Clinical characteristics and radiation therapy modality of younger patients with early-stage endometrial cancer, a multicenter study in China's real world.

BACKGROUND: Endometrial cancer is a prevalent gynecologic malignancy found in postmenopausal women. However, in the last two decades, the incidence of early-stage has doubled in women under 40 years old. This study aimed to investigate the clinical and pathological characteristics and adjuvant therapeutic modalities of both young and not -young patients with early-stage endometrial cancer in China's real world. METHODS: This retrospective study analyzed patients with early-stage endometrial cancer at 13 medical institutions in China from 1999 to 2015. The patients were divided into two groups: young (≤ 45 years old) and non-young (> 45 years old). Statistical comparisons were conducted between the two groups for clinical characteristics, pathological features, and survival. The study also identified factors that affect local recurrence-free survival (LRFS) using Cox proportional risk regression analysis. Propensity score matching (1:1) was used to compare the effects of local control between vaginal brachytherapy (VBT) alone and pelvic external beam radiotherapy (EBRT) ± VBT. RESULTS: The study involved 1,280 patients, 150 of whom were 45 years old or younger. The young group exhibited a significantly higher proportion of stage II, low-risk, lower uterine segment infiltration (LUSI), and cervical invasion compared to the non-young group. Additionally, the young patients had significantly larger maximum tumor diameters. The young group also had a significantly higher five-year overall survival (OS) and a five-year LRFS. Age is an independent risk factor for LRFS. There was no significant difference in LRFS between young patients with intermediate- to high-risk early-stage endometrial cancer who received EBRT ± VBT and those who received VBT alone. CONCLUSIONS: In the present study, young patients had better characteristics than the non-young group, while they exhibited higher levels of aggressiveness in certain aspects. The LRFS and OS outcomes were better in young patients. Age is an independent risk factor for LRFS. Additionally, VBT alone may be a suitable option for patients under 45 years of age with intermediate- to high-risk early-stage endometrial cancer, as it reduces the risk of toxic reactions and future second cancers while maintaining similar local control as EBRT.

Practice patterns of adjuvant radiotherapy in women with stage I to II endometrial carcinoma: a real-world multi-institutional analysis in China.

BACKGROUND: This study aimed to report clinical practice patterns of postoperative radiotherapy for stage I to II endometrial carcinoma (EC) patients treated in 13 Chinese medical centers. METHODS: We included early stage EC patients treated by hysterectomy and adjuvant RT between 2003 and 2017 from 13 institutions. Patients were classified into 4 risk groups based on ESMO-ESGO-ESTRO recommendations (2014). RESULTS: A total of 1,227 cases were analyzed. Along the 15 years of the study, an increasing tendency was found towards administration for vaginal brachytherapy (VBT) alone, while the proportion of external beam pelvic radiotherapy (EBRT) alone remained stable in the corresponding period. When radiation modalities were stratified by risk groups, proportion of VBT alone significantly increased in all risk groups. The higher the risk, the later VBT became the main adjuvant treatment modality. However, EBRT alone or with VBT remained the main adjuvant method for high-risk patients. There were 13 dose-fractionation schemes for VBT alone with the scheme of 30 Gy in 6 fractions prescribed at 0.5cm under the vaginal mucosa accounting for most. There were 17 schemes for VBT boost and the most common schedule was 10 Gy in 2 fractions. The upper 3-5cm part of vagina was the most frequent target. 89.6% of the practitioners performed two-dimensional VBT technique. The median dose for EBRT was 50 Gy. From 2003 to 2017, conventional radiotherapy was gradually replaced by three-dimensional conformal radiotherapy modality and intensity modulated radiotherapy. CONCLUSION: We report a significant shift from EBRT to VBT alone for high-intermediate-risk, intermediate-risk and low-risk EC patients from 2003 to 2017 while EBRT remained the main radiation modality for high-risk early stage patients. There has been remarkable heterogeneity among VBT dose fractionation schedules across China. TRIAL REGISTRATION: The clinical trial ID was ChiCTR-PRC-17010712. It was authorized by the Institutional Review Board of Peking Union Medical College Hospital (N0. S-K139).

The role of miR-143-3p/FNDC1 axis on the progression of non-small cell lung cancer.

