Non-metastatic Non-metastatic Nasopharyngeal Carcinoma 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.

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.

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.

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.

Low prognostic nutritional index is associated with poor outcome in middle-aged and elderly patients with non-metastatic nasopharyngeal carcinoma: a retrospective cohort study.

Prognostic nutritional index (PNI) and age are effective prognostic factors for patients with non-metastatic nasopharyngeal carcinoma (NPC), and an interaction between them may exist. However, the age cutoff value is generally set at 45years in current studies. The clinical implications of PNI in middle-aged and elderly patients are unclear. Therefore, we aimed to uncover this issue. We retrospectively collected data from 132 middle-aged and elderly (≥ 45years old) patients with non-metastatic NPC. The association between covariates and the PNI was analyzed using 2 or t-test. The effect of PNI on the prognosis was evaluated using univariate and multivariate Cox regression analyses. Unadjusted and multivariate-adjusted models were applied. Stratified and interactive analyses were performed to investigate the potential source of heterogeneity. Median age (61.0years versus 59.5years) and the proportion of patients aged ≥ 60years (57.6% versus 50.0%) in the low-PNI group were higher than those in the high-PNI group (P > 0.05). The patients with a low PNI had shorter overall survival (OS) (hazard ratio (HR) = 0.86, 95% confidence interval (CI) = 0.80-0.93; P < 0.001) and progression-free survival (PFS) (HR = 0.93, 95% CI = 0.87-0.99; P = 0.034). The results remained stable after three adjusted models of covariates, including age (P < 0.05). No significant interactions were observed in middle-aged (45-59years) and elderly (≥ 60years) subgroups for OS and PFS (P for interaction > 0.05). Although there is an interaction between PNI and age, PNI is an independent prognostic factor in middle-aged and elderly patients with non-metastatic NPC.

Institutionally validated nomogram predicting prognosis for older patients with nonmetastatic nasopharyngeal carcinoma.

Aim: Older adult patients with nonmetastatic nasopharyngeal carcinoma (NPC) have poor outcomes relative to younger patients. The authors' groupestablished a nomogram to predict the overall survival of older adults with NPC and inform patient management. Methods: Cases with NPC (n=782) were enrolled in this study; clinical data in the Surveillance, Epidemiology, and End Results database from 2010 to 2015 served as the training cohort (n=657), and patients from Jiangxi Cancer Hospital (n=125) served as the external validation cohort. Results: Training and external validation cohort C-index, receiver operator characteristicscurves and calibration curves showed that our nomogram has great predictive ability. Conclusions: Compared with tumor-node-metastasis staging, this nomogram can help clinicians better predict the prognosis of older adults with nonmetastatic NPC.

Pretreatment systemic immune-inflammation index predicts survival for non-metastatic nasopharyngeal carcinoma: two independent institutional studies

ObjectiveThis study aimed to evaluate the prognostic value of the pretreatment systemic immune-inflammation index (SII) in non-metastatic nasopharyngeal carcinoma (NPC). MethodsWe retrospectively analyzed the data of 839 patients with non-metastatic NPC recruited from two independent institutions. The training-set cohort and the external validation-set cohort was comprised of 459 and 380 patients from each institution, respectively. The optimal cut-off value of SII was determined, and a prognostic risk stratification model was developed based on the training cohort and further assessed in the validation cohort. The propensity score matching (PSM) method was applied to minimize the confounding effects of unbalanced covariables. ResultsThe optimal cut-off value of the SII in the training cohort was 686, which was confirmed using the validation cohort. Multivariate analysis showed that both before and after PSM, SII values > 686 were independently associated with worse progression-free survival (PFS) ratio in both cohorts (before PSM, P = 0.008 and P = 0.008; after PSM, P = 0.008 and P = 0.007, respectively). Based on the analysis of independent prognostic factors of SII and N stage, we developed a categorical risk stratification model, which achieved significant discrimination among risk indexes associated with PFS and distant metastasis-free survival (DMFS) in the training cohort. There was no significant difference in PFS between RT alone and combined therapies within the low- and intermediate-risk groups (5-year PFS, 77.5% vs. 75.3%, P = 0.275). Patients in the high-risk group who received concurrent chemoradiotherapy experienced superior PFS compared with those who received other therapies (5-year PFS, 64.9% vs. 40.3%, P = 0.003). ConclusionPretreatment SII predicts PFS of patients with non-metastatic NPC. Prognostic risk stratification incorporating SII is instructive for selecting individualized treatment.

