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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.

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]

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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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]

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

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]

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.)

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]

Copyright of Cukurova Medical Journal / Çukurova Üniversitesi Tip Fakültesi Dergisi is the property of Cukurova University, Faculty of Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor approved for recurrent glioblastoma (GBM), metastatic breast, colorectal and non-small-cell lung cancers (NSCLC). There has been a potentially increased risk of intracranial hemorrhage (ICH) in patients receiving bevacizumab. Methods: We retrospectively identified patients with ICH who received bevacizumab between 1 January 2001 and 10 January 2009. Results: We identified 1024 patients with ICH, 4191 patients who received bevacizumab and 12 (0.3%) who met both our criteria. There were eight women and four men with a median age of 66 years. Primary cancers were ovarian (n = 3), NSCLC (n = 3), colon (n = 1), angiosarcoma (n = 1) and GBM (n = 4). Intracranial tumors were present in 9 of the 12 patients; the remaining three (25%) had no evidence of intracranial pathology. Two hundred and fifty-seven patients with these same primary pathologies and brain tumors were treated with bevacizumab; ICH was seen in nine (3.7%), which was comparable to the 3.6% frequency seen in comparable patients not receiving bevacizumab. Conclusions: ICH with bevacizumab treatment in this population is rare and does not appear to increase its frequency over the baseline rate of ICH in a comparable population. Most bevacizumab-related ICH occurs into central nervous system tumors but spontaneous hemorrhages were seen. [ABSTRACT FROM PUBLISHER]

Brain metastases are the most common type of brain tumor in adults, commonly arising from primary tumor sites of the lung, breast, skin (melanoma), colon, and kidney. Isolated central nervous system (CNS) metastasis arising from urothelial carcinoma (UC) is a rare presentation yielding a poor prognosis. A 71-year-old male patient with a history of urothelial carcinoma, treated one year prior with partial cystectomy and adjuvant gemcitabine and cisplatin (GC) therapy, presented with worsening neurological symptoms, including progressively worsening dizziness, shuffling gait, drifting, expressive aphasia, and confusion. MRI revealed a left frontal 4.0 x 3.6 cm brightly contrast-enhancing tumor with possible hemorrhage, extensive vasogenic edema, and moderate mass effect. An additional smaller right cerebellar lesion was also noted. Outpatient CT of his chest, abdomen, and pelvis revealed no evidence of other malignant sites. He ultimately underwent a left craniotomy with a total resection of his left frontal mass. Pathological examination revealed a urothelial primary. Post-operative MRI revealed complete resection of the left frontal mass and the patient was discharged with no neurologic deficits on exam. In many cases, brain metastases may present years later following initial therapy of UC as the CNS may act as a sanctuary site during systemic chemotherapy. Chemotherapeutics such as gemcitabine with better penetration of the blood-brain barrier may be beneficial in delaying the onset of these metastases., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Sankhyan et al.)

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Background: Improving 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., Methods: Patients 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., Results: A 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/m 2 . Phase II proceeded with capecitabine at 750 mg/m 2 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., Conclusions: This 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 Registration: ClinicalTrials.gov: NCT01783756. Registered 05 February 2013, https://clinicaltrials.gov/ct2/show/NCT01783756., Competing Interests: Conflict of interest statement: SH: Research Funding: Amgen, Ambryx, Bayer, Boehringer-Ingelheim, Daiichi-Sankyo, Genentech/Roche, GSK, Immunomedics, Lilly, Macrogenics, Medivation, Merrimack, Novartis, Cascadian, OBI Pharma, Pfizer, Pieris, PUMA, Seattle Genetics, Dignitana (In addition to research funding) “Chief Medical Officer (unpaid position) for TRIO-U; AM: Employment: Genentech, stock ownership: Roche, research funding: Oncothyreon, EMD-Serono; JM: research funding: BMS; BD research funding: Astra Zeneca, Novartis, Syndax, Halozyme, Roche/Genentech, Takeda, Armo, BMS (online); RC: stock ownership-Merck, consulting: Novartis, Pfizer; AC: Consulting: Myriad, Biotheranostics; Research Funding: Cascadian Therapeutics, Pfizer, Novartis, PUMA Biotechnology; IS: Employment: Tower Imaging Medical Group, Consulting: Nektar; XW, BA, EH, RD, JT, IM, RS: None; DC: Stock: Abbvie, Gilead Sciences, Exelexis, Seattle Genetics, Loso, Tesaro, Exact Sciences, Consulting: Counsyl; DJS: Board Member: BioMarin, Stock Ownership: Pfizer, BioMarin, Amgen, Cascadian Therapeutics, Seattle Genetics, Consultant/Ad Board/Honoraria: Pfizer, Lilly, Novartis, Contracted Research: Pfizer, Syndax, Novartis, Lilly; DM: None; BMS: JB Research Funding.