Radiomics-based nomogram guides adaptive de-intensification in locoregionally advanced nasopharyngeal carcinoma following induction chemotherapy.

OBJECTIVES: This study aimed to construct a radiomics-based model for prognosis and benefit prediction of concurrent chemoradiotherapy (CCRT) versus intensity-modulated radiotherapy (IMRT) in locoregionally advanced nasopharyngeal carcinoma (LANPC) following induction chemotherapy (IC). MATERIALS AND METHODS: A cohort of 718 LANPC patients treated with IC + IMRT or IC + CCRT were retrospectively enrolled and assigned to a training set (n = 503) and a validation set (n = 215). Radiomic features were extracted from pre-IC and post-IC MRI. After feature selection, a delta-radiomics signature was built with LASSO-Cox regression. A nomogram incorporating independent clinical indicators and the delta-radiomics signature was then developed and evaluated for calibration and discrimination. Risk stratification by the nomogram was evaluated with Kaplan-Meier methods. RESULTS: The delta-radiomics signature, which comprised 19 selected features, was independently associated with prognosis. The nomogram, composed of the delta-radiomics signature, age, T category, N category, treatment, and pre-treatment EBV DNA, showed great calibration and discrimination with an area under the receiver operator characteristic curve of 0.80 (95% CI 0.75-0.85) and 0.75 (95% CI 0.64-0.85) in the training and validation sets. Risk stratification by the nomogram, excluding the treatment factor, resulted in two groups with distinct overall survival. Significantly better outcomes were observed in the high-risk patients with IC + CCRT compared to those with IC + IMRT, while comparable outcomes between IC + IMRT and IC + CCRT were shown for low-risk patients. CONCLUSION: The radiomics-based nomogram can predict prognosis and survival benefits from concurrent chemotherapy for LANPC following IC. Low-risk patients determined by the nomogram may be potential candidates for omitting concurrent chemotherapy during IMRT. CLINICAL RELEVANCE STATEMENT: The radiomics-based nomogram was constructed for risk stratification and patient selection. It can help guide clinical decision-making for patients with locoregionally advanced nasopharyngeal carcinoma following induction chemotherapy, and avoid unnecessary toxicity caused by overtreatment. KEY POINTS: • The benefits from concurrent chemotherapy remained controversial for locoregionally advanced nasopharyngeal carcinoma following induction chemotherapy. • Radiomics-based nomogram achieved prognosis and benefits prediction of concurrent chemotherapy. • Low-risk patients defined by the nomogram were candidates for de-intensification.

Benefit of [18F] FDG PET/CT in the diagnosis and salvage treatment of recurrent nasopharyngeal carcinoma.

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.

Benefit of [18F]-FDG PET/CT for treatment-naïve nasopharyngeal carcinoma.

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.

Development and validation of radiologic scores for guiding individualized induction chemotherapy in T3N1M0 nasopharyngeal carcinoma.

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.

A Pairwise Meta-Analysis of Induction Chemotherapy in Nasopharyngeal Carcinoma.

BACKGROUND: Locoregionally advanced nasopharyngeal carcinoma has high risk of distant metastasis and mortality. Induction chemotherapy is commonly administrated in clinical practice, but the efficacy was quite controversial in and out of randomized controlled trials. We thus conducted this pairwise meta-analysis. MATERIALS AND METHODS: Trials that randomized patients to receive radiotherapy or concurrent chemoradiotherapy with or without induction chemotherapy were identified via searches of PubMed, MEDLINE, and ClinicalTrials.gov. RESULTS: A total of ten trials (2,627 patients) were included. The pooled hazard ratios (HRs) based on fixed effect model were 0.68 (95% confidence interval [CI] 0.56-0.80, p < .001) for overall survival (OS) and 0.70 (95% CI 0.61-0.79, p < .001) for progression-free survival (PFS), which strongly favored the addition of induction chemotherapy. The absolute 5-year survival benefits were 8.47% in OS and 10.27% in PFS, respectively. In addition, based on the available data of eight trials, induction chemotherapy showed significant efficacy in reducing locoregional failure rate (risk ratio [RR] = 0.81, 95% CI 0.68-0.96, p = .017) and distant metastasis rate (RR = 0.69, 95% CI 0.58-0.82, p < .001). CONCLUSION: This pairwise meta-analysis confirms the benefit in OS, PFS, and locoregional and distant controls associated with the addition of induction chemotherapy in nasopharyngeal carcinoma. IMPLICATIONS FOR PRACTICE: According to the results of this meta-analysis of ten trials, induction chemotherapy can prolong overall survival and progression-free survival and improve locoregional and distant controls for nasopharyngeal carcinoma.

