Detailed analysis of 5-aminolevulinic acid induced fluorescence in different brain metastases at two specialized neurosurgical centers: experience in 157 cases

2020 ◽  
Vol 133 (4) ◽  
pp. 1032-1043 ◽  
Author(s):  
Franz Marhold ◽  
Petra A. Mercea ◽  
Florian Scheichel ◽  
Anna S. Berghoff ◽  
Patricia Heicappell ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Primary Tumor ◽  
Aminolevulinic Acid ◽  
Tumor Type ◽  
Strong Fluorescence ◽  
Fluorescence Pattern ◽  
Large Patient ◽  
Fluorescence Characteristics ◽  
Intraoperative Visualization ◽  
Histopathological Subtype

OBJECTIVEIncomplete neurosurgical resection of brain metastases (BM) due to insufficient intraoperative visualization of tumor tissue is a major clinical challenge and might result in local recurrence. Recently, visible 5-aminolevulinic acid (5-ALA) induced fluorescence was first reported in patients with BM. The aim of this study was thus to investigate, for the first time systematically, the value of 5-ALA fluorescence for intraoperative visualization of BM in a large patient cohort.METHODSAdult patients (≥ 18 years) with resection of suspected BM after preoperative 5-ALA administration were prospectively recruited at two specialized neurosurgical centers. During surgery, the fluorescence status (visible or no fluorescence); fluorescence quality (strong, vague, or none); and fluorescence homogeneity (homogeneous or heterogeneous) of each BM was investigated. Additionally, these specific fluorescence characteristics of BM were correlated with the primary tumor type and the histopathological subtype. Tumor diagnosis was established according to the current WHO 2016 criteria.RESULTSAltogether, 157 BM were surgically treated in 154 patients. Visible fluorescence was observed in 104 BM (66%), whereas fluorescence was absent in the remaining 53 cases (34%). In detail, 53 tumors (34%) showed strong fluorescence, 51 tumors (32%) showed vague fluorescence, and 53 tumors (34%) had no fluorescence. The majority of BM (84% of cases) demonstrated a heterogeneous fluorescence pattern. According to primary tumor, visible fluorescence was less frequent in BM of melanomas compared to all other tumors (p = 0.037). According to histopathological subtype, visible fluorescence was more common in BM of ductal breast cancer than all other subtypes (p = 0.008). It is of note that visible fluorescence was observed in the surrounding brain tissue after the resection of BM in 74 (67%) of 111 investigated cases as well.CONCLUSIONSIn this largest series to date, visible 5-ALA fluorescence was detected in two-thirds of BM. However, the characteristic heterogeneous fluorescence pattern and frequent lack of strong fluorescence limits the use of 5-ALA in BM and thus this technique needs further improvements.

scholarly journals SURG-13. EVALUATION OF 5-ALA FLUORESCENCE IN BRAIN METASTASES OF VARIOUS PRIMARY TUMORS: A MULTICENTER STUDY WITH EXPERIENCE IN 157 CASES

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i33-i33
Author(s):  
Petra Andreea Mercea ◽  
Franz Marhold ◽  
Florian Scheichel ◽  
Barbara Kiesel ◽  
Mario Mischkulnig ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Primary Tumor ◽  
Aminolevulinic Acid ◽  
World Health ◽  
Incomplete Resection ◽  
Strong Fluorescence ◽  
Primary Tumors ◽  
Fluorescence Pattern ◽  
Fluorescence Characteristics ◽  
Intraoperative Visualization

