Impact of 18F-FDG-PET/CT on surgical management in patients with advanced melanoma: an outcome based analysis

Forschner, Andrea; Olthof, Susann-Cathrin; Gückel, Brigitte; Martus, Peter; Vach, Werner; Fougère, Christian la; Nikolaou, Konstantin; Keim, Ulrike; Eigentler, Thomas; Garbe, Claus; Pfannenberg, Christina

doi:10.1007/s00259-017-3674-8

Cited by 23 publications

(9 citation statements)

References 28 publications

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“…Second, in the setting of detectable ctDNA, contemporaneously performed clinical examinations and imaging studies should be interpreted with a high index of suspicion. An alternative imaging modality (e.g., positron emission tomography/CT scan) should be considered in patients with detectable ctDNA and no CT‐based evidence of melanoma (Forschner et al ., ). Indeed, our investigation demonstrates that ctDNA measurements complement the current standard of care of serial clinical examinations and radiographic imaging.…”

Section: Discussionmentioning

confidence: 99%

From validity to clinical utility: the influence of circulating tumor DNA on melanoma patient management in a real‐world setting

et al. 2018

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Melanoma currently lacks a reliable blood‐based biomarker of disease activity, although circulating tumor DNA (ctDNA) may fill this role. We investigated the clinical utility (i.e., impact on clinical outcomes and interpretation of radiographic data) of measuring ctDNA in patients with metastatic or high‐risk resected melanoma. Patients were prospectively accrued into ≥ 1 of three cohorts, as follows. Cohort A: patients with radiographically measurable metastatic melanoma who underwent comparison of ctDNA measured by a BEAMing digital PCR assay to tissue mutational status and total tumor burden; when appropriate, determinations about initiation of targeted therapy were based on ctDNA data. Cohorts B and C: patients with BRAF‐ or NRAS‐mutant melanoma who had either undergone surgical resection of high‐risk disease (cohort B) or were receiving or had received medical therapy for advanced disease (cohort C). Patients were followed longitudinally with serial ctDNA measurements with contemporaneous radiographic imaging to ascertain times to detection of disease activity and progressive disease, respectively. The sensitivity and specificity of the ctDNA assay were 86.8% and 100%, respectively. Higher tumor burden and visceral metastases were found to be associated with detectable ctDNA. In two patients in cohort A, ctDNA test results revealed a targetable mutation where tumor testing had not; both patients experienced a partial response to targeted therapy. In four of 30 patients with advanced melanoma, ctDNA assessments indicated evidence of melanoma activity that predicted radiographic evidence of disease progression by 8, 14, 25, and 38 weeks, respectively. CtDNA was detectable in three of these four patients coincident with radiographic evaluations that alone were interpreted as showing no evidence of neoplastic disease. Our findings provide evidence for the clinical utility of integrating ctDNA data in managing patients with melanoma in a real‐world setting.

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Section: Discussionmentioning

confidence: 99%

From validity to clinical utility: the influence of circulating tumor DNA on melanoma patient management in a real‐world setting

et al. 2018

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“…Blank et al suggested a 'cancer immunogram' wherein a combination of biomarkers such as tumoral mutational load, presence of T-cell checkpoints, soluble cytokines, metabolic factors and host immune factors should be considered. Here we explore how existing non-invasive functional imaging might provide a readily translatable source of novel biomarkers, given the current increase of 18 F-fluorodeoxyglucose positron emission tomography/computerised tomography (FDG PET/CT) in the surveillance of high-risk melanoma [12] or at suspected relapse [13]. 18 F-fluoro-deoxy-glucose positron emission tomography (FDG PET) has long been the preferred functional imaging technique in melanoma in our facility [14].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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 18 F-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.

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“…For thick melanomas, (> 4 mm), SNB is recommended mainly for staging and for potential disease control, it is important to point out that this particular patient group is at higher risk of systemic disease; therefore, the therapeutic benefit is perhaps more limited. In certain cases of very thick melanomas, we conduct imaging a priori to surgery since this could lead to substantial changes in the surgical treatment [ 49 ].…”

Section: Introductionmentioning

confidence: 99%

Sentinel Lymph Node Biopsy and Complete Lymph Node Dissection for Melanoma

Delgado

Zommorodi

2019

Curr Oncol Rep

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Purpose of Review The main surgical treatment for invasive malignant melanoma consists of wide surgical and examination of the sentinel node and in selected cases complete lymph node dissection. The aim of this review is to present data for the optimal surgical management of patients with malignant melanoma. Recent Findings A surgical excision margin of 1–2 cm is recommended for invasive melanoma depending on the thickness of the melanoma. Sentinel node biopsy may be considered for patients with at least T1b melanomas thickness 0.8 to 1.0 mm or less than 0.8 mm Breslow thickness with ulceration, classified as T1b lesion, per recent AJCC guidelines. Two randomized controlled trials have been published—DeCOG (German Dermatologic Cooperative Oncology Group Selective Lymphadenectomy) and MSLT-2 (Multicenter Selective Lymphadenectomy Trial) comparing the complete lymph node dissection (CLND) with observation after positive sentinel node biopsy. In the MSLT-2 study, the disease control rate was improved in the immediate CLND group compared with observation but there was no difference in 3-year melanoma specific survival (86% ± 1.3% and 86% ± 1.2%, respectively; p = 0.42). Isolated limb perfusion (ILP) or isolated limb infusion (ILI) with melphalan and actinomycin D is recommended for large and multiple in-transit metastases and satellite metastases in the extremities when local excision is considered ineffective or too extensive. Summary In light of new adjuvant treatment options and new indications for checkpoint inhibitors, and the lack of survival benefit after CLND, we can expect open surgery to decrease in melanoma disease.

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Impact of 18F-FDG-PET/CT on surgical management in patients with advanced melanoma: an outcome based analysis

Abstract: The study confirms the high impact of PET/CT on clinical management in patients with advanced melanoma planned for radical metastasectomy. PET/CT resulted in frequent management changes, preventing futile surgery in half of the patients.

Cited by 23 publications

References 28 publications

From validity to clinical utility: the influence of circulating tumor DNA on melanoma patient management in a real‐world setting

From validity to clinical utility: the influence of circulating tumor DNA on melanoma patient management in a real‐world setting

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

Sentinel Lymph Node Biopsy and Complete Lymph Node Dissection for Melanoma

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