Delayed contrast and multiparametric MRI for treatment response assessment in brain metastases following stereotactic radiosurgery

Abstract Aims Following stereotactic radiosurgery (SRS), brain metastases can increase in size in up to a third of cases. Conventional magnetic resonance imaging (MRI) has a limited role to distinguish between tumour recurrence and SRS-induced changes, which can impact patient management. Delayed contrast MRI treatment response assessment maps (TRAM) use the principle of contrast clearance seen in other tumours, where high vascularity shows a rapid rise in contrast as well as rapid clearance, whereas areas of damaged or low vascularity show accumulation of contrast. We aimed to assess the ability of delayed contrast MRI and multiparametric MRI techniques of diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI) and MR spectroscopy (MRS) to distinguish between radiation-related effects and tumour tissue, as these techniques assess tissue physiological and metabolic information. Method A retrospective review was performed on 23 patients who had delayed contrast and multiparametric MRI between October 2018 to April 2020. Studies were restricted to cases with brain metastases enlarging post-SRS with uncertainty at the MDT meeting regarding progression or treatment-related change, impacting the patient’s management. MRI was performed at 3T including DWI, PWI, MRS with short and intermediate echo times, and 3D T1 MPRAGE at 3-5, 20-30 and 70-90 minutes after administration of intravenous contrast. Contrast clearance analysis was performed by selecting an enhancing region of interest (ROI), measuring signal intensities at the three different timepoints and taking apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) values from the ROI. Choline/Creatine values were calculated from a single-voxel (10 mm isotropic) encompassing the entire contrast-enhancing lesion. Outcome was established from MRI follow-up at 6 months, with a stable or responding lesion considered treatment-related changes and increase considered progression. Results Across 23 patients, 24 metastases were assessed. Two patients were excluded as appropriate follow-up was not available. Sites of primary tumours included breast (n=8), lung (n=6), melanoma (n=4), neuroendocrine tumour from the lung (n=2) and renal cell carcinoma (n=2). Mean age was 56 years and 50% were female. In this cohort, 59% (n=13) were classified as having radiation-related changes on follow-up. Delayed MRI contrast clearance between the 3-5 and 70-90 minute imaging was significantly higher in cases of progression (23.6% vs. 2.5% decrease, p<0.05), as were the rCBV and Cho/Cr ratio (rCBV 3.1 vs. 1.5 and Cho/Cr ratio 2.3 vs. 1.4, p<0.05). Accuracy, sensitivity and specificity of using TRAM alone (contrast clearance decrease of >0%) for progression was 63%/100%/38%, PWI alone (rCBV cut-off 2.0) yielded results of 77%/75%/79% and for both Cho/Cr ratio alone (cut-off 1.8) and combined with TRAM, it was 90%/88%/92%. Neuroradiologist assessment of all techniques was 95%/100%/92%. Conclusion This study shows the effectiveness of delayed contrast and multiparametric MRI for treatment response assessment in patients with brain metastases treated by SRS in clinical practice. Although a delayed contrast MRI study is a very sensitive tool for detecting tumour progression, it lacks specificity. The accuracy of differentiating between tumour and treatment-related effects increases when delayed contrast MRI is used in combination with other advanced techniques such as MRS. By combining all these techniques, neuroradiologists had the highest accuracy, sensitivity and specificity for detecting progression in post-SRS brain metastases.

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

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz014.091 ◽

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.

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Automatic Segmentation of Metastatic Breast Cancer Lesions on 18F-FDG PET/CT Longitudinal Acquisitions for Treatment Response Assessment

Cancers ◽

10.3390/cancers14010101 ◽

2021 ◽

Vol 14 (1) ◽

pp. 101

Author(s):

Noémie Moreau ◽

Caroline Rousseau ◽

Constance Fourcade ◽

Gianmarco Santini ◽

Aislinn Brennan ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Treatment Response ◽

Automatic Segmentation ◽

Metastatic Breast ◽

Response Assessment ◽

Imaging Biomarkers ◽

Pet Ct ◽

Treatment Response Assessment

Metastatic breast cancer patients receive lifelong medication and are regularly monitored for disease progression. The aim of this work was to (1) propose networks to segment breast cancer metastatic lesions on longitudinal whole-body PET/CT and (2) extract imaging biomarkers from the segmentations and evaluate their potential to determine treatment response. Baseline and follow-up PET/CT images of 60 patients from the EPICUREseinmeta study were used to train two deep-learning models to segment breast cancer metastatic lesions: One for baseline images and one for follow-up images. From the automatic segmentations, four imaging biomarkers were computed and evaluated: SULpeak, Total Lesion Glycolysis (TLG), PET Bone Index (PBI) and PET Liver Index (PLI). The first network obtained a mean Dice score of 0.66 on baseline acquisitions. The second network obtained a mean Dice score of 0.58 on follow-up acquisitions. SULpeak, with a 32% decrease between baseline and follow-up, was the biomarker best able to assess patients’ response (sensitivity 87%, specificity 87%), followed by TLG (43% decrease, sensitivity 73%, specificity 81%) and PBI (8% decrease, sensitivity 69%, specificity 69%). Our networks constitute promising tools for the automatic segmentation of lesions in patients with metastatic breast cancer allowing treatment response assessment with several biomarkers.

