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Oncology outcomes

Does ovarian-cancer clone diversity predict death?

Schwarz RF, Ng CK, Cooke SL, et al. · PLoS medicine · 2015

Open access · cc by · source: Europe PMC

In 14 women with high-grade serous ovarian cancer, high clonal expansion predicted worse PFS (10.1 vs 12.7 mo) and OS (23.5 vs 42.6 mo); an NF1-deleted relapse clone was already detectable before chemotherapy.

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Study at a glance

Design
Cohort — Phylogenetic MEDICC analysis of spatially/temporally separated HGSOC samples from women receiving platinum chemotherapy (CTCR-OV03/04)
N
N=14 · 135 samples from 14 patients in the phylogenetic/survival analysis; 177 arrays from 18 patients profiled, 17 remaining after QC
Population
Women with high-grade serous ovarian cancer on platinum-based chemotherapy in CTCR-OV03/04
Outcome
Clonal-expansion (CE) index vs progression-free and overall survival; origin of relapse clones

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Key findings

Median CE was 0.74 (IQR 0.66–1.15). CE-high tumors had PFS 10.1 vs 12.7 mo (p=0.009) and OS 23.5 vs 42.6 mo (p=0.003); CE-high remained independently prognostic. Bootstrapped HRs were 7.1 (PFS) and 11.4 (OS). An NF1 deletion marking relapse was already 5% and 26% of pre-treatment samples.

Methodology

Used MEDICC on whole-genome copy-number profiles from 135 spatially and temporally separated samples in 14 HGSOC patients on platinum therapy (CTCR-OV03/04; median follow-up 31 mo). Dichotomized clonal expansion (CE) at the median and related it to PFS/OS; digital PCR tracked an NF1 deletion at relapse.

Limitations

n=14 cannot precisely size the hazard; CE as a continuous variable was not significant in multivariable models, so the median split is a small-cohort signal, not a ready clinical test.

How this study connects

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