Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Mantle-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Mantle Cell Lymphoma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Amino Acids

Rituximab

Tyrosine Kinase Inhibitors

Tyrosine

An historical cohort of patients will be identified and selected both on a clinical base and according to the availability of Formaline-fixed paraffin-embedded (FFPE) material, frozen material or viable cryopreserved cells at Mantle Cell Lymphoma (MCL) diagnosis. Samples will be analyzed in 4 subgroups, each with different clinical specificity:

1. refractory to Induction Chemoimmunotherapy (CIT);
2. refractory to Bruton Tyrosine kinase (BTK) inhibitors (BTKi);
3. sensitive to Induction Chemoimmunotherapy (CIT);
4. sensitive to Bruton Tyrosine kinase (BTK) inhibitors (BTKi).

Marina Cesaretti

Elena Borgo

Elsa Pennese, MD

Alberto Fabbri, MD

Guido Gini

Guido Gini, MD

Pietro Bulian, MD

Attilio Guarini, MD

Alessandro Re, MD

Luca Nassi

Luca Nassi, MD

Nicola Di Renzo, MD

Andres Ferreri, Dott.

Francesca G Rossi, Dott.ssa

Francesca G Rossi, MD

Riccardo Moia, Dott.

Riccardo Moia, MD

Luca Arcaini, Prof.

Annalisa Arcari, MD

Angelo Fama, MD

Alice Di Rocco, MD

Stefan Hohaus, Prof.

Carola Boccomini, MD

Simone Ferrero, MD

Chandrakala Toldo, Dott.ssa

Chandrakala Toldo, MD

Piero Maria Stefani, MD

Michele Merli, MD

Francesca Maria Quaglia, Dott.ssa

Francesca Maria Quaglia, MD

Maria Chiara Tisi, Dott.ssa

Maria Chiara Tisi, MD

Francesca Maria Quaglia

Retrospective observational study with a prospective biological evaluation of an historical cohort of first relapsed-refractory patients with mantle cell lymphoma who were relapsed or refractory to rituximab and chemotherapy containing induction regimens with curative intent.

Biological samples from 80 Mantle Cell Lymphoma (MCL) patients will be collected and analyzed in 30 Italian sites in 36 months.

Patients will be identified and selected both on a clinical base and according to the availability of Formaline-fixed paraffin-embedded (FFPE) material, frozen material or viable cryopreserved cells at Mantle Cell Lymphoma (MCL) diagnosis. They will be analyzed in 4 subgroups, each with different clinical specificity: 1) refractory to Induction Chemoimmunotherapy (CIT); 2) refractory to Bruton Tyrosine kinase (BTK) inhibitors (BTKi); 3) sensitive to induction Induction Chemoimmunotherapy (CIT); 4) sensitive to BTK inhibitors (BTKi).

Each group will undergo central pathology revision with other immunohistochemical studies (Verona, Dr. Parisi; Milano, Prof. Ponzoni; Vicenza, Dr. D'Amore; Brescia, Prof. Facchetti). Formaline-fixed paraffin-embedded (FFPE) diagnostic specimens of Mantle Cell Lymphoma (MCL) will be screened by immunohistochemistry for the expression of immunoglobulin (Ig) heavy chains to identify Mantle Cell Lymphoma (MCL) cases lacking Immunoglobulin (Ig) expression.

Cytofluorimetric and molecular studies will be performed in the laboratories of the Verona University and at IFOM (Istituto FIRC di Oncologia Molecolare (FIRC = Fondazione Italiana per la Ricerca sul Cancro)). Specific methods will be used: Flow cytometry for the status of surface Ig expression and multiplexed phospho-specific flow cytometry, NGS (Next Generation Sequencing), Immunoglobulin (IgH/IgL V(D)J) profiling by BIOMED2 protocol-based, NGS (Next Generation Sequencing) technology in the relapsed-refractory mantle cell lymphoma (R/R MCL) cases, Chromatin accessibility studies by Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq) (on viable cell suspensions or frozen pellets) and Gene Expression Profiling (GEP) by RNA-sequencing and RNA studies of the MALT1-MYC ((Mucosa-associated lymphoid tissue lymphoma translocation protein 1 - MYC) pathway.

