Background Brain Metastases Research Articles

Resecting the dominant lesion: Patient outcomes after surgery and radiosurgery vs stand-alone radiosurgery in the setting of multiple brain metastases

BackgroundBrain metastases are the most common central nervous system (CNS) tumors, occurring in 300,000 people per year in the US. While there are immediate local benefits to surgical resection for dominant lesions, including reduction of tumor burden and edema, the survival benefits of surgical resection, over radiosurgery, remains unclear. MethodsThe University of Pennsylvania Health System database was retrospectively reviewed for patients presenting with multiple brain metastases from 1/1/16–8/31/18 with one dominant lesion > 2 cm in diameter, who underwent initial treatment with either resection of the dominant lesion or Gamma Knife radiosurgery (GKS). Inclusion criteria were age > 18, > 1 brain metastasis, and presence of a dominant lesion (>2 cm). We analyzed factors associated with mortality. Results129 patients were identified (surgery=84, GKS=45). The median number of intracranial metastases was 3 (IQR: 2–5). The median diameter of the largest lesion was 31 mm (IQR: 25–38) in the surgery group vs 21 mm (IQR: 20–24) in the GKS group (p < 0.001). Mortality did not differ between surgery and GKS patients (69.1% vs 77.8%, p = 0.292). In a multivariate survival analysis, there was no difference in mortality between the surgery and GKS cohorts (aHR: 1.35, 95% CI: 0.74–2.45 p = 0.32). Pre-operative KPS (aHR: 0.97, 95% CI: 0.95–0.99, p = 0.004), CNS radiotherapy (aHR: 0.33, 95% CI: 0.19–0.56 p < 0.001), chemotherapy (aHR: 0.27, 95% CI: 0.15–0.47, p < 0.001), and immunotherapy (aHR: 0.41, 95% CI: 0.25–0.68, p = 0.001) were associated with decreased mortality. ConclusionIn our institution, patients with multiple brain metastases and one symptomatic dominant lesion demonstrated similar survival after GKS when compared with up-front surgical resection of the dominant lesion.

The structure of blood\u2013tumor barrier and distribution of chemotherapeutic drugs in non-small cell lung cancer brain metastases

BackgroundBrain metastasis is an important cause of increased mortality in patients with non-small cell lung cancer (NSCLC). In brain metastasis, the blood–brain barrier (BBB) is frequently impaired, forming blood–tumor barrier (BTB). The efficacy of chemotherapy is usually very poor. However, the characteristics of BTB and the impacts of BTB on chemotherapeutic drug delivery remain unclear. The present study investigated the structure of BTB, as well as the distribution of routine clinical chemotherapeutic drugs in both brain and peripheral tumors.MethodsBioluminescent image was used to monitor the tumor load after intracranial injection of lung cancer Lewis cells in mice. The permeability of BBB and BTB was measured by fluorescent tracers of evans blue and fluorescein sodium. Transmission electron microscopy (TEM), immunohistochemistry and immunofluorescence were performed to analyze structural differences between BBB and BTB. The concentrations of chemotherapeutic drugs (gemcitabine, paclitaxel and pemetrexed) in tissues were assayed by liquid chromatography with tandem mass spectrometry (LC-MS/MS).ResultsBrain metastases exhibited increased BTB permeability compared with normal BBB detected by fluorescence tracers. TEM showed abnormal blood vessels, damaged endothelial cells, thick basement membranes, impaired intercellular endothelial tight junctions, as well as increased fenestrae and pinocytotic vesicles in metastatic lesions. Immunohistochemistry and immunofluorescence revealed that astrocytes were distributed surrounded the blood vessels both in normal brain and the tumor border, but no astrocytes were found in the inner metastatic lesions. By LC-MS/MS analysis, gemcitabine showed higher permeability in brain metastases.ConclusionsBrain metastases of lung cancer disrupted the structure of BBB, and this disruption was heterogeneous. Chemotherapeutic drugs can cross the BTB of brain metastases of lung cancer but have difficulty crossing the normal BBB. Among the three commonly used chemotherapy drugs, gemcitabine has the highest distribution in brain metastases. The permeability of chemotherapeutic agents is related to their molecular weight and liposolubility.

Clinicopathological characteristics and prognosis of brain metastases in elderly patients with esophageal carcinoma.

