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Background: The efficacy and safety of combining epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) with whole-brain radiotherapy (WBRT) for treating brain metastases in non-small cell lung cancer patients remains to be determined., Methods: A systematic search was conducted using databases including PubMed, Embase, Web of Science, Cochrane, Wanfang, and China National Knowledge Infrastructure (CNKI), aiming to identify relevant clinical studies on the treatment of brain metastases originating from non-small cell lung cancer through the combination of EGFR-TKI and WBRT. Statistical analysis was performed utilizing Stata 17.0 software, covering clinical studies published until March 1, 2023., Results: This analysis incorporated 23 randomized controlled trials (RCTs), involving a total of 2,025 patients. Of these, 1,011 were allocated to the group receiving both EGFR-TKI and WBRT, while 1,014 were assigned to the WBRT alone group. The findings reveal that the combination of EGFR-TKI and WBRT significantly improves the intracranial objective remission rate (RR = 1.57, 95% CI: 1.42-1.74, p  < 0.001), increases the intracranial disease control rate (RR = 1.30, 95% CI: 1.23-1.37, p  < 0.001), and enhances the 1-year survival rate (RR = 1.48, 95% CI: 1.26-1.73, p  < 0.001). Additionally, this combined treatment was associated with a significant survival advantage (RR = 1.48, 95% CI: 1.26-1.73, p  < 0.001) and a reduced incidence of adverse effects (RR = 0.65, 95% CI: 0.51-0.83, p  < 0.001), particularly with respect to nausea and vomiting (RR = 0.54, 95% CI: 0.37-0.81, p  = 0.002) and myelosuppression (RR = 0.59, 95% CI: 0.40-0.87, p = 0.008). However, no statistically significant differences were observed for diarrhea (RR = 1.15, 95% CI: 0.82-1.62, p  = 0.418), and skin rash (RR = 1.35, 95% CI: 0.88-2.07, p  = 0.164)., Conclusion: In contrast to WBRT alone, the combination of EGFR-TKI and WBRT significantly improves intracranial response, enhancing the objective response rate, disease control rate, and 1-year survival rate in NSCLC patients with brain metastases. Moreover, aside from mild cases of rash and diarrhea, there is no statistically significant increase in the incidence of additional adverse effects. Based on the comprehensive evidence collected, the use of third-generation EGFR-TKI combined with WBRT is recommended as the preferred treatment for NSCLC patients with brain metastases, offering superior management of metastatic brain lesions., Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#, CRD42023415566., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Xu, Li, Xue and He.)

During the V Siena Immuno-Oncology (IO) Think Tank meeting in 2021, conditions were discussed which favor immunotherapy responses in either primary or secondary brain malignancies. Core elements of these discussions have been reinforced by important publications in 2021 and 2022. In primary brain tumors (such as glioblastoma) current immunotherapies have failed to deliver meaningful clinical benefit. By contrast, brain metastases frequently respond to current immunotherapies. The main differences between both conditions seem to be related to intrinsic factors (e.g., type of driver mutations) and more importantly extrinsic factors, such as the blood brain barrier and immune suppressive microenvironment (e.g., T cell counts, functional differences in T cells, myeloid cells). Future therapeutic interventions may therefore focus on rebalancing the immune cell population in a way which enables the host to respond to current or future immunotherapies.

(1) Background: Neuroimaging differentiation of glioblastoma, primary central nervous system lymphoma (PCNSL) and solitary brain metastasis (BM) represents a diagnostic and therapeutic challenge in neurosurgical practice, expanding the burden of care and exposing patients to additional risks related to further invasive procedures and treatment delays. In addition, atypical cases and overlapping features have not been entirely addressed by modern diagnostic research. The aim of this study was to validate a previously designed and internally validated ResNet101 deep learning model to differentiate glioblastomas, PCNSLs and BMs. (2) Methods: We enrolled 126 patients (glioblastoma: n = 64; PCNSL: n = 27; BM: n = 35) with preoperative T1Gd-MRI scans and histopathological confirmation. Each lesion was segmented, and all regions of interest were exported in a DICOM dataset. A pre-trained ResNet101 deep neural network model implemented in a previous work on 121 patients was externally validated on the current cohort to differentiate glioblastomas, PCNSLs and BMs on T1Gd-MRI scans. (3) Results: The model achieved optimal classification performance in distinguishing PCNSLs (AUC: 0.73; 95%CI: 0.62–0.85), glioblastomas (AUC: 0.78; 95%CI: 0.71–0.87) and moderate to low ability in differentiating BMs (AUC: 0.63; 95%CI: 0.52–0.76). The performance of expert neuro-radiologists on conventional plus advanced MR imaging, assessed by retrospectively reviewing the diagnostic reports of the selected cohort of patients, was found superior in accuracy for BMs (89.69%) and not inferior for PCNSL (82.90%) and glioblastomas (84.09%). (4) Conclusions: We investigated whether the previously published deep learning model was generalizable to an external population recruited at a different institution—this validation confirmed the consistency of the model and laid the groundwork for future clinical applications in brain tumour classification. This artificial intelligence-based model might represent a valuable educational resource and, if largely replicated on prospective data, help physicians differentiate glioblastomas, PCNSL and solitary BMs, especially in settings with limited resources.

