scholarly journals Imaging challenges of immunotherapy and targeted therapy in patients with brain metastases: response, progression, and pseudoprogression

2019 ◽  
Vol 22 (1) ◽  
pp. 17-30 ◽  
Author(s):  
Norbert Galldiks ◽  
Martin Kocher ◽  
Garry Ceccon ◽  
Jan-Michael Werner ◽  
Anna Brunn ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Brain Metastases ◽  
Treatment Response ◽  
Checkpoint Inhibitors ◽  
Imaging Techniques ◽  
Additional Information ◽  
Contrast Enhanced ◽  
Amino Acid Pet ◽  
Cancer Types ◽  
Induced Changes

Abstract The advent of immunotherapy using immune checkpoint inhibitors (ICIs) and targeted therapy (TT) has dramatically improved the prognosis of various cancer types. However, following ICI therapy or TT—either alone (especially ICI) or in combination with radiotherapy—imaging findings on anatomical contrast-enhanced MRI can be unpredictable and highly variable, and are often difficult to interpret regarding treatment response and outcome. This review aims at summarizing the imaging challenges related to TT and ICI monotherapy as well as combined with radiotherapy in patients with brain metastases, and to give an overview on advanced imaging techniques which potentially overcome some of these imaging challenges. Currently, major evidence suggests that imaging parameters especially derived from amino acid PET, perfusion-/diffusion-weighted MRI, or MR spectroscopy may provide valuable additional information for the differentiation of treatment-induced changes from brain metastases recurrence and the evaluation of treatment response.

scholarly journals OTHR-14. TREATMENT MONITORING OF IMMUNOTHERAPY AND TARGETED THERAPY USING FET PET IN PATIENTS WITH MELANOMA AND LUNG CANCER BRAIN METASTASES: INITIAL EXPERIENCES

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i21-i21
Author(s):  
Norbert Galldiks ◽  
Diana Abdulla ◽  
Matthias Scheffler ◽  
Viola Schweinsberg ◽  
Max Schlaak ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Brain Metastases ◽  
Treatment Response ◽  
Checkpoint Inhibitors ◽  
Response Assessment ◽  
Treatment Monitoring ◽  
Mri Findings ◽  
Fet Pet ◽  
Additional Information

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.

Imaging of Response to Radiosurgery and Immunotherapy in Brain Metastases: Quo Vadis?

2021 ◽  
Vol 23 (3) ◽  
Author(s):  
Norbert Galldiks ◽  
Jan-Michael Werner ◽  
Philipp Lohmann ◽  
Martin Kocher ◽  
Gereon R. Fink ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Imaging Techniques ◽  
Low Cost ◽  
Response Assessment ◽  
High Throughput Analysis ◽  
Number Of Patients ◽  
Study Results ◽  
Amino Acid Pet ◽  
Quo Vadis ◽  
Induced Changes

Abstract Purpose of Review This review presents an overview of how advanced imaging techniques may help to overcome shortcomings of anatomical MRI for response assessment in patients with brain metastases who are undergoing stereotactic radiosurgery, immunotherapy, or combinations thereof. Recent Findings Study results suggest that parameters derived from amino acid PET, diffusion- and perfusion-weighted MRI, MR spectroscopy, and newer MRI methods are particularly helpful for the evaluation of the response to radiosurgery or checkpoint inhibitor immunotherapy and provide valuable information for the differentiation of radiotherapy-induced changes such as radiation necrosis from brain metastases. The evaluation of these imaging modalities is also of great interest in the light of emerging high-throughput analysis methods such as radiomics, which allow the acquisition of additional data at a low cost. Summary Preliminary results are promising and should be further evaluated. Shortcomings are different levels of PET and MRI standardization, the number of patients enrolled in studies, and the monocentric and retrospective character of most studies.

Treatment monitoring of immunotherapy and targeted therapy using FET PET in patients with melanoma and lung cancer brain metastases: Initial experiences.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13525-e13525 ◽  
Author(s):  
Norbert Galldiks ◽  
Diana S.Y. Abdulla ◽  
Matthias Scheffler ◽  
Viola Schweinsberg ◽  
Max Schlaak ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Brain Metastases ◽  
Treatment Response ◽  
Checkpoint Inhibitors ◽  
Response Assessment ◽  
Treatment Monitoring ◽  
Mri Findings ◽  
Fet Pet

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.

scholarly journals CMET-23. IMPACT OF SYSTEMIC THERAPY IN MELANOMA BRAIN METASTASIS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi56-vi56
Author(s):  
Soumya Sagar ◽  
Adam Lauko ◽  
Addison Barnett ◽  
Wei (Auston) Wei ◽  
Samuel Chao ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Systemic Therapy ◽  
Checkpoint Inhibitors ◽  
Care Center ◽  
Performance Status ◽  
Tertiary Care ◽  
P Value ◽  
Surgical Removal