BackgroundBrain metastases (BM) from esophageal carcinoma (EC) is clinically rare and has not yet been reported in elderly patients. This study aimed to investigate the clinicopathological characteristics, outcomes and prognostic factors of BM in elderly patients with EC, in order to provide guidance for clinical practice.MethodsA total of 20 EC patients older than 65 years who were diagnosed with BM were identified from the fourth Hospital of Hebei Medical University between January 1, 2009 and December 31, 2018. Survival was evaluated by the Kaplan–Meier method and Cox proportional hazards models.ResultsThe median time from diagnosis of EC to BM was 11.8 months (0–249.2 months). The median overall survival (OS) was 4.8 months (1.13–23.3 months), with 20% of patients achieving the 1‐year survival rate. Patients with KPS score of ≥70 had a significantly better OS than those with KPS score<70 (8.4 vs. 3.9 months, p = 0.033). Compared to patients without brain radiotherapy, patients with brain radiotherapy showed better outcomes in both median OS (8.4 vs. 2.9 months) and 1‐year survival rate (23.1% vs. 14.3%, p = 0.043). The median OS of patients with radiotherapy combined with chemotherapy and/or targeted therapy and radiotherapy alone was 9.7 months (3.4–23.3 months) and 7.2 months (1.7–18.4 months), respectively, with no significant difference between the two groups (p = 0.215).ConclusionsBrain radiotherapy provided clinically meaningful survival benefit for elderly patients with BM from EC. Thus, active treatments for those patients might be required.

The risk and prognostic factors for brain metastases in esophageal cancer patients: an analysis of the SEER database

BackgroundBrain metastases were rare in esophageal cancer patients. Using the Surveillance, Epidemiology, and End Results (SEER) database, the present study investigated the incidence, risk and prognostic factors of brain metastases in esophageal cancer patients.MethodsRetrieving esophageal cancer patients diagnosed between 2010 and 2018 from the SEER database, univariable and multivariable logistic and cox regression models were used to investigate the risk factors for brain metastases development and prognosis, respectively. The brain metastases predicting nomogram was constructed, evaluated and validated. The overall survival (OS) of patients with brain metastases was analyzed by Kaplan–Meier method.ResultsA total of 34,107 eligible esophageal cancer patients were included and 618 of them were diagnosed with brain metastases (1.8%). The median survival of the brain metastatic esophageal cancer patients was 5 (95% CI: 5–7) months. The presence of bone metastases and lung metastases were the homogeneously associated factors for the development and prognosis of brain metastases in esophageal cancer patients. Patients younger than 65 years, American Indian/Alaska Native race (vs. White), overlapping lesion (vs. Upper third), esophageal adenocarcinoma histology subtype, higher N stage, and liver metastases were positively associated with brain metastases occurrence. The calibration curve, ROC curve, and C-index exhibited good performance of the nomogram for predicting brain metastases.ConclusionsHomogeneous and heterogeneous factors were found for the development and prognosis of brain metastases in esophageal cancer patients. The nomogram had good calibration and discrimination for predicting brain metastases.

Brain Metastases From Differentiated Thyroid Carcinoma: A Retrospective Study of 22 Patients.

BackgroundBrain metastasis from differentiated thyroid cancer has followed a similar increasing trend to that of thyroid cancer in recent years. However, the characteristics and treatments for brain metastases are unclear. The aim of this study was to understand this disease by analyzing patients with brain metastases from differentiated thyroid cancer (DTC).MethodsBetween 2000 and 2020, the database of the Sun Yat-sen University Cancer Center was searched for differentiated thyroid cancer patients. We identified a cohort of 22 patients with brain metastases. The characteristics of the patients, histological features, treatments, and time of death were reviewed. The overall survival (OS) rate was calculated using the Kaplan Meier method. Survival curves of different subgroups were compared according to baseline characteristics and treatments received.ResultsA total of 22 (1.09%) out of 2013 DTC patients in the Sun Yat-sen University Cancer Center database were identified as having brain metastases. The overall median survival time was 17.5 months (range from 1–60 months) after diagnosis of brain metastasis. Performance statue (PS), tumor site, and neurosurgery impacted survival, according to Kaplan-Meier analysis. Prognosis of skull metastasis was superior to that of intracranial types. Neurosurgery was the only type of treatment that had an impact on patient OS.ConclusionsBrain metastasis from differentiated thyroid cancer has a poor prognosis. However, it can be improved by comprehensive treatment. PS of the patients can greatly affect survival. Skull metastases have improved prognosis over intracranial types. Radioiodine therapy (RAIT) appears to effectively improve the prognosis of patients with skull metastases from DTC.

