Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

patients with stages I-III lung cancer eligible for surgery

Lunxu Liu, M.D.,Ph.D.

This study aims to promote the rational use of liquid biopsy in the clinical detection of lung cancer. Lung cancer is a malignant tumor with high morbidity and mortality worldwide. The incidence of lung cancer in China is expected to increase in the next few years with the aging population and environmental pollution. Early diagnosis and effective intervention are necessary in the clinical treatment of lung cancer. Surgical resection could achieve a better prognosis for patients with early lung cancer. However, for advanced lung cancer, individualized treatment based on the pathological classification, molecular genetic characteristics, and body conditions of patients could effectively prolong the lifetime. The prevention, diagnosis, and intervention strategies for lung cancer depend on the oncology information of patients. The techniques and methods used for detecting lung cancer in clinic include imaging technology, pathological biopsy, screening of blood tumor markers, and liquid biopsy technology, which has been developed recently. The liquid biopsy can capture the oncology information, including tumor load, tumor gene mutation, and so on, from the blood of patients with cancer by detecting circulating tumor cells, tumor exosome, circulating tumor DNA, and circulating tumor RNA. Moreover, it has become an important direction for clinical tumor detection because of its noninvasiveness, convenient sampling, and potential for overcoming tumor heterogeneity. This study intends to include 400 patients with stage I-III lung cancer to research on lung cancer diagnosis, drug efficacy, surgical effect evaluation, recurrence monitoring, prognosis judgment, medication guidance, and molecular classification differentiation through the dynamic detection of blood ctDNA using the second-generation sequencing technology. The study also intends to analyze and establish the database with a large sample size.

Lung cancer is a malignant tumor with high morbidity and mortality worldwide. The incidence and mortality of lung cancer in China have topped the list of malignant tumors since 2010.Early diagnosis and effective intervention are extremely important in the clinical treatment of lung cancer. Surgical resection could achieve better prognosis in patients with early lung cancer (stages IA and IB).For patients with advanced lung cancer (stages II, III, and IV), individualized treatment with molecular classification researches and the application of targeted drugs based on the pathological classification, molecular genetic characteristics, and body conditions of patients has been confirmed to effectively prolong the lifetime. However, the lack of effective and convenient detection approaches for capturing oncology information of patients, promoting early diagnosis and effective intervention of lung cancer, and ultimately improving the prognosis of lung cancer are limitations in achieving successful clinical treatment of lung cancer.

At present, methods used in clinical screening of lung cancer,including detection of serological markers, imaging technology, and biopsy ,have some limitations:in the absence of imaging evidence, the serological assessment could not be used as the evidence for diagnosis and treatment strategy alteration for lung cancer. The application of low-dose computed tomography scan for lung cancer screening shows a high false-positive rate, which is liable to require excessive medical treatment. Biopsy does greater harm to patients with lung cancer; sampling is difficult, and effective information may be missed because of tumor heterogeneity. With the development of molecular pathology in cancer research in recent years, liquid biopsy has become an important developmental direction for clinical tumor detection because of its noninvasiveness, convenient sampling, and potential for overcoming tumor heterogeneity.Liquid biopsies include the detection of circulating tumor cells (CTCs), tumor exosome (exosome), circulating tumor RNA (ctRNA), and circulating tumor DNA (ctDNA) in peripheral blood.

ctDNA is a part of circulating free DNA (cfDNA), which is released by tumor cell necrosis, apoptosis, micrometastasis, or the cleavage of CTCs and proliferated tumor cells.ctDNA includes genetic information of tumor cells, such as mutation, recombination, and deletion (15). ctDNA was approved by the European Medicines Agency in 2014 and the National Comprehensive Cancer Network Guidelines for NSCLC in 2017 as a supplement sample to assess genetic variation when tumor tissue samples were difficult to obtain. Clinical studies have shown that ctDNA can effectively reflect tumor load, malignant degree, metastasis ability, and real-time information of genetic mutation, which has a certain correlation with the genetic information of tumor tissues. Moreover, the content of cfDNA in patients with cancer was significantly higher than that in healthy people. Also, ctDNA has been used for detecting tumor load, monitoring tumor recurrence, and assessing minimal residual disease in a number of cancer types. Some studies have suggested that ctDNA can be used to estimate tumor recurrence, even before imaging. Therefore, ctDNA detection has an important value in the clinical application of lung cancer diagnosis, drug efficacy, surgical effect evaluation, recurrence monitoring, prognosis judgment, medication guidance, and molecular classification differentiation.

