Fangfang Kong

Shanghai Clinical Research Center

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Chengrun Du

Fudan University Shanghai Cancer Center

Chaosu Hu

Shanghai Medical College of Fudan University

Ruiping Zhai

University of South China

Hongmei Ying

Second Affiliated Hospital of Nanchang University

Hongmei Ying

Fudan University Shanghai Cancer Center

Mengshan Ni

Ruijin Hospital

Xiayun He

University of South China

Chaosu Hu

Fudan University Shanghai Cancer Center

Ronald Wihal Oei

National University of Singapore

Chunying Shen

Shanghai Medical College of Fudan University

Cooperative Institutions

Fudan University Shanghai Cancer Center

Shanghai Medical College of Fudan University

Shanghai Clinical Research Center

Shanghai Institute of Hematology

Fudan University

Jiangxi Science and Technology Normal University

Southeast University

Shanghai Jiao Tong University

Chinese Academy of Sciences

State Key Laboratory of Millimeter Waves

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

European Archives of Oto-Rhino-Laryngology (2023)

Mengshan Ni Fangfang Kong Guang-Sen Pan Chengrun Du Ruiping Zhai

Univariate analysis

10.1007/s00405-023-08330-0

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

Radiation Oncology (2022)

Ruiping Zhai Yingchen Lyu Mengshan Ni Fangfang Kong Chengrun Du

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).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.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.Thyroid Vt40 highly predicted the risk of hypothyroidism after IMRT for NPC patients. We recommended plan optimization objectives to reduce thyroid Vt40 to 80%.Retrospectively registered.

Cumulative incidence

Univariate analysis

10.1186/s13014-022-02028-z

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Citations (15)

Clinical outcome of intensity modulated radiotherapy for carcinoma showing thymus-like differentiation

Oncotarget (2016)

Fangfang Kong Hongmei Ying Ruiping Zhai Chengrun Du Shuang Huang

To evaluate the efficacy and toxicity of adjuvant intensity-modulated radiotherapy (IMRT) after surgery for carcinoma showing thymus-like differentiation (CASTLE).Between September 2008 and June 2015, 14 CASTLE patients were retrospectively enrolled. The clinical features, treatment procedure and clinical outcomes were reviewed. All patients received postoperative IMRT. The radiation doses ranged from 56Gy/28 fractions to 66Gy/33 fractions. Treatment-related toxicities were graded by National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 3.0.After a median follow-up period of 42 months, only one patient suffered local recurrence and distant metastasis. The most frequently seen acute toxicities were mucositis and dermatitis (grade 1-2). No grade 3-4 toxicities were observed.Although based upon a small series of consecutively treated patients, our study showed that adjuvant IMRT provides satisfactory local-regional control for CASTLE, with acceptable toxicities. Further studies are still warranted to clarify our findings.

Mucositis

Distant metastasis

Adjuvant radiotherapy

10.18632/oncotarget.11914

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Pre-treatment Serum Lactate Dehydrogenase is Predictive of Survival in Patients with Nasopharyngeal Carcinoma Undergoing Intensity-Modulated Radiotherapy

Journal of Cancer (2017)

Ronald Wihal Oei Lulu Ye Fangfang Kong Chengrun Du Ruiping Zhai

Objective: To analyze the prognostic value of pre-treatment serum lactate dehydrogenase (SLDH) level in patients with nasopharyngeal carcinoma (NPC) receiving intensity-modulated radiotherapy (IMRT) with or without chemotherapy. Methods: From January 2010 to March 2013, 427 eligible patients were reviewed. Pre-treatment SLDH level was measured within 2 weeks prior to treatment. Receiver operating characteristic (ROC) curve analysis was performed to select the optimal cutoff point. The impact of pre-treatment SLDH on overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS) were analyzed using Kaplan-Meier method and Cox proportional hazards model. Further propensity score matching was carried out to adjust bias. Results: The optimal cutoff point of 168.5 IU/L was selected based on ROC curve analysis. Multivariate analysis showed that high pre-treatment SLDH level was an independent prognostic factor for OS (P=0.001), PFS (P=0.004) and DMFS (P=0.001). After propensity score matching was performed, it remained to be significantly associated with poor OS (P=0.009), PFS (P=0.015) and DMFS (P=0.008) in the adjusted model. Conclusion: High pre-treatment SLDH level predicts poor survival in patients with NPC treated with IMRT-based therapy. As a routinely performed biomarker, pre-treatment SLDH can be utilized in combination with current Tumor-Node-Metastasis staging to predict survival and to plan a personalized treatment in these patients.

