FDG PET/CT for tumoral and systemic immune response monitoring of advanced melanoma during first-line combination ipilimumab and nivolumab treatment

Iravani, Amir; Osman, Medhat; Weppler, Alison M.; Wallace, Roslyn; Galligan, Anna; Lasocki, Arian; Hunter, Morgan; Akhurst, Tim; Hofman, Michael S; Lau, Peter K. H.; Kee, Damien; Au-Yeung, George; Sandhu, Shahneen; Hicks, Rodney J.

doi:10.1007/s00259-020-04815-w

Cited by 46 publications

(34 citation statements)

References 24 publications

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“…The role of volumetric parameters in FDG-PET/CT as a predictive biomarker has been demonstrated in different types of cancers [5,[13][14][15][16][17]. The total metabolic tumor volume is a valuable parameter as it reflects the extent and activity of the tumor [18][19][20].…”

Section: Discussionmentioning

confidence: 99%

Early Reassessment of Total Metabolic Tumor Volume on FDG-PET/CT in Advanced Melanoma Patients Treated with Pembrolizumab Predicts Long-Term Outcome

et al. 2021

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PD-1 Immune checkpoint inhibitors, such as Pembrolizumab, can have a durable beneficial therapeutic effect in patients with advanced melanoma. However, not all patients will benefit equally from these therapies, and (potentially life-threatening) immune-related adverse events may occur. In this study, we investigate the value of early response assessment by FDG-PET/CT as a biomarker for predicting survival. We identified all patients with advanced melanoma who were treated with Pembrolizumab in our medical center and underwent a baseline and at least one follow-up FDG-PET/CT. The total metabolic tumor volume (TMTV) was calculated, and the evolution was compared to survival parameters. A total of 77 patients underwent a baseline and at least one follow-up FDG-PET/CT, 36 patients had follow-up imaging within 2–4 months, and 21 patients an FDG-PET/CT 5–6 months after baseline. When the TMTV evolution was categorized into two subgroups (stable/decrease versus increase), an association was found between stability or decrease in TMTV and better PFS and OS. A similar trend, however non-significant, was observed at 5–6 months. The evolution in TMTV as assessed by FDG-PET/CT 2–4 months after treatment initiation is associated with long-term outcomes in patients with advanced melanoma treated with Pembrolizumab.

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Section: Discussionmentioning

confidence: 99%

Early Reassessment of Total Metabolic Tumor Volume on FDG-PET/CT in Advanced Melanoma Patients Treated with Pembrolizumab Predicts Long-Term Outcome

et al. 2021

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“…Hitherto, a non-negligible number of studies have evaluated the efficacy of PET/CT in predicting treatment response of metastatic melanoma patients to ICIs. While most papers have focused on later time points during the course or after the end of treatment [26,28,[30][31][32]40], few of them also reported on application of the imaging modality early during immunotherapy. Our group previously showed in a cohort of 22 patients that PET/CT performed after two ipilimumab cycles-and after application of the EORTC criteria-correctly predicted treatment response after completion of the 4-cycle treatment in the majority (87%) of PMD patients and in all SMD patients [24].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, patterns of [ 18 F]FDG uptake on interim PET/CT suggestive of radiologic manifestations of irAEs to immunotherapy were documented. Based on our experience and the published literature in the field [ 29 , 32 ], we defined radiologic irAEs as sites of newly emerging, increased compared to baseline imaging, non-malignant [ 18 F]FDG accumulation in organs known to exhibit immune-related signs on PET/CT. In particular, a new, diffusely enhanced tracer uptake in organs such as the gastrointestinal tract (mostly colon), the thyroid gland and the bone marrow, or, respectively, a new, relatively symmetrical, increased uptake in lymph nodes (e.g., mediastinal/hilar, inguinal) and in joints following ICIs were considered suggestive of radiologic irAEs in these organs.…”

Section: Methodsmentioning

confidence: 99%

Interim [18F]FDG PET/CT can predict response to anti-PD-1 treatment in metastatic melanoma