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International working group for myelofibrosis research and treatment response assessment and long-term follow-up of 50 myelofibrosis patients treated with thalidomide-prednisone based regimens

American Journal of Hematology ◽

10.1002/ajh.21892 ◽

2010 ◽

Vol 86 (1) ◽

pp. 96-98 ◽

Cited By ~ 31

Author(s):

Prakash Thapaliya ◽

Ayalew Tefferi ◽

Animesh Pardanani ◽

David P. Steensma ◽

John Camoriano ◽

...

Keyword(s):

Treatment Response ◽

Working Group ◽

Response Assessment ◽

International Working Group ◽

Long Term Follow Up ◽

Treatment Response Assessment

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

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e13525 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e13525-e13525 ◽

Cited By ~ 3

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.

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Treatment Response Assessment Maps to Delineate Necrosis From Tumor After Stereotactic Radiation in Brain Metastases

Case Medical Research ◽

10.31525/ct1-nct04033497 ◽

2019 ◽

Author(s):

Keyword(s):

Brain Metastases ◽

Treatment Response ◽

Response Assessment ◽

Stereotactic Radiation ◽

Treatment Response Assessment

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The Value of FDG PET/CT in Treatment Response Assessment, Follow-Up, and Surveillance of Lung Cancer

American Journal of Roentgenology ◽

10.2214/ajr.16.16532 ◽

2017 ◽

Vol 208 (2) ◽

pp. 420-433 ◽

Cited By ~ 38

Author(s):

Sara Sheikhbahaei ◽

Esther Mena ◽

Anusha Yanamadala ◽

Siddaling Reddy ◽

Lilja B. Solnes ◽

...

Keyword(s):

Lung Cancer ◽

Treatment Response ◽

Fdg Pet ◽

Response Assessment ◽

Pet Ct ◽

Treatment Response Assessment ◽

Fdg Pet Ct

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Deep Learning-Based Computer-Aided Detection System for Automated Treatment Response Assessment of Brain Metastases on 3D MRI

Frontiers in Oncology ◽

10.3389/fonc.2021.739639 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jungheum Cho ◽

Young Jae Kim ◽

Leonard Sunwoo ◽

Gi Pyo Lee ◽

Toan Quang Nguyen ◽

...

Keyword(s):

Deep Learning ◽

Brain Metastases ◽

Treatment Response ◽

Response Assessment ◽

Computer Aided Detection ◽

Mr Images ◽

Test Set ◽

One Dimensional ◽

Computer Aided ◽

Treatment Response Assessment

BackgroundAlthough accurate treatment response assessment for brain metastases (BMs) is crucial, it is highly labor intensive. This retrospective study aimed to develop a computer-aided detection (CAD) system for automated BM detection and treatment response evaluation using deep learning.MethodsWe included 214 consecutive MRI examinations of 147 patients with BM obtained between January 2015 and August 2016. These were divided into the training (174 MR images from 127 patients) and test datasets according to temporal separation (temporal test set #1; 40 MR images from 20 patients). For external validation, 24 patients with BM and 11 patients without BM from other institutions were included (geographic test set). In addition, we included 12 MRIs from BM patients obtained between August 2017 and March 2020 (temporal test set #2). Detection sensitivity, dice similarity coefficient (DSC) for segmentation, and agreements in one-dimensional and volumetric Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria between CAD and radiologists were assessed.ResultsIn the temporal test set #1, the sensitivity was 75.1% (95% confidence interval [CI]: 69.6%, 79.9%), mean DSC was 0.69 ± 0.22, and false-positive (FP) rate per scan was 0.8 for BM ≥ 5 mm. Agreements in the RANO-BM criteria were moderate (κ, 0.52) and substantial (κ, 0.68) for one-dimensional and volumetric, respectively. In the geographic test set, sensitivity was 87.7% (95% CI: 77.2%, 94.5%), mean DSC was 0.68 ± 0.20, and FP rate per scan was 1.9 for BM ≥ 5 mm. In the temporal test set #2, sensitivity was 94.7% (95% CI: 74.0%, 99.9%), mean DSC was 0.82 ± 0.20, and FP per scan was 0.5 (6/12) for BM ≥ 5 mm.ConclusionsOur CAD showed potential for automated treatment response assessment of BM ≥ 5 mm.

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