Symptoms and General Pathology

All Conditions

Neoplasms

Digestive System Diseases

Recurrence

Colorectal Neoplasms

Adenocarcinoma

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Disease Attributes

Anti-Infective Agents

All Drugs and Chemicals

Formaldehyde

Survivors of T1 colorectal cancer who developed recurrent colorectal cancer within 36 months from primary tumor treatment, in the first cohort

Survivors of T1 colorectal cancer who did not develop recurrent colorectal cancer within 36 months from primary tumor treatment, in the first cohort

Survivors of T1 colorectal cancer who developed recurrent colorectal cancer within 36 months from primary tumor treatment, in the second cohort

Survivors of T1 colorectal cancer who did not develop recurrent colorectal cancer within 36 months from primary tumor treatment, in the second cohort

A panel of microRNA and messenger RNA, whose expression level is tested in macro-dissected formalin-fixed and paraffin-embedded (FFPE) samples derived from the primary tumor, with reverse transcriptase quantitative polymerase chain reaction (RT-qPCR)

Tw1CE

Ajay Goel, PhD

Takayuki Noma, MD

Alessandro Mannucci

Mitsuo Shimada, PhD

Katsuki Miyazaki

Yuma Wada, PhD

Mistuo Shimada, PhD

Maria Pellise

Karmele Saez de Gordoa

María Daca

Francesc Balaguer

Tumor recurrence significantly affects survival rates following the local resection of submucosal colorectal cancers (T1 CRC). Despite this, there are currently no reliable biomarkers established to predict recurrence in T1 CRC.

This study seeks to improve the prediction of recurrence-free survival in individuals who have survived T1 CRC.

The incidence of invasive submucosal colorectal cancer (T1 CRC) is increasing, likely as a reflection of improved screening and endoscopy use. Current treatment options for T1 CRC focus on less invasive methods (i.e., endoscopic submucosal dissection), and treatment decisions are based on the risk of lymph node metastasis (LNM). Up to 70-80% of T1 CRC patients may undergo surgery, with adjuvant chemotherapy recommended only for those with LNM.

However, current clinical practice guidelines are considered to be overly aggressive and recommend the administration of aggressive treatment to many patients who may be cured with non-invasive therapy alone. This results in the overtreatment of many patients, especially those that are currently defined as 'high-risk' T1 CRC. Existing surveillance methods may not adequately predict the prognosis of T1 CRC, lacking established biomarkers for assessing disease-free survival.

This study seeks to validate tissue-based biomarkers (micro-RNA and messenger RNA) that are associated with tumor recurrence after curative resection. The identification of patients at high risk of recurrence may help in the selection of patients who truly benefit from additional oncologic surgery or adjuvant therapy. Previous research by this group has identified miRNA signatures for detecting postoperative tumor recurrence and metastasis in CRC, highlighting their potential as biomarkers for disease progression.

Formalin-fixed, paraffin-embedded slide from the primary tumor

Predicting Local and Distant Recurrence in T1 Colorectal Cancer

Predicting Recurrence After Curative-Intent Resection of T1 Colorectal Cancer With Transcriptomics

Data collected for the study will be made available to others, including de-identified participant data, at publication, via a signed data access agreement and at the discretion of the investigators' approval of the proposed use of such data.

Time from curative-intent resection to the development of recurrence (or death)

City of Hope Medical Center

Rare Diseases

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Small Intestinal Adenocarcinoma

Dan Høgdall, MD PhD

Jakob HV Schou, MD

Elizaveta M Tabaksblat, MD PhD

Carsten P Hansen, MD DMSc

Dan Hogdall, MD PhD

Small bowel adenocarcinoma is a rare malignancy, and there is limited knowledge about its optimal clinical management and molecular background. The SBAMOL study is an observational biomarker study that aims to identify prognostic and predictive biomarkers. This effort is intended to lay the groundwork for personalized medicine tailored to this specific patient group.