Brain metastases (BMs) represent a negative prognostic factor for patients with solid malignancies. BMs are generally approached with loco-regional treatments and the blood–brain barrier limits the efficacy of some systemic drugs. The aim of this review is to summarize current knowledge about the role of immune checkpoint inhibitors for the management of brain metastases in patients with solid malignancies. We performed a review of available literature. Immune checkpoint inhibitors represent the standard treatment for several advanced solid malignancies. However, with the exception of melanoma their clinical role in other solid malignancies is not completely clear due to the exclusion of patients with BM from approval clinical trials. Immune-checkpoint inhibitors may be an effective treatment of brain metastases of melanoma while their clinical role on brain metastases from other solid malignancies is uncertain.

BackgroundNeuroimaging differentiation of glioblastoma, primary central nervous system lymphoma (PCNSL) and solitary brain metastasis (BM) remains challenging in specific cases showing similar appearances or atypical features. Overall, advanced MRI protocols have high diagnostic reliability, but their limited worldwide availability, coupled with the overlapping of specific neuroimaging features among tumor subgroups, represent significant drawbacks and entail disparities in the planning and management of these oncological patients.ObjectiveTo evaluate the classification performance metrics of a deep learning algorithm trained on T1-weighted gadolinium-enhanced (T1Gd) MRI scans of glioblastomas, atypical PCNSLs and BMs.Materials and MethodsWe enrolled 121 patients (glioblastoma: n=47; PCNSL: n=37; BM: n=37) who had undergone preoperative T1Gd-MRI and histopathological confirmation. Each lesion was segmented, and all ROIs were exported in a DICOM dataset. The patient cohort was then split in a training and hold-out test sets following a 70/30 ratio. A Resnet101 model, a deep neural network (DNN), was trained on the training set and validated on the hold-out test set to differentiate glioblastomas, PCNSLs and BMs on T1Gd-MRI scans.ResultsThe DNN achieved optimal classification performance in distinguishing PCNSLs (AUC: 0.98; 95%CI: 0.95 - 1.00) and glioblastomas (AUC: 0.90; 95%CI: 0.81 - 0.97) and moderate ability in differentiating BMs (AUC: 0.81; 95%CI: 0.70 - 0.95). This performance may allow clinicians to correctly identify patients eligible for lesion biopsy or surgical resection.ConclusionWe trained and internally validated a deep learning model able to reliably differentiate ambiguous cases of PCNSLs, glioblastoma and BMs by means of T1Gd-MRI. The proposed predictive model may provide a low-cost, easily-accessible and high-speed decision-making support for eligibility to diagnostic brain biopsy or maximal tumor resection in atypical cases.

Brain metastases, the most common metastases in adults, will develop in up to 40% of cancer patients, accounting for more than one-half of all intracranial tumors. They are most associated with breast and lung cancer, melanoma and, less frequently, colorectal and kidney carcinoma. Magnetic resonance imaging (MRI) is the gold standard for diagnosis. For the treatment plan, computed tomography (CT ) images are co-registered and fused with a gadolinium-enhanced T1-weighted MRI where tumor volume and organs at risk are contoured. Alternatively, plain and contrast-enhanced CT scans are co-registered. Single-fraction stereotactic radiotherapy (SRT ) is used to treat patients with good performance status and up to 4 lesions with a diameter of 30 mm or less that are distant from crucial brain function areas. Fractionated SRT (2-5 fractions) is used for larger lesions, in eloquent areas or in proximity to crucial or surgically inaccessible areas and to reduce treatment-related neurotoxicity. The single-fraction SRT dose, which depends on tumor diameter, impacts local control. Fractionated SRT may encompass different schedules. No randomized trial data compared the safety and efficacy of single and multiple fractions. Both single-fraction and fractionated SRT provide satisfactory local control rates, tolerance, a low risk of transient acute adverse events and of radiation necrosis the incidence of which correlated with the irradiated brain volume.

Cerebral radiation necrosis (RN), a complication of Gamma Knife radiosurgery, is difficult to treat, although bevacizumab seems to be effective. However, clinical data pertaining to bevacizumab treatment for RN are scarce, and its high price is problematic. This study explored the effectiveness of low-dose bevacizumab for RN caused by Gamma Knife. We retrospectively analyzed 22 patients who suffered cerebral RN post-Gamma Knife, and received bevacizumab treatment because of the poor efficacy of glucocorticoids. Low-dose bevacizumab (3 mg/kg) was administered for two cycles at 2-week intervals. T1- and T2-enhanced magnetic resonance imaging (MRI) images were examined for changes in RN status. We also monitored the dose of glucocorticoid, Karnofsky Performance Status (KPS) score, and adverse drug reactions. The mean volume of RN lesions decreased by 45% on T1-weighted images with contrast enhancement, and by 74% on T2-weighted images. All patients discontinued the use of glucocorticoids. According to the KPS scores, all patients showed an improvement in their symptoms and neurological function. No side effects were observed. Low-dosage bevacizumab at a dose of 3 mg/kg every 2 weeks is effective for treating cerebral RN after Gamma knife for brain metastases.