Assessment of Survival Model Performance Following Inclusion of Epstein-Barr Virus DNA Status in Conventional TNM Staging Groups in Epstein-Barr Virus–Related Nasopharyngeal Carcinoma

Nonanatomic prognostic factors complement the traditional anatomic staging system and could be incorporated into the tumor-node-metastasis (TNM) framework. Several diseases have incorporated nonanatomic prognostic factors into the determination of TNM staging groups. To refine TNM staging groups for Epstein-Barr virus (EBV)-related nonmetastatic nasopharyngeal carcinoma (NPC) by incorporating EBV DNA status. This multicenter prognostic study included patients with NPC treated with radiotherapy at 2 hospitals in China from January 2008 to December 2016. Progression-free survival and overall survival according to EBV DNA status and the TNM staging system were compared. Recursive partitioning analysis (RPA) combined with supervised clustering was applied to derive prognostic groupings, and then a refined RPA staging schema was developed, validated, and compared with existing staging schemes. Statistical analyses were conducted from October 1, 2020, to June 15, 2021. Curative intensity-modulated radiotherapy with or without platinum-based chemotherapy. The primary end point was progression-free survival. The performance of the staging system was assessed using the time-dependent area under the receiver operating characteristic curves and the TNM stage system's evaluation methodology. A total of 2354 patients (1709 men [72.6%]; median [interquartile range] age, 45 [38-53] years) were split into training (1372 [58.3%]), internal validation (672 [28.5%]), and external validation (310 [13.2%]) cohorts. Pretreatment EBV DNA was detected in 1338 (56.8%) patients. EBV DNA status was an independent prognostic factor: lower survival probability by higher TNM stage was evident in EBV DNA-positive patients but not in those with EBV DNA-negative disease. After integrating EBV DNA status and TNM stage, nonmetastatic NPC cases were categorized into RPA-I (T1-3N0 or EBV DNA-negative T1-3N1 cancers), RPA-II (EBV DNA-positive T1-3N1-2 or EBV DNA-negative T1-3N2-3/T4N0-3 cancers), and RPA-III (EBV DNA-positive T4N0-3/T1-3N3 cancers) groups, each with distinctly different prognosis. This system of RPA staging outperformed the current TNM stage system and 2 reported RPA staging schemes. These results were internally and externally validated. An RPA-based staging system for EBV-related NPC cases was associated with improved outcomes. This staging system may facilitate prognostic stratification and clinical trial designs.

Cutoff point of neutrophil-to-lymphocyte ratio for predicting survival in nasopharyngeal carcinoma.

Neutrophil-to-lymphocyte ratio (NLR) was reported as an independent prognostic factor in many studies, but its cutoff point was not yet concluded. We set forth to prove and validate cutoff point of NLR as a poor prognostic factor for overall survival (OS) in nonmetastatic nasopharyngeal carcinoma (NPC) patients.Retrospective cohort of nonmetastatic NPC adult patients treated with intensity-modulated radiotherapy with curative aim at Siriraj hospital during 2007 to 2014 was enrolled. NLR was defined as absolute neutrophil count divided by absolute lymphocyte count. OS was the primary outcome. We explored our cutoff value by maximum concordance index (C-index) method, and we validated our cutoff and previously reported cutoff values by categorizing patients as NLR ≤ 3 or >3. Internal validation was done by bootstrapping method.Four hundred sixty-three patients were included. The median follow-up time was 70.8 months. By the end of June 2019, 211 patients had died. In univariable analysis of OS by Cox model, an NLR value of 3 showed the highest C-index (0.548) with an HR of 1.43 (95% CI: 1.08–1.89). After adjustment for body mass index, overall staging, age, gender, and histology in multivariable analysis, an NLR >3 was still an independent prognostic factor of poor OS (HR = 1.34, 95% CI = 1.01–1.79). After internal validation, the resampling method shows no overfitting condition and corrected C-index was 0.547 for univariable analysis.A cutoff point of NLR of 3 from routine blood test was found to be an independent poor prognostic factor among patients with nonmetastatic NPC. This prognostic factor could be included in clinical prediction model of NPC and this further prediction model would select high risk patients for intensive treatment.