Small bowel adenocarcinoma (SBA), an orphan cancer, has annual diagnoses of 12,070 in the USA and 100 in Denmark. Despite its rarity, patient management should prioritize evidence-based care, but large trials are not feasible, leading to data scarcity and suboptimal care. As a result, SBA is treated like colorectal cancer, yet its prognosis is worse, indicating this parallel approach is insufficient. The grasp on SBAs molecular landscape is limited compared to prevalent cancers. Scant mutational profiling studies, suggest SBA is a heterogeneous disease where subsets resemble other gastrointestinal cancers. This underscores the potential for personalized treatments, including targeted therapies and immunotherapies. Comprehensive molecular characterization, using DNA, RNA, and T-cell receptor characteristics, can provide much-needed strategic direction for patient care and future trials. Capitalizing on this, the investigators propose a comprehensive molecular characterization aiming to develop consensus molecular subtypes that can direct future trials and SBA therapeutic strategies.

The investigators hypothesize that a consensus molecular profiling approach can identify subgroups of SBA with distinct molecular, cellular, and histological characteristics, that will benefit from tailored treatment strategies using chemotherapy, targeted therapy, and immunotherapy.

To explore this hypothesis, the investigators will: (WP1) perform molecular and immunological characterization of tumor tissues from SBA patients (n=200) to establish consensus molecular subtypes of SBA and define their biological attributes; (WP2) ascertain therapeutic avenues tailored to each subtype and devise a molecular algorithm to prospectively categorize individual tumors in real-time, laying the groundwork for molecularly-driven management.

Formalin-Fixed, Paraffin-Embedded or fresh frozen tissue for DNA, RNA and geospatial analyses

Molecularly Redefining Small Bowel Adenocarcinoma to Accelerate Precision Patient Care

Due to Danish ethical regulations, data can only be shared upon appropriate ethical amendment

Due to the scarce knowledge of the biological background of SBA. The primary endpoint of the study is to present a comprehensive descriptive molecular characterisation of patients with SBA.

DNA aberrations will associated with disease free, progression free and overall survival. Analysis will be performed using the Oncomine comprehensive plus gene panel. Potential aberrations indicative of targeted treatments will be explored and reported.

mRNA aberrations will associated with disease free, progression free and overall survival. Analysis will be performed using high-throughput sequencing. Potential aberrations indicative of targeted treatments will be explored and reported.

T-cell receptor clonality and diversity will associated with disease free, progression free and overall survival. Analysis will be performed using a high-throughput t-cell receptor sequencing.

Aarhus University Hospital

Rigshospitalet, Denmark

University of Copenhagen

Copenhagen University Hospital at Herlev

MD PhD

Blood and Lymph Conditions

Leukemia

Acute Disease

Hematologic Diseases

Acute Graft Versus Host Disease

blood draw

Urielle DESALBRES

Acute leukemias are a heterogeneous group of hematologic malignancies. They result from clonal expansion of immature cells whose number is greater than 20% in bone marrow. Childhood acute leukemias are the most common pediatric malignancies. In Europe and the United states, they represent about 35% of childhood cancers. 80% of them are acute lymphoblastic leukemia (ALL) and 15-20% of acute myeloid leukemia (AML). Current treatments allow a cure in about 80% of ALL, while this level is only 50% in AML.Acute leukemia diagnosis is based on the multidisciplinary exploration of leukemia cells by different techniques:

* Cellular: cytology, immunophenotyping and cytochemistry
* Cytogenetic: conventional (karyotype) and molecular (FISH) cytogenetic
* Molecular: RT-PCR and RQ-PCR

Cytogenetic studies are performed at time of acute leukemia diagnosis. Indeed, the WHO 2008 classification of acute leukemia is based largely on the presence of recurrent cytogenetic and molecular abnormalities. The most frequent chromosomal aberrations have been associated with specific clinical and biological characteristics and are now used as diagnosis and prognostic markers. These chromosomal abnormalities affect genes involving in the leukemogenesis process. These rearrangements are of several types:

* Fusion genes causing :

