Prognostic value of lymph node-to-primary tumor ratio of PET standardized uptake value for nasopharyngeal carcinoma: a recursive partitioning risk stratification analysis.

Background: Induction chemotherapy (IC) combined with concurrent chemoradiotherapy has become the standard treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Data on the prognostic value of the lymph node-to-primary tumor ratio (NTR) of positron emission tomography (PET) standardized uptake value (SUV) for patients treated with IC were limited. Objectives: To evaluate the prognostic value of the SUV NTR for patients with LA-NPC treated with IC. Design: In all, 467 patients with pretreatment 18F-fluorodeoxyglucose PET/computed tomography (CT) scans between September 2017 and November 2020 were retrospectively reviewed. Methods: The receiver operating characteristic (ROC) analysis was used to determine the optimal cut-off value of SUV NTR. Kaplan-Meier method was used to evaluate survival rates. The recursive partitioning analysis (RPA) was performed to construct a risk stratification model. Results: The optimal cutoff value of SUV NTR was 0.74. Multivariate analyses showed that SUV NTR and overall stage were independent predictors for distant metastasis-free survival (DMFS) and regional recurrent-free survival (RRFS). Therefore, an RPA model based on the endpoint of DMFS was generated and categorized the patients into three distinct risk groups: RPA I (low risk: SUV NTR < 0.74 and stage III), RPA II (medium risk: SUV NTR < 0.74 and stage IVa, or SUV NTR ⩾ 0.74 and stage III), and RPA III (high risk: SUV NTR ⩾ 0.74 and stage IVa), with a 3-year DMFS of 98.9%, 93.4%, and 84.2%, respectively. ROC analysis showed that the RPA model had superior predictive efficacy than the SUV NTR or overall stage alone. Conclusion: SUV NTR was an independent prognosticator for distant metastasis and regional recurrence in locoregionally advanced NPC. The RPA risk stratification model based on SUV NTR provides improved DMFS and RRFS prediction over the eighth edition of the TNM (Tumor Node Metastasis) staging system.

Multiply-mesoporous hydrophilic titanium dioxide nanohybrid for the highly-performed enrichment of N-glycopeptides from human serum.

N-glycopeptide is considered as one of significant biomarkers which provide guidance for the diagnosis and drug design of diseases. However, the direct analysis of N-glycopeptides is nearly impracticable mainly owing to their extremely low abundance and grave signal suppression from other interfering substances in the bio-samples. In this research, a multiply-mesoporous hydrophilic TiO2 nanohybrid (mM-TiO2@Cys) was synthesized by immobilizing Cys on a TiO2 substrate with hierarchical mesopores to achieve the highly-performed enrichment of N-glycopeptides. With the advantages of superior hydrophilicity and multiply-mesoporous structure, the obtained material exhibited an excellent selectivity (IgG digests and BSA digests at the molar ratio of 1/500), a high sensitivity (1 fmol µL-1 for IgG digests) and a good size-exclusion ability (IgG digests, IgG and BSA at the molar ratio of 1/500/500) in the enrichment of N-glycopeptides from IgG digests. As a result, 281 N-glycopeptides corresponded with 109 glycoproteins were identified from 2 µL serum digests of the patients with nasopharyngeal carcinoma, and 181 N-glycopeptides corresponded with 78 glycoproteins were identified from 2 µL serum digests of the healthy volunteers, revealing the potential application value of mM-TiO2@Cys in glycoproteomics.

Physical education and student well-being: Promoting health and fitness in schools.

The school students are facing mental health issues, and their performance is not improving in China. Health education policies are not implemented at the school level in China. However, scholars focus on college students' health education, but the school student is neglected. The research's primary objective is to answer the question: What is the impact of health education on the psychological well-being of school students? A sample of 549 10th grade students is collected from China's public and private sector institutes. The partial least square-structural equation modelling (PLS-SEM) is employed to analyze the data. The outcomes highlighted that the impact of health education is significant on the psychological well-being of school students in China. Furthermore, the study introduced that the moderating role of sustainable health exercise and sports participation is critical as it positively influences the relationship between health education and psychological wellbeing. This research improves literature as the novel contribution are highlighted in theory. Furthermore, the government education policies must be reframed under the light of this research' findings to improve students' health.

Radiation-induced nasopharyngeal ulcers after re-irradiation with intensity-modulated radiotherapy in locoregional recurrent nasopharyngeal carcinoma patients: a dose-volume-outcome analysis.