The study aimed to explore the functional role of fibronectin type III domain containing 1 (FNDC1) in nonsmall cell lung cancer (NSCLC), as well as the mechanism governing its expression. The expression levels of FNDC1 and related genes in tissue and cell samples were detected by qRT-PCR. Kaplan-Meier analysis was employed to analyze the association between FNDC1 level and the overall survival of NSCLC patients. Functional experiments such as CCK-8 proliferation, colony formation, EDU staining, migration and invasion assays were conducted to investigate the functional role of FNDC1 in regulating the malignancy of NSCLC cells. Bioinformatic tools and dual-luciferase reporter assay were used to identify the miRNA regulator of FNDC1 in NSCLC cells. Our data revealed the upregulation of FNDC1 at mRNA and protein levels in NSCLC tumor tissues cancer cell lines, compared with normal counterparts. NSCLC patients with higher FNDC1 expression suffered from a poorer overall survival. FNDC1 knockdown significantly suppressed the proliferation, migration and invasion of NSCLC cells, and had an inhibitory effect on tube formation. We further demonstrated that miR-143-3p was an upstream regulator of FNDC1 and miR-143-3p expression was repressed in NSCLC samples. Similar to FNDC1 knockdown, miR-143-3p overexpression inhibited the growth, migration and invasion of NSCLC cells. FNDC1 overexpression could partially rescue the effect of miR-143-3p overexpression.  FNDC1 silencing also suppressed the tumorigenesis of NSCLC cells in mouse model. In conclusion, FNDC1 promotes the malignant prototypes of NSCLC cells. miR-143-3p is a negative regulator of FNDC1 in NSCLC cells, which may serve as a promising therapeutic target in NSCLC.

Preoperative serum CA125 level and age at diagnosis: An effective prognosis prediction tool for patients with early-stage endometrial cancer.

OBJECTIVE: To investigate the combined predictive value of the preoperative serum cancer antigen 125 (CA125) level and age at diagnosis among patients with early-stage endometrial cancer (EC) after initial treatment. METHODS: We retrospectively analyzed data from patients with early-stage EC from 1999 to 2015 in multiple institutions in China. All 447 patients received postoperative adjuvant radiotherapy for FIGO 2009 stage I and II EC with complete data on preoperative serum CA125 levels. All patients were divided into four groups according to the ESMO-ESGO-ESTRO risk classification. The predictive probability of 5-year overall survival (OS) and the sensitivity and specificity of CA125 and age were calculated. RESULTS: The median follow-up time was 59 months (3-201 months). The 5-year OS and disease-free survival rates were 94.4% and 89.1%. Multivariate analysis showed that the preoperative CA125 level and age at diagnosis were independent prognostic factors for 5-year OS. The area under the curve for CA125 combined with age at diagnosis for 5-year OS was .692, and the corresponding sensitivity and specificity were 68.2% and 68.2% (p < .002), which were significantly better than the corresponding values for CA125 or age alone. After all 447 patients were divided into four groups according to CA125 combined with age, the 5-year OS of the elderly and higher CA125 group was only 73.7%. CONCLUSIONS: Although preoperative CA125 had limited sensitivity in predicting the prognosis for early-stage EC after initial treatment, it remains a useful serum marker for risk assessment of early-stage EC. Combining CA125 with age may increase its predictive sensitivity.

Utilization Trend and Comparison of Different Radiotherapy Modes for Patients with Early-Stage High-Intermediate-Risk Endometrial Cancer: A Real-World, Multi-Institutional Study.

This study aimed to compare the outcomes of RT modalities among patients who met different HIR criteria based on multicentric real-world data over 15 years. The enrolled patients, who were diagnosed with FIGO I-II EC from 13 medical institutes and treated with hysterectomy and RT, were reclassified into HIR groups according to the criteria of GOG-249, PORTEC-2, and ESTRO-ESMO-ESGO, respectively. The trends in RT modes utilization were reviewed using the Man-Kendall test. The rate of VBT alone increased from zero in 2005 to 50% in 2015, which showed a significant upward trend (p < 0.05), while the rate of EBRT + VBT utilization declined from 87.5% to around 25% from 2005 to 2015 (p > 0.05). There were no significant differences in OS, DFS, LRFS, and DMFS between VBT alone and EBRT ± VBT in three HIR cohorts. Subgroup analyses in the GOG-249 HIR cohort showed that EBRT ± VBT had higher 5-year DFS, DMFS, and LRFS than VBT alone for patients without lymph node dissection (p < 0.05). Thus, VBT could be regarded as a standard adjuvant radiation modality for HIR patients. EBRT should be administrated to selected HIR patients who meet the GOG-249 criteria and did not undergo lymph node dissection.

