Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Group 1 \[(A) subjects who are planning to receive surgery (mastectomy or BCS) as the first-line treatment for BC and followed by adjuvant therapy, or (B) subjects with BC recurrence at screening, who had received surgery for primary BC within 3 years prior to screening, and with primary tumor FFPE tissues available\]

subjects who are planning to receive neoadjuvant therapy as the first-line treatment for BC and followed by surgery

Group 3-1 (subjects diagnosed with de novo and treatment naïve stage IV BC); or Group 3-2 \[(A) stage IV subjects with BC recurrence beyond 3 years after surgery (mastectomy or BCS) or stage IV subjects who had received or are currently receiving treatments for BC\].

After enrollment, individual subject will be assigned into one of the four groups according to the medical management received, the diagnostic stage of breast cancer (BC), or the clinical outcome of BC at enrollment.

Diagnostic stage or the Clinical outcome

Hsiang-Chung Tseng

Ling-Ming Tseng, MD

The objectives of this study are:

1. To determine the difference in genetic profiling of subjects with breast cancer recurrence
2. To determine the comprehensive genetic profiling of subjects with late stage breast cancer
3. To determine the potential biomarkers for early detection and prognosis for breast cancer
4. To determine the genetic profiling of immune system in different subtypes of breast cancer

By integrating and analyzing the data generated using the methods of NGS, these information can be used for:

1. Understanding the genetic profiling of different subtypes of breast cancer in Taiwan
2. Assessing the efficacy of different treatments in breast cancer subjects
3. Defining the molecular risk factors and predicting the potential risk of breast cancer recurrence
4. Assessing the immune repertoire and the potential effects of immunotherapy in breast cancer subjects
5. Developing new strategies in treating patients with triple negative or late stage of breast cancer

Research on the Heterogeneity of Taiwanese Breast Cancer Patients by Next Generation Sequencing (NGS) Tools

Comprehensive Precision Medicine Research on the Heterogeneity of Taiwanese Breast Cancer Patients by Next Generation Sequencing (NGS) Tools

Discovery of comprehensive genetic profiles including copy number variation and single nucleotide polymorphism in group 1, 2 and 3 subjects.

Discovery of genetic mutations of T cell receptor

Breast cancer recurrence, overall survival and recurrence-free survival

YongLin Healthcare Foundation

vghtpe user

Chief of Comprehensive Breast Health Center, Department of Surgery

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

Patients with epithelial ovarian adenocarcinoma with archival tumor tissue available for analysis were identified through the Hellenic Cooperative Oncology Group (HeCOG)'s tumor repository. Patients had received treatment at HeCOG-affiliated institutions following standard international guidelines.

Tumor tissue processing and all NGS genotyping were performed at the Laboratory of Molecular Oncology (Hellenic Foundation for Cancer Research / AUTH). Paraffin H\&E sections from the retrieved tissue blocks were centrally reviewed for tumor histology and tissue adequacy for DNA extraction and were marked for macrodissection along with tumor DNA content \[(former tumor cell content (TCC%)\] assessment. DNA was extracted from macrodissected tissue fragments with the QIAamp® DNA mini kit (Qiagen, Hilden, Germany), measured in a Qubit fluorometer (Thermo Fisher Scientific, Paisley, UK), and genotyped with NGS in an Ion Torrent Proton sequencer (Thermo Fisher Scientific) by using a previously published custom panel (Kotoula, Lakis et al. 2019). Following stringent variant quality filtering (Kotoula, Chatzopoulos et al. 2021), 500 tumors

Tumor molecular profiling

ELENA FOUNTZILAS, MD

Molecular alterations in Homologous Recombination Repair (HRR) genes have been associated with clinical benefit from chemotherapy and/or Poly (ADP-ribose) polymerase (PARP) inhibitors in patients with epithelial ovarian cancer. Therefore, the performance of tumor molecular profiling is currently recommended by international guidelines at initial diagnosis, among other reasons, for the modification of the treatment plan. The investigators' hypothesis was that tumor molecular profiling reveals additional parameters that can improve the predictive and prognostic role of the mere presence of HRR gene mutations. The study aimed to investigate the prognostic and predictive role of clonality of pathogenic variants in HRR genes and/or concurrent pathogenic variants in other clinically relevant genes.

