-TRS group, the patients received RT alone had worse 5-year DMFS (58.7% vs 80.8% vs 90.8%, p=0.002) and OS (75.0% vs 94.1% vs 95.0%, p=0.001) than those received CCRT or IC plus CCRT. In the high-TRS group, the patients received RT alone and CCRT had worse 5-year DMFS (18.6% vs 31.3% vs 81.5%, p<0.001) and OS (26.9% vs 53.2% vs 88.8%, p<0.001) than those received IC plus CCRT. The developed nomogram_CHS had satisfactory prognostic accuracy in NPC patients and may individualize risk estimation to facilitate the identification of suitable IC candidates.

Two web-based dynamically interactive nomograms and risk stratification systems for predicting survival outcomes and guiding treatment in non-metastatic nasopharyngeal carcinoma.

A nomogram is a valuable and easily accessible tool for individualizing cancer prognosis. This study aims to establish and validate two prognostic nomograms for long-term overall survival (OS) and cancer-specific survival (CSS) in non-metastatic nasopharyngeal carcinoma (NPC) patients and to investigate the treatment options for the nomogram-based risk stratification subgroups. A total of 3959 patients with non-metastatic NPC between 2004 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The patients were randomly allocated to the training and validation cohorts in a 7:3 ratio. Prognostic nomograms were constructed to estimate OS and CSS by integrating significant variables from multivariate Cox regression employing a backward stepwise method. We examined the correlation indices (C-index) and areas under the curves (AUC) of time-dependent receiver operating characteristic curves to assess the discriminative ability of our survival models. The comprehensive enhancements of predictive performance were evaluated with net reclassification operating improvement (NRI) and integrated discrimination improvement (IDI). Reliability was validated using calibration plots. Decision curve analysis (DCA) was used to estimate clinical efficacy and capability. Finally, the nomogram-based risk stratification system used Kaplan-Meier survival analysis and log-rank tests to examine differences between subgroups. The following independent parameters were significant predictors for OS: sex, age, race, marital status, histological type, median household income, AJCC stage tumor size, and lymph node size. Except for the race variables mentioned above, the rest were independent prognostic factors for CSS. The C-index, AUC, NRI, and IDI indicated satisfactory discriminating properties. The calibration curves exhibited high concordance with the exact outcomes. Moreover, the DCA demonstrated performed well for net benefits. The prognosis significantly differed between low- and high-risk patients (p < 0.001). In a treatment-based stratified survival analysis in risk-stratified subgroups, chemotherapy benefited patients in the high-risk group compared to radiotherapy alone. Radiotherapy only was recommended in the low-risk group. Our nomograms have satisfactory performance and have been validated. It can assist clinicians in prognosis assessment and individualized treatment of non-metastatic NPC patients.

Prognostic value of EBV DNA and platelet-to-lymphocyte ratio in patients with non-metastatic nasopharyngeal carcinoma: a retrospective study

PurposeAnalyzing the prognostic value of Epstein-Barr virus (EBV) DNA load and platelet-to-lymphocyte ratio (PLR) in non-metastatic nasopharyngeal carcinoma (NPC) patients, thereby developing a reliable and effective marker.MethodsWe compared survival rates among different groups using the Kaplan-Meier method and the Log-rank test. The factors affecting the prognosis of NPC patients were determined using univariate and multivariate cox regression analysis. Receiver operating characteristic (ROC) curves were used to identify the cutoff-value and discriminant performance of the model.ResultsThe ROC curve indicated a cut-off value of 775 copies/ml for EBV DNA and 203.3 for PLR. Kaplan-Meier and Log-rank tests showed that 3-year overall survival (OS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) of NPC patients in high risk group (HRG) were significantly poorer than those in medium risk group (MRG) and low risk group (LRG). The 3-year OS of NPC patients was significantly correlated with age, N stage and EBV DNA-PLR. The 3-year LRFS were significantly correlated with sex, N stage, histology type, and EBV DNA-PLR. The 3-year DMFS were correlated with histology type. The ROC curve showed that area under the curve (AUC) values of EBV DNA-PLR of 3-year OS, LRFS and DMFS in NPC were higher than those of PLR and EBV DNA.ConclusionEBV DNA-PLR is an independent risk factor for the prognosis of NPC. Compared with PLR or EBV DNA alone, the combination of EBV DNA and PLR may be more accurate in predicting the prognosis of NPC patients.

