Impact of Molecular Pathological And Clinical Features for Adjuvant Treatment Selection in Endometrial Cancer: Multicentric Asian Registry (IMPACT-Endo-Asia)
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 300
- 试验地点
- 2
- 主要终点
- To study the Clinico-pathological characteristics in Endometrial Cancer
研究概览
简要总结
The treatment practices for endometrial cancer have significantly changed over the last two decades. Nowadays, in addition to standard pathology, additional tests are performed to understand the behaviour of tumour so that personalized treatment can be advised for every patient. This approach ensures that patients with good cancer cell features receive minimum essential radiotherapy or surgery treatment with fewer side effects, while those with poor cell features undergo more aggressive treatment to improve their chances of survival.
However, this approach is not widely adopted in Asian countries. To address this, investigators are launching a project to gather data from various hospitals across Asia. The project aims to understand how different cancer cell factors impact treatment decisions and identify better ways to select additional treatment plans based on a patient's cancer cell features.
The project will gather data from around 250-300 patients who were evaluated or treated between January 2021 and December 2023. It will run for two years to improve our understanding and gain insights into the best ways to treat endometrial cancer.
详细描述
Endometrial cancer (EC) is the second most common gynecological malignancy affecting women worldwide. As per GLOBOCAN data, the incidence was 382,069 with a mortality of 89,929 in 2018, out of which Asia accounts for 40% of the new cases. By 2040 global incidence is predicted to increase by more than 50% as per the International Agency for Research on Cancer. Although the incidence is higher in the Western world, there is a persistent rising trend among low- and middle-income countries. EC is the fourth most common cause of cancer death among women of low socioeconomic status .3-5% of patients have inherited (Mismatch repair) mutation and are diagnosed to have Lynch syndrome also suggesting an overlapping genetic predisposition. Historically Bokhman's dualistic EC histopathological classification was based on tumor biological behavior and prognosis. Type I (60-70%) included endometrioid histology with a 5-year overall survival (OS) of 83-88%. The rest of the non-endometrioid histology was included in Type II (30%) which was associated with a higher risk of relapse and showed a 5-year OS of 54-64%. This classification had limited risk stratification, which led to inter-observer error of 60% and poor reproducibility of patient outcomes when references to pathological subtypes. Later two-tier tumor grading systems as per the International Federation of Gynecology and Obstetrics (FIGO) defined criteria had combined Grade 1 and 2 EC as low grade and Grade 3 EC as high grade. Several other high-risk features like myometrial invasion (MI) of more than 50%, substantial lymph vascular space invasion (LVSI), lymph node involvement, and tumor size of more than 2 cm were also considered in the classification. Prognostic classification based on morphological features alone leads to inaccuracies in tumor biology characterization, non-reproducibility due to the overlap of clinical-genetic characteristics causing heterogeneous molecular groups, heterogenous adjuvant treatment decisions (due to pathology variation).
More recently developments in genetics and molecular characterization have integrated classification methods, which include genomic profiling along with histopathological features. The Cancer Genome Atlas (TCGA)molecular classification first described four distinct subgroups based on molecular features which estimated the recurrence risk and predicted the survival in serous and endometrioid EC.
- Pole ultra mutated (mutation in exonuclease domain of DNA polymerase epsilon)
- Hypermutated with MSI/MMRd (loss of Mismatch Repair protein immunoreactivity)
- Somatic copy number-low with frequent PI3K and WNT signaling abnormality (endometrioid-like)
- Somatic copy number-high with frequent pathological variants in TP53(serous-like)
This molecular classification when integrated with standard pathology provided a relatively clearer distinction of outcomes.
Key observations from molecular classification studies also looking into clinical outcomes were as follows:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •- Patients who were diagnosed to have EC and have access to standard histopathological reports and availability of treatment decisions.
排除标准
- •- Patients with final histopathological diagnosis of any other gynecological malignancy other than EC and its subtypes.
结局指标
主要结局
To study the Clinico-pathological characteristics in Endometrial Cancer
时间窗: 24 months
Proportion of Endometrial Cancer Molecular Subtypes (POLEmut, MMR-deficient, NSMP, p53 abnormal) and distribution of adjuvant radiation therapy types received (vaginal brachytherapy, external beam radiation therapy \[EBRT\], or combined radiation with chemotherapy) reported at treatment completion.
To study molecular characteristics in Endometrial Cancer.
时间窗: 24 Months
Proportion of Endometrial Cancer Cases by Tumor Grade, Histological Type, and Tumor Stage
To study the Clinicopathologic characteristics impact on treatment decision making across Asian regions
时间窗: 24 Months
proportion of patients who exhibit predefined clinicopathologic characteristics with percentages reported for each participating Asian region
To study molecular characteristics impact on treatment decision making across Asian regions.
时间窗: 24 Months
Proportion of participants whose treatment decisions are influenced by molecular characteristics. Data will be summarized by Asian region and analyzed in relation to clinical and demographic characteristics to assess the overall impact on treatment decision making.
次要结局
- Comparison of risk grouping using standard histopathological features versus standard histopathological features plus molecular profile(24 Months)
- To report the selection of adjuvant treatment based on standard histopathological features alone or along with molecular risk features(24 Months)
- To study the transition of staging towards FIGO 2023.(24 Months)
- To study the adequacy of risk grouping practices across Asian regions by comparing to ESTRO/ESGO/ESP and FIGO updates(24 Months)
- To study the choice of External beam radiotherapy technique and brachytherapy applicators utilized(24 Months)
- To report the 3 years disease free survival(From the date of treatment completion till the date of any signs of recurrence / relapse upto a period of 3 years)
- To study the family history in Endometrial Cancer(24 Month)
- To report the 3 years Local control.(From the date of treatment completion till the date of any signs of local control upto a period of 3 years)
研究者
Supriya Sastri (chopra)
Professor, Radiation Oncology
Tata Memorial Hospital