Neoplasms

Symptoms and General Pathology

All Conditions

Digestive System Diseases

Cysts

Pancreatic Cyst

Pathological Conditions, Anatomical

Pancreatic Diseases

Gastrointestinal Diseases

This study evaluates the use of contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) and cyst fluid molecular analysis in the differential diagnosis of pancreatic cysts and the detection of malignancy.

Pancreatic cyst are a frequent finding on cross-sectional imaging on general population. They are identified in up to 3% of the abdominal computed tomographies (CT) and 20% of magnetic resonance imaging (MRI) performed for other reasons but the risk of malignancy in pancreatic cysts discovered incidentally is low, representing 1-5% of the total malignant pancreatic neoplasms.

Pancreatic cysts are a broad group of pancreatic lesions that can be divided into benign and premalignant or malignant lesions. Pseudocyst and serous cystic neoplasm (SCN) don´t have malignant potential while others like mucinous cysts are premalignant lesions. But not all mucinous neoplasms have the same risk of malignancy. According to recent publications mucinous cystic neoplasm (MCN) have a potential for malignancy of around 15%, main duct intrapapillary mucinous neoplasm (MD-IPMN) of 62% and branch duct IPMN (BD-IPMN) of 25%. The correct identification of these premalignant lesions will allow to optimize the treatment and follow-up of these patients, but in many cases it is difficult to accurately differentiate between different types of cysts and their risk of malignancy. The differentiation between lmucinous and non-mucinous cysts is suboptimal, with diagnostic accuracy for CT and MRI of 61% and 50-73% with endoscopic ultrasound (EUS). The endosonographic characteristics that have been related with malignancy are the size larger than 3 cm, the presence of a solid component, wall thickening, Wirsung dilation, abrupt change of the size of the main pancreatic duct with distal atrophy of the gland and the presence of lymphadenopathies. However, endosonographic characteristics are not sufficient as an individual predictor of malignancy.

The puncture of the cyst and fine-needle aspiration (EUS-FNA) with biochemical and cytological assessment is generally indicated to differentiate between cysts and to asses for malignancy. The determination of carcinoembryonic antigen (CEA) and amylase have low specificity for the detection of malignancy and for mucinous cyst, and the cytological assessment is highly specific but lacks of sensibility (50%). So further methods are requested for an adequate detection of premalignant and malignant cyst.

Contrast-enhanced harmonic endoscopic ultrasound uses an ultrasonographic contrast agent to visualize blood flow in fine vessels and may aid in the diagnosis of pancreatic cysts by enabling assessment of the vascularization of structures such as cyst walls, septa, or mural nodules. Furthermore it allows the correct differentiation between contrast-enhanced mural nodules, that predict for malignancy, from non-enhancing mucus clots.

The molecular analysis of cyst fluid may detect mutations that are associated with premalignant cyst and with malignancy. Kirsten rat sarcoma (KRAS) gene has been related with mucinous cyst while von Hippel-Lindau gene (VHL) is present in serous cyst.

This study evaluates the use of contrast-enhanced EUS and the molecular analysis for pancreatic cyst diagnosis and malignant detection, and if their use may modify cyst management.

Contrast Enhanced Ultrasound and Molecular Analysis in the Diagnosis of Pancreatic Cyst

Prospective Analysis About the Utility of Contrast Enhanced Endoscopic Ultrasound and Molecular Analysis in the Study of Pancreatic Cyst

Number and type of mutations that are present on the molecular analysis of premalignant and malignant mucinous cyst.

To evaluate the correlation between morphological diagnosis made by endoscopic ultrasound and diagnosis made by cyst fluid analysis (biochemical, cytological and molecular)

Percentage of pancreatic cyst that can be correctly diagnosed with contrast-enhanced EUS compared to EUS alone

Number of adverse events that happen during or 7 days after de procedure

Percentage of mutations that are present in both pancreatic cyst fluid and serum or only in cyst fluid

Fundación de Investigación Biomédica - Hospital Universitario de La Princesa

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Patients with pulmonary parenchymal lesions suspected for malignancy in contact or adjacent to the esophagus which can be sampled by EUS-B-FNA

Endoscopic ultrasound with bronchoscope fine needle aspiration (EUS-B-FNA) is an endoscopic technique based on a trans-esophageal needle aspiration performed by an interventional pulmonologist with the echo-bronchoscope

EUS-B-FNA

Michele Mondoni, MD

The aim of this study is to evaluate the diagnostic accuracy, safety and tolerability, predictors of success of EUS-B-FNA in the diagnosis of malignant parenchymal lung lesions.