Rita Viglialoro,1,2,&ast; Enrica Esposito,1,2,&ast; Roberta Zanca,1,2 Marco Gessi,3 Tommaso Depalo,1,2 Gayane Aghakhanyan,1,2 Francesco Bartoli,1,2 Martina Sollini,4,5 Paola Anna Erba1,2,6 1Regional Center of Nuclear Medicine, Department of Translational Research and New Technology in Medicine, University of Pisa, Pisa, Italy; 2Azienda Ospedaliero Universitaria Pisana, Pisa, Italy; 3Neuropathology Unit, Division of Pathology Fondazione Policlinico Universitario “A.Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy; 4Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090, Italy; 5IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy; 6Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Centre, University Medical Center Groningen, Groningen, the Netherlands&ast;These authors contributed equally to this workCorrespondence: Paola Anna ErbaDepartment of Translational Research and New Technology in Medicine, via Savi 10, Pisa, 56126, ItalyTel +39-050-992115Fax +39-050-992124Email p.erba@unipi.itAbstract: Brain metastases from prostate cancer typically occur in the more advanced stages of the disease. Clinically, the early diagnosis of visceral disease is crucial, impacting on patient’s management and prognosis. Although magnetic resonance imaging (MRI) is the modality of choice for the detection of brain metastases, it is not routinely performed in the surveillance of prostate cancer patients unless neurological manifestations appear. Prostate-specific membrane antigen (PSMA) is a glycoprotein, a membrane-bound metallopeptidase, overexpressed in more than 90% of prostate cancer cells. This molecular target is a suitable tissue biomarker for prostate cancer functional imaging. We present a case of a 73-year gentleman diagnosed with prostate adenocarcinoma and surgically treated (pT3bN1Mx, Gleason Score of 9) in February 2016. Subsequently, he underwent androgen deprivation therapy because of the occurrence of a bone metastasis. Between 2016 and January 2019 PSA levels were maintained under control. Starting from September 2019, it progressively raised up to 0.85 ng/mL with a doubling time of 3.3 months. Therefore, he performed a [68Ga]Ga-PSMA-11 PET/CT which showed a focal radiopharmaceutical uptake in the right temporal lobe corresponding to the presence of a rounded cystic lesion on brain MRI. The subsequent excisional biopsy diagnosed a prostate adenocarcinoma metastasis. PSMA expression has been reported in brain parenchyma after ischemic strokes and in some brain tumors including gliomas, meningiomas, and neurofibromas. In our case, the lack of symptoms and the relatively low PSA level raised questions about the nature of the lesion, posing the differential diagnosis between brain metastases and primary brain tumor. Finally, our case shows the capability of [68Ga]Ga-PSMA-11 PET/CT to detect metachronous distant brain metastases in a low biochemical recurrent asymptomatic prostate cancer patient, indicating that proper acquisition – from the vertex to thigh – should be always considered, regardless of the PSA level.Keywords: [68Ga]Ga-PSMA-11 PET/CT, biochemical recurrence, brain metastases, multimodal imaging, prostate cancer, PSA

Background Stereotactic radiosurgery (SRS) has been increasingly applied for up to 10 brain metastases instead of whole brain radiation therapy (WBRT) to achieve local tumor control while reducing neurotoxicity. Furthermore, brain-metastasis incidence is rising due to the increasing survival of patients with cancer. Our aim was to analyze the efficacy and safety of CyberKnife (CK) radiosurgery for elderly patients. Methods We retrospectively identified all patients with brain metastases ≥ 65 years old treated with CK-SRS at our institution since 2011 and analyzed data of primary diseases, multimodality treatments, and local therapy effect based on imaging follow-up and treatment safety. Kaplan–Meier analysis for local progression-free interval and overall survival were performed. Results We identified 97 patients (233 lesions) fulfilling the criteria at the first CK-SRS. The mean age was 73.2 ± 5.8 (range: 65.0–87.0) years. Overall, 13.4% of the patients were > 80 years old. The three most frequent primary cancers were lung (40.2%), kidney (22.7%), and malignant melanoma (15.5%). In 38.5% (47/122 treatments) multiple brain metastases were treated with the CK-SRS, with up to eight lesions in one session. The median planning target volume (PTV) was 1.05 (range: 0.01–19.80) cm3. A single fraction was applied in 92.3% of the lesions with a median prescription dose of 19 (range: 12–21) Gy. The estimated overall survivals at 3-, 6-, and 12 months after SRS were 79, 55, and 23%, respectively. The estimated local tumor progression-free intervals at 6-, 12-, 24-, 36-, and 72 months after SRS were 99.2, 89.0, 67.2, 64.6, and 64.6%, respectively. Older age and female sex were predictive factors of local progression. The Karnofsky performance score remained stable in 97.9% of the patients; only one patient developed a neurological deficit after SRS of a cerebellar lesion (ataxia, CTCAE Grade 2). Conclusions SRS is a safe and efficient option for the treatment of elderly patients with brain metastases with good local control rates without the side effects of WBRT. Older age and female sex seem to be predictive factors of local progression. Prospective studies are warranted to clarify the role of SRS treatment for elderly patients.