This study intends to include 400 patients with stage I-III lung cancer. The capture sequencing of lung cancer-related genes in peripheral blood ctDNA and tumor tissue DNA will be performed during the diagnosis and treatment process using the liquid-phase hybridization approach. Thus, the study will establish a large sample size database of the genetic variants in patients with lung cancer during the diagnosis and treatment process, and promoted the development of an individualized diagnostic model of the lung cancer population. The patients with lung cancer undergoing surgery will be followed up, and the plasma concentration of cfDNA and genetic mutation of ctDNA will be detected to evaluate the postoperative residual cancer, monitor tumor recurrence, and timely guide the clinical treatment and intervention. The molecular classification differentiation analysis and screening of tumor recurrence-related genetic mutations will be performed after the surgery and during the course of disease progression to provide the referential clinical research model and ideas for the application of ctDNA detection-based liquid biopsy technique in tumor therapy.

Dynamic Monitoring Circulating Tumor DNA in Surgical Patients With Lung Cancer

A Study of the Value of Dynamic Monitoring Circulating Tumor DNA in Patients With Lung Cancer for Post-Operative Evaluation,Therapy Response Assessment,Relapse Prediction and Defining Molecular Phenotypes.

from the date of surgery until the date of first verified recurrence or death from any cause

from the date of surgery until the date of death from any cause

the relationship between heterogeneity of lung cancer and clinical results following surgery and adjuvant therapy

GeneCast Biotechnology Co., Ltd.

Sichuan Provincial People's Hospital

West China Hospital

Professor and Chair of Department of Thoracic surgery

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Axitinib

Immunomodulating Agents

Sunitinib

Immune Checkpoint Inhibitors

Angiogenesis Inhibitors

Growth Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Immunological

Programmed death-ligand 1 Inhibitor combined with axitinib

sunitinib or pazopanib

targeted therapy combined with immunotherapy

PD-1 inhibitor combined with axitinib

wei xue

jiwei huang, M.D

wei xue, M.D

Next-Generation Sequencing and whole transcriptome RNA sequencing were used to detect genomic variation and expression in tissues or blood, respectively. The treatment outcome of single targeted therapy or combined with immunotherapy was observed and followed up. Through this study, we intend to achieve RNA molecular classification of Chinese mRCC patients and to evaluate the correlation between ctDNA level, RNA molecular classification and treatment outcome, provide reference for metastatic RCC precise diagnosis and treatment.

Application Circulating Tumor DNA Dynamic Monitoring in Clinical Treatment of Metastatic Renal Cell Carcinoma

A Prospective Observational Study of Molecular Classification and Circulating Tumor DNA Dynamic Monitoring to Explore Related Factors That Predict the Efficacy of Single Targeted Therapy or Combined With Immunotherapy for Metastatic Renal Cell Carcinoma

Ruijin Hospital

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Xiangya Hospital of Central South University

Fudan University

Second Affiliated Hospital, School of Medicine, Zhejiang University

Second Affiliated Hospital of Nantong University

Peking University First Hospital

Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University

Shanghai Jiao Tong University Affiliated Sixth People's Hospital

Zhejiang University

First Affiliated Hospital of Wenzhou Medical University

Sir Run Run Shaw Hospital

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

The General Hospital of Eastern Theater Command

The First Affiliated Hospital with Nanjing Medical University

The First Affiliated Hospital of University of Science and Technology of China

The Second Hospital of Anhui Medical University

Tongji Hospital

The First Affiliated Hospital of Zhengzhou University

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Peking Union Medical College Hospital

The First Affiliated Hospital of Shanxi Medical University

Shanxi Provincial Cancer Hospital

Changzhi Medical College

First Affiliated Hospital Xi'an Jiaotong University

Second Affiliated Hospital of Xi'an Jiaotong University

Xijing Hospital of Air Force Military Medical University

Tang-Du Hospital

Quanzhou First Hospital Affiliated to Fujian Medical University

Third Affiliated Hospital, Sun Yat-Sen University

RenJi Hospital

Endometrial Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Paclitaxel

Carboplatin

Doxorubicin

Liposomal doxorubicin

Albumin-Bound Paclitaxel

Cisplatin

Establishment of molecular-clinicopathological classification to make adjuvant treatment decisions: observation for favourable group; vaginal brachytherapy(VBT) for intermediate group; external beam radiotherapy(EBRT) for unfavourable group.

Molecular-clinicopathological classification strategy：Favourable group：POLE-mutated. CTNNB1(wide-type)with IA (G1-3) or IB(G1-2)and LVSI(lymph-vascular space invasion) focal/-.

Intermediate group：MMRD and LVSI focal/-. CTNNB1(wide-type) and IB(G3) or II with LVSI focal/-. CTNNB1-mutated and IA(G1-3) or IB (G1-2) with LVSI focal/-.

Unfavourable group: TP53 mutation. CTNNB1-mutated and IB (G3) or II. Substantial LVSI.

Adjuvant vaginal brachytherapy alone for intermediate risk patients (IA G1-2 with LVSI present or age\>60, IA G3 or IB G1-2 regardless of LVSI status).

EBRT for high-intermediate risk (stage I B with G3, or stage II)

High-dose rate vaginal brachytherapy (VBT) was delivered with a vaginal cylinder.For VBT administered alone, the dose is recommended: 3 fractions of 7 Gy or 5 fractions of 6 Gy or 6 fractions of 5 Gy.