OBJECTIVE: To analyze the interrelation between radiation dose and radiation-induced nasopharyngeal ulcer (RINU) in locoregional recurrent nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). METHODS: Clinical data were collected from 363 patients with locoregional recurrent NPC who received re-irradiated with definitive IMRT from 2009 to 2017. Twenty-nine patients were diagnosed with RINU. Univariate and multivariate analyses were used to re-evaluate the first and second radiotherapy plans and to identify predictive dosimetric factors. RESULTS: All dosimetric parameters were notably associated with the progression to RINU (p < 0.01) using paired samples Wilcoxon signed rank tests. Multivariate analysis showed that EQD2_ [Formula: see text]D80 (dose for 80 percent volume of the unilateral nasopharynx lesion) was an independent prognostic factor for RINU (p = 0.001). The area under the ROC curve for EQD2_ [Formula: see text]D80 was 0.846 (p < 0.001), and the cutoff point of 137.035 Gy could potentially be the dose tolerance of the nasopharyngeal mucosa. CONCLUSIONS: The sum of equivalent dose in 2 Gy fractions (EQD2) in the overlapping volumes between initial and re-irradiated nasopharyngeal mucosal tissue can be effective in predicting the hazard of developing RINU in NPC patients undergoing radical re­irradiation with IMRT and we propose a EQD2_ [Formula: see text]D80 threshold of 137.035 Gy for the nasopharynx.

Nomograms containing body dose parameters for predicting survival in patients with nasopharyngeal carcinoma.

PURPOSE: To assess the impact of body dose on survival outcomes in nasopharyngeal carcinoma (NPC) patients and to create novel nomograms incorporating body dose parameters for predicting survival. METHODS: 594 of non-metastasis NPC patients (training group, 396; validation group, 198) received intensity-modulated radiation therapy at our institution from January 2012 to December 2016. Patient characteristics, body dose parameters in dose-volume histogram (DVH) and hematology profiles were collected for predicting overall survival (OS) and progression-free survival (PFS). Nomograms for OS and PFS were developed using the selected predictors. Each nomogram was evaluated based on its C-index and calibration curve. RESULTS: Body dose-based risk score for OS (RSOS), N stage, age, and induction chemotherapy were independent predictors for OS, with a C-index of 0.784 (95% CI 0.749-0.819) in the training group and 0.763 (95% CI 0.715-0.810) in the validation group for the nomogram. As for PFS, the most important predictors were the body dose-based risk score for PFS (RSPFS), N stage, and induction chemotherapy. C-index of PFS nomogram was 0.706 (95% CI 0.681-0.720) in the training group and 0.691 (95% CI 0.662-0.711) in the validation group. The two models outperformed the TNM staging system in predicting outcomes. CONCLUSIONS: Body dose coverage is a useful predictor of prognosis in clinical routine patients. The novel nomograms integrating body dose parameters can precisely predict OS and PFS in NPC patients.

Prognostic value of circulating Epstein-Barr virus DNA level post-induction chemotherapy for patients with nasopharyngeal carcinoma: A recursive partitioning risk stratification analysis.

BACKGROUND: To evaluate the prognostic value of plasma Epstein-Barr virus (EBV) DNA level post-induction chemotherapy (IC) for patients with nasopharyngeal carcinoma (NPC). METHODS: A total of 893 newly diagnosed NPC patients treated with IC were retrospectively reviewed. The recursive partitioning analysis (RPA) was performed to construct a risk stratification model. The receiver operating characteristic (ROC) analysis was applied to determine the optimal cut-off value of post-IC EBV DNA. RESULTS: Post-IC EBV DNA levels and overall stage were independent predictors for distant metastasis-free survival (DMFS), overall survival (OS), and progression-free survival (PFS). The RPA model base on post-IC EBV DNA and overall stage categorized the patients into three distinct risk groups: RPA I (low-risk: stage II-III and post-IC EBV DNA < 200 copies/mL), RPA II (median-risk: stage II-III and post-IC EBV DNA ≥ 200 copies/mL, or stage IVA and post-IC EBV DNA < 200 copies/mL), and RPA III (high-risk: stage IVA and post-IC EBV DNA ≥ 200 copies/mL), with 3-year PFS of 91.1%, 82.6%, and 60.2%, respectively (p < 0.001). The DMFS and OS rates in different RPA groups were also distinct. The RPA model showed better risk discrimination than either the overall stage or post-RT EBV DNA alone. CONCLUSIONS: Plasma EBV DNA level post-IC was a robust prognostic biomarker for NPC. We developed an RPA model that provides improved risk discrimination over the 8th edition of the TNM staging system by integrating the post-IC EBV DNA level and the overall stage.

