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

ABSTRACT: 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 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.

SUBMITTER: Wong A

PROVIDER: S-EPMC7227105 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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

Wong Annie A Callahan Jason J Keyaerts Marleen M Neyns Bart B Mangana Johanna J Aberle Susanne S Herschtal Alan A Fullerton Sonia S Milne Donna D Iravani Amir A McArthur Grant A GA Hicks Rodney J RJ

Cancer imaging : the official publication of the International Cancer Imaging Society 20200514 1

<h4>Background</h4>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>18</sup>F-fluorodeoxyglucose positron emission tomography/computerised tomography (FDG PET/CT) parameters to assess its correlation with patient outcome.<h4>Methods</h4>This retrospective study evalu ...[more]

PMID: 32408884

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Project description:Immune checkpoint inhibitors (ICIs) are now commonly used to treat patients with metastatic malignant melanoma. Although concerns have been raised that the inflammatory response induced by ICIs may limit the ability of 18F-FDG PET/CT to assess tumor response, systematic analyses on the use of 18F-FDG PET/CT in this setting are mostly lacking. Thus, we set out to evaluate the association between tumor response on 18F-FDG PET/CT and prognosis in patients with metastatic malignant melanoma treated with ipilimumab. Methods: We analyzed 60 consecutive patients with metastatic melanoma who underwent 18F-FDG PET/CT scans both before and after treatment to evaluate treatment response after completion of ipilimumab therapy. Tumor response was assessed by the change in the sum of SULpeak (voxels with the highest average SUL [SUV normalized to lean body mass]) of up to 5 lesions according to PERCIST5. New lesions on PET that appeared suggestive of metastases were considered progressive metabolic disease (PMD). Because immunotherapy may cause new inflammatory lesions that are detectable on 18F-FDG PET/CT, we also evaluated an immunotherapy-modified response classification (imPERCIST5). In this classification, new lesions do not define PMD per se; rather, PMD requires an increase in the sum of SULpeak by 30%. The correlation between tumor response according to these 3 definitions and overall survival (OS) was evaluated and compared with known prognostic factors. Results: In responders and nonresponders, the 2-y OS was 66% versus 29% for imPERCIST5 (P = 0.003). After multivariate analysis, imPERCIST5 remained prognostic (hazard ratio, 3.853; 95% confidence interval, 1.498-9.911; P = 0.005). New sites of focal 18F-FDG uptake occurred more often in patients with PMD (n = 24) by imPERCIST5 than in those with stable metabolic disease (n = 7) or partial metabolic response (n = 4). In patients with partial metabolic response, 2 of 4 isolated new lesions regressed spontaneously during follow-up. Conclusion: In patients with metastatic melanoma treated with ipilimumab, tumor response according to PERCIST was associated with OS. Our data suggest that PMD should not be defined by the appearance of new lesions, but rather by an increase in the sum of SULpeak.

Project description:Clinical data that support stereotactic body radiation therapy (SBRT) metastatic malignant melanoma (MM) are limited. Furthermore, functional imaging with 18F-fludeoxyglucose positron emission tomography (PET) may offer a more accurate post-SBRT assessment. Therefore, we assessed the clinical outcomes and metabolic response of metastatic MM after SBRT.Patients with MM who were treated with SBRT and had pre- and post-PET scans (>1) were included in this study. A total of 390 pre- and post-SBRT PET/computed tomography (CT) scans for 80 metastases were analyzed. The PET metabolic response was evaluated per the PET Response Criteria in Solid Tumors (PERCIST), version 1.0, criteria. Single-fraction equivalent dose (SFED) was calculated as per the standard. The Kaplan-Meier method was used for estimates of overall survival (OS) and progression-free survival. The cumulative incidence method was used to estimate metastasis control (MC). A Wilcoxon test was used to compare survival estimates. The prognostic factors for MC and OS were assessed using the Cox proportional hazards model, and the Likelihood Ratio was also used for comparisons between groups.A median of 6 PET scans (range, 2-6 scans) was evaluated for each metastasis. The median SFED was 42.8 Gy (range, 18-56.4 Gy) and the median biologically effective dose was 254.4 Gy2.5 (range, 100.8-540 Gy2.5). Twenty percent of patients received chemotherapy and 59% received immunotherapy: granulocyte-macrophage colony-stimulating factor (64%) and ipilimumab (34%). MC was 94% and 90% at 1 year and 3 years, respectively. The OS was 74% and 27% and 1 year and 3 years, respectively. Complete response was achieved in 90% at a median of 2.8 months (range, 0.4-25.2 months). SFED >24 Gy correlated with improved MC (93% vs 75%, P = .01). Acute and late grade 3+ toxicities were 4% and 11%, respectively, with no grade 5 toxicity.Post-SBRT PET/CT for extracranial metastatic MM resulted in high rates of complete response at a median of 2.8 months, and durable MC was achieved with SFED >24 Gy. SBRT, in addition to surgery and ablation, should be discussed with patients with MM, especially those with oligometastases.

Dataset Information

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

Publications

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

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