Development of Prognostic Nomogram Based on Lipid Metabolic Markers and Lactate Dehydrogenase in Non-Metastatic Nasopharyngeal Carcinoma.

To establish and verify a comprehensive prognostic nomogram for predicting survival outcomes and improving the prognosis for non-metastatic nasopharyngeal carcinoma (NPC). Our retrospective study screened 613 cases of non-metastatic NPC who received radiotherapy from July 2012 to December 2016. A reliable nomogram was formulated for predicting overall survival (OS) and progression-free survival (PFS) using all independent predictors selected by Cox regression analysis. A comparison is conducted between the current staging and the predictive performance of the nomogram. Internal validation was performed in a single center using the validation cohort to assess predictive accuracy and discrimination. High-density lipoprotein cholesterol, Epstein-Barr virus DNA and lactate dehydrogenase were determined to be valuable predictive indicators for predicting OS and PFS. Triglycerides were a valuable predictive indicator for predicting OS. Calibration curves demonstrated that the nomogram had remarkable correspondence between the prediction outcomes and the actual observations. Receiver operating characteristic curves showed that the nomogram had greater area under the curve and more satisfactory discrimination capability than the current TNM staging. Decision curve analysis revealed that the nomogram had high net clinical benefits. Significant differences were observed when low- and high-risk groups were stratified via Kaplan-Meier curves. Our proposed nomogram combining lipid metabolic markers and lactate dehydrogenase could assist clinicians in the accurate prognostic prediction of non-metastatic NPC patients and provide personalized treatment recommendations.

Conditional survival nomogram for monitoring real-time survival of young non-metastatic nasopharyngeal cancer survivors.

The aim of this study was to clarify the improvement of the overall survival (OS) over time in young non-metastatic nasopharyngeal carcinoma (NPC) survivors by conditional survival (CS) analysis and to construct a CS-nomogram for updating individualized real-time prognosis. The study included 3409 young non-metastatic NPC patients from the Surveillance, Epidemiology, and End Results (SEER) database (2004-2019). OS was estimated using the Kaplan-Meier method. CS was calculated based on CS(y|x) = OS(y + x)/OS(x), defined as the probability that a patient would survive for another y years after surviving for x years since diagnosis. We identified predictors using the least absolute shrinkage and selection operator (LASSO) regression and developed the CS-nomogram using multivariate Cox regression and the CS formula. CS analysis showed a continuous increase in 10-year OS for young non-metastatic NPC from the initial 60.4% to 65.0%, 70.2%, 74.2%, 78.2%, 82.6%, 86.9%, 91.1%, 96.2% and 97.0% (surviving 1-9years after diagnosis, respectively). After screening by LASSO regression, age, race, marital status, histological type, T- and N-status were used as predictors to construct the CS-nomogram. The model accurately estimated the real-time prognosis of survivors during follow-up with a stable time-dependent area under the curve (AUC). CS analysis based on SEER database calibrated the real-time prognosis of young non-metastatic NPC survivors, revealing a dynamic improvement during follow-up time. We developed a novel CS-nomogram to update survival data for real-time optimization of monitoring strategies, medical resource allocation, and patient counseling. However, it was important to note that the model still needed external data validation and continuous improvement.

Risk stratification and beneficiary selection among elderly nasopharyngeal carcinoma patients from concurrent chemoradiotherapy combined with induction chemotherapy.

