18F-FDG PET/CT During Neoadjuvant Targeted Therapy in Prior Unresectable Stage III Melanoma Patients: Can (Early) Metabolic Imaging Predict Histopathologic Response or Recurrence?

The aim of this study was to investigate whether 18F-FDG PET/CT can predict histopathological response or recurrence in BRAF-mutated unresectable locally advanced stage III melanoma treated with neoadjuvant BRAF/MEK inhibition followed by resection and the value of PET in detecting early recurrence after resection. Twenty BRAF-mutated, unresectable stage III melanoma patients received BRAF/MEK inhibitors before surgery. 18F-FDG PET/CT was performed at baseline and 2 and 8 weeks after initiation of therapy. After resection, PET/CT was performed at specific time points during 5 years of follow-up. Pathological response was assessed on the dissection specimen. Response monitoring was measured with SUVmax, SUVpeak, MATV, and TLG and according to EORTC and PERCIST criteria. Pathological response was assessed in 18 patients. Nine patients (50%) had a pathologic complete or near-complete response, and 9 (50%) had a pathologic partial or no response. EORTC or PERCIST response measurements did not correspond with pathologic outcome. SUVmax, SUVpeak, MATV, and TLG at all time points and absolute or percentage change among the 3 initial time points did not differ between the groups.During follow-up, 8 of 17 patients with R0 resection developed a recurrence, 6 recurrences were detected with imaging only, 4 of which with PET/CT in less than 6 months after surgery. PET parameters before surgery did not predict recurrence. Baseline 18F-FDG PET or PET response in previous unresectable stage III melanoma patients seems not useful to predict pathologic response after neoadjuvant BRAF/MEK inhibitors treatment. However, PET/CT seems valuable in detecting recurrence early after R0 resection.

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Conflicts of interest and sources of funding: AvA advisory board and consultancy honoraria for Amgen, Bristol-Myers Squibb, Novartis, MSD-Merck, Merck-Pfizer, Pierre Fabre, Sanofi, Sirius Medical, and 4SC; and research grant from Amgen and Merck-Pfizer, all unrelated and paid to institute. J.B.H. has advisory roles for Bristol-Myers Squibb, Ipsen, Iovance Biotherapeutics, Merck Serono, Molecular Partners, MSD, Novartis, Pfizer, Roche, Sanofi, Seattle Genetics, and Third Rock Ventures, all paid to institute; member of SAB of Achilles Tx, BioNTech, Gadeta, Immunocore, Instil Bio, PokeAcel, T-Knife, and Neogene Tx; received grant support from Amgen, Asher Bio, BioNTech, Bristol-Myers Squibb, MSD, Novartis, and Neogene Tx, all paid to institute; and has stock options in Neogene Tx.