Facile fabrication of hydrophilic covalent organic framework composites for highly selective enrichment of N-glycopeptides.

The development of facilely synthetic materials acts an essential role in glycoproteome analysis, especially for the highly efficient enrichment of N-linked glycopeptides. In this work, a facile and timesaving route was introduced in which COFTP-TAPT served as a carrier and poly (ethylenimine) (PEI) and carrageenan (Carr) were successively coated on the surface via electrostatic interaction. The resultant COFTP-TAPT@PEI@Carr showed remarkable performance in glycopeptide enrichment with high sensitivity (2 fmol µL-1), high selectivity (1:800, molar ratio of human serum IgG to BSA digests), large loading capacity (300 mg g-1), satisfactory recovery (102.4 ± 6.0%) and reusability (at least eight times). Due to the brilliant hydrophilicity and electrostatic interactions between COFTP-TAPT@PEI@Carr and positively charged glycopeptides, the prepared materials could be applied in the identification and analysis in the human plasma of healthy subjects and patients with nasopharyngeal carcinoma. As a result, 113 N-glycopeptides with 141 glycosylation sites corresponding to 59 proteins and 144 N-glycopeptides with 177 glycosylation sites corresponding to 67 proteins were enriched from 2 µL plasma trypsin digests of the control groups and patients with nasopharyngeal carcinoma, respectively. 22 glycopeptides were identified only from the normal controls and 53 glycopeptides were detected only from the other set. The results demonstrated that this hydrophilic material was promising on a large scale and further N-glycoproteome research.

Radiotherapy Alone Versus Concurrent or Adjuvant Chemoradiotherapy for Nasopharyngeal Carcinoma Patients with Negative Epstein-Barr Virus DNA after Induction Chemotherapy.

The purpose of this study was to compare the efficacy and toxicity of induction chemotherapy (IC) plus radiotherapy (RT) and IC plus concurrent or adjuvant chemoradiotherapy (CCRT/AC) in nasopharyngeal carcinoma (NPC) patients with negative Epstein-Barr virus DNA (EBV DNA) after IC. A total of 547 NPC patients with negative plasma EBV DNA post-IC were included. Patients were classified into the IC + RT group and the IC + CCRT/AC group. Locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), overall survival (OS), and progression-free survival (PFS) were estimated and compared using the Kaplan-Meier method. Propensity score matching (PSM) was performed to balance the variables. The median follow-up time was 37 months. The 3-year LRFS, DMFS, OS, and PFS rates for the whole group were 92.2%, 92.4%, 96.4%, and 84.4%, respectively. There was no significant difference in LRFS, DMFS, OS, and PFS between the IC + RT and the IC + CCRT/AC groups, both before PSM (3-year rates of 91.1% vs. 92.6%, p = 0.94; 95.6% vs. 91.5%, p = 0.08; 95.2% vs. 96.8%, p = 0.80; 85.9% vs. 84.0%, p = 0.38) and after PSM (90.7% vs. 92.7%, p = 0.77; 96.8% vs. 93.7%, p = 0.29; 94.5% vs. 93.9%, p = 0.57; 84.7% vs. 85.6%, p = 0.96). Multivariate analysis demonstrated that the treatment schedule was not an independent predictor for survival rates. Patients in the IC + RT group had fewer treatment-related acute toxicities and better tolerance. IC + RT displayed similar survival outcomes as IC + CCRT/AC for NPC patients with negative post-IC EBV DNA.

AntiPD-L1 antibody conjugated Au-SPIOs nanoplatform for enhancing radiosensitivity and triggering anti-tumor immune response.