Sachpekidis

Kopp‐Schneider

Pan

et al. 2020

Eur J Nucl Med Mol Imaging

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Purpose In an attempt to identify biomarkers that can reliably predict long-term outcomes to immunotherapy in metastatic melanoma, we investigated the prognostic role of [18F]FDG PET/CT, performed at baseline and early during the course of anti-PD-1 treatment. Methods Twenty-five patients with stage IV melanoma, scheduled for treatment with PD-1 inhibitors, were enrolled in the study (pembrolizumab, n = 8 patients; nivolumab, n = 4 patients; nivolumab/ipilimumab, 13 patients). [18F]FDG PET/CT was performed before the start of treatment (baseline PET/CT) and after the initial two cycles of PD-1 blockade administration (interim PET/CT). Seventeen patients underwent also a third PET/CT scan after administration of four cycles of treatment. Evaluation of patients’ response by means of PET/CT was performed after application of the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria and the PET Response Evaluation Criteria for IMmunoTherapy (PERCIMT). Response to treatment was classified into 4 categories: complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease (PMD). Patients were further grouped into two groups: those demonstrating metabolic benefit (MB), including patients with SMD, PMR, and CMR, and those demonstrating no MB (no-MB), including patients with PMD. Moreover, patterns of [18F]FDG uptake suggestive of radiologic immune-related adverse events (irAEs) were documented. Progression-free survival (PFS) was measured from the date of interim PET/CT until disease progression or death from any cause. Results Median follow-up from interim PET/CT was 24.2 months (19.3–41.7 months). According to the EORTC criteria, 14 patients showed MB (1 CMR, 6 PMR, and 7 SMD), while 11 patients showed no-MB (PMD). Respectively, the application of the PERCIMT criteria revealed that 19 patients had MB (1 CMR, 6 PMR, and 12 SMD), and 6 of them had no-MB (PMD). With regard to PFS, no significant difference was observed between patients with MB and no-MB on interim PET/CT according to the EORTC criteria (p = 0.088). In contrary, according to the PERCIMT criteria, patients demonstrating MB had a significantly longer PFS than those showing no-MB (p = 0.045). The emergence of radiologic irAEs (n = 11 patients) was not associated with a significant survival benefit. Regarding the sub-cohort undergoing also a third PET/CT, 14/17 patients (82%) showed concordant responses and 3/17 (18%) had a mismatch of response assessment between interim and late PET/CT. Conclusion PET/CT-based response of metastatic melanoma to PD-1 blockade after application of the recently proposed PERCIMT criteria is significantly correlated with PFS. This highlights the potential ability of [18F]FDG PET/CT for early stratification of response to anti-PD-1 agents, a finding with possible significant clinical and financial implications. Further studies including larger numbers of patients are necessary to validate these results.

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“…In conclusion, despite the more effective way of assessing the [ 18 F]FDG PET-based response in patients treated with ICPIs, available studies suggest that [ 18 F]FDG PET can support decision-making about the continuation/discontinuation of therapy, as it can open several windows able to capture different aspects associated with the effect of treatment (i.e., pseudoprogression, hyperprogression, and IRAE) [56]. Table 2 reports the characteristics of published studies involving the use of [ 18 F]FDG PET to assess the response to ICI [46][47][48]50,51,54,[57][58][59][60][61][62][63][64][65][66][67][68]. Figure 2 shows a representative example of baseline and post-treatment [ 18 F]FDG PET in a patient with advanced NSCLC treated with Nivolumab.…”

Section: Pet-based Response To Icpis In Patients With Nsclcmentioning

confidence: 99%

Positron Emission Tomography-Based Response to Target and Immunotherapies in Oncology

et al. 2020

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2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is a promising tool to support the evaluation of response to either target therapies or immunotherapy with immune checkpoint inhibitors both in clinical trials and, in selected patients, at the single patient’s level. The present review aims to discuss available evidence related to the use of [18F]FDG PET (Positron Emission Tomography) to evaluate the response to target therapies and immune checkpoint inhibitors. Criteria proposed for the standardization of the definition of the PET-based response and complementary value with respect to morphological imaging are commented on. The use of PET-based assessment of the response through metabolic pathways other than glucose metabolism is also relevant in the framework of personalized cancer treatment. A brief discussion of the preliminary evidence for the use of non-FDG PET tracers in the evaluation of the response to new therapies is also provided.

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FDG PET/CT for tumoral and systemic immune response monitoring of advanced melanoma during first-line combination ipilimumab and nivolumab treatment

Cited by 46 publications

References 24 publications

Early Reassessment of Total Metabolic Tumor Volume on FDG-PET/CT in Advanced Melanoma Patients Treated with Pembrolizumab Predicts Long-Term Outcome

Early Reassessment of Total Metabolic Tumor Volume on FDG-PET/CT in Advanced Melanoma Patients Treated with Pembrolizumab Predicts Long-Term Outcome

Interim [18F]FDG PET/CT can predict response to anti-PD-1 treatment in metastatic melanoma

Positron Emission Tomography-Based Response to Target and Immunotherapies in Oncology

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