Abstract INTRODUCTION: Local recurrence of brain metastases following incomplete resection is not uncommon. One reason is insufficient intraoperative visualization of tumor tissue. Recently, visible intraoperative 5-aminolevulinic acid (5-ALA) fluorescence was reported in the first brain metastases series. Thus, the aim of this study was to investigate intraoperative 5-ALA fluorescence in brain metastases at two specialized centers in the largest patient cohort up to date. METHODS: 5-ALA was administered prior to resection of 157 brain metastases in 154 patients. Intraoperatively, the fluorescence quality (strong, vague or none) and fluorescence homogeneity (homogeneous or heterogeneous) of each brain metastasis was investigated. These 5-ALA fluorescence characteristics were correlated with primary tumor and histopathological subtype according to the current World Health Organization (WHO) 2016 criteria. RESULTS: Visible 5-ALA fluorescence was observed in 104 brain metastases (66%), whereas fluorescence was absent in the remaining 53 cases (34%).53/104 (51%) brain metastases showed strong fluorescence and 51/104 (49%) vague fluorescence. The majority of brain metastases (84%) demonstrated a heterogeneous fluorescence pattern. In context of primary tumor, visible fluorescence was less frequent in brain metastases of melanomas compared to all other tumors (p=0.037). Moreover, visible fluorescence was more common for ductal breast cancer subtype than other subtypes (p=0.008). CONCLUSION: Our data indicate that 5-ALA fluorescence is a valuable for intraoperative visualization of brain metastases to improve the extent of resection and thus patient prognosis. However, the frequent heterogeneous 5-ALA fluorescence pattern and lack of strong fluorescence limits the use of 5-ALA in brain metastases, claiming for further technical refinement.

Brain metastases in patients diagnosed with a solid primary cancer during childhood: experience from a single referral cancer center

2014 ◽  
Vol 14 (4) ◽  
pp. 372-385 ◽  
Author(s):  
Dima Suki ◽  
Rami Khoury Abdulla ◽  
Minming Ding ◽  
Soumen Khatua ◽  
Raymond Sawaya
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Primary Tumor ◽  
Lung Metastases ◽  
Cancer Center ◽  
Leptomeningeal Disease ◽  
Tumor Type ◽  
Primary Cancer ◽  
Extracranial Metastases ◽  
The Brain

Object Metastasis to the brain is frequent in adult cancer patients but rare among children. Advances in primary tumor treatment and the associated prolonged survival are said to have increased the frequency of brain metastasis in children. The authors present a series of cases of brain metastases in children diagnosed with a solid primary cancer, evaluate brain metastasis trends, and describe tumor type, patterns of occurrence, and prognosis. Methods Patients with brain metastases whose primary cancer was diagnosed during childhood were identified in the 1990–2012 Tumor Registry at The University of Texas M.D. Anderson Cancer Center. A review of their hospital records provided demographic data, history, and clinical data, including primary cancer sites, number and location of brain metastases, sites of extracranial metastases, treatments, and outcomes. Results Fifty-four pediatric patients (1.4%) had a brain metastasis from a solid primary tumor. Sarcomas were the most common (54%), followed by melanoma (15%). The patients' median ages at diagnosis of the primary cancer and the brain metastasis were 11.37 years and 15.03 years, respectively. The primary cancer was localized at diagnosis in 48% of patients and disseminated regionally in only 14%. The primary tumor and brain metastasis presented synchronously in 15% of patients, and other extracranial metastases were present when the primary cancer was diagnosed. The remaining patients were diagnosed with brain metastasis after initiation of primary cancer treatment, with a median presentation interval of 17 months after primary cancer diagnosis (range 2–77 months). At the time of diagnosis, the brain metastasis was the first site of systemic metastasis in only 4 (8%) of the 51 patients for whom data were available. Up to 70% of patients had lung metastases when brain metastases were found. Symptoms led to the brain metastasis diagnosis in 65% of cases. Brain metastases were single in 60% of cases and multiple in 35%; 6% had only leptomeningeal disease. The median Kaplan-Meier estimates of survival after diagnoses of primary cancer and brain metastasis were 29 months (95% CI 24–34 months) and 9 months (95% CI 6–11 months), respectively. Untreated patients survived for a median of 0.9 months after brain metastasis diagnosis (95% CI 0.3–1.5 months). Those receiving treatment survived for a median of 8 months after initiation of therapy (95% CI 6–11 months). Conclusions The results of this study challenge the current notion of an increased incidence of brain metastases among children with a solid primary cancer. The earlier diagnosis of the primary cancer, prior to its dissemination to distant sites (especially the brain), and initiation of presumably more effective treatments may support such an observation. However, although the actual number of cases may not be increasing, the prognosis after the diagnosis of a brain metastasis remains poor regardless of the management strategy.