Brain metastases in gastroesophageal cancers\u2014an underestimated complication

BackgroundBrain metastases represent a severe complication in many gastrointestinal malignancies especially those arising from the upper gastrointestinal tract, including cancer of the esophagus, gastroesophageal junction, and stomach (GEC). However, there is little knowledge about the onset or potential risk factors for brain metastases (BRMs) in upper gastrointestinal cancers resulting in a lack of screening guidelines for BRMs.MethodsWe analyzed 827 patients from our cancer registry suffering from gastroesophageal cancer (GEC) and treated at the University Medical Center Göttingen between January 2013 and December 2019 for the presence of BRMs.ResultsFrom 827 patients with GEC we found 54 patients with BRMs, resulting in an incidence of 6.5%. BRMs are more frequent in male patients (90.74% vs 9.26%, p = 0.0051) and in adenocarcinomas (90.74% vs 9.26%, p = 0.0117). Mean duration for the onset of BRMs from initial cancer diagnoses was 20.9 months in limited disease (curative approach) and 9.3 months in advanced disease (palliative approach) (p = 0.0026). However, early detection of BRMs is a prognostic factor since patients with successful resection of BRMs have a better prognosis compared to those with unresectable BRMs (5.93 vs 2.07 months, p = 0.0091).ConclusionIn this single-center retrospective study, brain metastases (BRMs) occur with a high frequency (6.5%) in gastroesophageal cancer (GEC), significantly more often in male patients and adenocarcinomas. Since survival of these patients considerably correlates with successful BRMs resection, our observations propose further prospective trails to validate our hypothesis and ultimately the implementation of routine screening procedures to detect asymptomatic brain metastases.

Brain Metastases Status and Immunotherapy Efficacy in Advanced Lung Cancer: A Systematic Review and Meta-Analysis.

BackgroundBrain metastases (BMs) indicate poor outcomes and are commonly excluded in immunotherapy clinical trials in advanced lung cancer; moreover, the effect of BM status on immunotherapy efficacy is inconsistent and inconclusive. Therefore, we conducted a meta-analysis to assess the influence of BM status on immunotherapy efficacy in advanced lung cancer.MethodsElectronic databases and all major conference proceedings were searched without language restrictions according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. We extracted randomized clinical trials on lung cancer immunotherapy that had available overall survival (OS) and/or progression-free survival (PFS) data based on the BM status. All analyses were performed using random effects models.ResultsFourteen randomized clinical trials with 9,089 patients were identified. Immunotherapy conferred a survival advantage to BM patients [OS-hazard ratio (HR), 0.72; 95% confidence interval (CI), 0.58–0.90; P = 0.004; and PFS-HR, 0.68; 95% CI, 0.52–0.87, P = 0.003]. Non-BM patients could also derive a survival benefit from immunotherapy (OS-HR, 0.76; 95% CI, 0.71–0.80; P <0.001; and PFS-HR, 0.68; 95% CI, 0.56–0.82, P <0.001). The pooled ratios of OS-HRs and PFS-HRs reported in BM patients versus non-BM patients were 0.96 (95% CI, 0.78–1.18; P = 0.72) and 0.97 (95% CI, 0.79–1.20; P = 0.78), respectively, indicating no statistically significant difference between them. Subsequent sensitivity analyses did not alter the results. Subgroup analyses according to tumor type, line of therapy, immunotherapy type, study design, and representation of BM patients reconfirmed these findings.ConclusionWe demonstrated that BM status did not significantly influence the immunotherapy efficacy in lung cancer, suggesting that both BM and non-BM patients could obtain comparable benefits.Systematic Review Registration https://www.crd.york.ac.uk/prospero/, identifier (CRD42020207446).

