Effects Of Whole Brain Radiotherapy Research Articles

Whole-brain radiation therapy plus simultaneous integrated boost for brain metastases from breast cancers.

The effect of whole-brain radiation therapy (WBRT) plus simultaneous integrated boost (SIB) in brain metastasis from breast cancers has not been demonstrated. In this single-center retrospective study, we reviewed consecutive breast cancer patients who developed brain metastasis and were treated with hypofractionated radiation therapy plus WBRT using intensity-modulated radiation therapy (IMRT)-SIB approaches. We analyzed clinical outcomes, prognostic factors and patterns of treatment failure. A total of 27 patients were eligible for analysis. Four (14.8%) patients achieved clinical complete response and 14 (51.9%) had partial response of brain lesions. The other nine patients were not evaluated for brain tumor response. The median brain progression-free survival was 8.60 (95% CI [6.43-13.33]) months and the median overall survival was 16.8 (95% CI [13.3-27.7]) months. Three patients had in-field failure, five had out-field failure and two had in-field and out-field failure. WBRT plus SIB led to improved tumor control and clinical outcome in breast cancer patients with brain metastasis.

Effect of whole-brain radiotherapy with platinum-based chemotherapy in non-small cell lung cancer patients with multiple metastases including brain metastases

Current guidelines recommend that cytotoxic chemotherapy be considered first in non-small cell lung cancer (NSCLC) patients with multiple metastases, and whole-brain radiotherapy (WBRT) is not initially recommended even if brain metastases are present. However, cytotoxic chemotherapeutic agents are less effective in brain metastases due to poor blood–brain barrier permeability. We investigated the effect of WBRT in combination with cytotoxic chemotherapy on survival in NSCLC patients who were EGFR, ALK, and PD-L1 negative, had an ECOG PS of 2, and had multiple metastases including brain metastases. From January 2005 to December 2018, histologically confirmed NSCLC patients who were EGFR, ALK, and PD-L1 negative, had an ECOG PS of 2, and had multiple metastases including brain metastases were included in this study. Patients were classified into two groups based on receiving WBRT prior to or concurrently with administration of first-line chemotherapeutic agents or receiving chemotherapy only. We compared intracranial progression-free survival (iPFS) and overall survival (OS). Of the 240 NSCLC patients with brain metastases at diagnosis and an ECOG PS of 2, 67 patients were EGFR, ALK, and PD-L1 negative with multiple metastases including brain metastases. Among those patients, 43 (64.2%) received WBRT prior to or concurrently with platinum-based chemotherapy. Patients who received WBRT prior to or concurrently with chemotherapy had better iPFS (7.7 months [4.8–10.6] vs. 3.5 months [2.1–4.9], p = 0.009) and OS (10.8 months [5.9–15.7] vs. 6.1 months [1.9–10.3], p = 0.038) than those who did not receive WBRT. In multivariate analyses, WBRT was significantly associated with iPFS (HR: 1.94 and 95% CI 1.11–3.40, p = 0.020) and OS (HR: 1.92 and 95% CI 1.08–3.42, p = 0.027). In NSCLC patients who are EGFR, ALK, and PD-L1 negative, have an ECOG PS of 2, and have multiple metastases including brain metastases, WBRT prior to or concurrently with chemotherapy could improve iPFS and OS. Therefore, the combination of WBRT with cytotoxic chemotherapy should be considered in these patients.