Toxicity Profiles and Survival Outcomes Among Patients With Nonmetastatic Nasopharyngeal Carcinoma Treated With Intensity-Modulated Proton Therapy vs Intensity-Modulated Radiation Therapy

Patients with nonmetastatic nasopharyngeal carcinoma (NPC) are primarily treated by radiotherapy with curative intent with or without chemotherapy and often experience substantial treatment-related toxic effects even with modern radiation techniques, such as intensity-modulated radiation therapy (IMRT). Intensity-modulated proton therapy (IMPT) may improve the toxicity profile; however, there is a paucity of data given the limited availability of IMPT in regions with endemic NPC. To compare toxic effects and oncologic outcomes among patients with newly diagnosed nonmetastatic NPC when treated with IMPT vs IMRT with or without chemotherapy. This retrospective cohort study included 77 patients with newly diagnosed nonmetastatic NPC who received curative-intent radiotherapy with IMPT or IMRT at a tertiary academic cancer center from January 1, 2016, to December 31, 2019. Forty-eight patients with Epstein-Barr virus (EBV)-positive tumors were included in a 1:1 propensity score-matched analysis for survival outcomes. The end of the follow-up period was March 31, 2021. IMPT vs IMRT with or without chemotherapy. The main outcomes were the incidence of acute and chronic treatment-related adverse events (AEs) and oncologic outcomes, including locoregional failure-free survival (LRFS), progression-free survival (PFS), and overall survival (OS). We identified 77 patients (25 [32.5%] women; 52 [67.5%] men; median [interquartile range] age, 48.7 [42.2-60.3] years), among whom 28 (36.4%) were treated with IMPT and 49 (63.6%) were treated with IMRT. Median (interquartile range) follow-up was 30.3 (17.9-41.5) months. On multivariable logistic regression analyses, IMPT was associated with lower likelihood of developing grade 2 or higher acute AEs compared with IMRT (odds ratio [OR], 0.15; 95% CI, 0.03-0.60; P = .01). Only 1 case (3.8%) of a chronic grade 3 or higher AE occurred in the IMPT group compared with 8 cases (16.3%) in the IMRT group (OR, 0.21; 95% CI, 0.01-1.21; P = .15). Propensity score matching generated a balanced cohort of 48 patients (24 IMPT vs 24 IMRT) and found similar PFS in the IMPT and IMRT groups (2-year PFS, 95.7% [95% CI, 87.7%-100%] vs 76.7% [95% CI, 60.7%-97.0%]; hazard ratio [HR], 0.31; 95% CI, 0.07-1.47; P = .14). No locoregional recurrence or death was observed in the IMPT group from the matched cohort. Two-year LRFS was 100% (95% CI, 100%-100%) in the IMPT group and 86.2% (95% CI, 72.8%-100%) in the IMRT group (P = .08). Three-year OS was 100% (95% CI, 100%-100%) in the IMPT group and 94.1% (95% CI, 83.6%-100%) in the IMRT group (P = .42). Smoking history was the only clinical factor significantly associated with both poor LRFS (HR, 63.37; 95% CI, 3.25-1236.13; P = .006) and poor PFS (HR, 6.33; 95% CI, 1.16-34.57; P = .03) on multivariable analyses. In this study, curative-intent radiotherapy with IMPT for nonmetastatic NPC was associated with significantly reduced acute toxicity burden in comparison with IMRT, with rare late complications and excellent oncologic outcomes, including 100% locoregional control at 2 years. Prospective trials are warranted to direct the optimal patient selection for IMPT as the primary radiotherapy modality for nonmetastatic NPC.

