The management of BRAF mutant melanoma brain metastases upon tyrosine kinase failure.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21020-e21020
Author(s):  
Rahul Ladwa ◽  
Victoria Atkinson
Keyword(s):  
Brain Metastases ◽  
Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Systemic Disease ◽  
Whole Brain Radiotherapy ◽  
Mortality Data ◽  
Leptomeningeal Disease ◽  
Number Of Patients ◽  
The Brain ◽  
Braf Mutant

e21020 Background: Brain metastases (BM) failure on tyrosine kinase inhibitor (TKI) is a frequent complication in patients with BRAF mutant metastatic melanoma (MM) and is associated with a poor prognosis. We aimed to explore the outcome of these patients with modern therapeutic options. Methods: We retrospectively analysed 55 patients with treated BRAF mutant mm diagnosed with BM on TKI at a single site in Brisbane, QLD, Australia during 2009-2016. Basic clinico-pathological parameters, treatments used and mortality data were collected. Results: Patient characteristics included a median age of 53 (17-82) years, presence of seizures (N = 7), LDH > 250 (N = 23) and presence of systemic disease (N = 54). BM were categorised as solitary (N = 8), 2-6 (N = 23), more than 6 (N = 13) and leptomeningeal disease (N = 11). Management of BM included surgical resection (N = 6), stereotactic radiosurgery (SRS) (N = 14), whole brain radiotherapy (N = 13) and best supportive care (N = 16). BRAF use post progression with BM was used (N = 10). Immunotherapy with Ipilimumab (N = 17) and PD1 inhibitor (N = 24) was used. With a median follow up of 5 months, 47 (85%) patients had died from MM. Death occurred due to progressive disease in the brain (N = 24), systemically (N = 5) or both (N = 18). The number of patients surviving over 6 months (N = 27) were associated with < 6 BM, use of radiotherapy, use of anti PD1 antibodies and the use of ablative therapies with immunotherapy. Statistically improved overall survival (OS) were found with < 6 BM, SRS use and PD1 inhibitor use. Ablative treatments (resection or SRS) with subsequent immunotherapy confers a median OS of 13 months in select patients. Conclusions: Despite improvements in systemic treatment for mm the outcomes of those with BRAF mutant mm on TKI who develop BM remains poor. Death is frequently due to PD within the brain. The use of ablative techniques and immunotherapy are optimal treatment options in this poor prognostic group.

The changing paradigm of management in melanoma brain metastases.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21027-e21027
Author(s):  
Rahul Ladwa ◽  
Victoria Atkinson
Keyword(s):  
Brain Metastases ◽  
Surgical Resection ◽  
Kinase Inhibitor ◽  
Systemic Treatment ◽  
Treatment Options ◽  
Whole Brain Radiotherapy ◽  
Patient Characteristics ◽  
Mortality Data ◽  
Number Of Patients ◽  
Braf Mutant

e21027 Background: Brain metastases (BM) are a frequent complication in patients with metastatic melanoma (MM). We aimed to explore the outcome of these patient with modern therapeutic options. Methods: We retrospectively analysed 142 patients diagnosed with BM at a single site in Brisbane, QLD, Australia during 2009-2016. Basic clinico-pathological parameters, treatments used and mortality data were collected. Results: Patient characteristics included a median age of 57(17-82) years, presence of seizures (N = 18), dexamethasone use (N = 106) and BRAF mutant mm (N = 117). BM were categorised as solitary (N = 45), 2-6 (N = 65), more than 6 (N = 28) and leptomeningeal only (N = 4). BM were found on systemic treatment in 62 patients. Tyrosine kinase inhibitor (TKI) was used after the diagnosis of BM (N = 50). Management of BM included surgical resection (N = 39), Stereotactic radiosurgery (SRS) (N = 33) and Whole Brain Radiotherapy (N = 45). Immunotherapy with Ipilimumab (N = 35), Pembrolizumab (N = 36) and Nivolumab (N = 21) was used. With a median follow up of 8 months, 115 patients had died, 112 from MM. Death occurred due to progressive disease in the brain (N = 66), systemically (N = 13) or both (N = 33). The number of patients dying of mm were statistically higher on dexamethasone, increasing number of BM, BRAF mutants, absence of surgical resection or SRS and absence of immunotherapy use. Statistically Improved OS were found with solitary BM, treatment naive patients and surgical management of BM. In BRAF mutant patients who were TKI naïve at diagnosis of BM the mean OS was 14.7 versus 6.5 months in patients on TKI treatment (P < 0.05). In BRAF wild type patients mean OS was 11.7 months with PD1 use versus 8.3 months without PD1 use (Not Significant). Conclusions: Despite improvements in systemic treatment for mm the outcomes of those with BM remains poor. Solitary BM amenable to resection or ablation provides optimal treatment. The use of TKIs in BRAF mutant mm post BM diagnosis and the use of immunotherapy are effective treatment options.