Clinical characteristics, prognostic factors, and treatment modalities for head and neck lymphoepithelioma-like carcinoma: A real-world study from southern China.

BACKGROUND: We aimed to elucidate the clinical characteristics, prognostic factors and optimal treatment modalities of head and neck lymphoepithelioma-like carcinoma (HNLELC). METHODS: Consecutive patients newly-diagnosed with non-metastatic HNLELC between December 2001 and March 2021 treated with curative intent were retrospectively reviewed. RESULTS: A total of 288 patients were included, of whom 87 (30.2%) underwent radical surgery alone, 43 (14.9%) underwent definitive radiotherapy with or without concurrent chemotherapy, and 158 (54.9%) underwent surgery followed by postoperative radiotherapy (SRT). Epstein-Barr virus-encoded small RNA (EBER) was positive in 94.8% (239/252) of patients. Cervical node infiltration was seen in 52.8% (152/288) of patients. No significant difference was found in nodal metastasis rate between T1-2 and T3-4 classifications (49.5% vs. 56.5%, p = 0.308). The 3-year overall survival (OS), disease-free survival, locoregional relapse-free survival, and distant metastasis-free survival rates were 89.4%, 78.7%, 89.2%, and 87.7%, respectively. Compared to SRT, surgery alone associated with significant reduced 3-year local (92.8% vs. 96.5%, p = 0.012) and regional relapse-free survival rates (89.3% vs. 96.8%, p = 0.002). Definitive radiotherapy and SRT demonstrated comparable results in all 3-year survival outcomes (all p＞0.05). Multivariate analysis found EBER status was an independent favorable prognostic factor for OS (HR = 0.356, 95% CI: 0.144-0.882, p = 0.026). CONCLUSION: HNLELC was observed to associate with EBV infection and cervical nodal infiltration. Definitive radiotherapy achieved similar survival outcomes compared to SRT, and may serve as a good substitute for patients unfit or unwilling to undergo surgery.

Immunochemotherapy alone or immunochemotherapy plus subsequent locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Dosiomics Risk Model for Predicting Radiation Induced Temporal Lobe Injury and Guiding Individual Intensity-Modulated Radiation Therapy.

PURPOSE: We aimed to assess the value of dose distribution-based dosiomics and planning computed tomography-based radiomics to predict radiation-induced temporal lobe injury (TLI) and guide individualized intensity modulated radiation therapy. METHODS AND MATERIALS: 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 quantitative analyses of normal tissue effects in the clinic 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 computed tomography features and 10 selected dose distribution features, respectively, which were important predictors of TLI-free survival (all P <.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 quantitative analyses of normal tissue effects in the clinic model and Wen's model (all P <.001). The dosiomics risk model can further distinguish patients in a same risk category divided by other models (all P <.05). Conversely, the other models were unable to separate populations classified by the dosiomics risk model (all P > .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 ≤ .002). CONCLUSIONS: 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 radiation therapy.

Radiomics and dosiomics for predicting radiation-induced hypothyroidism and guiding intensity-modulated radiotherapy.

To guide individualized intensity-modulated radiotherapy (IMRT), we developed and prospectively validated a multiview radiomics risk model for predicting radiation-induced hypothyroidism in patients with nasopharyngeal carcinoma. And simulated radiotherapy plans with same dose-volume-histogram (DVH) but different dose distributions were redesigned to explore the clinical application of the multiview radiomics risk model. The radiomics and dosiomics were built based on selected radiomics and dosiomics features from planning computed tomography and dose distribution, respectively. The multiview radiomics risk model that integrated radiomics, dosiomics, DVH parameters, and clinical factors had better performance than traditional normal tissue complication probability models. And multiview radiomics risk model could identify differences of patient hypothyroidism-free survival that cannot be stratified by traditional models. Besides, two redesigned simulated plans further verified the clinical application and advantage of the multiview radiomics risk model. The multiview radiomics risk model was a promising method to predict radiation-induced hypothyroidism and guide individualized IMRT.

