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

Author(s):  
Christos Sachpekidis ◽  
Annette Kopp-Schneider ◽  
Leyun Pan ◽  
Dimitrios Papamichail ◽  
Uwe Haberkorn ◽  
...  

Abstract 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.

Author(s):  
Kazuhiro Kitajima ◽  
Tadashi Watabe ◽  
Masatoyo Nakajo ◽  
Mana Ishibashi ◽  
Hiromitsu Daisaki ◽  
...  

Abstract Objective In malignant melanoma patients treated with immune checkpoint inhibitor (ICI) therapy, three different FDG-PET criteria, European Organization for Research and Treatment of Cancer (EORTC), PET Response Criteria in Solid Tumors (PERCIST), immunotherapy-modified PERCIST (imPERCIST), were compared regarding response evaluation and prognosis prediction using standardized uptake value (SUV) harmonization of results obtained with various PET/CT scanners installed at different centers. Materials and methods Malignant melanoma patients (n = 27) underwent FDG-PET/CT examinations before and again 3 to 9 months after therapy initiation (nivolumab, n = 21; pembrolizumab, n = 6) with different PET scanners at five hospitals. EORTC, PERCIST, and imPERCIST criteria were used to evaluate therapeutic response, then concordance of the results was assessed using Cohen’s κ coefficient. Log-rank and Cox methods were employed to determine progression-free (PFS) and overall (OS) survival. Results Complete metabolic response (CMR)/partial metabolic response (PMR)/stable metabolic disease (SMD)/progressive metabolic disease (PMD) with harmonized EORTC, PERCIST, and imPERCIST was seen in 3/5/4/15, 4/5/3/15, and 4/5/5/13 patients, respectively. Nearly perfect concordance between each pair of criteria was noted (κ = 0.939–0.972). Twenty patients showed progression and 14 died from malignant melanoma after a median 19.2 months. Responders (CMR/PMR) showed significantly longer PFS and OS than non-responders (SMD/PMD) (harmonized EORTC: p < 0.0001 and p = 0.011; harmonized PERCIST: p < 0.0001 and p = 0.0012; harmonized imPERCIST: p < 0.0001 and p = 0.0012, respectively). Conclusions All harmonized FDG-PET criteria (EORTC, PERCIST, imPERCIST) showed accuracy for response evaluation of ICI therapy and prediction of malignant melanoma patient prognosis. Additional studies to determine their value in larger study populations will be necessary.


Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1019
Author(s):  
Christos Sachpekidis ◽  
Jessica C. Hassel ◽  
Annette Kopp-Schneider ◽  
Uwe Haberkorn ◽  
Antonia Dimitrakopoulou-Strauss

The advent of novel immune checkpoint inhibitors has led to unprecedented survival rates in advanced melanoma. At the same time, it has raised relevant challenges in the interpretation of treatment response by conventional imaging approaches. In the present prospective study, we explored the predictive role of quantitative, dynamic 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) performed early during immunotherapy in metastatic melanoma patients receiving treatment with programmed cell death protein 1 (PD-1) inhibitors. Twenty-five patients under PD-1 blockade underwent dynamic and static 18F-FDG PET/CT before the start of treatment (baseline PET/CT) and after the initial two cycles of therapy (interim PET/CT). The impact of semiquantitatively (standardized uptake value, SUV) and quantitatively (based on compartment modeling and fractal analysis) derived PET/CT parameters, both from melanoma lesions and different reference tissues, on progression-free survival (PFS) was analyzed. At a median follow-up of 24.2 months, survival analysis revealed that the interim PET/CT parameters SUVmean, SUVmax and fractal dimension (FD) of the hottest melanoma lesions adversely affected PFS, while the parameters FD of the thyroid, as well as SUVmax and k3 of the bone marrow positively affected PFS. The herein presented findings highlight the potential predictive role of quantitative, dynamic, interim PET/CT in metastatic melanoma under PD-1 blockade. Therefore, dynamic PET/CT could be performed in selected oncological cases in combination with static, whole-body PET/CT in order to enhance the diagnostic certainty offered by conventional imaging and yield additional information regarding specific molecular and pathophysiological mechanisms involved in tumor biology and response to treatment.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Riccardo Caruso ◽  
Emilio Vicente ◽  
Yolanda Quijano ◽  
Hipolito Duran ◽  
Isabel Fabra ◽  
...  