Introduction: Whole-brain radiation therapy (WBRT) is an effective therapeutic modality in patients with brain metastases. However, nearly 90% of patients undergoing WBRT suffer from a neurocognitive function (NCF) impairment at diagnosis, and up to two-thirds will experience a further decline within 2–6 months after WBRT. Focal-dose reduction on bilateral hippocampus is thought to improve NCF preservation. The aim was to present a systematic review of clinical results on NCF after hippocampal-sparing (HS) WBRT. Materials and Methods: A systematic review of published literature was performed on PubMed and the Cochrane Library. Only prospective clinical trials reporting NCF outcome in patients treated with HS-WBRT have been analyzed. Results: A total of 165 patients from three studies were included. These studies are characterized by small sample size and different methods in terms of WBRT technique but with similar planning analysis and NCF assessment tests. No significant changes in NCF (i.e., verbal and nonverbal learning memory, executive functions, and psychomotor speed) between baseline and 4-month follow-up after RT and only a mean relative decline in delayed recall at 4 months (7% compared to 30% of historical control) were observed. Conclusions: Considering preliminary results on NCF preservation, further studies seem justified in patients undergoing brain irradiation for brain metastases or referred for prophylactic cranial irradiation to evaluate long-term effects on NCF and quality of life.

AimTo assess the role of perilesional edema (PE) in non-small cell lung carcinoma (NSCLC) brain metastases (BM) undergoing radiosurgery (SRS).MethodsThis series includes 46patients with 1-2BM treated with SRS, selected out of all patients referred for radiotherapy (RT) for BMs over 5years (2013 to 2017). Both the PE and gross tumor volume (GTV) were contoured on MRI images, and the PE/GTV ratio and PE+GTV value (TV, total volume) were calculated. Our clinical endpoints were brain recurrence free-survival, divided into local brain control (in field, LBC) and distant brain control (out of field, DBC) and overall survival (OS). We analyzed the role of the previously described volumetric parameters and of known clinical prognosticators (disease specific GPA, DS-GPA; chemotherapy, CHT) with Cox regression analyses.ResultsOnly four patients (9%) developed in-field progression, whereas 10patients (22%) showed new out-of-field BM and thirty-eight patients died in the follow up (83%). In univariate analysis, both volumetric parameters and clinical parameters were correlated with DBC and OS, whereas we did not find any correlation with LBC. In the multivariate analysis of DBC, the significant parameters were PE/GTV ratio (HR 0.302), sex (HR 0.131), and DS-GPA (HR 0.261). The OS multivariate analysis showed that the only significant parameters were DS-GPA (HR 0.478) and TV (HR: 1.038).ConclusionOur study, although with the limitations of amonocentric retrospective study analyzing asmall cohort of patients, suggests the role of PE/GTV ratio for the development of new BMs. TV also seems to be correlated with OS, together with known clinical prognosticators. These findings, if validated in alarger prospective dataset, could help in selecting patients for the most suitable RT modality (or systemic therapy approach). ZusammenfassungZielBeurteilung der Rolle des perilesionalen odems (PE) bei der Radiochirurgie (SRS) von Hirnmetastasen (BM) beim nicht-kleinzelligen Lungenkarzinom (NSCLC).MethodenDiese Serie umfasst 46Patienten mit 1-2 mit SRS behandelten BM, die aus allen Patienten ausgewahlt wurden, bei denen uber einen Zeitraum von 5Jahren (2013-2017) eine Radiotherapie (RT) zur BM-Behandlung eingesetzt wurde. Sowohl das PE- als auch das Bruttovolumen des Tumors (GTV) wurde auf MRT-Bildern konturiert, um das PE/GTV-Verhaltnis und den PE+GTV-Wert (TV, Gesamtvolumen) zu erhalten. Unsere klinischen Endpunkte waren die rezidivfreie Zeit des Gehirns, welche in die lokale Hirnkontrolle (LBC, in field) und die entfernte Hirnkontrolle (DBC, out of field) unterteilt wurde, sowie das Gesamtuberleben des Patienten (OS). Wir haben die Rolle der zuvor beschriebenen volumetrischen Parameter und der bekannten klinischen Faktoren (krankheitsspezifische GPA: DS-GPA, Chemotherapie: CHT) mit den Cox-Regressionsanalysen analysiert.ErgebnisseNur 4Patienten (9%) entwickelten eine In-field-Progression, wohingegen 10Patienten (22%) neue Out-of-field-BM zeigten und 38Patienten im Follow-up starben (83%). Bei der univariaten Analyse wurden sowohl die volumetrischen Parameter als auch die klinischen Parameter mit DBC und OS korreliert, wohingegen wir keine Korrelation mit LBC fanden. Bei der multivariaten DBC-Analyse waren das PE/GTV-Verhaltnis (HR 0,302), das Geschlecht des Patienten (HR 0,131) und das DS-GPA (HR 0,261) signifikante Parameter.SchlussfolgerungUnsere Studie legt - trotz der Einschrankungen einer monozentrischen retrospektiven Studie, die eine kleine Patientengruppe analysiert - die Rolle des PE/GTV-Verhaltnisses fur die Entwicklung neuer BMs nahe.Das TV scheint auch mit OS, zusammen mit bekannten klinischen Faktoren, zu korrelieren. Diese Erkenntnisse konnten, wenn sie in einem gro ss eren, prospektiven Datensatz validiert wurden, bei der Auswahl der Patienten fur die geeignetste RT-Modalitat (oder den systemischen Therapieansatz) helfen.