Pathogenic Variants in Homologous Recombination Repair Genes in Patients With Epithelial Ovarian Cancer

Clonality of Pathogenic Variants in Homologous Recombination Repair Genes in Patients With Epithelial Ovarian Cancer

The time from ovarian cancer diagnosis to the date of death from any cause

The time from initiation of first-line chemotherapy to the first documented progression, death from any cause or last contact, whichever occurred first

Hellenic Cooperative Oncology Group

Leiomyoma

Myofibroma

Leiomyosarcoma

Neoplasms, Connective and Soft Tissue

Sarcoma

Neoplasms, Connective Tissue

Connective Tissue Diseases

Soft Tissue Sarcoma

Women between 18 and 75 years of age diagnosed with a myometrial tumor (probably leiomyoma) with suspected leiomyosarcoma

After obtaining informed consent, the samples (tumor tissue and peripheral blood) will be collected at the time of surgery, which the patient had already planned by medical indication according to the usual clinical practice. Part of the sample will be sent to histopathology for gold standard diagnosis while the rest of the sample will be sent to Igenomix for molecular analysis.

If samples are available from patients who underwent surgery prior to the study, after they sign the Informed Consent, the samples will be sent to Igenomix for molecular analysis and the results obtained by histopathology will be collected from the patient's medical record.

Biopsy and peripheral blood collection

Carlos Gomez, BSc, MSc

Diana Valbuena, MD, PhD

Sebastián Ortiz

Sebastián Ortiz, MD

Anibal Nieto, MD, PhD

Aníbal Nieto

Jose Antonio Lopez, PhD

Santiago Domingo Del Pozo, MD, PhD

Javier Monleón Sancho, MD, PhD

Javier Monleón, MD

Carlos Simón, MD, PhD

Aymara Mas, PhD

The development of an accurate and non-invasive diagnostic method is a priority in areas such as gynecology and oncology, specifically to improve the health of those patients with surgical indication for diagnosis of myometrial tumors: leiomyomas and/or leiomyosarcomas.

Recently, Next Generation Sequencing (NGS) technology has been successfully applied in different areas of knowledge, being effective not only for the detection of DNA mutations, but also providing through bioinformatic tools, new insights in the understanding of chromosomal instability. In addition, the detection of circulating tumor DNA (ctDNA) through this type of techniques could revolutionize the non-invasive detection and monitoring of this type of tumors.

The proposed study aims to perform the differential molecular analysis of myometrial tumor tissue (uterine leiomyomas / leiomyosarcomas), as well as peripheral blood of a group of patients with surgical indication of hysterectomy, laparoscopic or laparotomic myomectomy by diagnosis of myometrial tumors. Thus, the obtained samples will be processed for the realization of techniques of massive parallel sequencing or NGS that, together with a specialized bioinformatic software, will facilitate the interpretation of the obtained data.

Combination of both platforms, sequencing and bioinformatics, will offer a high potential for the discovery of genetic variants and genomic markers. Depending on the results of these analyses, differential diagnosis of leiomyoma and leiomyosarcoma could be determined, in addition to increasing knowledge of myometrial biology and associated pathologies in a clinical and therapeutic context. Moreover, the application of this technology could allow the development of biomarkers and targeted therapies effective in the treatment of uterine leiomyomas and/or leiomyosarcomas.

Leiomyomas (LM) are the most common benign gynecological tumors that affect approximately 70% of women of reproductive age, being responsible for 200,000 hysterectomies per year in the United States (USA). Despite its benign nature, LM represents a major public health problem due to its significant level of morbidity, which manifests as a spectrum of clinical symptoms such as heavy menstrual bleeding, anemia, pelvic pain, infertility and recurrent pregnancy loss, among others.

Uterine leiomyosarcoma (LMS) is a rare uterine malignancy that arises from the smooth muscle of uterine wall. It accounts for only 1-2% of uterine malignancies and occurs mainly after menopause. LMS is notorious for its aggressive nature and poor prognosis.

Although uterine LM and LMS are considered biologically unrelated tumors due to their cytogenetic and molecular disparity, both share morphological features that can complicate the diagnosis through current clinical tests or factors.

