Search Results (98)

Background/Objectives: Non-small-cell lung cancer (NSCLC) frequently metastasizes to the brain, significantly impacting patient prognosis and quality of life. Anlotinib, a novel tyrosine kinase inhibitor, has shown promise in treating NSCLC with brain metastasis. So, we aimed to evaluate the clinical efficacy of anlotinib and various types of radiotherapy combinations used to treat NSCLC patients with brain metastasis regarding overall survival and the treatment of internal and external lesions. Methods: A comprehensive literature search was conducted in the databases PubMed, Scopus, WoS, MedLine, and Cochrane Library up to April 2024. Studies assessing the efficacy of anlotinib combined with whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), or other radiotherapy modalities in NSCLC patients with brain metastasis were included. The primary outcomes were (a) the efficacy of anlotinib and radiotherapy on the intracranial lesions and OS and (b) the effectiveness of combined anlotinib and radiotherapy versus radiotherapy alone in NSCLC patients with brain metastasis. The secondary outcome was the efficacy of anlotinib and radiotherapy on extracranial progression. We used a combination of keywords and MeSH terms including ‘non-small cell lung cancer’ OR ‘NSCLC’, ‘brain metastases’, ‘anlotinib’, ‘radiotherapy’, ‘radiation therapy’, and ‘combined treatment’, among others. Boolean operators (AND, OR) were applied as appropriate to optimize the search strategy across databases. Results: Nine studies met the inclusion criteria, comprising 210 patients in the combination group and 228 patients in the radiotherapy alone group. The combination of anlotinib with radiotherapy showed a significant improvement in iPFS compared to radiotherapy alone, with a pooled risk ratio (RR) for iORR of 1.18 (95% CI: 1.00–1.39) and a pooled SMD for OS of 0.03 (95% CI: −0.29, 0.36). Radiotherapy combined with anlotinib also demonstrated enhanced intracranial and extracranial control rates. Conclusions: Anlotinib combined with radiotherapy, especially WBRT, offers a promising treatment strategy for NSCLC patients with brain metastasis, improving intracranial control. Further large-scale randomized controlled trials are needed to confirm these findings and optimize treatment protocols. Full article

Background/Objectives: Primary central nervous system lymphoma (PCNSL) is a rare but aggressive tumor, primarily affecting elderly patients. Radiotherapy (RT) remains an important treatment option, particularly for patients who are ineligible for systemic chemotherapy. This study aims to identify prognostic factors and evaluate recurrence patterns in a real-world cohort of PCNSL patients treated with RT. Methods: We retrospectively analyzed 64 PCNSL patients treated with radiotherapy at our institution between 2000 and 2022. Clinical characteristics, treatment details, and outcomes were collected by chart review. Overall survival (OS) was analyzed using Kaplan–Meier and Cox regression methods. Recurrence patterns were assessed based on available post-treatment imaging. Results: Median patient age was 71 years (range: 31–83); 53.1% had an Eastern Cooperative Oncology Group (ECOG) performance status ≥2. Radiotherapy was used as first-line treatment in 62.5% of cases, primarily due to contraindications to chemotherapy. Median OS was 10 months from diagnosis. Age, poor performance status, seizures at presentation, absence of systemic therapy, incomplete radiotherapy, and <80% applied dose of planned radiotherapy were associated with inferior OS in our univariable analysis. Multivariable analysis confirmed age, systemic therapy, seizures, and radiotherapy dose <80% as independent predictors. Among twenty-nine patients with imaging follow-up, eight recurrences after RT were documented: six of those within, and two outside of the initially affected areas. All recurrences occurred within previously irradiated areas. Conclusions: This study confirms known negative prognostic factors in PCNSL and underscores the importance of systemic chemotherapy for curatively intended treatments aiming for prolonged survival. The recurrence patterns observed question the added benefit of whole-brain irradiation in preventing distant relapses. These findings support the need for prospective trials to optimize radiotherapy strategies while balancing efficacy and neurotoxicity. Full article