Metastatic disease is a common complication of the most advanced malignancies. It may compromise the patients' quality of life, often posing a greater risk than the primary disease itself. Currently, several different therapeutic approaches are available to palliate or cure (single metastasis with primary neoplasm under control - radical surgery) secondary disease. In particular, radiation therapy is widely used, as it often leads to full or at least partial functional recovery, depending on the number and location of metastases. The aim of our study was to evaluate whether clinical improvement subsequent to radiation therapy may be related to anatomical recovery of the site of metastasis in cancer patients with metastatic disease. Given the heterogeneity of the diseases considered and the general complex conditions of the patients, a single method could not be used to evaluate the response to radiation treatment and its correlation with the performance status (PS). Thus, depending on the specific disease being assessed, we divided the patients into different groups. Patients in the same group were followed up with the same methods. This correlation was noted in a very high percentage of patients, predominantly in patients with vertebral and brain metastases. Moreover, we investigated the use of magnetic resonance imaging (MRI)-diffusion weighted imaging (DWI) in the study of spinal metastases. We propose its use in the local evaluation of vertebral secondary lesions, both in the diagnostic phase and during the assessment of treatment efficacy.

Jianping Xu, Xiaoyan Liu, Sheng Yang, Xiangru Zhang, Yuankai Shi Department of Internal Medicine, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China Objective: The objective of this study was to evaluate the efficacy and safety of icotinib in patients with brain metastases (BMs) from lung adenocarcinoma.Patients and methods: Clinical data of 28 cases with BMs from lung adenocarcinoma were retrospectively analyzed. All the patients took 125mg icotinib orally three times a day. Progression of disease, intolerable adverse reactions, and number of deaths were recorded.Results: For all the patients, the remission rate of icotinib was 67.8% and the disease control rate was 96.4%. The median overall survival time of patients was 21.2months, and the median progression-free survival time of patients was 10.9months. Only mild adverse events of grade 1/2 were observed during the treatment.Conclusion: Icotinib was an effective and safe strategy to treat patients with BMs from lung adenocarcinoma.Keywords: icotinib, lung adenocarcinoma, brain metastases&nbsp

Objectives The purpose of our study was to evaluate whether peritumoural perfusion weighted and proton spectroscopic magnetic resonance imaging can be used in differentiating between primary gliomas and solitary metastases. Methods Ten low-grade gliomas, eight high-grade gliomas and 10 metastases were prospectively evaluated with magnetic resonance imaging, dynamic susceptibility contrast enhanced perfusion imaging and single-voxel proton magnetic resonance spectroscopy before surgical resection or stereotactic biopsy. Maximal relative cerebral blood volume values were calculated drawing three regions of interest of 2 cm2 in the non-enhancing peritumoural areas. Maximal relative cerebral blood volume values were normalised to that of contralateral normal-appearing white matter. Maximal choline/creatine ratios were calculated from three voxels of 10 cm3 placed in the peritumoural areas defined as non-enhancing peritumoural white matter surrounding the tumour. The tumour grade presumed with these values was compared to histopathological grading. Differences in the study parameters between groups were assessed using the Mann–Whitney test. A receiver operating characteristic analysis was performed to determine cut-off values. Results A clear relative cerebral blood volume cut-off value of 1.88 was detected for differentiating low-grade gliomas from high-grade gliomas. A clear relative cerebral blood volume cut-off value of 1.20 was detected for differentiation of metastases from gliomas. The differences in the choline/creatine ratios in the peritumoural regions of high-grade gliomas and of solitary metastasis were statistically significant ( P Conclusion Our preliminary data support the hypothesis that peritumoural perfusion-weighted imaging can assist in preoperative differentiation between a glioma and a solitary metastasis.