To improve radiotherapy effect by inducing more toxicity for tumors and less for normal tissue and switching immunosuppressive microenvironment caused by expression of PD-L1 and tumor-associated macrophages (TAMs) to immunoreactive microenvironment, we designed a PD-L1-targeted nanoplatform consisting of gold nanoparticles and superparamagnetic iron oxide nanoparticles (antiPD-L1-SPIOs@PLGA@Au). In vivo T2-weighted images, the best contrast effect of tumor was achieved two hours after intravenous injection of antiPD-L1-SPIOs@PLGA@Au. The tumor control caused by irradiation combined with antiPD-L1-SPIOs@PLGA@Au was better than that by radiotherapy alone in clone formation assay and B16F10 subcutaneous tumor model. Radiosensitivity enhancement induced by the addition of antiPD-L1-SPIOs@PLGA@Au was achieved by increasing ROS production and attenuating DNA damage repair. AntiPD-L1-SPIOs@PLGA@Au could promote the polarization of tumor-associated macrophages (TAMs) to M1 and reverse the immunosuppression caused by TAMs. By increasing the expression of CRT in tumor and blocking the PD-L1/PD pathway, antiPD-L1-SPIOs@PLGA@Au with radiation activated the anti-tumor immune response. In conclusion, antiPD-L1-SPIOs@PLGA@Au could be used as a radiosensitizer and a MRI contrast targeting PD-L1, with the functions of blocking the PD-L1/PD-1 immune checkpoint pathway and reversing the immunosuppression caused by TAMs.

Failure pattern and suggestions for target volume delineation of carcinoma showing thymus-like differentiation treated with intensity-modulated radiotherapy.

BACKGROUND: To review our long-term clinical experience, analyze the failure patterns, and give suggestions for target volume delineation of carcinoma showing thymus-like differentiation (CASTLE) treated with intensity-modulated radiotherapy (IMRT). METHODS: From April 2008 to May 2019, 30 patients with CASTLE treated by postoperative or radical IMRT in our center were retrospectively reviewed. A total dose of 56-60 Gy in 28-30 fractions was prescribed to patients without residual disease and 66 Gy in 33 fractions for patients with residual or unresectable disease. Survival rates were calculated using the Kaplan-Meier method. Treatment-related toxicities were graded by National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0. RESULTS: Among the 30 patients, 12 (40%) received partial resection or biopsy. Lateral lymph node metastasis was observed in 7 (23.3%) patients. During follow-up, regional lymph node recurrence occurred in 2 patients and distant metastasis in 5 patients. With a median follow-up time of 63.5 months, the 5-year local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), overall survival (OS) and progression-free survival (PFS) rates were 100, 88.9, 78.9, 93.1 and 78.9%, respectively. For patients with no lateral neck node metastasis, prophylactic radiotherapy for lateral neck nodal regions failed to improve RRFS (p = 0.381) and OS (p = 0.153). CONCLUSION: Distant metastasis was the major failure pattern for CASTLE after surgery and IMRT. For patients with no lateral neck node metastasis, the omission of irradiation for lateral neck nodal regions seems to be safe and feasible.

Dual-Branch Convolutional Neural Network Based on Ultrasound Imaging in the Early Prediction of Neoadjuvant Chemotherapy Response in Patients With Locally Advanced Breast Cancer.

The early prediction of a patient's response to neoadjuvant chemotherapy (NAC) in breast cancer treatment is crucial for guiding therapy decisions. We aimed to develop a novel approach, named the dual-branch convolutional neural network (DBNN), based on deep learning that uses ultrasound (US) images for the early prediction of NAC response in patients with locally advanced breast cancer (LABC). This retrospective study included 114 women who were monitored with US during pretreatment (NAC pre) and after one cycle of NAC (NAC1). Pathologic complete response (pCR) was defined as no residual invasive carcinoma in the breast. For predicting pCR, the data were randomly split into a training set and test set (4:1). DBNN with US images was proposed to predict pCR early in breast cancer patients who received NAC. The connection between pretreatment data and data obtained after the first cycle of NAC was considered through the feature sharing of different branches. Moreover, the importance of data in various stages was emphasized by changing the weight of the two paths to classify those with pCR. The optimal model architecture of DBNN was determined by two ablation experiments. The diagnostic performance of DBNN for predicting pCR was compared with that of four methods from the latest research. To further validate the potential of DBNN in the early prediction of NAC response, the data from NAC pre and NAC1 were separately assessed. In the prediction of pCR, the highest diagnostic performance was obtained when combining the US image information of NAC pre and NAC1 (area under the receiver operating characteristic curve (AUC): 0.939; 95% confidence interval (CI): 0.907, 0.972; F1-score: 0.850; overall accuracy: 87.5%; sensitivity: 90.67%; and specificity: 85.67%), and the diagnostic performance with the combined data was superior to the performance when only NAC pre (AUC: 0.730; 95% CI: 0.657, 0.802; F1-score: 0.675; sensitivity: 76.00%; and specificity: 68.38%) or NAC1 (AUC: 0.739; 95% CI: 0.664, 0.813; F1-score: 0.611; sensitivity: 53.33%; and specificity: 86.32%) (p<0.01) was used. As a noninvasive prediction tool, DBNN can achieve outstanding results in the early prediction of NAC response in patients with LABC when combining the US data of NAC pre and NAC1.