This study aims to evaluate the risk stratification among elderly Nasopharyngeal carcinoma (NPC) patients (≥60 years old) and select the beneficiaries from concurrent chemotherapy (CCRT) combined with induction chemotherapy (IC). A total of 909 elderly non-metastatic NPC patients treated with cisplatin-based CCRT or IC + CCRT between January 2007 and December 2016 were included. Prognostic nomograms were generated according to clinical characteristics and serum biomarkers. The survival outcomes of patients treated with CCRT versus IC + CCRT were compared in three well-matched risk groups (high, medium, and low risk) after PSM analysis. Benefit of IC in people older or younger than 70 years and effect of different IC regimens and cycles on prognosis were analyzed. Nomograms of overall survival (OS) (C-index: 0.64, 95% CI, 0.61-0.89) and disease special survival (DSS) (C-index: 0.65, 95% CI, 0.62-0.71) showed good prognostic accuracy. The nomogram for DSS included variables of age, gender, ACE, EBV DNA, N stage, and T stage. OS included variables of age, smoking history, ACE, ALB, EBV DNA, N stage, and T stage. The corresponding 5-year OS rates of high, medium and low risk groups were 87.4%, 82.2%, and 60.9%, respectively (p < 0.001), while the 5-year DSS rates were 92.2%, 84.3%, and 69.0%, respectively (p < 0.001). In the high risk group, IC + CCRT led to significantly higher 5-year OS and DSS rate compared with CCRT (5-year OS rate, 73.5% versus 51.8%, p=0.006; 5-year DSS rate, 81.4% versus 61.3%, p=0.002). While in the medium and low risk groups, OS and DSS were not significantly different (OS: p=0.259, 0.186; DSS: p=0.29, 0.094). Subgroup analysis showed in the high risk group, only people younger than 70 years old could benefit from IC. TPF and IC cycles of three could lead to the best survival results. Compared with CCRT, OS, and DSS among high risk elderly patients were significantly improved by the addition of IC in patients younger than 70 years old. TPF and three IC cycles were recommended.

Pretreatment synthetic magnetic resonance imaging predicts disease progression in nonmetastatic nasopharyngeal carcinoma after intensity modulation radiation therapy

BackgroundTo investigate the potential of synthetic MRI (SyMRI) in the prognostic assessment of patients with nonmetastatic nasopharyngeal carcinoma (NPC), and the predictive value when combined with diffusion-weighted imaging (DWI) as well as clinical factors.MethodsFifty-three NPC patients who underwent SyMRI were prospectively included. 10th Percentile, Mean, Kurtosis, and Skewness of T1, T2, and PD maps and ADC value were obtained from the primary tumor. Cox regression analysis was used for analyzing the association between SyMRI and DWI parameters and progression-free survival (PFS), and then age, sex, staging, and treatment as confounding factors were also included. C-index was obtained by bootstrap. Moreover, significant parameters were used to construct models in predicting 3-year disease progression. ROC curves and leave-one-out cross-validation were used to evaluate the performance and stability.ResultsDisease progression occurred in 16 (30.2%) patients at a follow-up of 39.6 (3.5, 48.2) months. T1_Kurtosis, T1_Skewness, T2_10th, PD_Mean, and ADC were correlated with PFS, and T1_Kurtosis (HR: 1.093) and ADC (HR: 1.009) were independent predictors of PFS. The C-index of SyMRI and SyMRI + DWI + Clinic models was 0.687 and 0.779. Moreover, the SyMRI + DWI + Clinic model predicted 3-year disease progression better than DWI or Clinic model (p ≤ 0.008). Interestingly, there was no significant difference between the SyMRI model (AUC: 0.748) and SyMRI + DWI + Clinic model (AUC: 0.846, p = 0.092).ConclusionSyMRI combined with histogram analysis could predict disease progression in NPC patients, and SyMRI + DWI + Clinic model further improved the predictive performance.

