The Advantages and Challenges of Using FDG PET/CT for Response Assessment in Melanoma in the Era of Targeted Agents and Immunotherapy
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The treatment of melanoma has been revolutionised in recent years by advances in the understanding of the genomic landscape of this disease, which has led to the development of new targeted therapeutic agents, and the ability to therapeutically manipulate the immune system through inhibition of cancer cell-T-cell interactions that prevent an adaptive immune response. While these therapeutic interventions have dramatically improved the prospects of survival for patients with advanced melanoma, they bring significant complexity to the interpretation of therapeutic response because their mechanisms and temporal profile of response vary considerably. In this review, we discuss the mode of action of these emerging therapies and their toxicities to provide a framework for the use of FDG PET/CT in therapeutic response assessment. We propose that the greatest utility of PET in assessment of response to agents that abrogate signalling related to BRAF mutation is for early assessment of resistance, while in anti-CTLA4 therapy, immunological flare can compromise early assessment of response but can identify potentially life-threatening autoimmune reactions. For anti-PD1/PDL1 therapy, the role of FDG PET/CT is more akin to its use in other solid malignancies undergoing treatment with conventional chemotherapy. However, further research is required to optimise the timing of scans and response criteria in this disease.
KeywordsMelanoma Therapeutic monitoring PET Immune response BRAF
Compliance with ethical standards
This review does not report any previously unpublished studies with human participants or animals performed by any of the authors. Therefore, ethics committee approval is not applicable.
Professor Hicks is a National Health and Medical Research (NHMRC) Practitioner Fellow supported by grant APP110850 and both Professor Hicks and Professor McArthur are recipients of a NHMRC program grant (APP1053792), which supports their research.
Conflicts of interest
None of the authors has a conflict of interest to report.
- 1.Balch CM, Buzaid AC, Soong SJ, Atkins MB, Cascinelli N, Coit DG, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol. 2001;19(16):3635–48.Google Scholar
- 4.Weber JS, D’Angelo SP, Minor D, Hodi FS, Gutzmer R, Neyns B, et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. The Lancet Oncology. 2015;16:375–84.CrossRefPubMedGoogle Scholar
- 6.Hodi FS, Sznol M, Kluger HM, McDermott DF, Carvajal RD, Lawrence DP, et al. Long-term survival of ipilimumab-naive patients (pts) with advanced melanoma (MEL) treated with nivolumab (anti-PD-1, BMS-936558, ONO-4538) in a phase I trial. ASCO Annual Meeting Proceedings; 2014. p. 9002.Google Scholar
- 10.McArthur GA, Chapman PB, Robert C, Larkin J, Haanen JB, Dummer R, et al. Safety and efficacy of vemurafenib in BRAF V600E and BRAF V600K mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study. The lancet Oncology. 2014;15:323–32.CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Ascierto PA, McArthur GA, Dréno B, Atkinson V, Liszkay G, Di Giacomo AM, et al. Cobimetinib combined with vemurafenib in advanced BRAF V600-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial. The Lancet Oncology. 2016;17:1248–60.CrossRefPubMedGoogle Scholar
- 19.Mileshkin L, Hicks RJ, Hughes BG, Mitchell PL, Charu V, Gitlitz BJ, et al. Changes in 18F-fluorodeoxyglucose and 18F-fluorodeoxythymidine positron emission tomography imaging in patients with non–small cell lung cancer treated with erlotinib. Clinical Cancer Research. 2011;17:3304–15.CrossRefPubMedGoogle Scholar
