Computed Tomography-Derived Radiomic Metrics Can Identify Responders to Immunotherapy in Ovarian Cancer

Abstract

Purpose: To determine if radiomic measures of tumor heterogeneity derived from baseline contrast-enhanced computed tomography (CE-CT) are associated with durable clinical benefit and time to off-treatment in patients with recurrent ovarian cancer (OC) enrolled in prospective immunotherapeutic trials.

Materials and methods: This retrospective study included 75 patients with recurrent OC who were enrolled in prospective immunotherapeutic trials (n = 74) or treated off-label (n = 1) and had baseline CE-CT scans. Disease burden (total tumor volume, number of disease sites), radiomic measures of intertumor heterogeneity (cluster-site entropy, cluster-site dissimilarity), and intratumor heterogeneity of the largest lesion (Haralick texture features) were computed. Associations of clinical, conventional imaging, and radiomic measures with durable clinical benefit and time to off-treatment were examined.

Results: In univariable analysis, fewer disease sites, lower intertumor heterogeneity (lower cluster-site entropy, lower cluster-site dissimilarity), and lower intratumor heterogeneity of the largest lesion (higher energy) were significantly associated with durable clinical benefit (P ≤ .031). More disease sites, presence of pleural disease and/or distant metastases, higher intertumor heterogeneity (higher cluster-site entropy, higher cluster-site dissimilarity), and higher intratumor heterogeneity of the largest lesion (higher Contrastlargest-lesion) were significantly associated with shorter time to off-treatment (P ≤ .034). In multivariable analysis, higher Energylargest-lesion (indicator of lower intratumor heterogeneity; P = .006; odds ratio, 1.41) and fewer disease sites (P = .003; odds ratio, 1.64) remained significant indicators of durable clinical benefit (multivariable model C-index, 0.821). Higher cluster-site dissimilarity (indicator of higher intertumor heterogeneity) was a modest but single independent indicator of shorter time to off-treatment (P = .004; hazard ratio, 1.19; C-index, 0.6).

Conclusion: Fewer disease sites and lower intra- and intertumor heterogeneity modeled from the baseline CE-CT may indicate better response of OC to immunotherapy.

Conflict of interest statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center. Dmitriy ZamarinEmployment: Acorda Therapeutics (I) Consulting or Advisory Role: BioMed Valley Discoveries, Merck, PsiOxus Therapeutics, Synlogic, Western Oncolytics, Tesaro, Agenus, Trieza Therapeutics, ACM Biolabs Research Funding: Merck Patents, Royalties, Other Intellectual Property: I hold a patent regarding the use of recombinant Newcastle Disease Virus (NDV) for cancer therapy (Inst) Travel, Accommodations, Expenses: RocheAlexandra SnyderEmployment: Adaptive Biotechnologies, Merck Stock and Other Ownership Interests: Merck Consulting or Advisory Role: Driver Group Research Funding: Bristol-Myers Squibb Travel, Accommodations, Expenses: Genentech, Bristol-Myers SquibbMargaret CallahanEmployment: Bristol-Myers Squibb (I), Celgene (I), Kleo Pharmaceuticals (I), Bristol-Myers Squibb (I) Consulting or Advisory Role: AstraZeneca, Moderna Therapeutics, Merck Research Funding: Bristol-Myers Squibb (Inst) Other Relationship: Clinical Care Options, Potomac Center for Medical EducationEvis SalaHonoraria: Siemens Healthineers Speakers' Bureau: Siemens Healthineers Travel, Accommodations, Expenses: Siemens HealthineersYulia LakhmanStock and Other Ownership Interests: Y-mAbs Therapeutics No other potential conflicts of interest were reported.

© 2019 by American Society of Clinical Oncology.

Figures

FIG 1.

Illustration shows clinical variables and baseline contrast-enhanced computed tomography–derived features, including intra- and intertumor heterogeneity measures. FIGO, International Federation of Gynecology and Obstetrics.

FIG 2.

Axial baseline computed tomography (CT) images from two different patients with Energy (a measure of intratumor heterogeneity) overlaid on segmented tumors (arrow points to the largest lesion). Two box plots illustrate the univariable associations of baseline CT-derived number of disease sites and Energylargest-lesion (a measure of intratumor heterogeneity) with durable clinical benefit (progression-free survival ≥ 24 weeks). CE, contrast enhanced.

FIG 3.

Plots of receiver operating characteristic curves demonstrating the discriminatory ability of the model to identify patients with durable clinical benefit on the basis of number of disease sites, Energylargest lesion, or both.

FIG A1.

Flowchart shows the details of patient selection process. CE-CT, contrast-enhanced computed tomography; OC, ovarian cancer; PD-1, programmed cell death 1; PD-L1, programmed cell death ligand 1; PFS, progression-free survival.

FIG A2.

Axial baseline computed tomography (CT) images from two patients with Haralick texture subregions (used to compute intertumor heterogeneity measures) overlaid on segmented tumors illustrating the association between lower intertumor heterogeneity and longer time to off-treatment (top set of images) versus higher intertumor heterogeneity and shorter time to off-treatment (bottom set of images).