Molecular profiling using the 92-gene assay for tumor classification of brain metastases.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13583-e13583
Author(s):  
Andrew Jacob Brenner ◽  
Raul Collazo ◽  
Catherine A. Schnabel ◽  
F Anthony Greco
Keyword(s):  
Brain Metastases ◽  
Targeted Therapies ◽  
Primary Tumor ◽  
Tumor Type ◽  
Federal Drug Administration ◽  
Gene Assay ◽  
Clinical Series ◽  
The Us ◽  
Tumor Types

e13583 Background: Nearly 200,000 patients are diagnosed with brain metastases in the US annually. Advances in targeted therapies make definitive diagnosis of the primary tumor type important but can be challenging in many patients. The 92-gene assay is a validated gene expression classifier of 50 tumor types/subtypes for patients with uncertain diagnoses. Results from a clinical series of brain biopsies and potential impact on treatment were evaluated. Methods: An IRB-approved, de-identified database of clinical and molecular information from biopsies (N = 24,486) submitted for testing with the 92-gene assay (CancerTYPE ID, Biotheranostics, Inc.) as part of routine care were reviewed. Descriptive analysis included patient demographics and molecular diagnoses. Results: Analysis included 464 brain biopsies. A molecular diagnosis was provided in 433 (93.3%) tested ( < 5% assay failure rate) with 24 different tumor types. Six primary tumor types made up the majority (67.4%) with almost one-third of the molecular predictions being Lung (31.2%), followed by Neuroendocrine (NET) (9.9%), Sarcoma (7.9%), Skin (6.4%), Gastroesophageal (6.2%), and Urinary bladder (5.8%). All of these 6 tumor types, for which activity in the CNS has been documented, have immune checkpoint inhibitors or other targeted therapies approved in selected cases by the US Federal Drug Administration (FDA) (Table). Conclusions: Molecular classification of brain metastases can identify distinct tumor types for which there are FDA approved targeted medications. Improving diagnostic precision with the 92-gene assay helps identify a subset of therapy-responsive metastatic brain tumors, thus improving therapy and possibly providing better outcomes and survival. [Table: see text]

Racial and Gender Disparities and the Role of Primary Tumor Type on Inpatient Outcomes Following Craniotomy for Brain Metastases

2012 ◽  
Vol 19 (8) ◽  
pp. 2657-2663 ◽  
Author(s):  
Miriam Nuño ◽  
Debraj Mukherjee ◽  
Adam Elramsisy ◽  
Kristin Nosova ◽  
Shivanand P. Lad ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Primary Tumor ◽  
Gender Disparities ◽  
Tumor Type ◽  
Inpatient Outcomes ◽  
And Gender ◽  
Primary Tumor Type

Evaluation of invasion patterns and their correlation with integrin alphavbeta expression in brain metastases of solid cancers.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2059-2059
Author(s):  
Anna Sophie Berghoff ◽  
Orsolya Rajky ◽  
Frank Winkler ◽  
Michael Weller ◽  
Christoph Zielinski ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Primary Tumor ◽  
Brain Parenchyma ◽  
T Test ◽  
Integrin Expression ◽  
Tumor Type ◽  
Diffuse Infiltration ◽  
Invasion Pattern ◽  
Invasion Patterns