Longitudinal Genomic Evolution of Conventional Papillary Thyroid Cancer With Brain Metastasis

BackgroundBrain metastasis is extremely rare but predicts dismal prognosis in papillary thyroid cancer (PTC). Dynamic evaluation of stepwise metastatic lesions was barely conducted to identify the longitudinal genomic evolution of brain metastasis in PTC.MethodChronologically resected specimen was analyzed by whole exome sequencing, including four metastatic lymph nodes (lyn 1–4) and brain metastasis lesion (BM). Phylogenetic tree was reconstructed to infer the metastatic pattern and the potential functional mutations.ResultsContrasting with lyn1, ipsilateral metastatic lesions (lyn2–4 and BM) with shared biallelic mutations of TSC2 indicated different genetic originations from multifocal tumors. Lyn 3/4, particularly lyn4 exhibited high genetic similarity with BM. Besides the similar mutational compositions and signatures, shared functional mutations (CDK4R24C, TP53R342*) were observed in lyn3/4 and BM. Frequencies of these mutations gradually increase along with the metastasis progression. Consistently, TP53 knockout and CDK4R24C introduction in PTC cells significantly decreased radioiodine uptake and increased metastatic ability.ConclusionGenomic mutations in CDK4 and TP53 during the tumor evolution may contribute to the lymph node and brain metastasis of PTC.

Lipid polymeric nanoparticles modified with tight junction-modulating peptides promote afatinib delivery across a blood\u2013brain barrier model

BackgroundBrain metastases from non-small cell lung cancer (NSCLC) remain one of the most challenging malignancies. Afatinib (Afa) is an orally administered irreversible ErbB family blocker approved for epidermal growth factor receptor (EGFR)-mutated NSCLC. However, the incidence of brain metastases in patients with NSCLC and EGFR mutation is high. One of the major obstacles in the treatment of brain metastases is to transport drugs across the blood–brain barrier (BBB). A lipid polymeric nanoparticle (LPN) modified with a tight junction-modulating peptide is a potential formulation to deliver therapeutics across the BBB. FD7 and CCD are short peptides that perturb the tight junctions (TJs) of the BBB. In this study, the use of LPN modified with FD7 or CCD as a delivery platform was explored to enhance Afa delivery across the BBB model of mouse brain-derived endothelial bEnd.3 cells.ResultsOur findings revealed that Afa/LPN-FD7 and Afa/LPN-CCD exhibited a homogeneous shape, a uniform nano-scaled particle size, and a sustained-release profile. FD7, CCD, Afa/LPN-FD7, and Afa/LPN-CCD did not cause a significant cytotoxic effect on bEnd.3 cells. Afa/LPN-FD7 and Afa/LPN-CCD across the bEnd.3 cells enhanced the cytotoxicity of Afa on human lung adenocarcinoma PC9 cells. FD7 and CCD-modulated TJ proteins, such as claudin 5 and ZO-1, reduced transendothelial electrical resistance, and increased the permeability of paracellular markers across the bEnd.3 cells. Afa/LPN-FD7 and Afa/LPN-CCD were also partially transported through clathrin- and caveolae-mediated transcytosis, revealing the effective activation of paracellular and transcellular pathways to facilitate Afa delivery across the BBB and cytotoxicity of Afa on PC9 cells.ConclusionTJ-modulating peptide-modified LPN could be a prospective platform for the delivery of chemotherapeutics across the BBB to the brain for the potential treatment of the BM of NSCLC.

Primary tumor side is associated with prognosis of colorectal cancer patients with brain metastases

BackgroundBrain metastases (BM) are a rare complication in colorectal cancer (CRC) patients and associated with an unfavorable survival prognosis. Primary tumor side (PTS) was shown to act as a prognostic and predictive biomarker in several trials including metastatic CRC (mCRC) patients. Here, we aim to investigate whether PTS is also associated with the outcome of CRC patients with BM.MethodsPatients treated for CRC BM between 1988 and 2017 at an academic care center were included. Right-sided CRC was defined as located in the appendix, cecum and ascending colon and left-sided CRC was defined as located in the descending colon, sigma and rectum.ResultsTwo hundred and eighty-one CRC BM patients were available for this analysis with 239/281 patients (85.1%) presenting with a left-sided and 42/281 patients (14.9%) with a right-sided primary CRC. BM-free survival (BMFS) was significantly longer in left-sided compared with right-sided CRC patients (33 versus 20 months, P = 0.009). Overall survival from CRC diagnosis as well as from diagnosis of BM was significantly longer in patients with a left-sided primary (42 versus 25 months, P = 0.002 and 5 versus 4 months, P = 0.005, respectively). In a multivariate analysis including graded prognostic assessment, PTS remained significantly associated with prognosis after BM (hazard ratio 0.65; 95% confidence interval: 0.46-0.92 months, P = 0.0016).ConclusionsPTS was associated with survival times after the rare event of BM development in CRC patients. Therefore, its prognostic value remains significant even thereafter.