10.7150/jca.22190

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AntiPD-L1 antibody conjugated Au-SPIOs nanoparticles for enhancing radiosensitivity and activating anti-tumor immune response

Research Square (Research Square) (2022)

Chengrun Du Jianyun Jiang Caifeng Wan Guangsen Pan Fangfang Kong

Abstract To improve the radiation therapy outcomes by inducing more toxicity for tumors and less for normal tissue and switch microenvironment immunosuppressive caused by expression of PD-L1 and tumor-associated macrophages (TAMs) to immunoreactive, we designed a PD-L1-targeted nanoplatform consisting of gold nanoparticles (AuNPs) and superparamagnetic iron oxide nanoparticles (SPIOs)( antiPD-L1-SPIOs@PLGA@Au). AntiPD-L1-SPIOs@PLGA@Au targeted on the B16F10 cell membrane and in cytoplasm, and the association could be reduced by the antibody blocking. In vivo T2-weight image, the best enhancement effect of tumor was achieved two hours after intravenous injection of antiPD-L1-SPIOs@PLGA@Au. Compared with radiation alone, the Do sensitization ratios of antiPD-L1-SPIOs@PLGA@Au was 1.34. The inhibition effect of irradiation combined with antiPD-L1-SPIOs@PLGA@Au was higher than that of radiotherapy alone in the B16F10 subcutaneous tumor model. During the entire observation period, all mice in the antiPD-L1-SPIOs@PLGA@Au group lived longer than 3 weeks. AntiPD-L1-SPIOs@PLGA@Au enhancing radiosensitivity was achieved by increasing ROS production and attenuating DNA damage repair. In vitro and in vivo experiments showed that antiPD-L1-SPIOs@PLGA@Au could promote the polarization of tumor-associated macrophages (TAMs) to M1 and reverse the immunosuppressive regulation induced by TAMs. antiPD-L1-SPIOs@PLGA@Au could increase the expression of CRT in tumor, block the PD-L1/PD pathway, activate CD8+T cells, promote the increase of IFN-γ, TNF-α and IL-12 release, and finally activate the anti-tumor immune response. In conclusion, antiPD-L1-SPIOs@PLGA@Au was proved to have the ability to form targeted imaging and enhance radiosensitivity, block the PD-L1/PD-1 immune checkpoint pathway, reverse the immunosuppressive regulation caused by TAMs, successfully realizing the synergistic effect of radiotherapy combined with immunotherapy.

PLGA

Radiosensitivity

10.21203/rs.3.rs-1566279/v1

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

Cancers (2023)

Fangfang Kong Guangsen Pan Chengrun Du Chaosu Hu Hongmei Ying

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.

Induction chemotherapy

Chemoradiotherapy

10.3390/cancers15061689

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

Therapeutic Advances in Medical Oncology (2024)

Fangfang Kong Guang-Sen Pan Mengshan Ni Chengrun Du Chaosu Hu

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.

Standardized uptake value

Primary tumor

Recursive partitioning

Chemoradiotherapy

10.1177/17588359241233235

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Citations (2)

The prognostic value of tumor depth for cervical lymph node metastasis in hypopharyngeal and supraglottic carcinomas

Head & Neck (2019)

