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35 pages, 1236 KB  
Systematic Review
Integrating Radiomics and Artificial Intelligence (AI) in Stereotactic Body Radiotherapy (SBRT)/Stereotactic Radiosurgery (SRS): Predictive Tools for Tailored Cancer Care
by Ilaria Morelli, Marco Banini, Daniela Greto, Luca Visani, Pietro Garlatti, Mauro Loi, Michele Aquilano, Marianna Valzano, Viola Salvestrini, Niccolò Bertini, Andrea Lastrucci, Stefano Tamberi, Lorenzo Livi and Isacco Desideri
Cancers 2025, 17(17), 2906; https://doi.org/10.3390/cancers17172906 - 4 Sep 2025
Viewed by 216
Abstract
Purpose: This systematic review aims to analyze the literature on the application of AI in predicting patient outcomes and treatment-related toxicity in those undergoing SBRT or SRS across heterogeneous tumor sites. Materials and methods: Our review conformed to the Preferred Reporting Items for [...] Read more.
Purpose: This systematic review aims to analyze the literature on the application of AI in predicting patient outcomes and treatment-related toxicity in those undergoing SBRT or SRS across heterogeneous tumor sites. Materials and methods: Our review conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. PubMed, EMBASE and Scopus were systematically searched for English-language human studies evaluating AI for outcome and toxicity prediction in patients undergoing SBRT or SRS for solid tumors. Search terms included (“Stereotactic Body Radiotherapy” OR “SBRT” OR “Stereotactic Radiosurgery” OR “SRS” OR “Stereotactic Ablative Radiotherapy” OR “SABR”) AND (“Artificial Intelligence” OR “AI” OR “Machine Learning” OR “Deep Learning” OR “Radiomics”) AND (“Response Prediction” OR “Response to Treatment” OR “Outcome Prediction”) AND (“Toxicity” OR “Side Effects” OR “Treatment Toxicities” OR “Adverse Events”). Results: The search yielded 29 eligible retrospective studies, published between 2020 and 2025. Eight studies addressed early-stage primary lung cancer, highlighting the potential of AI-based models in predicting radiation-induced pneumonitis, fibrosis and local control. Five studies investigated AI models for predicting hepatobiliary toxicity following SBRT for liver tumors. Sixteen studies involved SRS-treated patients with brain metastases or benign intracranial neoplasms (e.g., arteriovenous malformations, vestibular schwannomas, meningiomas), exploring AI algorithms for predicting treatment response and radiation-induced changes. In the results, AI might have been exploited to both reaffirm already known clinical predictors and to identify novel imaging, dosimetric or biological biomarkers. Examples include predicting radiation pneumonitis in lung cancer, residual liver function in hepatic tumors and local recurrence in brain metastases, thus supporting tailored treatment decisions. Conclusions: Combining AI with SBRT could greatly enhance personalized cancer care by predicting patient-specific outcomes and toxicity. AI models analyze complex datasets, including imaging and clinical data, to identify patterns that traditional methods may miss, thus enabling more accurate risk stratification and reducing variability in treatment planning. With further research and clinical validation, this integration could make radiotherapy safer, more effective and contribute to advancement in precision oncology. Full article
(This article belongs to the Special Issue Application of Advanced Biomedical Imaging in Cancer Treatment)
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23 pages, 1499 KB  
Review
Immune Checkpoint Inhibition in Patients with Brain Metastases from Non-Small-Cell Lung Cancer: Emerging Mechanisms and Personalized Clinical Strategies
by Nicola J. Nasser, Kunal K. Sindhu, Loor Nasser, Zahra Shafaee, Joshua Li, Lucas Resende Salgado and Baoqing Li
Int. J. Mol. Sci. 2025, 26(17), 8624; https://doi.org/10.3390/ijms26178624 - 4 Sep 2025
Viewed by 330
Abstract
Brain metastases are a significant complication of non-small-cell lung cancer (NSCLC), contributing to high morbidity and mortality rates. The introduction of immune checkpoint inhibitors (ICIs) has opened new therapeutic avenues for patients with NSCLC, including those with brain metastases. However, the distinct microenvironment [...] Read more.