Overall survival after initial radiotherapy for brain metastases; a population based study of 2140 patients with non-small cell lung cancer

Background Brain metastases (BM) occur in about 30% of all patients with non-small cell lung cancer (NSCLC). BM treatment guidelines recommend more frequent use of stereotactic radiotherapy (SRT). Overall, studies report no difference in overall survival (OS) comparing SRT to whole-brain radiotherapy (WBRT). We examined survival after radiotherapy for BM in a population-based sample from the South-Eastern Norway Regional Health Authority treated 2006-2018. Methods We reviewed electronic medical records of 2140 NSCLC patients treated with SRT or WBRT for BM from 2006–2018. Overall survival (OS) was compared to predicted survival according to the prognostic systems DS-GPA and Lung-molGPA. Results Use of SRT increased during the period, from 19% (2006–2014) to 45% (2015–2018). Median OS for all patients was 3.0 months, increasing from 2.0 (2006) to 4.0 (2018). Median OS after SRT was 7.0 months (n = 435) and 3.0 months after WBRT (n = 1705). Twenty-seven percent of SRT patients and 50% of WBRT patients died within 90 days after start of RT. Age ≥70, male sex, KPS ≤70, non-adenocarcinoma histology, ECM present, multiple BM, and WBRT were associated with shorter survival (p < .001). Actual mOS corresponded best with predicted mOS by DS-GPA and Lung-molGPA for the SRT group. Conclusion Overall survival after radiotherapy (RT) for BM improved during the study period, but only for patients treated with SRT. Survival after WBRT remains poor; its use should be questioned. DS-GPA and Lung-molGPA seem most useful in predicting prognosis considered for SRT.

A nomogram for predicting brain metastasis in patients with de novo stage IV breast cancer.

BackgroundBrain metastasis (BM) is a very serious event in patients with breast cancer. The aim of this study was to establish a nomogram to predict the risk of BM in patients with de novo stage IV breast cancer.MethodsWe gathered female patients diagnosed with de novo stage IV breast cancer between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. After randomly allocating the patients to the training set and verification set, we used univariate and multivariate logistic regression to analyze the relationship between BM and clinicopathological features. Finally, we developed a nomogram which was validated by the analysis of calibration curve and receiver operating characteristic curve.ResultsOf 7,154 patients with de novo stage IV breast cancer, 422 developed BM. Age, tumor size, subtype, and the degree of lung involvement were significantly correlated with BM. The nomogram had discriminatory ability with an area under curve (AUC) of 0.640 [95% confidence interval (CI): 0.607 to 0.673] in the training set, and 0.644 (95% CI: 0.595 to 0.693) in the validation set.ConclusionsOur study developed a nomogram to predict BM for de novo stage IV breast cancer, thus helping clinicians to identify patients at high-risk of BM and implement early preventive interventions to improve their prognoses.

Differentiation of brain metastases from small and non-small lung cancers using apparent diffusion coefficient (ADC) maps

BackgroundBrain metastases are particularly common in patients with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), with NSCLC showing a less aggressive clinical course and lower chemo- and radio sensitivity compared to SCLC. Early adequate therapy is highly desirable and depends on a reliable classification of tumor type. The apparent diffusion coefficient is a noninvasive neuroimaging marker with the potential to differentiate between major histological subtypes. Here we determine the sensitivity and specificity of the apparent diffusion coefficient to distinguish between NSCLC and SCLC.MethodsWe enrolled all NSCLC and SCLC patients diagnosed between 2008 and 2019 at the University Medical Center Göttingen. Cranial MR scans were visually inspected for brain metastases and the ratio of the apparent diffusion coefficient (ADC) was calculated by dividing the ADC measured within the solid part of a metastasis by a reference ADC extracted from an equivalent region in unaffected tissue on the contralateral hemisphere.ResultsOut of 411 enrolled patients, we detected 129 patients (83 NSCLC, 46 SCLC) with sufficiently large brain metastases with histologically classified lung cancer and no hemorrhage. We analyzed 185 brain metastases, 84 of SCLC and 101 of NSCLC. SCLC brain metastases showed an ADC ratio of 0.68 ± 0.12 SD, and NSCLC brain metastases showed an ADC ratio of 1.47 ± 0.31 SD. Receiver operating curve statistics differentiated brain metastases of NSCLC from SCLC with an area under the curve of 0.99 and a 95% CI of 0.98 to 1, p < 0.001. Youden's J cut-point is 0.97 at a sensitivity of 0.989 and a specificity of 0.988.ConclusionsIn patients with lung cancer and brain metastases with solid tumor parts, ADC ratio enables an ad hoc differentiation of SCLC and NSCLC, easily achieved during routine neuroradiological examination. Non-invasive MR imaging enables an early-individualized management of brain metastases from lung cancer.Trial registration: The study was registered in the German Clinical Trials Register (DRKS00023016).