Background: Distinguishing tumor recurrence from radiation necrosis after radiotherapy for brain metastases remains a major diagnostic challenge. Perfusion MRI, particularly the measurement of relative cerebral blood volume (rCBV), is a commonly used technique to differentiate between these two entities. However, variations in the placement of regions of interest (ROIs) affect diagnostic accuracy. This study compares the diagnostic performance of different cerebral perfusion methods, including a novel volumetric 3D ROI method and automatic thresholding, to differentiate tumor recurrence from radiation necrosis. Methods: We retrospectively analyzed data from 23 patients, including 25 brain metastases treated with stereotactic radiotherapy, who were suspected of local recurrence and had histological confirmation via biopsy or surgical resection. Each patient underwent perfusion MRI before surgery. The diagnostic performance of the different ROI methods (manual and 3D) was evaluated using the area under the ROC curve (AUC), as well as sensitivity and specificity measures. An automatic thresholding method was also applied, generating tumor sub-volumes with predefined cut-off values to determine the rCBV threshold most specific for differentiating relapse from necrosis. Results: The 3D ROI method, considering the whole lesion and a healthy ROI in the head of the caudate nucleus, demonstrated superior diagnostic performance (AUC = 0.65), outperforming manual methods (AUC = 0.53). Robustness was moderate, with an intraclass correlation coefficient of 0.60 between Syngo.via and IntelliSpace. Conclusions: The 3D ROI method shows promise in improving diagnostic accuracy in distinguishing tumor recurrence from radiation necrosis. Further studies with standardized protocols and larger populations are needed to validate these results. Full article

To evaluate the factors influencing the outcomes of patients who underwent surgical resection of brain metastasis followed by either surveillance or post-operative stereotactic radiosurgery/fractionated radiotherapy (SRS/SFRT), a retrospective multi-center chart review was performed on all patients who underwent brain metastases resection in British Columbia between 2018 and 2020. Patients with prior whole-brain radiotherapy were excluded from the study. The primary study endpoints included local recurrence, distant intracranial control, radionecrosis (RN), leptomeningeal disease (LMD), and overall survival (OS). The Kaplan–Meier method was used to analyze survival. The Cox proportional hazards model was used to perform univariable (UVA) and multivariable (MVA) analyses to identify predictors of local control. A total of 113 patients met the inclusion criteria. A total of 31 patients received adjuvant SRS/SFRT to the surgical cavity, while 82 went on observation. The 12-month local control was 69% (50–88%) for the SRS/SFRT cohort and 31% (18–45%) for the observation cohort (p < 0.001). The 12-month distant intracranial control was 44% (26–63%) for the SRS/SFRT cohort and 46% (30–62%) for the observation cohort (p = 0.9). Sensitivity analysis did not show a difference in overall survival (p = 0.6). En bloc resection (p < 0.05), resection without residual disease (p < 0.05), and SRS/SFRT (p < 0.001) were predictive of local control on MVA. Three SRS/SFRT patients (10%) and two observation patients (2%) developed LMD. Four SRS/SFRT patients experienced RN (13%), with no grade 3 or higher toxicities observed. Post-operative SRT outcomes based on real-world population data are consistent with the data from clinical trials and support the established guidelines. For patients requiring surgical resection of brain metastasis, en bloc gross total resection should be encouraged when feasible to reduce local recurrence. Full article

Background/Objectives: Connectomics is an evolving branch of neuroscience that determines structural and functional connectivity in the brain. The objective of this prospective imaging study is to evaluate the effect of whole brain radiotherapy (WBRT) on the connectome. Methods: A combination of diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) was used to study the structural and functional connectivity of the brain, and a machine learning algorithm trained to analyze subject-specific data was applied to create individualized brain maps with 15 neuronal networks for each patient. These brain maps were compared to normal brains from the human connectome project, producing an anomaly matrix. Connectome analysis and multi-dimensional neurocognitive testing on a web-based platform were performed at baseline and 3 months post-WBRT. The change in anomaly frequency was co-related with neurocognitive outcomes. Results: At baseline, connectome analysis revealed that the multiple demand network had the most anomalies (46%). Pre- and post-WBRT comparison revealed increases in proportional anomaly frequency across multiple networks. Pearson correlation showed correlation between neurocognitive domain decline and anomaly changes: learning and memory domain with subcortical network [Verbal recall (Pearson coefficient −0.94; p < 0.01), verbal revision (Pearson coefficient −0.89; p = 0.01), and verbal recognition (Pearson coefficient −0.94; p < 0.01)]. Conclusions: This proof-of-concept study integrated data from DTI and fMRI in the form of connectome and revealed significant changes in brain connectivity, with WBRT that also correlated with neurocognitive outcomes. Further studies in a larger cohort are underway, and correlations with white matter changes and tumor locations/numbers will be performed. Full article

