scholarly journals Treatment Monitoring of Immunotherapy and Targeted Therapy using 18F-FET PET in Patients with Melanoma and Lung Cancer Brain Metastases: Initial Experiences

2020 ◽  
pp. jnumed.120.248278
Author(s):  
Norbert Galldiks ◽  
Diana SY Abdulla ◽  
Matthias Scheffler ◽  
Fabian Wolpert ◽  
Jan-Michael Werner ◽  
...  
2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13525-e13525 ◽  
Author(s):  
Norbert Galldiks ◽  
Diana S.Y. Abdulla ◽  
Matthias Scheffler ◽  
Viola Schweinsberg ◽  
Max Schlaak ◽  
...  

e13525 Background: Due to the lack of specificity of contrast-enhanced (CE) MRI, the differentiation of progression from pseudoprogression (PsP) following immunotherapy using checkpoint inhibitors (IT) or targeted therapy (TT) may be challenging, especially when IT or TT is applied in combination with radiotherapy (RT). Similarly, for response assessment of RT plus IT or targeted therapy (TT), the use of CE MRI alone may also be difficult. For problem solving, the integration of advanced imaging methods may add valuable information. Here, we evaluated the value of amino acid PET using O-(2-[18F]fluoroethyl)-L-tyrosine (FET) in comparison to CE MRI for these important clinical situations in patients with brain metastases (BM) secondary to malignant melanoma (MM) and non-small cell lung cancer (NSCLC). Methods: From 2015-2018, we retrospectively identified 31 patients with 74 BM secondary to MM (n = 20 with 42 BM) and NSCLC (n = 11 with 32 BM) who underwent 52 FET PET scans during the course of disease. All patients had RT prior to IT or TT initiation (61%) or RT concurrent to IT or TT (39%). In 13 patients, FET PET was performed for treatment response assessment of IT or TT using baseline and follow-up scans (median time between scans, 4.2 months). In the remaining 18 patients, FET PET was used for the differentiation of progression from PsP related to RT plus IT or TT. In all BM, metabolic activity on FET PET was evaluated by calculation of tumor/brain ratios. FET PET imaging findings were compared to CE MRI and correlated to the clinical follow-up or neuropathological findings after neuroimaging. Results: In 4 of 13 patients (31%), FET PET provided additional information for treatment response evaluation beyond the information provided by CE MRI alone. Furthermore, responding patients on FET PET had a median stable clinical follow-up of 10 months. In 10 of 18 patients (56%) with CE MRI findings suggesting progression, FET PET detected PsP. In 9 of these 10 patients, PsP was confirmed by a median stable clinical follow-up of 11 months. Conclusions: FET PET may add valuable information for treatment monitoring in individual BM patients undergoing RT in combination with IT or TT.


2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i21-i21
Author(s):  
Norbert Galldiks ◽  
Diana Abdulla ◽  
Matthias Scheffler ◽  
Viola Schweinsberg ◽  
Max Schlaak ◽  
...  

Abstract BACKGROUND: Due to the lack of specificity of contrast-enhanced (CE) MRI, both the response assessment and differentiation of progression from pseudoprogression (PsP) following immunotherapy using checkpoint inhibitors (ICI) or targeted therapy (TT) may be challenging, especially when ICI or TT is applied in combination with radiotherapy (RT). Here, we evaluated the value of amino acid PET using O-(2-[18F]fluoroethyl)-L-tyrosine (FET) as a problem-solving tool in comparison to CE-MRI in patients with brain metastases (BM) secondary to malignant melanoma (MM) and NSCLC. METHODS: We retrospectively identified 31 patients with 74 BM secondary to MM (n=20 with 42 BM) and NSCLC (n=11 with 32 BM) who underwent 52 FET-PET scans during the course of disease. All patients had RT prior to ICI or TT initiation (61%) or RT concurrent to ICI or TT (39%). In 13 patients, FET-PET was performed for treatment response assessment of ICI or TT using baseline and follow-up scans (median time between scans, 4.2 months). In the remaining 18 patients, FET-PET was used for the differentiation of progression from PsP related to RT plus ICI or TT. In all BM, metabolic activity on FET-PET was evaluated by calculation of tumor/brain ratios. FET-PET imaging findings were compared to CE-MRI and correlated to the clinical follow-up or neuropathological findings after neuroimaging. RESULTS: In 4 of 13 patients (31%), FET-PET provided additional information for treatment response evaluation beyond the information provided by CE-MRI alone. Furthermore, responding patients on FET-PET had a median stable clinical follow-up of 10 months. In 10 of 18 patients (56%) with CE-MRI findings suggesting progression, FET-PET detected PsP. In 9 of these 10 patients, PsP was confirmed by a median stable clinical follow-up of 11 months. CONCLUSIONS: FET-PET may add valuable information for treatment monitoring in individual BM patients undergoing RT in combination with ICI or TT.


