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.
Highlights
Immune checkpoint inhibitors have yielded promising clinical responses in patients with advanced malignant melanoma[1,2,3,4,5,6]
We hypothesized that vascular health might influence outcome to immunotherapy because the vascular status might be a surrogate of fitness, which in turn might influence outcome to immunotherapy as the effect of immunotherapies depends on host-inherent resources, i.e. the immune system of the patient, to fight cancer
We investigated the value of different body composition measures to predict response to immunotherapy with ipilimumab
Summary
Immune checkpoint inhibitors have yielded promising clinical responses in patients with advanced malignant melanoma[1,2,3,4,5,6]. As non-specific immunotherapies such as the CTLA-4 antibody ipilimumab do not directly target the tumor but augment the pre-existing, but clinically insufficient body-inherent immune system to fight cancer, the conventional pharmacodynamic model applied to standard chemotherapeutics is not completely applicable. Previous morphomics studies focused on conventional therapies such as surgery, radio- or chemotherapy and the few which investigated the correlation of morphomics and outcome after immunotherapy again concentrated on the sarcopenia-frailty-concept[17,18,19]. We hypothesized that vascular health might influence outcome to immunotherapy because the vascular status might be a surrogate of fitness, which in turn might influence outcome to immunotherapy as the effect of immunotherapies depends on host-inherent resources, i.e. the immune system of the patient, to fight cancer. Consecutive inappropriate regulation of the vascular tone, permeability, coagulation, fibrinolysis as well as cell adhesion and proliferation might hypothetically interact with effects of immunotherapy[20,21,22]
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