The Investigators will also evaluated the adequacy of samples obtained for molecular analysis in patients with Non-Small Cell Lung Cancer (NSCLC)

Lung cancer is by far the leading cause of cancer death among both men and women worldwide. Non-Small Cell Lung Cancer (NSCLC) represents about 80-90% of all lung cancers. Endoscopic ultrasound with bronchoscope fine needle aspiration (EUS-B-FNA) is a safe and accurate technique that has been mostly described for the diagnosis and the mediastinal nodal staging of NSCLC, as a complementary technique to endobronchial ultrasound trans-bronchial needle aspiration (EBUS-TBNA) or when EBUS-TBNA may be difficult and/or contraindicated for clinical reasons (e.g. excessive cough, respiratory failure etc).

Few retrospective studies evaluated the sensitivity and the safety of this technique in the diagnosis of parenchymal pulmonary lesions suspected for lung cancer, in contact or adjacent to the esophagus. Few data are available on the adequacy of the samples obtained by EUS-B-FNA for molecular analysis in NSCLC. The main predictors of success are still unclear.

The primary aim of this prospective study is to evaluate the diagnostic accuracy of EUS-B-FNA in the diagnosis of malignant parenchymal lung lesions. The Investigators will also evaluate the safety and tolerability of the technique, the main predictors of success and the adequacy of samples obtained for molecular analysis in patients with NSCLC

EUS-B-FNA in the Diagnosis of Malignant Parenchymal Lung Lesions

Observational, Prospective, Multicenter Study on the Diagnostic Accuracy, Safety and Tolerability, Predictors of Success of EUS-B-FNA in the Diagnosis of Malignant Parenchymal Lung Lesions

Diagnostic accuracy (i.e., sensitivity and specificity) of EUS-B-FNA in the diagnosis of malignant pulmonary parenchymal lesions, discriminating those with a malignant disease in comparison with those without the malignant disease. A specific unit of measure is not included, being the computation of the present outcome based on the absolute number of malignant/non malignant cases to the total number of diagnosed individuals.

Proportional number (percentage) of samples obtained with EUS-B-FNA containing sufficient material (i.e. malignant cells) for molecular analysis in NSCLC following assessment by a pathologist/molecular biologist. A specific unit of measure is not included, being the computation of the present outcome based on the absolute number of malignant cells in the single sample.

Implementation of regression models (logistic regression analysis) to detect variables related to a successful aspirate: anatomical (i.e. lung, lobe of the lesion), endoscopic (type of endoscope, type of needle, number of needle passes, needle aspiration technique), pathological (presence/absence of rapid on-site evaluation (ROSE), health personnel performing ROSE (i.e pathologist, respiratory physician, cytotechnician), pathological technique used for diagnosis and molecular analysis (smear, cell-block, liquid based cytology). A specific unit of measure is not included, being the computation of the present variables based on the measurement of absolute numbers not recorded with a specific unit of measure. The unit of measure is basically identified by the single element of the variable.

Incidence rate and qualitative and quantitative description of adverse events in patients undergoing EUS-B-FNA. A specific unit of measure is not included, being the computation of the present outcome based on the absolute number of the adverse events detected by the attending physician.

University of Milan

MD, Principal Investigator

Colonic Neoplasms

Adenoma

Colonic Polyps

Polyps

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Intestinal Polyps

Herbal and Botanical

All Drugs and Chemicals

Cola

Individuals scheduled for colonoscopy at Hospital Universitari i Politècnic La Fe, participating in the Valencian CRC screening program, will be recruited.

Polypectomy or biopsy will be performed if necessary (following current guidelines).

Specific molecular analysis of serrated lesions and CRC will be carried out.

A colonoscopy will be performed to all individuals.

Colonoscopy

All lesions will be removed or biopsied during the procedure

Polypectomy or biopsy

Molecular analysis will be performed in all colorectal cancers and in those polyps diagnosed with "serrated lesion"

Molecular analysis

Marco Bustamante, M.D.;Ph.D.

Different subtypes of serrated lesions have been recently described. Among them, both sessile serrated polyp/adenoma (SSP/A) and traditional serrated adenoma (TSA) could have malignant potential through the serrated pathway or CIMP. These lesions, as a potential source of interval cancer, should also be considered in colorectal cancer (CRC) population-based screening programs. It is believed that this new described pathway could be responsible for up to 30% of all CRC.

Unlike the traditional adenoma, serrated lesions are difficult to diagnose because of their particular endoscopic appearance and their still unclear histological criteria. Furthermore, they have specific molecular changes and, through them, they could evolve into CRC faster than the adenoma. The real prevalence of the serrated lesions and their specific risk for developing new synchronous/metachronous lesions, or even malignancy, remains unknown. For all these reasons, we don't know if these patients could constitute a different CRC-risk group and if specific recommendations are needed during their follow-up.

This is a prospective longitudinal study developed within the framework of the CRC-screening program in the Valencian Community (Spain). We expect to include a total of 700 individuals who will be followed during 10 years.

