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Purpose: Stereotactic Radiosurgery (SRS) is the primary treatment for patients with limited numbers of small brain metastases. Head fixation is usually performed with framed-based (FB) fixation; however, mask-based (MB) fixation has emerged as a less invasive alternative. A comparative meta-analysis between both approaches has not been performed. Methods: Databases were searched until August 28th, 2023, to identify studies comparing MB and FB SRS in the treatment of brain metastases. Our outcomes of interest included local tumor control (LTC), radiation necrosis (RN), mortality, and treatment time (TT). Mean difference (MD), risk ratio (RR), and hazard ratio (HR) were used for statistical comparisons. Results: From 295 articles initially identified, six studies (1 clinical trial) involving 509 patients were included. LTC revealed comparable RR at 6-months (RR = 0.95[95%CI = 0.89–1.01], p = 0.12) and a marginal benefit in FB SRS at 1-year (RR = 0.87[95%CI = 0.78–0.96], p = 0.005). However, in oligometastases exclusively treated with single-fraction SRS, LTC was similar among groups (RR = 0.92 [95%CI = 0.89–1.0], p = 0.30). Similarly, in patients with oligometastases treated with single-fraction SRS, RN (HR = 1.69; 95%CI = 0.72–3.97, p = 0.22), TT (MD = -29.64; 95%CI = -80.38–21.10, p = 0.25), and mortality were similar among groups (RR = 0.62; 95%CI = 0.22–1.76, p = 0.37). Conclusion: Our findings suggest that FB and MB SRS, particularly oligometastases treated with single-fraction, are comparable in terms of LTC, RN, TT, and mortality. Further research is essential to draw definitive conclusions. [ABSTRACT FROM AUTHOR]

Abstract Metastatic brain tumors, also called brain metastasis (BM), represent a challenging complication of advanced tumors. Tumors that commonly metastasize to the brain include lung cancer and breast cancer. In recent years, the prognosis for BM patients has improved, and significant advancements have been made in both clinical and preclinical research. This review focuses on BM originating from lung cancer and breast cancer. We briefly overview the history and epidemiology of BM, as well as the current diagnostic and treatment paradigms. Additionally, we summarize multiomics evidence on the mechanisms of tumor occurrence and development in the era of artificial intelligence and discuss the role of the tumor microenvironment. Preclinically, we introduce the establishment of BM models, detailed molecular mechanisms, and cutting‐edge treatment methods. BM is primarily treated with a comprehensive approach, including local treatments such as surgery and radiotherapy. For lung cancer, targeted therapy and immunotherapy have shown efficacy, while in breast cancer, monoclonal antibodies, tyrosine kinase inhibitors, and antibody–drug conjugates are effective in BM. Multiomics approaches assist in clinical diagnosis and treatment, revealing the complex mechanisms of BM. Moreover, preclinical agents often need to cross the blood–brain barrier to achieve high intracranial concentrations, including small‐molecule inhibitors, nanoparticles, and peptide drugs. Addressing BM is imperative.

Brainmetastatic cancer poses a significant clinical challenge, with limited treatment options and poor prognosis for patients. In recent years, immunotherapy has emerged as a promising strategy for addressing brain metastases, offering distinct advantages over conventional treatments. This review explores the evolving landscape of tumor immunotherapy in the context of brain metastatic cancer, focusing on the intricate interplay between the tumor microenvironment (TME) and immunotherapeutic approaches. By elucidating the complex interactions within the TME, including the role of immune cells, cytokines, and extracellular matrix components, this review highlights the potential of immunotherapy to reshape the treatment paradigm for brain metastases. Leveraging immune checkpoint inhibitors, cellular immunotherapies, and personalized treatment strategies, immunotherapy holds promise in overcoming the challenges posed by the blood-brain barrier and immunosuppressive microenvironment of brain metastases. Through a comprehensive analysis of current research findings and future directions, this review underscores the transformative impact of immunotherapy on the management of brain metastatic cancer, offering new insights and opportunities for personalized and precise therapeutic interventions. [ABSTRACT FROM AUTHOR]

Simple Summary: In the present study, the intraoperative fluorescence of brain metastases after the administration of 5-aminolevulinic acid (5-ALA) is investigated in 80 cases. Brain metastases fluoresced in 57.5% of cases, with no significant correlation between fluorescence and primary tumor or histological subtype. Complete resection of brain metastases was detected in 82.5%, of which 56.1% were fluorescence positive, compared to 43.9% which were non-fluorescent. Thus, prior administration of 5-ALA tended to improve the resectability rate by 12.1%. Fluorescence-positive and -negative metastases showed significantly different overall survival in this study. Therefore, administration of 5-ALA as a surgical adjuvant may be beneficial in resecting brain metastases and may potentially optimize the surgical procedure. (1) Background: In this study, the intraoperative fluorescence behavior of brain metastases after the administration of 5-aminolevulinic acid (5-ALA) was analyzed. The aim was to investigate whether the resection of brain metastases using 5-ALA fluorescence also leads to a more complete resections and thus to a prolongation of survival; (2) Methods: The following variables have been considered: age, sex, number of metastases, localization, involvement of eloquent area, correlation between fluorescence and primary tumor/subtype, resection, and survival time. The influence on the degree of resection was determined with a control MRI within the first three postoperative days; (3) Results: Brain metastases fluoresced in 57.5% of cases. The highest fluorescence rates of 73.3% were found in breast carcinoma metastases and the histologic subtype adenocarcinoma (68.1%). No correlation between fluorescence behavior and localization, primary tumor, or histological subtype was found. Complete resection was detected in 82.5%, of which 56.1% were fluorescence positive. There was a trend towards improved resectability (increase of 12.1%) and a significantly longer survival time (p = 0.009) in the fluorescence-positive group; (4) Conclusions: 5-ALA-assisted extirpation leads to a more complete resection and longer survival and can therefore represent a low-risk addition to modern surgery for brain metastases. [ABSTRACT FROM AUTHOR]

Abstract Background Oligoprogression is an emerging issue in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, the surgical treatment for central nervous system (CNS) oligoprogression is not widely discussed. We investigated the outcomes of craniotomy with adjuvant whole-brain radiotherapy (WBRT) and subsequent therapies for CNS oligoprogression in patients with EGFR-mutated NSCLC. Methods NSCLC patients with CNS oligoprogression were identified from a tertiary medical center. The outcomes of surgery with adjuvant WBRT or WBRT alone were analyzed, along with other variables. Overall survival and progression-free survival were analyzed using the log-rank test as the primary and secondary endpoints. A COX regression model was used to identify the possible prognostic factors. Results Thirty-seven patients with CNS oligoprogression who underwent surgery or WBRT were included in the study after reviewing 728 patients. Twenty-one patients underwent surgery with adjuvant WBRT, and 16 received WBRT alone. The median overall survival for surgery and WBRT alone groups was 43 (95% CI 17–69) and 22 (95% CI 15–29) months, respectively. Female sex was a positive prognostic factor for overall survival (OR 0.19, 95% CI 0.06–0.57). Patients who continued previous tyrosine kinase inhibitors (OR 3.48, 95% CI 1.06–11.4) and induced oligoprogression (OR 3.35, 95% CI 1.18–9.52) were associated with worse overall survival. Smoking history (OR 4.27, 95% CI 1.54–11.8) and induced oligoprogression (OR 5.53, 95% CI 2.1–14.7) were associated with worse progression-free survival. Conclusions Surgery combined with adjuvant WBRT is a feasible treatment modality for CNS oligoprogression in patients with EGFR-mutated NSCLC. Changing the systemic-targeted therapy after local treatments may be associated with improved overall survival.