Effects of whole-brain radiation therapy on the blood–brain barrier in immunocompetent and immunocompromised mouse models

BackgroundApproximately 20% of all cancer patients will develop brain metastases in their lifespan. The standard of care for patients with multiple brain metastases is whole-brain radiation therapy, which disrupts the blood–brain barrier. Previous studies have shown inflammatory mediators play a role in the radiation-mediated increase in permeability. Our goal was to determine if differential permeability post-radiation occurs between immunocompetent and immunocompromised mice.MethodsWe utilized a commissioned preclinical irradiator to irradiate brains of C57Bl/6J wild-type and athymic nude mice. Acute (3–24 h) effects on blood–brain barrier integrity were evaluated with our in-situ brain perfusion technique and quantitative fluorescent and phosphorescent microscopy. The presence of inflammatory mediators in the brain and serum was determined with a proinflammatory cytokine panel.ResultsBlood–brain barrier integrity and efflux transporter activity were altered in the immunocompetent mice 12 h following irradiation without similar observations in the immunocompromised mice. We observed increased TNF-α concentrations in the serum of wild-type mice immediately post-radiation and nude mice 12 h post-radiation. The brain concentration of CXCL1 was also increased in both mouse strains at the 12-h time point.ConclusionsThe immune response plays a role in the magnitude of blood–brain barrier disruption following irradiation in a time- and size-dependent manner.

Whole brain radiotherapy and association with rapid brain aging as determined by anatomic surface morphology.

e14007 Background: Brain metastases are the most common intracranial tumors in adults and are associated with significant morbidity and mortality. Whole brain radiotherapy (WBRT) is used frequently in patients for palliation, but can result in neurocognitive deficits. While dose-dependent injury to individual areas such as the hippocampus have been demonstrated, global structural changes after WBRT remain to be studied. Our group previously published a magnetic resonance imaging (MRI) deep learning model based on anatomic brain surface morphology to accurately predict brain age in healthy subjects. We now report the effect of WBRT on aging pace of the irradiated brain. Methods: We studied patients with brain metastases and examined MRI brain anatomic surface data before and after WBRT. We implemented a graph convolutional neural network model to estimate patient’s brain age. We further developed a mixed-effects linear model to compare age of whole brain and substructures before and after WBRT, written as follows: ΔAge = c + β(ΔScan) + 1|patient_ID; where for each patient, ΔAge = [(model_predicted_age_at_follow up – actual_age_at_follow up) – (model_predicted_age_pre_treatment – actual_age_pre_treatment)], ΔScan = time interval between pre-and post-treatment MRI scans, β = aging coefficient (β =0 corresponds to normal aging), and c = intercept (model_predicted_age_pre_treatment – actual_age_pre_treatment). Results: 56 patients were analyzed. The median age was 62 (range 32 – 85). Two-thirds of patients were female. Primary organ site was breast or lung in 87% of cases and 77% of patients had five or more metastases. Median radiation dose was 30Gy (range 25 – 37.5Gy). Results of aging analysis are presented in Table. Small c values demonstrate that model accurately predicted age pre-treatment. The whole brain and substructures underwent rapid aging compared to normal aging pace (β>>0). Based on median follow up of 6.3 months, the whole brain aged approximately 4.94 years, the cortex aged approximately 4.53 years, the subcortical structures aged approximately 5.94 years, and the hippocampus aged approximately 5.17 years. Conclusions: Our findings suggest that WBRT causes the brain and its substructures to age at a pace of 9-11x of the normal aging pace, mirroring deficits in long-term neurocognition seen post-treatment. Given post-treatment aging pace and increasing survival for many patients with brain metastases, WBRT needs to be used judiciously. [Table: see text]

OTME-6. Deep sequencing reveals heterogeneity of brain metastasis-associated macrophages and microglia and uncovers their cell type-specific functions within the tumor microenvironment