Prognostic Value of the Albumin-to-Alkaline Phosphatase Ratio before Chemoradiotherapy in Patients with Nonmetastatic Nasopharyngeal Carcinoma

Introduction: The aim of this study was to evaluate the prognostic value of the albumin-to-alkaline phosphatase ratio (AAPR) in patients with nonmetastatic nasopharyngeal carcinoma (NPC). Methods: Patients with nonmetastatic NPC who underwent chemoradiotherapy (CRT) were retrospectively analyzed. The AAPR was calculated using the last value of albumin to alkaline phosphatase that was measured within 1 week before CRT. The optimal cutoff value for the AAPR value was determined by an X-tile plot. Propensity score matching (PSM) was performed to balance the differences of the baseline characteristics. The Kaplan-Meier method and log-rank test were used to calculate the survival. A Cox proportional hazards regression model was conducted for the multivariate analysis. Results: Totally, 87 patients with nonmetastatic NPC who underwent CRT were included in the analysis. The optimal cutoff level for the AAPR was 0.46. The group with an AAPR ≤0.46 was more likely to have poorer overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) (p = 0.023, p = 0.031 and p = 0.027, for OS, PFS, and DMFS, respectively). In Cox proportional hazards analysis, high AAPR was a better prognostic predictor. Conclusion: AAPR may be a reliable prognostic index for nonmetastatic NPC patients.

Development and Validation of Web-Based Nomograms to Precisely Predict Survival Outcomes of Non-metastatic Nasopharyngeal Carcinoma in an Endemic Area.

PurposeThis study aimed to develop web-based nomograms to precisely predict survival outcomes in patients with non-metastatic nasopharyngeal carcinoma (NPC) in an endemic area.Materials and MethodsA total of 10,126 patients who underwent radical intensity-modulated radiotherapy at Sun Yat-sen University Cancer Center (SYSUCC) from 2009 to 2015 were analyzed. We assigned patients into a training cohort (SYSUCC-A, n=6,751) and an internal validation cohort (SYSUCC-B, n=3,375) based on computer-generated random numbers. Patients collected from Wuzhou Red Cross Hospital (WZRCH) between 2012 and 2015 were used as the independent external validation cohort (WZRCH, n=450). Concordance index (C-index) was used to determine predictive accuracy and discriminative ability for the nomogram. The web-based clinicopathologic prediction models for predicting survival were based on Cox regression.ResultsThe C-indexes for SYSUCC-A, SYSUCC-B, and WZRCH cohorts for the established nomograms to predict 3-year overall survival (OS) was 0.736, 0.715, and 0.691. Additionally, C-indexes to predict 3-year distant metastasis-free survival (DMFS) was 0.717, 0.706, and 0.686, disease-free survival (DFS) was 0.713, 0.697, and 0.656, local relapse-free survival was 0.695, 0.684, and 0.652, and regional relapse-free survival was 0.672, 0.650, and 0.616. The calibration plots showed great agreement between nomogram-predicted 3-year survival outcomes and actual 3-year survival outcomes. Moreover, C-indexes of the nomograms for OS, DMFS, and DFS were significantly superior than TNM stage (p < 0.001 for all).ConclusionThese user-friendly nomograms can precisely predict survival endpoints in patients with non-metastatic NPC. They may serve as a useful tool for providing patient counseling and help physicians to make individual follow-up plans.

