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Background: We aimed to assess the value of dose distribution-based dosiomics and planning CT-based radiomics to predict radiation-induced temporal lobe injury (TLI) and guide individualized intensity-modulated radiotherapy.Materials and Methods: A total of 5599 nasopharyngeal carcinoma patients were enrolled, including 2503, 1072, 988, and 1036 patients in the training, validation, prospective test, and external test cohorts, respectively. The concordance index (C-index) was used to compare the performance of the radiomics and dosiomics models with that of the QUANTEC and Wen's models. The predicted TLI-free survival rates of redesigned simulated plans with the same dose-volume histogram but different dose distributions for same patient in a cohort of 30 randomly selected patients were compared by the Wilcoxon matched-pairs signed-rank test.Results: The radiomics and dosiomics signatures were constructed based on 30 selected CT features and 10 selected dose distribution features, respectively, which were important predictors of TLI-free survival (all P<0.001). However, the radiomics signature had a low C-index. The dosiomics risk model combining the dosiomics signature, D1cc, and age had favorable performance, with C-index values of 0.776, 0.811, 0.805, and 0.794 in the training, validation, prospective test, and external test cohorts, respectively, which were better than those of the QUANTEC model and Wen's model (all P<0.001). The dosiomics risk model can further distinguish patients in a same risk category divided by other models (all P<0.05). Conversely, the other models were unable to separate populations classified by the dosiomics risk model (all P>0.05). Two simulated plans with the same dose-volume histogram but different dose distributions had different TLI-free survival rates predicted by dosiomics risk model (all P≤0.002).Conclusion: The dosiomics risk model was superior to traditional models in predicting the risk of TLI. This is a promising approach to precisely predict radiation-induced toxicities and guide individualized intensity-modulated radiotherapy. [ABSTRACT FROM AUTHOR]

Purpose: To compare PET/CT, MRI and ultrasonography in detecting recurrence of nasopharyngeal carcinoma and identify their benefit in staging, contouring and overall survival (OS). Methods: Cohort A included 1453 patients with or without histopathology-confirmed local recurrence, while cohort B consisted of 316 patients with 606 histopathology-confirmed lymph nodes to compare the sensitivities and specificities of PET/CT, MRI and ultrasonography using McNemar test. Cohorts C and D consisted of 273 patients from cohort A and 267 patients from cohort B, respectively, to compare the distribution of PET/CT-based and MRI-based rT-stage and rN-stage and the accuracy of rN-stage using McNemar test. Cohort E included 30 random patients from cohort A to evaluate the changes in contouring with or without PET/CT by related-samples T test or Wilcoxon rank test. The OS of 61 rT3-4N0M0 patients staged by PET/CT plus MRI (cohort F) and 67 MRI-staged rT3-4N0M0 patients (cohort G) who underwent similar salvage treatment were compared by log-rank test and Cox regression. Results: PET/CT had similar specificity to MRI but higher sensitivity (93.9% vs. 79.3%, P < 0.001) in detecting local recurrence. PET/CT, MRI and ultrasonography had comparable specificities, but PET/CT had greater sensitivity than MRI (90.9% vs. 67.6%, P < 0.001) and similar sensitivity to ultrasonography in diagnosing lymph nodes. According to PET/CT, more patients were staged rT3-4 (82.8% vs. 68.1%, P < 0.001) or rN + (89.9% vs. 69.3%, P < 0.001), and the rN-stage was more accurate (90.6% vs. 73.8%, P < 0.001). Accordingly, the contours of local recurrence were more precise (median Dice similarity coefficient 0.41 vs. 0.62, P < 0.001) when aided by PET/CT plus MRI. Patients staged by PET/CT plus MRI had a higher 3-year OS than patients staged by MRI alone (85.5% vs. 60.4%, P = 0.006; adjusted HR = 0.34, P = 0.005). Conclusion: PET/CT more accurately detected and staged recurrence of nasopharyngeal carcinoma and accordingly complemented MRI, providing benefit in contouring and OS. [ABSTRACT FROM AUTHOR]