Macrophages represent a highly plastic cell type,indispensable for tissue and organ homeostasis, as well as innate immunity. Basic and translational research attributed tumor-promoting functions to macrophages, and their presence is often associated to poor patient prognosis and therapy resistance. While brain-resident macrophages, the so-called microglia (MG), represent the major immune cell type in the parenchyma under normal conditions, primary and metastatic brain tumors induce the recruitment of different immune cell types from the periphery, including monocyte-derived macrophages (MDM). Controversy remained about the redundancy of disease-associated molecular signatures and functions. The identification of markers that reliably distinguish brain-resident from blood-borne tumor-associated macrophages (TAMs) allowed the interrogation of molecular traits of different TAM populations in mouse and human brain tumors.Using RNA-Seq, we demonstrated that TAMs rapidly acquire disease-associated transcriptional programs upon initial tumor infiltration, while gene expression remained stable during different stages of BrM progression. Across different BrM models, disease-associated transcriptional changes revealed lineage-specific, non-redundant functions of TAM populations, which was further reflected by cell type-specific occupation of different niches within the BrM microenvironment. Furthermore, we observed dose- and cell type-specific immune modulatory effects of whole brain radiotherapy on myeloid cells in BrM leading to a transient loss of disease-associated transcriptional programs predominately in blood-borne myeloid populations. This effect can at least in part be attributed to a replenishment of the recruited macrophage pool. This observation was further supported by scRNA-Seq analyses revealing higher heterogeneity of TAM-MDM compared to TAM-MG under treatment-naïve conditions and in response to radiotherapy.Together, our results point towards the phenotypic plasticity of TAMs, especially MDMs, and the contribution of each compartment in instigating cancer-associated inflammation or the establishment of an immuno-suppressive TME. While TAM-MG exert functions related to pro-inflammatory responses, TAM-MDM are rather involved in tissue repair and regulation of adaptive immune cell functions.

Neurocognitive functioning and radiologic changes in primary CNS lymphoma patients: results from the HOVON 105/ALLG NHL 24 randomized controlled trial.

To analyze the effect of treatment on neurocognitive functioning and the association of neurocognition with radiological abnormalities in primary central nervous system lymphoma (PCNSL). One hundred and ninety-nine patients from a phase III trial (HOVON 105/ALLG NHL 24), randomized to standard chemotherapy with or without rituximab, followed in patients ≤60 years old by 30-Gy whole-brain radiotherapy (WBRT), were asked to participate in a neuropsychological evaluation before and during treatment, and up to 2 years posttreatment. Scores were transformed into a standardized z-score; clinically relevant changes were defined as a change in z-score of ≥1 SD. The effect of WBRT was analyzed in irradiated patients. All MRIs were centrally assessed for white matter abnormalities and cerebral atrophy, and their relation with neurocognitive scores over time in each domain was calculated. 125/199 patients consented to neurocognitive evaluation. Statistically significant improvements in neurocognition were seen in all domains. A clinically relevant improvement was seen only in the motor speed domain, without differences between the arms. In the follow-up of irradiated patients (n = 43), no change was observed in any domain score, compared to after WBRT. Small but significant inverse correlations were found between neurocognitive scores over time and changes in white matter abnormalities (regression coefficients: -0.048 to -0.347) and cerebral atrophy (-0.212 to -1.774). Addition of rituximab to standard treatment in PCNSL patients did not impact neurocognitive functioning up to 2 years posttreatment, nor did treatment with 30-Gy WBRT in patients ≤60 years old. Increased white matter abnormalities and brain atrophy showed weak associations with neurocognition.

Observed Effects of Whole-Brain Radiation Therapy on Focused Ultrasound Blood–Brain Barrier Disruption

As focused ultrasound for blood–brain barrier disruption (FUS-BBBD) has progressed to human application, it has become necessary to consider the potential effects of prior irradiation treatments. Using a murine model, we examined the effects of whole-brain irradiation on FUS-BBBD. We first subjected half of the experimental cohort to daily 3-Gy whole-brain irradiation for 10 consecutive days. Then, microbubble-assisted FUS-BBBD was performed unilaterally while the contralateral sides served as unsonicated controls. FUS-BBBD, as evident by measuring the fluorescence yield of extravasated trypan blue dye, was identified at all sites with minimal or no apparent pathology. The peak fluorescence intensity caused by extravasated dye in the sonicated region was 17.5 ± 12.1% higher after radiation and FUS-BBBD than after FUS-BBBD alone, suggesting that prior radiation of the brain may be a sensitizing factor for FUS-BBBD. Radiation alone—without FUS-BBBD—resulted in mild BBB disruption. Hemorrhagic petechiae were observed in 9 of 12 radiated brains, with 77% of them clearly located outside the sonicated area; no petechiae were found in non-irradiated animals. This radiation protocol did not appear to increase the risk for vascular damage associated with FUS-BBBD.