In our study, we will collect epidemiologic variables related to the patient, variables related to all the polyps, and mutational (BRAF, KRAS, MSI), and CpG-island methylation status of serrated lesions. Strict endoscopic and histological criteria will be applied for the diagnosis of serrated lesions. All lesions detected at the index colonoscopy and during follow-up will be evaluated.

The purpose of this study is to correlate epidemiologic data, histological characteristics and the molecular profile of the serrated lesions with findings during follow-up, in order to define stratified groups according to their risk of developing new lesions or CRC in the future.

BACKGROUND Colorectal cancer (CRC) is, by its frequency and consequences, a relevant public health problem that has led to the implementation of population screening programs in many countries. The purpose of these programs is to reduce the incidence and mortality of CRC by early diagnosis of the disease, in the so-called pre-symptomatic phase. That is, to identify and remove all precursor lesions, essentially colon adenomas.

However, there is increasing evidence that these programs are not fully effective in preventing CRC. Cancers that appear before the next scheduled endoscopic control, called interval cancer (IC), occur in up to 2.5 / 1000 patients / year of observation, and the cumulative probability of developing a CRC within the first 5 years after an adenoma removal could be up to 2%. Recent studies suggest that the cause of more than 50% of ICs is the failure detecting premalignant lesions in the colon, either due to a poor colon preparation, technical deficiencies in the performance of colonoscopy or the characteristics of the lesions that make them barely visible.

A possible origin of the ICs could be the serrated polyp (SP). This is actually not a single lesion, but a heterogeneous group of lesions, different from the conventional adenoma, and characterized by the serration of the crypts in the histology. Serrated lesions, especially some subgroups, have macroscopic features that make them particularly difficult to detect in conventional colonoscopy: indistinct borders, cloud-like appearance, often covered by a mucous cap and interruption of the underlying mucosal vascular pattern. But the true diagnosis of serrated lesions is made by morphological criteria with the microscopic examination of the sample obtained by biopsy. Although all lesions that showed these features were initially identified as hyperplastic polyps (HP), in the last decade three subtypes of serrated lesions with different clinical implications have been described \[HP, sessile serrated polyp/adenoma (SSA/P) and traditional serrated adenoma (TSA)\]. However, the histological criteria are not yet fully clarified, and there is confusion in the terms to be used. Therefore, the agreement among pathologists is generally poor.

As a consequence, many serrated lesions are misdiagnosed and incorrectly classified. This has clinical relevance since some of them have malignant capacity. Both SSA/P and TSA can evolve to CRC through the so-called serrated pathway or cytosine-phosphate-guanosine (CpG) island methylator phenotype (CIMP), which could be responsible for up to 30% of all CRC. In this pathway, an aberrant hypermethylation of the genome is produced, which leads to transcriptional silencing and inhibition of expression in some genes promoter regions (epigenetic modification). CRCs that arise from a SP are not homogeneous and may have different molecular and histological characteristics depending on whether the origin mutation in the precursor lesion occurs in BRAF or Kirsten rat sarcoma (KRAS) gene, which leads to the development of SSA/P or TSA. And depending on if a mutL homolog 1 (MLH1) gene methylation is produced thereafter, a unstable (MSI) or stable (MSS) CRC will develop. The presence of a high CIMP rate also depends on the initial mutation. Therefore, serrated lesions could originate MSI/CIMP-H CRC (11%), MSS/CIMP-H CCR (4%) and MSS/CIMP-L CRC (15%). It is thought that some of the ICs may be directly related to the SP because they share morphological and molecular characteristics. The evolution from SSP/SSA to invasive carcinoma has been described to occur in only eight months.

This theoretical risk of developing advanced premalignant lesions and IC and its clinical significance has not been clearly shown in clinical practice because data on the prevalence of serrated lesions are limited and there is also a lack of longitudinal follow-up studies in patients with serrated lesions. The prevalence described is very variable and ranges from 0.6% to 13%, depending on the study, and the data are even scarcer in fecal occult blood test (FOBT) -based screening population. The presence of serrated lesions (other than HP) has been associated with the development of advanced synchronous adenomas in the colon, but also with advanced metachronous lesions during follow-up. This situation could place these patients in a special risk group. Patients with large SP may have a similar risk to develop a future CRC to those patients with advanced adenomas. Most Scientific Societies recommend endoscopic follow-up of serrated lesions, but the evidence is weak and specific intervals are proposed based only on expert recommendations.

In summary, there are still many unresolved questions about serrated polyps and their importance in CRC screening programs. Their prevalence on CRC screening population is not fully clarified because of the lack of prospective trials and the difficulty in diagnosis and histological classification. Their malignant potential is not clarified either because of the uncertainty about the prevalence of dysplasia in serrated lesions, and the lack of well-designed longitudinal studies for the detection of metachronic lesions. The current criteria for classifying these lesions seem weak to define the CRC risk for a specific patient, thus the proposed follow-up intervals are not based on strong scientific evidence. A thorough study of serrated lesions relating their molecular and histological characteristics with lesions found on colonoscopic follow-up could establish a new molecular classification aimed to design a patient-oriented follow-up strategy.