2059 Background: Understanding the pathobiology of brain metastases (BM) could guide the establishment of new targeted therapies. Methods: We collected 57 autopsy specimens of BM (primary tumor: 27 lung cancer, 6 breast cancer, 8 melanoma, 1 kidney cancer, 2 colorectal cancer, 13 other) and histologically evaluated the patterns of invasion into the surrounding brain parenchyma. Expression of the following integrins was evaluated using immunohistochemistry: with novel antibodies for αv subunit, αvβ3, αvβ5, αvβ6 and αvβ8 integrin. Results: We observed three main invasion patterns: well-demarcated (29/57, 51%), vascular co-option (10/57, 18%) and diffuse infiltration (18/57, 32%). There was no association of invasion pattern with primary tumor type, although vascular co-option was most common in melanomas (4/10, 40%). αv subunit expression was lowest in the vascular co-option group (p = 0.05, t-test). αvβ6 levels were higher in the well-demarcated group than in the vascular co-option group (p = 0.025; t-test) and were higher in lung cancer BM than in melanoma BM (0.01, t-test). αvβ3 and αvβ5 were frequently expressed in tumoral (αvβ3: 30/57, 53%; αvβ5: 55/57, 97%) and peritumoral (αvβ3: 29/57, 51%, αvβ5: 54/57 (95%) vascular structures and 27/57 (47%) specimens showed avb5 and 6/57 (11%) αvβ3 expression on tumor cells. Prior radio- or chemotherapy did not correlate with invasion pattern or integrin expression. Conclusions: We delineate three distinct invasion patterns of BM into the brain parenchyma: well-demarcated growth, vascular co-option and diffuse infiltration. Integrin expression is frequent on tumor and vascular cells in BM and associated with distinct invasion patterns. Anti-integrin therapy could be a valid treatment option in patients with BM.

scholarly journals OTHR-16. MOLECULAR PROFILING USING THE 92-GENE ASSAY FOR TUMOR CLASSIFICATION OF BRAIN METASTASES

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i21-i21
Author(s):  
Andrew Brenner ◽  
Raul Collazo ◽  
Catherine Schnabel ◽  
Anthony Greco
Keyword(s):  
Brain Metastases ◽  
Targeted Therapies ◽  
Primary Tumor ◽  
Tumor Type ◽  
Federal Drug Administration ◽  
Gene Assay ◽  
Clinical Series ◽  
The Us ◽  
Tumor Types

Abstract BACKGROUND: Nearly 200,000 patients are diagnosed with brain metastases in the US annually. Advances in targeted therapies make definitive diagnosis of the primary tumor type important but can be challenging in many patients. The 92-gene assay is a validated gene expression classifier of 50 tumor types for patients with uncertain tissue of origin diagnoses. Results from a clinical series of brain biopsies and potential impact on treatment were evaluated. METHODS: An IRB approved, de-identified database of clinical and molecular information from biopsies (N = 24,486) submitted for testing with the 92-gene assay (CancerTYPE ID, Biotheranostics, Inc.) as part of routine care were reviewed. Descriptive analysis included patient demographics and molecular diagnoses. RESULTS: Analysis included 464 brain biopsies. A molecular diagnosis was provided in 433 (93.3%) tested (&lt; 5% assay failure rate) with 24 different tumor types. Six primary tumor types made up the majority (67.4%) with almost one-third of the molecular predictions being Lung (31.2%), followed by Neuroendocrine (NET) (9.9%), Sarcoma (7.9%), Skin (6.4%), Gastroesophageal (6.2%), and Urinary bladder (5.8%). All of these 6 tumor types, for which activity in the CNS has been documented, have immune checkpoint inhibitors or other targeted therapies approved in selected cases by the US Federal Drug Administration (FDA). CONCLUSIONS: Molecular classification of brain metastases can identify distinct tumor types for which there are FDA approved targeted medications. Improving diagnostic precision with the 92-gene assay helps identify a subset of therapy-responsive metastatic brain tumors, thus improving therapy and possibly providing better outcomes and survival.

scholarly journals Impact of Immunotherapy on the Survival of Patients With Cancer and Brain Metastases

2020 ◽  
Vol 18 (7) ◽  
pp. 832-840
Author(s):  
Saber Amin ◽  
Michael Baine ◽  
Jane Meza ◽  
Chi Lin
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Primary Tumor ◽  
Small Cell ◽  
Tumor Type ◽  
National Cancer Database ◽  
Small Cell Lung ◽  
The Impact