Health-related quality of life after chemotherapy with or without rituximab in primary central nervous system lymphoma patients: results from a randomised phase III study

The impact of rituximab on health-related quality of life (HRQoL) in primary central nervous system lymphoma patients is not well known. We determined the impact of rituximab added to standard high-dose methotrexate-based treatment on HRQoL in patients in a large randomised trial. Patients from a large phase III trial (HOVON 105/ALLG NHL 24), randomly assigned to receive standard chemotherapy with or without rituximab and followed by 30 Gy whole brain radiotherapy (WBRT) in patients ≤60 years, completed the EORTC QLQ-C30 and QLQ-BN20 questionnaires before and during treatment, and up to 24months of follow-up or progression. Differences between treatment arms over time in global health status, role functioning, social functioning, fatigue, and motor dysfunction were assessed. Differences ≥10 points were deemed clinically relevant. The effect of WBRT on HRQoL was analysed in irradiated patients. A total of 160/175 patients eligible for the HRQoL study completed at least one questionnaire and were included. Over time, scores improved statistically significantly and were clinically relevant in both arms. Between arms, there were no differences on any scale (range:-3.8 to+4.0). Scores on all scales were improved to a clinically relevant extent at 12 and 24 months compared with baseline in both arms, except for fatigue and motor dysfunction at 12 months (-7.4 and-8.8, respectively). In irradiated patients (n= 59), scores in all preselected scales, except motor dysfunction, remained stable up to 24 months compared with shortly after WBRT, overall mean difference ranging between 0.02 and 4.570. Compared with baseline, treatment resulted in improved HRQoL scores. The addition of rituximab to standard chemotherapy did not impact HRQoL over time. WBRT did not result in deterioration of HRQoL in the first 2 years.

Therapeutic effect of whole brain radiotherapy on advanced NSCLC between EGFR TKI-na\xefve and TKI-resistant

BackgroundThe development of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has dramatically improved the prognosis of patients with EGFR-mutant non-small-cell lung cancer (NSCLC). The purpose of this study is to investigate the clinical outcome with or without EGFR-TKI resistance before WBRT and the sequence between EGFT-TKIs and whole brain radiotherapy (WBRT) of EGFR-mutant NSCLC patients who developed multiple brain metastases (BMs).Patients and methodsThree hundred forty-four EGFR-mutant NSCLC patients with multiple BMs were reviewed. Enrolled patients were divided into TKI-naïve group and TKI-resistant group. The intracranial progression-free survival (PFS) and overall survival (OS) were analyzed via the Kaplan-Meier method.ResultsFor patients with multiple BMs treated by WBRT, the median intracranial PFS and OS were longer in the TKI-naïve group than those in the TKI-resistant group, but there were no statistically significant between two groups (Intracranial PFS: 7.7 vs. 5.4 months, p = 0.052; OS: 11.2 vs. 9.2 months, p = 0.106). For patients with Lung-molGPA 0–2, no significant differences in median intracranial PFS (6.2 vs. 5.2 months, p = 0.123) and OS (7.8 vs. 6.7 months, p = 0.514) between TKI-naïve and TKI-resistant groups. For patients with Lung-molGPA 2.5–4, intracranial PFS: 12.8 vs. 10.1 months; OS: 23.3 vs. 15.3 months.ConclusionsOur study found that there were no difference in intracranial PFS and OS in all patients between the two groups of TKI-naïve and TKI-resistant. But for patients in subgroup of Lung-molGPA 2.5–4, there were a better intracranial PFS and OS in TKI-naïve group.