Background: The aim of this work was to determine whether patients with intermediate-risk head and neck squamous cell carcinoma (HNSCC) can benefit from postoperative chemoradiotherapy (POCRT).Methods: Patients without extracapsular extension (ECE) or positive margins (PMs) who received POCRT or postoperative radiotherapy (PORT) at our center were retrospectively (December 2009 to October 2018) included for analysis, in particular, using a propensity score-matching method.Results: After matching, 264 patients were enrolled, including 142 (41.2%) patients with pT3-4, 136 (38.3%) patients with pN2-3, 68 (21.1%) patients with perineural invasion, and 45 (12.8%) patients with lymphatic/vascular space invasion. With a median follow-up of 52 months, 3-year overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and disease-free survival (DFS) rates were 72.4%, 79.3%, 83.5% and 62.5%, respectively. pN2-3 was an independent risk factor for OS (p < 0.001), DFS (p < 0.001), LRFS (p < 0.001) and DMFS (p = 0.002), while pT3-4 was a poor prognostic factor for DMFS (p = 0.005). Overall, patients receiving POCRT had no significant differences from those receiving PORT in OS (p = 0.062), DFS (p = 0.288), LRFS (p = 0.076) or DMFS (p = 0.692). But notably, patients with pN2-3 achieved better outcomes from POCRT than PORT in 3-year OS (p = 0.050, 63.9% vs. 47.9%) and LRFS (p = 0.019, 74.6% vs. 54.9%). And patients with pT3-4 also had higher 3-year LRFS (p = 0.014, 88.5% vs. 69.1%) if receiving POCRT.Conclusions: Among all intermediate-risk pathological features, pN2-3 and pT3-4 were independent unfavorable prognostic factors for patients with HNSCC without PMs or ECE. POCRT can improve the survival outcomes of patients with pN2-3 or pT3-4. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to validate and compare the 7th and 8th edition of AJCC staging systems for non-metastatic nasopharyngeal carcinoma, and proposed staging systems from Hong Kong, Guangzhou, and Guangxi.Materials and Methods: We retrospectively included 899 patients treated between November 5, 2002 and May 27, 2010. Separation and discrimination of each staging system in overall survival were primarily compared.Results: Compared with the 7th AJCC, the 8th AJCC and all proposed staging systems well separated across T-classification. T-classification from Guangzhou seemed to perform best in discrimination (C-index 0.6454), followed by the 8th AJCC (0.6451), the 7th AJCC (0.6386), Hong Kong (0.6376) and Guangxi (0.5889). For N-classification, no staging systems improved the weakness of the 7th AJCC in separating N2 and N1, except that suggestion from Guangzhou showed higher potential (P=0.096). Besides, N-classification from Guangzhou had a C-index of 0.6444, larger than that of the 8th AJCC (0.6235), the 7th AJCC (0.6179), Hong Kong (0.6175) and Guangxi (0.6175). Accordingly, stage group of staging system from Guangzhou showed higher discrimination (C-index 0.6839), compared with the 8th AJCC (0.6791), the 7th AJCC (0.6766), Hong Kong (0.6765) and Guangxi (0.6688), despite that stage I and II remained inseparable (P=0.322).Conclusions: The 8th AJCC staging system appeared to be better than the 7th AJCC. But the proposed staging system from Guangzhou was more likely to improve the separation and discrimination abilities. [ABSTRACT FROM AUTHOR]

Background: The incidence of diabetes is increasing. But the impact of diabetes and prediabetes on survival of patients with nasopharyngeal carcinoma (NPC) has received little evaluation. Methods: In a cohort of 5,860 patients, we compared the disease specific survival (DSS), locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS) of patients with diabetes, prediabetes and normoglycemia defined by pretreatment fasting plasma glucose (FPG) using Kaplan–Meier method, log-rank test and Cox proportional hazards model. Results: Comparing to normoglycemic patients, the diabetic and the prediabetic were generally older, fatter, had hypertension, heart diseases and hyperlipaemia and usually received radiotherapy alone. But both the diabetic and the prediabetic had similar DSS, LRFS and DMFS to normoglycemic