Does ovarian-cancer clone diversity predict death?
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.
Source
Spatial and temporal heterogeneity in high-grade serous ovarian cancer: a phylogenetic analysis
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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Does ovarian-cancer clone diversity predict death?
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135 samples from 14 HGSOC patients.
135 spatially and temporally separated samples from 14 patients with HGSOC who received platinum-based chemotherapy.
CE-high: PFS 12.7 vs 10.1 mo; OS 42.6 vs 23.5 mo.
PFS 12.7 versus 10.1 mo, p = 0.009; OS 42.6 versus 23.5 mo, p = 0.003
What they did
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.
What they found
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.
The limits
What it doesn't show
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.
Key terms
- HGSOC
- High-grade serous ovarian cancer, typically TP53-mutant with extensive copy-number change.
- Clonal expansion (CE)
- MEDICC index of how much genomes cluster into expanding subclones; high CE tracked shorter survival.
- MEDICC
- Minimum Event Distance for Intra-tumour Copy Number Comparisons—algorithm for phylogenetic distances from copy number.
- NF1
- Tumour-suppressor gene; a subclonal NF1 deletion expanded during chemotherapy and dominated relapse.
- PFS
- Progression-free survival from pathology date to RECIST/CA125/symptomatic progression.
- TH index
- Temporal heterogeneity: mutational-landscape distance between biopsy and surgery samples during neoadjuvant treatment.
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Phylogenetic analysis used samples from:
Common questions
How many patients/samples in the main analysis?
135 samples from 14 patients (177 arrays from 18 profiled).
CE-high survival?
PFS 10.1 vs 12.7 mo; OS 23.5 vs 42.6 mo.
Was the NF1 relapse clone new?
No—already 5% and 26% in pre-treatment samples.
Median follow-up?
31 months (IQR 22–46).
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