Brain metastases are a significant complication of non-small-cell lung cancer (NSCLC), contributing to high morbidity and mortality rates. The introduction of immune checkpoint inhibitors (ICIs) has opened new therapeutic avenues for patients with NSCLC, including those with brain metastases. However, the distinct microenvironment of the brain presents unique challenges to the effectiveness of these treatments. This review examines the mechanisms by which ICIs impact brain metastases from NSCLC, with particular focus on immune cell trafficking across the blood–brain barrier (BBB), tumor microenvironment modulation, and transcriptomic evolution of brain-tropic tumor clones. Unlike prior reviews, we integrate emerging data from single-cell and spatial transcriptomic studies, BBB disruption mechanisms, and the tumor-supportive role of brain-resident glia. We also critically evaluate key clinical trials and real-world evidence, highlighting differences in ICI efficacy across patient subgroups and therapeutic contexts. Additionally, we address the evolving role of surgical resection, stereotactic radiosurgery, and cerebrospinal-fluid-based biomarkers in optimizing ICI-based treatment strategies. This synthesis provides a comprehensive, mechanistic, and clinically relevant framework for improving outcomes in patients with NSCLC brain metastases treated with immunotherapy. Full article
(This article belongs to the Special Issue Challenges of Immune Checkpoint Inhibitor Therapy)
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27 pages, 415 KB  
Review
Radiotherapy in Glioblastoma Multiforme: Evolution, Limitations, and Molecularly Guided Future
by Castalia Fernández, Raquel Ciérvide, Ana Díaz, Isabel Garrido and Felipe Couñago
Biomedicines 2025, 13(9), 2136; https://doi.org/10.3390/biomedicines13092136 - 1 Sep 2025
Viewed by 595
Abstract
Glioblastoma multiforme (GBM), the most aggressive primary brain tumor in adults, has a poor prognosis due to rapid recurrence and treatment resistance. This review examines the evolution of radiotherapy (RT) for GBM management, from whole-brain RT to modern techniques like intensity-modulated RT (IMRT) [...] Read more.
Glioblastoma multiforme (GBM), the most aggressive primary brain tumor in adults, has a poor prognosis due to rapid recurrence and treatment resistance. This review examines the evolution of radiotherapy (RT) for GBM management, from whole-brain RT to modern techniques like intensity-modulated RT (IMRT) and volumetric modulated arc therapy (VMAT), guided by 2023 European Society for Radiotherapy and Oncology (ESTRO)-European Association of Neuro-Oncology (EANO) and 2025 American Society for Radiation Oncology (ASTRO) recommendations. The standard Stupp protocol (60 Gy/30 fractions with temozolomide [TMZ]) improves overall survival (OS) to 14.6 months, with greater benefits in O6-methylguanine-DNA methyltransferase (MGMT)-methylated tumors (21.7 months). Tumor Treating Fields (TTFields) extend median overall survival (mOS) to 31.6 months in MGMT-methylated patients and 20.9 months overall in supratentorial GBM (EF-14 trial). However, 80–90% of recurrences occur within 2 cm of the irradiated field due to tumor infiltration and radioresistance driven by epidermal growth factor receptor (EGFR) amplification, phosphatase and tensin homolog (PTEN) mutations, cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletions, tumor hypoxia, and tumor stem cells. Pseudoprogression, distinguished using Response Assessment in Neuro-Oncology (RANO) criteria and positron emission tomography (PET), complicates response evaluation. Targeted therapies (e.g., bevacizumab; PARP inhibitors) and immunotherapies (e.g., pembrolizumab; oncolytic viruses), alongside advanced imaging (multiparametric magnetic resonance imaging [MRI], amino acid PET), support personalized RT. Ongoing trials evaluating reirradiation, hypofractionation, stereotactic radiosurgery, neoadjuvant therapies, proton therapy (PT), boron neutron capture therapy (BNCT), and AI-driven planning aim to enhance efficacy for GBM IDH-wildtype, but phase III trials are needed to improve survival and quality of life. Full article
(This article belongs to the Special Issue Glioblastoma: From Pathophysiology to Novel Therapeutic Approaches)
17 pages, 675 KB  
Systematic Review
Stereotactic Radiosurgery for Recurrent Meningioma: A Systematic Review of Risk Factors and Management Approaches
by Yuka Mizutani, Yusuke S. Hori, Paul M. Harary, Fred C. Lam, Deyaaldeen Abu Reesh, Sara C. Emrich, Louisa Ustrzynski, Armine Tayag, David J. Park and Steven D. Chang
Cancers 2025, 17(17), 2750; https://doi.org/10.3390/cancers17172750 - 23 Aug 2025
Viewed by 676
Abstract
Background/Objectives: Recurrent meningiomas remain difficult to manage due to the absence of effective systemic therapies and comparatively high treatment failure rates, particularly in high-grade tumors. Stereotactic radiosurgery (SRS) offers a minimally-invasive and precise option, particularly for tumors in surgically complex locations. However, [...] Read more.
