Evaluation Of Brain Metastases Research Articles

Alectinib vs. Lorlatinib in the Front-Line Setting for ALK-Rearranged Non-Small-Cell Lung Cancer (NSCLC): A Deep Dive into the Main Differences across ALEX and CROWN Phase 3 Trials.

Various next-generation ALK TKIs are available as first-line options for ALK-positive NSCLC, with alectinib and lorlatinib being commonly preferred. However, no direct comparison between them has been conducted, making it impossible to pick a winner. We performed an analytic, 'non-comparative' assessment of the two phase 3 pivotal clinical trials showing superiority of alectinib (ALEX) and lorlatinib (CROWN) in comparison to crizotinib. Overall, the two studies were very similar in the study design and patient characteristics, with the exception of the selection and evaluation of brain metastases. PFS hazard ratios numerically favored lorlatinib, both according to the investigator and to BICR. Notably, the 3-year PFS rate was numerically higher with lorlatinib (64%) than with alectinib (46.4%). Despite similar response rates and overall intracranial response, the rate of complete intracranial response was higher with lorlatinib, with a cumulative incidence risk of CNS disease progression at 12 months of 9.4% with alectinib and 2.8% with lorlatinib. The peculiar toxicities of lorlatinib were related to lipidic profile alterations, peripheral oedema and cognitive effects, with no impact on cardiovascular risk nor impairment in quality of life versus crizotinib. Furthermore, the rate of permanent treatment discontinuation due to adverse events was numerically higher with alectinib (26%) than with lorlatinib (7%). In conclusion, despite the immature OS data for both drugs, the efficacy of lorlatinib appears higher than alectinib while maintaining a manageable toxicity profile.

Challenges in radiological evaluation of brain metastases, beyond progression

MRI is the cornerstone in the evaluation of brain metastases. The clinical challenges lie in discriminating metastases from mimickers such as infections or primary tumors and in evaluating the response to treatment. The latter sometimes leads to growth, which must be framed as pseudo-progression or radionecrosis, both inflammatory phenomena attributable to treatment, or be considered as recurrence. To meet these needs, imaging techniques are the subject of constant research. However, an exponential growth after radiotherapy must be interpreted with caution, even in the presence of results suspicious of tumor progression by advanced techniques, because it may be due to inflammatory changes. The aim of this paper is to familiarize the reader with inflammatory phenomena of brain metastases treated with radiotherapy and to describe two related radiological signs: "the inflammatory cloud" and "incomplete ring enhancement", in order to adopt a conservative management with close follow-up.

Perfusion MRI in the evaluation of brain metastases: current practice review and rationale for study of baseline MR perfusion imaging prior to stereotactic radiosurgery (STARBEAM-X).

Stereotactic radiosurgery is an established focal treatment for brain metastases with high local control rates. An important side-effect of stereotactic radiosurgery is the development of radionecrosis. On conventional MR imaging, radionecrosis and tumour progression often have similar appearances, but have contrasting management approaches. Perfusion MR imaging is often used in the post-treatment setting in order to help distinguish between the two, but image interpretation can be fraught with challenges.Perfusion MR plays an established role in the baseline and post-treatment evaluation of primary brain tumours and a number of studies have concentrated on the value of perfusion imaging in brain metastases. Of the parameters generated, relative cerebral blood volume is the most widely used variable in terms of its clinical value in differentiating between radionecrosis and tumour progression. Although it has been suggested that the relative cerebral blood volume tends to be elevated in active metastatic disease following treatment with radiosurgery, but not with treatment-related changes, the literature available on interpretation of the ratios provided in the context of defining tumour progression is not consistent.This article aims to provide an overview of the role perfusion MRI plays in the assessment of brain metastases and introduces the rationale for the STARBEAM-X study (Study of assessment of radionecrosis in brain metastases using MR perfusion extra imaging), which will prospectively evaluate baseline perfusion imaging in brain metastases. We hope this will allow insight into the vascular appearance of metastases from different primary sites, and aid in the interpretation of post-treatment perfusion imaging.

Los retos en la evaluación radiológica de las metástasis cerebrales, más allá de la progresión

MRI is the cornerstone in the evaluation of brain metastases. The clinical challenges lie in discriminating metastases from mimickers such as infections or primary tumors and in evaluating the response to treatment. The latter sometimes leads to growth, which must be framed as pseudo-progression or radionecrosis, both inflammatory phenomena attributable to treatment, or be considered as recurrence. To meet these needs, imaging techniques are the subject of constant research. However, an exponential growth after radiotherapy must be interpreted with caution, even in the presence of results suspicious of tumor progression by advanced techniques, because it may be due to inflammatory changes. The aim of this paper is to familiarize the reader with inflammatory phenomena of brain metastases treated with radiotherapy and to describe two related radiological signs: «the inflammatory cloud» and «incomplete ring enhancement», in order to adopt a conservative management with close follow-up.