HYPOTHESIS The correlation of epidemiological data of the patient, histological characteristics and molecular alterations of SP of the colon, along with findings in the endoscopic follow-up, would allow to identify stratified groups of patients according to their risk of developing advanced lesions and CRC in the future.

OBJECTIVE

* To deepen the knowledge of histology and genetic alterations of SP and thereby try to establish a molecular classification that may serve as a basis for new endoscopic follow-up guidelines. These recommendations would be more reliable and adjusted to the patient's individual risk profile.
* To establish the prevalence of serrated lesions, especially SSP/SSA and SSP with dysplasia, in the FOBT positive CRC screening population.

colonic polyp or colorectal cancer samples

Molecular and Histological Characteristics of Serrated Lesions of the Colon

Molecular and Histological Characteristics of Serrated Lesions of the Colon: Development of an Individual Risk Profile Applicable to Population-based Colorectal Cancer Screening Programs

To assess the risk of developing metachronous advanced lesions or cancers in FOBT screening population

Analysis of molecular changes in colorectal cancer and serrated lesions in FOBT screening population

To assess the prevalence of serrated lesions in FOBT screening population

Hospital Universitario La Fe

Gastrointestinal Endoscopy Consultant

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Lymphoma

Lymphoma, Follicular

Lymphoma, B-Cell, Marginal Zone

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Lymphoma, Non-Hodgkin

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Follicular Lymphoma

B-cell Lymphoma

Marginal Zone Lymphoma

Diffuse Large B-Cell Lymphoma

Anti-Infective Agents

Formaldehyde

Chrysanthemum

Diagnoses of follicular lymphomas based on the last World Health Organization (WHO) classification of haematolymphoid tumours at the time of occurrence of the disease. Fluorescence in situ hybridization (FISH) utilizes Vysis' Dual-Color Break-Apart Rearrangement Probes to detect BCL6 gene alterations. FISH patterns have been interpreted following established protocols.

Diagnoses of marginal zone lymphomas based on the last WHO classification of haematolymphoid tumours at the time of occurrence of the disease. FISH utilizes Vysis' Dual-Color Break-Apart Rearrangement Probes to detect BCL6 gene alterations. FISH patterns have been interpreted following established protocols.

Diagnoses of diffuse large B-cells lymphomas based on the last WHO classification of haematolymphoid tumours at the time of occurrence of the disease. FISH utilizes Vysis' Dual-Color Break-Apart Rearrangement Probes to detect BCL6 gene alterations. FISH patterns have been interpreted following established protocols.

Morphological analysis will include the description of architectural patterns and cytological features on formalin-fixed and paraffin-embedded (FFPE) tissue samples retrieved from the routine diagnostic archives of the Pathology Department of the University Hospital Lyon Sud.

A panel of immunohistochemical staining will be analyzed including CD20, CD3, CD10, Bcl-6, Bcl-2, CD5, CD23, CD38, MUM1, Ig kappa, Ig lambda, MEF2B, LMO2, MNDA, IRTA1, P53, CMYC and Ki67 . /MIB1. Diffuse large B-cells lymphomas will be classified into two distinct subgroups: centro-germinative (GC) and non-centro-germinative (nGC), using the Hans algorithm.

Histopathological analysis

Next-generation sequencing (NGS) analysis will be performed on FFPE tissue samples retrieved from the routine diagnostic archives of the Pathology Department of the University Hospital Lyon Sud. A panel of 73 genes dedicated to lymphoma diagnosis determined by a consensus of French Lysa experts will be used. The identification of genetic variants will be followed by the attribution of pathogenicity class in accordance with the guidelines for validation of NGS-based oncology panels.

RNA extraction will classify DLBCLs into two distinct subgroups: germinal-centre B-cell-like (GCB-DLBCL) and activated B-cell-like (ABC-DLBCL).

Non-Hodgkin lymphomas (NHLs) constitute a heterogeneous group of malignant neoplasms, with diverse clinical behaviors and distinct pathologic and molecular characteristics. Among these lymphomas, follicular lymphomas (FLs), marginal zone lymphomas (MZLs) and diffuse large B-cell lymphomas (DLBCLs) emerge as the most prevalent entities. While FL and MZL are representative of indolent B-cell lymphomas, characterized by a slow progression of the disease and favorable clinical outcomes, DLBCL stands out as an aggressive lymphoma, often occuring from the transformation of a pre-existing indolent lymphoma.

Chromosome translocations are a hallmark of some NHL subtypes, offering insights into their molecular pathogenesis. For instance, the conventional FL is genetically characterized by the t(14;18) chromosomal translocation, found in 85-90% of cases, resulting in sustained elevation of the antiapoptotic protein B-cell lymphoma 2 (BCL2). However, certain FL cases lack BCL2 translocations and exhibit distinct clinical, morphological and phenotypical features with genetic heterogeneity.