Optimal cumulative dose of cisplatin for concurrent chemoradiotherapy among patients with non-metastatic nasopharyngeal carcinoma: a multicenter analysis in Thailand

BackgroundChemoradiotherapy (CRT) with high cumulative doses (CDs) of cisplatin has been considered the standard of care for non-metastatic nasopharyngeal carcinoma (NPC). However, given most patients’ inability to tolerate high CDs due to cisplatin-related toxicities, the optimal CD of cisplatin during CRT remains undetermined.MethodsPatients with non-metastatic NPC who received CRT with cisplatin between 2007 and 2017 were identified through the Thai head and neck cancer multicenter database and then categorized according to cisplatin CD (mg/m2) received. All complications and cisplatin-related toxicities during CRT were recorded.ResultsWe identified 779 non-metastatic NPC patients receiving low (≤150; n = 97), intermediate (151–250; n = 411), and high (> 250; n = 271) CDs of cisplatin. Low CD patients had significantly lower mean actual radiation dose (p < 0.001) and more radiotherapy delay (p = 0.010), while intermediate CD patients had the least hospitalization (p < 0.001). Overall, 39.3% of the patients experienced cisplatin-related toxicity, which was associated with poor overall survival (OS) (p = 0.001). Acute kidney injury was observed in 7% in all patients, which was highest among low CD patients (15.5%; p = 0.002). Intermediate CD patients had significantly longer median OS than the low and high groups (64 vs. 49.8 vs. 53.2, respectively; p = 0.015). Univariate, but not multivariate, analysis showed that CD of cisplatin was significantly associated with OS.ConclusionCD of cisplatin during CRT was not an independent prognostic factor for OS. An intermediate CD induced minimal toxicity without compromising survival and should be considered the optimal CD. Nonetheless, a randomized phase 3 study evaluating the optimal CD of cisplatin is warranted.

Predicting Progression-Free Survival Using MRI-Based Radiomics for Patients With Nonmetastatic Nasopharyngeal Carcinoma.

Objectives: This study aimed to explore the predictive value of MRI-based radiomic model for progression-free survival (PFS) in nonmetastatic nasopharyngeal carcinoma (NPC).Methods: A total of 327 nonmetastatic NPC patients [training cohort (n = 230) and validation cohort (n = 97)] were enrolled. The clinical and MRI data were collected. The least absolute shrinkage selection operator (LASSO) and recursive feature elimination (RFE) were used to select radiomic features. Five models [Model 1: clinical data, Model 2: overall stage, Model 3: radiomics, Model 4: radiomics + overall stage, Model 5: radiomics + overall stage + Epstein–Barr virus (EBV) DNA] were constructed. The prognostic performances of these models were evaluated by Harrell's concordance index (C-index). The Kaplan–Meier method was applied for the survival analysis.Results: Model 5 incorporating radiomics, overall stage, and EBV DNA yielded the highest C-indices for predicting PFS in comparison with Model 1, Model 2, Model 3, and Model 4 (training cohorts: 0.805 vs. 0.766 vs. 0.749 vs. 0.641 vs. 0.563, validation cohorts: 0.874 vs. 0.839 vs. 836 vs. 0.689 vs. 0.456). The survival curve showed that the high-risk group yielded a lower PFS than the low-risk group.Conclusions: The model incorporating radiomics, overall stage, and EBV DNA showed better performance for predicting PFS in nonmetastatic NPC patients.