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

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

Dissecting the heterogeneity of the microenvironment in primary and recurrent nasopharyngeal carcinomas using single-cell RNA sequencing.

Nasopharyngeal carcinoma (NPC) has a 10-15% recurrence rate, while no long term or durable treatment options are currently available. Single-cell profiling in recurrent NPC (rNPC) may aid in designing effective anticancer therapies, including immunotherapies. For the first time, we profiled the transcriptomes of ∼60,000 cells from four primary NPC and two rNPC cases to provide deeper insights into the dynamic changes in rNPC within radiation fields. Heterogeneity of both immune cells (T, natural killer, B, and myeloid cells) and tumor cells was characterized. Recurrent samples showed increased infiltration of regulatory T cells in a highly immunosuppressive state and CD8+ T cells in a highly cytotoxic and dysfunctional state. Enrichment of M2-polarized macrophages and LAMP3+ dendritic cells conferred enhanced immune suppression to rNPC. Furthermore, malignant cells showed enhanced immune-related features, such as antigen presentation. Elevated regulatory T cell levels were associated with a worse prognosis, with certain receptor-ligand communication pairs identified in rNPC. Even with relatively limited samples, our study provides important clues to complement the exploitation of rNPC immune environment and will help advance targeted immunotherapy of rNPC.

Taxane/gemcitabine-containing chemotherapy plus locoregional IMRT for patients with de novo metastatic nasopharyngeal carcinoma: the treatment outcomes and prognostic factors analysis.

PURPOSE: To evaluate treatment outcomes of de novo metastatic nasopharyngeal carcinoma (mNPC) patients receiving taxane/gemcitabine-containing chemotherapy followed by locoregional intensity-modulated radiotherapy (IMRT) and analyze potential prognostic factors. METHODS: A total of 118 patients between March 2008 and November 2018 were retrospectively analyzed. All the patients were treated with taxane/gemcitabine-containing systemic chemotherapy followed by definitive locoregional IMRT. Potential prognostic factors including baseline absolute lymphocyte count (ALC) and the subdivision of metastasis were analyzed. RESULTS: The median follow-up time for the whole group was 31.5 months (range 5-138 months). Of the 118 patients, 9 (7.6%) patients experienced local regional failure and 60 (50.8%) patients had progression of distant metastasis. At the time of the last follow-up, 61 (51.7%) patients were dead. The 5-year actuarial progression free survival (PFS), overall survival (OS),distant metastasis relapse free survival (DMFS) and local regional recurrence free survival (LRFS) were 34.2%, 44%, 41.1% and 82.6%, respectively. Baseline lymphocyte count ≥ 1600/µl prior to the treatment conferred better locoregional control (5y-LRFS 96% vs. 64.7%, p < 0.001) and distant metastasis control (5y-MFS 50.4% vs. 32.4%, p = 0.023). The multivariate analysis showed that high lymphocyte count was the most relevant predictor of superior PFS (HR = 0.236, p < 0.001) and OS (HR = 0.518, p = 0.04). M subdivision was found as another independent prognostic factor for OS but not for PFS. CONCLUSION: Taxane/gemcitabine-containing chemotherapy combined with IMRT represents an effective treatment modality for mNPC. Baseline ALC is an independent significant prognostic factor for PFS and OS.

Progression-Free Survival Prediction in Patients with Nasopharyngeal Carcinoma after Intensity-Modulated Radiotherapy: Machine Learning vs. Traditional Statistics.