Background: Immunotherapy has shown excellent efficacy in various cancers. However, there is a lack of knowledge regarding the significant role of immunotherapy in patients with brain metastases (BMs). The objective of this study was to investigate, using the National Cancer Database, the impact of immunotherapy on the overall survival (OS) of patients with BMs who did not receive definitive surgery of the primary tumor. Patients and Methods: Patients diagnosed with the primary cancer of non–small cell lung cancer, small cell lung cancer, other types of lung cancer, breast cancer, melanoma, colorectal cancer, or renal cancer who had BMs at the time of diagnosis were identified from the National Cancer Database. We assessed OS using a Cox proportional hazards model adjusted for age at diagnosis, sex, race, education level, income level, residential area, treatment facility type, insurance status, Charlson-Deyo comorbidity status, year of diagnosis, primary tumor type, and receipt of chemotherapy, radiation therapy (RT), and/or immunotherapy, because these factors were significantly associated with OS in the univariable analysis. Results: Of 94,215 patients who were analyzed, 3,097 (3.29%) received immunotherapy. In the multivariable analysis, immunotherapy was associated with significantly improved OS (hazard ratio [HR], 0.694; 95% CI, 0.664–0.726; P<.0001) compared with no immunotherapy. Treatment using chemotherapy plus immunotherapy was significantly associated with improved OS (HR, 0.643; 95% CI, 0.560–0.738; P<.0001) compared with chemotherapy without immunotherapy. RT plus immunotherapy was also associated with significantly improved OS (HR, 0.389; 95% CI, 0.352–0.429; P<.0001) compared with RT alone. Furthermore, chemoradiation (CRT) plus immunotherapy was associated with significantly improved OS (HR, 0.793; 95% CI, 0.752–0.836; P<.0001) compared with CRT alone. Conclusions: In this comprehensive analysis, the addition of immunotherapy to chemotherapy, RT, and CRT was associated with significantly improved OS in patients with BMs. The study warrants future clinical trials of immunotherapy in patients with BMs, who have historically been excluded from these trials.

Use of 5-aminolevulinic acid in fluorescence-guided resection of meningioma with high risk of recurrence

2007 ◽  
Vol 106 (6) ◽  
pp. 1070-1074 ◽  
Author(s):  
Yoshinaga Kajimoto ◽  
Toshihiko Kuroiwa ◽  
Shin-Ichi Miyatake ◽  
Tsugumichi Ichioka ◽  
Minoru Miyashita ◽  
...  
Keyword(s):  
High Risk ◽  
Tumor Tissue ◽  
Aminolevulinic Acid ◽  
Superior Sagittal Sinus ◽  
Residual Tumor ◽  
Strong Fluorescence ◽  
Glioma Surgery ◽  
Risk Of Recurrence ◽  
Sagittal Sinus ◽  
Atypical Meningiomas

✓It has been established that fluorescence-guided resection using 5-aminolevulinic acid (5-ALA) is useful in glioma surgery. The authors report on a 65-year-old woman who had a huge atypical left-hemisphere meningioma, which extended into the skull and to the superior sagittal sinus and demonstrated fluorescence in response to administration of 5-ALA. After the tumor was removed, the operative field was observed under the fluorescent mode of a fluorescence surgical microscopy system. Several minute areas of residual tumor tissue were visualized as strong fluorescence behind the vein and sinus, in a part of the hypertrophic dura, and along the edge of the skull. These remnants were completely removed. The authors concluded that fluorescence-guided resection using 5-ALA is useful in cases of atypical meningiomas with a high risk of recurrence.

scholarly journals Prognostic factors and a new scoring system for survival of patients irradiated for bone metastases