Nowadays, long-term therapeutic options for LM are limited. Currently, laparoscopic morcellation is the most widely used surgical technique in the treatment of large LM. However, this type of surgery carries the risk of occult dissemination of malignant tumors such as LMS, characterized by early metastases, poor prognosis and high recurrence rates, with limited therapeutic efficacy. In fact, the United States Food and Drug Administration (FDA) has estimated that 1 in 352 of women with surgical indication of LM could have LMS, and treatment in this case could result in tumor spread. Given this need, Igenomix, through a recent pilot study with 26 samples, has identified new genetic targets that potentially differentiate leiomyosarcomas and leiomyomas, through integrated comparative genomic and transcriptomic analyses. This allowed to lay the foundations, not only to improve the understanding of the pathogenesis of these uterine tumors, but also provides a first step towards the preoperative diagnosis of leiomyomas and leiomyosarcomas by liquid biopsy.

Based on this pilot study, a new clinical study is proposed to proceed with further identification of genetic markers and develop a preoperative diagnosis of LM and LMS by liquid biopsy. A total sample size of 1,000 patients with suspected LMS is expected to be recruited in this study, considering the frequency of surgeries in which obtaining a sample is intended, as well as the frequency of patients who will accept tissue donation for research. Moreover, a cut-off point with a preliminary analysis every 100 patients will be established, in which the laboratory data is combined with those derived from the Pathological Anatomy (Gold Standard), so that when a total of 40 LMS is reached the study will end.

During the development of the study, after obtaining informed consent from eligible patients, the samples (tumor tissue and peripheral blood) will be collected at the time of surgery, which the patient had already planned by medical indication according to the usual clinical practice. Thus, the participation of the subject in this study will entail only a single visit coinciding with the day of the surgery. In addition, samples available from patients that underwent surgery before the study could be also included if, after being duly informed, the patient agrees to participate in the study and signs the study consent form. Exceptionally, samples from patients who could not consent due to major reasons (such as death of the subject or impossibility to be found) could also be included in the study upon approval of the appropriated Ethic Committee according to the local regulations for this type of situations. In any case, the investigators will ensure that there is no expressed objection from the donors in their clinical history and that samples will be codified in order to assure anonymity.

Samples will be sent to histopathological diagnosis and to Igenomix, that will develop and optimize laboratory protocols to detect changes at the DNA (Whole Exome Sequencing) and RNA (RNAseq) level in order to achieve the described outcomes. This new approaches focused on NGS, could allow not only the detection of tumor-specific mutations but, in combination with bioinformatics tools, could provide new knowledge to understand chromosomal instability in the tumors.

According to the histopathological diagnosis, patients will be treated by their respective doctors and followed up to determine their evolution. If the proposed hypothesis from NGS results is confirmed and the objectives are achieved, in a second phase of the project, a diagnostic tool will be developed to extend the non-invasive genetic diagnosis of uterine leiomyomas and leiomyosarcomas in peripheral blood through the free DNA analysis of circulating tumor cells. The possibility of being able to quantify and characterize the circulating tumor DNA (ctDNA) by means of this type of techniques, could revolutionize the non-invasive detection and the follow-up of this type of tumors.

Development of a Predictive Model for Early Differential Diagnosis of Uterine Leiomyomas and Leiomyosarcomas

Prospective, National and Multicenter Biomedical Study of Cohorts, Aimed at Patients With Surgical Indication of Hysterectomy, Laparoscopic or Laparotomic Myomectomy Due to Diagnosis of Myometrial Tumors (Leiomyoma / Leiomyosarcoma)

Identification of genetic markers that allow the classification of myometrial tumors into leiomyomas and leiomyosarcomas by NGS.

Single-cell DNA/RNAseq characterization of the uterine leiomyomas and leiomyosarcomas cell populations in order to assess the heterogeneity in these myometrial tumors.

Study of methylation patterns that could identify tumorigenic processes

Igenomix

Symptoms and General Pathology

Diseases and Abnormalities at or Before Birth

Syndrome

Genetic Predisposition to Disease

Disease Susceptibility

Neoplastic Syndromes, Hereditary

Disease Attributes

Genetic Diseases, Inborn

For the retrospective data analysis, patients with genetic diseases of any age and, if available, other family members, for whom genetic analyzes were carried out between 10/2016 and 12/2020, should be included. This equates to approximately 13,000 records, minus combined analyzes in the same patient, an estimated 12,000 individuals.