BACKGROUND: The Cox proportional hazards (CPH) model is the most commonly used statistical method for nasopharyngeal carcinoma (NPC) prognostication. Recently, machine learning (ML) models are increasingly adopted for this purpose. However, only a few studies have compared the performances between CPH and ML models. This study aimed at comparing CPH with two state-of-the-art ML algorithms, namely, conditional survival forest (CSF) and DeepSurv for disease progression prediction in NPC. METHODS: From January 2010 to March 2013, 412 eligible NPC patients were reviewed. The entire dataset was split into training cohort and testing cohort in a ratio of 90%:10%. Ten features from patient-related, disease-related, and treatment-related data were used to train the models for progression-free survival (PFS) prediction. The model performance was compared using the concordance index (c-index), Brier score, and log-rank test based on the risk stratification results. RESULTS: DeepSurv (c-index = 0.68, Brier score = 0.13, log-rank test p = 0.02) achieved the best performance compared to CSF (c-index = 0.63, Brier score = 0.14, log-rank test p = 0.38) and CPH (c-index = 0.57, Brier score = 0.15, log-rank test p = 0.81). CONCLUSIONS: Both CSF and DeepSurv outperformed CPH in our relatively small dataset. ML-based survival prediction may guide physicians in choosing the most suitable treatment strategy for NPC patients.

Induction Chemotherapy Combined With Intensity-Modulated Radiotherapy for 129 Nasopharyngeal Carcinoma Patients With Synchronous Metastases: A Retrospective Study.

OBJECTIVE: To analyze the therapeutic effect and prognostic factors of nasopharyngeal carcinoma (NPC) patients with distant metastases at initial diagnosis receiving induction chemotherapy with intensity-modulated radiotherapy (IMRT). METHODS: A total of 129 patients who underwent platinum-based induction chemotherapy followed by definitive IMRT with or without concurrent or adjuvant chemotherapy for newly diagnosed distant metastatic NPC in our center between March 2008 and November 2018 were retrospectively analyzed. 41 patients underwent local therapy for metastatic sites. Kaplan-Meier method was used to estimate survival rates, Log-rank test and Cox proportional hazards model were used to figure out independent prognostic factors of overall survival (OS). RESULTS: A total of 66 patients had been dead (median follow-up time, 51.5 months). The median overall survival (OS) time was 54.2 months (range, 7-136 months), and the 1-year, 2-year, 3-year, 5-year overall survival rates were 88.0%,71.0%,58.0%, and 47.0%. Multivariate analysis found that the factors correlated with poor overall survival were pre-treatment serum lactate dehydrogenase (SLDH) >180U/L, chemotherapy cycles<4, and M1 stage subdivision (M1b, single hepatic metastasis and/or multiple metastases excluding the liver; and M1c, multiple hepatic metastases). The 5-year OS rates for M1a, M1b and M1c were 62.6%,40.4% and 0%, respectively. CONCLUSION: Platinum-containing induction chemotherapy combined with IMRT seemed to be advantageous to prolong survival for some NPC patients with synchronous metastases at initial diagnosis. The independent factors to prognosticate OS were pre-treatment SLDH, number of chemotherapy cycles, and M1 subcategories. Prospective clinical trials are needed to confirm the result.

Clinical characteristics and prognosis of elderly nasopharyngeal carcinoma patients receiving intensity-modulated radiotherapy.

PURPOSE: To evaluate the clinical characteristics and prognosis of elderly nasopharyngeal carcinoma (NPC) patients receiving intensity-modulated radiotherapy (IMRT). METHODS: From June 2008 to October 2014, 148 newly diagnosed non-metastatic elderly NPC patients (aged ≥ 70 years) receiving IMRT were recruited. Comorbid condition was evaluated using the age-adjusted Charlson Comorbidity Index (ACCI). Kaplan-Meier method was used to estimate survival rates and the differences were compared using log-rank test. Hazard ratio (HR) and the associated 95% confidence interval (CI) were calculated using Cox proportional hazard model by means of multivariate analysis. RESULTS: The median follow-up time was 66.35 months. Estimated OS rate at 5 years for the entire group was 61.8% (95% confidence interval [CI] 0.542-0.703). The 5-year OS rate of RT alone group was 58.4% (95% [CI] 0.490-0.696) compared with 65.2% (95% [CI] 0.534-0.796) in CRT group (p = 0.45). In patients receiving IMRT only, ACCI score equal to 3 was correlated with superior 5-year OS rate in comparison with higher ACCI score 62.1% (95% [CI] 0.510-0.766) to 48.5% (95% [CI] 0.341-0.689), respectively; p = 0.024). A 5-year OS rate of 63.1% (95% [CI] 0.537-0.741) was observed in patients younger than 75 years old compared with 57.5% (95% [CI] 0.457-0.723) in patients older (p = 0.026). Patients with early-stage disease (I-II) showed better prognosis than patients with advanced-stage (III-IV) disease (5-year OS, 72.3-55.4%, respectively; p = 0.0073). The Cox proportional hazards model suggested that age independently predicted poorer OS (HR, 1.07; 95%CI 1.00-1.15, p = 0.04). CONCLUSION: The survival outcome of patients aged ≥ 70 years receiving IMRT only was similar to chemoradiotherapy with significantly less acute toxicities. Among the population, age is significantly prognostic for survival outcomes.