- 20.Blanke CD, Demetri GD, Von Mehren M, Heinrich MC, Eisenberg B, Fletcher JA, et al. Long-term results from a randomized phase II trial of standard-versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT. Journal of Clinical Oncology. 2008;26:620–5.CrossRefPubMedGoogle Scholar
- 21.Su H, Bodenstein C, Dumont RA, Seimbille Y, Dubinett S, Phelps ME, et al. Monitoring tumor glucose utilization by positron emission tomography for the prediction of treatment response to epidermal growth factor receptor kinase inhibitors. Clinical Cancer Research. 2006;12:5659–67.CrossRefPubMedGoogle Scholar
- 25.Wong C, Silverman DH, Seltzer M, Schiepers C, Ariannejad M, Gambhir SS, et al. The impact of 2-deoxy-2[18F] fluoro-D-glucose whole body positron emission tomography for managing patients with melanoma: the referring physician’s perspective. Mol Imaging Biol. 2002;4:185–90.CrossRefPubMedGoogle Scholar
- 26.Subesinghe M, Marples M, Scarsbrook AF, Smith JT. Clinical impact of (18)F-FDG PET-CT in recurrent stage III/IV melanoma: a tertiary centre Specialist Skin Cancer Multidisciplinary Team (SSMDT) experience. Insights into imaging. 2013;4:701–9. doi: 10.1007/s13244-013-0285-1.CrossRefPubMedPubMedCentralGoogle Scholar
- 33.Strobel K, Dummer R, Steinert HC, Conzett KB, Schad K, Lago MP, et al. Chemotherapy response assessment in stage IV melanoma patients-comparison of 18F-FDG-PET/CT, CT, brain MRI, and tumormarker S-100B. European journal of nuclear medicine and molecular imaging. 2008;35:1786–95. doi: 10.1007/s00259-008-0806-1.CrossRefPubMedGoogle Scholar
- 37.McArthur GA, Callahan J, Ribas A, Gonzalez R, Pavlick AC, Hamid O, et al. Metabolic tumor burden for prediction of overall survival following combined BRAF/MEK inhibition in patients with advanced BRAF mutant melanoma. ASCO Annual Meeting Proceedings; 2014. p. 9006.Google Scholar
- 38.Carlino MS, Saunders CA, Haydu LE, Menzies AM, Curtis CM, Lebowitz PF, et al. 18 F-labelled fluorodeoxyglucose–positron emission tomography (FDG–PET) heterogeneity of response is prognostic in dabrafenib treated BRAF mutant metastatic melanoma. European journal of cancer. 2013;49:395–402.CrossRefPubMedGoogle Scholar
- 40.Frederick DT, Piris A, Cogdill AP, Cooper ZA, Lezcano C, Ferrone CR, et al. BRAF inhibition is associated with enhanced melanoma antigen expression and a more favorable tumor microenvironment in patients with metastatic melanoma. Clinical cancer research. 2013;19:1225–31.CrossRefPubMedPubMedCentralGoogle Scholar
- 43.Hu-Lieskovan S, Mok S, Moreno BH, Tsoi J, Robert L, Goedert L, et al. Improved antitumor activity of immunotherapy with BRAF and MEK inhibitors in BRAFV600E melanoma. Science Translational medicine. 2015;7:279ra41–1.Google Scholar
- 45.Atkins MB, Kunkel L, Sznol M, Rosenberg SA. High-dose recombinant interleukin-2 therapy in patients with metastatic melanoma: long-term survival update. The Cancer Journal. 2000;6:S11.Google Scholar
- 67.Bier G, Hoffmann V, Kloth C, Othman AE, Eigentler T, Garbe C, et al. CT imaging of bone and bone marrow infiltration in malignant melanoma--Challenges and limitations for clinical staging in comparison to 18FDG-PET/CT. Eur J Radiol. 2016;85:732–8. doi: 10.1016/j.ejrad.2016.01.012.CrossRefPubMedGoogle Scholar
- 71.Barrington SF, Mikhaeel NG, Kostakoglu L, Meignan M, Hutchings M, Müeller SP, et al. Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on Malignant Lymphomas Imaging Working Group. Journal of clinical oncology. 2014;32:3048–58.CrossRefPubMedPubMedCentralGoogle Scholar