The relationship between nutritional status before chemotherapy with nutritional status after chemotherapy in locoregionally advanced nasopharyngeal carcinoma patients

Background: Malnutrition in nasopharyngeal carcinoma (NPC) patients is caused by various factors such as tumor localization, metabolic derangement, and side effects of therapy. Poor nutritional status in cancer patients is associated with serious clinical consequences such as poor quality of life, higher treatment toxicity, and poor prognosis. The purpose of this study was to determine the effect of nutritional status before chemotherapy on the nutritional status after chemotherapy in non-metastatic advance-stage NPC patients. Methods: This study was an observational study with a cross sectional design using secondary data involving non-metastatic advanced-stage NPC patients undergoing chemotherapy at dr. Kariadi Hospital Semarang in January 2020 – June 2022. The sampling technique used was consecutive sampling. Nutritional status was measured by malnutrition criteria according to the American Society for Parenteral and Enteral Nutrition (ASPEN). Statistical analysis was performed with Chi-Square and McNemar analysis test. Results: Total sample of this study was 55 subjects. The results of this study were there was a relationship between nutritional status before chemotherapy and nutritional status after chemotherapy in non-metastatic advanced-stage NPC patients (P&lt;0.05). All subjects were malnourished before chemotherapy, with 12.7% moderately malnourished and 87.3% severely malnourished. All subjects were malnourished after chemotherapy, with 41.8% moderately malnourished and 58.2% severely malnourished, decreased nutritional status of post-chemotherapy non-metastatic advanced NPC patients was related to the length of chemotherapy (p&lt;0.05), but not related to comorbidities, age, and stage of chemotherapy (p&gt;0.05). Conclusion: There is a relationship between nutritional status before chemotherapy and nutritional status after chemotherapy in non-metastatic advanced-stage NPC patients.

Long-term outcomes of nasopharyngeal carcinoma treated with helical tomotherapy using simultaneous integrated boost technique: A 10-year result.

To evaluate the long-term survival and treatment-related toxicities of helical tomotherapy (HT) in nasopharyngeal carcinoma (NPC) patients. One hundred and ninety newly diagnosed non-metastatic NPC patients treated with HT from September 2007 to August 2012 were analyzed retrospectively. The dose at D95 prescribed was 70-74Gy, 60-62.7Gy and 52-56Gy delivered in 33 fractions to the primary gross tumor volume (pGTVnx) and positive lymph nodes (pGTVnd), the high risk planning target volume (PTV1), and the low risk planning target volume (PTV2), respectively, using simultaneous integrated boost technique. The statistical analyses were performed and late toxicities were evaluated and scored according to the Common Terminology Criteria for Adverse Events (version 3.0). The median follow-up time was 145 months. The 10-year local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 94%, 95%, 86%, and 77.8%; respectively. Fifty (26.3%) patients had treatment-related failures at the last follow-up visit. Distant metastasis, occurred in 25 patients, was the major failure pattern. Multivariate analysis showed that age and T stage were independent predictors of DMFS and OS, Concomitant chemotherapy improved overall survival, but anti-EGFR monoclonal antibody therapy failed. The most common late toxicities were mainly graded as 1 or 2. Helical tomotherapy with simultaneous integrated boost technique offered excellent long-term outcomes for NPC patients, with mild late treatment-related toxicities. Age and clinical stage were independent predictors of DMFS and OS. And, concurrent chemotherapy means better OS. Further prospective study is needed to confirm the superiority of this technology and to evaluate the roles of anti-EGFR monoclonal antibody treatment.

Thyroid dysfunction in Chinese nasopharyngeal carcinoma after anti-PD-1 therapy and its association with treatment response