For the primary objective of the study: Formaline-fixed paraffin-embedded (FFPE) material.

For the secondary objectives of the study: viable cell suspensions, DNA extracted from Formaline-fixed paraffin-embedded (FFPE) tissue sections or frozen pellets, frozen cell suspensions.

Biological Insights of First Relapsed-refractory Patients With Mantle Cell Lymphoma: the MANTLE-FIRST BIO Study.

Histopathological characterization of patients with mantle cell lymphoma (MCL) who were relapsed or refractory to rituximab and chemotherapy containing induction regimens with curative intent. 80 Mantel Cell Lymphoma (MCL) patients stratified according to Chemo-immunotherapy (CIT) or Bruton Tyrosine kinase inhibitors (BTKi) resistance (20 for each of the groups previously identified) will undergo central pathology revision with assessment of Immunoglobulin (Ig) expression and other histopathological studies.

Performed on formalin-fixed paraffin-embedded (FFPE) tissue sections as well as, when available, on frozen material or viable cryopreserved cells at Mantle Cell Lymphoma (MCL) diagnosis. The aim is to perform a mutational analysis for Mantle Cell Lymphoma (MCL) driver genes: Next Generation Sequencing (NGS) on approximately 80 cases of Mantle Cell Lymphoma (MCL), including 20 cases Relapsed/Refractory (R/R) to Bruton Tyrosine kinase inhibitors (BTKi)

Performed on formalin-fixed paraffin-embedded (FFPE) tissue sections as well as, when available, on frozen material or viable cryopreserved cells at Mantle Cell Lymphoma (MCL) diagnosis. The aim is to perform a functional study of the B-Cell Receptor (BCR) activity: multiplexed phospho-specific flow cytometry on 10-20 Relapsed/Refractory (R/R) Mantle Cell Lymphoma cases.

Performed on formalin-fixed paraffin-embedded (FFPE) tissue sections as well as, when available, on frozen material or viable cryopreserved cells at Mantle Cell Lymphoma (MCL) diagnosis. The aim is to understand the mechanisms of evasion from B-Cell Receptor (BCR) requirement as follow:

* Immunoglobulin (IgH/IgL V(D)J) profiling by Next Generation Sequencing (NGS) on 80 mantle cell lymphoma (MCL) cases;
* Chromatin accessibility studies (Assay for Transposase-Accessible Chromatin sequencing, ATAC-seq) on approximately 20 cases among the Immunoglobulin (Ig)-negative identified cases or Bruton Tyrosine kinase inhibitors (BTKi) refractory cases, irrespective of their B-Cell Receptor (BCR) status, and on other 20 cases, from the group of patients sensitive to Bruton Tyrosine kinase inhibitors (BTKi);
* Gene Expression Profiling (GEP) by RNA-seq, on about 20 cases selected on the basis of results of the Assay for Transposase-Accessible Chromatin sequencing (ATAC-Seq) analysis;

Performed on formalin-fixed paraffin-embedded (FFPE) tissue sections as well as, when available, on frozen material or viable cryopreserved cells at Mantle Cell Lymphoma (MCL) diagnosis. The aim is to perform RNA studies on 20 cases

About 80 cases of Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL) with available tissue samples will be considered for correlation between biological studies with clinical characteristics of patients, response to treatment and conventional outcomes (Progression Free Survival, Progression Free Survival at 2 years, Overall Survival, Overall Survival at 2 years)

Fondazione Italiana Linfomi - ETS

Respiratory Tract (Lung and Bronchial) Diseases

Diseases and Abnormalities at or Before Birth

Lung Neoplasms

Lung Diseases

Congenital Abnormalities

Lung Diseases, Interstitial

Respiratory Tract Diseases

All CT Lung Cancer Screening patients at LHMC from January 1st, 2012 to September 30th, 2014 with an in-network PCP that had baseline CT scans will be scored. A subset of these patients with T4 screening scans will be scored for progression.

