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.

Pretreatment anemia and survival in nasopharyngeal carcinoma.

Due to the low incidence of pretreatment anemia in nasopharyngeal carcinoma (NPC), the true prognostic impact of pretreatment anemia may be underestimated before. We retrospectively analyzed the association of pretreatment anemia with disease-specific survival (DSS), distant-metastasis-free survival (DMFS), and locoregional-relapse-free survival (LRFS) by Cox regression in a cohort of 5830 patients, stratifying by midtreatment anemia, smoking, body mass index (BMI), etc. Pretreatment anemia was significantly associated with adverse DSS (hazard ratio (HR) = 2.15, 95 % confidence interval (CI) 1.62-2.85, P < 0.001) and DMFS (HR = 1.53, 95 % CI 1.08-2.17, P = 0.018), comparing to patients with normal hemoglobin, after adjusting for covariates. Moreover, the association with DSS remained unchanged regardless of smoking status and clinical stage, whereas it was limited in the subgroups of above 45 years, male sex, and BMI <25 kg/m(2). With restriction to midtreatment anemic patients, pretreatment anemia was still strongly correlated with inferior DSS and DMFS. This study, in the largest reported cohort, is the first to show the adverse prognostic impact of pretreatment anemia on DSS and DMFS in NPC.

Long-term outcomes of concurrent chemoradiotherapy versus radiotherapy alone in stage II nasopharyngeal carcinoma treated with IMRT: a retrospective study.

This study aimed to evaluate the efficacy of concurrent chemoradiotherapy (CCRT) for stage II nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiation therapy (IMRT). A total of 249 patients were retrospectively reviewed. All patients were treated with IMRT. One hundred forty-three patients treated with CCRT and 106 patients treated with IMRT alone. With a median follow-up of 59.4 months, adding concurrent chemotherapy did not statistically significantly improve the 5-year overall survival (OS) (89.7 % vs 99.0 %, p = 0.278), locoregional relapse-free survival (LRFS) (94.8 % vs 89.3 %, p = 0.167), and distant metastases-free survival (DMFS) (93.4 % vs 97.5 %, p = 0.349). The patients with CCRT significantly experienced more acute toxic effects. The main grades 3-4 toxicity reactions were mucositis (26.6 % vs 15.1 %, p = 0.03) and leukopenia/neutropenia (9.1 % vs 0.9 %, p = 0.005). In subgroup analysis of patients with concurrent platinum single-agent chemotherapy the 5-year OS (98.4 % vs 81.9 %, p = 0.013) and DMFS (96.9 % vs 84.4 %, p = 0.043) of patients with platinum every 3 weeks (Q3W) were significantly higher than those with platinum weekly (QW) and no significant difference for LRFS (96.8 % vs 90.4 %, p = 0.150). CCRT did not improve the survival of patients with stage II NPC but increased the acute toxicity reactions. Patients with platinum Q3W improved the 5-year OS and DMFS, compared with those with platinum QW.

The prognostic impact of preoperative blood monocyte count in pathological T3N0M0 rectal cancer without neoadjuvant chemoradiotherapy.

It remains controversial whether adjuvant therapy should be delivered to pathological T3N0M0 rectal cancer without neoadjuvant chemoradiotherapy. Thus identification of patients at high risk is of particular importance. Herein, we aimed to evaluate whether the absolute peripheral blood monocyte count can stratify the pathological T3N0M0M0 rectal cancer patients in survival. A total of 270 pathological T3N0M0 rectal cancer patients with total mesorectal excision-principle radical resection were included. The optimal cut-off value of preoperative monocyte count was determined by receiver operating characteristic curve analysis. Overall survival and disease-free survival between low- and high-monocyte were estimated by Kaplan-Meier method and Cox regression model. The optimal cut-off value for monocyte count was 595 mm(3). In univariate analysis, patients with monocyte counts higher than 595/mm(3) had significantly inferior 5-year overall survival (79.2 vs 94.2 %, P = 0.006) and disease-free survival (67.8 vs 86.0 %, P < 0.001). With adjustment for the known covariates, monocyte count remained to be associated with poor overall survival (HR = 2.55, 95 % CI 1.27-5.10; P = 0.008) and disease-free survival (HR = 2.63, 95 % CI 1.48-4.69; P = 0.001). Additionally, the significant association of monocyte count with disease-free survival was hardly influenced in the subgroup analysis, whereas this correlation was restricted to the males and patients with normal carcinoembryonic antigen (CEA) level (<5 µg/L), tumor grade II, and with adjuvant therapy. High preoperative monocyte count is independently predictive of worse survival of pathological T3N0M0 rectal cancer patients without neoadjuvant chemoradiotherapy. Postoperative adjuvant therapy might be considered for patients with high-monocyte count.