BackgroundProgrammed cell death protein-1 (PD-1) blockade therapies have demonstrated efficacy in nasopharyngeal carcinoma (NPC). Thyroid dysfunction is among the most common immune-related adverse events. This study aimed to explore the clinical pattern of thyroid dysfunction and its relationship with survival marker in nonmetastatic NPC after immunotherapy.MethodsFrom January 1, 2019, to December 31, 2021, 165 pairs of nonmetastatic NPC patients (165 with and 165 without anti-PD-1 immunotherapy) matched by the propensity score matching method were included in this study. Thyroid function was assessed retrospectively before the first treatment and during each immunotherapy cycle.ResultsThe spectrum of thyroid dysfunction was different between the immunotherapy and control groups (P < 0.001). Compared with the control group, patients in the immunotherapy group developed more hypothyroidism (14.545% vs. 7.273%), less hyperthyroidism (10.909% vs. 23.636%), and a distinct pattern, biphasic thyroid dysfunction (3.030% vs. 0%). Immunotherapy also accelerates the onset of hypothyroidism, which was earlier with a median onset time difference of 32 days (P < 0.001). Patients who acquired thyroid dysfunction during immunotherapy had better complete biological response to treatment (OR, 10.980; P = 0.042).ConclusionsFor nonmetastatic NPC, thyroid dysfunction was associated with better response to treatment in immunotherapy but not in routine treatment. Thyroid function could be used as a predictor for survival and should be under regular and intensive surveillance in clinical practice of anti-PD-1 immunotherapy for nonmetastatic NPC.

Combination of smoking and Epstein-Barr virus DNA is a predictor of poor prognosis for nasopharyngeal carcinoma: a long-term follow-up retrospective study

BackgroundThis retrospective study was performed to determine the prognostic potential of smoking and its combination with pre-treatment plasma Epstein-Barr virus (EBV) DNA levels in patients with nasopharyngeal carcinoma (NPC).MethodsMedical records of 1080 non-metastatic NPC patients who received intensity-modulated radiotherapy were reviewed. Male patients were categorized as never and ever smokers, and the smoking amount, duration, and cumulative consumption were used to evaluate dose-dependent effects. Survival outcomes were assessed using Kaplan-Meier survival analysis and the multivariate Cox regression analysis. Propensity score matching (PSM) was constructed.ResultsThe 5-year overall survival (OS) was worse for ever smokers than never smokers, and significantly decreased with the increase of smoking amount, duration, and cumulative consumption. Compared with never smokers, the multivariate-adjusted hazard ratio (HR) of death was higher in ever smokers (HR = 1.361, P = 0.049), those smoked ≥20 cigarettes/day (HR = 1.473, P = 0.017), those smoked for ≥30 years (HR = 1.523, P = 0.023), and those cumulative smoked for ≥30 pack-years (HR = 1.649, P = 0.005). The poor prognostic effects of smoking was also confirmed in the PSM analysis. The combination of cumulative smoking consumption and pre-treatment EBV DNA levels was proven to be an independent poor prognostic factor for male NPC, and the risk of death, progression, and distant metastases gradually increased with both factors (P < 0.001).ConclusionsCombination of smoking and pre-treatment EBV DNA levels as a predictor of poor prognosis could further improve the risk stratification and prognostication for NPC.

Anti-PD-1 Immunotherapy Changed the Spectrum of Thyroid Dysfunction during Radiotherapy in Patients with Nasopharyngeal Carcinoma