Background/Objectives: Recurrent meningiomas remain difficult to manage due to the absence of effective systemic therapies and comparatively high treatment failure rates, particularly in high-grade tumors. Stereotactic radiosurgery (SRS) offers a minimally-invasive and precise option, particularly for tumors in surgically complex locations. However, the risks associated with re-irradiation, and recent changes in the WHO classification of CNS tumors highlight the need for more personalized and strategic treatment approaches. This systematic review evaluates the safety, efficacy, and clinical considerations for use of SRS for recurrent meningiomas. Methods: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature search was conducted using the PubMed, Scopus, and Web of Science databases for studies reporting outcomes of SRS in recurrent, pathologically confirmed intracranial meningiomas. Studies were excluded if they were commentaries, reviews, case reports with fewer than three cases, or had inaccessible full text. The quality and risk of bias of the included studies were assessed using the modified Newcastle-Ottawa Scale. Data on patient and tumor characteristics, SRS treatment parameters, clinical outcomes, adverse effects, and statistical analysis results were extracted. Results: Sixteen studies were included. For WHO Grade I tumors, 3- to 5-year progression-free survival (PFS) ranged from 85% to 100%. Grade II meningiomas demonstrated more variable outcomes, with 3-year PFS ranging from 23% to 100%. Grade III tumors had consistently poorer outcomes, with reported 1-year and 2-year PFS rates as low as 0% and 46%, respectively. SRS performed after surgery alone was associated with superior outcomes, with local control rates of 79% to 100% and 5-year PFS ranging from 40.4% to 91%. In contrast, tumors previously treated with radiotherapy, with or without surgery, showed substantially poorer outcomes, with 3- to 5-year PFS ranging from 26% to 41% and local control rates as low as 31%. Among patients with prior radiotherapy, outcomes were particularly poor in Grade II and III recurrent tumors. Toxicity rates ranged from 3.7% to 37%, and were generally higher for patients with prior radiation. Predictors of worse PFS included prior radiation, older age, and Grade III histology. Conclusions: SRS may represent a reasonable salvage option for carefully selected patients with recurrent meningioma, particularly following surgery alone. Outcomes were notably worse in high-grade recurrent meningiomas following prior radiotherapy, emphasizing the prognostic significance of both histological grade and treatment history. Notably, the lack of molecular and genetic data in most existing studies represents a key limitation in the current literature. Future prospective studies incorporating molecular profiling may improve risk stratification and support more personalized treatment strategies. Full article
(This article belongs to the Special Issue Meningioma Recurrences: Risk Factors and Management)
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12 pages, 1033 KB  
Article
A Time-Series Approach for Machine Learning-Based Patient-Specific Quality Assurance of Radiosurgery Plans
by Simone Buzzi, Pietro Mancosu, Andrea Bresolin, Pasqualina Gallo, Francesco La Fauci, Francesca Lobefalo, Lucia Paganini, Marco Pelizzoli, Giacomo Reggiori, Ciro Franzese, Stefano Tomatis, Marta Scorsetti, Cristina Lenardi and Nicola Lambri
Bioengineering 2025, 12(8), 897; https://doi.org/10.3390/bioengineering12080897 - 21 Aug 2025
Viewed by 423
Abstract
Stereotactic radiosurgery (SRS) for multiple brain metastases can be delivered with a single isocenter and non-coplanar arcs, achieving highly conformal dose distributions at the cost of extreme modulation of treatment machine parameters. As a result, SRS plans are at a higher risk of [...] Read more.