FSCN1 Promotes Glycolysis and Epithelial-Mesenchymal Transition in Prostate Cancer through a YAP/TAZ Signaling Pathway.

Objective: The aim of the study is to investigate the role and possible mechanism of fascin-1 (FSCN1) in the invasion, migration, glycolysis, and epithelial-mesenchymal transition (EMT) of prostate cancer. Methods: Real-time quantitative polymerase chain reaction (qRT-PCR) was utilized to determine the mRNA expression level of FSCN1 in prostate cancer tissues and prostate cancer cells PC-3 and DU145. The transwell and the scratch test were applied to detect the invasion and migration abilities of cells, respectively. A metabolic assay was used for measuring the glucose consumption, lactate production, and the extracellular acidification rate (ECAR) in cells; western blot was used for checking FSCN1, EMT, and yes-associated protein/transcriptional co-activators with the PDZ-binding motif (YAP/TAZ) signaling pathway-related protein expression level in cells or tissues. Results: FSCN1 was significantly highly expressed in prostate cancer tissues and cells. On the one hand, interference with the expression of FSCN1 could inhibit the invasion, migration, EMT, and glycolysis of prostate cancer cells. On the other hand, overexpression of FSCN1 promoted the invasion, migration, EMT, and glycolysis of prostate cancer cells. Besides, further mechanistic studies revealed that FSCN1 could activate the YAP/TAZ signaling pathway in prostate cancer cells. Conclusion: FSCN1 promotes invasion, migration, EMT, and glycolysis in prostate cancer cells by activating the YAP/TAZ signaling pathway. FSCN1 may be used as a biomarker for the diagnosis or treatment in prostate cancer.

Overview of adjuvant radiotherapy on survival, failure pattern and toxicity in stage I to II endometrial carcinoma: a long-term multi-institutional analysis in China.

BACKGROUND: This research aimed to provide an overview of the impact of adjuvant vaginal brachytherapy (VBT) and external beam pelvic radiotherapy (EBRT) with or without VBT on survival in stage I to II EC patients in China from a long-term multi-institutional analysis. METHODS: We retrospectively analyzed stage I to II EC patients from 13 institutions treated between 2003 and 2015. All patients underwent surgical staging and received adjuvant RT. Patients were divided into groups of low-risk (LR), intermediate-risk (IR), high-intermediate-risk (HIR) and high-risk (HR). Survival statistics, failure pattern, and toxicity of different radiation modalities in different risk groups were analyzed. RESULTS: A total of 1048 patients were included. HR disease represented 27.6%, HIR 17.7%, IR 27.7% and LR 27.1%, respectively. Endometrioid adenocarcinoma (EAC) and non-endometrioid carcinoma (NEC) accounted for 92.8 and 7.2%. A total of 474 patients received VBT alone and 574 patients received EBRT with or without VBT. As for EAC patients, the 5-year overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) rate was: 94.6, 90.4, 93.0 and 91.6%, respectively. For LR patients, EBRT (with or without VBT) seemed to be a risk factor. With the higher risk category, the survival benefit of EBRT gradually became remarkable. EBRT (with or without VBT) significantly increased DFS, LRFS and DMFS compared to VBT alone in the HR group (p < 0.05). Distant metastasis was the main failure pattern for all risk groups. As for NEC patients, the 5-year OS, DFS, LRFS and DMFS rate was: 93.4, 87.2, 91.7 and 89.3%, respectively. As for toxicity, EBRT (with or without VBT) significantly increased the incidence of grade 1-2 gastrointestinal, urinary, and hematological toxicity. CONCLUSIONS: For stage I to II EC patients, EAC accounted for the majority and had better prognosis than NEC. For EAC patients, VBT alone resulted in comparable survival to EBRT in the LR, IR and HIR groups, while EBRT significantly increased survival in the HR group. EBRT had higher rate of toxicity than VBT.