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

Previous studies demonstrated that the radiation therapy, image technology, and the application of chemotherapy have developed in the last 2 decades. This study explored the survival trends and treatment failure patterns of patients with nonmetastatic nasopharyngeal carcinoma (NPC) treated with radiation therapy. Furthermore, we evaluated the survival benefit brought by the development of radiation therapy, image technology, and chemotherapy based on a large cohort from 1990 to2012. Data from 20,305 patients with nonmetastatic NPC treated between 1990 and 2012 were analyzed. Patients were divided into 4 calendar periods (1990-1996, 1997-2002, 2003-2007, and 2008-2012). Overall survival (OS) was the primary endpoint. Magnetic resonance imaging has replaced computed tomography as the most important imaging technique since 2003. Conventional 2-dimensional radiation therapy, which was the main radiation therapy technique in our institution before 2008, was replaced by intensity modulated radiation therapy later. An increasing number of patients have undergone chemotherapy since 2003. The 5-year OS across the 4 calendar periods increased at each TNM stage with progression-free survival (PFS) and locoregional relapse-free survival (LRFS) showing a similar trend, whereas distant metastasis-free survival showed small differences. Multivariate analyses showed that the application of intensity modulated radiation therapy and magnetic resonance imaging were independent protective factors in OS, PFS, LRFS, and distant metastasis-free survival. Chemotherapy benefited patients in OS, PFS, and LRFS. The main pattern of treatment failure shifted from recurrence to distant metastasis. The development of radiation therapy, image technology, and chemotherapy increased survival rates among patients with NPC because of excellent locoregional control. Distant failure has become the greatest challenge for NPC treatment.

Radiomics Model to Predict Early Progression of Nonmetastatic Nasopharyngeal Carcinoma after Intensity Modulation Radiation Therapy: A Multicenter Study.

To examine the prognostic value of a machine learning model trained with pretreatment MRI radiomic features in the assessment of patients with nonmetastatic nasopharyngeal carcinoma (NPC) who are at risk for 3-year disease progression after intensity-modulated radiation therapy and to explain the radiomics features in the model. A total of 277 patients with nonmetastatic NPC admitted between March 2008 and December 2014 at two imaging centers were retrospectively reviewed. Patients were allocated to a discovery or validation cohort based on where they underwent MRI (discovery cohort, n = 217; validation cohort, n = 60). A total of 525 radiomics features extracted from contrast material-enhanced T1- or T2-weighted MRI studies and five clinical features were subjected to radiomic machine learning modeling to predict 3-year disease progression. Feature selection was performed by analyzing robustness to resampling, reproducibility between observers, and redundancy. Features for the final model were selected with Kaplan-Meier analysis and the log-rank test. A support vector machine was used as the classifier for the model. To interpret the pattern learned from the model, Shapley additive explanations (SHAP) was applied. The final model yielded an area under the receiver operating characteristic curve of 0.80 in both the discovery (95% bootstrap confidence interval: 0.80, 0.81) and independent validation (95% bootstrap confidence interval: 0.73, 0.89) cohorts. Analysis with SHAP revealed that tumor shape sphericity, first-order mean absolute deviation, T stage, and overall stage were important factors in 3-year disease progression. These results add to the growing evidence of the role of radiomics in the assessment of NPC. By using explanatory techniques, such as SHAP, the complex interaction of features learned by the model may be understood.© RSNA, 2019Supplemental material is available for this article.

Radiomics on multi-modalities MR sequences can subtype patients with non-metastatic nasopharyngeal carcinoma (NPC) into distinct survival subgroups.

To explore and evaluate the feasibility of radiomics in stratifying nasopharyngeal carcinoma (NPC) into distinct survival subgroups through multi-modalities MRI. A total of 658 patients (training cohort: 424; validation cohort: 234) with non-metastatic NPC were enrolled in the retrospective analysis. Each slice was considered as a sample and 4863 radiomics features on the tumor region were extracted from T1-weighted, T2-weighted, and contrast-enhanced T1-weighted MRI. Consensus clustering and manual aggregation were performed on the training cohort to generate a baseline model and classification reference used to train a support vector machine classifier. The risk of each patient was defined as the maximum risk among the slices. Each patient in the validation cohort was assigned to the risk model using the trained classifier. Harrell's concordance index (C-index) was used to measure the prognosis performance, and differences between subgroups were compared using the log-rank test. The training cohort was clustered into four groups with distinct survival patterns. Each patient was assigned to one of the four groups according to the estimated risk. Our method gave a performance (C-index = 0.827, p< .004 and C-index = 0.814, p< .002) better than the T-stage (C-index = 0.815, p= .002 and C-index = 0.803, p= .024), competitive to and more stable than the TNM staging system (C-index = 0.842, p= .003 and C-index = 0.765, p= .050) in the training cohort and the validation cohort. Through investigating a large one-institutional cohort, the quantitative multi-modalities MRI image phenotypes reveal distinct survival subtypes. • Radiomics phenotype of MRI revealed the subtype of nasopharyngeal carcinoma (NPC) patients with distinct survival patterns. • The slice-wise analysis method on MRI helps to stratify patients and provides superior prognostic performance over the TNM staging method. • Risk estimation using the highest risk among slices performed better than using the majority risk in prognosis.