Abstract BACKGROUND Melanoma is the third most common malignancy that results in brain metastasis and is associated with a median overall survival (OS) of approximately 9 months. In recent years, management of melanoma brain metastases (MBM) by surgery and radiation [stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT)] has been bolstered by targeted therapy and immune checkpoint inhibitors (ICI). METHODS 351 patients, treated for MBM at our tertiary care center from 2000–2018, were grouped into: received chemotherapy, ICI, or targeted therapy. 34% of patients treated with ICI had received other systemic therapies as well as part of their management. OS was calculated from the date of diagnosis of the brain metastases. The Kaplan Meier analysis was utilized to determine median OS and difference in OS was determined by utilizing the Cox proportional hazard model. RESULTS The median survival after the diagnosis of brain metastasis was 10.4, 11.96, and 7.06 months in patients who received ICI, chemotherapy and targeted therapy respectively. A multivariate model was developed including the type of systemic therapy, presence of extracranial metastases, age, KPS and number of intracranial lesions. 114 patients underwent SRS alone, 56 underwent SRS and WBRT, 43 underwent SRS and surgical removal, 28 had surgical removal, SRS and WBRT, and 78 had no intracranial therapy. Compared to patients who received chemotherapy, patients who received immunotherapy had a hazard ratio, HR = 0.628 (confidence interval = 0.396 – 0.994, p-value = 0.047). Presence of EC metastases (HR= 1.25, p-value < .001), lower KPS (HR = .97, p-value < .0001) and multiple brain lesions (HR = 1.117, p-value < .0001) were associated with significantly worse OS. CONCLUSIONS Addition of ICI significantly improves the OS in MBM compared to chemotherapy. Lower performance status, multiple brain metastases, and EC metastases are associated with poor OS.

scholarly journals 32. TREATMENT MONITORING OF IMMUNOTHERAPY AND TARGETED THERAPY USING AMINO ACID PET IN PATIENTS WITH BRAIN METASTASES

2020 ◽  
Vol 2 (Supplement_2) ◽  
pp. ii5-ii6
Author(s):  
Norbert Galldiks ◽  
Diana Abdulla ◽  
Matthias Scheffler ◽  
Fabian Wolpert ◽  
Jan-Michael Werner ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Amino Acid ◽  
Brain Metastases ◽  
Response Assessment ◽  
Diagnostic Value ◽  
Treatment Monitoring ◽  
Fet Pet ◽  
Time To Peak ◽  
Amino Acid Pet

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.

scholarly journals THER-02. IMPACT OF SYSTEMIC THERAPY IN MELANOMA BRAIN METASTASIS

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i11-i11
Author(s):  
Soumya Sagar ◽  
Adam Lauko ◽  
Addison Barnett ◽  
Wei Wei ◽  
Samuel Chao ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Systemic Therapy ◽  
Checkpoint Inhibitors ◽  
Care Center ◽  
Tertiary Care ◽  
P Value ◽  
Surgical Removal ◽  
Melanoma Brain Metastasis

Abstract BACKGROUND: Melanoma brain metastasis is associated with a median overall survival (OS) of approximately 9 months. In recent years, management of melanoma brain metastases (MBM) by surgery and radiation [stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT)] has been bolstered by targeted therapy and immune checkpoint inhibitors (ICI). METHODS: 351 patients, who underwent treatment for MBM at our tertiary care center from 2000 to 2018, were grouped into those that received chemotherapy, ICI, or targeted therapy. Thirty-four percent of patients treated with ICI had received other systemic therapies as well as part of their management. OS was calculated from the date of diagnosis of the brain metastases. The Kaplan Meier analysis was utilized to determine median OS and difference in OS was determined by utilizing the Cox proportional hazard model. RESULTS: The median survival after the diagnosis of brain metastasis was 10.4, 11.96, and 7.06 months in patients who received ICI, chemotherapy and targeted therapy respectively. A multivariate model was developed including the type of systemic therapy, presence of extracranial metastases, age, KPS and number of intracranial lesions. 114 patients underwent SRS alone, 56 underwent SRS and WBRT, 43 underwent SRS and surgical removal, 28 had surgical removal, SRS and WBRT, and 78 had no intracranial therapy. Compared to patients who received chemotherapy, patients who received immunotherapy had a hazard ratio, HR = 0.628 (confidence interval = 0.396 – 0.994, p-value = 0.047). Presence of EC metastases (HR= 1.25, p-value &lt; .001), lower KPS (HR = .97, p-value &lt; .0001) and multiple brain lesions (HR = 1.117, p-value &lt; .0001) were associated with significantly worse OS. CONCLUSIONS: Addition of ICI significantly improves the OS in MBM compared to chemotherapy. Lower performance status, multiple brain metastases, and EC metastases are associated with poor OS.