• Surgery alone for metastases often results in local recurrence due to microscopic residual tumor. • Hypofractionation could be an alternative to single fraction for larger surgical beds. • Hypofractionation is a safe post-operative adjuvant therapy with minimal severe adverse effects. Surgery alone for metastatic brain tumors (METs) often results in local recurrence due to microscopic residual tumor tissue. While stereotactic radiosurgery (SRS) is commonly used post-surgery, hypofractionation may be required for large surgical beds. This study evaluated the efficacy and safety of hypofractionated Gamma Knife radiosurgery (hf-GKRS) for the first time as a post-operative adjuvant therapy. This retrospective study involved 24 patients (28 surgical beds) who underwent hf-GKRS within four weeks after surgery. The study primarily focused on local control (LC) rate and analyzed distant intracranial failure (DICF), intracranial progression-free survival (PFS), leptomeningeal disease (LMD), overall survival (OS), and radiation necrosis (RN). During a median follow-up of 9 months, LC was achieved in 89.3 % of surgical beds. LC estimates at 6, 12, and 24 months were 96.4 %, 82.7 %, and 82.7 %, respectively. DICF was observed in 45.8 % of patients, and LMD was identified in two patients (8.3 %). At the end of the follow-up, 58.3 % of patients were alive, and the median OS was 20 months. RN occurred in only one surgical bed (3.6 %). No grade 5 toxicity was observed. The univariate analysis identified a longer interval to GKRS (HR 11.842, p = 0.042) and a larger treatment volume (HR 1.103, p = 0.037) as significant factors for local failure. hf-GKRS shows potential as an effective and safe adjuvant treatment for surgical beds. It offers an alternative to SRS, SRT, or WBRT, particularly for larger volumes or tumors near critical structures. Further research is needed to confirm these results and optimize treatment approaches. [ABSTRACT FROM AUTHOR]

Astrocytes are highly plastic cells whose activity is essential to maintain the cerebral homeostasis, regulating synaptogenesis and synaptic transmission, vascular and metabolic functions, ions, neuro- and gliotransmitters concentrations. In pathological conditions, astrocytes may undergo transient or long-lasting molecular and functional changes that contribute to disease resolution or exacerbation. In recent years, many studies demonstrated that non-neoplastic astrocytes are key cells of the tumor microenvironment that contribute to the pathogenesis of glioblastoma, the most common primary malignant brain tumor and of secondary metastatic brain tumors. This Mini Review covers the recent development of research on non-neoplastic astrocytes as tumor-modulators. Their double-edged capability to promote cancer progression or to represent potential tools to counteract brain tumors will be discussed. [ABSTRACT FROM AUTHOR]

Purpose: This paper presents a deep learning model for use in the automated segmentation of metastatic brain tumors and associated perilesional edema. Methods: The model was trained using Gamma Knife surgical data (90 MRI sets from 46 patients), including the initial treatment plan and follow-up images (T1-weighted contrast-enhanced (T1cWI) and T2-weighted images (T2WI)) manually annotated by neurosurgeons to indicate the target tumor and edema regions. A mask region-based convolutional neural network was used to extract brain parenchyma, after which the DeepMedic 3D convolutional neural network was in the segmentation of tumors and edemas. Results: Five-fold cross-validation demonstrated the efficacy of the brain parenchyma extraction model, achieving a Dice similarity coefficient of 96.4%. The segmentation models used for metastatic tumors and brain edema achieved Dice similarity coefficients of 71.6% and 85.1%, respectively. This study also presents an intuitive graphical user interface to facilitate the use of these models in clinical analysis. Conclusion: This paper introduces a deep learning model for the automated segmentation and quantification of brain metastatic tumors and perilesional edema trained using only T1cWI and T2WI. This technique could facilitate further research on metastatic tumors and perilesional edema as well as other intracranial lesions. [ABSTRACT FROM AUTHOR]

Astrocytes are highly plastic cells whose activity is essential to maintain the cerebral homeostasis, regulating synaptogenesis and synaptic transmission, vascular and metabolic functions, ions, neuro- and gliotransmitters concentrations. In pathological conditions, astrocytes may undergo transient or long-lasting molecular and functional changes that contribute to disease resolution or exacerbation. In recent years, many studies demonstrated that non-neoplastic astrocytes are key cells of the tumor microenvironment that contribute to the pathogenesis of glioblastoma, the most common primary malignant brain tumor and of secondary metastatic brain tumors. This Mini Review covers the recent development of research on non-neoplastic astrocytes as tumor-modulators. Their double-edged capability to promote cancer progression or to represent potential tools to counteract brain tumors will be discussed.

Background: Oligoprogression is an emerging issue in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, the surgical treatment for central nervous system (CNS) oligoprogression is not widely discussed. We investigated the outcomes of craniotomy with adjuvant whole-brain radiotherapy (WBRT) and subsequent therapies for CNS oligoprogression in patients with EGFR-mutated NSCLC. Methods: NSCLC patients with CNS oligoprogression were identified from a tertiary medical center. The outcomes of surgery with adjuvant WBRT or WBRT alone were analyzed, along with other variables. Overall survival and progression-free survival were analyzed using the log-rank test as the primary and secondary endpoints. A COX regression model was used to identify the possible prognostic factors. Results: Thirty-seven patients with CNS oligoprogression who underwent surgery or WBRT were included in the study after reviewing 728 patients. Twenty-one patients underwent surgery with adjuvant WBRT, and 16 received WBRT alone. The median overall survival for surgery and WBRT alone groups was 43 (95% CI 17–69) and 22 (95% CI 15–29) months, respectively. Female sex was a positive prognostic factor for overall survival (OR 0.19, 95% CI 0.06–0.57). Patients who continued previous tyrosine kinase inhibitors (OR 3.48, 95% CI 1.06–11.4) and induced oligoprogression (OR 3.35, 95% CI 1.18–9.52) were associated with worse overall survival. Smoking history (OR 4.27, 95% CI 1.54–11.8) and induced oligoprogression (OR 5.53, 95% CI 2.1–14.7) were associated with worse progression-free survival. Conclusions: Surgery combined with adjuvant WBRT is a feasible treatment modality for CNS oligoprogression in patients with EGFR-mutated NSCLC. Changing the systemic-targeted therapy after local treatments may be associated with improved overall survival. [ABSTRACT FROM AUTHOR]