Her2-Targeted Multifunctional Nano-Theranostic Platform Mediates Tumor Microenvironment Remodeling and Immune Activation for Breast Cancer Treatment.

PURPOSE: The treatment of breast cancer is often ineffective due to the protection of the tumor microenvironment and the low immunogenicity of tumor cells, leading to a poor therapeutic effect. In this study, we designed a nano-theranostic platform for these obstacles: a photothermal effect mediated by a gold shell could remodel the tumor microenvironment by decreasing cancer-associated fibroblasts (CAFs) and promote the release of doxorubicin (DOX) from nanoparticles. In addition, it could realize photoacoustic (PA)/MRI dual-model imaging for diagnose breast cancer and targeted identification of Her2-positive breast cancer. METHODS: Her2-DOX-superparamagnetic iron oxide nanoparticles (SPIOs)@Poly (D, L-lactide-co-glycolide) acid (PLGA)@Au nanoparticles (Her2-DSG NPs) were prepared based on a single emulsion oil-in-water (O/W) solvent evaporation method, gold seed growing method, and carbon diimide method. The size distribution, morphology, PA/MRI imaging, drug loading capacity, and drug release were investigated. Cytotoxicity, antitumor effect, cellular uptake, immunogenic cell death (ICD) effect, and targeted performance on human Her2-positive BT474 cell line were investigated in vitro. BT474/Adr cells were constructed and the antitumor effect of NPs on it was evaluated in vitro. Moreover, chemical-photothermal therapy effect, PA/MRI dual-model imaging, ICD effect induced by NPs, and tumor microenvironment remodeling in human BT474 breast cancer nude mice model were also investigated. RESULTS: Nanoparticles were spherical, uniform in size and covered with a gold shell. NPs had a photothermal effect, and can realize photothermal-controlled drug release in vitro. Chemical-photothermal therapy had a good antitumor effect on BT474/Adr cells and on BT474 cells in vitro. The targeting evaluation in vitro showed that Her2-DSG NPs could actively target and identify Her2-positive tumor cells. The PA/MRI imaging was successfully validated in vitro/vivo. Similarly, NPs could enhance the ICD effect in vitro/vivo, which could activate an immune response. Immunofluorescence results also proved that photothermal effect could decrease CAFs to remodel the tumor microenvironment and enhance the accessibility of NPs to tumor cells. According to the toxicity results, targeted drug delivery combined with photothermal-responsive drug release proved that NPs had good biosafety in vivo. Chemical-photothermal therapy of Her2-targeted NPs has a good antitumor effect in the BT474 nude mice model. CONCLUSION: Our study showed that chemical-photothermal therapy combined with tumor microenvironment remodeling and immune activation based on the Her2-DSG NPs we developed are very promising for Her2-positive breast cancer.

Induction chemotherapy followed by radiotherapy for N3 head and neck squamous cell carcinoma.

BACKGROUND: The treatment outcomes for N3 HNSCC treated with induction chemotherapy (ICT) followed by definitive radiation were reported to clarify the role of ICT and potential prognostic factors. METHODS: A retrospective study was conducted on 120 patients with N3 (≥6 cm) HNSCC, who were treated with ICT as initial treatment. Survival outcomes and potential prognostic factors were reported. RESULTS: The response rate to ICT was 68.3%. There was a statistically significant difference between responders and non-responders in terms of 5-year OS (35.1% vs 13.3%, P < .001) and PFS (29.4% vs 7.4%, P < .001). Good response to ICT (P < .001) and upfront neck dissection (UFND) before radiotherapy (P = .016) were factors predicting for better OS. However, UFND before radiotherapy was not associated with improved outcomes among responders. CONCLUSIONS: This study suggests that ICT could be one treatment option for N3 HNSCC. Among responders to ICT, UFND before radiotherapy could be avoided.