Effect of Whole-Brain Radiotherapy in Alleviating Symptoms and Improving Quality of life in Patients with Brain Metastases – A Prospective Study

Effect of Whole-Brain Radiotherapy in Alleviating Symptoms and Improving Quality of life in Patients with Brain Metastases – A Prospective Study

NCOG-05. IMPACT OF ADDITIONAL RITUXIMAB TO STANDARD THERAPY ON COGNITIVE PERFORMANCES IN PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA PATIENTS

Abstract BACKGROUND The goal of treatment of primary central nervous system lymphoma patients is to improve survival, without compromising neurocognitive functioning. The aim of this study was to analyze the effect of Rituximab and low-dose whole brain radiotherapy (WBRT) on cognition. METHODS 199 patients from a phase III trial (HOVON 105/ ALLG NHL 24), randomized to standard chemotherapy (and 30Gy WBRT for patients < 61 years-old only) with or without Rituximab, were asked to participate in a short neuropsychological evaluation (NPE) before and during treatment, and up to 2 years of follow-up or until progression. A difference in z-score, corrected for sex, age and education, of ≥ 1 point was considered as clinically relevant. The primary outcome was a difference over time between the arms in multiple cognitive domains, assessed by linear mixed models (LMM). Changes in cognitive performances between baseline and 24 months after treatment were assessed for both arms in cross-sectional analyses. Effect of WBRT was analyzed in irradiated patients only. RESULTS 105/199 patients completed at least one NPE; baseline characteristics were similar to the total trial population. Compliance was >60% at all evaluation points. No clinically relevant differences over time between the arms were seen in all domains in LMM analysis. Comparing changes from baseline to 24 months of follow-up, mean cognitive scores remained stable in both arms for attention, executive functioning (TMT B), and information processing speed. A clinically relevant improvement was seen in both arms for executive functioning (TMT A), memory and motor speed. In the irradiated patients (n=33) all scores remained stable after WBRT, up to 24 months of follow-up in all domains. CONCLUSION Cognitive performance remained stable or improved after treatment. Addition of Rituximab to standard treatment did not impact cognitive performance over time. After low-dose WBRT, cognition remained stable up to 2 years.

OS7.1 Impact of the addition of Rituximab to standard therapy with high dose methotrexate on health-related quality of life in primary central nervous system lymphoma patients

Abstract BACKGROUND Data on the impact of treatment with Rituximab on health-related quality of life (HRQoL) in primary central nervous system lymphoma (PCNSL) patients are scarce. To determine the net clinical benefit of a new treatment, analyzing the effect on HRQoL is warranted. MATERIAL AND METHODS Patients from a phase III trial (HOVON 105/ ALLG NHL 24), randomized to standard chemotherapy with or without Rituximab, were asked to fill in the EORTC QLQ-C30 and QLQ-BN20 questionnaires before and during treatment, and up to 2 years follow-up or progression. Five predetermined scales were selected for primary analyses: global health status (GH), role (RF) and social functioning (SF), fatigue (FA), and motor dysfunction (MD). A difference ≥10 points was defined as clinically relevant. Cross-sectional analyses were performed comparing changes in HRQoL scores from baseline between the two arms at 12 and 24 months after treatment. Effect of whole brain radiotherapy (WBRT) was analyzed in irradiated patients only. Differences in HRQoL over time between the treatment arms, i.e. the primary outcome, were assessed using linear mixed models (LMM). RESULTS 175/199 patients completed at least one HRQoL questionnaire, and compliance was >60% at all evaluation points. Median age was 61 (IQR 55–66), 74% had a WHO performance score <2, and 38% received WBRT, similar to the total trial population. HRQoL scores on all five scales were significantly and to a clinically relevant extent improved at 12 and 24 months follow-up when compared to baseline in both arms (range: 11.6–42.4), except for FA and MD at 12 months (both -7.2). Differences in HRQoL changes from baseline to 12 and 24 months between the two arms were not statistically significant (range: 3.6–10.9). In the irradiated patients (n=52), HRQoL scores remained stable up to 24 months compared to shortly after WBRT for GH, SF, FA and MD (range -8.1 - 7.6). A clinically relevant and statically significant improvement was seen in RF for both arms at 12 and 24 months compared to ‘after WBRT’(range: +16.7 - +22.2). After correction for multiple testing, LMM analyses showed no statistically significant and clinically relevant differences between the arms for any of the scales over time (range: -3.8 to +4.0). CONCLUSION Treatment resulted in improved HRQoL, but the addition of Rituximab to standard chemotherapy did not further impact HRQoL over time. WBRT did not result in deterioration of HRQoL up to 2 years of follow-up.