  * Repression of transcriptional activity of genes involved in differentiation of hematopoietic cells (AML1-ETO, PML-RARA...)
  * Deregulation of signal transduction pathway (eg BCR-ABL chimeric protein with constitutive tyrosine kinase activity)
  * Changing in the state of chromatin condensation resulting changes of transcription (MLL gene rearrangements in 11q23, MOZ en 8p11...)
* Deregulation of genes expression: chromosomal rearrangements can sometimes induce deregulation of adjacent genes to the breakpoint. For example, inv(3)(q21q26) or t(3;3)(q21;q26) induce over expression of transcriptional factor EVI-1.
* Loss of function due to deletion of variable size in genomic regions containing genes with a role in the differentiation, apoptosis, or cell proliferation (eg IKZF1, PAX5...)

In addition to the karyotype, which allows to have a global view of the genome; FISH, a targeted technique, is used to highlight invisible abnormalities on karyotype (cryptic abnormalities) or the time of karyotype failure. However, conventional and molecular cytogenetic techniques do not highlight any abnormalities (eg different partners involved in the formation of fusion genes in particular for MLL gene rearrangement, mutations) hence our interest in next generation sequencing.Indeed, the high throughput targeted sequencing messenger RNAs (RNA-seq) has the avantage of allow identification of different types of mutations in a single test, with exception of epigenetic mutations. The importance of RNAs sequencing rather than DNA genomic is the one hand, a very significant decrease in the volume of sequences to analyze because transcribed mRNA genes represent about 5% of the genome size and secondly, a better identification of chimeric genes. The RNA-seq has used as a research tool in hematologic malignancies. The purpose of this project is to use innovative technology to develop a new diagnostic and prognostic new tool in hematological malignancies. 50 acute leukemias will be tested and results will be analyzed according to three criteria:

* Quantity, quality and relevance of information provided for the diagnosis, monitoring and therapeutic management compared to a conventional strategy
* Period required to obtain results and methods to decrease the analysis time so that results can be integrated into therapeutic decisions.
* Economic evaluation, which will calculate the cost of this diagnosis option and assess the cost/benefit ratio In future, other innovative approaches will be implemented (study of imbalances genomic abnormalities by array-CGH, transcriptome analysis with micro-array, and study of methylome) to identify the "molecular signature" of each leukemia and set of informative abnormalities for diagnosis, prognosis and treatment of disease and monitoring of residual disease.

Targeted High Throughput Sequencing in the Diagnosis of Pediatric Acute Leukemia

use high throughput targeted sequencing messenger RNA to develop a new innovative diagnostic and prognostic tool in hematologic malignancies.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Predicting Local and Distant Recurrence in T1 Colorectal Cancer	NCT06314971	Colorectal Canc... Colorectal Neop... Colorectal Aden... Colorectal Canc... Colorectal Neop... Colorectal Canc...	Tw1CE	18 Years -	City of Hope Medical Center
Predicting Local and Distant Recurrence in T1 Colorectal Cancer	NCT06314971	Colorectal Canc... Colorectal Neop... Colorectal Aden... Colorectal Canc... Colorectal Neop... Colorectal Canc...	Tw1CE	18 Years -	City of Hope Medical Center
Molecularly Redefining Small Bowel Adenocarcinoma to Accelerate Precision Patient Care	NCT06234306	Small Bowel Ade...		18 Years -	Copenhagen University Hospital at Herlev
Targeted High Throughput Sequencing in the Diagnosis of Pediatric Acute Leukemia	NCT01991249	Pediatric Acute...	blood draw	- 18 Years	Assistance Publique Hopitaux De Marseille
Targeted High Throughput Sequencing in the Diagnosis of Pediatric Acute Leukemia	NCT01991249	Pediatric Acute...	blood draw	- 18 Years	Assistance Publique Hopitaux De Marseille
Molecularly Redefining Small Bowel Adenocarcinoma to Accelerate Precision Patient Care	NCT06234306	Small Bowel Ade...		18 Years -	Copenhagen University Hospital at Herlev

Spots Global Cancer Trial Database for messenger rna