Artificial intelligence aided precise detection of local recurrence on MRI for nasopharyngeal carcinoma: a multicenter cohort study.

Background: MRI is the routine examination to surveil the recurrence of nasopharyngeal carcinoma, but it has relatively lower sensitivity than PET/CT. We aimed to find if artificial intelligence (AI) could be competent pre-inspector for MRI radiologists and whether AI-aided MRI could perform better or even equal to PET/CT. Methods: This multicenter study enrolled 6916 patients from five hospitals between September 2009 and October 2020. A 2.5D convolutional neural network diagnostic model and a nnU-Net contouring model were developed in the training and test cohorts and used to independently predict and visualize the recurrence of patients in the internal and external validation cohorts. We evaluated the area under the ROC curve (AUC) of AI and compared AI with MRI and PET/CT in sensitivity and specificity using the McNemar test. The prospective cohort was randomized into the AI and non-AI groups, and their sensitivity and specificity were compared using the Chi-square test. Findings: The AI model achieved AUCs of 0.92 and 0.88 in the internal and external validation cohorts, corresponding to the sensitivity of 79.5% and 74.3% and specificity of 91.0% and 92.8%. It had comparable sensitivity to MRI (e.g., 74.3% vs. 74.7%, P = 0.89) but lower sensitivity than PET/CT (77.9% vs. 92.0%, P < 0.0001) at the same individual-specificities. The AI model achieved moderate precision with a median dice similarity coefficient of 0.67. AI-aided MRI improved specificity (92.5% vs. 85.0%, P = 0.034), equaled PET/CT in the internal validation subcohort, and increased sensitivity (81.9% vs. 70.8%, P = 0.021) in the external validation subcohort. In the prospective cohort of 1248 patients, the AI group had higher sensitivity than the non-AI group (78.6% vs. 67.3%, P = 0.23), albeit nonsignificant. In future randomized controlled trials, a sample size of 3943 patients in each arm would be required to demonstrate the statistically significant difference. Interpretation: The AI model equaled MRI by expert radiologists, and AI-aided MRI by expert radiologists equaled PET/CT. A larger randomized controlled trial is warranted to demonstrate the AI's benefit sufficiently. Funding: The Sun Yat-sen University Clinical Research 5010 Program (2015020), Guangdong Basic and Applied Basic Research Foundation (2022A1515110356), and Guangzhou Science and Technology Program (2023A04J1788).

Deep learning-based precise prediction and early detection of radiation-induced temporal lobe injury for nasopharyngeal carcinoma.

Background: Radiotherapy is the mainstay of treatment for nasopharyngeal carcinoma. Radiation-induced temporal lobe injury (TLI) can regress or resolve in the early phase, but it is irreversible at a later stage. However, no study has proposed a risk-based follow-up schedule for its early detection. Planning evaluation is difficult when dose-volume histogram (DVH) parameters are similar and optimization is terminated. Methods: This multicenter retrospective study included 6065 patients between 2014 and 2018. A 3D ResNet-based deep learning model was developed in training and validation cohorts and independently tested using concordance index in internal and external test cohorts. Accordingly, the patients were stratified into risk groups, and the model-predicted risks were used to develop risk-based follow-up schedules. The schedule was compared with the Radiation Therapy Oncology Group (RTOG) recommendation (every 3 months during the first 2 years and every 6 months in 3-5 years). Additionally, the model was used to evaluate plans with similar DVH parameters. Findings: Our model achieved concordance indexes of 0.831, 0.818, and 0.804, respectively, which outperformed conventional prediction models (all P < 0.001). The temporal lobes in all the cohorts were stratified into three groups with discrepant TLI-free survival. Personalized follow-up schedules developed for each risk group could detect TLI 1.9 months earlier than the RTOG recommendation. According to a higher median predicted 3-year TLI-free survival (99.25% vs. 99.15%, P < 0.001), the model identified a better plan than previous models. Interpretation: The deep learning model predicted TLI more precisely. The model-determined risk-based follow-up schedule detected the TLI earlier. The planning evaluation was refined because the model identified a better plan with a lower risk of TLI. Funding: The Sun Yat-sen University Clinical Research 5010 Program (2015020), Guangdong Basic and Applied Basic Research Foundation (2022A1515110356), Medical Scientific Research Foundation of Guangdong Province (A2022367), and Guangzhou Science and Technology Program (2023A04J1788).