scholarly journals BSCI-20. THERAPEUTIC TARGETING OF HLA-G IN BRAIN METASTASES

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i5-i5
Author(s):  
Sheila Singh ◽  
Blessing Bassey-Archibong ◽  
Nikoo Aghaei ◽  
Agata Kieliszek ◽  
Chitra Venugopal ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Systemic Disease ◽  
Human Leukocyte ◽  
Genetic Profile ◽  
Whole Brain Radiation ◽  
Metastatic Cells ◽  
Metastatic Process ◽  
Xenograft Models ◽  
Sphere Formation ◽  
The Brain

Abstract Brain metastases (BM) are the most common brain tumor in adults, with an incidence ten times greater than that of primary brain tumors. The most common sources of BM in adult cancer patients include cancers of the lung, breast and melanoma, which together account for almost 80% of all BM. Current clinical modalities for BM include surgery, whole brain radiation therapy and stereotactic radiosurgery but these therapies still offer limited efficacy and reduced survival of only months in treated patients, emphasizing the need for novel BM research approaches and better therapeutic strategies. Our laboratory recently discovered that stem-like cells exist in patient-derived BM from lung, breast and melanoma cancers, which we termed “brain metastasis-initiating cells” or BMICs. Through clinically relevant human-mouse xenograft models established with these patient-derived BMICs, we captured lung, breast and melanoma BMICs at pre-metastasis – a key stage where circulating metastatic cells extravasate and initially seed the brain, prior to organization into micro-metastatic foci. Transcriptome analysis of pre-metastatic BMICs revealed a unique genetic profile and several genes commonly up-regulated among lung, breast and melanoma BM, including the non-classical human leukocyte class I antigen-G (HLA-G). Loss of HLA-G in lung, breast and melanoma BMICs using two HLA-G specific shRNAs attenuated sphere formation, migratory and tumor initiating abilities of lung, breast and melanoma BMICs compared to control BMICs. HLA-G knockdown also resulted in reduced phospho(p)-STAT3 expression in patient-derived BMICs suggesting a potential cooperative role between HLA-G and pSTAT3 in BM. Since HLA-G is highly expressed at the cell surface in control tumors, ongoing experiments are focused on developing HLA-G specific chimeric antigen receptor -T cells (CAR-Ts) and determining their efficacy in targeting lung-, breast- and melanoma-BM as blocking the brain metastatic process will markedly extend patient survival and ultimately transform a fatal systemic disease into a more treatable one.

scholarly journals The Brain Metastases Symptom Checklist as a novel tool for symptom measurement in patients with brain metastases undergoing whole-brain radiotherapy

2016 ◽  
Vol 23 (3) ◽  
pp. 239 ◽  
Author(s):  
D. Rodin ◽  
B. Banihashemi ◽  
L. Wang ◽  
A. Lau ◽  
S. Harris ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Intraclass Correlation ◽  
Whole Brain Radiotherapy ◽  
Assessment Tools ◽  
Symptom Checklist ◽  
Retest Reliability ◽  
Brain Radiotherapy ◽  
Test Retest Reliability ◽  
The Brain ◽  
Responsiveness To Change