For VBT administered after completion of EBRT: 2-3 fractions of 4-6 Gy.

Vaginal brachytherapy

EBRT was delivered to the pelvic area using a total dose of 45-50.4Gy in 25-28 fractions over 5-6 weeks with the intensity-modulated radiotherapy (IMRT) technique, three-dimensional conformal radiotherapy (3D-CRT) modality

Pelvic external beam radiotherapy

No radiotherapy is administrated, but active follow-up and quality of life questionnaires is needed after surgery.

Observation

Intravenous concurrent or sequential adjuvant chemotherapy consists of carboplatin/paclitaxel, cisplatin/doxorubicin or cisplatin/doxorubicin/paclitaxel, etc.

Chemotherapy

Xiaorong Hou, PhD

The purpose of this study is to compare the efficacy and toxicity of early stage endometrial cancer based on molecular classification and conventional risk stratification adjuvant therapy decision-making, and to provide high-quality evidence-based medical evidence for individualized adjuvant therapy selection under the guidance of fine stratification system of endometrial cancer.

This is an investigator-initiated prospective, national multicentre, phase III, randomised, open, non-inferiority clinical study. The study hypothesis is that adjuvant radiotherapy decision for early-stage endometrial cancer which is based on molecular classification can achieve de-escalation of adjuvant treatment without reducing local tumour control and survival, thereby potentially further reducing radiotherapy-related toxicity and improving quality of life, compared to using conventional risk stratification. The primary endpoint of this study is the 3-year local recurrence rate.

Study of Early Stage Endometrial Cancer Based on Molecular Classification and Traditional Risk Stratification to Guide Adjuvant Radiotherapy Decisions

A Prospective Multicentre Phase III Randomised Open Clinical Study of Early Stage Endometrial Cancer Based on Molecular Classification and Traditional Risk Stratification to Guide Adjuvant Radiotherapy Decisions

Loco-regional recurrence (LRR) is defined as the first recurrence in the vagina or pelvic cavity during follow-up, which was confirmed by imaging examination or biopsy pathology.

FFS is defined as the time from randomization to recurrence,distant metastasis or death from any cause,whichever is first.

Overall survival is calculated from randomization to death from any cause.

Recurrence in the vaginal area during follow-up

Recurrence in the pelvic area, including the vagina, during follow-up

Distant metastasis (such as bone, lung, liver, brain, non-pelvic regional lymph node metastasis).

Comparison of the proportion of patients in two groups with the same clinicopathologic factors (FIGO, G, LVSI, age) downgraded from EBRT to VBT or from adjuvant radiotherapy (EBRT or VBT) to observation.

General quality of life and general cancer related symptoms is accessed by Quality of Life Core Questionnaire (QLQC-30), ,scored as quite a bit/very much vs no or mild symptoms

Acute radiation enteritis, radiation cystitis, radiation lymphopenia, late radiation enteritis, radiation cystitis, vaginal stenosis or shortening, lymphedema, bone marrow suppression according to CTCAE v 5.0.

All hospital based health care costs used with primary treatment or during follow-up for treatment of adverse events and/or treatment for relapse.

Xijing Hospital, Air Force Medical University of PLA

The Second Affiliated Hospital of Dalian Medical University

The second hospital Affiliated by Jilin University

The Affiliated Hospital of Inner Mongolia Medical University

Third Affiliated Hospital of Xinjiang Medical University

The 940th Hospital of Joint Logistics Support Force，PLA.

Digestive System Diseases

Stomach Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Stomach Cancer

Marcelo Garrido, MD

Background. Gastric cancer (GC) is the world's second leading cause of neoplastic mortality. Genetic alterations, response to treatments and mortality rates are highly heterogeneous across different regions. In Chile, GC is the leading cause of cancer death, affecting 20 per 100,000 people and \>3,000 deaths/year. Clinical outcomes and response to "one size fits all" therapies are highly heterogeneous and thus a better stratification of patients may aid cancer treatment and response.

Study design/methods. The Gastric Cancer Task Force (GCTF) is a Chilean collaborative, non-interventional retrospective study that seeks to stratify gastric adenocarcinomas (GACs) using retrospect clinical outcomes and genomic, epigenomic and protein alterations in a cohort of 200 patients. Tumor samples from the pathology department and the Cancer Center at UC Christus healthcare network at Pontificia Universidad Católica de Chile will be analyzed using a panel of 143 known cancer genes (Oncomine Comprehensive Assay) at the Center of Excellence of Precision Medicine (CEMP) in Santiago, Chile. Additionally, gene promoter methylation will be performed and selected clinically relevant proteins (e.g. PD-L1, Erb-2, VEGFR2 among others) will be assessed by Tissue Microarray, Epstein-Barr virus (EBV) status will also be assessed. Observations will be correlated to 120 clinical parameters, including general patient information, cancer history, laboratory studies, comorbidity index, chemotherapy, targeted therapies, efficacy and follow-up.

