Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Lenalidomide

Retrospective Cohort： Participants who diagnosed with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) patients and treated with BTK inhibitor or lenalidomide and its biosimilars.

Diagnostic Test:

The Canhelp-COO Assay (Canhelp Genomics CO., Ltd) for differentiating COO subtypes using gene expression analysis by real-time PCR (RT-PCR)

Gene expression profile

Peng Liu, MD,PhD

The purpose of the study is to investigate the proportion of the cell-of-origin (COO) subtypes in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) treated with BTK inhibitor or lenalidomide and its biosimilars.

This is a multi-center, observational, retrospective study that examines approximately 200 R/R DLBCL patients treated with BTK inhibitors or lenalidomide and its biosimilars. For patients meet the inclusion criteria, gene expression analysis is performed on formalin fixed paraffin-embedded tissue by using Canhelp-COO Assay, and determine the COO subtype for each specimen. The proportion of COO subtypes in R/R DLBCL and the correlation between COO subtypes and clinicopathological information are further analyzed.

Translational Study of Molecular Classification of Relapsed/Refractory Diffuse Large B-cell Lymphoma

Investigate the proportion of the cell of origin (COO) subtypes in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) treated with BTK inhibitor or lenalidomide and its biosimilars.

Based on the objective response rate (ORR) measured by the investigator, explore the correlation between COO subtypes and the efficacy of BTK inhibitors, lenalidomide and its biosimilars in the treatment of R/R DLBCL.

Based on the progression-free survival (PFS) and overall survival (OS) measuredd by the investigator, explore the correlation between COO subtypes and the efficacy of BTK inhibitors, lenalidomide and its biosimilars in the treatment of R/R DLBCL .

Wuxi People's Hospital

Shanghai Minhang Central Hospital

Shanghai Zhongshan Hospital

Chief of hematology department

Digestive System Diseases

Gland and Hormone Related Diseases

Adenocarcinoma

Pancreatic Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Pancreatic Cancer

Patients experiencing favorable prognosis (defined as RFS≥60 months) following resection for pancreatic adenocarcinoma

Patients experiencing unfavorable prognosis (defined as RFS\<12 months) following resection for pancreatic adenocarcinoma

The study aims at evaluating spatially resolved gene expression profiles of pancreatic and ampullary adenocarcinoma at favorable prognosis after surgical resection, in order to identify molecular features associated to a less aggressive biologic behavior that may benefit from upfront surgery.

Despite technical improvements, surgery for pancreatic adenocarcinoma is still burdened by poor survival outcomes of only 10% at 5 years, due to very high locoregional and distant recurrence rates. In order to improve such disappointing results, several studies are now focusing on the role of neoadjuvant treatment. Recent evidence shows that neoadjuvant treatment may achieve improved intention-to-treat survival outcome, increased rates of margin-negative resections and decreased incidence of lymph node metastases. However, all surgical series report that a limited subset of patients achieve long-term survival following radical surgical resection.

After a systematic review of the available evidence on molecular profiling of pancreatic adenocarcinoma published until today the investigators have undertaken a retrospective study aimed at investigating the presence of possible genetic factors associated to a less aggressive clinical behavior. Clinical, biological and pathological features collected in a prospectively maintained database of radical surgery for pancreatic adenocarcinoma will be retrospectively reviewed together with an analysis of molecular features on surgical samples belonging to patients radically operated at the National Institute of Cancer of Milan. Such features may be used to identify those patients who may benefit from upfront surgery; in such group, vascular resections and reconstructions could be considered more liberally.

The study will consist of 2 phases:

1. A preliminary exploratory phase (group A) based on approximately 20 surgical samples of patients with surgically resected pancreatic adenocarcinoma, not treated by neoadjuvant chemotherapy, in order to evaluate the intrinsic role of tumor biology and avoid the selection of molecular features associated to treatment response. This cohort will consist of 2 groups of 10 patients each with prognostically favorable (RFS≥60 months) and unfavorable tumors (RFS\<12 months), respectively. Patients from the 2 groups will be matched for clinicopathological tumor-related features. Spatially resolved transcriptomic analysis will be performed by the GeoMx Digital Spatial Profiler (DSP) (NanoString Technologies, Seattle, WA, USA) on samples of the two groups and the resulting gene expression profiles will be compared, in order to identify different patterns of gene expression in prognostically different pancreatic adenocarcinomas. Such patterns will also be compared with the TCGA database.
2. A subsequent expanded phase, based on the results of the previous exploration, will take place in case a different gene expression profile is identified. The internal validation set (group B) consists in additional 20 surgical samples associated to favorable and unfavorable prognosis (10 patients each), respectively, belonging to the same institutional series and matched for clinicopathological tumor-related features. RNA-seq analysis will be carried out on these surgical samples, aiming at confirming the results of the exploratory analysis and refine the gene expression profile. In this subset, the enrolment of patients who underwent neoadjuvant treatment will be allowed.

Due to the limited number, samples from patients affected by ampullary adenocarcinoma with favorable prognosis will be analyzed in one step and compared to matched cases with unfavorable prognosis (8 patients each, group C).

Following the identification of gene expression profiles both for pancreatic and ampullary adenocarcinoma, an external validation set will be enrolled in order to perform RNA-seq analysis on additional 60-80 surgical samples from other institutions and validate the prognostic relevance of the identified pattern in predicting a less aggressive disease course.

Gene Expression Profile of Resected Pancreatic and Ampullary Adenocarcinoma at Favorable Prognosis

Identification of Gene Expression Profile Associated With Favorable Prognosis in Patients Undergoing Radical Surgery for Pancreatic and Ampullary Adenocarcinoma

Identification of DSP gene aberrations associated to favorable prognosis (≥60-month RFS) after radical surgery for pancreatic and ampullary adenocarcinoma, through comparison of prognostically favorable and unfavorable gene expression profiles found in different tumor and microenvironment compartments.

Comparison of the gene expression profile found at DSP with the TCGA database in order to confirm the clinical relevance of the identified gene expression pattern associated to prognostically favorable tumors

Identification of clinical, biological and pathological prognostic factors associated to favorable prognosis (≥60-month RFS) after radical surgery for pancreatic adenocarcinoma

External validation of the identified gene expression profile through gene expression analysis of surgical samples from patients undergoing radical surgery for pancreatic adenocarcinoma in a different institution

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Translational Study of Molecular Classification of Relapsed/Refractory Diffuse Large B-cell Lymphoma	NCT05318391	Lymphoma, Large... Gene Expression...	Gene expression...	18 Years -	Shanghai Zhongshan Hospital
Gene Expression Profile of Resected Pancreatic and Ampullary Adenocarcinoma at Favorable Prognosis	NCT05754788	Resectable Panc...		18 Years - 80 Years	Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Spots Global Cancer Trial Database for gene expression profile