Retrospective observational study

Lee Gazourian, MD

Interstitial Lung Abnormalities (ILA) have been previously defined as nondependent changes affecting more than 5% of any lung zone on computed tomography (CT) scans of the lung. Several studies suggest that the prevalence of ILA in participants in non-pulmonary research studies ranges anywhere from 7-9%. Work over the last decade has shown that, despite previous characterization as an asymptomatic research finding, ILA has significant clinical and biological consequences. These include reduced exercise capacity, functional limitations, decreased lung volumes, increased mortality, and in some cases histopathology similar to Idiopathic Pulmonary Fibrosis (IPF). ILA have been detected in lung cancer screening cohorts, where the prevalence of ILA is estimated to be between (10%-20%) to those noted in other research cohorts. Given that a significant proportion of those will have progression, CT lung cancer screening (CTLS) cohorts represent an ideal catchment population for future research and clinical trials. Lahey Hospital and Medical Center was one of the earliest clinical centers to develop a CTLS program in the country. Investigators propose to qualitatively characterize ILA in a large clinical CTLS population.

Investigators propose a retrospective, single-center study with following aims:

1. Characterize the prevalence and incidence of ILA at baseline and 5 year follow-up, respectively, and associated imaging phenotypes in CTLS cohort.
2. Baseline qualitative ILA features associated with clinical outcomes: Lung Cancer, Hospitalization, and Mortality.
3. Baseline qualitative ILA features associated with progressive ILA and fibrotic lung disease.
4. Clinical opportunity: to determine the % of CTLS patients with ILA who are at risk for progressive and development of fibrotic lung disease and who would benefit from specialized care referral and potential enrollment in clinical trials utilizing proven antifibrotic therapies

Patient Selection:

All clinical CT Lung Cancer Screening (CTLS) patients at Lahey Hospital and Medical Center (LHMC), Burlington, MA from January 1st, 2012 through September 30th, 2014 who had an in network primary care physician (n=1703). Patients with T4 screening scans will be scored for progression (n=653). To qualify for our study, patients had to satisfy the National Comprehensive Cancer Network (NCCN) Guidelines® Lung Cancer Screening Version 1.2012 high-risk criteria for lung cancer. Based on the NCCN Guidelines®, individuals eligible for lung cancer screening can be classified into NCCN group 1 and 2 as previously described. Patients in both groups were asymptomatic and had a physician order for CTLS, were free of lung cancer for ≥ 5 years, and had no known metastatic disease.

Clinical Variables:

Clinical variables were collected prospectively as part of the CTLS program and stored in a centralized data repository. Additional clinical variables not already available in this data repository will be collected retrospectively by manual review of the electronic medical record or pulled directly from the EMR and stored utilizing a custom-designed database (FileMaker ProVersion 11; Filemaker Inc, Santa Clara, California). Data was obtained through September 30th, 2019, patient demographics, past medical history, PFTs, immunization records, whether the patient was managed by a pulmonologist, and for hospital admissions with principal admission diagnoses. Hospital admissions will be collected using Lahey administrative coding data. Principal admission diagnoses of COPD, PNA, and CHF will be characterized based on diagnosis codes per 2018 Center for Medicare and Medicaid Services (CMS) condition-specific measures.

CT Imaging:

Clinically acquired, CTLS examinations which were performed on ≥64-row multidetector CT scanners (LightSpeed VCT and Discovery VCT \[GE Medical Systems, Milwaukee, Wisconsin\]; Somatom Definition \[Siemens AG, Erlangen, Germany\]; iCT \[Philips Medical Systems, Andover, Massachusetts\]) at 100 kV and 30 to 100 mA, depending on the scanner and the availability of iterative reconstruction software. Axial images were obtained at 1.25- to 1.5-mm thickness with 50% overlap and reconstructed with both soft tissue and lung kernels.

Qualitative ILA Scoring:

CT images will be scored utilizing Philips Intellispace PACS version 4.4 with clinical grade monitors. Scoring will be performed independently by two thoracic radiologists as described previously. Scores that are discordant between the two radiologists will be scored by a third by a pulmonologist with expertise in ILD.

ILA: The presence of ILA features will be scores as (Yes/No/Indeterminate). Indeterminate will be defined as features identified unilaterally/focal involvement.

ILA features that will be scored include: A) non dependent ground glass, B) reticular abnormalities, C) traction bronchiectasis and D) honeycombing.