Discussion. The development of a clinically meaningful classification that encompasses comprehensive clinical and molecular parameters may improve patient treatment, predict clinical outcomes, aid patient selection for clinical trials and offer insights into future preventive and/or therapeutic strategies.

Participating entities: The Chilean Gastric Cancer Task Force (GCTF) is a collective effort between two principal identities: 1- The Center of Excellence of Precision Medicine (CEMP), which was established through a joint funding by the government agency for economic development (Corporacion de Fomento de la Produccion, CORFO) and Pfizer Chile and 2- The Center UC for Investigation in Oncology (CITO) based at the Pontificia Universidad Católica de Chile. Both entities are non-profit research organizations aimed at enhancing public education and implementing strategies to improve clinical outcomes in oncology treatment and cancer prevention.

Primary objective: To stratify Chilean GC patients into prognostic subgroups, and to correlate therapy response according to clinical, protein, epigenetic and genetic alterations in a cohort of 200 GAC patients.

Secondary objectives

* To determine the mutation profile in Chilean GC patients.
* To assess the percentage of Chilean GC patients that could benefit from currently available druggable targets (actionable genes).
* To correlate EBV presence to clinical parameters.
* To assess the expression levels of proteins associated with molecular stratifications and currently targeted therapies (eg. PD-L1 and antiangiogenics)
* To determine the profile of SNPs in the DPYD and TYMS genes in Chilean GC patients and their correlation with adverse events.

Study design

Ethics approval The GCTF is a non-interventional, collaborative, prospective non-concurrent study that seeks to stratify GAC patients based on their prognosis and therapy response. The study will strictly adhere to all legal requirements, regulations and general principles established by international agencies governing the ethical conduct in biomedical research on human subjects, following the good clinical practices and the declaration of Helsinki. The GCTF study protocol has been approved by the Ethics Committee of the University hospital (Pontificia Universidad Catolica de Chile , CEC MED UC approval number 16-046, resolution dated April 21st, 2016).

Patient recruitment \& characteristics Diagnosed GC patients will be recruited from the Red UC Christus network in Santiago, Chile. Patient recruitment and signing of informed consent forms, maintenance and monitoring of patient medical records, biological material and sample extractions will be managed by CITO.

Patient and treatment history reveals that besides surgery and chemotherapy, approximately 10% of patients received Trastuzumab (ERBB2 targeted therapy, also called Herceptin), another 10% received immunotherapy including pembrolizumab and Ipilimumab (checkpoint inhibitors). Finally approximately 5% of patients received antiangiogenic therapy (consisting of VEGFR2 targeted therapy with Ramucirumab). Additionally, histological analysis showed that approximately 50% of patients were classified as intestinal type, 30% as diffuse, and 20% were either mixed or undetermined.

Inclusion criteria

* Adult male or female, aged \>18 years
* Diagnosed with gastric cancer (histological or cytological)
* Attending health centers of the Red UC Christus network for at least 3 months with clinical follow-up
* Capable to read and speak Spanish
* Willing and able to provide written informed consent to the study that should be dated and signed at the time of enrollment.

Exclusion criteria

Patients:

* With small biopsy samples insufficient for analysis.
* Whose medical records cannot be collected or are unavailable.
* Without signed informed consent.

Clinical data Clinical data from patients will be obtained by healthcare providers and entered into an online electronic platform. Samples will be coded and patient identity known only to the attending physician. Clinical variables are divided into sections: General Patient Information, Cancer History, Laboratory Studies, Comorbidity (Charlson) Index, Chemotherapy, Efficacy \& Follow Up and Toxicity. Patient chemotherapy will be classified by: regime, number of cycles \& time of treatment and chemotherapy dose-intensity during the first 6 months. Chemotherapy regimens representing the first line chemotherapy prescribed to the patients. Full chemotherapy dose intensity during the first 6 months will be obtained through patient interviews and entered directly into the online platform. Finally, efficacy \& follow-up and toxicity data obtained from patients.

Main clinical outcomes Main outcomes will be inferred from obtained clinical data, these include overall survival, progression-free, and recurrence-free survival rates.

Biological samples \& Oncomine Comprehensive Assay Biological materials obtained at the Red UC Christus will be transported to CEMP in Santiago de Chile under standardized protocols. A total of 200 patient tumor samples will be obtained from archived Formalin Fixed Paraffin Embedded (FFPE) samples. Nucleic acids will be extracted using the RecoverAll kit (Thermo Fisher Cat #AM1975) and analyzed using the commercially available Oncomine Comprehensive Assay kit. This assay simultaneously analyzes DNA and RNA from samples allowing the assessment of 73 gene hotspots (based on DNA), 49 focal copy number variations (CNVs, DNA based), 26 full coding sequences (for mutations and CNV loss), and 22 gene fusion drivers (RNA). Notably, 72 of these genes are drug targets. Genomic raw data obtained (.vcf and .pdf files) will be stored and backed up in a local Data Center for subsequent genomic analysis. Upon publication of the findings of this study, the Oncomine results along with clinical classification of individual tumors will be made publicly available.