Objective The interplay of static factors and their effect on metastatic brain tumor survival, especially in low-to-middle-income countries (LMICs), has been rarely studied. To audit our experience, and explore novel survival predictors, we performed a retrospective analysis of brain metastases (BM) patients at Shaukat Khanum Memorial Cancer Hospital (SKMCH), Pakistan. Materials and Methods A retrospective review was conducted of consecutive patients who presented with BM between September 2014 and September 2019 at SKMCH. Patients with incomplete records were excluded. Statistical Analysis SPSS (v.25 IBM, Armonk, New York, United States) was used to collect and analyze data via Cox-Regression and Kaplan–Meier curves. Results One-hundred patients (mean age 45.89 years) with confirmed BM were studied. Breast cancer was the commonest primary tumor. Median overall survival (OS) was 6.7 months, while the median progression-free survival (PFS) was 6 months. Age (p = 0.001), gender (p = 0.002), Eastern Cooperative Oncology Group (p < 0.05), anatomical site (p = 0.002), herniation (p < 0.05), midline shift (p = 0.002), treatment strategies (p < 0.05), and postoperative complications (p < 0.05) significantly impacted OS, with significantly poor prognosis seen with extremes of age, male gender (hazard ratio [HR]: 2.0; 95% confidence interval [CI]: 1.3–3.1; p = 0.003), leptomeningeal lesions (HR: 5.7; 95% CI: 1.1–29.7; p = 0.037), and patients presenting with uncal herniation (HR: 3.5; 95% CI: 1.9–6.3; p < 0.05). Frontal lobe lesions had a significantly better OS (HR: 0.5; 95% CI: 0.2–1.0; p = 0.049) and PFS (HR: 0.08; 95% CI: 0.02–0.42; p = 0.003). Conclusion BM has grim prognoses, with comparable survival indices between developed countries and LMICs. Early identification of both primary malignancy and metastatic lesions, followed by judicious management, is likely to significantly improve survival. [ABSTRACT FROM AUTHOR]

BackgroundImproving outcomes for patients with human epidermal growth factor 2-positive (HER2+) central nervous system (CNS) metastases remains an unmet clinical need. This trial evaluated a novel combination of everolimus, lapatinib and capecitabine for this disease.MethodsPatients with trastuzumab-pretreated, HER2+ breast cancer brain metastasis without prior therapy with a mammalian target of rapamycin (mTOR) inhibitor were eligible. Patients received lapatinib and everolimus daily (continuously) and capecitabine twice daily (d1-14) in 21-d cycles. The primary endpoint was the 12-week CNS objective response rate (ORR). Secondary endpoints included safety, progression-free survival (PFS), overall survival (OS), best CNS ORR and extra-CNS ORR.ResultsA total of 19 participants were enrolled and treated with ⩾1 dose of the study drug. The median age was 58.5 years, the median number of therapies for metastatic breast cancer was 2.5 (0-11). Pretrial, 74% of participants had received prior lapatinib, capecitabine or both. A total of 63% had received previous CNS radiation or surgical resection and CNS radiation. The maximum tolerated doses were lapatinib at 1000 mg, everolimus at 10 mg, and capecitabine at 1000 mg/m2. Phase II proceeded with capecitabine at 750 mg/m2 due to better tolerability. The most common grade 3/4 adverse events were mucositis (16%), diarrhea, fatigue, and hypokalemia (11% each). Of 11 participants evaluable for 12-week CNS ORR, 3 (27%) had partial response and 7 (64%) had stable disease. The best CNS ORR in eligible participants was 28% (5/18). The median PFS and OS were 6.2 and 24.2 months, respectively.ConclusionsThis novel triplet combination of lapatinib, everolimus, and capecitabine is well tolerated and yielded a 27% response rate in the CNS at 12 weeks in heavily pretreated participants. Larger studies are warranted to further evaluate this regimen.Trial registrationClinicalTrials.gov: NCT01783756. Registered 05 February 2013, https://clinicaltrials.gov/ct2/show/NCT01783756.

Abstract Background Taenia solium, present in most developing countries, infects many individuals and may result in their death. Neurocysticercosis (NCC) develops after invasion of the brain by parasitic larvae. It is the most common parasitic disease of the human central nervous system. On imaging scans it can be similar to brain tumors. We report a patient with a metastatic brain tumor and NCC. The co-presence of NCC was diagnosed based on specific neuroimaging- and epidemiologic findings. Case presentation A 36-year-old non-smoking Japanese woman with a history of non-small-cell lung cancer had undergone resection of the lower lobe followed by cytotoxic chemotherapy 2 years before apparently suffering recurrence. A positron emission computed tomography (PET) scan incidentally revealed multiple intracranial cold spots exhibiting differences in their shape and size. On brain magnetic resonance imaging (MRI) scans we observed many different patterns of peripheral edema and gadolinium-enhancing effects. As she had often visited Latin America and Southeast Asia and had eaten raw pork and Kimchi, we suspected that the brain lesions were due to NCC rather than metastatic brain tumors. However, serum immunoblotting assay and DNA analysis were negative for T. solium. Rather than performing resection, we administered albendazole (ABZ) and dexamethasone because her earlier cytotoxic chemotherapy had elicited severe pancytopenia. Except for a single large lesion in the left frontal lobe, this treatment resulted in a significant reduction in the size of these lesions and a decrease in perilesional edema. She underwent resection of the residual lesion 10 months later. Histology revealed it to be a metastatic tumor. Polymerase chain reaction (PCR) assay for NCC was negative. In the course of 11-months follow-up there has been no recurrence. Conclusion This is the first presentation of NCC in a Japanese woman with a metastatic brain tumor. NCC was incidentally discovered on PET scans and, based on her travel history and epidemiological findings; it was diagnosed and successfully treated with ABZ. NCC is endemic in most developing countries and as visits to such countries have increased, NCC must be ruled out in patients with multiple cystic nodular brain lesions.

Aim:We investigated the reflection of tumor dyeing (staining), an auxiliary technique for the resection of metastases, which are the most prevalent group among brain tumors, via microsurgery.Materials and Methods:Twenty one patients, who were operated under surgical white light, and 27 patients who were operated via sodium fluorescein (FL) dyeing (staining) due to metastatic brain tumors were evaluated retrospectively. The gross total resection (GTR) rates, surgical time, amount of blood loss, and the duration of hospital stay for both groups were compared. The contribution of FL dyeing (staining) to surgery was evaluated for the group with FL dyeing (staining).Results:The study comprised of 48 patients in total. The median age of patients was 61.5 years (minimum: 20, maximum: 80), the average age was 59.1±11.8 years. There was no difference between the group with FL dyeing and the one without dyeing in terms of gender, age, tumor size, GTR rates and surgical time. Blood loss and duration of hospital stay in the FL used group was significantly less. In the group with FL dyeing (staining) (92.5%), this method contributed to the surgery by giving yellow highlights.Conclusion:It has been found out that in the surgery of metastatic brain tumors, FL dyeing decreases the blood loss, shortens the surgical time, and aids in the differentiation of tumor glial tissue.

The anaplastic lymphoma kinase (ALK) gene plays crucial roles in both normal brain development and oncogenesis, particularly in non-small cell lung cancer (NSCLC). Metastatic ALK-positive NSCLC is characterized by ALK tyrosine kinase domain rearrangements, prompting the use of ALK tyrosine kinase inhibitors (TKIs) to target the mutation. While first-line treatment options include alectinib, brigatinib, and lorlatinib per National Comprehensive Cancer Network (NCCN) guidelines, therapeutic challenges arise in cases of disease progression. Management strategies may involve radiation therapy, switching to alternative ALK inhibitors, or testing for resistance mutations like ALK G1202R to guide treatment selection, with lorlatinib emerging as an alternative treatment option. Here, we present the case of a 35-year-old male diagnosed with metastatic ALK-positive NSCLC. Despite initial stability on alectinib therapy, disease progression necessitated therapeutic modification, including a switch to brigatinib and subsequent treatment with lorlatinib monotherapy. Notably, the patient achieved complete remission radiologically and clinically following treatment with lorlatinib, highlighting its efficacy in refractory disease settings. While molecular research supports lorlatinib's superior central nervous system (CNS) penetrability and systemic efficacy, the absence of head-to-head clinical trials presents a significant gap in evidence. Direct comparison of second and third-generation ALK inhibitors is essential to elucidate their comparative efficacy and adverse event profiles, which could refine current management guidelines. Furthermore, if lorlatinib proves superior in terms of progression-free survival, it may offer the potential to delay or obviate the need for radiation therapy, thus mitigating the risk of neurotoxic adverse events associated with these modalities., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Narlapati et al.)