A subset of BCL2-negative FLs displays rearrangements within chromosomal region 3q27, inducing abnormal modulation of B-cell lymphoma 6 (BCL6) expression. The BCL6 gene plays a critical role in germinal center development and B-cell differentiation. Previous investigations indicate that BCL6 rearrangements (BCL6-R) manifest distinct pathological and genetic features, diverging from classical FL presentations.

FLs carrying BCL6-R commonly share a specific CD10- Bcl-2- Bcl-6+ phenotype, often accompanied by a monocytoid component and increased frequency of diffuse architectural patterns. Patients with BCL6-R tend to exhibit advanced clinical stages and complex genetic profiles.

MZLs present differential diagnostic challenges due to shared monocytoid components, phenotypes traits, and common genetic features. The similarities observed between BCL6-R FL and MZL suggest a convergence in both morphological and genetic aspects, leading to intricate differentiation. Traditionally, these indolent NHLs with BCL6-R were categorized as FL and incorporated into the FL category in the WHO classification. However, few studies highlight the occurrence of BCL6-R in MZLs. This observation gives rise to the hypothesis that indolent NHLs exhibiting BCL6-R might correspond to a continuum comprising both FL and MZL.

Additionally, BCL6-R has been frequently documented in DLBCL cases with residual MZL component. These DLBCL cases might display a mutational profile reminiscent of MZL. This suggests a plausible origin of BCL6-R DLBCL from indolent BCL6-R MZLs or BCL6-R FLs cases.

The samples analyzed will have been collected as part of routine medical care for each patient before inclusion in the study.

These are formalin-fixed, paraffin-embedded (FFPE) tissue samples. They will be packaged and stored in the Biological Resources Center of the Hospices Civils de Lyon.

BCL6-rearrangements Implications in Non-Hodgkin Lymphomas.

Study of Clinical, Histological, Immunohistochemical and Molecular Impact of BCL6 Gene Rearrangement in Most Prevalent Non-Hodgkin Lymphomas

An examination of morphological attributes, including tissue architecture and cellular patterns will be performed on LF and MZL with BCL6-R. An extended immunohistochemical staining panel employing incorporated novel centro-germinative markers (LMO2 and MEF2B) and recently identified MZL-specific markers (IRTA1 and MNDA) is planned.

Fluorescence in situ hybridization (FISH) will be employed for cytogenetic evaluation to detect BCL2 and BCL6 gene rearrangements. In parallel, targeted next-generation sequencing (NGS) analysis will enable genetic variant detection.

Hospices Civils de Lyon

Adenocarcinoma

Neuroendocrine Tumors

Carcinoma, Neuroendocrine

Carcinoma

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neuroendocrine Tumor

Neuroepithelioma

Hematinics

Gastrointestinal Agents

Liver Extracts

Pancrelipase

Pancreatin

Patients aged at diagnosis from18 to 39 years of age with neuroendocrine neoplasm NEN from Gastroenteropancreatic (GEP) or lung/thymus origin

Patients aged at diagnosis from18 to 39 years of age with carcinoma (without limitations for histologic subtypes) from any primary sites: esophagus, stomach, pancreas, biliary tract, liver, small bowel, colon, rectum, anus and cancer of unknown origin.

Lorenzo Gervaso, MD

Cristina Mazzon

Chiara Alessandra Cella, MD

Luca Mazzarella, MD

Francesca Spada, MD

The objective of the study is to create a common and unique platform for the acquisition of biological samples and, subsequently, the possible identification of predictive and prognostic biomarkers for young adults with gastrointestinal and neuroendocrine cancers.The definition "adolescent and young adults (AYA)" covers a broad group of patients ranging from the upper limit of the paediatric competence to the youngest patients usually considered and treated as adults. However, a well-defined and universally accepted age range is still not established. Young adults with cancer have distinct epidemiological, biological, and clinical characteristics, as well as special medical and psychosocial needs that are often unmet. In consideration of their poor representation in clinical studies, as well as the rarer, albeit increasing, frequency at an epidemiological level, knowledge of the risk factors associated with cancers in young adults is very poor. It is therefore of fundamental importance to focus attention on this specific cohort of patients, in order to describe in ever more detail any specific biomolecular aspects, and make full use of the pharmacological resources currently available.

The definition "adolescent and young adults (AYA)" covers a broad group of patients ranging from the upper limit of the paediatric competence to the youngest patients usually considered and treated as adults. However, a well-defined and universally accepted age range is still not established. In fact, AYA includes patients from 16 to 24 years old according to the Britannic association "Teenage Cancer Trust" or 39 years old for the American National Cancer Institute definitions, respectively. Over the past 30 years, the incidence of cancer in AYA patients has increased globally by approximately 30%, estimating, in 2020 in U.S, 89,500 new cases and 9,270 deaths due to cancer among AYAs. Although the most frequent tumors are germ cell cancer for males and breast and thyroid cancers for female across the world, and confirmed also in Italian registries (https://www.aiom.it/wpcontent/uploads/2020/10/2020_Numeri_Cancro-operatori-web.pdf), malignancies arising from the gastrointestinal tract account all together for around 10% of cases. These are mainly represented by gastric cancer (up to 5%) followed by colorectal, neuroendocrine and hepatobiliary tumors.