<h3>Purpose/Objective(s)</h3> Programmed cell death protein-1 (PD-1) blockade therapies have demonstrated their efficacy in a variety of malignancies, including nasopharyngeal carcinoma (NPC). Thyroid dysfunction is among the most common immune-related adverse event. However, presently we have a paucity of data on thyroid dysfunction associated with PD-1 blockade in non-metastatic NPC. This study aimed to study the incidence and pattern of immune-related thyroid dysfunction in non-metastatic NPC during radiotherapy <h3>Materials/Methods</h3> From January 1, 2019 to December 31, 2021, 165 pairs of non-metastatic NPC patients matching by propensity score matching (PSM) method to balance prognostic factors were included in this study: 165 cases in control group received conventional treatment (introduction chemotherapy and concurrent chemoradiotherapy), 165 cases in immunotherapy group received conventional treatment and anti-PD-1 immunotherapy before completion of radiotherapy. Thyroid function test and antithyroid antibodies were assessed prospectively before each immunotherapy cycle, beginning before the first treatment. Incidence and clinical pattern of thyroid dysfunction, and association with anti-thyroid antibodies was evaluated. <h3>Results</h3> In control group, 51 patients (30.91%) had thyroid dysfunctions. Among them, 12 patients had hypothyroidism (23.53%), 39 had thyrotoxicosis (76.47%) and none had biphasic hypothyroidism. In immunotherapy group, 47 patients (28.49%) had thyroid dysfunctions. Among them, 24 patients had hypothyroidism (51.06%), 18 had thyrotoxicosis (38.31%) and 5 had biphasic hypothyroidism (10.63%), a distinct pattern only observed in patients received immunotherapy. The positive rates of antithyroid peroxidase antibody (A-TPO) were similar between two groups, 12.12% in control group and 12.73% in immunotherapy group (<i>P</i> = 1). A-TPO was positive in 12 of 47 patients who developed thyroid dysfunction, compared with 11 of 118 who did not (25.53% vs 9.32%, <i>P</i> = 0.014). Especially, all patients with biphasic hypothyroidism had positive A-TPO, and the onset of A-TPO was earlier than that of transient hyperthyroidism. In patients with positive A-TPO and hypothyroidism or thyrotoxicosis, the A-TPO onset coincided with onset of thyroid dysfunction. <h3>Conclusion</h3> In non-metastatic NPC patients, thyroid dysfunction is common during treatment. Hypothyroidism and thyrotoxicosis are the most frequent presentations. Compared with conventional treatment, anti-PD-1 immunotherapy changed the spectrum of thyroid dysfunction but not the incidence. Patients who received anti-PD-1 immunotherapy developed a distinct pattern of thyroid dysfunction, biphasic hypothyroidism. The early elevation of A-TPO without aberrant TSH and FT4 may be a predictive marker for biphasic hypothyroidism. Our result suggested that thyroid functions should be under regular and intensive surveillance in clinical practice of anti-PD-1 immunotherapy in non-metastatic NPC patients.

Development and validation of an MRI-based radiomic model for predicting overall survival in nasopharyngeal carcinoma patients with local residual tumors after intensity-modulated radiotherapy

BackgroundTo investigate the potential value of the pretreatment MRI-based radiomic model in predicting the overall survival (OS) of nasopharyngeal carcinoma (NPC) patients with local residual tumors after intensity-modulated radiotherapy (IMRT).MethodsA total of 218 consecutive nonmetastatic NPC patients with local residual tumors after IMRT [training cohort (n = 173) and validation cohort (n = 45)] were retrospectively included in this study. Clinical and MRI data were obtained. Univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) were used to select the radiomic features from pretreatment MRI. The clinical, radiomic, and combined models for predicting OS were constructed. The models’ performances were evaluated using Harrell’s concordance index (C-index), calibration curve, and decision curve analysis.ResultsThe C-index of the radiomic model was higher than that of the clinical model, with the C-index of 0.788 (95% CI 0.724–0.852) versus 0.672 (95% CI 0.599–0.745) in the training cohort and 0.753 (95% CI 0.604–0.902) versus 0.634 (95% CI 0.593–0.675) in the validation cohort. Calibration curves showed good agreement between the radiomic model-predicted probability of 2- and 3-year OS and the actual observed probability in the training and validation groups. Decision curve analysis showed that the radiomic model had higher clinical usefulness than the clinical model. The discrimination of the combined model improved significantly in the training cohort (P < 0.01) but not in the validation cohort, with the C-index of 0.834 and 0.734, respectively. The radiomic model divided patients into high- and low-risk groups with a significant difference in OS in both the training and validation cohorts.ConclusionsPretreatment MRI-based radiomic model may improve OS prediction in NPC patients with local residual tumors after IMRT and may assist in clinical decision-making.

Platinum Plus Tegafur-Uracil versus Platinum Alone during Concurrent Chemoradiotherapy in Patients with Nonmetastatic Nasopharyngeal Carcinoma: A Propensity-Score-Matching Analysis.