Stereotactic radiosurgery (SRS) for multiple brain metastases can be delivered with a single isocenter and non-coplanar arcs, achieving highly conformal dose distributions at the cost of extreme modulation of treatment machine parameters. As a result, SRS plans are at a higher risk of patient-specific quality assurance (PSQA) failure compared to standard treatments. This study aimed to develop a machine-learning (ML) model to predict the PSQA outcome (gamma passing rate, GPR) of SRS plans. Five hundred and ninety-two consecutive patients treated between 2020 and 2024 were selected. GPR analyses were performed using a 3%/1 mm criterion and a 95% action limit for each arc. Fifteen plan complexity metrics were used as input features to predict the GPR of an arc. A stratified and a time-series approach were employed to split the data into training (1555 arcs), validation (389 arcs), and test (486 arcs) sets. The ML model achieved a mean absolute error of 2.6% on the test set, with a 0.83% median residual value (measured/predicted). Lower values of the measured GPR tended to be overestimated. Sensitivity and specificity were 93% and 56%, respectively. ML models for virtual QA of SRS can be integrated into clinical practice, facilitating more efficient PSQA approaches. Full article
(This article belongs to the Special Issue Radiation Imaging and Therapy for Biomedical Engineering)
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17 pages, 2539 KB  
Article
Auxiliary Value of [18F]F-Fluorocholine PET/CT in Evaluating Post-Stereotactic Radiosurgery Recurrence of Lung Cancer Brain Metastases: A Comparative Analysis with Contrast-Enhanced MRI
by Yafei Zhang, Mimi Xu, Shuye Yang, Lili Lin, Huatao Wang, Kui Zhao, Hong Yang and Xinhui Su
Cancers 2025, 17(15), 2591; https://doi.org/10.3390/cancers17152591 - 7 Aug 2025
Viewed by 553
Abstract
Background/Objectives: This study aims to evaluate the additional value of [18F]F-fluorocholine ([18F]F-FCH) PET/CT over contrast-enhanced magnetic resonance imaging (CE-MRI) in detecting the recurrence of brain metastases (BMs) after stereotactic radiosurgery (SRS) in patients with lung cancer brain metastases (LCBMs). [...] Read more.
Background/Objectives: This study aims to evaluate the additional value of [18F]F-fluorocholine ([18F]F-FCH) PET/CT over contrast-enhanced magnetic resonance imaging (CE-MRI) in detecting the recurrence of brain metastases (BMs) after stereotactic radiosurgery (SRS) in patients with lung cancer brain metastases (LCBMs). Methods: Thirty-one patients with suspected recurrence of BM in LCBM after SRS were enrolled in this retrospective study. They underwent both [18F]F-FCH PET/CT and CE-MRI within 2 weeks. The tumor imaging parameters and clinical features were analyzed. The results of histopathology or radiographic follow-up served as the reference standard for the final diagnosis. Results: In these 31 patients, there were 54 lesions, of which 27 lesions were proven to be BM recurrence, while 27 lesions were non-recurrence. [18F]F-FCH PET/CT showed high radiotracer uptake in recurrent lesions of BM and identified 24 positive lesions (88.89% of sensitivity), while CE-MRI indicated 23 positive lesions (85.19% of sensitivity). [18F]F-FCH PET/CT indicated higher specificity (81.48%) and accuracy (85.19%) in detecting recurrence of BM than CE-MRI (40.74% and 62.96%, both p < 0.05), particularly in frontal lobes and cerebella. For lesion sizes, the accuracy of [18F]F-FCH PET/CT in detecting recurrent lesions was higher than that of CE-MRI for lesions over 1.0 cm but below 2.0 cm (p = 0.016). The detective performance of [18F]F-FCH PET/CT combined with CE-MRI was higher than [18F]F-FCH PET/CT or CE-MRI alone (all p < 0.05). Interestingly, TLC (≥4.11) was significantly correlated with poor intracranial PFS (iPFS), meaning it was a significant prognostic factor for iPFS. Conclusions: This study identified that compared with CE-MRI, [18F]F-FCH PET/CT demonstrated higher specificity and accuracy in diagnosing recurrence of BM in LCBM after SRS. Combining [18F]F-FCH PET/CT with CE-MRI has the potential to improve diagnostic performance for recurrence of BM and management of patient treatment. TLC was an independent risk factor for iPFS. Full article
(This article belongs to the Section Cancer Metastasis)
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22 pages, 716 KB  
Article
Survival in Patients with Colorectal Cancer and Isolated Brain Metastases: Temporal Trends and Prognostic Factors from the National Cancer Database (2010–2020)
by Zouina Sarfraz, Diya Jayram, Ahmad Ozair, Lydia Hodgson, Shreyas Bellur, Arun Maharaj, Vyshak A. Venur, Sarbajit Mukherjee and Manmeet S. Ahluwalia
Cancers 2025, 17(15), 2531; https://doi.org/10.3390/cancers17152531 - 31 Jul 2025
Viewed by 500
Abstract
Background: The development of brain metastases (BM) is a relatively uncommon but significantly adverse event in the spread of colorectal cancer (CRC). Although management of CRC BM has improved with advances in imaging and systemic therapies, clinical outcomes remain poor. Methods: This retrospective [...] Read more.