Background: Cystic formation due to radiation necrosis in metastatic brain tumors is a rare condition. Surgical intervention is necessary if symptoms develop. Additionally, excising radiation necrosis lesions within the cyst is essential to prevent recurrence. Neuroendoscopic surgery is a minimally invasive method suitable for treating cystic diseases and accessing deep lesions in the brain. The authors herein present a method for removing radiation necrotic tissue from deep lesions of cystic radiation necrosis using neuroendoscopy., Observations: Endoscopic surgery was performed in two patients with symptomatic cystic radiation necrosis. Both cases involved multilocular cysts, with radiation necrosis located deep within the cyst. The authors performed a small craniotomy of approximately 3 cm and opened the cyst. After removing its contents, an endoscope was used to closely observe the interior of the cyst. Removal of the septum within the cyst allowed the endoscope to be inserted deeply. The authors identified and excised the nodular lesion diagnosed as radiation necrosis in the deep tissue. Following the surgery, the cyst shrank rapidly, and symptoms disappeared. Both patients showed no recurrence of the lesions., Lessons: The authors performed minimally invasive surgery and achieved good outcomes. Endoscopic surgery was considered beneficial for treating cystic radiation necrosis. https://thejns.org/doi/10.3171/CASE24250.

Background: Taenia solium, present in most developing countries, infects many individuals and may result in their death. Neurocysticercosis (NCC) develops after invasion of the brain by parasitic larvae. It is the most common parasitic disease of the human central nervous system. On imaging scans it can be similar to brain tumors. We report a patient with a metastatic brain tumor and NCC. The co-presence of NCC was diagnosed based on specific neuroimaging- and epidemiologic findings.Case Presentation: A 36-year-old non-smoking Japanese woman with a history of non-small-cell lung cancer had undergone resection of the lower lobe followed by cytotoxic chemotherapy 2 years before apparently suffering recurrence. A positron emission computed tomography (PET) scan incidentally revealed multiple intracranial cold spots exhibiting differences in their shape and size. On brain magnetic resonance imaging (MRI) scans we observed many different patterns of peripheral edema and gadolinium-enhancing effects. As she had often visited Latin America and Southeast Asia and had eaten raw pork and Kimchi, we suspected that the brain lesions were due to NCC rather than metastatic brain tumors. However, serum immunoblotting assay and DNA analysis were negative for T. solium. Rather than performing resection, we administered albendazole (ABZ) and dexamethasone because her earlier cytotoxic chemotherapy had elicited severe pancytopenia. Except for a single large lesion in the left frontal lobe, this treatment resulted in a significant reduction in the size of these lesions and a decrease in perilesional edema. She underwent resection of the residual lesion 10 months later. Histology revealed it to be a metastatic tumor. Polymerase chain reaction (PCR) assay for NCC was negative. In the course of 11-months follow-up there has been no recurrence.Conclusion: This is the first presentation of NCC in a Japanese woman with a metastatic brain tumor. NCC was incidentally discovered on PET scans and, based on her travel history and epidemiological findings; it was diagnosed and successfully treated with ABZ. NCC is endemic in most developing countries and as visits to such countries have increased, NCC must be ruled out in patients with multiple cystic nodular brain lesions. [ABSTRACT FROM AUTHOR]

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The brain is one of the most common metastatic sites in non-small cell lung cancer (NSCLC), which is associated with an extremely poor prognosis. Despite the availability of several therapeutic options, the treatment efficacy remains unsatisfactory for NSCLC brain metastases. Anti-programmed cell death-1 (PD-1) and its ligand (PD-L1) monoclonal antibodies have reshaped therapeutic strategies in advanced NSCLC. Preliminary evidence has shown that anti-PD-(L)1 monotherapy is also effective in NSCLC patients with brain metastases. However, the traditional view asserted that these therapeutic antibodies were incapable of crossing the blood-brain barrier (BBB) with large molecular size, thus most patients with brain metastases were excluded from most studies on anti-PD-(L)1 immunotherapy. Therefore, the efficacy and its mechanisms of action of anti-PD-(L)1 immunotherapy against brain metastases in NSCLC have not been clarified. In this review, we will survey the underlying mechanisms and current clinical advances of anti-PD-(L)1 immunotherapy in the treatment of brain metastases in NSCLC. The trafficking of activated cytotoxic T cells that are mainly derived from the primary tumor and deep cervical lymph nodes is critical for the intracranial response to anti-PD-(L)1 immunotherapy, which is driven by interferon-γ (IFN-γ). Additionally, promising combined strategies with the rationale in the treatment of brain metastases will be presented to provide future directions for clinical study design. Several significant challenges in the preclinical and clinical studies of brain metastases, as well as potential solutions, will also be discussed. [ABSTRACT FROM AUTHOR]

Objective: Although the incidence of Central Nervous System(CNS) tumors in adults is quite low, it has been increasing all over the world. CNS tumors have high morbidity and mortality rates, the prevalence of histological types, gender distribution and anatomical localizations are different worldwide. Although there are a few limited studies available on the epidemiology of CNS tumors in Turkey, there is no study reporting the population of Aydın. The aim of this study is to show distribution of CNS tumors in the population of Aydın and its comparison with International data. Method: 266 cases of primary-metastatic intracranial tumors which were diagnosed between 2008-2017 in Aydın Adnan Menderes University, Department of Pathology were included in the study. The patients were grouped according to age, sex, anatomical localization, primary/metastatic, histological types and grade. Results: The mean age in males was higher than in females(p = 0.001). The frequency was significant in women of 40-49 years and men of 60-69 years old(p = 0.001). The higher incidence of meningiomas in women, metastatic tumors in men(p = 0.002), and right-sided tumors in general(p = 0.001) were significant. Frontal lobe originated primary tumors and metastatic tumors situated in the cerebellum were most frequently detected(p = 0.001). Conclusion: In this study, gender, anatomical localization and grade distributions of primary CNS tumors were consistent with the literature. Age distribution was found to be similar to the American population however, tumors became evident at an older age than they are in the Asian and European populations. Tumor group distribution and histological types were closer to Asian and European data. Right sided tumors were more frequent. This study depicts epidemiological characteristics of CNS tumors in population of Aydın and its comparison with International data. [ABSTRACT FROM AUTHOR]

Purpose: To investigative the diagnostic performance of radiomics-based machine learning in differentiating glioblastomas (GBM) from metastatic brain tumors (MBTs).Method: The current study involved 134 patients diagnosed and treated in our institution between April 2014 and December 2018. Radiomics features were extracted from contrast-enhanced T1 weighted imaging (T1C). Thirty diagnostic models were built based on five selection methods and six classification algorithms. The sensitivity, specificity, accuracy, and area under curve (AUC) of each model were calculated, and based on these the optimal model was chosen.Result : Two models represented promising diagnostic performance with AUC of 0.80. The first model was a combination of Distance Correlation as the selection method and Linear Discriminant Analysis (LDA) as the classification algorithm. In the training group, the sensitivity, specificity, accuracy, and AUC were 0.75, 0.85, 0.80, and 0.80, respectively; and in the testing group, the sensitivity, specificity, accuracy, and AUC of the model were 0.69, 0.86, 0.78, and 0.80, respectively. The second model was the Distance Correlation as the selection method and logistic regression (LR) as the classification algorithm, with sensitivity, specificity, accuracy, and AUC of 0.75, 0.85, 0.80, 0.80 in the training group and 0.69, 0.86, 0.78, 0.80 in the testing group.Conclusion: Radiomic-based machine learning has potential to be utilized in differentiating GBM from MBTs.