The outlined evaluation contributes to the improvement of molecular genetic diagnostics in patient care - for example when which diagnostics can be sensibly recommended for patients with which indications or not. Diagnostic gaps can be systematically evaluated and specifically addressed in the future. This potentially affects every examination assignment for current and future patients. In addition, the evaluation of the PRSs for example, can contribute significantly to the timely introduction to routine diagnostics. For familial breast cancer, according to the guidelines, there may be very specific preventive measures. Estimates currently assume up to 5% of patients, which would mean up to 25 cases per year with a potentially adapted management for patients with the question of a tumor disease alone.

Retrospective data analysis

Tobias Haack, Dr.

Olaf Rieß, Prof. Dr.

Haack Tobias, Dr.

The methodological developments of the last few years allow the broad use of next-generation-sequencing (NGS) -based methods in the routine molecular genetic diagnosis of genetic diseases.The aim of the retrospective data analysis is to create a solid data basis for further discussion regarding the development and mapping of diagnostic algorithms and subsequent supply routes. For the genome data, this evaluation is to be expanded to include the evaluation of the Polygenic risk scores (PRSs) in the sense of an additional finding.

Diagnostic Value of Exome/ Genome Sequencing, Conventional Methods in Rare Diseases and Familial Tumor Syndromes

Diagnostic Value of Exome and Genome Sequencing as Well as Conventional Methods in Rare Diseases and Familial Tumor Syndromes

Number of established probable diagnosis using molecular genetic diagnostics

University Hospital Tuebingen

Blood and Lymph Conditions

Immune System Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Lymphosarcoma

John T. Sandlund, MD

Familial aggregation is well recognized in some cancers. Though a number of familial cancer predisposition syndromes have been described, the nature of inherited genetic alterations in patients with a strong history of familial cancer is currently unknown, as is the case with childhood acute lymphoblastic leukemia (ALL).

The investigators are seeking to learn more about what causes leukemia and why some people and families may be at a higher risk of developing this disease. By understanding the origin of the disease, better treatments may be identified for patients with leukemia.

PRIMARY OBJECTIVE: To identify variants in genes that are inherited, have altered gene structure and/or function, and influence the risk of developing acute lymphoblastic leukemia (ALL) and other cancers.

SECONDARY OBJECTIVE: To collect demographic, clinical and laboratory information including detailed family cancer history and response of cancers to therapy for correlation with the primary objective.

This study entails clinical interviews, submission of a peripheral germline blood sample for non-tumor DNA and permission to perform biologic studies on previously stored tumor tissue if applicable and available. Participants diagnosed with cancer at outside institutions will be requested to sign a release form to allow the outside institution to send germline and/or tumor tissue to St Jude if available. For patients who have undergone a stem cell transplant, a buccal swab or saliva sample will be requested (for germline DNA). For patients with active leukemia, non-tumor cells (for germline DNA) may be obtained using a remission blood sample, a skin biopsy (to obtain fibroblasts) or may be purified by fluorescence activated cell sorting of leukemia samples. The skin biopsy will be obtained in participants 18 years of age and older. In participants less than 18 years, the skin biopsy will be accessed only if it was already collected as part of another research protocol or for clinical care.

All patients being considered for enrollment will have a clinical genetics consult by one of the study team members at which time a family history will be taken and information about genomic testing will be introduced. Detailed medical history will be obtained which includes but is not limited to demographics, clinical data including laboratory results, cancer history/diagnosis, treatment outcomes, environmental exposures and cancer risk factors to enable phenotype/genotype correlations.

Genetic Study of Familial Acute Lymphoblastic Leukemia

Probands and cancer affected and unaffected relatives from selected families will be sequenced using Whole Genome Sequencing (WGS) or possibly Whole Exome Sequencing (WES) and analyzed to identify new predisposing genetic variants that co-segregate with the tumor phenotype.

St. Jude Children's Research Hospital

Digestive System Diseases

Carcinoma, Hepatocellular

Cholangiocarcinoma

Liver Neoplasms

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Bile Duct Cancer

Primary Liver Cancer

Intrahepatic Cholangiocarcinoma

Antineoplastic Agents

All Drugs and Chemicals

Hematinics

Immune Checkpoint Inhibitors

Liver Extracts

observe the association of ctDNA with efficacy of treatment

Observation

Feng Shen, MD PhD

To evaluate the predictive value of ctDNA in response, relapse for liver cancer patients treated with immune checkpoint inhibitors