Background: The development of brain metastases (BM) is a relatively uncommon but significantly adverse event in the spread of colorectal cancer (CRC). Although management of CRC BM has improved with advances in imaging and systemic therapies, clinical outcomes remain poor. Methods: This retrospective cohort study used the U.S. National Cancer Database to evaluate survival outcomes, treatment patterns, and prognostic factors in CRC patients diagnosed with BM between 2010 and 2020. Patients with isolated brain-only metastases formed the primary analytic cohort, while those with additional extracranial metastases were included for descriptive comparison. Multivariable Cox proportional hazards and logistic regression models were used to assess factors associated with of survival. Proportional hazards assumptions were tested using Schoenfeld residuals. Accelerated failure time models were also employed. Results: From a cohort of 1,040,877 individuals with CRC, 795 had metastatic disease present along with relevant data, of which 296 had isolated BM. Median overall survival (mOS) in BM-only metastatic disease group was 7.82 months (95% CI: 5.82–9.66). The longest survival was observed among patients treated with stereotactic radiosurgery combined with systemic therapy (SRS+Sys), with a median OS of 23.26 months (95% CI: 17.51–41.95) and a 3-year survival rate of 35.8%. In adjusted Cox models, SRS, systemic therapy, and definitive surgery of the primary site were each independently associated with reduced hazard of death. Rectal cancer patients had longer survival than those with colon primaries (mOS: 10.35 vs. 6.08 months). Age, comorbidity burden, and insurance status were not associated with survival in adjusted analyses. Conclusions: SRS+Sys was associated with longer survival compared to other treatment strategies. However, treatment selection is highly dependent on individual clinical factors such as performance status, comorbidities, and disease extent; therefore, these findings must be interpreted with caution Future prospective studies incorporating molecular and biomarker data are warranted to better guide care in this rare and high-risk group. Full article
(This article belongs to the Section Cancer Metastasis)
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40 pages, 1203 KB  
Review
Overview of Preclinical and Clinical Trials of Nanoparticles for the Treatment of Brain Metastases
by Muhammad Izhar, Mohamed Al Gharyani, Ahed H. Kattaa, Juan J. Cardona, Ruchit P. Jain, Elaheh Shaghaghian, Yusuke S. Hori, Fred C. Lam, Deyaaldeen Abu Reesh, Sara C. Emrich, Louisa Ustrzynski, Armine Tayag, Maciej S. Lesniak, Steven D. Chang and David J. Park
Pharmaceutics 2025, 17(7), 899; https://doi.org/10.3390/pharmaceutics17070899 - 11 Jul 2025
Viewed by 1025
Abstract
Brain metastases (BM), which most commonly originate from lung, breast, or skin cancers, remain a major clinical challenge, with standard treatments such as stereotactic radiosurgery (SRS), surgical resection, and whole-brain radiation therapy (WBRT). The prognosis for patients with BM remains poor, with a [...] Read more.