Development and prospective validation of a risk score model in guiding individualized concurrent chemoradiotherapy in stage II nasopharyngeal carcinoma in intensity-modulated radiotherapy era.

PURPOSE: We aimed to develop and prospectively validate a risk score model to guide individualized concurrent chemoradiotherapy (CCRT) for patients with stage II nasopharyngeal carcinoma (NPC) in intensity-modulated radiotherapy (IMRT) era. MATERIALS AND METHODS: In total, 1220 patients who received CCRT or IMRT alone were enrolled in this study, including a training cohort (n = 719), a validation cohort (n = 307), and a prospective test cohort (n = 194). Patients were stratified into different risk groups by a risk score model based on independent prognostic factors, which were developed in the training cohort. Survival rates were compared by the log-rank test. The validation and prospective test cohorts were used for validation. RESULTS: Total tumor volume, Epstein-Barr virus DNA, and lactate dehydrogenase were independent risk factors for failure-free survival (FFS, all p < 0.05). A risk score model based on these three risk factors was developed to classify patients into low-risk group (no risk factor, n = 337) and high-risk group (one or more factors, n = 382) in the training cohort. In the high-risk group, CCRT had better survival rates than IMRT alone (5-year FFS: 82.6% vs. 74.0%, p = 0.028). However, there was no survival difference between CCRT and IMRT alone either in the whole training cohort (p = 0.15) or in the low-risk group (p = 0.15). The results were verified in the validation and prospective test cohorts. CONCLUSION: A risk score model was developed and prospectively validated to precisely select high-risk stage II NPC patients who can benefit from CCRT, and thus guided individualized treatment in IMRT era.

Role of postoperative chemoradiotherapy in head and neck cancer without positive margins or extracapsular extension: a propensity score-matching analysis.

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.

Effect of Induction Chemotherapy in Nasopharyngeal Carcinoma: An Updated Meta-Analysis.

BACKGROUND: Previous meta-analysis had evaluated the effect of induction chemotherapy in nasopharyngeal carcinoma. But two trials with opposite findings were not included and the long-term result of another trial significantly differed from the preliminary report. This updated meta-analysis was thus warranted. METHODS: Literature search was conducted to identify randomized controlled trials focusing on the additional efficacy of induction chemotherapy in nasopharyngeal carcinoma. Trial-level pooled analysis of hazard ratio (HR) for progression free survival and overall survival and risk ratio (RR) for locoregional control rate and distant control rate were performed. RESULTS: Twelve trials were eligible. The addition of induction chemotherapy significantly prolonged both progression free survival (HR=0.68, 95% confidence interval [CI] 0.60-0.76, p<0.001) and overall survival (HR=0.67, 95% CI 0.54-0.80, p<0.001), with 5-year absolute benefit of 11.31% and 8.95%, respectively. Locoregional (RR=0.80, 95% CI 0.70-0.92, p=0.002) and distant control (RR=0.70, 95% CI 0.62-0.80) rates were significantly improved as well. The incidence of grade 3-4 adverse events during the concurrent chemoradiotherapy was higher in leukopenia (p=0.028), thrombocytopenia (p<0.001), and fatigue (p=0.038) in the induction chemotherapy group. CONCLUSIONS: This meta-analysis supported that induction chemotherapy could benefit patients with nasopharyngeal carcinoma in progression free survival, overall survival, locoregional, and distant control rate.