Abstract Objectives Neoadjuvant chemoradiation (nCRT) is universally considered to be a valid treatment to achieve downstaging, to improve local disease control and to obtain better resectability in locally advanced rectal cancer (LARC). The aim of this study is to correlate the change in the tumour 18F-FDG PET-CT standardized uptake value (SUV) before and after nCRT, in order to obtain an early prediction of the pathologic response (pR) achieved in patients with LARC. Data description We performed a retrospective analysis of patients with LARC diagnosis who underwent curative resection. All patients underwent a baseline 18F-FDG PET-CT scan within the week prior to the initiation of the treatment (PET-CT SUV1) and a second scan (PET-CT SUV2) within 6 weeks of the completion of nCRT. We evaluated the prognostic value of 18F-FDG PET-CT in terms of disease-free survival (DFS) and overall survival (OS) in patients with LARC.A total of 133 patients with LARC were included in the study. Patients were divided in two groups according to the TRG (tumour regression grade): 107 (80%) as the responders group (TRG0-TRG1) and 26 (25%) as the no-responders group (TRG2-TRG3). We obtained a significant difference in Δ%SUV between the two different groups; responders versus no-responders (p < 0.012). The results of this analysis show that 18F-FDG PET-CT may be an indicator to evaluate the pR to nCRT in patients with LARC. The decrease in 18F-FDG PET-CT uptake in the primary tumour may offer important information in order for an early identification of those patients more likely to obtain a pCR to nCRT and to predict those who are unlikely to significantly regress.


Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 559
Author(s):  
Talitha Bent ◽  
Derya Yakar ◽  
Thomas C. Kwee

Background: Biopsy of 18F-fluoro-2-deoxy-D-glucose (FDG)-avid lesions suspected for malignancy remains an invasive procedure associated with a variety of risks. It is still unclear if the positive predictive value (PPV) of positron emission tomography (PET)/computed tomography (CT) is sufficiently high to avoid tissue sampling. Therefore, the purpose of this study was to determine the PPV of 18F-FDG-PET/CT for malignancy in patients with a clinical suspicion of active malignant disease. Methods: This single-center retrospective study included 83 patients who had undergone FDG-PET/CT within 60 days before CT- or ultrasonography-guided tissue sampling and whose request form for CT- or US-guided tissue sampling requested mutation analyses. The latter implies a high clinical suspicion of active malignant disease. The nature of each biopsied lesion was determined based on the results of the pathological analysis and/or clinical and imaging follow-up of at least 12 months. Results: In total, eighty-eight FDG-avid lesions were biopsied. The PPV of FDG-PET/CT for malignancy was 98.9% (95% CI: 93.8–99.8%). For patients with an oncological history, the PPV was 98.7% (95% CI: 92.9–99.8%), and for patients with no oncological history, the PPV was 100% (95% CI: 74.1–100.0%). There was no significant difference between the PPV of the group with and without an oncological history (p = 0.71). In two cases, an unsuspected malignancy was diagnosed. Conclusion: Although the PPV of FDG-PET/CT for malignancy in patients with a clinical suspicion of active malignant disease is high, biopsy remains recommended to avoid inappropriate patient management due the non-negligible chance of dealing with FDG-avid benign disease or unexpected malignancies.


2021 ◽  
Vol 20 ◽  
pp. 153303382110246
Author(s):  
Seokmo Lee ◽  
Yunseon Choi ◽  
Geumju Park ◽  
Sunmi Jo ◽  
Sun Seong Lee ◽  
...  

