18F-FDG PET/CT based spleen to liver ratio associates with clinical outcome to ipilimumab in patients with metastatic melanoma

Background Immune checkpoint blockade such as ipilimumab and anti-PD1 monoclonal antibodies have significantly improved survival in advanced melanoma. Biomarkers are urgently needed as a majority of patients do not respond, despite treatment-related toxicities. We analysed pre-treatment .sup.18F-flu...

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Published in:Cancer imaging 2020-05, Vol.20 (1), p.1-36, Article 36
Main Authors: Wong, Annie, Callahan, Jason, Keyaerts, Marleen, Neyns, Bart, Mangana, Johanna, Aberle, Susanne, Herschtal, Alan, Fullerton, Sonia, Milne, Donna, Iravani, Amir, McArthur, Grant A, Hicks, Rodney J
Format: Article
Language:English
Subjects:
Biomarker
Biomarkers
Cable television broadcasting industry
Cancer
Cancer metastasis
Care and treatment
Clinical outcomes
Computed tomography
Correlation analysis
Development and progression
Emission analysis
Evaluation
Fluorine isotopes
Health services
Immune checkpoint blockade
Immunotherapy
Ipilimumab
Liver
Lymphocytes
Mathematical models
Medical research
Melanoma
Metabolism
Metastasis
Monoclonal antibodies
Nivolumab
Parameters
Patient outcomes
Patients
Pembrolizumab
Positron emission
Positron emission tomography
Response rates
Spleen
Spleen to liver ratio
Survival
Targeted cancer therapy
Tomography
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Summary:Background Immune checkpoint blockade such as ipilimumab and anti-PD1 monoclonal antibodies have significantly improved survival in advanced melanoma. Biomarkers are urgently needed as a majority of patients do not respond, despite treatment-related toxicities. We analysed pre-treatment .sup.18F-fluorodeoxyglucose positron emission tomography/computerised tomography (FDG PET/CT) parameters to assess its correlation with patient outcome. Methods This retrospective study evaluated pre-treatment FDG PET/CT scans in a discovery cohort of patients with advanced melanoma treated with ipilimumab or anti-PD1. Pre-treatment scans were assessed for maximum tumoral standardised uptake value (SUVmax), metabolic tumour volume (MTV) and spleen to liver ratio (SLR). Progression-free survival (PFS) and overall survival (OS) were characterised and modelled using univariable and multivariable analyses. Correlation of SLR and OS was validated in an independent cohort. Blood parameters and stored sera of patients from the discovery cohort was analysed to investigate biological correlates with SLR. Results Of the 90 evaluable patients in the discovery cohort: 50 received ipilimumab monotherapy, 20 received anti-PD1 monotherapy, and 20 patients received ipilimumab followed by anti-PD1 upon disease progression. High SLR > 1.1 was associated with poor PFS (median 1 vs 3 months; HR 3.14, p = 0.008) for patients treated with ipilimumab. High SLR was associated with poor OS after ipilimumab (median 1 vs 21 months; HR 5.83, p = 0.0001); as well as poor OS after first line immunotherapy of either ipilimumab or anti-PD1 (median 1 vs 14 months; HR 3.92, p = 0.003). The association of high SLR and poor OS after ipilimumab was validated in an independent cohort of 110 patients (median 2.3 months versus 11.9 months, HR 3.74). SLR was associated with poor OS in a multi-variable model independent of stage, LDH, absolute lymphocyte count and MTV. Conclusions Pre-treatment Spleen to liver ratio (SLR) > 1.1 was associated with poor outcome after ipilimumab in advanced melanoma. This parameter warrants prospective evaluation. Keywords: Melanoma, Immune checkpoint blockade, Biomarker, Positron emission tomography, Spleen to liver ratio
ISSN:1470-7330
1740-5025
1470-7330
DOI:10.1186/s40644-020-00313-2