Leucopenia and treatment efficacy in advanced nasopharyngeal carcinoma.

BACKGROUND: Leucopenia or neutropenia during chemotherapy predicts better survival in several cancers. We aimed to assess whether leucopenia could be a biological measure of treatment and a marker of efficacy in advanced nasopharyngeal carcinoma (ANPC). METHODS: We retrospectively analyzed 3826 patients with ANPC who received chemoradiotherapy. Leucopenia was categorised on the basis of worst grade during treatment according to the National Cancer Institute Common Toxicity Criteria version 4.0: no leucopenia (grade 0), mild leucopenia (grade 1-2), and severe leucopenia (grade 3-4). Associations between leucopenia and survival were estimated by Cox proportional hazards model. RESULTS: Of the 3826 patients, 2511 (65.6 %) developed mild leucopenia (grade 1-2) and 807 (21.1 %) developed severe leucopenia (grade 3-4) during treatment; 508 (13.3 %) did not. A multivariate Cox model that included leucopenia determined that the hazard ratios (HR) of death for patients with mild and severe leucopenia were 0.69 [95 % confidence interval (95 %CI) 0.56-0.85, p < 0.001] and 0.75 (95 %CI 0.59-0.95, p = 0.019), respectively; the HR of distant metastasis for patients with mild and severe leucopenia were 0.77 (95 %CI 0.61-0.96, p = 0.023) and 0.99 (95 %CI 0.77-1.29, p = 0.995), respectively. Leucopenia had no effect on locoregional relapse. CONCLUSIONS: Our results indicate that mild leucopenia during chemoradiotherapy is associated with improved overall survival and distant metastasis-free survival in ANPC. Mild leucopenia may indicate appropriate dosage of chemotherapy. We can identify the patients who may benefit from chemotherapy if they experienced leucopenia during the treatment. Prospective trials are required to assess whether dosing adjustments based on leucopenia may improve chemotherapy efficacy.

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.

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.

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).

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).

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.

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.

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.

Prognostic impact of family history of cancer in Southern Chinese patients with esophageal squamous cell cancer.

Background: First degree family history of cancer is associated with developing esophageal cancer and sparse data is about the impact on poor survival among established esophageal squamous cell cancer (ESCC) patients. In this study, we investigated the prognoses of patients with ESCC with a family history. Methods: A total of 479 ESCC patients were retrospectively enrolled from a Southern Chinese institution. A positive family history was defined as having malignant cancer among parents and siblings. Kaplan-Meier plots and Cox proportional hazards regressions were applied for overall survival (OS) and progression-free survival (PFS). Results: Among 479 patients, 119 (24.8%) and 68 (14.2%) reported a first-degree family history of cancer and digestive tract cancer, respectively. Compared with patients without a family history of cancer, the adjusted hazard ratios (HR) among those with it were 1.40 (95% CI, 1.08-1.82, p=0.011) for death, 1.36 (95% CI, 1.05-1.76, p=0.018) for progression. Similar results were observed in those with a family history of digestive tract cancer (HR=1.69, 95%CI, 1.24-1.98, p=0.001 for death and HR=1.77, 95%CI, 1.30-2.37, p<0.001 for progression, respectively). Furthermore, there was a trend for increasing risk of overall mortality (p=0.021, p=0.004, respectively), and progression (p=0.022, p=0.001, respectively) with an increasing number of affected family members. Conclusion: A first-degree family history of cancer, especially digestive tract cancer is associated with poor survival for established ESCC patients and plays an important role in prognosis. The patients with a family history of cancer might need a greater intensity of treatment and more frequent follow-up.