Purpose: To investigative the diagnostic performance of radiomics-based machine learning in differentiating glioblastomas (GBM) from metastatic brain tumors (MBTs). Method: The current study involved 134 patients diagnosed and treated in our institution between April 2014 and December 2018. Radiomics features were extracted from contrast-enhanced T1 weighted imaging (T1C). Thirty diagnostic models were built based on five selection methods and six classification algorithms. The sensitivity, specificity, accuracy, and area under curve (AUC) of each model were calculated, and based on these the optimal model was chosen. Result : Two models represented promising diagnostic performance with AUC of 0.80. The first model was a combination of Distance Correlation as the selection method and Linear Discriminant Analysis (LDA) as the classification algorithm. In the training group, the sensitivity, specificity, accuracy, and AUC were 0.75, 0.85, 0.80, and 0.80, respectively; and in the testing group, the sensitivity, specificity, accuracy, and AUC of the model were 0.69, 0.86, 0.78, and 0.80, respectively. The second model was the Distance Correlation as the selection method and logistic regression (LR) as the classification algorithm, with sensitivity, specificity, accuracy, and AUC of 0.75, 0.85, 0.80, 0.80 in the training group and 0.69, 0.86, 0.78, 0.80 in the testing group. Conclusion: Radiomic-based machine learning has potential to be utilized in differentiating GBM from MBTs. [ABSTRACT FROM AUTHOR]

In recent years, several drugs have been approved for the treatment of patients with metastatic cutaneous melanoma, completely reshaping the landscape of this aggressive disease. Immune therapy with cytotoxic T-lymphocyte antigen 4 and programmed cell death-1 inhibitors yielded significant and durable responses, achieving long-term disease control in up to 40% of the patients. BRAF inhibitors (BRAFi), in combination with MEK inhibitors, also resulted in improved overall survival compared with single-agent BRAFi in patients with BRAFV600 -mutated metastatic melanoma. The optimized sequencing and duration of treatment, however, is yet to be found. In this article, we thoroughly review current data and discuss how to best sequence the various treatment modalities available at present, based on four distinct clinical presentations commonly seen in clinic. In addition, we review treatment options beyond checkpoint inhibitors and targeted therapy, which may be required by patients failing such effective treatments. [ABSTRACT FROM AUTHOR]

Purpose: This study seeks to ascertain whether different primary tumor types have a propensity for brain metastases (BMs) in different cerebral vascular territories and cerebral edema. Methods: Consecutive adult patients who underwent surgical resection of a BM at a tertiary care institution between 2001 and 2011 were retrospectively reviewed. Only patients with the most common primary cancers (lung, breast, skin-melanoma, colon, and kidney) were included. Preoperative MRIs were reviewed to classify all tumors by cerebral vascular territory (anterior cerebral artery-ACA, lenticulostriate, middle cerebral artery-MCA, posterior cerebral artery-PCA, posterior fossa, and watershed), and T2-weighted FLAIR widths were measured. Chi square analyses were performed to determine differences in cerebral vascular distribution by primary tumor type, and one-way ANOVA analyses were performed to determine FLAIR signal differences. Results: 669 tumors from 388 patients were classified from lung (n = 316 BMs), breast (n = 144), melanoma (n = 119), renal (n = 47), and colon (n = 43). BMs from breast cancer were less likely to be located in PCA territory (n = 18 [13%]; χ2 = 6.10, p = 0.01). BMs from melanoma were less likely to be located in cerebellar territory (n = 11 [9%]; χ2 = 14.1, p < 0.001), and more likely to be located in lateral (n = 5 [4%]; χ2 = 4.56, p = 0.03) and medial lenticulostriate territories (n = 2 [2%]; χ2 = 6.93, p = 0.009). BMs from breast and melanoma had shorter T2-FLAIR widths, with an average [IQR] of 47.2 [19.6–69.2] mm (p = 0.01) and 41.2 [14.4–62.7] mm (p = 0.002) respectively. Conversely, BMs from renal cancer had longer T2-FLAIR widths (64.2 [43.6–80.8] mm, p = 0.002). Conclusions: These findings suggest that different primary tumor types could have propensities for different cerebral vascular territories and cerebral edema. [ABSTRACT FROM AUTHOR]

Background and Study Aims/Objective Metastatic brain tumors are the most common type of adult brain tumors. Treatment involves surgery and/or radiation therapy. Surgery is typically reserved for patients with good neurologic function, solitary and accessible lesions, symptomatic lesions, and/or those with good systemic control of their primary cancer. Deep-seated lesions, however, are typically treated with palliative options including radiation and medical therapies. We summarize our personal experience with minimally invasive surgical approaches for these deep-seated metastatic brain tumors using tubular retractors with exoscopic visualization. Material and Methods Patients with deep-seated metastatic brain tumors who were operated on from January 2016 to December 2017 by the senior author were collected prospectively. "Deep seated" was defined as any subcortical location below the deepest adjacent sulcus in close proximity to the basal ganglia and/or thalamus. "Minimally invasive" was defined as the use of tubular retractors with exoscopic visualization. Results A total of 15 consecutive patients with an average ± standard deviation age of 63 ± 12 years underwent surgical resection of a deep-seated metastasis. The tumor was located in the centrum semiovale in seven (47%) (3 corticospinal tract, 2 superior longitudinal fasciculus, 1 visual tract, 1 inferior frontal occipital fasciculus), basal ganglia in three (20%), thalamus in two (13%), and cerebellum in three (20%). Median percentage resection was 100% (interquartile range:100–100%), and, following surgery, seven (47%), seven (47%), and one (7%) had an improved, stable, and worse Karnofsky Performance Score, respectively. No patients had notable local complications including stroke, infection, hemorrhage, and/or seizure. All patients underwent postoperative stereotactic radiosurgery. Conclusion This minimally invasive approach can be used to achieve extensive resection with minimal morbidity for arguably the highest risk metastatic brain tumors. [ABSTRACT FROM AUTHOR]