patients, even adjusting for such important factors as age, gender, smoking, drinking, hypertension, heart diseases, body mass index, hyperlipaemia, titer of VCA-IgA and EA-IgA, pathology, T-stage, N-stage, chemotherapy and radiotherapy (P>0.05 for all). Additionally, the findings remained unchanged in sensitivity analysis by excluding patients with known diabetes history and in subgroups of the various factors. Conclusions: The diabetic and prediabetic NPC patients had similar survival to normoglycemic NPC patients. These data, in the largest reported cohort, are the first to evaluate the association between diabetes, prediabetes and the survival in NPC. The findings are relevant to patient management and provided evidence of the effect on this disease exerted by comorbidities. [ABSTRACT FROM AUTHOR]

The impact of combining epidermal growth factor receptor tyrosine kinase inhibitors (EGFR–TKIs) and chemotherapy as first-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) remains controversial. Therefore, randomized trials that compared this combined regimen with chemotherapy or EGFR–TKIs monotherapy were included for this meta-analysis. We used published hazard ratios (HRs), if available, or derived treatment estimates from other survival data. Pooled estimates of treatment efficacy of the combined regimen in the entire unselected population and selected patients by EGFR-mutation status and smoking history were calculated. Eight trials eventually entered into this meta-analysis, including 4585 patients. Overall, the combined regimen significantly delayed disease progression (HR = 0.81, 95% CI 0.69–0.95, P = 0.01); subgroup analysis showed significantly higher progression free survival advantages in Asian patients (P<0.001), with sequential combination of TKIs and chemotherapy (P = 0.02). In selected patients by EGFR-mutation, both mutation positive (HR = 0.48, 95% CI 0.28–0.83, P = 0.009) and negative (HR = 0.84, 95% CI 0.72–0.98, P = 0.02) patients gained progression free survival benefit from the combined regimen, albeit the magnitude of benefit was marginally larger in mutation positive patients (P = 0.05). In selected patients by smoking history, never/light smokers achieved a great progression free survival benefit from the combined regimen (HR = 0.51, 95% CI 0.35–0.74, P = 0.0004). Unfortunately, the combined regimen had no significant impact on overall survival, irrespective of ethnicity, dose schedules or EGFR-mutation status. Severe anorexia (RR = 2.01, 95% CI 1.11–3.63; P = 0.02) and diarrhea (RR = 2.70, 95% CI 1.94–3.76; P<0.001) were more frequent in the combined regimen arm. This strategy of combining EGFR–TKIs and chemotherapy deserved to be considered in the future, although it is not approved for advanced NSCLC at the moment. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate initial hyperleukocytosis and neutrophilia as prognostic indicators in patients with nasopharyngeal carcinoma. Methods: A retrospective analysis of 5,854 patients identified from a cohort of 6,035 patients diagnosed with nasopharyngeal carcinoma was performed with initial hyperleukocytosis and neutrophilia analyzed as prognostic factors. Multivariate Cox proportional hazards analyses were applied. Results: Hyperleukocytosis was observed in 508 patients (8.7%). Multivariate analysis showed that initial hyperleukocytosis was an independent predictor of death (HR 1.40, 95%CI 1.15–1.70, p = 0.001), progression (HR 1.25, 95%CI 1.06–1.47, p = 0.007) and, marginally, distant metastasis (HR 1.21, 95%CI 0.97–1.52, p = 0.088). Neutrophilia was also an independent predictor of death (HR 1.46, 95%CI 1.18–1.81, p = 0.001), progression (HR 1.31, 95%CI 1.10–1.56, p = 0.003), and distant metastasis (HR 1.29, 95%CI 1.02–1.65, p = 0.036), after adjusting for prognostic factors and excluding hyperleukocytosis. Conclusion: Initial hyperleukocytosis and neutrophilia were independent, poor prognostic factors and may be convenient and useful biological markers for survival of patients with nasopharyngeal carcinoma. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to develop and validate radiologic scores from [18F]FDG PET/CT and MRI to guide individualized induction chemotherapy (IC) for patients with T3N1M0 nasopharyngeal carcinoma (NPC). Methods: A total of 542 T3N1M0 patients who underwent pretreatment [18F]FDG PET/CT and MRI were enrolled in the training cohort. A total of 174 patients underwent biopsy of one or more cervical lymph nodes. Failure-free survival (FFS) was the primary endpoint. The radiologic score, which was calculated according to the number of risk factors from the multivariate model, was used for risk stratification. The survival difference of patients undergoing concurrent chemoradiotherapy (CCRT) with or without IC was then compared in risk-stratified subgroups. Another cohort from our prospective clinical trial (N = 353, NCT03003182) was applied for validation. Results: The sensitivity of [18F]FDG PET/CT was better than that of MRI (97.7% vs. 87.1%, p < 0.001) for diagnosing histologically proven metastatic cervical lymph nodes. Radiologic lymph node characteristics were independent risk factors for FFS (all p < 0.05). High-risk patients (n = 329) stratified by radiologic score benefited from IC (5-year FFS: IC + CCRT 83.5% vs. CCRT 70.5%; p = 0.0044), while low-risk patients (n = 213) did not. These results were verified again in the validation cohort. Conclusions: T3N1M0 patients were accurately staged by both [18F]FDG PET/CT and MRI. The radiologic score can correctly identify high-risk patients who can gain additional survival benefit from IC and it can be used to guide individualized treatment of T3N1M0 NPC. Key Points: • [18F]FDG PET/CT was more accurate than MRI in diagnosing histologically proven cervical lymph nodes. • Radiologic lymph node characteristics were reliable independent risk factors for FFS in T3N1M0 nasopharyngeal carcinoma patients. • High-risk patients identified by the radiologic score based on [18F]FDG PET/CT and MRI could benefit from the addition of induction chemotherapy. [ABSTRACT FROM AUTHOR]

Background: To test the advantages of positron emission tomography and computed tomography (PET/CT) for diagnosing lymph nodes and staging nasopharyngeal carcinoma and to investigate its benefits for survival and treatment decisions. Methods: The performance of PET/CT and magnetic resonance imaging (MRI) in diagnosis was compared based on 460 biopsied lymph nodes. Using the propensity matching method, survival differences of T3N1M0 patients with (n = 1093) and without (n = 1377) PET/CT were compared in diverse manners. A radiologic score model was developed and tested in a subset of T3N1M0 patients. Results: PET/CT performed better than MRI with higher sensitivity, accuracy, and area under the receiver operating characteristic curve (96.7% vs. 88.5%, p < 0.001; 88.0% vs. 81.1%, p < 0.001; 0.863 vs. 0.796, p < 0.05) in diagnosing lymph nodes. Accordingly, MRI-staged T3N0-3M0 patients showed nondifferent survival rates, as they were the same T3N1M0 if staged by PET/CT. In addition, patients staged by PET/CT and MRI showed higher survival rates than those staged by MRI alone (p < 0.05), regardless of the Epstein-Barr virus DNA load. Interestingly, SUVmax-N, nodal necrosis, and extranodal extension were highly predictive of survival. The radiologic score model based on these factors performed well in risk stratification with a C-index of 0.72. Finally, induction chemotherapy showed an added benefit (p = 0.006) for the high-risk patients selected by the model but not for those without risk stratification (p = 0.78). Conclusion: PET/CT showed advantages in staging nasopharyngeal carcinoma due to a more accurate diagnosis of lymph nodes and this contributed to a survival benefit. PET/CT combined with MRI provided prognostic factors that could identify high-risk patients and guide individualized treatment. [ABSTRACT FROM AUTHOR]