Brain metastases (BM), which most commonly originate from lung, breast, or skin cancers, remain a major clinical challenge, with standard treatments such as stereotactic radiosurgery (SRS), surgical resection, and whole-brain radiation therapy (WBRT). The prognosis for patients with BM remains poor, with a median overall survival (OS) of just 10–16 months. Although recent advances in systemic therapies, including small molecule inhibitors, monoclonal antibodies, chemotherapeutics, and gene therapies, have demonstrated success in other malignancies, their effectiveness in central nervous system (CNS) cancers is significantly limited by poor blood–brain barrier (BBB) permeability and subtherapeutic drug concentrations in the brain. Nanoparticle-based drug delivery systems have emerged as a promising strategy to overcome these limitations by enhancing CNS drug penetration and selectively targeting metastatic brain tumor cells while minimizing off-target effects. This review summarizes recent preclinical and clinical developments in nanoparticle-based therapies for BM. It is evident from these studies that NPs can carry with them a range of therapeutics, including chemotherapy, immunotherapy, small molecule inhibitors, gene therapies, radiosensitizers, and modulators of tumor microenvironment to the BM. Moreover, preclinical studies have shown encouraging efficacy in murine models, highlighting the potential of these platforms to improve therapeutic outcomes. However, clinical translation remains limited, with few ongoing trials. To close this translational gap, future work must address clinical challenges such as trial design, regulatory hurdles, and variability in BBB permeability while developing personalized nanoparticle-based therapies tailored to individual tumor characteristics. Full article
(This article belongs to the Special Issue Development of Novel Tumor-Targeting Nanoparticles, 2nd Edition)
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19 pages, 2151 KB  
Systematic Review
Optimizing Stereotactic Intracranial Neoplasm Treatment: A Systematic Review of PET Integration with Gamma Knife Radiosurgery
by Robert C. Subtirelu, Eric M. Teichner, Milo Writer, Kevin Bryan, Shiv Patil, Talha Khan, Lancelot Herpin, Raj N. Patel, Emily Christner, Chitra Parikh, Thomas Werner, Abass Alavi and Mona-Elisabeth Revheim
Diseases 2025, 13(7), 215; https://doi.org/10.3390/diseases13070215 - 10 Jul 2025
Viewed by 659
Abstract
Objective: Traditional imaging modalities for the planning of Gamma Knife radiosurgery (GKRS) are non-specific and do not accurately delineate intracranial neoplasms. This study aimed to evaluate the utility of positron emission tomography (PET) for the planning of GKRS for intracranial neoplasms (ICNs) and [...] Read more.
Objective: Traditional imaging modalities for the planning of Gamma Knife radiosurgery (GKRS) are non-specific and do not accurately delineate intracranial neoplasms. This study aimed to evaluate the utility of positron emission tomography (PET) for the planning of GKRS for intracranial neoplasms (ICNs) and the post-GKRS applications of PET for patient care. Methods: PubMed, Scopus, and ScienceDirect were searched in order to assemble relevant studies regarding the uses of PET in conjunction with GKRS for ICN treatment. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed to identify relevant studies on the use of PET in conjunction with GKRS. Particular emphasis was placed on review articles and medical research investigating tumor delineation and post-operative care. Relevant studies were selected and assessed based on quality measures, including study design, sample size, and significance. Inclusion and exclusion criteria were used to examine the yield of the initial search (n = 105). After a secondary review, the included results were identified (n = 50). Results: This study revealed that PET imaging is highly accurate for the planning of GKRS. In fact, many cases indicate that it is more specific than traditional imaging modalities. PET is also capable of complementing traditional imaging techniques through combination imaging. This showed significant efficacy for the planning of GKRS for ICNs. Conclusions: While PET shows a multitude of applications for the treatment of ICNs with GKRS, further research is necessary to assemble a complete set of clinical guidelines for treatment specifications. Importantly, future studies need a greater standardization of methods and expanded trials with a multitude of radiotracers. Full article
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9 pages, 641 KB  
Article
Long-Term Outcomes of Pediatric Cerebral Arteriovenous Malformations: A Ten-Year Single-Center Retrospective Study
by Mei-Cheng Hsiao, Yuang-Seng Tsuei, Hung-Chuan Pan, Ming-Hsi Sun, Wen-Hsien Chen, Hung-Chieh Chen, Chiung-Chyi Shen, Chi-Ruei Li and Yu-Cheng Chou
Medicina 2025, 61(7), 1177; https://doi.org/10.3390/medicina61071177 - 29 Jun 2025
Viewed by 750
Abstract
Background and Objectives: Pediatric cerebral arteriovenous malformations (AVMs) are associated with significant morbidity and mortality. The aim of this study was to assess the long-term outcomes of surgical excision and stereotactic radiosurgery (SRS) of cerebral AVMs in pediatric patients. Materials and Methods [...] Read more.