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Dirk Rades ◽  
Rapha Haus ◽  
Steven E. Schild ◽  
Stefan Janssen
Keyword(s):  
Multivariate Analysis ◽  
Bone Metastases ◽  
Primary Tumor ◽  
Scoring System ◽  
Survival Rates ◽  
Karnofsky Performance Score ◽  
Tumor Type ◽  
Factor Scores ◽  
Survival Times ◽  
Primary Tumor Type

Abstract Background Personalized therapy for bone metastases should consider the patients’ remaining lifespan. Estimation of survival can be facilitated with scoring tools. A new tool was developed, specifically designed to estimate 12-month survival. Methods In 445 patients irradiated for bone metastases, radiotherapy regimen plus 13 factors (age, gender, Karnofsky performance score (KPS), primary tumor type, interval between cancer diagnosis and RT of bone metastases, visceral metastases, other (non-irradiated) bone metastases, sites of bone metastases, number of irradiated sites, pathological fracture, fractionation of RT, pre-RT surgery, pre-RT administration of bisphosphonates/denosumab, pre-RT systemic anticancer treatment) were retrospectively analyzed for survival. Factors achieving significance (p < 0.05) or borderline significance (p < 0.055) on multivariate analysis were used for the scoring system. Twelve-month survival rates were divided by 10 (factor scores); factor scores were summed for each patient (patient scores). Results On multivariate analysis, survival was significantly associated with KPS (hazard ratio (HR) 1.91, p < 0.001) and primary tumor type (HR 1.12, p < 0.001); age achieved borderline significance (HR 1.14, p = 0.054). These factors were used for the scoring tool. Patient scores ranged from 8 to 17 points. Three groups were designated: 8–9 (A), 10–14 (B) and 15–17 (C) points. Twelve-month survival rates were 9, 38 and 72% (p < 0.001); median survival times were 3, 8 and 24 months. Conclusions This new tool developed for patients irradiated for bone metastases at any site without spinal cord compression allows one to predict the survival of these patients and can aid physicians when assigning the treatment to individual patients.

scholarly journals 90-gene signature assay for tissue origin diagnosis of brain metastases

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Yulong Zheng ◽  
Yongfeng Ding ◽  
Qifeng Wang ◽  
Yifeng Sun ◽  
Xiaodong Teng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Brain Tumors ◽  
Brain Metastases ◽  
Expression Profiles ◽  
Gene Expression Signature ◽  
Similarity Score ◽  
Primary Site ◽  
Tumor Type ◽  
Metastatic Brain Tumors ◽  
Expression Signature

Abstract Background Brain metastases (BM) are the most common intracranial tumors. 2–14% of BM patients present with unknown primary site despite intensive evaluations. This study aims to evaluate the performance of a 90-gene expression signature in determining the primary sites for BM samples. Methods The sequence-based gene expression profiles of 708 primary brain tumors (PBT) collected from The Cancer Genome Atlas (TCGA) database were analyzed by the 90-gene expression signature, with a similarity score for each of 21 common tumor types. We then used Optimal Binning algorithm to generate a threshold for separating PBT from BM. Eighteen PBT samples were analyzed to substantiate the reliability of the threshold. In addition, the performance of the 90-gene expression signature for molecular classification of metastatic brain tumors was validated in a cohort of 48 BM samples with the known origin. For each BM sample, the tumor type with the highest similarity score was considered tissue of origin. When a sample was diagnosed as PBT, but the similarity score below the threshold, the second prediction was considered as the primary site. Results A threshold of the similarity score, 70, was identified to discriminate PBT from BM (PBT: > 70, BM: ≤ 70) with an accuracy of 99% (703/708, 95% CI 98–100%). The 90-gene expression signature was further validated with 18 PBT and 44 BM samples. The results of 18 PBT samples matched reference diagnosis with a concordance rate of 100%, and all similarity scores were above the threshold. Of 44 BM samples, the 90-gene expression signature accurately predicted primary sites in 89% (39/44, 95% CI 75–96%) of the cases. Conclusions Our findings demonstrated the potential that the 90-gene expression signature could serve as a powerful tool for accurately identifying the primary sites of metastatic brain tumors.

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