Tissue Micro Array (TMA) Analysis The following genes will be further analyzed by a TMA using specific antibodies against: PD-L1 (Dako, Cat # SK00521), PD-L2 (Thermo Cat# B7-DC/CD273), Phosphorylated mTOR (Abcam Cat#AB118815), p53 (Cat # 5278074001), VEGFR2 (Abcam Cat #AB39256), Phosphorylated Akt (Thermo Cat #473), HER2 (Roche, Cat # 05278368001), p16 (Roche, Cat # 06695221001), Met (Abcam Cat #AB51067), HA-4 (Abcam Cat #AB24480) and four microsatellite markers (all from Roche): MLH1 (Cat # 06472966001), MSH2 (Cat # 05269270001), MSH6 (Cat # 5929911001), PMS2 (Cat # 06419216001). Manual TMA will be prepared as described previously. Briefly, paraffin blocks will be obtained and cut and stained by Hematoxylin \& Eosin (H\&E) in order to select the best histological area. Subsequently selected tissue area will be placed into the TMA by circling the identified area in the corresponding block. Cylindrical core biopsies will be extracted from each paraffin block using a 1 mm stylet and placed into a new recipient block. Selected adequate cases had tumors that occupied at least 10% of the core area. Each case will be processed in triplicate to prevent tissue loss during cutting. Sections from each tissue array block will be cut, de-paraffinized and dehydrated for H\&E and immunohistochemical procedures.

Gene methylation Promoter gene methylation on six selected genes that have previously shown promoter regulation by methylation associated with GC will be assessed. Methylation analysis will include the reprimo gene and other mRNAs associated with GC progression. Analysis will be performed by bisulfite sequencing as described previously using the EZ DNA methylation Gold kit (Zymo Research) with minor modifications. Briefly, bisulfite treated DNA is amplified using specific PCR primers, with PCR products subsequently cloned and sequenced.

EBV identification EBV subtypes in patient samples will be assessed using the chromogenic in situ hybridization (CISH) method with minor modifications.

Single Nucleotide Polymorphism (SNP) analysis A significant proportion of GC patients can develop serious toxicity from 5-FU treatment including bone marrow suppression, neuropathy, low white blood cell numbers, fever, infections, nausea, vomiting, severe diarrhea, mouth and digestive tract inflammation, all of which are recorded in the patient history of other cohorts. Subtle personal and population changes in DNA, called SNPs can account for increases in the risk of 5-FU toxicity; 5-FU metabolism is predominantly hepatic, where the enzyme DPYD is responsible for metabolizing \>80% of the drug, producing the inactive metabolite 5,6 dihydroxy-5-FU. It is widely documented that a decreased DPYP activity is associated with severe toxicity. Non-metabolised fraction of 5-FU (20%) is transformed by a series of enzymes (e.g TP, TK), producing the active metabolites that will cause TYMS inhibition, thereby promoting DNA/RNA damage. Variations in TYMS and MTHFR genes (related to reduced folate synthesis, increased 5-FU effect), have been associated with toxicity by treatment with 5-FU. The approach that was used to select the genetic variants consisted of a search in the database, PharmGKB. A total of six non-synonymous SNPs will be analyzed: four of them comprise the DPYD gene, one for TYMS and one for MTHFR. Analysis will be performed using TaqMan™ SNP Genotyping Assay technology (Applied Biosystems™). SNPs will be assessed in DNA isolated from paraffin embedded patient samples.

Sample size and statistical analysis

The minimum sample number will be calculated in order to ensure the goals of the project are fully accomplished. Considering that approximately 90% of GC cases are indeed GAC, at 5% error rate and at 95% confidence interval the investigators originally projected a sample size of 200 patients. However the investigators have also considered a 15% rate of sample loss (defective samples or patient drop-out), which gave a total of 230 patients to be recruited.

Standard descriptive statistics will be utilized to analyze qualitative and quantitative variables, such as relative and absolute frequencies, frequency tables, average, median, standard deviation, range and quartiles. A 95% confidence will be considered appropriate for analysis. Descriptive statistics will also be used to characterize the most relevant clinical parameters measured. The association of categorized variables will be performed by chi-square or Fisher's exact tests. One arm Analysis of Variance will compare continuous variables among groups. Survival outcome studies will be accomplished using the Kaplan-Meier method. Prognostic factors will be evaluated according to the Cox proportional hazards regression model.

Principal component analysis (PCA) of the genes variants will be conducted and the association of the first principal components with a small pre-defined set of genomic alteration signatures will be assessed. To define molecular subgroups, the investigators will utilize unsupervised clustering. The correlation of the molecular subtypes with clinical data (e.g. age, gender, Lauren class) and clinical outcomes (e.g. overall survival, response rate) will be assessed. Moreover, supervised classification will be performed based on clinical outcomes and the resulting groups of both approaches will be compared with other reported molecular subtypes.