MRI evaluation of the effects of whole brain radiotherapy on breast cancer brain metastasis

Purpose: To assess early changes in brain metastasis in response to whole brain radiotherapy (WBRT) by longitudinal Magnetic Resonance Imaging (MRI).Materials and methods: Using a 7T system, MRI examinations of brain metastases in a breast cancer MDA-MD231-Br mouse model were conducted before and 24 hours after 3 daily fractionations of 4 Gy WBRT. Besides anatomic MRI, diffusion-weighted (DW) MRI and dynamic contrast-enhanced (DCE) MRI were applied to study cytotoxic effect and blood-tumor-barrier (BTB) permeability change, respectively.Results: Before treatment, high-resolution T2-weighted images revealed hyperintense multifocal lesions, many of which (∼50%) were not enhanced on T1-weighted contrast images, indicating intact BTB in the brain metastases. While no difference in the number of new lesions was observed, WBRT-treated tumors were significantly smaller than sham controls (p < .05). DW MRI detected significant increase in apparent diffusion coefficient (ADC) in WBRT tumors (p < .05), which correlated with elevated caspase 3 staining of apoptotic cells. Many lesions remained non-enhanced post WBRT. However, quantitative DCE MRI analysis showed significantly higher permeability parameter, Ktrans, in WBRT than the sham group (p < .05), despite marked spatial heterogeneity.Conclusions: MRI allowed non-invasive assessments of WBRT induced changes in BTB permeability, which may provide useful information for potential combination treatment.

Effects of Whole-brain Radiotherapy Combined with Targeted Therapy on Improving Survival of HER2-positive Breast Cancer Patients with Brain Metastases

Effects of Whole-brain Radiotherapy Combined with Targeted Therapy on Improving Survival of HER2-positive Breast Cancer Patients with Brain Metastases

Survival Effect Difference of Whole-Brain Radiation Therapy and TKIs in Patients with Brain Metastases from Non-Small Cell Lung Cancer Stratified by EGFR Mutation Status

