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 ◽  
...  

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.

2020 ◽  
Vol 133 (4) ◽  
pp. 1032-1043 ◽  
Author(s):  
Franz Marhold ◽  
Petra A. Mercea ◽  
Florian Scheichel ◽  
Anna S. Berghoff ◽  
Patricia Heicappell ◽  
...  

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.


2020 ◽  
Vol 22 (9) ◽  
pp. 1359-1367 ◽  
Author(s):  
Paul W Sperduto ◽  
Shane Mesko ◽  
Jing Li ◽  
Daniel Cagney ◽  
Ayal Aizer ◽  
...  

Abstract Background Breast cancer treatment is based on estrogen receptors (ERs), progesterone receptors (PRs), and human epidermal growth factor receptor 2 (HER2). At the time of metastasis, receptor status can be discordant from that at initial diagnosis. The purpose of this study was to determine the incidence of discordance and its effect on survival and subsequent treatment in patients with breast cancer brain metastases (BCBM). Methods A retrospective database of 316 patients who underwent craniotomy for BCBM between 2006 and 2017 was created. Discordance was considered present if the ER, PR, or HER2 status differed between the primary tumor and the BCBM. Results The overall receptor discordance rate was 132/316 (42%), and the subtype discordance rate was 100/316 (32%). Hormone receptors (HR, either ER or PR) were gained in 40/160 (25%) patients with HR-negative primary tumors. HER2 was gained in 22/173 (13%) patients with HER2-negative primary tumors. Subsequent treatment was not adjusted for most patients who gained receptors—nonetheless, median survival (MS) improved but did not reach statistical significance (HR, 17–28 mo, P = 0.12; HER2, 15–19 mo, P = 0.39). MS for patients who lost receptors was worse (HR, 27–18 mo, P = 0.02; HER2, 30–18 mo, P = 0.08). Conclusions Receptor discordance between primary tumor and BCBM is common, adversely affects survival if receptors are lost, and represents a missed opportunity for use of effective treatments if receptors are gained. Receptor analysis of BCBM is indicated when clinically appropriate. Treatment should be adjusted accordingly. Key Points 1. Receptor discordance alters subtype in 32% of BCBM patients. 2. The frequency of receptor gain for HR and HER2 was 25% and 13%, respectively. 3. If receptors are lost, survival suffers. If receptors are gained, consider targeted treatment.


2020 ◽  
pp. 1-9
Author(s):  
Matthias Millesi ◽  
Barbara Kiesel ◽  
Vanessa Mazanec ◽  
Lisa I. Wadiura ◽  
Adelheid Wöhrer ◽  
...  

OBJECTIVEGross-total resection (GTR) is the treatment of choice in the majority of patients suffering from spinal ependymal tumors. In such tumors, the extent of resection (EOR) is considered the key factor for tumor recurrence and thus patient prognosis. However, incomplete resection is not uncommon and leads to increased risk of tumor recurrence. One important cause of incomplete resection is insufficient intraoperative visualization of tumor tissue as well as residual tumor tissue. Therefore, the authors investigated the value of 5-aminolevulinic acid (5-ALA)–induced fluorescence in a series of spinal ependymal tumors for improved tumor visualization.METHODSAdult patients who underwent preoperative 5-ALA administration and surgery for a spinal ependymal tumor were included in this study. For each tumor, a conventional white-light microsurgical resection was performed. Additionally, the fluorescence status (strong, vague, or no fluorescence) and fluorescence homogeneity (homogenous or inhomogeneous) of the spinal ependymal tumors were evaluated during surgery using a modified neurosurgical microscope. In intramedullary tumor cases with assumed GTR, the resection cavity was investigated for potential residual fluorescing foci under white-light microscopy. In cases with residual fluorescing foci, these areas were safely resected and the corresponding samples were histopathologically screened for the presence of tumor tissue.RESULTSIn total, 31 spinal ependymal tumors, including 27 intramedullary tumors and 4 intradural extramedullary tumors, were included in this study. Visible fluorescence was observed in the majority of spinal ependymal tumors (n = 25, 81%). Of those, strong fluorescence was noted in 23 of these cases (92%), whereas vague fluorescence was present in 2 cases (8%). In contrast, no fluorescence was observed in the remaining 6 tumors (19%). Most ependymal tumors demonstrated an inhomogeneous fluorescence effect (17 of 25 cases, 68%). After assumed GTR in intramedullary tumors (n = 15), unexpected residual fluorescing foci within the resection cavity could be detected in 5 tumors (33%). These residual fluorescing foci histopathologically corresponded to residual tumor tissue in all cases.CONCLUSIONSThis study indicates that 5-ALA fluorescence makes it possible to visualize the majority of spinal ependymal tumors during surgery. Unexpected residual tumor tissue could be detected with the assistance of 5-ALA fluorescence in approximately one-third of analyzed intramedullary tumors. Thus, 5-ALA fluorescence might be useful to increase the EOR, particularly in intramedullary ependymal tumors, in order to reduce the risk of tumor recurrence.