Tamoxifen suppresses brain metastasis of estrogen receptor-deficient breast cancer by skewing microglia polarization and enhancing their immune functions

BackgroundBrain metastasis of breast cancer exhibits exceedingly poor prognosis, and both triple negative (TN) and Her2+ subtypes have the highest incidence of brain metastasis. Although estrogen blockers are considered to be ineffective for their treatment, recent evidence indicates that estrogen blockade using tamoxifen showed certain efficacy. However, how estrogen affects brain metastasis of triple negative breast cancer (TNBC) remains elusive.MethodsTo examine the effect of estrogen on brain metastasis progression, nude mice were implanted with brain metastatic cells and treated with either estrogen supplement, tamoxifen, or ovariectomy for estrogen depletion. For clinical validation study, brain metastasis specimens from pre- and post-menopause breast cancer patients were examined for microglia polarization by immunohistochemistry. To examine the estrogen-induced M2 microglia polarization, microglia cells were treated with estrogen, and the M1/M2 microglia polarization was detected by qRT-PCR and FACS. The estrogen receptor-deficient brain metastatic cells, SkBrM and 231BrM, were treated with conditioned medium (CM) derived from microglia that were treated with estrogen in the presence or absence of tamoxifen. The effect of microglia-derived CM on tumor cells was examined by colony formation assay and sphere forming ability.ResultsWe found that M2 microglia were abundantly infiltrated in brain metastasis of pre-menopausal breast cancer patients. A similar observation was made in vivo, when we treated mice systemically with estrogen. Blocking of estrogen signaling either by tamoxifen treatment or surgical resection of mice ovaries suppressed M2 microglial polarization and decreased the secretion of C-C motif chemokine ligand 5, resulting in suppression of brain metastasis. The estrogen modulation also suppressed stemness in TNBC cells in vitro. Importantly, estrogen enhanced the expression of signal regulatory protein α on microglia and restricted their phagocytic ability.ConclusionsOur results indicate that estrogen promotes brain metastasis by skewing polarity of M2 microglia and inhibiting their phagocytic ability, while tamoxifen suppresses brain metastasis by blocking the M2 polarization of microglia and increasing their anti-tumor phagocytic ability. Our results also highlight a potential therapeutic utility of tamoxifen for treating brain metastasis of hormone receptor-deficient breast cancer.

The construction and validation of the model for predicting the incidence and prognosis of brain metastasis in lung cancer patients.

BackgroundBrain metastasis (BM) causes high morbidity and mortality rates in lung cancer (LC) patients. The present study aims to develop models for predicting the development and prognosis of BM using a large LC cohort.MethodsA total of 266,522 LC cases diagnosed between 2010 and 2016 were selected from the Surveillance, Epidemiology, and End Results (SEER) Program cohort. Risk factors for developing BM and prognosis were calculated by univariable and multivariable logistic and Cox regression analysis, respectively, and nomograms were constructed based on risk factors. Nomogram performance was evaluated with receiver operating characteristics (ROC) curve, or C-index and calibration curve.ResultsThe prevalence of BM was 13.33%. Associated factors for developing BM include: advanced age; Asian or Pacific Islander race; uninsured status; primary tumor site; higher T stage; higher N stage; poorly differentiated grade; the presence of lung, liver, and bone metastases; and adenocarcinoma histology. Median overall survival (OS) was 4 months; associated prognosis factors were similar to risk factors plus female gender, unmarried status, and surgery. The calibration curve showed good agreement between predicted and actual probability, and the AUC/C-index was 73.1% (95% CI: 72.6–73.6%) and 0.88 (95% CI: 0.87–0.89) for risk and prognosis predictive models, respectively.ConclusionsBM was highly developed in LC patients, and homogeneous and heterogeneous factors were found between risk and prognosis for BM. The nomogram showed good performance in predicting BM development and prognosis.