Background and Objectives: Pediatric cerebral arteriovenous malformations (AVMs) are associated with significant morbidity and mortality. The aim of this study was to assess the long-term outcomes of surgical excision and stereotactic radiosurgery (SRS) of cerebral AVMs in pediatric patients. Materials and Methods: A single-center retrospective analysis was conducted using data obtained from a single medical center between January 2012 and July 2022. The Modified Rankin Scale (mRS) at admission and discharge and the Spetzler–Martin (SM) scores were analyzed. Results: Among 45 patients (mean age 11.8 years), 19 patients (42.2%) received surgical resection, with good outcomes (mRS 0–2) in 16 patients and complete obliteration in all patients. In total, 26 patients (57.8%) were managed with SRS. After 36.3 months on average, complete obliteration in 19 of 26 patients (69.2%) was confirmed. Among the 7 SRS patients without complete obliteration, 6 had residual cerebral AVMs at the last follow-up, and 1 had recurrence. All patients receiving SRS had favorable outcomes (mRS 0–1) and no apparent radiosurgery-related complications. Conclusions: In our study, the surgical resection or SRS was selected based on individual patient conditions, and the overall outcomes were satisfactory. Both surgical resection and SRS proved to be effective treatment options. Microsurgical resection demonstrated a high rate of obliteration and remains a favorable therapeutic choice with acceptable risks for pediatric AVMs. Full article
(This article belongs to the Section Neurology)
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19 pages, 2746 KB  
Systematic Review
Is Anlotinib and Radiotherapy Combination Effective for Non-Small-Cell Lung Cancer with Brain Metastases? A Systematic Scoping Review and Meta-Analysis
by Helal F. Hetta, Mostafa A. Sayed Ali, Saleh F. Alqifari, Hoda A. Salem, Khulood A. Qasem, Fawaz E. Alanazi, Amirah Alhowiti, Amirah M. Alatawi, Hyder Mirghani, Tariq Alrasheed, Salwa Q. Bukhari, Khalid A. Almazyad, Sultan A. Alhumaid, Noura H. Abd Ellah, Hashim M. Aljohani, Yasmin N. Ramadan and Reem Sayad
Pharmaceuticals 2025, 18(7), 974; https://doi.org/10.3390/ph18070974 - 28 Jun 2025
Viewed by 807
Abstract
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 [...] Read more.
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
(This article belongs to the Section Radiopharmaceutical Sciences)
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12 pages, 445 KB  
Article
Stereotactic Radiosurgery for Patients with Brain Metastases from Sarcomas
by Andrew Hoang, Zhishuo Wei, Constantinos G. Hadjipanayis, Ajay Niranjan and L. Dade Lunsford
Cancers 2025, 17(13), 2118; https://doi.org/10.3390/cancers17132118 - 24 Jun 2025
Cited by 1 | Viewed by 960
Abstract
Purpose: We present our single-institution experience of sarcomatous brain metastasis patients who underwent stereotactic radiosurgery (SRS) over the past 35 years. Methods: In total, 31 patients (16 males) who underwent SRS for sarcoma brain metastases were identified. Median age at presentation to SRS [...] Read more.
Purpose: We present our single-institution experience of sarcomatous brain metastasis patients who underwent stereotactic radiosurgery (SRS) over the past 35 years. Methods: In total, 31 patients (16 males) who underwent SRS for sarcoma brain metastases were identified. Median age at presentation to SRS was 47 (range: 4–78) months. Common histopathologies included leiomyosarcoma (eight patients), osteosarcoma (six patients), alveolar sarcoma (three patients), Ewing sarcoma (three patients), and undifferentiated/unclassified sarcoma (three patients). The median Karnofsky Performance Score (KPS) was 90. Nine patients underwent pre-SRS craniotomy. The median dose prescribed was 18 Gy. The median cumulative tumor volume was 1.4 cc. Results: Median patient overall survival (OS) after SRS was 7 (range: 0–155) months. Local tumor control (LTC) was achieved in 105 out of 113 tumors, at a median time of 3 (range: 0–17) months between SRS and progression. LTC rates per patient and per tumor were 74.2% and 92.9%, respectively. Following SRS, 10 patients (32.3%) developed new tumors at a median time of 6 (range: 1–25) months. Four patients experienced adverse radiation effects (AREs). At the last follow-up, all patients died, one patient from intracranial progression, 27 from systemic disease progression, and the remaining from unrelated medical conditions. Conclusions: Given high LTC and low ARE rates, this suggests SRS as a strong candidate for the non-invasive management of sarcomatous brain metastases, which typically present late following initial presentation of the primary disease. Full article
(This article belongs to the Special Issue Radiosurgery for Brain Tumors)
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35 pages, 994 KB  
Review
Understanding the Radiobiology of Central Nervous System Diseases in the Golden Age of Radiosurgery—Does It Matter?
by Fred C. Lam, John Byun, Santosh Guru, Deyaldeen AbuReesh, Yusuke S. Hori, Elham Rahimy, Erqi Liu Pollom, Scott Soltys, David J. Park and Steven D. Chang
Brain Sci. 2025, 15(6), 649; https://doi.org/10.3390/brainsci15060649 - 17 Jun 2025
Cited by 1 | Viewed by 1348
Abstract
Stereotactic radiosurgery (SRS) deploys image-guidance to deliver multiple beams of highly focused ionizing radiation to tightly conformed anatomical targets, leading to precise dosing of radiation-induced cellular injury and predictable biological responses that can be applied to treat a multitude of central nervous system [...] Read more.
