ArticleCancer chemotherapy and pharmacology2021
Molecular predictors of the outcome of paclitaxel plus carboplatin neoadjuvant therapy in high-grade serous ovarian cancer patients.
Article in Cancer chemotherapy and pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 24 citations in OpenAlex.
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- Discrimination between Complete versus Non-Complete Pathologic Response to Neoadjuvant Therapy Using Ultrasensitive Mutation Analysis: A Proof-of-Concept Study inInternational journal of molecular sciences · 2023Article
- Integrative Genomic Tests in Clinical Oncology.International journal of molecular sciences · 2022Review
- Somatic loss of the remaining allele occurs approximately in half of CHEK2-driven breast cancers and is accompanied by a border-line increase of chromosomal instability.Breast cancer research and treatment · 2022Article
- Case Report: Primary Leptomeningeal Medulloblastoma in a Child: Clinical Case Report and Literature Review.Frontiers in pediatrics · 2022Article
- Olaparib and paclitaxel in combination with carboplatin in treatment of ovarian cancer: influence on disease control.American journal of translational research · 2022Article
- Cancer Therapy Guided by Mutation Tests: Current Status and Perspectives.International journal of molecular sciences · 2021Review
- Cytotoxic and targeted therapy for BRCA1/2-driven cancers.Hereditary cancer in clinical practice · 2021Review
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPatients with advanced high-grade serous ovarian cancer (HGSOC) are usually treated with paclitaxel and carboplatin; however, predictive markers for this drug combination are unknown.
methodsTumor samples from 71 consecutive HGSOC patients, who received neoadjuvant chemotherapy with paclitaxel and carboplatin, were subjected to molecular analysis.
resultsBRCA1/2 germline mutation carriers (n = 22) had longer treatment-free interval (TFI) than non-carriers (n = 49) (9.5 months vs. 3.8 months; P = 0.007). Fifty-one HGSOCs had sufficient quality of tumor DNA for the next-generation sequencing (NGS) analysis by the SeqCap EZ CNV/LOH Backbone Design panel. All 13 tumors obtained from BRCA1/2 germline mutation carriers and 12 sporadic HGSOCs showed a high number of evenly spread chromosomal breaks, which was defined as a BRCAness phenotype; median TFI for this combined group approached 9.5 months. The remaining 26 HGSOCs had similarly high global LOH score (above 20%); however, in contrast to BRCAness tumors, LOH involved large chromosomal segments; these patients had significantly lower TFI (3.7 months; P = 0.006). All patients with CCNE1 amplification (n = 7), TP53 R175H substitution (n = 6), and RB1 mutation (n = 4) had poor response to paclitaxel plus carboplatin.
conclusionThis study describes a cost-efficient method of detecting the BRCAness phenotype, which is compatible with the laboratory-scale NGS equipment. Some molecular predictors allow the identification of potential non-responders to paclitaxel plus carboplatin, who may need to be considered for other treatment options.
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