The Prognostic Value of Albumin-to-Alkaline Phosphatase Ratio before Radical Radiotherapy in Patients with Non-metastatic Nasopharyngeal Carcinoma: A Propensity Score Matching Analysis.

PurposeWe first analyzed the prognostic power of albumin-to-alkaline phosphatase ratio (AAPR) before radical radiotherapy (RT) in non-metastatic nasopharyngeal carcinoma (NPC) patients.Materials and MethodsThe records of 170 patients with biopsy-proven, non-metastatic NPC treated by radical RT between 1998 and 2016 at our institution were retrospectively reviewed. Median follow-up duration was 50.6 months. All patients received intensity-modulated RT and cisplatin based chemotherapy before, during, or after RT. The major treatment of patients was based on concurrent chemoradiotherapy (92.4%). The AAPR was calculated by the last value of both albumin and alkaline phosphatase within 1 month immediately preceding RT. The optimal cut-off level of AAPR was determined by using Cutoff Finder, a web-based system. Propensity score matching (PSM) analysis was performed.ResultsThe optimal cut-off level of AAPR was 0.4876. After PSM analysis of whole cohort, an AAPR was not related to survival outcomes. In PSM analysis for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC), an AAPR ≥ 0.4876 was related to better overall survival (OS), progression-free survival (PFS), and locoregional relapse–free survival (LRRFS) (OS: hazard ratio [HR], 0.341; 95% confidence interval [CI], 0.144 to 0.805; p=0.014; PFS: HR, 0.416; 95% CI, 0.189 to 0.914; p=0.029; and LRRFS: HR, 0.243; 95% CI, 0.077 to 0.769; p=0.016, respectively).ConclusionThe AAPR, inexpensive and readily derived from a routine blood test, could be an independent prognostic factor for patients with LA-NPC. And it might help physicians determine treatment plans by identifying the patient's current status. Future prospective clinical trials to validate its prognostic value are needed.

Symptomatic venous thromboembolism associated with peripherally inserted central catheters predicts a worse survival in nasopharyngeal carcinoma: results of a large cohort, propensity score\u2013matched analysis

BackgroundDespite increasing use, symptomatic venous thromboembolism (VTE) associated with peripherally inserted central catheter (PICC) is a common complication in nonmetastatic nasopharyngeal carcinoma (NPC) patients.MethodsA total of 3012 nonmetastatic NPC patients were enrolled in this retrospective study, and we applied Cox regression and log-rank tests to assess the association between PICC-VTE and survival using the propensity score method (PSM) to adjust for gender, age, radiotherapy technique, tumor stage, node stage, UICC clinical stage and pre-treatment EBV DNA.Results217 patients developed PICC-VTE, with an incidence of 7.20%. PSM identified 213 patients in the cohort with VTE and 852 in that without. Patients who developed PICC-VTE had a shorter 5-year PFS (77.5% vs 87.6%, p < 0.001), DMFS (85.0% vs 91.2%, p < 0.001), LRRFS (93.9% vs 97.7%, p < 0.001) and OS (85.4% vs 87.6%, p < 0.001). Subgroup analyses indicated that no significant survival difference was found between PICC-related superficial venous thrombosis and deep vein thrombosis, nor did different anticoagulant treatment methods.ConclusionsPICC-VTE was associated with a worse survival outcome in nonmetastatic NPC patients. A prospective randomized clinical trial is required to verify the results.