Background/aim: Brain metastasis (BM) is a complex multi-step process involving various immune checkpoint proteins. Mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases 1/2 (ERK1/2), and signal transducer and activator of transcription 3 (STAT3) are implicated in tumorigenesis and are critical upstream regulators of Programmed Death Ligand 1 (PD-L1), an immunotherapy target. Tumor suppressor p53, dysregulated in cancers, regulates STAT3 and ERK1/2 signaling. This study examined the roles of STAT3, MAPK and p53 status in BM initiation and maintenance., Materials and Methods: Twenty-six BM, with various primary malignancies, were used (IRB-approved) to determine mutant p53 (p53 mt ), pSTAT3 Tyr705 , pERK1/2 Thr202/Tyr204 , and PD-L1 expression using immunohistochemistry. cDNA microarray was used for gene expression analysis. Brain-metastatic breast cancer cells (MDA-MB-231) were treated with STAT3 (NSC74859) or MAPK/ERK1/2 (U0126) inhibitors in regular or astrocytic media. ERK1/2 pathway was assessed using western blotting, and cell proliferation and migration were determined using MTT and scratch-wound assays, respectively., Results: pSTAT3 Tyr705 and pERK1/2 Thr202/Tyr204 were expressed at tumor margins, whereas p53 mt and PD-L1 were uniformly expressed, with significant overlap between expression of these proteins. Gene expression analysis identified alterations in 18 p53- and 32 STAT3- or MAPK-associated genes contributing to dysregulated immune responses and cell cycle regulation. U0126 and NSC74859 reduced pERK1/2 Thr202/Tyr204 expression. Cell proliferation decreased following each treatment (p≤0.01). Migration stagnated following U0126 treatment in astrocytic media (p≤0.01)., Conclusion: Activation of STAT3 and ERK1/2 promotes BM and provides compelling evidence for use of STAT3, ERK1/2 and p53 status as potential immunotherapeutic targets in BM., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The present study sought to evaluate the predictive accuracy of preoperative lab values (PLV) on postoperative metastatic brain tumor resection (MBTR) outcomes using data queried from a large prospective international surgical registry, representing over 700 hospitals in 11 countries. Adult metastatic brain tumor patients (N = 5943) were queried from the American College of Surgeons National Quality Improvement Program (ACS-NSQIP) database, from 2015 to 2019, using diagnostic and procedural coding. The relationship between preoperative lab values and key indicators of adverse postoperative outcomes following metastatic brain tumor resection were assessed with univariate and multivariate analyses. Adverse postoperative outcomes of interest included: 30-day mortality, Clavien-Dindo Grade IV (CDIV) complications, extended length of stay (eLOS), and discharge to non-home destination (NHD), as well as secondary outcomes: non-Clavien-Dindo Grade IV complications, unplanned reoperation, and unplanned readmission. Independent PLV most strongly associated with 30-day mortality were hypernatremia, increased serum creatinine, and thrombocytopenia. Significant predictors of CDIV complications were hypoalbuminemia and thrombocytopenia. eLOS was associated with hypoalbuminemia, anemia, and hyponatremia. The strongest independent predictors of NHD were anemia, hyperbilirubinemia, and hypoalbuminemia. Several pre-operative lab values independently predicted worse outcomes for metastatic brain tumor resection patients. Hypoalbuminemia, thrombocytopenia, and anemia had the strongest association with the study's adverse postoperative outcomes. These baseline lab values may be considered for preoperative risk stratification of metastatic brain tumor patients. [ABSTRACT FROM AUTHOR]

Metastatik tümör; orjinini Santral Sinir Sistemi (SSS) dışındaki dokulardan alan primer sistemik kanserlerin sekonder olarak SSS ne yayılmasıdır. Erişkinde SSS ne en sık metastaz sırasıyla akciğer, meme, malign melanom, renal hücreli Ca, kolon ve tiroid kanserinden gelir. Akciğer kanseri %30-60 oranında beyine metastaz yapar. Çocukta beyin metastazı oldukça azdır. En sık lösemi, lenfoma, osteogenik sarkom, rhabdamyosarkom ve germ hücreli tümörler beyne metastaz yaparlar. Malign melanom, akciğer, meme ve kolon kanserleri %50 oranında multipl metastaz yaparken renal tümörler tek metastaz yapmaya meyillidir. Akciğer kanseri tanı koyduktan 6-9 ay sonra beyne metastaz yaparken, renal kanser 1 yıl, kolon kanseri 2 yıl, meme kanseri ve malign melanom 3 yıl sonra beyine metastaz yapabilir. %6 olguda primer tümöre ait hiçbir bulgu yokken beyine metastaz olmaktadır. Tedavide verilen ilk ilaç kortikosteroiddir, daha sonra ameliyat, Radyoterapi (RT), Kemoterapi (KT) ve Stereotaktik Radyosurgery (SRS) yapılabilir. Küçük hücreli akciğer kanseri, lenfoma, germ hücreli tümörler RT ve KT"ye hassastırlar. Non small akciğer kanserleri, renal, kolon, malign melanom radiorezistandır. Eğer hastada 3-4 aydan uzun yaşam süresi bekleniyorsa agresif tedavi uygulanır. RT"de verilen dozun total miktarı ve veriliş süresi ile ilgili akut ve kronik komplikasyonlar meydana gelir. Metastatik tümörlerin ameliyatlarında amaç nörolojik defisit olmadan tümörün total çıkartılması, intrakranial basıncın azaltılması ve eğer postoperatuar RT yapılacaksa dozun mümkün olduğu kadar düşük tutulmasıdır. Önceleri multipl metastazlar opere edilmemekte idi ancak ne kadar çok metastaz alınırsa RT ve KT den o kadar çok cevap alındığından günümüzde ameliyat önemlidir. Anahtar Kelimeler: Metastatik beyin tümörleri, Stereotaktik radyosurgery, Malign melanom, Akciğer kanserleri, Renal hücreli karsinom, Radyoterapi, Kemoterapi

Brain metastases (BM) are one of the most common types of brain tumors and are a relatively common event in the disease process for several high-incidence cancer types, including breast and lung cancers. Historically, information on metastases including BM have not been collected as part of national cancer registration in the US, but BM at time of primary cancer diagnosis (SBM), is now collected by the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results (SEER) system. Using data from 18 SEER registries from 2010 to 2013, we assessed the frequency of SBM at time of primary diagnosis in the US by site, histology group, sex, race, age, and insurance status. There were 1,634,954 total primary cancer cases in SEER from 2010 to 2013, 1.7% of which presented with SBM. The cancer type with the highest proportion of SBM was lung cancer (10.8% of cases with SBM), followed by esophageal (1.5%), kidney (1.4%), and melanoma (1.2%). SBM varied by age, sex, race, and insurance status for most histologies. Our results reflect the high proportion of patients who are diagnosed with lung cancer at late stages and present with SBM, in contrast to other common cancers in the US where SBM is less common. Demographic variation in molecular subtype and risk behavior may influence variation in SBM. BM is a relatively common event in late stage cancer and cause significant morbidity and mortality, and assessment of accurate population-based data is critical to estimate total disease burden. [ABSTRACT FROM AUTHOR]

Purpose: When treating large metastatic brain tumors with stereotactic radiotherapy (SRT), high dose conformity to target is difficult to achieve. Employing a modified planning target volume (mPTV) instead of the original PTV may be one way to improve the dose distribution in linear accelerator-based SRT using a dynamic conformal technique. In this study, we quantitatively analyzed the impact of a mPTV on dose distribution.Materials and Methods: Twenty-four tumors with a maximum diameter of >2 cm were collected. For each tumor, two plans were created: one used a mPTV and the other did not. The mPTV was produced by shrinking or enlarging the original PTV according to the dose distribution in the original plan. The dose conformity was evaluated and compared between the plans using a two-sided paired t test.Results: The conformity index defined by the Radiation Therapy Oncology Group was 1.34 ± 0.10 and 1.41 ± 0.13, and Paddick's conformity index was 0.75 ± 0.05 and 0.71 ± 0.06, for the plans with and without a mPTV, respectively. All of these improvements were statistically significant (P < 0.05).Conclusion: The use of a mPTV can improve target conformity when planning SRT for large metastatic brain tumors. [ABSTRACT FROM AUTHOR]

