The aim of this study was to associate and predict B-Rapidly Accelerated Fibrosarcoma Valine 600 (BRAFV600) mutation status with both conventional- and radiomics fluorodeoxyglucose Positron Emission Tomography/Computer Tomography (¹⁸F-FDG PET/CT) features, while exploring several methods of feature selection in melanoma radiomics. Methods: Seventy unresectable stage III-IV melanoma patients who underwent a baseline ¹⁸F-FDG PET/CT scan were identified. Patients were assigned to the BRAFV600 group or BRAF wild-type group according to mutational status. ¹⁸F-FDG uptake quantification was performed by semi-automatic lesion delineation. Four hundred eighty radiomics features and four conventional PET features (maximum, mean and peak standardized uptake value, and total lesion glycolysis) were extracted per lesion. Six different methods of feature selection were implemented and ten-fold cross validated predictive models were built for each. Model performances were evaluated with Area Under the Curves (AUC) of the Receiver Operating Characteristic curves. Results: Thirty-five BRAFV600 mutated patients (100 lesions) and thirty-five BRAF wild-type patients (79 lesions) were analyzed. AUCs predicting the BRAFV600 mutation varied from 0.54-0.62 and were susceptible to feature selection method. The best AUCs were achieved by feature selection based on literature, a penalized binary logistic regression model and random forest model. No significant difference was found between the BRAFV600 and BRAF wild-type group in conventional PET features, nor predictive value. Conclusion: BRAFV600 mutation status is not associated with- nor can be predicted with conventional PET features, while radiomics features were of low predictive value (AUC=0.62). We showed feature selection methods influence predictive model performance, describing and evaluating six unique methods. Detecting BRAFV600 status in melanoma based on ¹⁸F-FDG PET/CT alone does not yet provide clinically relevant knowledge.

AJCC stage IIIB and IIIC melanoma patients are at risk for disease relapse or progression. The advent of effective systemic therapies has made curative treatment of progressive disease a possibility. As resection of oligometastatic disease can confer a survival benefit and as immunotherapy is possibly most effective in a low tumor load setting, there is a likely benefit to early detection of progression. The aim of this pilot study was to evaluate a PET/computed tomography (CT) surveillance schedule for resected stage IIIB and IIIC melanoma. From 1–2015, stage IIIB and IIIC melanoma patients at our institution underwent 6-monthly surveillance with PET/CT, together with 3-monthly S100B assessment. When symptoms or elevated S100B were detected, an additional PET/CT was performed. Descriptive statistics were used to evaluate outcomes for this surveillance schedule. Fifty-one patients were followed up, 27 patients developed a recurrence before surveillance imaging, five were detected by an elevated S100B, and one patient was not scanned according to protocol. Eighteen patients were included. Thirty-two scans were acquired. Eleven relapses were suspected on PET/CT. Ten scans were true positive, one case was false positive, and one case was false negative. All recurrences detected by PET/CT were asymptomatic at that time, with a normal range of S100B. The number of scans needed to find one asymptomatic relapse was 3.6. PET/CT surveillance imaging seems to be an effective strategy for detecting asymptomatic recurrence in stage IIIB and IIIC melanoma patients in the first year after complete surgical resection.

In patients with BRAFV600 mutated unresectable stage IIIc or metastatic melanoma, molecular targeted therapy with combined BRAF/MEK-inhibitor vemurafenib plus cobimetinib has shown a significantly improved progression-free survival and overall survival compared to treatment with vemurafenib alone. Nevertheless, the majority of BRAFV600 mutation-positive melanoma patients will eventually develop resistance to treatment. Molecular imaging with 18F-Fluorodeoxyglucose (18F-FDG) PET has been used to monitor response to vemurafenib in some BRAFV600 mutated metastatic melanoma patients, showing a rapid decline of 18F-FDG uptake within 2 weeks following treatment. Furthermore, preliminary results suggest that metabolic alterations might predict the development of resistance to treatment. 18F-Fluoro-3′-deoxy-3’L-fluorothymidine (18F-FLT), a PET-tracer visualizing proliferation, might be more suitable to predict response or resistance to therapy than 18F-FDG. This phase II, open-label, multicenter study evaluates whether metabolic response to treatment with vemurafenib plus cobimetinib in the first 7 weeks as assessed by 18F-FDG/18F-FLT PET can predict progression-free survival and whether early changes in 18F-FDG/18F-FLT can be used for early detection of treatment response compared to standard response assessment with RECISTv1.1 ceCT at 7 weeks. Ninety patients with BRAFV600E/K mutated unresectable stage IIIc/IV melanoma will be included. Prior to and during treatment all patients will undergo 18F-FDG PET/CT and in 25 patients additional 18F-FLT PET/CT is performed. Histopathological tumor characterization is assessed in a subset of 40 patients to unravel mechanisms of resistance. Furthermore, in all patients, blood samples are taken for pharmacokinetic analysis of vemurafenib/cobimetinib. Outcomes are correlated with PET/CT-imaging and therapy response. The results of this study will help in linking PET measured metabolic alterations induced by targeted therapy of BRAFV600 mutated melanoma to molecular changes within the tumor. We will be able to correlate both 18F-FDG and 18F-FLT PET to outcome and decide on the best modality to predict long-term remissions to combined BRAF/MEK-inhibitors. Results coming from this study may help in identifying responders from non-responders early after the initiation of therapy and reveal early development of resistance to vemurafenib/cobimetinib. Furthermore, we believe that the results can be fundamental for further optimizing individual patient treatment. Clinicaltrials.gov identifier: NCT02414750. Registered 10 April 2015, retrospectively registered.

The aim of this study was to systematically review literature, exploring the role of radioguided surgery with iodine-labeled metaiodobenzylguanidine (MIBG) in resection of neuroendocrine tumors. PubMed, EMBASE, Web of Science, COCHRANE, CINAHL, Academic Search Premier, ScienceDirect, Wiley, and references of key articles were searched to identify potentially relevant studies. Twenty studies were included. A total of 130 procedures in 120 patients were performed. Ninety percent of included studies concerned case reports or case series. It is described that radioguided surgery with iodine-labeled MIBG can improve the quality of macroscopic resection of neuroendocrine tumors in selected cases, ie, in cases where the tumor is small, nonpalpable, difficult to visualize on conventional imaging studies, or located in an area with adhesional scar tissue from previous surgery. However, in a substantial number of cases the gamma probe failed due to technical problems. Since there is limited evidence that radioguided surgery contributes substantially in resection of neuroendocrine tumors, we cannot advocate its use in general. However, we can conclude that it can seemingly improve the quality of resection in selected cases. When radioguided surgery is performed in neuroendocrine tumors, we advocate the use of I to label MIBG.