The Role of Simultaneous Standardized Uptake Value and MRI Diffusion Weighted Heterogeneity Index from Hybrid PET/MR in the Evaluation of Brain Metastases

The Role of Simultaneous Standardized Uptake Value and MRI Diffusion Weighted Heterogeneity Index from Hybrid PET/MR in the Evaluation of Brain Metastases

Diffusion and Perfusion MRI Predicts Response Preceding and Shortly After Radiosurgery to Brain Metastases: A Pilot Study.

To determine the ability of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict long-term response of brain metastases prior to and within 72 hours of stereotactic radiosurgery (SRS). In this prospective pilot study, multiple b-value DWI and T1-weighted DCE-MRI were performed in patients with brain metastases before and within 72 hours following SRS. Diffusion-weighted images were analyzed using the monoexponential and intravoxel incoherent motion (IVIM) models. DCE-MRI data were analyzed using the extended Tofts pharmacokinetic model. The parameters obtained with these methods were correlated with brain metastasis outcomes according to modified Response Assessment in Neuro-Oncology Brain Metastases criteria. We included 25 lesions from 16 patients; 16 patients underwent pre-SRS MRI and 12 of 16 patients underwent both pre- and early (within 72 hours) post-SRS MRI. The perfusion fraction (f) derived from IVIM early post-SRS was higher in lesions demonstrating progressive disease than in lesions demonstrating stable disease, partial response, or complete response (q = .041). Pre-SRS extracellular extravascular volume fraction, ve , and volume transfer coefficient, Ktrans , derived from DCE-MRI were higher in nonresponders versus responders (q = .041). Quantitative DWI and DCE-MRI are feasible imaging methods in the pre- and early (within 72 hours) post-SRS evaluation of brain metastases. DWI- and DCE-MRI-derived parameters demonstrated physiologic changes (tumor cellularity and vascularity) and offer potentially useful biomarkers that can predict treatment response. This allows for initiation of alternate therapies within an effective time window that may help prevent disease progression.

Preliminary application of 3.0\u2009T magnetic resonance chemical exchange saturation transfer imaging in brain metastasis of lung cancer

BackgroundLung cancer brain metastases are very common and one of the common causes of treatment failure. We aimed to examine the clinical use of chemical exchange saturation transfer (CEST) technology in the evaluation of brain metastases for lung cancer diagnosis and prognosis.MethodsWe included26 cases of lung cancer brain metastases, 15 cases of gliomas, and 20 cases with normal tests. The magnetization transfer ratio (MTR;3.5 ppm) image from the GRE-EPI-CEST sequence was analyzed using the ASSET technique and APT technology. The MTR values were measured in the lesion-parenchymal, edema, and non-focus regions, and the MTR image was compared with the conventional MRI. ANOVA and t-test were used for statistical analysis.ResultsThe lesion-parenchymal, edema, and non-focus areas in the metastatic-tumor-group were red-yellow, yellow-green, and green-blue, and the MTR values were 3.29 ± 1.14%,1.28 ± 0.36%,and 1.26 ± 0.31%, respectively. However, in the glioma-group, the corresponding areas were red, red-yellow, and green-blue, and the MTR values were 6.29 ± 1.58%, 2.87 ± 0.65%, and 1.03 ± 0.30%, respectively. The MTR values of the corresponding areas in the normal-group were 1.07 ± 0.22%,1.04 ± 0.23%, and 1.06 ± 0.24%, respectively. Traditional MR images are in black-white contrast and no metabolic information is displayed.The MTRvalues of the three regions were significantly different among the three groups. The values were also significantly different between the parenchymal and edema areas in the metastatic-tumor-group. There were significant differences in the MTR values between the non-lesion and edema regions, but there was no significant difference between the edema and non-focus areas. In the glioma-group, there were significant differences in the MTR values between the parenchymal and edema areas, between the parenchymal and non-focus areas, and between the edema and non-focus areas.ConclusionsCEST reflects the protein metabolism; therefore, early diagnosis of brain metastases and assessment of the prognosis can be achieved using molecular imaging.

Defining the endpoints: how to measure the efficacy of drugs that are active against central nervous system metastases.