Background: Breast cancer can be classified based on the immunohistochemistry (IHC) phenotypes, defined by the presence or absence of the main IHC markers. IHC phenotyping is important as it determines the prognosis and guides treatment. For example, human epidermal growth factor receptor 2 (HER2) overexpression, which triggers cell growth and division, is observed in HER2-positive breast cancer. Methods: The standard treatment is based on trastuzumab plus pertuzumab in combination with taxane chemotherapy. The possibility of developing metastases depends on those phenotypes. Approximately 25–50% of patients with HER2-positive breast cancer experience brain metastases. This aspect is especially important, as 20% of those patients die as a result. Results: Through the years, many advanced therapies have been introduced to treat brain metastases, including whole brain radiotherapy, stereotactic radiosurgery, and a tyrosine kinase inhibitor (TKI), neratinib. Nonetheless, this still remains a therapeutic challenge. Conclusions: In this review, we focus on the treatment and efficiency of therapies targeting HER2-positive breast cancer, mainly concentrating on the current and newly developed treatment options for brain metastases, such as trastuzumab deruxtecan and tucatinib. Full article

The therapeutic management of melanoma brain metastases has undergone a profound revolution during recent decades. Optimal integration of systemic therapies with local treatments seems to represent the strategy to pursue in order to maximize clinical outcomes, stressing the need for real multidisciplinary care in this setting of patients. However, the current approach in the clinics does not necessarily reflect what the current guidelines state, and several pending issues are present, from the ideal therapeutic sequence between stereotactic radiosurgery (SRS) and drug administration to the current role of surgery and whole brain radiotherapy (WBRT), all of which need to be addressed. This narrative review aims to provide practical help for navigating the current controversies, with an eye towards possible future advancements in the field, which could help to obtain a comprehensive molecular characterization of the tumor and a more personalized patient-centered therapeutic approach. Full article

Lung cancer, both non-small cell and small cell, harbors a high propensity for spreading to the central nervous system. Radiation therapy remains the backbone of the management of brain metastases. Recent advances in stereotactic radiosurgery have expanded its indications and ongoing studies seek to elucidate optimal fractionation and coordination with systemic therapies, especially targeted inhibitors with intracranial efficacy. Efforts in whole-brain radiotherapy aim to preserve neurocognition and to investigate the need for prophylactic cranial irradiation. As novel combinatorial strategies are tested and prognostic/predictive biomarkers are identified and tested, the management of brain metastases in lung cancer will become increasingly personalized to optimally balance intracranial efficacy with preserving neurocognitive function and patient values. Full article

Background: Differences in radiation-induced lymphopenia and prognosis between methods of radiotherapy (RT) for brain metastases remain unclear. Methods: In this retrospective analysis of patients who underwent whole-brain radiotherapy (WBRT) or stereotactic radiosurgery/radiotherapy (SRS/SRT) for brain metastases, baseline total lymphocyte count (TLC) data were obtained within 2 weeks before RT initiation. Follow-up TLC data were evaluated at 0–2, 2–4, and 4–8 weeks after RT completion. Persistent lymphopenia was defined as <800/μL at any time point. Results: Overall, 138 RT courses in 128 patients were eligible (94 WBRT; 44 SRS/SRT). In the WBRT courses, the median baseline TLC was 1325/μL (IQR: 923–1799). Follow-up TLC decreased significantly to 946/μL (626–1316), 992/μL (675–1291), and 1075/μL (762–1435) (p < 0.001). SRS/SRT courses showed no significant TLC decrease. Multivariate analysis revealed female sex, prior RT, baseline TLC < 800/μL, and WBRT use were significantly associated with persistent lymphopenia. In the WBRT group, overall survival was significantly different between those with and without persistent lymphopenia (median, 2.6 and 6.1 months; p < 0.001). However, there was no significant difference in survival in the SRS/SRT group (p = 0.60). Conclusion: This study suggests SRS/SRT might be preferable for lymphocyte preservation in brain metastasis patients. Full article

Leptomeningeal disease (LMD) is a devastating sequelae of metastatic spread that affects approximately 5% of cancer patients. The incidence of LMD is increasing due to advancements in systemic therapy and enhanced detection methods. The purpose of this review is to provide a detailed overview of the evidence in the detection, prognostication, and treatment of LMD. A comprehensive literature search of PUBMED was conducted to identify articles reporting on LMD including existing data and ongoing clinical trials. We found a wide array of treatment options available for LMD including chemotherapy, targeted agents, and immunotherapy as well as several choices for radiotherapy including whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), and craniospinal irradiation (CSI). Despite treatment, the prognosis for patients with LMD is dismal, typically 2–4 months on average. Novel therapies and combination approaches are actively under investigation with the aim of improving outcomes and quality of life for patients with LMD. Recent prospective data on the use of proton CSI for patients with LMD have demonstrated its potential survival benefit with follow-up investigations underway. There is a need for validated metrics to predict prognosis and improve patient selection for patients with LMD in order to optimize treatment approaches. Full article

