Outcomes of icotinib combined with concurrent chemoradiotherapy in locally advanced cervical cancer.

Concurrent chemoradiotherapy (CRT) based on cisplatin is recognized as the current standard treatment for locally advanced cervical cancer. The treatment of cervical cancer has reached a plateau in the last 20 years. Previous studies have proven that the epidermal growth factor receptor is correlated with chemo- and radioresistance and treatment failure. Hence, the purpose of this study was to investigate the efficacy and safety of icotinib combined with CRT in the treatment of locally advanced cervical cancer. Eligibility criteria included patients treated in the radiotherapy department of Taizhou Central Hospital of Zhejiang Province for stage IIB to IIIB cervical cancers who had not received anti-tumor treatment before and a performance status of 0 to 2. Patients were given icotinib 125 mg three times a day for 6 weeks, which was one week before the start of radiotherapy (500 centigrays in 28 fractions) and chemotherapy (40 mg/m2 administered weekly for 3-5 cycles). There were 29 patients who completed the I+CRT treatment, and it was tolerated well. The median follow-up time was 50 months and 27 patients (93.10%) achieved complete responses. The 5-year cumulative overall survival rate and disease-free survival rate were 58.4% and 60.9%, respectively. The treatment with I+CRT is safe and effective for locally advanced cervical cancer. As far as we know, this is the first study to report the 5-year survival rate of locally advanced cervical cancer with targeted therapy combined with chemoradiotherapy.

Tumor mutation burden in Chinese cancer patients and the underlying driving pathways of high tumor mutation burden across different cancer types.

BACKGROUND: Tumor mutation burden (TMB) has an important association with immunotherapy responses. TMB in the Chinese population has not been well established. Finding differences between the Chinese and Caucasian populations and elucidating the underlying biological mechanisms of high TMB might help develop more precise and effective means for TMB and immunotherapy response prediction. METHODS: Chinese cancer patients fresh tissue (n=2,177), formalin-fixed, paraffin-embed (FFPE) specimens (n=3,294), and pleural fluid (n=189) were profiled using a 295- or 520-gene next-generation sequencing (NGS) panel. The association of the TMB status with a series of molecular features and biological pathways was determined using bootstrapping. RESULTS: TMB, measured by 295- or 520-cancer-related gene panels, was correlated with whole-exome sequencing (WES) TMB based on the in silico simulation in The Cancer Genome Atlas cohort. The median TMB of our data was slightly higher than that from the Foundation Medicine Inc. (FMI) dataset. TMB was also slightly different within the same cancer type between the Chinese and Caucasian population. We discovered that the underlying pathways of TMB status varied greatly and sometimes had an opposite association with TMB across different cancer types. Moreover, we developed a 23-gene and a 16-gene signature to predict TMB prediction for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), respectively, indicating a histology-specific mechanism for driving high-TMB in lung cancer. CONCLUSIONS: TMB varies among different ethnic populations. Our findings extend the knowledge of the underlying biological mechanisms for high TMB and might be helpful for developing more precise and accessible TMB assessment panels and algorithms in more cancer types.

Outcome and prognostic factors in cervical cancer patients treated with surgery and concurrent chemoradiotherapy: a retrospective study.

BACKGROUND: The objective of this study is to analyze the treatment outcome and secondary reactions in 98 patients with stage I-III cervical carcinoma who underwent postoperative radiotherapy. METHODS: From 2006 to 2014, 98 patients with stage I-III cervical carcinoma were treated with postoperative radiotherapy. The major histological type, found in 92.86% of the patients (91 cases), was squamous cell carcinoma. Patients were staged according to the 2002 TNM guidelines. The postoperative radiotherapy methods included two-field irradiation (16 patients, 16.32%), four-field box irradiation (16 patients, 16.32%), and intensity-modulated radiotherapy (IMRT; 66 patients, 67.36%). The survival rates were represented using Kaplan-Meier curves, and prognosis analyses were performed using Cox multivariate analyses. RESULTS: The 5-year overall survival and progression-free survival rates were 82.0 and 76.0%, respectively. Only one patient (1.02%) developed a grade 3 acute radiation enteritis, while grade 3 and 4 myelosuppression was noted in 17 patients (17.35%) and one patient (1.02%), respectively. Multivariate analyses showed that anemia before radiotherapy and tumor size were predictors of the OS (P = 0.008, P = 0.045) rates. CONCLUSIONS: Postoperative radiotherapy for patients with risk factors of cervical cancer procured good efficacy levels with mild side effects. Anemia and tumor size were important OS predictors.

Expression of HIF-1α and HIF-2α correlates to biological and clinical significance in papillary thyroid carcinoma.

BACKGROUND: The aim of this study was to detect the expression of hypoxia-inducible factor (HIF)-1α and HIF-2α in papillary thyroid carcinoma (PTC) compared with normal thyroid tissues. METHODS: The mRNA levels and protein levels of HIF-1α and HIF-2α were detected by real-time PCR and Western blot separately in 30 pairs of PTCs and normal thyroid cases. The protein levels were also detected by immunohistochemistry (IHC) using 92 samples of PTC group and 46 normal samples as control group for analyzing the biological and clinical significance of the expression of HIF-1α/HIF-2α. RESULTS: Real-time PCR results showed the mRNA level of HIF-1α and HIF-2α were significantly higher in PTC than normal group (P<0.001). Also, significantly higher positive rates (73%/65%) of HIF-1α and HIF-2α were observed in PTC compared with the control group (27%/35%) by IHC (P<0.01); the consistent results were gotten with Western blot. Although we did not find a significant correlation between the expression of HIF-1α and HIF-2α with gender, age, calcification, or Hashimoto's disease in the present study (P>0.05), both of their expressions were correlated to lymph node metastasis (P<0.05), capsular invasion (P<0.05), and TNM stage (P<0.05). CONCLUSIONS: Overexpression of HIF-1α and HIF-2α are associated with the carcinogenesis of PTC, served as potential biomarkers of PTC.