Breast Cancer Subtypes and Mortality of Breast Cancer Patients With Brain Metastasis at Diagnosis: A Population-Based Study.

BackgroundBrain metastasis is an important cause of breast cancer-related death.AimWe evaluated the relationships between breast cancer subtype and prognosis among patients with brain metastasis at the initial diagnosis.MethodsThe Surveillance, Epidemiology, and End Results database was searched to identify patients with brain metastasis from breast cancer between 2010 and 2015. Multivariable Cox proportional hazard models were used to identify factors that were associated with survival among patients with initial brain metastases. The Kaplan–Meier method was used to compare survival outcomes according to breast cancer subtype.ResultsAmong 752 breast cancer patients with brain metastasis at diagnosis, 140 patients (18.6%) underwent primary surgery and 612 patients (81.4%) did not undergo surgery, while 460 patients (61.2%) received chemotherapy and 292 patients (38.8%) did not receive chemotherapy. Multivariable analysis revealed that, relative to HR+/HER2– breast cancer, HR–/HER2– breast cancer was associated with significantly poorer overall survival (hazard ratio: 2.52, 95% confidence interval: 1.99–3.21), independent of age, sex, race, marital status, insurance status, grade, liver involvement, lung involvement, primary surgery, radiotherapy, and chemotherapy. The median overall survival intervals were 12 months for HR+/HER2−, 19 months for HR+/HER2+, 11 months for HR−/HER2+, and 6 months for HR–/HER2– (P < .0001). Relative to HR+/HER2– breast cancer, HR–/HER2– breast cancer was associated with a significantly higher risk of mortality among patients, and the association was stronger among patients who received chemotherapy (p for interaction = .005).ConclusionsBreast cancer subtype significantly predicted overall survival among patients with brain metastasis at diagnosis.

Brain metastases assessment by FDG-PET/CT: can it eliminate the necessity for dedicated brain imaging?

BackgroundBrain metastases (BM) are the most common intracranial tumors in adults outnumbering all other intracranial neoplasms. Positron emission tomography combined with computed tomography (PET/CT) is a widely used imaging modality in oncology with a unique combination of cross-sectional anatomic information provided by CT and the metabolic information provided by PET using the [18F]-2-fluoro-2-deoxy-d-glucose (FDG) as a tracer. The aim of the study is to assess the role and diagnostic performance of brain-included whole-body PET/CT in detection and evaluation of BM and when further imaging is considered necessary. The study was conducted over a period of 12 months on 420 patients suffering from extra-cranial malignancies utilizing brain-included whole-body PET/CT.ResultsThirty patients with 71 brain lesions were detected, 18 patients (60%) had BM of unknown origin while 12 patients (40%) presented with known primary tumors. After brain-included whole-body FDG-PET/CT examination, the unknown primaries turned out to be bronchogenic carcinoma in 10 patients (33.3%), renal cell carcinoma in 2 patients (6.7%), and lymphoma in 2 patients (6.7%), yet the primary tumors remained unknown in 4 patients (13.3%). In 61 lesions (85.9%), the max SUV ranged from 0.2- < 10, while in 10 lesions (14.1%) the max SUV ranged from 10 to 20. Hypometabolic lesions were reported in 41 (57.7%) lesions, hypermetabolic in 3 lesions (4.2%), whereas 27 lesions (38.0%) showed similar FDG uptake to the corresponding contralateral brain matter. PET/CT overall sensitivity, specificity, positive and negative predictive, and accuracy values were 78.1, 92.6, 83.3, 90, and 88% respectively.ConclusionBrain-included whole-body FDG-PET/CT provides valuable complementary information in the evaluation of patients with suspected BM. However, the diagnostic performance of brain PET-CT carries the possibility of false-negative results with consequent false sense of security. The clinicians should learn about the possible pitfalls of PET/CT interpretation to direct patients with persistent neurological symptoms or high suspicion for BM for further dedicated CNS imaging.