Background: Primary meningeal melanocytic tumors are ultra-rare entities with distinct histological and molecular features compared with other melanocytic or pigmented lesions, such as brain and leptomeningeal metastases from metastatic melanoma. Methods: The European Network for Rare Cancers (EURACAN) Task Force on Ultra-Rare Brain Tumors (domain 10, subdomain 10) performed a literature review from January 1985 to December 2023 regarding the epidemiologic and clinical characteristics, histological and molecular features, radiological findings, and efficacy of local treatments (surgery and radiotherapy) and systemic treatments for these entities. Results: Molecular analysis can detect specific mutations, including GNAQ, GNA11, SF3B1, EIF1AX, BAP1, that are typically found in circumscribed primary meningeal melanocytic tumors and not in other melanocytic lesions, whereas NRAS and BRAF mutations are typical for diffuse primary meningeal melanocytic tumors. The neuroimaging of the whole neuroaxis suggests a melanocytic nature of a lesion, depicts its circumscribed or diffuse nature, but cannot predict the tumor’s aggressiveness. Gross-total resection is the first choice in the case of circumscribed meningeal melanocytoma and melanoma; conversely, meningeal biopsy may be reserved for patients with diffuse and multinodular leptomeningeal spread to achieve a definitive diagnosis. High-dose radiotherapy is rarely indicated in diffuse melanocytic tumors except as palliative treatment to alleviate symptoms. Last, a definitive advantage of a specific systemic treatment could not be concluded, as most of the data available derive from case reports or small cohorts. Conclusions: As primary meningeal melanocytic tumors are extremely rare, the correlations between the clinical characteristics, molecular profile, radiological findings at diagnosis and progression are weak, and poor evidence on the best therapeutic approach is available. There is a need to develop shared platforms and registries to capture more knowledge regarding these ultra-rare entities. Full article

Intracranial metastases from thyroid cancer are rare. Although the prognosis of thyroid cancer patients is generally favorable, the prognosis of patients with intracranial metastases from thyroid cancer has been considered unfavorable owing to lower survival rates among such patients compared to those without intracranial involvement. Many questions about their management remain unclear. The aim of the present study was to analyze the characteristics, treatment modalities, and outcomes of patients with brain metastases from thyroid cancer. Among 4320 patients with thyroid cancer recorded in our institutional database over a 30-year period, the data of 20 patients with brain metastasis were retrospectively collected and analyzed. The clinical characteristics, histological type of primary cancer and metastatic brain tumor, additional previous distant metastasis, treatment modalities, locations and characteristics on radiologic findings, time interval between the first diagnosis of primary thyroid cancer and brain metastasis, and survival were analyzed. Among our patient cohort, the mean age at initial diagnosis was 59.3 ± 14.1 years, and at the manifestation of diagnosis of cerebral metastasis, the mean age was found to be 64.8 ± 14.9 years. The histological types of primary thyroid cancer were identified as papillary in ten patients, follicular in seven, and poorly differentiated carcinoma in three. The average interval between the diagnosis of thyroid cancer and brain metastasis was 63.4 ± 58.4 months (range: 0–180 months). Ten patients were identified as having a single intracranial lesion, and ten patients were found to have multiple lesions. Surgical resection was primarily performed in fifteen patients, and whole-brain radiotherapy, radiotherapy, or tyrosine kinase inhibitors were applied in the remaining five patients. The overall median survival time was 15 months after the diagnosis of BMs from TC (range: 1–252 months). Patients with thyroid cancer can develop brain metastasis even many years after the diagnosis of the primary tumor. The results of our study demonstrate increased overall survival in patients younger than 60 years of age at the time of diagnosis of brain metastasis. There was no difference in survival between patients with brain metastasis from papillary carcinoma and those with follicular thyroid carcinoma. Full article