To compare overall (OS) and intracranial progression-free survival (iPFS) effects of whole-brain radiotherapy (WBRT) and tyrosine kinase inhibitors (TKIs) in NSCLC patients with brain metastases (BM) stratified by EGFR mutation status (positive+, negative-, unknown). We performed a retrospective analysis of 595 NSCLC BM patients diagnosed in 2013-2015 and followed-up to December 1 2016. The stratified K-M curves and multivariate Cox models were used to evaluate effects of WBRT (defined as ≥30Gy, ' W ') and TKIs application (after BM, ' T ') on OS and iPFS independently and jointly. Covariates includes sex, age, KPS,CVD,NSCLC history length, resection of primary tumor, number of BM lesions, brain/brainstem/meningeal involvement status, BM resection, BM chemotherapy after screening. two-sided p>0.05 as ns. BM age mean (range) was 59 (22 - 87) and female 44%. Overall MTS of OS and iPFS were 9.3 and 8.9 months respectively. EGFR+ (114 pts, 53% of mutation tests), W+31% and T+76%. Multivariate HR(p) of W+ and T+ were OS - 0.768 (ns), 0.180 (0.00), iPFS - 1.057(ns) and 0.255 (0.00). Compared with W-T- (14 pts), multivariate HR(p) of W+T+(22 pts),W-T+(65) and W+T- (13) were OS - 0.196 (0.00), 0.114 (0.00), 0.434 (ns) and iPFS - 0.272 (0.01), 0.200 (0.00), 0.622 (ns). W+T+ vs. W-T+ had OS 1.717(ns) and iPFS 1.361 (ns). EGFR- (101 pts), W+43%. Multivariate HR(p) of W+ vs. W- were OS - 0.539 (0.11), iPFS - 0.485(0.05). EGFR unknown (380 pts), W+38%, T+17%. Compared with W-T- (202 pts), multivariate HR(p) of W+T+(30 pts),W-T+(35) and W+T- (113) were OS-0.304 (0.00), 0.370 (0.00), 0.465 (ns) and iPFS - 0.365(0.00), 0.556 (0.01), 0.562 (ns). W+T+ vs. W-T+ had OS 0.821(ns) and iPFS 0.657 (ns). Compared with EGFR-, TKIs use in EGFR+ or EGFR-unknown patients reduces the survival effect of WBRT on OS and iPFS in patients with NSCLC brain metastases. Whether to delay WBRT in TKIs users for EGFR+ BM patients for better survival or QOL benefit deserves RCTs.

Stereotactic radiosurgery (SRS) alone versus whole brain radiotherapy plus SRS in patients with 1 to 4 brain metastases from non-small cell lung cancer stratified by the graded prognostic assessment: A meta-analysis (PRISMA) of randomized control trials.

Background:The present study aims to assess the therapeutic effect of whole brain radiotherapy (WBRT) for brain metastases from non-small cell lung cancer stratified by graded prognostic assessment (GPA) through meta-analysis.Methods:The Cochrane Library, PubMed, Ovid (Elsevier) were retrieved. The included randomized controlled trials (RCT) were evaluated, and the statistical analysis was performed using RevMan 5.3 software. Cochrane handbook was applied to evaluate the methodological quality. Statistical significance was considered as P < .05.Results:There were 2 randomized control trials identified eligible for the meta-analysis. Stereotactic radiosurgery (SRS)+WBRT did not significantly improved overall survival (OS) in 2 subgroups. (GPA <2: HR, 0.93; 95% confidence interval [CI], 0.61–1.40; P = .71), (GPA ≥2: HR, 1.28; 95% CI, 0.58–2.80; P = .54). The use of SRS+WBRT significantly extended brain tumor recurrence (BTR) free time in both subgroups (GPA <2: HR, 5.46; 95% CI: 2.09–14.22; P = .0005), (GPA ≥2: HR, 4.24; 95% CI: 2.24–8.04; P < .00001). The meta-analysis showed salvage therapy was more frequent among the SRS-alone in 2 subgroups (GPA <2: RR, 5.83; 95% CI: 1.47–23.06; P = .01), (GPA ≥2: RR, 2.53; 95% CI: 1.30–4.93; P = .006). The rate of grade 3 or 4 late radiation toxic effects was similar in 2 subgroups between SRS and SRS+WBRTConclusions:Because there are few studies to meet inclusion criteria, we cannot include more researches. The results of this analysis must be carefully interpreted in view of the unclear risk of bias in inclusion in the study. This meta-analysis of 2 randomized trails indicated that the combined treatment group did not show a survival benefit over SRS alone. However, SRS+WBRT improved BTR free time in the subgroup both GPA <2 and GPA ≥2 with the similar grade 3 or 4 late radiation toxicities.