A) Non Dependent ground glass: (Yes/No/Indeterminate) defined as hazy increased attenuation of the lung with preservation of bronchial and vascular margins.

B) Reticular abnormalities: (Yes/No/Indeterminate) defined as a collection of innumerable small linear opacities that, by summation, produce an appearance resembling a net.

C) Traction Bronchiectasis: (Yes/No/Indeterminate) defined Traction bronchiectasis and traction bronchiolectasis respectively represents irregular bronchial and bronchiolar dilatation caused by surrounding retractile pulmonary fibrosis.

D) Honeycombing: (Yes/No/Indeterminate) defined on CT as clustered cystic air spaces, typically of comparable diameters on the ordered of 3-10 mm but occasionally as large as 2.5 cm.

Pattern: The overall pattern/Type of ILA findings will also be scored as the following: Subpleural, centrilobular, mixed or consistent with ILD (see UIP below).

Subpleural: Defined as less than 1 cm from the pleural surface.

Centrilobular: Defined as region of the bronchiolovascular core of the secondary pulmonary lobule.

Location: Overall location ILA will then be scored as Upper lobe, lower lobe or diffuse.

Extent: Overall extent of disease will be scored as Mild, Moderate and Marked.

Usual Interstitial Pneumonia: Finally, the subset of scans that have evidence of fibrotic disease defined as traction bronchiectasis/honeycombing will then be classified as consistent with usual interstitial pneumonia (UIP) (Yes/Probable/No) based on Fleischner Criteria. UIP defined as Honey-combing with basal and subpleural distribution.

Progression: The subset of patients who have had their T4 (5 year post baseline) screening scanned will be independently scored as above and in addition will be compared to their baseline scans and scored for progression: Stable, improved, and progressed.

ILAs in CT Lung Cancer Screening Population

Interstitial Lung Abnormalities--Qualitative Imaging Cohort Study in CT Lung Cancer Screening Population

Both presence and absence of ILA, as well as phenotypes, will be described for the entire cohort.

Kaplan-Meier plots will be generated to visualize the associations between ILA variables and cancer, hospital admission and mortality. The log-rank test will be used to evaluate for a significant association. Cox regression proportional hazards models will be used to test for this association in both univariate and multivariable models. The multivariable model will be adjusted for age, sex, smoking status and pack years exposure.

Progression of ILA, defined as worsening of existing ILA or incidence of ILA over 5 years, will be described for the subset of patients with T4 imaging at 5 years. Univariate and multivariable analyses using logistic regression will be performed to test for associations between qualitative ILA characteristics (presence and absence, as well as individual phenotypes in separate models) and progression (yes/no). Stable and improved will be considered no progression, while incident ILA and worsening of existing ILA will be considered progression. Models will be checked for influential points. Multivariable models will be adjusted for sex, age, currently smoking, and pack years exposure.

Using Kaplan-Meier plots and Cox regression analysis to examine association between phenotypes of ILA with time to first hospitalization, cancer, and mortality. The proportional hazards assumption will be checked for all Cox regression models.

Investigators will investigate the association between ILA (presence/absence) and time to cause-specific mortality (pulmonary, cardiac, cancer, other), as well as cause-specific hospitalization based on primary diagnosis (COPD, PNA, and CHF). The proportional hazards assumption will be checked for all Cox regression models.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Biological Insights of First Relapsed-refractory Patients With Mantle Cell Lymphoma: the MANTLE-FIRST BIO Study.	NCT04882475	Mantle Cell Lym...		18 Years - 80 Years	Fondazione Italiana Linfomi - ETS
ILAs in CT Lung Cancer Screening Population	NCT04503044	Interstitial Lu... IPF	Retrospective o...	18 Years - 80 Years	Lahey Clinic
ILAs in CT Lung Cancer Screening Population	NCT04503044	Interstitial Lu... IPF	Retrospective o...	18 Years - 80 Years	Lahey Clinic
Biological Insights of First Relapsed-refractory Patients With Mantle Cell Lymphoma: the MANTLE-FIRST BIO Study.	NCT04882475	Mantle Cell Lym...		18 Years - 80 Years	Fondazione Italiana Linfomi - ETS

Spots Global Cancer Trial Database for retrospective observational study