OS03.3.A Characterization of long-term metabolic changes of irradiated brain metastases using serial dynamic FET PET imaging

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii6-ii6
Author(s):  
N Galldiks ◽  
G Stoffels ◽  
J Werner ◽  
E K Bauer ◽  
C Baues ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Checkpoint Inhibitors ◽  
Mri Findings ◽  
Fet Pet ◽  
Radiation Induced ◽  
Induced Changes ◽  
Pet Scans ◽  
Dynamic Fet Pet

Abstract BACKGROUND In the present study, we characterized the long-term metabolic changes of brain metastases irradiated with stereotactic radiosurgery (SRS) by sequential dynamic PET imaging using the radiolabeled amino acid O-(2-[18F]-fluoroethyl)-L-tyrosine (FET). We hypothesized that this approach is of considerable clinical value to diagnose delayed radiation-induced changes. MATERIAL AND METHODS From 2010–2021, we retrospectively identified patients with brain metastases from solid extracranial primary tumors who (i) were treated with SRS with or without concurrent immunotherapy using checkpoint inhibitors, (ii) had equivocal or progressive MRI findings after SRS, and (iii) subsequently underwent at least two additional dynamic FET PET scans during follow-up for long-term evaluation. Mean tumor-to-brain ratios (TBR) and the dynamic FET PET parameter time-to-peak were obtained. Diagnostic performances were calculated using receiver operating characteristic curve analyses. Diagnoses were confirmed histologically or clinicoradiologically. RESULTS We identified 36 patients with 98 FET PET scans (median number, 3; range, 2–6). Concurrent to SRS, 8 patients (22%) were treated with checkpoint inhibitors. Following SRS, suspicious MRI findings occurred after a median time of 11 months (range, 2–64 months). Subsequently, FET PET scans were acquired over a median period of 13 months (range, 5–60 months). The overall median follow-up time was 26 months (range, 8–101 months). Twenty-one patients (58%) had delayed radiation-induced changes. TBRs calculated from the last available FET PET scan showed the highest accuracy (92%) to identify delayed radiation-induced changes (threshold, 1.95; P&lt;0.001). CONCLUSION FET PET has a high diagnostic accuracy for characterizing the long-term changes of irradiated brain metastases.

NIMG-06. CHARACTERIZATION OF LONG-TERM METABOLIC CHANGES OF IRRADIATED BRAIN METASTASES USING SERIAL DYNAMIC FET PET IMAGING

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi128-vi128
Author(s):  
Norbert Galldiks ◽  
Gabriele Stoffels ◽  
Jan Werner ◽  
Elena Bauer ◽  
Christian Baues ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Checkpoint Inhibitors ◽  
Mri Findings ◽  
Fet Pet ◽  
Radiation Induced ◽  
Induced Changes ◽  
Pet Scans ◽  
Dynamic Fet Pet

Abstract BACKGROUND In the present study, we characterized the long-term metabolic changes of brain metastases irradiated with stereotactic radiosurgery (SRS) by sequential dynamic PET imaging using the radiolabeled amino acid O-(2-[18F]-fluoroethyl)-L-tyrosine (FET). We hypothesized that this approach is of considerable clinical value to diagnose delayed radiation-induced changes. PATIENTS AND METHODS From 2010-2021, we retrospectively identified patients with brain metastases from solid extracranial primary tumors who (i) were treated with SRS with or without concurrent immunotherapy using checkpoint inhibitors, (ii) had equivocal or progressive MRI findings after SRS, and (iii) subsequently underwent at least two additional dynamic FET PET scans during follow-up for long-term evaluation. Mean tumor-to-brain ratios (TBR) and the dynamic FET PET parameter time-to-peak were obtained. Diagnostic performances were calculated using receiver operating characteristic curve analyses. Diagnoses were confirmed histologically or clinicoradiologically. RESULTS We identified 36 patients with 98 FET PET scans (median number, 3; range, 2-6). Concurrent to SRS, 8 patients (22%) were treated with checkpoint inhibitors. Following SRS, suspicious MRI findings occurred after a median time of 11 months (range, 2-64 months). Subsequently, FET PET scans were acquired over a median period of 13 months (range, 5-60 months). The overall median follow-up time was 26 months (range, 8-101 months). Twenty-one patients (58%) had delayed radiation-induced changes. TBRs calculated from the last available FET PET scan showed the highest accuracy (92%) to identify delayed radiation-induced changes (threshold, 1.95; P&lt; 0.001). CONCLUSIONS FET PET has a high diagnostic accuracy for characterizing the long-term changes of irradiated brain metastases.

Dynamic contrast-enhanced MR imaging pharmacokinetic parameters as predictors of treatment response of brain metastases in patients with lung cancer

2017 ◽  
Vol 27 (9) ◽  
pp. 3733-3743 ◽  
Author(s):  
Grégory Kuchcinski ◽  
Emilie Le Rhun ◽  
Alexis B. Cortot ◽  
Elodie Drumez ◽  
Romain Duhal ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Mr Imaging ◽  
Brain Metastases ◽  
Treatment Response ◽  
Pharmacokinetic Parameters ◽  
Dynamic Contrast Enhanced ◽  
Contrast Enhanced
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