Cohort studyindependent cross-checkabstract checked I-CHM-129 standard review
More stroma, more chemotherapy resistance in ovarian cancer?
Tumor-Stroma Proportion to Predict Chemoresistance in Patients With Ovarian Cancer.
Overview
Lou E et al.. JAMA Netw Open 2024 · PMID 38411963 · DOI 10.1001/jamanetworkopen.2024.0407
In a German cohort, tumours with much stroma resisted platinum chemotherapy more often; a US cohort showed no such link.
Does the study support the specific claim? Partly · Methodological quality: moderate
Plain-language summary
Study explained simply
- What did the researchers want to find out?
Test stroma as a resistance marker
- How was the study done?
Two retrospective cohorts
- How many people, animals or samples were studied?
295 patients
- What was actually found?
Association in one cohort, not the other
- How large was the observed effect?
OS HR 1.867 (Tuebingen); null in TCGA
- What do the results mean in everyday life?
Stroma may matter for some tumours
- What are the study's limitations?
Inconsistent; retrospective
- What does it say about Elawady's specific claim?
Partly supports the mechanism only
- Do the results apply to Germany and Europe?
Moderate
- What can explicitly not be concluded from this study?
Cannot support avoiding chemotherapy
Scientific in-depth review
1. Full reference
- Authors
- Lou E et al.
- Journal
- JAMA Netw Open
- Year
- 2024
- Identifier
- PMID 38411963 DOI 10.1001/jamanetworkopen.2024.0407
- Verification
- verified – PubMed efetch 2026-10-26 (PublicationType and CommentsCorrections checked); Crossref 2026-10-26
- Retracted
- no
- Corrections
- none
- Extent checked
- abstract only
- Conflicts of interest and funding
US government and non-US-government support; COI not stated in abstract.
2. Research question
Does tumour-stroma proportion predict platinum chemoresistance and survival in high-grade serous ovarian cancer?
3. Study design and population
- Study design
- Cohort study – Prognostic study in two retrospective cohorts
- Population
Patients with high-grade serous ovarian carcinoma
- Country
USA (TCGA), Germany (Tuebingen)
- Period
TCGA 1993-2013; Tuebingen 2004-2014
- Sample size
103 (TCGA) + 192 (Tuebingen; 185 tissue microarrays)
- Inclusion and exclusion criteria
HGSC with available slides
4. Methods and endpoints
- Exposure / intervention
High tumour-stroma proportion (>=50% stroma)
- Comparator
Low tumour-stroma proportion
- Endpoints
Platinum chemoresistance, PFS, OS
- Statistical methods
Kaplan-Meier; hazard ratios
5. Actual results
- Results
TCGA: no significant association of TSP with chemoresistance, PFS or OS. Tuebingen: high TSP associated with shorter PFS (HR 1.586, 1.093-2.302) and OS (HR 1.867, 1.249-2.789); chemoresistant tumours 'twice as likely' to have high TSP (reported as HR 2.861, 1.256-6.515); TMA: PFS HR 1.675 (1.012-2.772), OS HR 2.491 (1.585-3.912).
- Absolute risks
not reported
- Authors' conclusion
TSP was a consistent and reproducible marker of outcomes including platinum chemoresistance.
6. Strengths
- Two cohorts
- Simple reproducible measure
7. Weaknesses
- Not replicated in TCGA cohort (contradicts 'consistent')
- Retrospective; confounding by stage/residual disease possible
- Chemoresistance association labelled as HR although it compares proportions
8. Risk of bias
- Orienting tool
- ROBINS-E
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- some concerns
- Rationale
Prognostic association; inconsistent between cohorts.
9. Assessment of the statistical interpretation
Statistic wording mismatch: 'twice as likely' vs 'HR 2.861' for a cross-sectional comparison (stats/C-CHM-11.py).
10. Relevance to the specific claim
Supports the narrow mechanistic point that stroma-rich tumours may respond worse to chemotherapy in some cohorts; it is a prognostic association, not evidence that chemotherapy is useless, and patients in both groups were treated with chemotherapy.
11. Independent contrary findings
TCGA cohort null result in the same paper; HALO-301 (I-CHM-118).
12. Transferability to Germany and Europe
Applicable biology.
13. Overall methodological judgement
Inconsistent prognostic marker.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | moderate |
| Risk of bias | some concerns |
| Precision of results | low |
| Directness | indirect |
| Reproducibility | not replicated |
| Consistency with the overall evidence | inconsistent |
| Regional transferability | moderate |
| Adequacy of the interpretation (by the archive) | partly correct but over-interpreted |
14. Open questions
Prospective validation.