Brain metastases (BMs) are the most common cause of malignant central nervous system (CNS) tumors in adults. In the recent past, patients with BMs were excluded from clinical trials, but now, with the advent of new biological and immunological drugs, their inclusion is more common. In the last era response and progression criteria used across clinical trials have defined the importance to consider not only measurement changes of brain lesions but also the modification of parameters related to the metastases such as metabolism of tissue and its pathological features. Magnetic resonance imaging (MRI) represents the first choice in the evaluation of BMs; the computed tomography (CT) scan will be made only in case of MRI's contraindication. CT, MRI and positron emission tomography (PET-CT), may be used to monitor response to treatment as part of clinical and radiological follow up. In the evaluation of response to treatment, MRI shows superior accuracy in comparison to CT; PET-CT is useful in particularly in cases of BMs underwent to locoregional therapies in the differential diagnosis between recurrence or radionecrosis. Now is possible to use functional imaging as CT-perfusion, dynamic susceptibility contrast (DSC) MR imaging, dynamic contrast-enhanced (DCE) MR imaging, diffusion-weighted MR imaging and MR-Spectroscopy in the evaluation of treatment response; these imaging techniques can provide qualitative and quantitative imaging parameters that allow pathophysiologic correlation. In the evaluation of the response to immunotherapy treatments, the immune-related response criteria (irRC) are considered as the gold standard. The irRC utilizes bidimensional measurements, quantifying the tumor dimension using a product of the longest diameter and the longest perpendicular diameter. We analyze clinical and radiological criteria to better define outcome of drugs for BMs from solid tumors in the new era of biological and immunological therapies.

Genomic profiling of brain metastases: current knowledge and new frontiers.

Brain metastases (BM) constitute the majority of intracranial cancers and carry with them a dismal prognosis. Several common cancers have a particular predilection for spread to the brain, amongst them lung cancer, breast cancer, melanoma, renal cell carcinoma (RCC), and more rarely gastrointestinal (GI) cancers. While prognosis has historically been poor and multimodality treatment combining surgery and radiation therapy was the mainstay of treatment, the genomic revolution in cancer therapy is finding increasing applications in treatment of central nervous system (CNS) disease. Targeted therapy, combined with advances in the evaluation of BM for targetable mutations, is showing increased efficacy. Developments in the understanding of brain tropism and targetable signaling pathways in metastasis are elucidating entirely new treatment approaches. This review focuses on advances made in the understanding of the genomics of BM and how this may change the role of targeted therapeutics in this common complication of cancer.

Molecular imaging of brain tumors with 18F-DOPA PET and PET/CT

The objective of this study was to give an overview of the potential clinical utility of [18F]-L-dihydroxyphenylalanine (18F-DOPA) PET and PET/CT for imaging of brain tumors. Review articles and reference lists were used to supplement the search findings. 18F-DOPA has been investigated as a PET tracer for primary brain tumors, metastases of somatic cancer, and evaluation of relapse of pathology in patients with brain tumor after surgery and/or radiotherapy on the basis of enhanced cell proliferation. Available studies have provided encouraging preliminary results for diagnosis of brain tumors and relapse after surgery/radiotherapy. In the brain, excellent discrimination between tumor and normal tissue can be achieved because of the low physiological uptake of 18F-DOPA and the high ratio between tumor and normal hemispheric tissue. Information on evaluation of brain metastases is limited but encouraging. PET and PET/CT with 18F-DOPA are useful in diagnosing primary brain tumors and should be recommended in the diagnosis of relapse of disease after surgical treatment and/or radiotherapy. Semiquantitative analysis could improve diagnosis while correlative imaging with MRI is essential. Limits are due to low knowledge of potential pitfalls.

Imaging of brain tumours with special emphasis on metastatic disease

Advances in MR imaging techniques have made considerable progress in recent years. Both high resolution anatomical imaging and functional parameters when using higher advanced MR techniques have become a valuable adjunct to conventional imaging, helping to further differentiate a lesion or to better determine an adequate therapy or biopsy site. Diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI) are available on virtually every MR scanner, although especially for DTI the post processing is somewhat more demanding. The use of MR perfusion and MR spectroscopy (MRS) has become more and more routine. BOLD imaging (fMRI) is able to correlate brain activation with specific tasks (paradigms), which have also added information for presurgical evaluation of brain metastases or brain tumour in general.