Patient protection/written informed consent forms

All parties guarantee the protection of the patients' personal records. Patient names are not included in any form in sheet-reports, publications, or in any type of publishable document derived from the study with the exception of documents required by law. Informed consent forms are elaborated strictly following legal and local regulations. The written informed consent forms, including all changes made throughout the study must be prospectively approved by the Internal Review Board/independent Ethics Committee, and CEMP prior to be incorporated into the study.

The investigators, representatives or healthcare providers will obtain written informed consent forms from every patient or a legal representative before any specific activity of the study is performed.

Chilean Gastric Cancer Task Force (FORCE 1)

Chilean Gastric Cancer Task Force (FORCE 1): A Study Protocol to Obtain a Clinical and Molecular Classification of a Cohort of Gastric Cancer Patients.

Overall survival of patients with gastric cancer

Center of Excellence of Precision Medicine (CEMP)

Advanced Center for Chronic Diseases (ACCDiS)

Millennium Institute on Immunology and Immunotherapy

Center UC for Investigation in Oncology (CITO)

Centre of Clinical Research, Health Technology Assessment Unit

National Scientific and Technical Research Council (CONICET), Argentina

Grupo Oncologico Cooperativo del Sur (GOCS), Argentina

Hospital Universitario central de Asurias, Oviedo, España

Hospital Morales Meseger, Murcia, España

Centro de Cancer. Pontificia Universidad Católica de Chile

Hematology and Oncology Department

Pontificia Universidad Catolica de Chile

Pharmaceutical Solutions

The mutational and copy number analyses will be complemented by transcriptomic profiling. RNA will be extracted from FFPE samples using miRNAeasy FFPE kit (Qiagen) and checked for quality and quantify by 2100 Bioanalyzer instrument (Agilent) and Qubit Fluorometer (ThermoFisher), respectively. Transcriptome analyses will be performed by RNA-seq. We will apply total RNAseq using the Illumina® TruSeq Stranded Total RNA workflow that provides a solution allowing the detection of whole transcriptome, splicing variants, and transcript fusions of human RNA isolated from FFPE samples. Libraries will be run using the Illumina's Novaseq6000 system, with a least 50 millions of reads/sample, the minimum read depth for the correct evaluation of low expressed transcripts.

trascriptomic profiling

francesco fanfani

The aim is to develop radiogenomics models to stratify patients into three main risk categories (Favorable, Intermediate, and Unfavorable) according to the ProMisE model (9) and use these models to predict the most prognostically relevant EC histopathological features (i.e. FIGO stage, degree of tumor differentiation, histotype, LVSI status, myometrial and cervical invasion, lymph node metastases).

These models would support clinicians in personalizing surgical and adjuvant treatment choice among the options considered by the international guidelines.

As far as the sample size concerns, the number of images required for the analysis are a figure of at least 100 positive cases (15). We considered as positive patients with a favorable prognostic profile according to PORTEC-4a and also low and intermediate risk class according to ESGO/ESTRO/ESP 2020 recommendations.Therefore, we estimate to enroll at least 1000 patients in order to reach the 100 positive cases.

Radiomics and Radiogenomics Models to Predict Molecular Integrated Risk Classes and Prognostic Factors in Endometrial Cancer.

Radiomics and Radiogenomics Models to Predict Molecular Integrated Risk Classes and Prognostic Factors in Endometrial Cancer ID: ROMANTIC STUDY

Receiver operating characteristic (ROC) curve and 95% confidence interval (CI) will be performed to determine cut-off values for the studied quantitative variables.

To test the validity of different clinical and ultrasound variables Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) will be determined

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Professor

All patients must undergo total hysterectomy and bilateral salpingo-oophorectomy or bilateral salpingectomy if premenopausal status and the lymph-node assessment according to European guidelines and local protocol. A comprehensive surgical peritoneal staging is required, which includes omentectomy/omental biopsies and six peritoneal biopsies.

Surgical treatment will consist of total hysterectomy with bilateral salpingo-oophorectomy according to international guidelines.

In low- and intermediate-risk EC patients, staging will include a sentinel lymph node (SLN) procedure. In high intermediate-risk and high-risk EC patients, lymph node staging will involve SLN procedure and/or pelvic and para-aortic lymph node dissection (LND), depending on the local protocol.

The Study-related procedures include infracolic omentectomy or two separate omental representative biopsies, biopsies of all suspicious lesions as well as six peritoneal sites (bladder, pouch of Douglas, bilateral paracolic gutter and bilateral diaphragm).

