ArticleThe oncologist2023
A Novel HRD Signature Is Predictive of FOLFIRINOX Benefit in Metastatic Pancreatic Cancer.
Article in The oncologist, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Efficacy and toxicities of modified FOLFIRINOX versus gemcitabine plus nab-paclitaxel as first-line chemotherapy for unresectable pancreatic cancer: a systematic review and meta-analysis.Frontiers in oncology · 2026Pooled it
- A Phase II Trial of Niraparib in Patients with Advanced Pancreatic Cancer Harboring Pathogenic Variants in ATM, BRCA1, BRCA2, PALB2, and CHEK2.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- DNA/RNA-Based Next-Generation Sequencing Improves the Early Diagnosis and Management of Neoplastic Bile Duct Strictures: A 6-Year, Prospective, Multi-Institutional, Real-Time Study.Gastroenterology · 2026Article
- Genomic Biomarkers for First-Line Treatment Selection in Metastatic Pancreatic Ductal Adenocarcinoma: A Narrative Review.Cancers · 2026Review
- FOLFIRINOX vs. Gemcitabine/Nab-Paclitaxel for Pancreatic Cancer by BRCA2 and TMB Status: A Japanese C-CAT Database Study.Cancer science · 2026Article
- Comparison of Familial and Sporadic Pancreatic Cancer: Clinicopathological and Genomic Features.Annals of surgical oncology · 2026Article
- Whole genome sequencing improves tissue-of-origin diagnosis and treatment options for cancer of unknown primary.Nature communications · 2025Article
- Genomic landscape and homologous recombination repair deficiency signature in stage I-III and de novo stage IV primary breast cancers.The oncologist · 2025Article
- Clinical utility of comprehensive genomic profiling for advanced pancreatic cancer: insights from real-world data analysis.International journal of clinical oncology · 2025Article
- Association between homologous recombination deficiency and time to treatment failure to platinum-based chemotherapy for pancreatic cancer by using the C-CAT database.Journal of gastroenterology · 2025Article
- Prognostic impact of gene alterations via homologous recombination DNA repair gene alteration status in pancreatic ductal adenocarcinoma.Frontiers in medicine · 2025Article
- Real-world genome profiling in Japanese patients with pancreatic ductal adenocarcinoma focusing on HRD implications.Cancer science · 2024Observational
- Effectiveness of PARP Inhibitor Maintenance Therapy in Ovarian Cancer by BRCA1/2 and a Scar-Based HRD Signature in Real-World Practice.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Targeting BRCA and PALB2 in Pancreatic Cancer.Current treatment options in oncology · 2024Review
- HRD Score: A Promising Biomarker for Genomic Instability Evaluation for Targeted Treatments Among Pancreatic Cancer Patients.Technology in cancer research & treatmentArticle
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundPancreatic cancer (PC) represents an aggressive disease with median overall survival (OS) of less than 1 year in the front-line setting. FOLFIRINOX and gemcitabine and paclitaxel (GP) are standard of care options for these patients; however, optimal selection of therapy is challenging.
methodsComprehensive genomic profiling was performed on 8358 PC patients. Outcomes were available for 1149 metastatic PC patients treated with 1L FOLFIRINOX or GP. A scar-based measure of HRD was called using a machine learning-based algorithm incorporating copy number and indel features.
resultsA scar-based HRD signature (HRDsig) was identified in 9% of patients. HRDsig significantly co-occurred with biallelic alterations in BRCA1/2, PALB2, BARD1, and RAD51C/D, but encompassed a larger population than that defined by BRCA1/BRCA2/PALB2 (9% vs. 6%). HRDsig was predictive of 1L FOLFIRNOX chemotherapy benefit with doubled OS relative to gemcitabine and paclitaxel (GP) (rwOS aHR 0.37 [0.22-0.62]), including 25% of the population with long-term (2 year+) survival in a real-world cohort of patients. Less benefit from FOLFIRINOX was observed in the HRDsig(-) population. Predictive value was seen in both the BRCA1/2/PALB2 mutant and wildtype populations, suggesting additional value to mutational profiling.
conclusionA scar-based HRD biomarker was identified in a significant fraction of PC patients and is predictive of FOLFIRINOX benefit. Incorporating a biomarker like HRDsig could identify the right patients for platinum chemotherapy and potentially reduce FOLFIRINOX use by over 40%, minimizing toxicities with similar survival outcomes. Confirmatory studies should be performed.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.