Circulating Tumor DNA Analysis and Functional Imaging Provide Complementary Approaches for Comprehensive Disease Monitoring in Metastatic Melanoma

2017 ◽  
pp. 1-14 ◽  
Author(s):  
Stephen Q. Wong ◽  
Jeanette M. Raleigh ◽  
Jason Callahan ◽  
Ismael A. Vergara ◽  
Sarah Ftouni ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Metastatic Melanoma ◽  
Fdg Pet ◽  
Disease Burden ◽  
Circulating Tumor Dna ◽  
Tumor Burden ◽  
Disease Monitoring ◽  
Ctdna Analysis ◽  
Mutant Braf

Purpose Circulating tumor DNA (ctDNA) allows noninvasive disease monitoring across a range of malignancies. In metastatic melanoma, the extent to which ctDNA reflects changes in metabolic disease burden assessed by 18F-labeled fluorodeoxyglucose positron emission tomography (FDG-PET) is unknown. We assessed the role of ctDNA analysis in combination with FDG-PET to monitor tumor burden and genomic heterogeneity throughout treatment. Patients and Methods We performed a comprehensive analysis of serial ctDNA and FDG-PET in 52 patients who received systemic therapy for metastatic melanoma. Next-generation sequencing and digital polymerase chain reaction were used to analyze plasma samples from the cohort. Results ctDNA levels were monitored across patients with mutant BRAF, NRAS, and BRAF/NRAS wild type disease. Mutant BRAF and NRAS ctDNA levels correlated closely with changes in metabolic disease burden throughout treatment. TERT promoter mutant ctDNA levels also paralleled changes in tumor burden, which provide an alternative marker for disease monitoring. Of note, subcutaneous and cerebral disease sites were not well represented in plasma. Early changes in ctDNA and metabolic disease burden were important indicators of treatment response. Patients with an early decrease in ctDNA post-treatment had improved progression-free survival compared with patients in whom ctDNA levels remained unchanged or increased over time (hazard ratio, 2.6; P = .05). ctDNA analysis contributed key molecular information through the identification of putative resistance mechanisms to targeted therapy. A detailed comparison of the genomic architecture of plasma and multiregional tumor biopsy specimens at autopsy revealed the ability of ctDNA to comprehensively capture genomic heterogeneity across multiple disease sites. Conclusion The findings highlight the powerful role of ctDNA in metastatic melanoma as a complementary modality to functional imaging that allows real-time monitoring of both tumor burden and genomic changes throughout therapy.

scholarly journals Detection of Circulating Tumor DNA in Patients With Leiomyosarcoma With Progressive Disease

2019 ◽  
pp. 1-11 ◽  
Author(s):  
Matthew L. Hemming ◽  
Kelly Klega ◽  
Justin Rhoades ◽  
Gavin Ha ◽  
Kate E. Acker ◽  
...  
Keyword(s):  
Disease Progression ◽  
Tumor Size ◽  
Disease Burden ◽  
Progressive Disease ◽  
Circulating Tumor Dna ◽  
Tumor Burden ◽  
Blood Draw ◽  
Cell Free Dna ◽  
Free Dna ◽  
Tumor Dna

Purpose Leiomyosarcoma (LMS) is a soft-tissue sarcoma characterized by multiple copy number alterations (CNAs) and without common recurrent single-nucleotide variants. We evaluated the feasibility of detecting circulating tumor DNA (ctDNA) with next-generation sequencing in a cohort of patients with LMS whose tumor burden ranged from no evidence of disease to metastatic progressive disease. Patients and Methods We evaluated cell-free DNA in plasma samples and paired genomic DNA from resected tumors from patients with LMS by ultra-low passage whole-genome sequencing. Sequencing reads were aligned to the human genome and CNAs that were identified in cell-free DNA and tumor DNA by ichorCNA software to determine the presence of ctDNA. Clinical data were reviewed to assess disease burden and clinicopathologic features. Results We identified LMS ctDNA in 11 (69%) of 16 patients with disease progression and total tumor burden greater than 5 cm. Sixteen patients with stable disease or low disease burden at the time of blood draw were found to have no detectable ctDNA. Higher ctDNA fraction of total cell-free DNA was associated with increasing tumor size and disease progression. Conserved CNAs were found between primary tumors and ctDNA in each case, and recurrent CNAs were found across LMS samples. ctDNA levels declined after resection of progressive disease in one case and became detectable upon disease relapse in another individual patient. Conclusion These results suggest that ctDNA, assayed by a widely available sequencing approach, may be useful as a biomarker for a subset of patients with uterine and extrauterine LMS. Higher levels of ctDNA correlate with tumor size and disease progression. Liquid biopsies may assist in guiding treatment decisions, monitoring response to systemic therapy, surveying for disease recurrence, and differentiating benign and malignant smooth muscle tumors.