2020 ◽  
Vol 14 ◽  
pp. 117955492094733
Author(s):  
Li Li ◽  
Zhulin Liu ◽  
Rui Han ◽  
Lin Li ◽  
Mengyao Wang ◽  
...  

Purpose: About one-third of nonsmall cell lung cancer (NSCLC) patients develop brain metastases (BM). However, there is an unmet need for early diagnosis and treatment of BM. The precise mechanism for BM is still unknown. However, the genetic heterogeneity between primary tumor and paired BM indicates that sampling from the primary tumor may not be able to fully represent the mutational status in metastases. In this study, the genetic heterogeneity of primary lung adenocarcinoma and paired BM was analyzed. Patients and methods: A total of 11 paired samples of primary tumors and BM from lung cancer patients were included, in which 7 paired samples of patients were finally analyzed. Samples were sequenced by whole-exome sequencing (WES) to investigate the common and unique mutations in the primary tumors and BM, and the similarities and differences in copy number variation (CNV). Results: The consistency of gene mutation between primary lung adenocarcinoma and paired BM was 33% to 86%. FAM129C and ADAMTSs specifically mutated in BM, along with NKX2-1 high amplification and SAMD2/4 copy number deletion. Conclusion: The consistency of gene mutation between primary lung adenocarcinoma and corresponding BM is relatively high, while the individual differences were significant. FAM129C and ADAMTSs mutations and high amplification of NKX2-1 may be related to BM of lung cancer. The loss of copy number of SAMD2/4 may be a potential therapeutic target for BM from lung adenocarcinoma.


Author(s):  
Wojciech Dudek ◽  
Waldemar Schreiner ◽  
Mohamed Haj Khalaf ◽  
Horia Sirbu

Abstract Background Despite weak evidence, pulmonary metastasectomy (PM) is widely performed with intent to improve patient survival. Our single-institution analysis aims to evaluate outcomes and to identify factors influencing survival of patients undergoing PM for metastases from wide range of primary tumors. Materials and Methods All patients undergoing curative-intent PM between 2008 and 2018 were retrospectively analyzed. The impact of factors related to primary tumor, metastases, and associated therapy on overall survival (OS) was evaluated using univariable and multivariable Cox proportional hazard models. Cutoff values of continuous variables were determined by a receiver operating characteristic analysis. Results In this study, 281 patients (178 male, median age 61 years) underwent PM. Two (0.7%) perioperative deaths and 23 (8.2%) major complications occurred. Median interval between the treatment of primary tumor and PM was 21 months. Median size of largest metastasis was 1.4 cm. After the median follow-up of 29 months, 134 patients (47.7%) had died. Five-year OS rate after first PM was 47.1%. Complete resection was achieved in 274 (97.5%) patients. Multivariable analysis identified genitourinary origin (hazard ratio [HR]: 0.30, 95% confidence interval [CI]: 0.15–0.60, p = 0.0008) as independent positive survival prognosticator; incomplete resection (HR: 3.53, 95% CI: 1.40–8.91, p = 0.0077) and age at PM of ≥66 years (HR: 1.97, 95% CI: 1.36–2.85, p = 0.0003) were negative prognosticators. Conclusion The use of PM as a part of multimodal treatment is in selected population justified. Our analysis identified age, primary tumor origin, and completeness of resection as independent survival prognosticators.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii79-ii79
Author(s):  
Yuzaburo Shimizu ◽  
Mario Suzuki ◽  
Osamu Akiyama ◽  
Akihide Kondo

