TY - JOUR
T1 - The Predictive Value of FDG PET/CT for Determining Progression-Free Survival in Advanced Stage III-IV BRAF-Mutated Melanoma Patients Treated With Targeted Therapy-What Can Be Learned From Progression?
AU - van der Hiel, Bernies
AU - Aalbersberg, Else A
AU - van den Eertwegh, Alfons J M
AU - de Wit-van der Veen, Linda J
AU - Stokkel, Marcel P M
AU - Lopez-Yurda, Marta
AU - Boellaard, Ronald
AU - Kapiteijn, Ellen W
AU - Hospers, Geke A P
AU - Aarts, Maureen J B
AU - de Vos, Filip Y F L
AU - Boers-Sonderen, Marye J
AU - van der Veldt, Astrid A M
AU - de Groot, Jan Willem B
AU - Haanen, John B A G
N1 - Publisher Copyright:
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2024/2/1
Y1 - 2024/2/1
N2 - PURPOSE: The aims of this study were to investigate whether (early) PERCIST response monitoring with 18F-FDG PET/CT is predictive for progression-free survival (PFS) in unresectable stage III or IV melanoma patients treated with BRAF/MEK inhibitor (MEKi) and to define dissemination patterns at progression with a lesion-based evaluation in direct comparison to baseline to improve our understanding of 18F-FDG PET/CT during BRAF/MEKi.PATIENTS AND METHODS: This prospective multicenter single-arm study included 70 patients with unresectable stage III/IV BRAF-mutated melanoma who underwent contrast-enhanced CT and 18F-FDG PET/CT at baseline and 2 and 7 weeks during treatment with vemurafenib plus cobimetinib and at progression if possible. Tumor response assessment was done with RECIST1.1 and PERCIST. Follow-up PET/CT scans were visually compared with baseline to assess dissemination patterns.RESULTS: Using RECIST1.1, PFS was not significantly different between the response groups (P = 0.26). At 2 weeks, PERCIST median PFS was 15.7 months for patients with complete metabolic response (CMR) versus 8.3 months for non-CMR (P = 0.035). The hazards ratio (HR) for progression/death in non-CMR versus CMR was 1.99 (95% confidence interval [CI], 1.03-3.84; P = 0.040) and 1.77 (95% CI, 0.91-3.43; P = 0.0935) when adjusting for lactate dehydrogenase (LDH). At 7 weeks, median PFS for PERCIST CMR was 16.7 months versus 8.5 months for non-CMR (P = 0.0003). The HR for progression/death in the non-CMR group was significantly increased (HR, 2.94; 95% CI, 1.60-5.40; P = 0.0005), even when adjusting for LDH (HR, 2.65; 95% CI, 1.43-4.91; P = 0.0020). At week 7, 18F-FDG PET/CT was false-positive in all 4 (6%) patients with new FDG-avid lesions but CMR of known metastases. When 18F-FDG PET/CT was performed at progressive disease, 18/22 (82%) patients had progression of known metastases with or without new 18F-FDG-avid lesions.CONCLUSIONS: This study shows that PERCIST response assessment at week 7 is predictive for PFS, regardless of LDH. At 2 weeks, patients with CMR have longer PFS than patients with non-CMR, but different PET parameters should be investigated to further evaluate the added value of early 18F-FDG PET/CT. Disease progression on PET/CT is predominated by progression of known metastases, and new 18F-FDG-avid lesions during BRAF/MEKi are not automatically a sign of recurrent disease.
AB - PURPOSE: The aims of this study were to investigate whether (early) PERCIST response monitoring with 18F-FDG PET/CT is predictive for progression-free survival (PFS) in unresectable stage III or IV melanoma patients treated with BRAF/MEK inhibitor (MEKi) and to define dissemination patterns at progression with a lesion-based evaluation in direct comparison to baseline to improve our understanding of 18F-FDG PET/CT during BRAF/MEKi.PATIENTS AND METHODS: This prospective multicenter single-arm study included 70 patients with unresectable stage III/IV BRAF-mutated melanoma who underwent contrast-enhanced CT and 18F-FDG PET/CT at baseline and 2 and 7 weeks during treatment with vemurafenib plus cobimetinib and at progression if possible. Tumor response assessment was done with RECIST1.1 and PERCIST. Follow-up PET/CT scans were visually compared with baseline to assess dissemination patterns.RESULTS: Using RECIST1.1, PFS was not significantly different between the response groups (P = 0.26). At 2 weeks, PERCIST median PFS was 15.7 months for patients with complete metabolic response (CMR) versus 8.3 months for non-CMR (P = 0.035). The hazards ratio (HR) for progression/death in non-CMR versus CMR was 1.99 (95% confidence interval [CI], 1.03-3.84; P = 0.040) and 1.77 (95% CI, 0.91-3.43; P = 0.0935) when adjusting for lactate dehydrogenase (LDH). At 7 weeks, median PFS for PERCIST CMR was 16.7 months versus 8.5 months for non-CMR (P = 0.0003). The HR for progression/death in the non-CMR group was significantly increased (HR, 2.94; 95% CI, 1.60-5.40; P = 0.0005), even when adjusting for LDH (HR, 2.65; 95% CI, 1.43-4.91; P = 0.0020). At week 7, 18F-FDG PET/CT was false-positive in all 4 (6%) patients with new FDG-avid lesions but CMR of known metastases. When 18F-FDG PET/CT was performed at progressive disease, 18/22 (82%) patients had progression of known metastases with or without new 18F-FDG-avid lesions.CONCLUSIONS: This study shows that PERCIST response assessment at week 7 is predictive for PFS, regardless of LDH. At 2 weeks, patients with CMR have longer PFS than patients with non-CMR, but different PET parameters should be investigated to further evaluate the added value of early 18F-FDG PET/CT. Disease progression on PET/CT is predominated by progression of known metastases, and new 18F-FDG-avid lesions during BRAF/MEKi are not automatically a sign of recurrent disease.
KW - BRAF mutation
KW - PERCIST
KW - PET
KW - melanoma
KW - progression-free survival
KW - targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=85181762366&partnerID=8YFLogxK
U2 - 10.1097/RLU.0000000000004988
DO - 10.1097/RLU.0000000000004988
M3 - Article
C2 - 38113329
SN - 0363-9762
VL - 49
SP - 138
EP - 145
JO - Clinical Nuclear Medicine
JF - Clinical Nuclear Medicine
IS - 2
ER -