The role of interim 18F-FDG PET/CT in prediction of response to ipilimumab treatment in metastatic melanoma

2018 ◽  
Vol 45 (8) ◽  
pp. 1289-1296 ◽  
Author(s):  
Christos Sachpekidis ◽  
Hoda Anwar ◽  
Julia Winkler ◽  
Annette Kopp-Schneider ◽  
Lionel Larribere ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Fdg Pet ◽  
Prediction Of Response ◽  
Pet Ct ◽  
18F Fdg ◽  
Fdg Pet Ct

Role of 18 F-FDG PET in demonstrating disease burden in patients with tuberculous meningitis

2016 ◽  
Vol 370 ◽  
pp. 196-200 ◽  
Author(s):  
Sanjay Gambhir ◽  
Mritunjai Kumar ◽  
Mudalsha Ravina ◽  
Sanjeev Kumar Bhoi ◽  
Jayantee Kalita ◽  
...  
Keyword(s):  
Tuberculous Meningitis ◽  
Fdg Pet ◽  
Disease Burden

scholarly journals The Emerging Role of Circulating Tumor DNA in the Management of Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3813
Author(s):  
Mira Shoukry ◽  
Sacha Broccard ◽  
Jamie Kaplan ◽  
Emmanuel Gabriel
Keyword(s):  
Breast Cancer ◽  
Treatment Approach ◽  
Circulating Tumor Dna ◽  
Liquid Biopsies ◽  
Novel Technologies ◽  
Potential Biomarker ◽  
Ctdna Analysis ◽  
Tumor Dna ◽  
Current Standards

With the incidence of breast cancer steadily rising, it is important to explore novel technologies that can allow for earlier detection of disease as well more a personalized and effective treatment approach. The concept of “liquid biopsies” and the data they provide have been increasingly studied in the recent decades. More specifically, circulating tumor DNA (ctDNA) has emerged as a potential biomarker for various cancers, including breast cancer. While methods such as mammography and tissue biopsies are the current standards for the detection and surveillance of breast cancer, ctDNA analysis has shown some promise. This review discusses the versatility of ctDNA by exploring its multiple emerging uses for the management of breast cancer. Its efficacy is also compared to current biomarkers and technologies.

Heterogeneity of FDG-PET response to GSK2118436, an inhibitor of oncogenic mutant BRAF-kinase in BRAF-mutant metastatic melanoma.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. 8539-8539 ◽  
Author(s):  
M. S. Carlino ◽  
C. A. Saunders ◽  
V. Gebski ◽  
A. M. Menzies ◽  
B. Ma ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Fdg Pet ◽  
Braf Mutant ◽  
Mutant Braf

The role of F-18 FDG PET/CT in evaluating the impact of HIV infection on tumor burden and therapy outcome in patients with Hodgkin lymphoma

2017 ◽  
Vol 44 (12) ◽  
pp. 2025-2033 ◽  
Author(s):  
Ismaheel O. Lawal ◽  
Nozipho E. Nyakale ◽  
Lerwine M. Harry ◽  
Moshe R. Modiselle ◽  
Alfred O. Ankrah ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Hodgkin Lymphoma ◽  
Fdg Pet ◽  
Tumor Burden ◽  
Therapy Outcome ◽  
Pet Ct ◽  
Fdg Pet Ct ◽  
The Impact

scholarly journals Quantitative Dynamic 18F-FDG PET/CT in Survival Prediction of Metastatic Melanoma under PD-1 Inhibitors

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1019
Author(s):  
Christos Sachpekidis ◽  
Jessica C. Hassel ◽  
Annette Kopp-Schneider ◽  
Uwe Haberkorn ◽  
Antonia Dimitrakopoulou-Strauss
Keyword(s):  
Metastatic Melanoma ◽  
Fdg Pet ◽  
Whole Body ◽  
Conventional Imaging ◽  
Interim Pet ◽  
Pet Ct ◽  
Predictive Role ◽  
18F Fdg ◽  
Fdg Pet Ct

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.

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

2020 ◽  
Author(s):  
Christos Sachpekidis ◽  
Annette Kopp-Schneider ◽  
Leyun Pan ◽  
Dimitrios Papamichail ◽  
Uwe Haberkorn ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Metastatic Melanoma ◽  
Fdg Pet ◽  
Metabolic Response ◽  
European Organization ◽  
Interim Pet ◽  
Pet Ct ◽  
Eortc Criteria ◽  
Significant Difference ◽  
Fdg Pet Ct

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.

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