Purpose: To evaluate the dosimetric performance and planning/delivery efficiency of a dual-layer MLC system for treating multiple brain metastases with a single isocenter.Materials and Methods: 10 patients each with 6–10 targets with volumes from 0.11 to 8.57 cc, and prescription doses from 15 to 24 Gy, were retrospectively studied. Halcyon has only coplanar delivery mode. Halcyon V1 MLC modulates only with the lower layer at 1 cm resolution, whereas V2 MLC modulates with both layers at an effective resolution of 0.5 cm. For each patient five plans were compared varying MLC and beam arrangements: the clinical plan using multi-aperture dynamic conformal arc (DCA) and non-coplanar arcs, Halcyon-V1 using coplanar-VMAT, Halcyon-V2 using coplanar-VMAT, HDMLC-0.25 cm using coplanar-VMAT, and HDMLC-0.25 cm using non-coplanar-VMAT. All same-case plans were generated following the same planning protocol and normalization. Conformity index (CI), gradient index (GI), V12Gy, V6Gy, V3Gy, and brain mean dose were compared.Results: All VMAT plans met clinical constraints for critical structures. For targets with diameter < 1 cm, Halcyon plans showed inferior CI among all techniques. For targets with diameter >1 cm, Halcyon VMAT plans had CI similar to non-coplanar VMAT plans, and better than non-coplanar clinical DCA plans. For GI, Halcyon MLC plans performed similarly to coplanar HDMLC plans and inferiorly compared to non-coplanar HDMLC plans. All coplanar VMAT plans (Halcyon MLC and HDMLC) and clinical DCA plans had similar V12Gy, but were inferior compared to non-coplanar VMAT plans. Halcyon plans had slightly reduced V3Gy and mean brain dose compared to HDMLC plans. The difference between Halcyon V1 and V2 is only significant in CI of tumors less than 1cm in diameter. Halcyon plans required longer optimization than Truebeam VMAT plans, but had similar delivery efficiency.Conclusion: For targets with diameter >1 cm, Halcyon's dual-layer stacked and staggered MLC is capable of producing similar dose conformity compared to HDMLC while reducing low dose spill to normal brain tissue. GI and V12Gy of Halcyon MLC plans were, in general, inferior to non-coplanar DCA or VMAT plans using HDMLC, likely due to coplanar geometry and wider MLC leaves. HDMLC maintained its advantage in CI for smaller targets with diameter

Objective: Brain metastases (BMs) from biliary tract cancer (BTC) are extremely rare. The aim of our study was to report the incidence of BMs in patients with BTC. Methods: We retrospectively analyzed a series of 450 patients with BTC. Presence of brain lesions was investigated only when symptoms were evident. Cumulative incidence, median overall survival (OS) from detection of BMs, median OS from cancer diagnosis, and median time from cancer diagnosis to detection of BMs were evaluated. Results: In our series, 6 patients developed BMs with an incidence of about 1.4%. Median OS from detection of BMs and from cancer diagnosis was, respectively, 3.7 (0.9-17.8) and 23 (9.9-57.6) months. Median time between cancer diagnosis and detection of BMs was 13.6 (7.3-52.8) months. Moreover, we observed a significant association between BMs and bone metastases (particularly vertebral lesions). Discussion: Despite the retrospective design, this is the first study evaluating the incidence of BMs among patients with BTC in Western countries. BMs from BTC remain atypical, although their incidence is probably a little higher than previously assumed. Patients with BMs had poor prognosis. Unpredictably, bone involvement occurred in 5 out of 6 patients.

BACKGROUND : Stereotactic irradiation is widely used in brain oligo-metastases treatment. The aim of this study is to evaluate the prognostic value of magnetic resonance imaging (MRI) texture analysis (TA) of brain metastases (BM) of non-small cell lung cancer (NSCLC). MATERIALS AND METHODS : This study included thirty-eight consecutive patients undergoing stereotactic irradiation, that is, stereotactic fractionated radiotherapy (SRT) or radiosurgery (SRS), from January 2011 to December 2014 for 1-2 brain BM from NSCLC. Whole-brain radiotherapy (WBRT) was not delivered. The diagnostic MRI DICOM (Digital Imaging and Communications in Medicine) images were collected and analyzed with a homemade ImageJ macro, and typical TA parameters (mean, standard deviation, skewness, kurtosis, entropy, and uniformity) were evaluated for: brain progression-free survival; modality of brain metastatic progression (local progression or/and new metastases); and overall survival, after SRT/SRS. RESULTS: After SRT/SRS 14 patients (36.8%) experienced recurrence in the brain, with a recurrence in the irradiated site (five patients, 13.2%), new metastases (11 patients, 28.9%), local recurrence and new metastases (two patients, 5.25%). Nineteen patients (50%) died of tumor progression or other causes. Entropy and uniformity were significantly associated with local progression, whereas kurtosis was significantly associated with both local progression and new brain metastases. CONCLUSIONS : These results appear promising, since the knowledge of factors correlated with the modality of brain progression after stereotactic irradiation of brain oligo-metastatic foci of NSCLC might help in driving the best treatment in these patients (association of SRT/SRS with WBRT? Increase of SRT/SRS dose?). Our preliminary data needs confirmation in large patient series.