Purpose We evaluated the feasibility, reliability, and validity of the Brain Metastases Symptom Checklist (BMSC), a novel self-report measure of common symptoms experienced by patients with brain metastases.Methods Patients with first-presentation symptomatic brain metastases (n = 137) referred for whole-brain radiotherapy (WBRT) completed the BMSC at time points before and after treatment. Their caregivers (n = 48) provided proxy ratings twice on the day of consultation to assess reliability, and at week 4 after WBRT to assess responsiveness to change. Correlations with 4 other validated assessment tools were evaluated.Results The symptoms reported on the BMSC were largely mild to moderate, with tiredness (71%) and difficulties with balance (61%) reported most commonly at baseline. Test–retest reliability for individual symptoms had a median intraclass correlation of 0.59 (range: 0.23–0.85). Caregiver proxy and patient responses had a median intraclass correlation of 0.52. Correlation of absolute scores on the BMSC and other symptom assessment tools was low, but consistency in the direction of symptom change was observed. At week 4, change in symptoms was variable, with improvements in weight gain and sleep of 42% and 41% respectively, and worsening of tiredness and drowsiness of 62% and 59% respectively.Conclusions The BMSC captures a wide range of symptoms experienced by patients with brain metastases, and it is sensitive to change. It demonstrated adequate test–retest reliability and face validity in terms of its responsiveness to change. Future research is needed to determine whether modifications to the BMSC itself or correlation with more symptom-specific measures will enhance validity. 

scholarly journals Advances in radiotherapy for brain metastases

2021 ◽  
Vol 3 (Supplement_5) ◽  
pp. v26-v34
Author(s):  
Vinai Gondi ◽  
Jacquelyn Meyer ◽  
Helen A Shih
Keyword(s):  
Brain Metastases ◽  
Management Strategy ◽  
Metastatic Cancer ◽  
Treatment Options ◽  
Management Strategies ◽  
Whole Brain Radiotherapy ◽  
Brain Radiotherapy ◽  
Contemporary Management ◽  
The Brain ◽  
Systemic Therapies

Abstract As novel systemic therapies yield improved survival in metastatic cancer patients, the frequency of brain metastases continues to increase. Over the years, management strategies have continued to evolve. Historically, stereotactic radiosurgery has been used as a boost to whole-brain radiotherapy (WBRT) but is increasingly being used as a replacement for WBRT. Given its capacity to treat both macro- and micro-metastases in the brain, WBRT has been an important management strategy for years, and recent research has identified technologic and pharmacologic approaches to delivering WBRT more safely. In this review, we outline the current landscape of radiotherapeutic treatment options and discuss approaches to integrating radiotherapy advances in the contemporary management of brain metastases.

scholarly journals Postoperative Survival in Patients With Multiple Brain Metastases

Medicina ◽  
2012 ◽  
Vol 48 (6) ◽  
pp. 41 ◽  
Author(s):  
Kaspars Auslands ◽  
Daina Apškalne ◽  
Kārlis Bicāns ◽  
Rolfs Ozols ◽  
Henrijs Ozoli
Keyword(s):  
Brain Metastases ◽  
Radiation Therapy Oncology Group ◽  
Whole Brain Radiotherapy ◽  
Postoperative Survival ◽  
Clinical Factors ◽  
Factors Affecting ◽  
Multiple Brain Metastases ◽  
Brain Radiotherapy ◽  
Number Of Patients ◽  
Radiotherapy Alone

Background and Objective. Although surgery is traditionally performed for patients with a single brain metastasis, an increasing number of patients with multiple brain metastases may also be treated surgically. The objective of the study was to analyze postoperative survival results and the clinical factors affecting these results. Material and Methods. The records of the patients who underwent surgical resection of 2 or more lesions between January 2005 and January 2010 were retrospectively reviewed. Survival was calculated from the date of surgery to the last follow-up evaluation or death, and different clinical factors were analyzed in regard to patient survival. Results. In total, 36 patients underwent one or more craniotomies. The survival of the total group ranged from 16 days to 37.5 months (mean, 29 months). There were 4 deaths within 30 days. When divided into Radiation Therapy Oncology Group RPA classes, the survival time was 11.75, 8.58, and 5.31 months for classes 1, 2, and 3, respectively. Regarding an impact on the survival, a significant association with a favorable outcome was found for the following factors: the number of brain metastases (2–3 vs. 4–6, P=0.046), RPA classes (1 vs. 2 or 3, P=0.0192), and extent of metastasis resection (all vs. partial, P=0.018). Conclusions. Well-selected patients with multiple brain metastases appear to benefit from surgery compared with historical controls of patients treated with whole-brain radiotherapy alone.

scholarly journals TRLS-01. RADIOSURGERY FOLLOWED BY TUMOR TREATING FIELDS (TTFIELDS) FOR BRAIN METASTASES (1–10) FROM NSCLC IN THE PHASE 3 METIS TRIAL