• Immunochemotherapy plus radiotherapy prolonged the survival of metastatic NPC. • A scoring model could facilitate individualized treatment in the era of immunotherapy. • The toxicities of patients receiving combination therapy were tolerable. To demonstrate whether the benefit of locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma remains in the immunotherapy era and which patients can benefit from radiotherapy. A total of 273 histopathology-confirmed de novo metastatic nasopharyngeal carcinoma was enrolled between May 2017 and October 2021 if receiving immunochemotherapy with or without subsequent intensity-modulated radiotherapy to the nasopharynx and neck. We compared the progression-free survival, overall survival, and safety between the two groups. Additionally, subgroup analysis was conducted and a scoring model was developed to identify suitable patients for radiation. There were 95 (34.8 %) patients with immunochemotherapy alone, and 178 (65.2 %) with immunochemotherapy plus subsequent locoregional radiotherapy. With a median follow-up time of 18 months, patients with immunochemotherapy plus subsequent radiotherapy had higher 1-year progression-free survival (80.6 % vs. 65.1 %, P < 0.001) and overall survival (98.3 % vs. 89.5 %, P = 0.001) than those with immunochemotherapy alone. The benefit was retained in multivariate analysis and propensity score-matched analysis. Mainly, it was more significant in patients with oligometastases, EBV DNA below 20,200 copies/mL, and complete or partial relapse after immunochemotherapy. The combined treatment added grade 3 or 4 anemia and radiotherapy-related toxicities. Immunochemotherapy plus subsequent locoregional radiotherapy prolonged the survival of de novo metastatic nasopharyngeal carcinoma with tolerable toxicities. A scoring model based on oligometastases, EBV DNA level, and response after immunochemotherapy could facilitate individualized management. [ABSTRACT FROM AUTHOR]

Objectives: To analyze the correlation between dose-volume-histograms (DVHs) with three patterns (edema, enhancement, and necrosis) of temporal lobe injury (TLI) in patients receiving intensity modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC) and to determine optimal thresholds to predict the incidence of each TLI pattern, with particular emphasis on the relationship between edema volume and the risk of enhancement and necrosis.Materials and Methods: A cohort of 4186 NPC patients treated with IMRT was retrospectively reviewed with TLI presenting in 188 patients. The atlases of complication incidence (ACI) for each pattern were constructed using DVH curves of temporal lobes. Optimal threshold for predicting incidence of each pattern was determined using the point closest to top-left of the plot. The accuracy of using edema volume to predict enhancement and necrosis incidence was evaluated via area under curve (AUC) of receiver operator characteristics (ROC).Results: All DVH parameters, Dmean, Dmax, D0.25cc, D0.5cc, D1cc, D3cc, D6cc, V20Gy, V30Gy, V40Gy, V50Gy, V60Gy, and V70Gy, except Dmin showed statistically significant differences between subgroups of each pattern (p < 0.05). For predicting incidence of each pattern, optimal DVH thresholds over the range of D0.25-D1cc, Dmean and V20-V70 were derived. The optimal thresholds of edema volume for predicting enhancement were 0.96 and 2.2cc and for predicting necrosis were 0.94 and 11.5cc.Conclusion: Optimal DVH thresholds were generated for limiting risk of each injury pattern. Edema volume was a strong predictor for risk of enhancement and necrosis, which could potentially be reduced by lowering edema volume below threshold. [ABSTRACT FROM AUTHOR]

Objectives: We have attempted to validate two published nomograms in nasopharyngeal carcinoma (NPC) and individualize induction chemotherapy (IC) accordingly.Materials and Methods: From 2007 to 2011, 920 patients were included in the study. The validity of the nomograms was assessed by Harrell's concordance index (C-index), areas under the curve (AUC), and calibration curves. Disease-free survival (DFS) and overall survival (OS) by IC were evaluated in and out of risk stratified patients with and without propensity score matching analysis.Results: Compared with the 7th edition of the Union for International Cancer Control (UICC) staging system, Tang's nomogram better discriminated DFS (C-index 0.629 versus 0.569, P=0.002; AUC 0.635 versus 0.576, P=0.018), whereas Yang's nomogram had no advantage in predicting OS (C-index 0.648 versus 0.606, P=0.184; AUC 0.643 versus 0.604, P=0.157). Calibration curves indicated good agreement between predicted and observed