Lu‐Lu Ye Jia Rao Xingwen Fan Fangfang Kong Chaosu Hu

Abstract Background To analyze the prognostic value of the clinicopathological parameters of primary lesions for predicting cervical lymph node metastasis in patients with hypopharyngeal and/or supraglottic carcinoma. Methods We enrolled 127 patients with squamous cell carcinomas originating in the hypopharyngeal and/or supraglottic regions. Results Multivariate analysis identified the tumor depth as an independent predictive factor for lymph node metastasis (odds ratio, 4.959; 95% confidence interval, 2.290‐10.739; P < 0.0001) with a predictive value of 0.966. A cutoff value of 4.5 mm was determined. Conclusion The tumor depth of the primary lesion is a potent predictor of cervical lymph node metastasis in hypopharyngeal and supraglottic carcinomas. In cases with clinically negative nodal status, elective neck dissection should be adopted for patients with a tumor depth reaching 4.5 mm. Regular outpatient follow‐up is recommended for patients with a tumor depth less than 1.0 mm. Close follow‐up or preventative therapy should be considered between 1.0 and 4.5 mm.

Neck dissection

Hypopharyngeal cancer

Primary tumor

Cervical lymph nodes

10.1002/hed.25667

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Citations (16)

MRI-based radiomics signature is a quantitative prognostic biomarker for nasopharyngeal carcinoma

Scientific Reports (2019)

Xue Ming Ronald Wihal Oei Ruiping Zhai Fangfang Kong Chengrun Du

Abstract This study aimed to develop prognosis signatures through a radiomics analysis for patients with nasopharyngeal carcinoma (NPC) by their pretreatment diagnosis magnetic resonance imaging (MRI). A total of 208 radiomics features were extracted for each patient from a database of 303 patients. The patients were split into the training and validation cohorts according to their pretreatment diagnosis date. The radiomics feature analysis consisted of cluster analysis and prognosis model analysis for disease free-survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional recurrence-free survival (LRFS). Additionally, two prognosis models using clinical features only and combined radiomics and clinical features were generated to estimate the incremental prognostic value of radiomics features. Patients were clustered by non-negative matrix factorization (NMF) into two groups. It showed high correspondence with patients’ T stage (p < 0.00001) and overall stage information (p < 0.00001) by chi-squared tests. There were significant differences in DFS (p = 0.0052), OS (p = 0.033), and LRFS (p = 0.037) between the two clustered groups but not in DMFS (p = 0.11) by log-rank tests. Radiomics nomograms that incorporated radiomics and clinical features could estimate DFS with the C-index of 0.751 [0.639, 0.863] and OS with the C-index of 0.845 [0.752, 0.939] in the validation cohort. The nomograms improved the prediction accuracy with the C-index value of 0.029 for DFS and 0.107 for OS compared with clinical features only. The DFS and OS radiomics nomograms developed in our study demonstrated the excellent prognostic estimation for NPC patients with a noninvasive way of MRI. The combination of clinical and radiomics features can provide more information for precise treatment decision.

Nomogram

Distributed File System

10.1038/s41598-019-46985-0

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Citations (45)

microRNA- 145 在宫颈癌中的表达及其对Wnt/β-catenin信号通路的抑制作用

中国肿瘤临床 (2019)

王香青 Xiangqing Wang 马振军 Ma Zhenjun 包洪云

目的探讨microRNA-145在宫颈癌中表达的临床意义及其对Wnt/β-catenin信号通路的调控作用。方法收集2002年1月至2004年12月解放军464医院62例宫颈癌患者的组织标本, 采用实时荧光定量PCR 方法检测microRNA-145表达并将其分为高表达组和低表达组, 分析其与临床病理参数的关系。将microRNA-145表达质粒和无义对照质粒分别转染入宫颈癌HeLa中, 分为过表达microRNA-145组和对照组, 采用细胞免疫荧光染色法分析细胞中β-catenin表达定位的变化, 双荧光素酶报告系统检测细胞中TCF/LEF转录活性及与Cateninδ-1的直接作用, 采用Western blot法检测microRNA-145对Cateninδ-1、C-MYC和Cy- clinD1表达的影响。结果microRNA-145低表达组患者的总生存期为(41.28±2.00)个月, 高表达组为(46.06±0.95)个月, 两者比较差异具有统计学意义(P 结论microRNA-145可通过与Cateninδ-1直接作用, 抑制Wnt/β-catenin信号通路转导, 从而发挥抑制宫颈癌演进的生物学功能。

10.3969/j.issn.1000-8179.2019.03.870

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