Tumor Characteristics in Patients With Paraneoplastic Neurological Syndromes (PNS) (GenePNS)

Genomic Profile and Tumor Immune Attack in Paraneoplastic Neurological Syndromes (PNS)

Paraneoplastic neurological syndromes (PNS) are immune-mediated complications of cancer that can affect any part of the central or peripheral nervous system.

PNS occurs at the intersection between immune system and the tumor, where a combination of genetical and environmental factors may play a role.

Mechanisms leading to immune tolerance breakdown and autoimmunity in PNS remain largely unknown, and this reflects in an unsatisfactory repertoire of treatments available. Moreover, a better understanding of the biological mechanisms underlying PNS would allow a more precise identification of the modalities that permit PNS patients to have a better oncological prognosis than cancer patient without PNS, with obvious repercussions in clinical oncology.

To this effect, an extremely innovative approach involves directly exploring the tumoral tissue of patients suffering from specific PNS via genomic and transcriptomic analysis.

The study team hypothesizes that antigen ectopic expression by tumour cells may contribute to the generation of PNS.

In the present study, the investigators will analyze the salient features of tumors associated with PNS, namely the histological and immune cells infiltrate characteristics, their transcriptomic profile, and mutational status of involved antigens.

Study Overview

• Status: Unknown
• Conditions: Cancer; Paraneoplastic Syndromes; Neurologic Disorder; Immune System and Related Disorders; Tumor Genetics

• Study Type: Observational
• Enrollment (Anticipated): 980

Contacts and Locations

Study Locations

• France
  • Lyon, France
    • Centre de référence des syndromes neurologiques paranéoplasiques et encéphalites auto-immunes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with cancer and suspected Paraneoplastic neurological syndrome (PNS) whose sample was sent for analysis at the Centre de référence des syndromes neurologiques paranéoplasiques et encéphalites auto-immunes, Lyon, France, for paraneoplastic antibody study and then stored at the biobank Neurobiotec.

Description

Inclusion Criteria:

• presence of well characterized antibodies in serum or cerebrospinal fluid;
• histologically proven cancer with available tumour sample;
• Paraneoplastic neurological syndrome (PNS) diagnosis according to the international guidelines;
• Age: at least 18 years old.

Exclusion Criteria:

• Absence of complete clinicopathological data

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Cancer patients with Paraneoplastic neurological syndromes; Cancer patients with Paraneoplastic neurological syndromes presenting various autoimmune anomalies: Anti-Hu also known as anti-Neuron specific cell Nuclear Antibodies (anti-ANNA1) (350 patients), uncommon form of brain inflammation associated with an underlying cancer; anti-Yo (130 patients), antibody associated with paraneoplastic cerebellar degeneration; anti-Ma2 (50 patients), antibody associated with paraneoplastic encephalitis; anti-N-methyl-d-aspartate (NMDA) Receptor (350 patients), autoimmune disorder in which antibodies attack N-methyl-D-aspartate-type glutamate receptors; anti-gamma-aminobutyric acid-B (GABAb) receptor (35 patients), autoimmune disorder in which antibodies attack gamma-aminobutyric acid-B receptors; anti-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor (15 patients), autoimmune disorder in which antibodies attack alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors; without antibodies (50 patients).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of mutations in cancer genes coding for onconeural proteins and inflammatory response mediators.	Genetic alterations in tumors associated with Paraneoplastic neurological syndromes (PNS)	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of different immune cells in the tumor's immune infiltrate	Histological immune infiltrate characteristics	36 months

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 1, 2019
• Primary Completion (ANTICIPATED): January 1, 2022
• Study Completion (ANTICIPATED): January 1, 2022

Study Registration Dates

• First Submitted: April 26, 2019
• First Submitted That Met QC Criteria: May 23, 2019
• First Posted (ACTUAL): May 28, 2019

Study Record Updates

• Last Update Posted (ACTUAL): May 30, 2019
• Last Update Submitted That Met QC Criteria: May 28, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Syndrome; Disease; Nervous System Diseases; Paraneoplastic Syndromes
• Other Study ID Numbers: GenePNS

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No