2020 ◽  
Vol 2 (Supplement_2) ◽  
pp. ii5-ii6
Author(s):  
Norbert Galldiks ◽  
Diana Abdulla ◽  
Matthias Scheffler ◽  
Fabian Wolpert ◽  
Jan-Michael Werner ◽  
...  

Abstract PURPOSE Recently, the RANO group has analyzed the additional diagnostic value of amino acid PET in patients with primary and secondary brain tumors and recommended the use of this imaging technique in addition to conventional MRI. Here, we investigated the value of PET using the radiolabled amino acid O-(2-[18F]fluoroethyl)-L-tyrosine (FET) for treatment monitoring of immune checkpoint inhibition (ICI) or targeted therapy (TT) alone or in combination with radiotherapy in patients with brain metastases (BM) since contrast-enhanced MRI often remains inconclusive. METHODS We retrospectively identified 40 patients with 107 BM secondary to melanoma (n=29 with 75 BM) or non-small cell lung cancer (n=11 with 32 BM) treated with ICI or TT who had FET PET (n=60 scans) for treatment monitoring from 2015–2019. The majority of patients (n=37; 92.5%) had radiotherapy during the course of disease. In 27 patients, FET PET was used for the differentiation of treatment-related changes from BM relapse following ICI or TT. In 13 patients, FET PET was performed for response assessment to ICI or TT using baseline and follow-up scans (median time between scans, 4.2 months). In all lesions, static and dynamic FET PET parameters were obtained (i.e., mean tumour-to-brain ratios (TBR), time-to-peak values). Diagnostic accuracies of PET parameters were evaluated by receiver-operating-characteristic analyses using the clinical follow-up or neuropathological findings as reference. RESULTS A TBR threshold of 1.95 differentiated BM relapse from treatment-related changes with an accuracy of 85% (P=0.003). Metabolic Responders to ICI or TT on FET PET had a significantly longer stable follow-up (threshold of TBR reduction relative to baseline, ≥10%; accuracy, 82%; P=0.004). Furthermore, at follow-up, time-to-peak values in metabolic responders increased significantly (P=0.019). CONCLUSIONS FET PET may add valuable information for treatment monitoring in BM patients treated with ICI or TT.


2019 ◽  
Vol 30 ◽  
pp. ii64-ii65
Author(s):  
D.S. Abdulla ◽  
M. Ruge ◽  
M. Scheffler ◽  
L. Nogova ◽  
S. Koleczko ◽  
...  

2015 ◽  
Vol 17 (7) ◽  
pp. 1022-1028 ◽  
Author(s):  
Tony J. C. Wang ◽  
Shumaila Saad ◽  
Yasir H. Qureshi ◽  
Ashish Jani ◽  
Tavish Nanda ◽  
...  

2020 ◽  
Vol 45 (2) ◽  
pp. 113-117 ◽  
Author(s):  
Dilara Akhoundova ◽  
Stefanie Hiltbrunner ◽  
Cäcilia Mader ◽  
Robert Förster ◽  
Johannes Kraft ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3668
Author(s):  
Anna Cho ◽  
Helena Untersteiner ◽  
Dorian Hirschmann ◽  
Abdallah Shaltout ◽  
Philipp Göbl ◽  
...  