In the study, 300 advanced primery liver cancer patients who received immune checkpoint inhibitors at first-line setting (N=200) or second-line setting (N=100) will be recruited. By analyzing the ctDNA and peripheral blood mononuclear cell (PBMC) collected before and after the first cycle of ICI treatment, the dynamic changes of bTMB, ctDNA and the composition of immune cells will be detected. Combined with the tumor markers AFP, DCP and CA19-9, a noninvasive multiparameter model will be developed.

whole blood (including plasma, white cells), tissue

Therapeutic ResistAnce and Clonal Evolution Assessed With Liquid Biopsy in ICIs Treated Primary Liver Cancer

The time length from the date of randomization to any of the following events: disease progression or death from any cause.

The proportion of patients with complete response or partial response.

The time length from the date of randomization to the date of death.

The time length from the date of randomization to the date of treatment discontinuation.

Eastern Hepatobiliary Surgery Hospital

Geneplus-Beijing Co. Ltd.

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Pancreatic Neoplasms

Mesothelioma

Mesothelioma, Malignant

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Pancreatic Diseases

Adenoma

Neoplasms, Mesothelial

Pleural Neoplasms

Pancreatic Cancer

Malignant Mesothelioma

Immunomodulating Agents

Apheresis procedure performed for collection of PBMCs.

Apheresis

NGS on tumor tissue and a matched normal sample for loss of heterozygosity in tumor tissue and tumor tissue markers.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Research on the Heterogeneity of Taiwanese Breast Cancer Patients by Next Generation Sequencing (NGS) Tools	NCT04626440	Next Generation... Breast Cancer	Diagnostic stag...	20 Years -	Taipei Veterans General Hospital, Taiwan
Research on the Heterogeneity of Taiwanese Breast Cancer Patients by Next Generation Sequencing (NGS) Tools	NCT04626440	Next Generation... Breast Cancer	Diagnostic stag...	20 Years -	Taipei Veterans General Hospital, Taiwan
Pathogenic Variants in Homologous Recombination Repair Genes in Patients With Epithelial Ovarian Cancer	NCT04716374	Epithelial Ovar...	Tumor molecular...	18 Years -	Hellenic Cooperative Oncology Group
Development of a Predictive Model for Early Differential Diagnosis of Uterine Leiomyomas and Leiomyosarcomas	NCT04214457	Leiomyoma Leiomyosarcoma	Biopsy and peri...	18 Years - 75 Years	Igenomix
Diagnostic Value of Exome/ Genome Sequencing, Conventional Methods in Rare Diseases and Familial Tumor Syndromes	NCT04731857	Rare Diseases Genetic Predisp...	Retrospective d...	-	University Hospital Tuebingen
Genetic Study of Familial Acute Lymphoblastic Leukemia	NCT03067584	Acute Lymphobla...		-	St. Jude Children's Research Hospital
Therapeutic ResistAnce and Clonal Evolution Assessed With Liquid Biopsy in ICIs Treated Primary Liver Cancer	NCT05292443	Primary Liver C... Hepatocellular ... Intrahepatic Ch... Combined Hepato...	Observation	18 Years - 80 Years	Geneplus-Beijing Co. Ltd.
Research on the Heterogeneity of Taiwanese Breast Cancer Patients by Next Generation Sequencing (NGS) Tools	NCT04626440	Next Generation... Breast Cancer	Diagnostic stag...	20 Years -	Taipei Veterans General Hospital, Taiwan
Solid Tumor Analysis for HLA Loss of Heterozygosity (LOH) and Apheresis for CAR T- Cell Manufacturing	NCT04981119	Solid Tumor, Ad... Colorectal Canc... Non Small Cell ... Pancreatic Canc... CRC NSCLC Pancreas Cancer Mesothelioma Ovarian Cancer Ovarian Neoplas... Ovarian Carcino... Mesothelioma, M... Mesothelioma; L... Cancer	Apheresis Next Generation... Long Range NGS ...	18 Years -	A2 Biotherapeutics Inc.
Therapeutic ResistAnce and Clonal Evolution Assessed With Liquid Biopsy in ICIs Treated NSCLC Patients	NCT04566432	Lung Neoplasms Lung Cancer, No... Adenocarcinoma ... Squamous Cell L...	Observation	18 Years -	Geneplus-Beijing Co. Ltd.

Spots Global Cancer Trial Database for next generation sequencing (ngs)