Contrast‐enhanced FLAIR imaging in combination with pre‐ and postcontrast magnetization transfer T1‐weighted imaging: Usefulness in the evaluation of brain metastases

To assess whether the use of postcontrast fluid-attenuated inversion recovery (FLAIR) imaging in combination with pre- and postcontrast magnetization transfer (MT) T1-weighted imaging (T1WI) can increase diagnostic confidence in the evaluation of brain metastases. Brain MR images from 41 patients with suspected brain metastases were reviewed. Two radiologists viewed pre- and postcontrast MT-T1W images for the presence of metastatic tumors and rated the possible enhanced lesions using a five-point confidence scale (session 1). The postcontrast FLAIR images were then viewed together with pre- and postcontrast MT-T1W images, and the presence of metastasis was rated again (session 2). A total of 240 possible enhanced lesions were detected in session 1. Judging by follow-up MR examinations, 196 were considered to be nonmetastatic findings and 44 were determined to be metastasis. In session 2 the confidence rating for nonmetastasis increased significantly in the subset of nonmetastatic findings (P < 0.001), and the confidence rating for metastasis increased significantly in the subset of metastases (P < 0.05). The addition of postcontrast FLAIR imaging to pre- and postcontrast MT-T1WI improves diagnostic confidence in evaluation of brain metastases.

Evaluation of brain metastases with dynamic susceptibility-contrast MR imaging

目的 研究治疗前不同来源脑转移瘤的动态增强磁化率(DSC)MR灌注成像特点.方法 对28例经病理或随访证实为脑转移瘤的患者行手术前DSC MR灌注成像扫描.分析MR灌注曲线及伪彩图像,测量肿瘤实质部分及瘤周水肿区最大相对脑血容积(rCBV)值及相应部位相对平均通过时间(rMTT)数值,并将所测量数值进行t检验分析,P＜0.05为差异具有统计意义.结果 不同来源脑转移瘤的MR灌注曲线、伪彩图像特点无明显差异.脑转移瘤肿瘤实质部分灌注程度与正常脑灰质相仿,瘤周水肿区表现为低灌注,两者的灌注时间均延长.12例来源于肺癌与5例来源于乳腺癌的脑转移瘤肿瘤实质部分的最大rCBV值(分别为272.5±34.3和210.8±59.4)及相应部位的rMTT数值(分别为117.7±4.3和105.2±21.3)之间以及两者瘤周水肿区rCBV值(分别为122.0±16.3和68.4±6.1)和rMTT值(分别为112.7±8.3和139.8±37.9)之间差异均无统计学意义(P＞0.05).结论 不同来源脑转移瘤的MR灌注成像特点趋于一致。

First-Line Chemotherapy with Vinorelbine, Gemcitabine, and Carboplatin in the Treatment of Brain Metastases from Non-Small-Cell Lung Cancer: A Phase II Study

On the basis of the hypothesis that responsiveness of brain metastases (BM) to chemotherapy is primarily determined by the chemosensitivity of primary tumor, rather than the ability of cytotoxic agents to penetrate the blood–brain barrier, we addressed the role of a new combination regimen with Vinorelbine (VNR), Gemcitabine (GEM), and Carboplatin (CBDCA) as a primary treatment modality in non-small-cell lung cancer (NSCLC) patients with BM. Twenty-two consecutive chemotherapy-naïve patients with documented BM from NSCLC and at least 1 evaluable extracerebral lesion were enrolled in this phase II study. Vinorelbine (25 mg/m2) and GEM (1000 mg/m2) were given on day 1, combined with a fixed daily dose of CBDCA at AUC=5.0 for three consecutive days. The cycle was repeated every three weeks in an outpatient setting. A total of 116 cycles was given (median 4, range 3–9 per patient). Specific evaluation of BM by contrast-enhanced computed tomography (CT) scan showed an overall response rate of 45% in 20 evaluable patients (95% confidence interval, 26–66%), with 3 (15%) complete and 6 (30%) partial remissions; in addition, three minor regressions, five disease stabilizations, and three progressions were found. Patients who responded for the brain also had a response at the extracerebral sites, and a benefit by a remission of symptoms and improvement of performance index was observed in 77% of the whole group. Median time to response was 10 weeks (range 6–12 weeks) and median response duration was 25 weeks (range 12–32 weeks). Median survival time was 33 weeks (range 18–62+weeks) in the whole group and 48 weeks in responders (range 26–62+weeks). The adopted schedule was well tolerated and easy to use in the outpatient setting, with good patient compliance. Our results, which are consistent with the study hypothesis, suggest that BM respond to chemotherapy in the same way as systemic disease and primary tumor, and further support the need for reconsideration of the role of chemotherapy in such a clinical setting. Controlled trials comparing chemotherapy with radiotherapy or concomitant sequential chemo-radiotherapy would be appropriate.