Stage IV patients will be treated according to European guidelines. When feasible, full surgical intervention (i.e. debulking) is recommended. If this cannot be achieved, a radiologic and/or histologic confirmation of tumor spread beyond the uterus will be accepted.

total hysterectomy with bilateral salpingo-oophorectomy, lymph node staging and comprehensive peritoneal staging

Frédéric Amant, MD, PhD

Ayaka Wakatsuki, Msc

Ayaka Wakatsuki

EUGENIE is a prospective multicentre interventional study, focused on improving endometrial cancer (EC) assessment by combining the new technique of genomic profiling with surgical extra uterine disease assessment. The investigators aim to correlate EC stage to each of the molecular subgroups of disease and thereby guide surgical treatment and staging of EC by determining the association between molecular classification and disease stage and evaluating if and how disease stage in each of the molecular subgroups associates with prognosis.

Current treatment for endometrial cancer (EC) includes a hysterectomy with bilateral salpingo-oophorectomy. Further surgical staging procedures (lymphadenectomy, peritoneum, and/or omentum biopsies) can be performed in order to detect metastases and determine the disease stage. The type and extent of this surgical staging depend on a pre-operative risk assessment and guides adjuvant treatment (chemo- or radiotherapy). However, this pre-operative risk assessment based on histology and imaging is relatively inaccurate: first, preoperative histology presents high intersubjective variability leading to poor reproducibility in the assignment of histotype and the concordance between preoperative histology and final histology is poor. In addition, preoperative imaging modalities are expensive, time-consuming, hampered by non-perfect accuracies, require specialized expertise, or present limitations in reproducibility and availability. As a result, this leads to an incorrect risk estimation of metastases at diagnosis in EC patients with a consequent over- or undertreatment of patients. Thus, there is an urgent need to develop risk stratification strategies that will better predict the presence and localization of metastases in EC patients and therefore more efficiently tailor surgical staging procedures.

In 2013 The Cancer Genome Atlas (TCGA) Research Network developed a new molecularly driven classification system, that divides EC tumours into the well-known four molecular subgroups (POLE, MMRd, p53abn, NSMP) and has shown to surpass histologic subtyping and grading to more efficiently predict prognosis. However, the relation between the four molecular subgroups and the risk of tumour spread beyond the uterus at diagnosis has insufficiently been investigated so far and, as a consequence, surgical staging should not yet be adapted based on the molecular endometrial cancer subtype.

Thus, new studies are needed to assess the value of surgical staging in this molecular era and EUGENIE Study has been developed to bridge this knowledge gap.

The investigators believe that the future is in integrating morphologic and molecular findings, so the preoperative diagnosis will also support accurate surgical decision making and therefore a more tailored management of all EC patients.

Improving Endometrial Cancer Assessment by Combining Genomic Profiling and Surgical Assessment

Improving Endometrial Cancer Assessment by Combining the New techniqUe of GENomic Profiling With Surgical Extra uterIne disEase Assessment

Endometrial cancer stage assessed according to the 2009 an 2023 International Federation of Gynecology and Obstetrics (FIGO) staging

Tumor classification using the molecular classification as proposed by either ProMisE or TRANSPORTEC.

Groups will be classified as follows:

1. MMR: Mismatch Repair Protein Status will be determined as a surrogate for microsatellite instability (MSI) by considering the immunohistochemical (IHC) staining of the MMR proteins. In case of loss of staining of one or more MMR proteins, the EC will be classified as MMR deficient (MMRd), otherwise, the carcinoma will be coded as MMR proficient (MMRp).
2. POLE: if the POLE exonuclease domain mutations (EDM) gene is mutated (i.e. a pathogenic mutation), the tumour will be classified as POLE.
3. p53 IHC: TP53 mutation status will be determined via IHC and in case of inconclusive p53 staining, also sequencing.
4. NSMP: a carcinoma that has not been stratified into groups 1), 2) or 3) will be categorized into the NSMP (no specific molecular profile or copy number low).

University Medical Centre Maribor

University Hospital, Gasthuisberg

Head of the scientific Unit of Gynecologic Oncology, Full professor at Faculty of Medicine and Clinical Staff Specialist at Gynecological Oncology at UZ Leuven, Full professor at Faculty of Medicine, University of Amsterdam

p53 abn stage I-II MI (myometrial invasion) \>0%; MMR-D/NSMP nonendometrioid stage I-II MI \>0%

MMR-D stage IA-B grade 1-2, substantial LVSI; MMR-D stage IA grade 3, substantial LVSI; MMR-D stage IB grade 3; MMR-D stage II grade 1-3;

NSMP stage IA-B grade 1-2, substantial LVSI; NSMP stage IA grade 3, substantial LVSI; NSMP stage IB grade 3; NSMP stage II grade 1-3;

Chemotherapy (paclitaxel-carboplatin) vs. chemoradiotherapy (paclitaxel-carboplatin followed by whole pelvic radiotherapy)

Patients assigned to chemotherapy receive paclitaxel (175 mg/m2) and carboplatin (area under curve, 5) every 3 weeks for 6 cycles. The pelvic radiotherapy dose is 45 to 50.4 Gy over 5 to 6 weeks (1.8 Gy per day for 25 to 28 fractions).