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i8-i8
Author(s):  
Minesh Mehta ◽  
Vinai Gondi ◽  
Manmeet Ahluwalia ◽  
Paul Brown
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Electric Fields ◽  
Systemic Disease ◽  
Data Monitoring Committee ◽  
Rank Test ◽  
Progression Rate ◽  
Tumor Treating Fields ◽  
Nsclc Patients ◽  
The Brain

Abstract Tumor Treating Fields (TTFields) are non-invasive, loco-regional, anti-mitotic treatment comprising alternating electric fields that have demonstrated efficacy in preclinical non-small cell lung cancer (NSCLC) models. TTFields to the brain was safe and extended overall survival in newly-diagnosed glioblastoma. The METIS study [NCT02831959] investigates the efficacy and safety of TTFields in NSCLC patients with brain metastases. NSCLC patients (N=270) with 1–10 brain metastases are randomized 1:1 to stereotactic radio surgery (SRS) followed by continuous TTFields ((150 kHz, &gt; 18 hours/day) within 7 days of SRS or supportive care. The TTFields portable device delivers TTFields to the brain using 4 transducer arrays, while patients receive the best standard-of-care for their systemic disease. Patients are followed every two months until second intracranial progression. Key inclusion criteria: KPS ≥70, new diagnosis of 1 inoperable or 2–10 supra- and/or infratentorial brain metastases from NSCLC amenable to SRS; KPS ≥70; and optimal therapy for extracranial disease. Prior WBRT or surgical resection of metastases, a single resectable lesion or recurrent brain metastases were exclusionary. Primary endpoint was time to 1st intracranial progression. Secondary endpoints included time to neurocognitive failure (HVLT, COWAT and TMT), overall survival, radiological response rate (RANO-BM and RECIST V1.1); quality-of-life; adverse events; time to first/second intracranial progression for patients with 1–4 and 5–10 brain metastases; bi-monthly intracranial progression rate from 2–12 months; and time to second intracranial and distant progression. The sample size (N=270) was calculated using a log-rank test (Lakatos 1988 and 2002) with 80% power at a two sided alpha of 0.05 to detect a hazard ratio of 0.57. In August 2018, an independent Data Monitoring Committee (DMC) performed a review of the METIS trial data collected to that point. The DMC concluded that no unexpected safety issues have emerged on the study, and recommended to continue the METIS study as planned.

scholarly journals A Retrospective Analysis about Frequency of Monitoring in Italian Chronic Myeloid Leukemia Patients after Discontinuation

2020 ◽  
Vol 9 (11) ◽  
pp. 3692
Author(s):  
Matteo Dragani ◽  
Giovanna Rege Cambrin ◽  
Paola Berchialla ◽  
Irene Dogliotti ◽  
Gianantonio Rosti ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Chronic Phase ◽  
Molecular Response ◽  
Molecular Monitoring ◽  
Delay In Diagnosis ◽  
Number Of Patients

Successful discontinuation of tyrosine kinase inhibitors has been achieved in patients with chronic-phase chronic myeloid leukemia (CML). Careful molecular monitoring after discontinuation warrants safe and prompt resumption of therapy. We retrospectively evaluated how molecular monitoring has been conducted in Italy in a cohort of patients who discontinued tyrosine kinase inhibitor (TKI) treatment per clinical practice. The outcome of these patients has recently been reported—281 chronic-phase CML patients were included in this subanalysis. Median follow-up since discontinuation was 2 years. Overall, 2203 analyses were performed, 17.9% in the first three months and 38.4% in the first six months. Eighty-six patients lost major molecular response (MMR) in a mean time of 5.7 months—65 pts (75.6%) during the first six months. We evaluated the number of patients who would experience a delay in diagnosis of MMR loss if a three-month monitoring schedule was adopted. In the first 6 months, 19 pts (29.2%) would have a one-month delay, 26 (40%) a 2-month delay. Very few patients would experience a delay in the following months. A less intense frequency of monitoring, particularly after the first 6 months off treatment, would not have affected the success of treatment-free remission (TFR) nor put patients at risk of progression.