Simple SummaryThe current guidelines suggest that concurrent chemoradiotherapy (CCRT) with a cisplatin-based regimen is the standard treatment for patients with nonmetastatic NPC. However, little is known regarding the addition of tegafur–uracil (UFUR) to CCRT in patients with NPC. Our study showed that the median RFS was not reached (NR) in the CCRT-UP group, and it was 12.5 months in the CCRT-P group (p < 0.001). The median OS was NR in the CCRT-UP group, and it was 15.9 months in the CCRT-P group (p < 0.001). Grade 3–4 AEs were insignificant between the CCRT-UP and CCRT-P arms. In summary, CCRT-UP had better RFS and OS in nonmetastatic NPC patients with similar toxic profiles.Concurrent chemoradiotherapy (CCRT) with a cisplatin-based regimen is the standard treatment for patients with nasopharyngeal carcinoma (NPC). Our study was a propensity-score-matching analysis and it aimed to investigate the oncologic outcomes of platinum plus tegafur–uracil versus platinum alone during CCRT in patient with nonmetastatic NPC. Patients with pathologic confirmed NPC in 2018–2022 were reviewed. Patients treated with platinum plus tegafur–uracil (CCRT-UP) or platinum alone (CCRT-P) during CCRT were recruited into this study. A propensity-score-matching analysis was conducted to diminish the selection bias. The recurrence-free survival (RFS) and overall survival (OS) were presented with Kaplan–Meier curves. The treatment-related adverse effects (AEs) were recorded according to the National Cancer Institute’s Common Terminology Criteria V3.0. A total of 44 patients with CCRT-UP and 44 patients with CCRT-P were identified after propensity score matching. The median RFS was not reached (NR) in the CCRT-UP group, and it was 12.5 months in the CCRT-P group (p < 0.001). The median OS was NR in the CCRT-UP group, and it was 15.9 months in the CCRT-P group (p < 0.001). The overall response rate and disease-control rate were insignificant between the CCRT-UP and CCRT-P groups. A subgroup analysis showed that the median OS was significantly longer in the CCRT-UP group than in the CCRT-P group, regardless of the clinical stage. A multivariate analysis exhibited that CCRT-UP was independently correlated with survival. The grade 3–4 AEs were insignificant between the CCRT-UP and CCRT-P arms. CCRT-UP had better RFS and OS in nonmetastatic NPC patients with similar toxic profiles. Further larger-scaled prospective randomized control trials are warranted to validate our conclusions.

Prognostic Value of a Serum Panel of Inflammatory Factors in Non-Metastatic Nasopharyngeal Carcinoma Patients Undergoing Radical Radiotherapy with Adjuvant Chemotherapy.

PurposeTo evaluate the prognostic value of interleukin (IL)-6, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), leukemia inhibitory factor (LIF), and macrophage migration inhibitory factor (MIF) in non-metastatic nasopharyngeal carcinoma (NPC) patients undergoing radical radiotherapy.Patients and MethodsA serum panel compromising the inflammatory factors was analyzed in 372 NPC patients before and after radiotherapy. Independent prognostic factors were screened out using multivariate Cox regression analysis. A prediction model was built based on the training set data and validated using the test set data. The prognostic value of these factors was evaluated using the time-dependent receiver operating characteristic (ROC) curve and an integrated time-averaged area under the curve (AUC).ResultsThe baseline levels of IL-6, GM-CSF, and MIF were independent factors associated with poor OS and DMFS. A predictive model base established combining the baseline levels of these factors. The AUC values for the test set were 0.9828, 0.9968, and 0.9571 at 1, 3, and 5 years, respectively, compared to 0.9978, 0.9981, and 0.9222 for the training set, respectively. The AUC values for DMFS at 1, 3, and 5-years for the training set were 0.8744, 0.8951, and 0.9358, respectively, compared to 0.9525, 0.9663, and 0.9625 for the test set, respectively. The combination of post-treatment levels of IL-6, GM-CSF, and LIF also had good predictive value for OS with an AUC value > 0.85 during follow-up.ConclusionIL-6, GM-CSF, and MIF baseline levels are powerful prognostic factors for non-metastatic NPC patients. The combination of these factors effectively predicts OS and DMFS in non-metastatic NPC patients.

