Radiological Response Heterogeneity Is of Prognostic Significance in Metastatic Renal Cell Carcinoma Treated with Vascular Endothelial Growth Factor-targeted Therapy.

Benzodioxoles / therapeutic use Carcinoma, Renal Cell / diagnostic imaging Double-Blind Method Enzyme Inhibitors / therapeutic use Female Humans Kidney Neoplasms / diagnostic imaging Male Prognosis Quinazolines / therapeutic use Retrospective Studies Tomography, X-Ray Computed Treatment Outcome Vascular Endothelial Growth Factor A / antagonists & inhibitors

Heterogeneity Prognostic factor Radiological response Renal cell carcinoma Vascular endothelial growth factor

Journal

European urology focus

ISSN: 2405-4569

Titre abrégé: Eur Urol Focus

Pays: Netherlands

ID NLM: 101665661

Informations de publication

Date de publication:
15 09 2020

Historique:

received: 04 12 2018

revised: 07 01 2019

accepted: 16 01 2019

pubmed: 11 2 2019

medline: 21 5 2021

entrez: 11 2 2019

Statut: ppublish

Résumé

Response evaluation criteria in solid tumours (RECIST) is widely used to assess tumour response but is limited by not considering disease site or radiological heterogeneity (RH). To determine whether RH or disease site has prognostic significance in patients with metastatic clear-cell renal cell carcinoma (ccRCC). A retrospective analysis was conducted of a second-line phase II study in patients with metastatic ccRCC (NCT00942877), evaluating 138 patients with 458 baseline lesions. The phase II trial assessed vascular endothelial growth factor-targeted therapy±Src inhibition. RH at week 8 was assessed within individual patients with two or more lesions to predict overall survival (OS) using Kaplan-Meier method and Cox regression model. We defined a high heterogeneous response as occurring when one or more lesion underwent a ≥10% reduction and one or more lesion underwent a ≥10% increase in size. Disease progression was defined by RECIST 1.1 criteria. In patients with a complete/partial response or stable disease by RECIST 1.1 and two or more lesions at week 8, those with a high heterogeneous response had a shorter OS compared to those with a homogeneous response (hazard ratio [HR] 2.01; 95% confidence interval [CI]: 1.39-2.92; p<0.001). Response by disease site at week 8 did not affect OS. At disease progression, one or more new lesion was associated with worse survival compared with >20% increase in sum of target lesion diameters only (HR 2.12; 95% CI: 1.43-3.14; p<0.001). Limitations include retrospective study design. RH and the development of new lesions may predict survival in metastatic ccRCC. Further prospective studies are required. We looked at individual metastases in patients with kidney cancer and showed that a variable response to treatment and the appearance of new metastases may be associated with worse survival. Further studies are required to confirm these findings.

Sections du résumé

BACKGROUND

Response evaluation criteria in solid tumours (RECIST) is widely used to assess tumour response but is limited by not considering disease site or radiological heterogeneity (RH).

OBJECTIVE

To determine whether RH or disease site has prognostic significance in patients with metastatic clear-cell renal cell carcinoma (ccRCC).

DESIGN, SETTING, AND PARTICIPANTS

A retrospective analysis was conducted of a second-line phase II study in patients with metastatic ccRCC (NCT00942877), evaluating 138 patients with 458 baseline lesions.

INTERVENTION

The phase II trial assessed vascular endothelial growth factor-targeted therapy±Src inhibition.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS

RH at week 8 was assessed within individual patients with two or more lesions to predict overall survival (OS) using Kaplan-Meier method and Cox regression model. We defined a high heterogeneous response as occurring when one or more lesion underwent a ≥10% reduction and one or more lesion underwent a ≥10% increase in size. Disease progression was defined by RECIST 1.1 criteria.

RESULTS AND LIMITATIONS

In patients with a complete/partial response or stable disease by RECIST 1.1 and two or more lesions at week 8, those with a high heterogeneous response had a shorter OS compared to those with a homogeneous response (hazard ratio [HR] 2.01; 95% confidence interval [CI]: 1.39-2.92; p<0.001). Response by disease site at week 8 did not affect OS. At disease progression, one or more new lesion was associated with worse survival compared with >20% increase in sum of target lesion diameters only (HR 2.12; 95% CI: 1.43-3.14; p<0.001). Limitations include retrospective study design.

CONCLUSIONS

RH and the development of new lesions may predict survival in metastatic ccRCC. Further prospective studies are required.

PATIENT SUMMARY

We looked at individual metastases in patients with kidney cancer and showed that a variable response to treatment and the appearance of new metastases may be associated with worse survival. Further studies are required to confirm these findings.

Identifiants

DOI: 10.1016/j.euf.2019.01.010 PMID: 30738795

pubmed: 30738795

pii: S2405-4569(19)30010-0

doi: 10.1016/j.euf.2019.01.010

pii:

doi:

Substances chimiques

Benzodioxoles 0

Enzyme Inhibitors 0

Quinazolines 0

Vascular Endothelial Growth Factor A 0

saracatinib 9KD24QGH76

cediranib NQU9IPY4K9

Banques de données

ClinicalTrials.gov

['NCT00942877']

Types de publication

Clinical Trial, Phase II Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

999-1005

Subventions

Organisme : Cancer Research UK

Pays : United Kingdom