Precise Gene Signature for Predicting Outcomes in PDAC

Gene Signature Developed Using Machine Learning for Precise Prediction of Relapse and Survival in Resected Stage I-II Pancreatic Ductal Adenocarcinoma

The current TNM staging system is not sufficient for prediction of prognosis and cannot precisely identify the patients who are in greater need of adjuvant therapy in pancreatic ductal adenocarcinoma (PDAC). Tumor mutation and copy number variation (CNV) markers may have a higher predictive value. In this study, whole exosome sequencing was performed for patients with stage I-II PDAC undergoing R0 resection. The investigators aimed to identify genes with discrepant statuses of mutations or CNVs between patients with and without relapse within 1 year after R0 resection, and then to construct a support vector machine (SVM)-based prognostic classifier (the SVM signature) for PDAC using machine learning; the investigators then aimed to further validate the SVM signature in an independent cohort.

Study Overview

• Status: Completed
• Conditions: Stage I-II Pancreatic Ductal Adenocarcinoma (PDAC); Precise Prognostic and Predictive Signature
• Intervention / Treatment: Procedure: Resection

• Study Type: Observational
• Enrollment (Actual): 70

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The investigators enrolled two independent cohorts of consecutive patients with incident, primary, microscopically-confirmed stage I-II PDAC undergoing radical R0 resection only. For the training cohort, data were retrieved for 30 patients undergoing resection between March 2015 and December 2016 at Chinese PLA General Hospital in Beijing, China. Patients who did not relapse or die within 1 year after resection had follow-up of at least 1 year. The investigators also included 40 patients from The Cancer Genome Atlas (TCGA) database (https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga) as the validation cohort, with the same criteria as above; they were diagnosed between January 2010 and December 2013.

Description

Inclusion Criteria:

• Availability of hematoxylin and eosin slides with invasive tumor components
• Availability of clinicopathologic characteristics and follow-up data
• No previous history of cancer

Exclusion Criteria:

• No formalin-fixed, paraffin-embedded (FFPE) tumor sample of primary tumor
• Receipt of any neoadjuvant and/or adjuvant cancer-directed therapy
• Survival time <3 months after resection

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
training cohort; 30 patients undergoing resection between March 2015 and December 2016 at Chinese PLA General Hospital in Beijing, China	Procedure: Resection; radical R0 resection of pancreatic adenocarcinoma
validation cohort; 40 patients from The Cancer Genome Atlas (TCGA) database (https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga)	Procedure: Resection; radical R0 resection of pancreatic adenocarcinoma

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival	the time to recurrence at any site or all-cause death, whichever occurred first	3-year
Overall survival	the time to death from any cause	3-year

Collaborators and Investigators

• Sponsor: The Fourth Affiliated Hospital of Anhui Medical University

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2021
• Primary Completion (Actual): May 1, 2022
• Study Completion (Actual): June 22, 2022

Study Registration Dates

• First Submitted: June 23, 2022
• First Submitted That Met QC Criteria: June 30, 2022
• First Posted (Actual): July 1, 2022

Study Record Updates

• Last Update Posted (Actual): July 7, 2022
• Last Update Submitted That Met QC Criteria: July 1, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma
• Other Study ID Numbers: PaC-SVM1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Not decided yet

Drug and device information, study documents

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