Abstract BACKGROUND The diagnosis of a brain metastases is generally made during the follow up examinations of patients with primary known cancer. However, there are some patients presenting brain metastases as the first manifestation of a previously undiagnosed primary tumor (UDP) pathological confirmation of the diagnosis. The timing of a subsequent neurosurgical intervention is influenced by the distribution of primary tumors in UDP patients. The purpose of this study was to investigate the optimal diagnostic approach and the role of surgery for UDP patients. METHODS In a retrospective study, 35 patients admitted to our institution and underwent brain tumor removal from 2017 to 2019 with the diagnosis of cerebral metastases and diagnosed lung cancer as primary tumor subsequently, or previously diagnosed lung cancer. RESULTS UDP patients represented 46% of the whole group. Primary tumor subtype was the adenocarcinoma (n=13, 81%), small cell carcinoma (n=2, 13%), and neuroendocrine carcinoma (n=1, 6%). They did not have bronchoscopy nor excision of lung cancer. On the other hand, the patients previously diagnosed lung cancer represented 54% and subtype was adenocarcinoma (n=14, 74%) and small cell carcinoma (n=5, 26%). EGFR mutation was detected from 7 patients (44%) in UDP group and treated by EGFR tyrosine kinase inhibitor. CONCLUSION The significance of surgical intervention in metastatic brain tumors has been limited. However, active surgical intervention in UDP patients could identify not only histological diagnosis but also molecular biological characteristics. Our study suggests the possibility to avoid whole brain radiation in UDP patient by the active surgery.


2010 ◽  
Vol 113 (Special_Supplement) ◽  
pp. 48-52 ◽  
Author(s):  
Toru Serizawa ◽  
Masaaki Yamamoto ◽  
Yasunori Sato ◽  
Yoshinori Higuchi ◽  
Osamu Nagano ◽  
...  

Object The authors retrospectively reviewed the results of Gamma Knife surgery (GKS) used as the sole treatment for brain metastases in patients who met the eligibility criteria for the ongoing JLGK0901 multi-institutional prospective trial. They also discuss the anticipated results of the JLGK0901 study. Methods Data from 1508 consecutive cases were analyzed. All of the patients were treated at the Gamma Knife House of Chiba Cardiovascular Center or the Mito Gamma House of Katsuta Hospital between 1998 and 2007 and met the following JLGK0901 inclusion criteria: 1) newly diagnosed brain metastases, 2) 1–10 brain lesions, 3) less than 10 cm3 volume of the largest tumor, 4) no more than 15 cm3 total tumor volume, 5) no findings of CSF dissemination, and 6) no impairment of activities of daily living (Karnofsky Performance Scale score < 70) due to extracranial disease. At the initial treatment, all visible lesions were irradiated with GKS without upfront whole-brain radiation therapy. Thereafter, gadolinium-enhanced MR imaging was performed every 2–3 months, and new distant lesions were appropriately retreated with GKS. Patients were divided into groups according to numbers of tumors: Group A, single lesions (565 cases); Group B, 2–4 tumors (577 cases); and Group C, 5–10 tumors (366 cases). The differences in overall survival (OS) were compared between groups. Results The median age of the patients was 66 years (range 19–96 years). There were 963 men and 545 women. The primary tumors were in the lung in 1114 patients, gastrointestinal tract in 179, breast in 105, urinary tract in 66, and other sites in 44. The overall mean survival time was 0.78 years (0.99 years for Group A, 0.68 years for Group B, and 0.62 years for Group C). The differences between Groups A and B (p < 0.0001) and between Groups B and C (p = 0.0312) were statistically significant. Multivariate analysis revealed significant prognostic factors for OS to be sex (poor prognostic factor: male, p < 0.0001), recursive partitioning analysis class (Class I vs Class II and Class II vs III, both p < 0.0001), primary site (lung vs breast, p = 0.0047), and number of tumors (Group A vs Group B, p < 0.0001). However, no statistically difference was detected between Groups B and C (p = 0.1027, hazard ratio 1.124, 95% CI 0.999–1.265). Conclusions The results of this retrospective analysis revealed an upper CI of 1.265 for the hazard ratio, which was lower than the 1.3 initially set by the JLGK0901 study. The JLGK0901 study is anticipated to show noninferiority of GKS as sole treatment for patients with 5–10 brain metastases compared with those with 2–4 in terms of OS.


2008 ◽  
Vol 109 (Supplement) ◽  
pp. 118-121 ◽  
Author(s):  
Toru Serizawa ◽  
Masaaki Yamamoto ◽  
Osamu Nagano ◽  
Yoshinori Higuchi ◽  
Shinji Matsuda ◽  
...  