Due to the high impact in terms of social impairment, a new and specific classification system based on the International Classification of Diseases for Oncology (ICD-O) and the World Health Organization (WHO) Classification of Tumors series for AYA cancers has been recently presented in order to sharpen the medical needs of this population.

However, AYA cohort remains a major clinical challenge, especially because of its poor representation in clinical trials, which prevent from the possibility to create a profile with specific molecular and etiopathogenetic features. Even though a significant part of these tumors rises from a hereditary basis (often in patients already followed by medical Genetic Unit), in most cases, cancers are sporadic, only partially associated to earlier exposure to carcinogenic factors such as alcohol and smoking, as well as a sedentary lifestyle and poor dietary education. Therefore, many questions remain unsolved regarding carcinogenesis, treatment, prognosis, and, eventually, prevention for family members of these patients.

Moreover, AYAs have a higher risk - even if lower than pediatric patients - to present long-term and late-onset side effects, concerning infertility, sexual disfunction, cardiotoxicity and second tumors. Early predictors biomarkers of these potential consequences are strongly needed. Considering current scarce information regarding how to improve outcomes of young patients affected by GI cancers and neuroendocrine neoplasms, this study aims to shed light on the biological behavior and the unmet needs of this population, by correlating clinical and biological factors to clinical outcomes. The main goal will be, firstly, the creation of a common and unique platform for acquiring biological samples and subsequently, potentially the identification of predictive and prognostic biomarkers.This study comprises both a retrospective and prospective phase. For the retrospective one, AYA patients will be included with GI or NeuroEndocrine (NE) malignancies (histologically confirmed). In the prospective part, when the study will be actively recruiting, clinical and biological data of all AYA patients will be collected and analyzed, according to specific outcomes.

YOUNg Adults With Gastro-inteSTinal (GI) and nEuroendocrine canceRs.

YOUNg Adults With Gastro-inteSTinal (GI) and nEuroendocrine canceRs (YOUNGSTER).

Prospective and retrospective observational study to analyze the frequency of tumors in young adults (18-49 years) with gastrointestinal and neuroendocrine tumors. Identification of genetic alterations with correlation between somatic and germline alterations.

Describe survival outcomes (overall survival and progression-free survival) according to the main clinical-pathological features and treatment received.

Describe potential toxicities developed as results of treatments according to clinical-pathological, genomic features and treatment received.

European Institute of Oncology

Skin and Connective Tissue Diseases

Breast Neoplasms

Neoplasm Metastasis

Breast Diseases

Skin Diseases

for the patients recruited retrospectively collection of biopsy is not considered intervention, as the relapse samples were collected according to standard of care in the participating hospitals.

For the prospective collection of samples, the relapsed patients will be asked to donate tissue and blood samples

collection of the biopsy, blood samples

Within the 1st step MINDACT patients who have already relapsed will be asked to participate. For these patients a biopsy of the metastasis should have been taken. A molecular analysis of the stored primary tumor sample and of the metastatic sample, using new technologies, will be performed, and the characteristics of both samples will be compared.

Within the 2nd step a prospective collection of the metastasis samples will be implemented and analysis of biological material from relapsing MINDACT patients is foreseen.

This process will provide insights on the biology of breast cancer and allow us to better understand mechanisms of resistance to therapies, contributing to overcoming this important problem.

Dissecting the Pathways of Therapy Resistance in Early Breast Cancer

Dissecting the Pathways of Therapy Resistance in Early Breast Cancer: A Sub-study of the EORTC 10041/BIG 3-04 MINDACT Study

The access to the data collected within this study, upon study completion could be requested by filling in the request form on EORTC website.

Collection of tissue from the first site of relapse or new primary breast cancer, and blood samples for patients still alive that have relapsed (retrospective collection) or will relapse (prospective collection)

Characterization of disease progression using molecular characterization of tumour and germline molecular markers in tissue and blood.

Treatment resistance studies aiming to verify if a given mechanism is responsible for the relapse after exposure to anticancer agents will be performed using molecular characterization of tumour and germline molecular markers in tissue and blood..