Patients with solid tumor brain metastases that progress after whole-brain radiation have limited options. This prospective trial investigated the efficacy, safety, and tolerability of bevacizumab as salvage therapy in this population. Eligible patients received bevacizumab 10 mg/kg intravenously every 2 weeks until progression. The primary endpoint was radiologic response using Response Assessment in Neuro-Oncology (RANO) criteria. The secondary endpoints were progression-free survival (PFS), overall survival (OS), duration of response, and safety. Quality of life (QOL) was studied using the Functional Assessment of Cancer Therapy-Brain (FACT-Br) scale. Twenty-seven patients were enrolled, with twenty-four having evaluable data for response. The majority of histologies (n = 21, 78%) were breast cancer. The remaining histologies were non-small-cell lung cancer (n = 4, 15%), neuroendocrine cancer (n = 1, 3%), and papillary fallopian serous adenocarcinoma (n = 1, 3%). Eighteen patients had radiologic response, with two patients demonstrating partial response (8.33%) and sixteen patients demonstrating stable disease (66.7%). The median duration of response was 203 days. PFS at 6 months was 46%, median PFS was 5.3 m, and median OS was 9.5 m. Treatment was well tolerated, with six patients experiencing grade 3 lymphopenia and hypertension. There was one grade 3 thromboembolism. QOL was not negatively impacted. Bevacizumab is a safe and feasible salvage treatment with durable response and favorable overall survival for patients with progressive brain metastases after whole-brain radiation. Full article

For patients with recurrent brain metastases, there is an urgent need for a more effective and less toxic treatment approach. Accumulating evidence has shown that spatially fractionated radiation therapy (SFRT) is able to provide a significantly higher therapeutic ratio with lower toxicity compared to conventional radiation using a uniform dose. The purpose of this study was to explore the potential low toxicity benefit of mini-beam radiotherapy (MBRT), a form of SFRT, for whole-brain re-irradiation in a healthy mouse model. Animals first received an initial 25 Gy of uniform whole-brain irradiation. Five weeks later, they were randomized into three groups to receive three different re-irradiation treatments as follows: (1) uniform irradiation at 25 Gy; (2) MBRT at a 25 Gy volume-averaged dose (106.1/8.8 Gy for peak/valley dose, 25 Gy-MBRT); and (3) MBRT at a 43 Gy volume-averaged dose (182.5/15.1 Gy for peak/valley dose, 43 Gy-MBRT). Animal survival and changes in body weight were monitored for signs of toxicity. Brains were harvested at 5 weeks after re-irradiation for histologic evaluation and immunostaining. The study showed that 25 Gy-MBRT resulted in significantly less body weight loss than 25 Gy uniform irradiation in whole-brain re-irradiation. Mice in the 25 Gy-MBRT group had a higher level of CD11b-stained microglia but also maintained more Ki67-stained proliferative progenitor cells in the brain compared to mice in the uniform irradiation group. However, the high-dose 43 Gy-MBRT group showed severe radiation toxicity compared to the low-dose 25 Gy-MBRT and uniform irradiation groups, indicating dose-dependent toxicity. Our study demonstrates that MBRT at an appropriate dose level has the potential to provide less toxic whole-brain re-irradiation. Future studies investigating the use of MBRT for brain metastases are warranted. Full article

The circadian system, a vital temporal regulator influencing physiological processes, has implications for cancer development and treatment response. Our study assessed circadian timing’s impact on whole-brain radiotherapy outcomes in brain metastases for personalized cancer therapy insights. The aim of the study was to evaluate circadian influence on radiation treatment timing and its correlation with clinical outcomes and to identify patient populations benefiting from interventions synchronizing circadian rhythms, considering subgroup differences and potential disparities. An IRB-approved retrospective analysis of 237 patients undergoing whole-brain radiotherapy for brain metastases (2017–2021), receiving over 80% of treatments in the morning or afternoon, was performed. Survival analyses utilized Kaplan–Meier curves. This was a single-institution study involving patients receiving whole-brain radiotherapy. Demographic, disease, and socioeconomic parameters from electronic medical records were collected. Morning treatment (n = 158) showed a trend toward improved overall survival vs. afternoon (n = 79); the median survival was 158 vs. 79 days (p = 0.20, HR = 0.84, CI_95% 0.84–0.91). Subgroup benefits for morning treatment in females (p = 0.04) and trends in controlled primary disease (p = 0.11) and breast cancer metastases (p = 0.08) were observed. Black patients exhibited diminished circadian influence. The present study emphasized chronobiological factors’ relevance in brain metastases radiation therapy. Morning treatment correlated with improved survival, particularly in specific subgroups. Potential circadian influence disparities were identified, laying a foundation for personalized cancer therapy and interventions synchronizing circadian rhythms for enhanced treatment efficacy. Full article