Object The authors compared results of Gamma Knife surgery (GKS) for brain metastases obtained at 2 institutions in Japan. Methods They analyzed a consecutive series of 2390 patients with brain metastases who underwent GKS from 1998 through 2005 in 2 institutes (1181 patients in Chiba; 1209 in Mito). In the 2 facilities, 1 neurosurgeon each was responsible for diagnosis, patient selection, GKS procedures, and follow-up (T.S. in Chiba, M.Y. in Mito). Even if tumor numbers exceeded 4, all visible lesions were irradiated with a total skull integral dose (TSID) of ≤ 10–12 J. No prophylactic whole-brain radiotherapy (WBRT) was applied. If new distant lesions were detected, salvage GKS was appropriately performed. Results The distributions of patient and treatment factors did not differ between institutes. The most common primary tumors were lung cancer (1572 patients), followed by gastrointestinal tract (316), breast (211), kidney (113), and other cancers (159). The median survival periods were 7.7 months in Chiba and 7.0 months in Mito (p = 0.0635). The significant poor prognostic factors for overall survival were active extracranial disease status, male sex, and low initial Karnofsky Performance Scale score on multivariate analysis (all p < 0.0001). The neurological survival rates at 1 year were 86.6% in Chiba and 84.2% in Mito (p = 0.3310). Conclusions This 2-institute study demonstrated no significant institutional differences in any of the treatment result items. Gamma Knife surgery for brain metastases without prophylactic WBRT prevents neurological death and allows a patient to maintain good brain condition. However, there is 1 important patient selection criterion: regardless of how many tumors there are, all lesions can be irradiated with a TSID of ≤12 J.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii46-ii46
Author(s):  
Jonathan Weller ◽  
Sophie Katzendobler ◽  
Philipp Karschnia ◽  
Stefanie Lietke ◽  
Rupert Egensperger ◽  
...  

Abstract BACKGROUND Current treatment guidelines for oligodendrogliomas (OD) recommend watch-and-wait strategies after gross total resection and radiation with subsequent chemotherapy (procarbazine, CCNU and vincristine (PCV)) after incomplete resection. The value of chemotherapy alone as an option to delay the risk of late cognitive deficits is not well defined yet. Here, we retrospectively investigated long-term outcome in OD WHO II with respect to initial therapy and tumor volume in magnetic resonance imaging (MRI). METHODS A total of 142 patients with OD WHO (World Health Organization) II according to WHO 2016 were retrospectively included. Patients either had watch and wait (W&W) after histological sampling through stereotactic biopsy (n=59) or tumor resection (n=27) or else stereotactic biopsy with subsequent temozolomide (TMZ) (n=26) or PCV (n=30). Pre- and post-therapeutic T2 tumor volumes were obtained. Progression-free survival (PFS), post-recurrence PFS (PR-PFS) and rate of secondary malignization after 10 years (MR-10yrs) were correlated with clinical and volumetric data. RESULTS PFS was significantly longer in the PCV cohort compared to TMZ (9.1 vs. 3.6 years, p = 0.04), even after matching patients according to age and initial tumor volume (9.1 vs 4.7 yrs, p = 0.03). PFS in the W&W cohort was 5.1 years and 4.4 years in those receiving tumor resection only. MR-10yrs was 4% in PCV cohort, 18% in the W&W cohort and 52% in the resection only cohort (p = 0.01). In the W&W cohort, patients treated with PCV at first relapse had a longer PR-PFS than those treated with TMZ (in years, 7.2 vs 4.0, p = 0.04). Multivariate analysis confirmed initial PCV therapy (p = 0.01) and initial T2 tumor volume (p = 0.02) to be prognostic. CONCLUSION In oligodendrogliomas WHO II PCV chemotherapy alone is superior in terms of PFS and rate of secondary malignization compared to TMZ chemotherapy alone or tumor resection only.


Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1213
Author(s):  
Zihe Huo ◽  
Mariana Sá Santos ◽  
Astrid Drenckhan ◽  
Stefan Holland-Cunz ◽  
Jakob R. Izbicki ◽  
...  

Despite continuous improvements in multimodal therapeutic strategies, esophageal carcinoma maintains a high mortality rate. Metastases are a major life-limiting component; however, very little is known about why some tumors have high metastatic potential and others not. In this study, we investigated thermogenic activity and adhesion strength of primary tumor cells and corresponding metastatic cell lines derived from two patients with metastatic adenocarcinoma of the esophagus. We hypothesized that the increased metastatic potential of the metastatic cell lines correlates with higher thermogenic activity and decreased adhesion strength. Our data show that patient-derived metastatic esophageal tumor cells have a higher thermogenic profile as well as a decreased adhesion strength compared to their corresponding primary tumor cells. Using two paired esophageal carcinoma cell lines of primary tumor and lymph nodes makes the data unique. Both higher specific thermogenesis profile and decreased adhesion strength are associated with a higher metastatic potential. They are in congruence with the clinical patient presentation. Understanding these functional, biophysical properties of patient derived esophageal carcinoma cell lines will enable us to gain further insight into the mechanisms of metastatic potential of primary tumors and metastases. Microcalorimetric evaluation will furthermore allow for rapid assessment of new treatment options for primary tumor and metastases aimed at decreasing the metastatic potential.


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