European Organisation for Research and Treatment of Cancer - EORTC

Neoplastic Processes

Anti-Inflammatory Agents

Triamcinolone

Triamcinolone Acetonide

Triamcinolone hexacetonide

Triamcinolone diacetate

patients in whom lung metastasis were resected for therapeutic purposes

patients in whom lung metastasis were removed for diagnostic purposes only

The mutational analysis of the main oncogenes and tumor suppressor genes involved in the genesis and tumor progression will be performed on the genomic DNA extracted from each sample using the Ion Torrent TM Oncomine TM Comprehensive Assay version 3 (OCAv3) kit. This panel includes 161 cancer-related genes and allows the identification of all genomic alterations affecting oncogenes and recurrently altered tumor suppressor genes in solid tumors. The study of gene expression will be carried out using Nanostring Technology using the Pancancer IO 360 TM panel which allows simultaneous analysis for each sample of multiple mRNAs associated with crucial pathways in carcinogenesis and the immunological profile of the tumor, defining its up and down conditions gene regulation.

Analysis of genetic mutations and the gene expression profile of lung metastasis and primary neoplasia

This study will be performed using the SPAARC IBSI (International Biomarker Standardization Initiative) compliant software implemented in the MatLab environment (MathWorks, Boston, USA) through several steps: (a) CT imaging retrieval, (b) image segmentation and rendering, (c) feature extraction and (d) qualification/quantification. Approximately 200 radiomics characteristics will be extracted, such as: Morphology, Statistical, Intensity Histogram, Gray Level Co-occurrence Matrix 3D_average, Gray Level Co-occurrence Matrix 3D_combined, Gray Level Run Length 3D_average, Gray Level Run Length 3D_combined, Gray Level Size Zone Matrix 3D, Neighbor Gray Tone Difference Matrix 3D, Gray Level Distance Zone Matrix 3D.

Radiomics analysis on TAC imaging at diagnosis of lung metastasis and, if possible, of the primary tumor

Giulia Orsi, MD

Maria Maddalena Valente, PhD

Francesco De Cobelli, Prof.

Diego Palumbo, MD

Michele Reni, MD

Claudio Doglioni, Prof.

Giampiero Negri, Prof.

Angelo Carretta, MD

The aim of this study is the characterization from epidemiological, radiomics and molecular point of view of lung metastasis of patients at beginning affected by pancreatic adenocarcinoma (PDAC), which after the resection of primitive tumor have met with initial recurrence of the disease exclusively at the lung level.

Radical surgical treatment of primitive PDAC, associated with adjuvant cancer treatments, is possible only in 15-20% of patients, and, to date, represents the best therapeutic strategy. Nevertheless, remote recurrence is frequent after radical surgical treatment of primitive neoplasia. Among the main locations of metastasis from PDAC, the lung represent the second metastatic location with a better prognosis than other remote metastasis. Surgical treatment of lung metastasis has a consolidated role in the treatment of other neoplasms such as sarcomas, colorectal and renal neoplasms while in the context of PDAC the resection of lung metastases is a rather rare and also debated event.

In absence of consolidated data on the results of surgical treatment and on the clinical outcomes of patients with lung metastasis from PDAC the investigators designed this retrospective observational study in order to analyze the clinical and pathological characteristics of patients suffering from lung metastasis from PDAC treated at San Raffaele Hospital in a period between 2008 and 2019. To this purpose, the investigators will analyze and compare two patient cohorts: 1-patients in whom lung metastasis were resected for therapeutic purposes; 2-patients in whom lung metastasis were removed for diagnostic purposes only.

An analysis of genetic mutations and the gene expression profile of lung metastasis and primary neoplasia will also be performed to evaluate any predictive elements of lung metastasis and the prognostic role of these mutations.

In parallel, the investigators will perform radiomics analysis on TAC imaging at diagnosis of lung metastasis and, if possible, of the primary tumor.

All the data necessary for the completion of the study were collected as part of the usual outpatient visits in the appropriate outpatient medical records and include: date of birth, date of diagnosis, gender, performance status, stage of the disease, comorbidity, concomitant chronic therapies, level of tumor markers (CEA and Ca19.9) before treatment and variations during therapy, type of chemotherapy, start and end date of chemotherapy, number of cycles, possible dosage reduction of the drugs used in the various chemotherapy regimes, dates and results of instrumental revaluations according to RECIST 1.1, main chemotherapy toxicities and grade according to CTCAE 5.0, date and type of surgery, mutation analysis results and last follow-up date. In the event of death, the dates of death are communicated by the registry office of the municipality of residence of the patient, according to the official procedure. All data will be collected in an electronic database in coded form (pseudonymization).

Power size calculation:

All patients who meet the inclusion and exclusion criteria and who have been treated at the Medical Oncology and Thoracic Surgery Units of the San Raffaele Hospital between 2008 and 2019 will be taken into consideration, for a total of 44 patients. To identify predictive and/or prognostic clinical and pathological factors that can influence the outcome of these patients, the two cohorts described above will be analyzed and compared through univariate and multivariate analyzes. Overall survival (OS) and progression-free survival (PFS) will also be assessed using the Kaplan Meier method and the long-rank test will be used to compare OS and PFS between the two cohorts under study. All tests will be double-tailed and a p \<0.05 will be considered significant. The ninety-five percent confidence intervals (CI) will be calculated to assess the accuracy of the estimates obtained.