External validity of a prognostic nomogram for locoregionally advanced nasopharyngeal carcinoma based on the 8th edition of the AJCC/UICC staging system: a retrospective cohort study.

BACKGROUND: The tumor-node-metastasis (TNM) staging system does not perform well for guiding individualized induction or adjuvant chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma (NPC). We attempted to externally validate the Pan's nomogram, developed based on the 8th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) staging system, for patients with locoregionally advanced disease. In addition, we investigated the reliability of Pan's nomogram for selection of participants in future clinical trials. METHODS: This study included 535 patients with locoregionally advanced NPC who were treated between March 2007 and January 2012. The 5-year overall survival (OS) rates were calculated using the Kaplan-Meier method and compared with predicted outcomes. The calibration was tested using calibration plots and the Hosmer-Lemeshow test. Discrimination ability, which was assessed using the concordance index, as compared with other predictors. RESULTS: Pan's nomogram was observed to underestimate the 5-year OS of the entire cohort by 8.65% [95% confidence interval (CI) - 9.70 to - 7.60%, P < 0.001] and underestimated the 5-year OS of each risk group. The differences between the predicted and observed 5-year OS rates were smallest among low-risk patients (< 135 points calculated using Pan's nomogram; which predicted minus observed OS, - 6.41%, 95% CI - 6.75 to - 6.07%, P < 0.001) and were largest among high-risk patients (≥ 160 points) (- 13.56%, 95% CI - 15.48 to - 11.63%, P < 0.001). The Hosmer-Lemeshow test suggested that the predicted and observed 5-year OS rates had no ideal relationship (P < 0.001). Pan's nomogram had better discriminatory ability compared with the levels of Epstein-Barr virus DNA acid (EBV DNA) and the 7th or 8th AJCC/UICC staging system, although not better compared with the combination of EBV DNA and the 8th staging system. Additionally, Pan's nomogram was marginally inferior to our predictive model, which included the 8th AJCC/UICC N-classification, age, gross primary tumor volume, lactate dehydrogenase, and body mass index. CONCLUSIONS: Pan's nomogram underestimated the 5-year OS of patients with locoregionally advanced NPC at our cancer center, and may not be a precise tool for selecting participants for clinical trials.

Temporal lobe injury patterns following intensity modulated radiotherapy in a large cohort of nasopharyngeal carcinoma patients.

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.

Outcomes of adding induction chemotherapy to concurrent chemoradiotherapy for stage T3N0-1 nasopharyngeal carcinoma: a propensity-matched study.

OBJECTIVE: Our objective was to examine whether adding induction chemotherapy to concurrent chemoradiotherapy improved survival in stage III nasopharyngeal carcinoma (NPC) patients, especially in low-risk patients at stage T3N0-1. MATERIALS AND METHODS: We retrospectively analyzed 687 patients with stage T3N0-1 NPC treated with intensity-modulated radiation therapy (IMRT) plus concurrent chemotherapy (CC) with or without induction chemotherapy (IC). Propensity score matching (PSM) method was used to select 237 pairs of patients from two cohorts. Overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS) were assessed by using the Kaplan-Meier method, log-rank test, and Cox regression analysis. RESULTS: No significant survival differences were observed between IC plus CC and CC cohorts with similar 4-year OS (91.7% vs 92.6%, P=0.794), LRFS, (92.7% vs 96.8%, P=0.138), DMFS (93.5% vs 94.3%, P=0.582), and PFS (87.5% vs 91.1%, P=0.223). In a univariate analysis, lower Epstein-Barr virus deoxyribonucleic acid (EBV DNA; <4,000 copies/mL) significantly improved 4-year DMFS (95.5% vs 91.6%, P=0.044) compared with higher EBV DNA (≥4,000 copies/mL). No factors were associated with 4-year OS, LRFS, DMFS, and PFS in a multivariate analysis. IC plus CC group experienced higher rates of grade 3-4 leucopenia (P<0.001) and neutropenia (P<0.001). CONCLUSION: The addition of IC to CC in stage T3N0-1 NPC patients treated with IMRT did not significantly improve their survival. The IC group experienced higher rates of grade 3-4 hematological toxicities. Therefore, further investigation is required.