Impact of pre-OP independence in patients with limited brain metastases on long-term survival

BackgroundBrain metastasis represents a major complication with a significantly shorter overall survival of many oncological diseases, in particular of lung cancer, breast cancer and malignant melanoma patients. However, despite the poor prognosis, sometimes clinical decision-making, between on the one hand not to harm the patient and on the other hand not withholding a potential therapeutic option, is very challenging. Thus the aim of this retrospective study was to compare various scores, including scores for activities of daily living (ADL) before resection of brain metastases and to analyse their impact on survival.MethodsOur single institution retrospective patient cohort (N = 100) with a median age of 63.6 years, which had all undergone resection of one or more brain metastases, was categorized using the original patient files. The cohort includes 52 patients with lung cancer, 27 patients with breast cancer, 8 patients with colorectal carcinoma and 13 patients with kidney cancer. To categorize, we used different score systems which were capable to evaluate the patient in relation to self-sufficiency, activity and self-determination as part of ADL. The retrospective analysis includes the ECOG-Status, Karnofsky-Index, Barthel-Index, ASA-Classification and Katz-Index. Pre-processing and the analysis of the data was implemented using KNIME, where we used the R-plugin nodes to perform the final statistical tests with R.ResultsOur analysis reveals that most of the ADL scores we tested are able to give a reliable prediction on overall survival after brain metastasis surgery. The survival rates decrease significantly with a lower score in all tested score systems, with the exception of the ASA-Risk score. In particular, the Katz Index < 6 was identified to have a significant correlation with a lower cancer specific survival (CSS) (HR 3.33, 95%-CI [2.17–5.00]; p-Value = 9.6*10− 9), which is easy to use and has reproducible measurements.ConclusionsPre-operative independence assessment by indices of ADL represents a predictor for overall survival after resection of brain metastases. Especially the easily, objectively and rapidly applicable Katz-Score is a very helpful tool to assess the pre-operative status, which could be additionally included in clinical decision making in daily practice.

Neurologically asymptomatic cerebral oligometastatic prostate carcinoma metastasis identified on [Ga]Ga-THP-PSMA PET/CT

BackgroundBrain metastases from prostate cancer are rare and usually only occur in the context of widespread systemic disease. This is the first case report of a solitary brain oligometastasis, in a neurologically intact prostate cancer patient with no other systemic disease, detected using [68Ga]Ga-THP-PSMA PET/CT and only the second one using a PSMA-based radiopharmaceutical.Case presentationWe report the case of a prostate cancer patient presenting 5 years after robot-assisted laparoscopic prostatectomy with biochemical recurrence, no neurological symptoms, and in the absence of metastatic lesions in the body on conventional imaging. A solitary cerebral metastasis was detected using [68Ga]Ga-THP-PSMA PET/CT, surgically resected, leading to a drop in serum PSA and a good recovery.ConclusionIn this case, [68Ga]Ga-THP-PSMA PET/CT resulted in a major change in clinical management and avoided additional morbidity associated with delayed diagnosis and treatment. This report demonstrates the importance of considering the presence of metastatic disease outside the conventional locations of prostate cancer spread, as well as the importance of ensuring comprehensive [68Ga]Ga-PSMA PET/CT coverage from vertex to upper thighs.

HER2-positive breast cancer brain metastasis: A new and exciting landscape.

BackgroundBrain metastases (BrM) incidence is 25% to 50% in women with advanced human epidermal growth factor receptor 2 (HER2)‐positive breast cancer. Radiation and surgery are currently the main local treatment approaches for central nervous system (CNS) metastases. Systemic anti‐HER2 therapy following a diagnosis of BrM improves outcomes. Previous preclinical data has helped elucidate HER2 brain trophism, the blood‐brain/blood‐tumor barrier(s), and the brain tumor microenvironment, all of which can lead to development of novel therapeutic options.Recent findingsSeveral anti‐HER2 agents are currently available and reviewed here, some of which have recently shown promising effects in BrM patients, specifically. New strategies driven by and focusing on brain metastasis‐specific genomics, immunotherapy, and preventive strategies have shown promising results and are under development.ConclusionsThe field of HER2+ breast cancer, particularly for BrM, continues to evolve as new therapeutic strategies show promising results in recent clinical trials. Increasing inclusion of patients with BrM in clinical studies, and a focus on assessing their outcomes both intracranially and extracranially, is changing the landscape for patients with HER2+ CNS metastases by demonstrating the ability of newer agents to improve outcomes.