Stereotactic radiosurgery (SRS) deploys image-guidance to deliver multiple beams of highly focused ionizing radiation to tightly conformed anatomical targets, leading to precise dosing of radiation-induced cellular injury and predictable biological responses that can be applied to treat a multitude of central nervous system (CNS) disorders. Herein we review the principles of CNS radiobiology, comparing differences between SRS and conventional radiation therapy. We then review the radiobiology of SRS as it pertains to the treatment of CNS tumors and vascular malformations and the emerging application of SRS for the treatment of functional and psychiatric neurological disorders. Finally, we look toward the future in combining SRS with other novel technologies to improve treatment outcomes for patients with CNS disorders. Full article
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14 pages, 667 KB  
Article
MRI-Based Radiomics Ensemble Model for Predicting Radiation Necrosis in Brain Metastasis Patients Treated with Stereotactic Radiosurgery and Immunotherapy
by Yijun Chen, Corbin Helis, Christina Cramer, Michael Munley, Ariel Raimundo Choi, Josh Tan, Fei Xing, Qing Lyu, Christopher Whitlow, Jeffrey Willey, Michael Chan and Yuming Jiang
Cancers 2025, 17(12), 1974; https://doi.org/10.3390/cancers17121974 - 13 Jun 2025
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Abstract
Background: Radiation therapy is a primary and cornerstone treatment modality for brain metastasis. However, it can result in complications like necrosis, which may lead to significant neurological deficits. This study aims to develop and validate an ensemble model with radiomics to predict radiation [...] Read more.
Background: Radiation therapy is a primary and cornerstone treatment modality for brain metastasis. However, it can result in complications like necrosis, which may lead to significant neurological deficits. This study aims to develop and validate an ensemble model with radiomics to predict radiation necrosis. Method: This study retrospectively collected and analyzed MRI images and clinical information from 209 stereotactic radiosurgery sessions involving 130 patients with brain metastasis. An ensemble model integrating gradient boosting, random forest, decision tree, and support vector machine was developed and validated using selected radiomic features and clinical factors to predict the likelihood of necrosis. The model performance was evaluated and compared with other machine learning algorithms using metrics, including the area under the curve (AUC), sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). SHapley Additive exPlanations (SHAP) analysis and local interpretable model-agnostic explanations (LIME) analysis were applied to explain the model’s prediction. Results: The ensemble model achieved strong performance in the validation cohort, with the highest AUC. Compared to individual models and the stacking ensemble model, it consistently outperformed. The model demonstrated superior accuracy, generalizability, and reliability in predicting radiation necrosis. SHAP and LIME were used to interpret a complex predictive model for radiation necrosis. Both analyses highlighted similar significant factors, enhancing our understanding of prediction dynamics. Conclusions: The ensemble model using radiomic features exhibited high accuracy and robustness in predicting the occurrence of radiation necrosis. It could serve as a novel and valuable tool to facilitate radiotherapy for patients with brain metastasis. Full article
(This article belongs to the Special Issue Brain Metastases: From Mechanisms to Treatment)
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15 pages, 614 KB  
Article
Population-Based Real-World Outcomes of Post-Operative Adjuvant Brain Cavity Radiotherapy Versus Observation
by Zhang Hao (Jim) Li, Linden Lechner, Jennifer Wang, Nan Hui (Susan) Yao, Andrew Lee, Serge Makarenko, Mostafa Fatehi, Herve H. F. Choi, Ermias Gete, Fred Hsu, Waseem Sharieff, Shrinivas Rathod, Hannah Carolan, Jessica Chan, Roy Ma, Alan Nichol, Thi Nghiem and Justin Oh
Curr. Oncol. 2025, 32(6), 345; https://doi.org/10.3390/curroncol32060345 - 11 Jun 2025
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Abstract
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 [...] Read more.
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
(This article belongs to the Section Neuro-Oncology)
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