Immunotherapy agents such as ipilimumab and nivolumab are immensely effective in the treatment of various malignancies. Despite this, neurologic immune-related sequelae (NIRS) have been observed. Prompt diagnosis and treatment is critical to improve patient outcomes. We present a case of a 63-year-old man with stage IV metastatic melanoma beginning treatment with ipilimumab and nivolumab. Gathered history from the patient showed that he had a 3-year presentation of bradykinesia, shuffling gait, and muscle cramping. After one dose, the patient began to have progressively worsening generalized weakness; after receiving the immunotherapy, there was a rapid decline in his health. In addition to weakness, the patient developed diplopia, impaired single breath count, lingual and upper/lower extremity fasciculations, and brisk reflexes. While the lumbar puncture and myasthenia panel were non-diagnostic, the electromyography (EMG) revealed axonal neuropathy and diffuse denervation/reinnervation changes. Furthermore, a magnetic resonance imaging (MRI) displayed fatty replacement of the tongue with a bright tongue sign. These results pointed to the diagnosis of amyotrophic lateral sclerosis (ALS) superimposed onto myastheniclike syndrome. The patient was started on various treatments; however, unfortunately he died due to acute hypoxic respiratory failure. This case highlights important considerations that must be taken when using immunotherapy, especially in patients with pre-existing neurological deficits. Furthermore, it shows the importance of early diagnosis as treatment can potentially cure adverse sequelae. [ABSTRACT FROM AUTHOR]

A woman with hypertension and hyperglycemia was diagnosed a metastatic brain carotid body paraganglioma. Her blood pressure, glucose, and norepinephrine were normal after craniotomy. Although most carotid body tumors are benign, a few show distant metastasis. This is the first reported case of intracerebral metastases from a carotid body tumor. [ABSTRACT FROM AUTHOR]

Objective To observe the clinical efficacy of Ommaya sac implantation combined with radiation and chemotherapy for treatment of cystic brain metastases from lung adenocarcinoma. Methods Clinical efficacy and imaging results of 48 patients with cystic brain metastases from lung adenocarcinoma were analyzed retrospectively using the treatment of Ommaya sac implantation combined with radiation and chemotherapy. Results Various degrees of high intracranial pressure were observed in 48 patients before treatment,which caused headache in 39 patients,vomit in 27 and blurred vision in 8. Focal nervous damages were observed including physical impairment in 27 patients, epileptic seizure in 12,defect of visual field in 10 and aphasia in 8. Improvement of clinical symptoms and activity of daily living were noted in 36 patients, imaging re-cheek indicated focus shrink <50% in 36 patients, enjoying an effective rate of 75%. Progressive disease was noted in 4 patients and deaths was noted in 3. Conclusion Treatment of cystic lung adenocarcinoma with brain metastases through Ommaya sac implantation combined with radiation therapy and chemotherapy is effective and safe. [ABSTRACT FROM AUTHOR]

Introduction Although rectal cancer is thought to have a higher rate of metastasis to the brain compared with colon cancer, there is limited and contradictory data on the subject. This study aims to determine the prevalence of brain metastasis for colon and rectal cancers (CRC), and to explore associations and predictors of brain metastasis (BM). Methods The 2010-2016 National Cancer Database (NCDB) was queried for patients with stage IV CRC. Patients with missing data on site of metastasis and primary tumor location were excluded. Chi-square test was used for categorical data and multivariate logistic regression analysis was performed to evaluate the predictors of BM. Results Of 108,540 stage IV CRC patients, the prevalence of BM was 1.21% from the right colon, 1.29% from the left colon, and 1.59% from the rectal adenocarcinoma (p<0.001). The presence of lung, bone, and liver metastases were the strongest predictors for BM. Bone and lung metastases increased the odds for BM by 3.87 (95% CI: 3.36-4.46) and 3.38 (95% CI: 3.01-3.80), respectively while the presence of liver metastasis decreased odds for BM by 55% (OR: 0.45; 95% CI: 0.40-0.50). On multivariate analysis, primary tumor location was not predictive of BM. Discussion This study helps to characterize the prevalence and associations of BM from CRC using the NCDB. The correlation between BM and bone and lung metastases, along with negative association of liver metastasis further supports the hypothesis of systemic transmission of tumor cells. Further identification of predictors and correlations with BM may help guide surveillance among patients with advanced CRC., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Franceschi et al.)

Brain metastasis is a common cause of mortality in patients with cancer, and is associated with poor prognosis. There is a current requirement for the identification of relevant brain metastasis tumor models, which may be used to test novel therapeutic agents and delivery systems in pre-clinical studies. The present study aimed to investigate the development of a murine model of brain metastasis, and the application of bioluminescence imaging (BLI) for monitoring tumor growth and response to targeted toxins (TT). A luciferase-modified human brain metastasis cell line was implanted into the caudate-putamen of athymic mice using a stereotactic frame. Tumor growth was monitored by BLI, and tumor volume was calculated from three-dimensional measurements of serial histopathological sections. Histopathological analyses revealed the presence of tumor growth within the caudate-putamen of all of the mice, and BLI was shown to be correlated with tumor volume. To evaluate whether this model would allow the detection of a therapeutic response, mice bearing metastatic brain tumor cell xenografts were treated with TT delivered by convection-enhanced delivery (CED), via a micro-osmotic pump system. The TT-treated groups were submitted to metastatic brain tumor cell experiments, the results of which suggested that TT treatment delayed tumor growth, as determined by BLI monitoring, and significantly extended the survival of the mice. The results of the present study demonstrated the efficacy of a brain metastasis model for CED of TT via a micro-osmotic pump system in athymic mice, in which tumor growth and response to therapy were accurately monitored by BLI. In conclusion, this model may be well-suited for pre-clinical testing of potential therapeutics for the treatment of patients with metastatic brain tumors. [ABSTRACT FROM AUTHOR]

Gamma knife radiosurgery (GKRS) has emerged as a possible treatment option for metastasis brain tumor (MBTs) originated from breast cancer. However, the intermediate or long-term outcome of GKRS on MBTs originated from breast carcinoma is not well defined. The outcome of GKRS on MBTs derived from breast carcinoma was reviewed in our institution's case series. We performed a retrospective review (2000-2013) of 50 patients with MBTs originated from breast cancer who received GKRS. Out of 50 patients, 11 patients had recurrent tumors after microsurgical resection and the other 39 patients received GKRS alone. The study population was followed clinically and radiographically after GKRS treatment. GKRS on MBTs metastasized from breast cancer showed significant variations in tumor growth control (decreased in 14 (31.9 %) patients, arrested growth in 17 (38.6 %) patients, and progressed tumor in 13 (29.5 %) patients). The overall median survival in this case series was 33 months. In our case series, overall survival rate after 5 years was 20 %, whereas progression-free survival rate after 5 years was 30 %. The prognostic factors for improving survival in the patients with MBTs from breast cancer were recursive partitioning analysis (RPA) class I ( p = 0.014), age ≤65 years ( p = 0.025), controlled primary tumor ( p = 0.04), and single number of MBTs ( p = 0.022). Recent follow-up revealed that GKRS offers good overall survival period in both new and recurrent patients with MBTs originated from breast carcinoma. Thus, GKRS is a therapeutic option for new and recurrent patients with MBTs derived from breast cancer. [ABSTRACT FROM AUTHOR]