The combination of Gamma Knife radiosurgery (GKRS) and systemic immunotherapy (IT) or targeted therapy (TT) is a novel treatment method for brain metastases (BMs) in non-small cell lung cancer (NSCLC). To elucidate the safety and efficacy of concomitant IT or TT on the outcome after GKRS, 496 NSCLC patients with BMs, who were treated with GKRS were retrospectively reviewed. The median time between the initial lung cancer diagnosis and the diagnosis of brain metastases was one month. The survival after the initial BM diagnosis was significantly longer than the survival predicted by prognostic BM scores. After the first Gamma Knife radiosurgery treatment (GKRS1), the estimated median survival was 9.9 months (95% CI = 8.3–11.4). Patients with concurrent IT or TT presented with a significantly longer survival after GKRS1 than patients without IT or TT (p < 0.001). These significant differences in the survival were also apparent among the four treatment groups and remained significant after adjustment for Karnofsky performance status scale (KPS), recursive partitioning analysis (RPA) class, sex, and multiple BMs. About half of all our patients (46%) developed new distant BMs after GKRS1. Of note, no statistically significant differences in the occurrence of radiation reaction, radiation necrosis, or intralesional hemorrhage in association with IT or TT at or after GKRS1 were observed. In NSCLC-BM patients, the concomitant use of GKRS and IT or TT showed an increase in overall survival without increased complications related to GKRS. Therefore, the combined treatment with GKRS and IT or TT seems to be a safe and powerful treatment option and emphasizes the role of radiosurgery in modern BM treatment.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20604-e20604 ◽  
Author(s):  
Robert H. Press ◽  
Xinyan Zhang ◽  
Richard John Cassidy ◽  
Matthew Jeffrey Ferris ◽  
Jim Zhong ◽  
...  

e20604 Background: Historically, survival in patients (pts) with NSCLC brain metastases (BM) is poor, however, improved systemic therapies are now available including targeted therapies and immunotherapy. We sought to evaluate the prevalence of genetic alterations in pts with BM from non-squamous (NS) lung cancer, and to determine clinical outcomes in the modern era. Methods: With IRB approval, pts with BM from NS-NSCLC from 1/2010-1/2016 with genetic testing were captured and retrospectively reviewed. Snapshot genotyping was performed prior to 1/2014, after which Next Generation Sequencing was utilized, along with FISH lung cancer panel. Genes examined included: EGFR, ALK, RET, ROS1, TP53, KRAS, NRAS, MET, PTEN, BRAF, FBXW7, MAP2K1, APC, PIK3CA, CTNNB1, and SMAD4. Univariable and multivariable analysis (MVA) were utilized to assess factors associated with overall survival (OS). Results: 92 pts were included. Median number of BM was 4 (range 1-45). Median age was 64 (32-90 years). 59.8% were male. 38% received targeted therapy, 11% received immunotherapy, and 70% received conventional chemotherapy. 52.2% and 47.8% received whole brain radiotherapy and stereotactic radiosurgery, respectively. Median OS from first brain radiotherapy (RT) was 10.7 months (0.1-56.4). EGFR mutation, ALK fusion, ROS1 rearrangement, and RET rearrangement occurred in 27.5%, 5.2%, 1.7%, and 0% of pts. EGFR L858 and EGFR T790 mutations occurred in 19.2% and 2.7% of all pts. TP53, KRAS, and NRAS mutations occurred in 63.9%, 28.8% and 7% of pts. All other mutations had an incidence of less than 3%. On MVA, targeted therapy (HR 0.43 95% CI 0.22-0.86), immunotherapy (HR 0.04 95% CI 0.01-0.3), surgical resection (HR 0.38 95% CI 0.18-0.81), and ECOG performance status (0.23 95% CI 0.1-0.54) were associated with improved OS. No specific genetic aberration, RT modality, or number of BM was associated with OS. Conclusions: In pts with BM from NS-NSCLC, the most common molecular aberrations include TP53, EGFR, and KRAS mutations. Treatment with brain RT and modern systemic therapies yields a median survival greater than ten months. The use of targeted therapy or immunotherapy was associated with increased OS.


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