Predictors of radiation-induced hypothyroidism in nasopharyngeal carcinoma survivors after intensity-modulated radiotherapy

BackgroundThe aim of the study is to identify clinical and dosimetric factors that could predict the risk of hypothyroidism in nasopharyngeal carcinoma (NPC) patients following intensity-modulated radiotherapy (IMRT).MethodsA total of 404 non-metastatic NPC patients were included in our study. All patients were treated with IMRT. The thyroid function were performed for all patients before and after radiation at regular intervals. The time onset for developing hypothyroidism was defined as the time interval between the completion of RT and the first recorded abnormal thyroid hormone test. The cumulative incidence rates of hypothyroidism were estimated using Kaplan–Meier method. Univariate and multivariate Cox regression analyses were performed to detect the most promising factors that were associated with hypothyroidism.ResultsMedian follow up was 60.6 months. The 3-, 5- and 7- year cumulative incidence rate of hypothyroidism was 39.4%, 49.1% and 54.7%, respectively. The median time to primary hypothyroidism and central hypothyroidism were 15.4 months (range 2.9–83.8 months) and 29.9 months (range 19.8–93.6 months), respectively. Univariate and multivariate analyses revealed that younger age, female gender and small thyroid volume were the most important factors in predicting the risk of hypothyroidism. Dtmean (mean dose of thyroid), V30-V50 (percentage of thyroid volume receiving a certain dose level) and VS45-VS60 (the absolute volumes of thyroid spared from various dose levels) remained statistically significant in multivariate analyses. Cutoff points of 45 Gy (Dtmean), 80% (Vt40) and 5 cm3 (VS45Gy) were identified to classify patients as high-risk or low-risk group.ConclusionThyroid Vt40 highly predicted the risk of hypothyroidism after IMRT for NPC patients. We recommended plan optimization objectives to reduce thyroid Vt40 to 80%.Trial registration: Retrospectively registered.

Long-term outcomes of replanning during intensity-modulated radiation therapy in patients with nasopharyngeal carcinoma: An updated and expanded retrospective analysis

Background and purposeRecent studies show that adaptive replanning for patients with nasopharyngeal carcinoma (NPC) during intensity-modulated radiation therapy (IMRT) improve the short-term local–regional recurrence-free survival (LRFS), and quality of life (QoL). We aimed to assess the long-term survival outcomes and QoL in patients with non-metastatic NPC who received IMRT with replanning compared to those who received IMRT without replanning. Methods and materialsWe conducted an updated and expanded retrospective analysis from an existing prospective cohort for non-metastatic NPC patients undergoing IMRT in our institution. Non-metastatic NPC patients receiving IMRT from June 2007 to December 2015 were consecutively enrolled based on electronic medical record. Patients who were still alive were eligible for the QoL study. The survival outcomes and QoL were compared between patients with and without replanning. ResultsAmong 290 patients, 147 (50.7%) received IMRT without replanning and 143 (49.3%) received IMRT with replanning. Replanning group had a higher 8-year LRFS rate (87.4% vs. 75.6%, P = 0.025). However, 8-year overall survival rate was not statistically significant. Patients with replanning compared to those who without replanning had significant improvements in social functioning (P = 0.016), insomnia (P = 0.048), dry mouth (P = 0.004), and sticky saliva (P = 0.005). Additionally, the score of the role functioning was marginally higher in patients treated with IMRT replanning (P = 0.063). ConclusionThis extended follow-up study demonstrates the long-term security and validity for adaptive radiotherapy in IMRT for non-metastatic NPC patients. We highly recommend that adaptive replanning should be routinely implemented for non-metastatic NPC patients.