Introduction: ALK rearranged Non Small Cell Lung Cancers (NSCLCs) represent a distinct subgroup of patients with peculiar clinic-pathological features. These patients exhibit dramatic responses when treated with the ALK tyrosine kinase inhibitor Crizotinib, albeit Central Nervous System (CNS) activity is much less impressive than that observed against extracranial lesions. CNS involvement has become increasingly observed in these patients, given their prolonged survival. Several novel generation ALK inhibitors have been developing to increase CNS penetration and to provide more complete ALK inhibition. Areas covered: The CNS activity of Crizotinib and novel generation ALK inhibitors will be summarized in this review, evaluating the strengths and weaknesses of the therapeutic strategies developed to date in this specific subgroup of NSCLCs with a look towards the future. Expert commentary: In the next few years, the results of ongoing comparative head-to-head trials will provide the definitive conclusions on the optimal treatment sequence in ALK-rearranged NSCLCs. Moreover, ongoing clinical trials with novel-generation ALK inhibitors will produce more evidences on the best approach in the growing number of ALK-positive NSCLCs with CNS involvement.

In this retrospective study, we evaluated the overall survival (OS) and local control (LC) of brain metastases (BM) in patients treated with stereotactic radiosurgery (SRS). The scope was to identify host, tumor, and treatment factors predictive of LC and survival and define implications for clinical decisions. A total of 223 patients with 360 BM from various histologies treated with SRS alone or associated with whole brain radiotherapy (WBRT) in our institution between July 1, 2008 and August 31, 2013 were retrospectively reviewed. Among other prognostic factors, we had also evaluated retrospectively Karnofsky performance status scores (KPS) and graded prognostic assessment (GPA). Overall survival (OS) and local control (LC) were the primary endpoints. Kaplan-Meier and Cox proportional hazards models were used to estimate OS and LC and identify factors predictive of survival and local control. The median duration of follow-up time was 9 months (range 0.4-51 months). Median overall survival of all patients was 11 months. The median local control was 38 months. No statistical difference in terms of survival or LC between patients treated with SRS alone or associated with WBRT was found. On multivariate analysis, KPS was the only statistically significant predictor of OS (hazard ratio [HR] 2.53, p = 0.006). On univariate analysis, KPS and GPA were significantly prognostic for survival. None of the host, tumor, or treatment factors analyzed in the univariate model factors were significantly associated with local failure.

Objectives: To assess the effectiveness of a SHort-course Accelerated RadiatiON therapy (SHARON) in the treatment of patients with multiple brain metastases. Materials and Methods: A phase II clinical trial was designed. Eligibility criteria included patients with at least 3 brain metastases or metastatic disease in >3 organ systems, and Eastern Cooperative Oncology Group performance status of ≤3. Fifty patients were treated with whole brain radiotherapy at 18 Gy (4.5 Gy per fraction) in 2 days with a twice daily fractionation. The primary endpoint was the assessment of efficacy in terms of overall survival. Results: Characteristics of the 50 enrolled patients were: male/female: 24/26; median age: 65 years (range, 45 to 80 y). Eastern Cooperative Oncology Group performance status was

Intracranial metastases are the most common form of intra-axial brain tumor. Management approaches to brain metastases include surgical resection, whole-brain radiotherapy, and stereotactic radiosurgery (SRS). The management approach that is selected is based typically on algorithms that incorporate the number, size, and location of lesions. SRS is the treatment of choice when metastases detected on imaging are few (maximum, 3-5) and/or of small size (≤30 mm) and offers the advantages of noninvasiveness and the ability to treat inaccessible lesions compared with surgical resection. Contrast-enhanced magnetic resonance imaging (MRI) is the standard imaging technique for determining the number, size, and location of metastatic lesions. In SRS, the capability of MRI to delineate lesion borders precisely in 3 dimensions helps reduce recurrence rates and minimize radiation necrosis in surrounding tissue. Optimization of the MRI protocol, including selection of the appropriate gadolinium-based contrast agent (GBCA), is paramount for accurate lesion imaging. GBCAs differ in their safety, tolerability, and efficacy because of their diverse physicochemical properties. Gadobutrol and gadobenate dimeglumine are high-relaxivity GBCAs that demonstrate superior efficacy for imaging metastatic lesions compared with other GBCAs, whereas gadobutrol additionally provides macrocyclic stability. This article reviews recent comparative trials of GBCAs and discusses their relevance for optimizing MRI protocols in the management of brain metastases, with particular relevance to SRS. ABBREVIATIONS:: CNR, contrast-to-noise ratioCNS, central nervous systemGBCA, gadolinium-based contrast agentNSF, nephrogenic systemic fibrosisSRS, stereotactic radiosurgeryWBRT, whole-brain radiotherapy. © 2013 by the Congress of Neurological Surgeons.