Comparison of adjuvant therapies

Vaginal brachytherapy vs. whole pelvic radiotherapy

Patients randomized to vaginal brachytherapy receive cuff brachytherapy at 21 Gy in 3 fractions of 7 Gy at 0.5 cm depth. The pelvic radiotherapy dose is 45 to 50.4 Gy over 5 to 6 weeks (1.8 Gy per day for 25 to 28 fractions).

Mikko Loukovaara

Ralf Bützow

Mikko Loukovaara, MD

Ralf Bützow, MD

The goal of this clinical trial is to compare the efficacy of adjuvant therapies in women with stage I-II molecular integrated high-intermediate or high-risk endometrial carcinoma. Specifically, the invesigators want to compare:

* Chemotherapy vs. chemoradiotherapy in p53 abn subtype and nonendometrioid carcinomas.
* Vaginal brachytherapy vs. whole pelvic radiotherapy in the MMR-D molecular subgroup.
* Vaginal brachytherapy vs. whole pelvic radiotherapy in the NSMP molecular subgroup.

Endometrial carcinomas can be classified into four molecular subgroups, i.e. mismatch repair deficient (MMR-D), p53 abnormal (p53 abn), polymerase-ϵ (POLE) ultramutated, and "no specific molecular profile" (NSMP). Molecular subgroups can be considered to be distinct diseases as they are associated with different clinicopathologic characteristics, prognoses and, possibly, responses to adjuvant therapy. Molecular classification of endometrial carcinoma is recommended to be implemented in routine clinical practice to improve prognostication and triage to adjuvant therapy. The PErsonalized TReatment for Endometrial Carcinoma (PETREC) trial, led by the Finnish Gynecologic Oncology Group (FINGOG), is a multicenter prospective clinical trial for women with stage I-II molecular integrated high-intermediate or high-risk endometrial carcinoma. The efficacy of chemotherapy vs. chemoradiotherapy is compared in p53 abn subtype and nonendometrioid carcinomas, and vaginal brachytherapy vs. whole pelvic radiotherapy in MMR-D and NSMP molecular subgroups. Patients who consent to follow-up within the trial but not to randomization are treated as recommended in multidisciplinary meetings and enrolled for follow-up only (comprehensive cohort study design). The primary outcome is the 5-year cumulative incidence of disease recurrence. Secondary outcomes are vaginal, pelvic, and distant recurrence rates, 5-year recurrence-free and overall survival, adverse events, and patient-reported symptoms and quality of life. The findings of the trial may eventually help decrease under- and overtreatment and, consequently, improve patient outcome and decrease treatment-associated adverse effects.

Eligibility not based on self-representation of gender identity.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Dynamic Monitoring Circulating Tumor DNA in Surgical Patients With Lung Cancer	NCT03317080	Lung Cancer		-	West China Hospital
Application Circulating Tumor DNA Dynamic Monitoring in Clinical Treatment of Metastatic Renal Cell Carcinoma	NCT05816642	Metastatic Rena...	sunitinib or pa... PD-1 inhibitor ...	-	RenJi Hospital
Study of Early Stage Endometrial Cancer Based on Molecular Classification and Traditional Risk Stratification to Guide Adjuvant Radiotherapy Decisions	NCT05524389	Endometrial Can... Adjuvant Radiot... Molecular Class...	Vaginal brachyt... Pelvic external... Observation Chemotherapy	18 Years - 75 Years	Peking Union Medical College Hospital
Chilean Gastric Cancer Task Force (FORCE 1)	NCT03158571	Biomarkers		18 Years - 99 Years	Pontificia Universidad Catolica de Chile
Radiomics and Radiogenomics Models to Predict Molecular Integrated Risk Classes and Prognostic Factors in Endometrial Cancer.	NCT06279832	Endometrial Can...	trascriptomic p...	18 Years -	Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Improving Endometrial Cancer Assessment by Combining Genomic Profiling and Surgical Assessment	NCT06354738	Endometrial Can...	total hysterect...	18 Years -	University Hospital, Gasthuisberg
Improving Endometrial Cancer Assessment by Combining Genomic Profiling and Surgical Assessment	NCT06354738	Endometrial Can...	total hysterect...	18 Years -	University Hospital, Gasthuisberg
PErsonalized TReatment for Endometrial Carcinoma	NCT05655260	Endometrial Ade...	Comparison of a... Comparison of a...	18 Years - 100 Years	University of Helsinki
Dynamic Monitoring Circulating Tumor DNA in Surgical Patients With Lung Cancer	NCT03317080	Lung Cancer		-	West China Hospital
Study of Early Stage Endometrial Cancer Based on Molecular Classification and Traditional Risk Stratification to Guide Adjuvant Radiotherapy Decisions	NCT05524389	Endometrial Can... Adjuvant Radiot... Molecular Class...	Vaginal brachyt... Pelvic external... Observation Chemotherapy	18 Years - 75 Years	Peking Union Medical College Hospital

Spots Global Cancer Trial Database for molecular classification