DNA from histological samples fixed in formalin and included in paraffin

Evaluation of Clinical, Radiomics and Molecular Features of Lung Metastasis in PDAC Patients (LUMACA Trial)

Retrospective Observational Study on Patients With Lung Metastases From Pancreatic Adenocarcinoma: Evaluation of Clinical Features and Correlation With Molecular and Radiomics Features

Analyze the clinical and pathological characteristics of the two cohorts of patients affected by lung metastasis from PDAC

Correlate the pathological characteristics of the two cohorts of patients affected by lung metastasis from PDAC with radiomics and molecular features, in order to identify prognostic and/or predictive factors related to lung metastasis in the PDAC

Highlight any differences between the two cohorts of patients examined

IRCCS San Raffaele

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Carcinoma, Squamous Cell

Microsatellite Instability

Mouth Neoplasms

Oropharyngeal Neoplasms

Head and Neck Neoplasms

Mouth Diseases

Stomatognathic Diseases

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Pharyngeal Diseases

Otorhinolaryngologic Diseases

Oral Cancer

Lip and Oral Cavity Cancer

Radiotherapy 50 Gy

Stephane Temam

There is no consensus on the indication of postoperative radiotherapy for early stages oral and oropharyngeal squamous cell carcinoma with complete pathological resection and no neck node metastasis, but most of the institutions do not give any post-operative treatment. Loco-regional control rates range between 80-85% at five years. Surgical margins molecular analysis for microsatellite instability (MSI) marker could help to select the high-risk patients who should receive postoperative radiotherapy. We expect to include 120 patients in five years and have 60 informative tumors for MSI marker. Patients with positive molecular margins will receive postoperative radiotherapy (50 Gy). Patients with negative molecular margins will not receive radiotherapy.

Postoperative Radiotherapy According to Molecular Analysis of Surgical Margins of Oral and Oropharyngeal SCC

Postoperative Radiotherapy According to Molecular Analysis of Surgical Margins of Early Stages Oral and Oropharyngeal Squamous Cell Carcinomas: A Prospective Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Contrast Enhanced Ultrasound and Molecular Analysis in the Diagnosis of Pancreatic Cyst	NCT03740360	Pancreatic Cyst		18 Years -	Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
EUS-B-FNA in the Diagnosis of Malignant Parenchymal Lung Lesions	NCT03983005	Lung Cancer	EUS-B-FNA	18 Years -	University of Milan
EUS-B-FNA in the Diagnosis of Malignant Parenchymal Lung Lesions	NCT03983005	Lung Cancer	EUS-B-FNA	18 Years -	University of Milan
Molecular and Histological Characteristics of Serrated Lesions of the Colon	NCT03089268	Colonic Neoplas... Colorectal Canc... Sessile Serrate... Polyp of Colon	Colonoscopy Polypectomy or ... Molecular analy...	50 Years - 75 Years	Hospital Universitario La Fe
BCL6-rearrangements Implications in Non-Hodgkin Lymphomas.	NCT06424379	Non Hodgkin Lym... Follicular Lymp... Marginal Zone L... Diffuse Large B...	Histopathologic... Molecular analy...	25 Years - 100 Years	Hospices Civils de Lyon
YOUNg Adults With Gastro-inteSTinal (GI) and nEuroendocrine canceRs.	NCT06337760	Neuroendocrine ... Adenocarcinoma		18 Years - 39 Years	European Institute of Oncology
Dissecting the Pathways of Therapy Resistance in Early Breast Cancer	NCT04995575	Breast Cancer	collection of t...	-	European Organisation for Research and Treatment of Cancer - EORTC
Evaluation of Clinical, Radiomics and Molecular Features of Lung Metastasis in PDAC Patients (LUMACA Trial)	NCT04435067	Pancreas Adenoc...	Analysis of gen... Radiomics analy...	18 Years -	IRCCS San Raffaele
BCL6-rearrangements Implications in Non-Hodgkin Lymphomas.	NCT06424379	Non Hodgkin Lym... Follicular Lymp... Marginal Zone L... Diffuse Large B...	Histopathologic... Molecular analy...	25 Years - 100 Years	Hospices Civils de Lyon
Dissecting the Pathways of Therapy Resistance in Early Breast Cancer	NCT04995575	Breast Cancer	collection of t...	-	European Organisation for Research and Treatment of Cancer - EORTC
Postoperative Radiotherapy According to Molecular Analysis of Surgical Margins of Oral and Oropharyngeal SCC	NCT00232960	Oral Cancer Oropharynx Canc...	Radiotherapy 50...	18 Years -	Gustave Roussy, Cancer Campus, Grand Paris

Spots Global Cancer Trial Database for molecular analysis