Intracranial Metastatic Disease

Nearly 30% of patients with cancer will develop intracranial metastatic disease (IMD), and more than half of these patients will die within a few months following their diagnosis. In light of the profound effect of IMD on survival and quality of life, there is significant interest in identifying biomarkers that could facilitate the early detection of IMD or identify patients with cancer who are at high IMD risk. In this review, we will highlight early efforts to identify biomarkers of IMD and consider avenues for future investigation.

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[18F]-Fluciclovine PET discrimination of recurrent intracranial metastatic disease from radiation necrosis

10.21203/rs.3.rs-62435/v2 ◽

2020 ◽

Author(s):

Ephraim Edward Parent ◽

Dhruv Patel ◽

Jonathon A Nye ◽

Li Zhuo ◽

Jeffrey Olson ◽

...

Keyword(s):

Metastatic Disease ◽

Recurrent Disease ◽

Radiation Necrosis ◽

Brain Parenchyma ◽

Normal Brain ◽

Time Activity ◽

Time Points ◽

Contralateral Normal Brain ◽

Intracranial Metastatic Disease ◽

Time Point

Abstract Background Stereotactic radiosurgery (SRS) is often the primary treatment modality for patients with intracranial metastatic disease. Despite advances in magnetic resonance imaging, including use of perfusion and diffusion sequences and molecular imaging, distinguishing radiation necrosis from progressive tumor remains a diagnostic and clinical challenge. We investigated the sensitivity and specificity of 18F-fluciclovine PET to accurately distinguish radiation necrosis from recurrent intracranial metastatic disease in patients who had previously undergone SRS. Methods Fluciclovine PET imaging was performed in 8 patients with a total of 15 lesions that had previously undergone SRS and had subsequent MRI and clinical features suspicious for recurrent disease. The SUVmax of each lesion and the contralateral normal brain parenchyma were summated and evaluated at 4 different time points (5 minutes, 10 minutes, 30 minutes, and 55 minutes). Lesions were characterized as either recurrent disease (11 of 15 lesions) or radiation necrosis (4 of 15 lesions) and confirmed with histopathological correlation (7 lesions) or through serial MRI studies (8 lesions). Results Time activity curve analysis found statistically greater radiotracer accumulation for all lesions, including radiation necrosis, when compared to contralateral normal brain. While the mean and median SUVmax for recurrent disease was statistically greater than that of radiation necrosis at all time points, the difference was more significant at the earlier time points (p = 0.004 at 5 min – 0.025 at 55 min). Using a SUVmax threshold of ≥1.3, fluciclovine PET demonstrated a 100% accuracy in distinguishing recurrent disease from radiation necrosis up to 30 minutes after injection and an accuracy of 87% (sensitivity = 0.91, specificity = 0.75) at the last time point of 55 minutes. However, tumor to brain ratios (TBRmax) were not significantly different between recurrent disease and radiation necrosis at any time point due to variable levels of fluciclovine uptake in the background brain parenchyma. Conclusions Fluciclovine PET may play an important role in distinguishing active intracranial metastatic lesions from radiation necrosis in patients previously treated with SRS but needs to be validated in larger studies.

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04. ASSESSMENT OF EFFICACY AND SAFETY OF OSIMERTINIB FOR PATIENTS WITH INTRACRANIAL METASTATIC DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa073.000 ◽

2020 ◽

Vol 2 (Supplement_2) ◽

pp. ii1-ii1

Author(s):

Anders Erickson ◽

Priscilla Brastianos ◽

Sunit Das

Keyword(s):

Targeted Therapy ◽

Metastatic Disease ◽

Meta Analysis ◽

Growth Factor Receptor ◽

Risk Of Bias ◽

Egfr Mutations ◽

Efficacy And Safety ◽

Eligibility Criteria ◽

Egfr Mutant ◽

Intracranial Metastatic Disease

Abstract INTRODUCTION Intracranial metastatic disease (IMD) is a serious and life-altering complication for many patients with cancer. Targeted therapy may address limitations of current treatments as an additional agent to achieve intracranial disease control in some patients with IMD. Osimertinib is a mutant epidermal growth factor receptor (EGFR) inhibitor that can penetrate the blood-brain barrier and inhibit tumor cell survival and proliferation in patients with non-small cell lung cancer (NSCLC) with specific EGFR mutations. The purpose of this study is to assess the efficacy and safety of osimertinib in the management of IMD. METHODS Studies reporting intracranial outcomes for patients with EGFR-mutant NSCLC and IMD treated with osimertinib were included. Among 271 records identified in MEDLINE and EMBASE, 15 studies fulfilled eligibility criteria. Outcomes were pooled using a random-effects model. Risk of bias was assessed using the Cochrane Risk of Bias tool and modified Newcastle-Ottawa scale. Information extracted included study characteristics, intracranial efficacy measures, and safety measures. Meta-analyses were conducted to pool applicable outcomes. RESULTS 15 studies reporting on 324 patients were included in the analysis. Combined CNS ORR and CNS DCR were calculated to be 64% (95% CI, 53–76%; n = 195), and 90% (95% CI, 85–93%; n = 246). Risk ratios for CNS ORR and CNS DCR were calculated to be 1.44 (95% CI, 1.06–1.96; n = 52) and 1.13 (95% CI, 0.96–1.33; n = 52). Included studies reported complete intracranial response rates of 7–23%, median best decrease in intracranial lesion size of 40–64%, and grade 3+ adverse event rates of 19–39%. CONCLUSIONS Findings reported here support a potential role for osimertinib for patients with EGFR-mutant NSCLC and IMD. Clinical decision-makers would benefit from the inclusion of patients with IMD in future trials to identify factors that predict responses to targeted therapy.

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