Treatment of Brain Metastases of Small-Cell Lung Cancer: Comparing Teniposide and Teniposide With Whole-Brain Radiotherapy—A Phase III Study of the European Organization for the Research and Treatment of Cancer Lung Cancer Cooperative Group

2000 ◽  
Vol 18 (19) ◽  
pp. 3400-3408 ◽  
Author(s):  
Pieter E. Postmus ◽  
Hanny Haaxma-Reiche ◽  
Egbert F. Smit ◽  
Harry J. M. Groen ◽  
Hanna Karnicka ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Response Rate ◽  
Whole Brain Radiotherapy ◽  
Phase Iii ◽  
Time To Progression ◽  
Brain Radiotherapy ◽  
Combined Modality ◽  
Phase Iii Study ◽  
The Brain

PURPOSE: Approximately 60% of patients with small-cell lung cancer (SCLC) develop brain metastases. Whole-brain radiotherapy (WBRT) gives symptomatic improvement in more than 50% of these patients. Because brain metastases are a sign of systemic progression, and chemotherapy was found to be effective as well, it becomes questionable whether WBRT is the only appropriate therapy in this situation. PATIENTS AND METHODS: In a phase III study, SCLC patients with brain metastases were randomized to receive teniposide with or without WBRT. Teniposide 120 mg/m2 was given intravenously three times a week, every 3 weeks. WBRT (10 fractions of 3 Gy) had to start within 3 weeks from the start of chemotherapy. Response was measured clinically and by computed tomography of the brain. RESULTS: One hundred twenty eligible patients were randomized. A 57% response rate was seen in the combined-modality arm (95% confidence interval [CI], 43% to 69%), and a 22% response rate was seen in the teniposide-alone arm (95% CI, 12% to 34%) (P < .001). Time to progression in the brain was longer in the combined-modality group (P = .005). Clinical response and response outside the brain were not different. The median survival time was 3.5 months in the combined-modality arm and 3.2 months in the teniposide-alone arm. Overall survival in both groups was not different (P = .087). CONCLUSION: Adding WBRT to teniposide results in a much higher response rate of brain metastases and in a longer time to progression of brain metastases than teniposide alone. Survival was poor in both groups and not significantly different.

scholarly journals 30. RADIOSURGERY FOLLOWED BY TUMOR TREATING FIELDS FOR BRAIN METASTASES (1–10) FROM NSCLC IN THE PHASE 3 METIS TRIAL

2020 ◽  
Vol 2 (Supplement_2) ◽  
pp. ii5-ii5
Author(s):  
Minesh P Mehta ◽  
Vinai Gondi ◽  
Paul Brown ◽  
Manmeet Ahluwalia
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Electric Fields ◽  
Systemic Disease ◽  
Data Monitoring Committee ◽  
Rank Test ◽  
Progression Rate ◽  
Tumor Treating Fields ◽  
Nsclc Patients ◽  
The Brain

Abstract BACKGROUND Tumor Treating Fields (TTFields) are non-invasive, loco-regional, anti-mitotic treatment modality comprising alternating electric fields. TTFields have demonstrated efficacy in preclinical non-small cell lung cancer (NSCLC) models. TTFields treatment to the brain was safe and extended overall survival in newly-diagnosed glioblastoma. The objective of the METIS study [NCT02831959] is evaluation of the efficacy and safety of TTFields in NSCLC patients with brain metastases. METHODS NSCLC patients (N=270) with 1–10 brain metastases were randomized 1:1 to stereotactic radio surgery (SRS) followed by continuous TTFields ((150 kHz, &gt; 18 hours/day) within 7 days of SRS or supportive care. The portable device delivered TTFields to the brain using 4 transducer arrays, while patients received the best standard-of-care for systemic disease. Patients were followed every two months until second intracranial progression. Key inclusion criteria: KPS ≥70, new diagnosis of 1 inoperable or 2–10 supra- and/or infratentorial brain metastases from NSCLC amenable to SRS; and optimal therapy for extracranial disease. Prior WBRT, surgical resection of metastases, or recurrent brain metastases were exclusionary. Primary endpoint was time to 1st intracranial progression. Secondary endpoints included time to neurocognitive failure (HVLT, COWAT and TMT), overall survival, radiological response rate (RANO-BM and RECIST V1.1); quality-of-life; adverse events; time to first/second intracranial progression for patients with 1–4 and 5–10 brain metastases; bi-monthly intracranial progression rate from 2–12 months; and time to second intracranial and distant progression. The sample size (N=270) was calculated using a log-rank test (Lakatos 1988 and 2002) with 80% power at two sided alpha of 0.05 to detect a hazard ratio of 0.57. On September, 2019, an independent Data Monitoring Committee (DMC) reviewed METIS trial data collected to that point. The DMC concluded that no unexpected safety issues had emerged and recommended continuation of the METIS study as planned.

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

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

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

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