Effect of age as a continuous variable in early-stage endometrial carcinoma: a multi-institutional analysis in China.

OBJECTIVE: To explore the effect of age at diagnosis as a continuous variable on survival and treatment choice of patients with early-stage endometrial carcinoma (EC). MATERIALS AND METHODS: We retrospectively analyzed data from patients with early-stage EC from January 1999 to December 2015 in multiple institutions in China. All patients received primary hysterectomy/bilateral salpingo-oophorectomy and adjuvant radiotherapy for EC confirmed pathology of stage I and II disease (FIGO 2009 staging). All patients were divided into low-risk, intermediate-risk, high-intermediate-risk and high-risk groups according to ESMO-ESGO-ESTRO risk classification. RESULTS: The median follow-up time was 57months, and the 5-year cancer-specific survival (CSS) was 95.7%. Age as a continuous variable was an independent prognostic factor for CSS. With an increase in age, the hazard ratio (HR) for CSS increases gradually. Other independent prognostic factors included myometrial invasion (MI), grade, and chemotherapy. In the stratified analysis of age, the HRs of age on CSS in patients >70y were 5.516, 5.015, 4.469, 4.618, 5.334, and 5.821 after adjusting for cancer characteristics, local treatment, chemotherapy and treatment-related late toxicity. In patients 66-70-year-old, the HRs were 2.509, 2.074, 2.101, 2.091, 2.157 and 1.621 after adjusting for the above covariates. In patients ≤65y, there was no significant difference in the HR of age on CSS after adjustment. CONCLUSION: Age as a continuous variable is an independent prognostic factor and 65 year-old may be the best cut-off point for CSS in patients with early-stage EC in the Asian population. Quality of life should be given greater weight in the choice of therapeutic schedule for those patients >70 y.

Treatment optimization of pelvic external beam radiation and/or vaginal brachytherapy for patients with stage I to II high-risk Endometrioid adenocarcinoma: a retrospective multi-institutional analysis.

BACKGROUND: For stage I to II high-risk endometrioid adenocarcinoma patients, the optimal adjuvant radiotherapy modality remains controversial. The present study sought to optimize the treatment of pelvic external beam radiation (EBRT) with/or vaginal brachytherapy (VBT) for high-risk endometrioid adenocarcinoma patients in multiple radiation oncology centers across China. METHODS: This article retrospectively reviewed stage I to II patients with resected endometrioid adenocarcinoma treated at 13 radiation centers from 1999 to 2015. Patients were eligible if they had high-risk features (stage IB Grade 3 disease or stage II Grade 1-3 disease) on the basis of ESMO-ESGO-ESTRO risk group consensus. RESULTS: A total of 218 patients were included. Fifty-one patients received EBRT, 25 patients received VBT, and 142 patients were administered EBRT combined with VBT. The three groups were comparable in baseline characteristics, except the proportion of stage IB and Grade 3 disease in the VBT group was significantly higher and their age was older. Survival analysis showed that OS, DFS, LRFS and DMFS were significantly different among the three groups. Two out of three groups were compared with each other, and results demonstrated that DFS, LRFS and DMFS were worse in the VBT group than in the EBRT or EBRT + VBT group. The 3-year OS rates were 95.2, 85.2 and 95.1% in the EBRT, VBT and EBRT + VBT groups, respectively (p = 0.043). There was no significant difference in survival outcomes between EBRT group and EBRT + VBT group. A propensity matching analysis was performed to eliminate group differences. The results demonstrated that DFS and LRFS were significantly improved in the pelvic radiation group compared to the VBT group. Distant failure accounted for most of the failure patterns. Patients in the VBT group had significantly increased local and regional recurrence rates than patients in the EBRT or EBRT + VBT group. Acute and chronic radiation-induced toxicities were well tolerated for all patients. CONCLUSION: For patients with postoperative stage I to II high-risk endometrioid adenocarcinoma, compared with VBT alone, radiotherapy modalities including EBRT significantly improved DFS, LRFS and DMFS with tolerable adverse effects. Overall survival was not significantly different between EBRT and EBRT + VBT modalities.