AIM To evaluate brain metastases volume control capabilities of stereotactic radiosurgery (SRS) through serial magnetic resonance (MR) imaging follow-up. METHODS MR examinations of 54 brain metastases in 31 patients before and after SRS were reviewed. Patients were included in this study if they had a pre-treatment MR examination and serial follow-up MR examinations at 6 wk, 9 wk, 12 wk, and 12 mo after SRS. The metastasis volume change was categorized at each follow-up as increased (> 20% of the initial volume), stable (± 20% of the initial volume) or decreased (< 20% of the initial volume). RESULTS A local tumor control with a significant (P < 0.05) volume decrease was observed in 25 metastases at 6-wk follow-up. Not significant volume change was observed in 23 metastases and a significant volume increase was observed in 6 metastases. At 9-wk follow-up, 15 out of 25 metastases that decreased in size at 6 wk had a transient tumor volume increase, followed by tumor regression at 12 wk. At 12-wk follow-up there was a significant reduction in volume in 45 metastases, and a significant volume increase in 4 metastases. At 12-mo follow-up, 19 metastases increased significantly in size (up to 41% of the initial volume). Volume tumor reduction was correlated to histopathologic subtype. CONCLUSION SRS provided an effective local brain metastases volume control that was demonstrated at follow-up MR imaging.

Choroid plexus carcinoma which is a rare malign tumor of central nervous system. These tumors constitue 20-30% of the primary choroid plexus tumors and are more frequently situate in the lateral ventricle. Choroid plexus carcinoma is invasive and involves areas of necrosis and hemorrhage. Our case is a 4 year old girl who was admitted to university hospital presented with headache, stupor and lethargy. In cranial computerized tomography, a tumor was detected in right temporoparietal lob. Histopathologically the tumor cells were composed of branching papillary structures surrounding a fibrovascular core and infiltrate in brain parenchyma. Large areas of necrosis were detected within the tumor. High mitotic activity was also present. Tumor were not showed to react with mucicarmen, but diffuse reaction for S-100 and focal positive reaction for GFAP, pankeratin(Clone AE1/AE3) and CK7 were observed. Finally, the tumor was diagnosed as choroid plexus carcinoma. This case is presented here, because of its rarity and importance in differential diagnosis of papillary tumors of central nervous system.

Introduction: The primary tumour type most likely to metastasize to the brain is lung cancer. In heavily pre-treated patients, limited therapeutic option is available and the results of availability therapies reported in literature are disappointing. The present phase II study was designed to assess the efficacy and safety of temozolomide (TMZ) as palliative treatment for brain metastases (BrM) in NSCLC patients pre-treated with WBRT and at least one line of chemotherapy for metastatic brain disease. Material and methods: Temozolomide was administered orally at 150 mg/mq/day for five consecutive days for the first cycle, doses were increased to 200 mg/mq/day for 5 days every 28 days for subsequent cycles if no grade 3/4 haematological toxicity was observed. Eligibility criteria included cytological or histological confirmed NSCLC; BrM, recurrent or progressing after WBRT and at least one line of chemotherapy. A total of 30 consecutive patients entered the study and received the allocated treatment. Results: Three patients (10%) achieved an objective response (OR) of BrM with two complete remission. Stable disease and progressive disease were achieved in 3 (10%) and 24 patients (80%), respectively. A correlation between response to TMZ and sensitivity to the previous first line chemotherapy was reported. Time to progression and overall survival were examined both for responder patients and for all included patients. For long-term survivors, we considered the patients who survived >12 months after the start of TMZ. According to this definition, three patients resulted long-term survivors: 2 with OR and 1 with stable brain disease. No grades 3 or 4 toxicity occurred. The total of treatment-related adverse events were mild or moderate (G1-2) in intensity. No patients discontinued TMZ as a result of treatment-related toxicity. Discussion: The results of the present trial clearly demonstrates that TMZ is active and safe in BrM NSCLC patients previously treated with WBRT and at least one line of chemotherapy. © 2005 Elsevier Ireland Ltd. All rights reserved.

Central nervous system involvement by gynecological tumors is considered an uncommon event. Among 47 patients registered for tubal carcinoma in our institution between 1982 and 1994, 3 (6.4%) developed brain metastases. The median age at the time of the diagnosis of central nervous system metastases was 61 years. The median interval between diagnosis of tubal cancer and documentation of brain involvement was 37 months. All deposits were diagnosed as contrast-enhancing, space-occupying lesions on computed tomography scans. Two patients had cerebral metastases, 1 had cerebellar involvement. The central nervous system was the only site of recurrent disease in 1 patient 37 months after diagnosis of tubal carcinoma. The median survival from diagnosis of brain metastases was 1 month. Attention should be paid to the possibility of distant metastases associated with tubal carcinoma in order to treat these patients promptly.