Background: Beta-adrenergic antagonists have demonstrated beneficial effects in tumor progression and survivability in patients with various cancers by inhibiting norepinephrine-induced tumor cell migration. However, little is known about their effects on the outcomes of metastatic brain tumors (MBTs). This study was undertaken to evaluate the effects of beta-blockers, if any, on the outcome of MBTs, and their possible role in controlling tumor progression and survivability. Materials and Methods: A retrospective cohort analysis of 225 patients identified as having MBTs presenting to our institution from 2001 through 2013 was conducted by reviewing electronic patient records. Patients were categorized into three groups: Group A comprised hypertensives on beta-blockers only (40, 18%), Group B comprised hypertensive patients on antihypertensive medications other than beta-agonists (65, 29%), and Group C comprised normotensives (120, 53%). All outcomes were compared using the data on pre - and post-gamma knife radiosurgery (GKRS) for these groups. One-way analysis of variance (ANOVA) was used to compare the radiological and clinical outcomes in the patient population following beta-blockers usage in Group A versus groups B and C. Cox regression model was used to demonstrate prognostic factors for the outcome in patients having different primaries. Overall survival period was plotted on Kaplan-Meier curves. The log-rank (Mantel-Cox) test was used to analyze the survival difference in the cases. P < 0.05 was considered significant. Results: The mean age of patients was 57.34 ± 10.98 years (range: 30-87 years) and 44% were males. More than half (130/225, 58%) of patients with MBT had their primary tumor source in the lung, 16% in the breast, and 7% each in the kidneys and the rectum. Frontal lobe was the most commonly affected (80, 35.5%). Statistically significant control of tumor growth (P = 0.001), tumor progression (P = 0.0001), and higher survival outcomes (P = 0.015) were observed in Group A as compared to other groups. In comparing the different groups, breast primaries showed the strongest correlation to survival benefit (P = 0.049) from beta-blocker usage as a primary antihypertensive medication. Conclusion: Concomitant use of beta-blockers with conventional therapy may offer potential benefit to hypertensive patients developing MBTs by ameliorating tumor progression and conferring a survival advantage. This effect was most notable in patients with primary tumors originating in the breast. Prospective studies, molecular research, and randomized controlled trials are warranted to further explore this promising effect. [ABSTRACT FROM AUTHOR]

Background: Gamma knife radiosurgery (GKRS) has emerged as an important treatment option for metastasis brain tumors (MBTs). However, the long-term outcome of GKRS on MBTs originating from lung carcinoma is not well understood. The treatment of MBTs derived from lung cancer with GKRS at our institution is reviewed. Methods: We performed a retrospective review (2000-2013) of 173 patients with MBTs from lung cancer who received GKRS. Out of 173 patients, 38 patients had recurrent tumors after microsurgical resection and whole brain radiotherapy (WBT). Results: GKRS in MBTs metastasized from lung carcinoma showed significant variations in tumor growth control (decreased in 79 [45.7%] patients, arrested growth in 54 [31.2%] patients, and increased tumor size in 40 [23.1%] patients). The median survival in the study population was 14 months. Overall survival after 3 years was 25%, whereas progression-free survival after 3 years was 45%. The predictive factors for improving survival in the patients with MBTs were recursive partitioning analysis (RPA) class I (P = 0.005), absence of hydrocephalus (P = 0.001), Karnofsky performance scale (KPS) >70 (P = 0.007), age ⩽65 (P = 0.041), tumor size ⩽3 cm (P = 0.023), controlled primary tumor (P = 0.049), and single number of MBTS (P = 0.044). Conclusion: Long-term follow-up revealed that GKRS offers a high rate of tumor control and good overall survival period in both new and recurrent patients with MBTs originating from lung carcinoma. Thus, GKRS is an effective treatment option for new patients with MBTs from lung cancer, as well as an adjuvant therapy in patients with recurrent MBTs derived from lung cancer. [ABSTRACT FROM AUTHOR]

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Abstract: Background: Brain metastases (BM) are a common in patients with lung cancer. Although whole-brain radiation therapy (WBRT) is the standard therapy, it may have a risk of decline in cognitive function of patients. In this study, we evaluated the efficacy of gefitinib alone without radiation therapy for the treatment of patients with BM from lung adenocarcinoma. Materials and methods: Eligible patients had BM from lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutations. Gefitinib was given at 250mg orally once a day until tumor progression or unacceptable toxicity. Results: Forty-one patients were enrolled. The response rate was 87.8%. No patient experienced grade ≥4 toxicity. The median progression-free survival time was 14.5 months (95% CI, 10.2–18.3 months), and the median overall survival time was 21.9 months (95% CI, 18.5–30.3 months). In compared with L858R, exon 19 deletion was associated with better outcome of patients after treatment with gefitinib in both progression-free (p =0.003) and overall survival (p =0.025). Conclusion: Favorable response of BM to gefitinib even without irradiation was demonstrated. Exon 19 deletion was both a predictive and prognostic marker of patients with BM treated by gefitinib. [Copyright &y& Elsevier]

A 76-year-old woman came to us because of staggering, fever, dysarthria, and appetite loss. Magnetic resonance imaging (MRI) of the brain revealed multiple masses with surrounding edema. Chest X-ray and computed tomography demonstrated a mass-like lesion in the left lung and left pleural effusion. Lung cancer and multiple brain metastases were suspected. However, the brain lesions demonstrated a high intensity through diffusion-weighted MRI. The finding was an important key to differentiate brain abscesses from lung cancer metastases. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate the anti-cancer effect of the bispecific diphtheria toxin (DT) based immunotoxin DTATEGF, which targets both the epidermal growth factor (EGF) receptor (EGFR) and the urokinase-type plasminogen activator (uPA) receptor (uPAR) in vitro and in vivo when delivered by convection-enhanced delivery (CED) via an osmotic minipump in a human metastatic non-small cell lung cancer (NSCLC) brain tumor mouse xenograft model. The effects of the bispecific immunotoxin DTATEGF, and monospecific DTAT, DTEGF and control DT at various concentrations were tested for their ability to inhibit the proliferation of human metastatic NSCLC PC9-BrM3 cells in vitro by MTT assay. A xenograft model of human metastatic NSCLC intracranial model was established in nude mice using the human NSCLC PC9-BrM3 cell line genetically marked with a firefly luciferase reporter gene. One microgram of DTATEGF in the treatment group or control DT in the control group was delivered intracranially by CED via an osmotic minipump. The bioluminescent imaging (BLI) was performed at day 7, 14, 1 month, 2 months, and 3 months. Kaplan-Meier survival curves for the two groups were generated. The brain tissue samples were stained by hematoxylin and eosin for histopathological assessment. In vitro, DTATEGF could selectively kill PC9-BrM3 cells and showed an IC less than 0.001 nM, representing a more than 100- to 1000-fold increase in activity as compared to monospecific DTAT and DTEGF. In vivo, mice with tumors were treated intracranially with drug via CED where the results showed the treatment was successful in providing a survival benefit with the median survival of mice treated with DTATEGF being significantly prolonged relative to controls (87 vs. 63 days, P = 0.006). The results of these experiments indicate that DTATEGF kills the NSCLC PC9-BrM3 cell line in vitro, and when it is delivered via CED intracranially, it is highly efficacious against metastatic NSCLC brain tumors. DTATEGF is a safe and effective drug where further preclinical and clinical development is warranted for the management of metastatic brain tumors. [ABSTRACT FROM AUTHOR]