DFS or OS probability. Without risk stratification, patients achieved no benefit from IC in DFS (P⩾0.101) or OS (P⩾0.370). However, among 580 high-risk patients stratified by Tang's nomogram, IC improved five-year DFS from 68.8 to 74.8% (P=0.072), and OS from 82.6 to 87.9% (P=0.065), and the improvement of DFS and OS increased to 9.3% (P=0.019) and 7.3% (P=0.036), respectively, in 426 propensity-matched patients.Conclusions: Tang's nomogram helps to stratify stage III-IVa-b NPC, and IC is beneficial to high-risk patients in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: The value of adding induction chemotherapy to chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) remains controversial, yet high-risk patients with LA-NPC have poor outcomes after chemoradiotherapy. We aimed to assess the survival benefits of induction chemotherapy in stage IVa-b NPC. Patients and Methods: A total of 602 patients with stage IVa-b NPC treated with intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy with or without induction chemotherapy were retrospectively analyzed. Overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method, log-rank test and Cox regression analysis. Results: In univariate analysis, 5-year OS was 83.2% for induction chemotherapy plus concurrent chemotherapy and 74.8% for concurrent chemotherapy alone, corresponding to an absolute risk reduction of 8.4% (P = 0.022). Compared to concurrent chemotherapy alone, addition of induction chemotherapy improved 5-year DMFS (83.2% vs. 74.4%, P = 0.018) but not 5-year LRFS (83.7% vs. 83.0%, P = 0.848) or PFS (71.9% vs. 66.0%, P = 0.12). Age, T category, N category, chemotherapy strategy and clinical stage were associated with 5-year OS (P = 0.017, P = 0.031, P = 0.007, P = 0.022, P = 0.001, respectively). In multivariate analysis, induction chemotherapy plus concurrent chemotherapy was an independent favorable prognostic factor for OS (HR, 0.62; 95% CI, 0.43–0.90, P = 0.012) and DMFS (HR, 0.57; 95% CI, 0.38–0.83, P = 0.004). In subgroup analysis, induction chemotherapy significantly improved 5-year DMFS in stage IVa (86.8% vs. 77.3%, P = 0.008), but provided no significant benefit in stage IVb. Conclusions: In patients with stage IVa-b NPC treated with IMRT, addition of induction chemotherapy to concurrent chemotherapy significantly improved 5-year OS and 5-year DMFS. This study provides a basis for selection of high risk patients in future clinical therapeutic trials. [ABSTRACT FROM AUTHOR]

Objectives: The effect of taxanes-based induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) was quite contradictory in two phase II randomized controlled trials with small sample size. We aimed to investigate it in this large scale propensity-matched study.Materials and Methods: Totally, 779 LA-NPC patients who underwent intensity-modulated radiotherapy (IMRT) plus concurrent chemotherapy with or without taxanes-based IC were included. Patients in both treatment arms were matched using propensity score matching method at the ratio of 1:1. Failure-free survival (FFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRFS) were assessed with Kaplan-Meier method, log-rank test and Cox regression analysis.Results: After matching, 534 patients were identified for analysis. In univariate analysis, both treatment arms resulted in parallel survival (4-years FFS 78.0% vs 74.1%, P = 0.304; OS 87.5% vs 87.3%, P = 0.595; DMFS 88.2% vs 84.4%, P = 0.154; and LRFS 91.2% vs 90.1%, P = 0.960). In multivariate analysis, taxanes-based IC did not improve any survival (P ⩾ 0.139). And this association remained unchanged in subgroup analysis by age, sex and histology, and among patients with stage III and T4N0M0. But among patients with T4N1-2M0 and stage IVb, taxanes-based IC significantly prolonged the 4-year DMFS by 11.2% (86.1% vs 74.9%, P = 0.034), and marginally improved FFS (P = 0.133) and OS (P = 0.215) in both univariate and multivariate analysis.Conclusions: In this large scale propensity-matched study, LA-NPC patients could not benefit from taxanes-based IC on the whole. But the risk of distant metastasis significantly decreased by above 10% for patients with T4N1-2M0 and stage IVb. [ABSTRACT FROM AUTHOR]