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. 2019 Jul 5;9(1):9728.
doi: 10.1038/s41598-019-46189-6.

Macroangiopathy Is a Positive Predictive Factor for Response to Immunotherapy

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Free PMC article

Macroangiopathy Is a Positive Predictive Factor for Response to Immunotherapy

Katerina Deike-Hofmann et al. Sci Rep. .
Free PMC article

Abstract

Immunotherapies demand for predictive biomarkers to avoid unnecessary adverse effects and costs. Analytic morphomics is the technique to use body composition measures as imaging biomarkers for underlying pathophysiology to predict prognosis or outcome to therapy. We investigated different body composition measures to predict response to immunotherapy. This IRB approved retrospective analysis encompassed 147 patients with ipilimumab therapy. Degree of macroangiopathy was quantified with the newly defined total plaque index (TPI), i.e. the body height corrected sum of the soft and hard plaque volume of the infrarenal aorta on portalvenous CT scans. Furthermore, mean psoas density (MPD), different adipose tissue parameters as well as degree of cerebral microangiopathy were extracted from the imaging data. Subsequent multivariate Cox regression analysis encompassed TPI, MPD, serum LDH, S100B, age, gender, number of immunotherapy cycles as well as extent of distant metastases. TPI and MPD correlated positively with PFS in multivariate analysis (p = 0.03 and p = 0.001, respectively). Furthermore, single visceral organ and/or soft tissue involvement significantly decreased progression risk (p = 0.01), whereas increased S100B level showed a trend towards PFS shortening (p = 0.05). In conclusion, degree of macroangiopathy and sarcopenia were independent predictors for outcome to immunotherapy and of equivalent significance compared to other clinical biomarkers.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Kaplan-Meier survival curves of (A) the total plaque index (TPI) and (B) the mean psoas density (MPD). (A) The total plaque index (TPI) was defined as the body height adjusted sum of the hard and soft plaque volume of the infrarenal aorta. Patients with a TPI in the upper quartile Q3 (blue) had nearly half the risk of disease progression at every time point compared to patients with a TPI in the lower quartile Q1 (black) (univariate Cox regression analysis, p = 0.02, hazard ratio (HR) 0.56, confidence interval (CI) 0.35–0.92). Patients with a TPI in the interquartile range are outlined in grey color and display an intermediate risk for disease progression (univariate analysis, p = 0.09, HR 0.69, CI 0.46–1.06). (B) The mean psoas density (MPD) was measured on the fourth lumbar vertebrae level on both sides and averaged. Patients with an MPD greater than Q1 (blue) had a 40% reduced risk of disease progression compared to patients with an MPD in the lower quartile (black) (univariate Cox regression analysis, p = 0.01, HR 0.60, CI 0.40–0.88).
Figure 2
Figure 2
Example of applied image analysis. Portal-venous CT scans of the abdomen of a (AB) 56-year-old female, (C, D) 64-year-old male and (E, F) 67-year-old male with malignant melanoma prior to immunotherapy with ipilimumab. (A) Semi-automatic segmentation of the psoas muscles in the axial plane at the L4 level for calculation of the mean psoas area and the mean psoas density. (B) Semi-automatic segmentation of the visceral and subcutaneous adipose tissue area in the axial plane at the L4 level with fat density thresholds set to −190 HU to −30 HU. (C–F) Three-dimensional segmentation of the soft (D) and hard (F) plaque volume compared to the non-segmented images (C, E). Mean applied density thresholds were 100 (range 60–100) HU and 185 (180–220) HU for soft and hard plaques, respectively.
Figure 3
Figure 3
Example of the applied Fazekas scoring system (FS) for quantification of deep white matter hyperintensities (dWMH) on axial fluid-attenuated inversion recovery MRI (FLAIR). (A) Absence of hyperintense lesions in the deep white matter on FLAIR MRI (FS 0). (B) Punctate hyperintense foci of dWMHs on FLAIR MRI (FS 1). (C) Beginning confluence of dWMHs on FLAIR MRI (FS 2). (D) Large confluent areas of hyperintense lesions on FLAIR MRI (FS 3).

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