Background and Aims: This study evaluated the prognostic value of 18F-fluorodeoxyglucose positron emission tomography with integrated computed tomography (18F-FDG PET/CT) performed before and after concurrent chemoradiotherapy (CCRT) in esophageal cancer. Methods: We analyzed the prognosis of 50 non-metastatic squamous cell esophageal cancer (T1-4N0-2) patients who underwent CCRT with curative intent at Inje University Busan Paik Hospital and Haeundae Paik Hospital from 2009 to 2019. Median total radiation dose was 54 Gy (range 34-66 Gy). Our aim was to investigate the relationship between PET/CT values and prognosis. The primary end point was progression-free survival (PFS). Results: The median follow-up period was 9.9 months (range 1.7-85.7). Median baseline maximum standard uptake value (SUVmax) was 14.2 (range 3.2-27.7). After treatment, 29 patients (58%) showed disease progression. The 3-year PFS and overall survival (OS) were 24.2% and 54.5%, respectively. PFS was significantly lower ( P = 0.015) when SUVmax of initial PET/CT exceeded 10 (n = 22). However, OS did not reach a significant difference based on maximum SUV ( P = 0.282). Small metabolic tumor volume (≤14.1) was related with good PFS ( P = 0.002) and OS ( P = 0.001). Small total lesion of glycolysis (≤107.3) also had a significant good prognostic effect on PFS ( P = 0.009) and OS ( P = 0.025). In a subgroup analysis of 18 patients with follow-up PET/CT, the patients with SUV max ≤3.5 in follow-up PET/CT showed longer PFS ( P = 0.028) than those with a maximum SUV >3.5. Conclusion: Maximum SUV of PET/CT is useful in predicting prognosis of esophageal cancer patients treated with CCRT. Efforts to find more effective treatments for patients at high risk of progression are still warranted.


2018 ◽  
Vol 68 (2) ◽  
pp. 297-303 ◽  
Author(s):  
Christos Sachpekidis ◽  
Lionel Larribère ◽  
Annette Kopp-Schneider ◽  
Jessica C. Hassel ◽  
Antonia Dimitrakopoulou-Strauss

PLoS ONE ◽  
2018 ◽  
Vol 13 (7) ◽  
pp. e0199529 ◽  
Author(s):  
Edouard Depardon ◽  
Salim Kanoun ◽  
Olivier Humbert ◽  
Aurélie Bertaut ◽  
Jean-Marc Riedinger ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Jun Wang ◽  
Liang Zhang ◽  
Jian Guo Wu ◽  
Ruohua Chen ◽  
Jia lin Shen

PurposeTo evaluate the value of F-18 FDG PET/CT in the differentiation of malignant and benign upper urinary tract-occupying lesions.Patients and Methods64 patients with upper urinary tract-occupying lesions underwent F-18 FDG PET/CT at RenJi Hospital from January 2015 to February 2019 in this retrospective study. Of the 64 patients, 50 patients received nephroureterectomy or partial ureterectomy; 14 patients received ureteroscopy and biopsy. The comparisons of PET/CT parameters and clinical characteristics between malignant and benign upper urinary tract-occupying lesions were investigated.ResultsOf the 64 patients, 49 were found to have malignant tumors. Receiver operating characteristic analysis determined the lesion SUVmax value of 6.75 as the threshold for predicting malignant tumors. There were significant associations between malignant and benign upper urinary tract-occupying lesions and SUVmax of lesion (P&lt;0.001), lesion size (P&lt;0.001), and patient age (P=0.011). Multivariate analysis showed that SUVmax of lesion (P=0.042) and patient age (P=0.009) as independent predictors for differentiation of malignant from benign upper urinary tract-occupying lesions. There was a significant difference in tumor size between the positive (SUVmax &gt;6.75) and negative (SUVmax ≤6.75) PET groups in 38 of the 49 patients with malignant tumors.ConclusionThe SUVmax of lesion and patient age is associated with the nature of upper urinary tract-occupying lesions. F-18 FDG PET/CT may be useful to distinguish between malignant and benign upper urinary tract-occupying lesions and determine a suitable therapeutic strategy.


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