Good control of diffuse brain metastasis with lapatinib plus capecitabine in a patient with HER2-positive breast cancer

S&#x0D; We present the case of a patient affected by HER2-positive breast carcinoma, relapsed at supraclavicular and mediastinal lymph nodes level, after three and eight years from initial diagnosis. These relapses were successfully treated by local radiotherapy, hormone therapy and trastuzumab. After 10 years from onset, the patient developed cerebral progression with a number of seizable lesions, overt clinical symptoms. To avoid the short- and long-term side effects of whole brain radiotherapy, the patient is initially treated with lapatinib and capecitabine in light of the favorable data on the efficacy of this combination on brain metastases from HER2-positive breast carcinoma. This therapy results in a considerable lesions reduction, allowing to postpone the panencephalic radiotherapy to a later time with a lower tumor burden. The response to radiotherapy is significant and sustanined for a progression-free interval of about 10 months. This case suggests that lapatinib may represent the treatment of choice in cases of indolent disease, characterized by long progression free intervals with minor symptoms with the aim to postpone the use of more invasive treatments (Oncology).

Effect of Whole Brain Radiotherapy Dose on Breast Cancer Brain Metastases Survival

This paper sets to study the effect of whole brain radiotherapy (WBRT) dose on the survival after breast cancer brain metastases (BM) in order to reduce the mortality rates of breast cancer. We collect relevant information on the patient, operation, and post-operation systematic treatment, diagnosis and treatment of BM from the medical record inquiry system. The results show that under implications of multiple factors, local supplement dose, to some extent, has good prognosis tendency, but does not extend the intracranial progression free survival (PFS), while the WBRT dose can. It is the conclusion of this paper that WBRT can improve the overall survival (OS) and PFS, but WBRT cannot further extend the OS after exceeding a certain amount.

Whole brain radiotherapy for the treatment of newly diagnosed multiple brain metastases.

This is an update to the review published in the Cochrane Library (2012, Issue 4).It is estimated that 20% to 40% of people with cancer will develop brain metastases during the course of their illness. The burden of brain metastases impacts quality and length of survival. To assess the effectiveness and adverse effects of whole brain radiotherapy (WBRT) given alone or in combination with other therapies to adults with newly diagnosed multiple brain metastases. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase to May 2017 and the National Cancer Institute Physicians Data Query for ongoing trials. We included phase III randomised controlled trials (RCTs) comparing WBRT versus other treatments for adults with newly diagnosed multiple brain metastases. Two review authors independently assessed trial quality and abstracted information in accordance with Cochrane methods. We added 10 RCTs to this updated review. The review now includes 54 published trials (45 fully published reports, four abstracts, and five subsets of data from previously published RCTs) involving 11,898 participants.Lower biological WBRT doses versus controlThe hazard ratio (HR) for overall survival (OS) with lower biological WBRT doses as compared with control (3000 cGy in 10 daily fractions) was 1.21 (95% confidence interval (CI) 1.04 to 1.40; P = 0.01; moderate-certainty evidence) in favour of control. The HR for neurological function improvement (NFI) was 1.74 (95% CI 1.06 to 2.84; P = 0.03; moderate-certainty evidence) in favour of control fractionation.Higher biological WBRT doses versus controlThe HR for OS with higher biological WBRT doses as compared with control (3000 cGy in 10 daily fractions) was 0.97 (95% CI 0.83 to 1.12; P = 0.65; moderate-certainty evidence). The HR for NFI was 1.14 (95% CI 0.92 to 1.42; P = 0.23; moderate-certainty evidence).WBRT and radiosensitisersThe addition of radiosensitisers to WBRT did not confer additional benefit for OS (HR 1.05, 95% CI 0.99 to 1.12; P = 0.12; moderate-certainty evidence) or for brain tumour response rates (odds ratio (OR) 0.84, 95% CI 0.63 to 1.11; P = 0.22; high-certainty evidence).Radiosurgery and WBRT versus WBRT aloneThe HR for OS with use of WBRT and radiosurgery boost as compared with WBRT alone for selected participants was 0.61 (95% CI 0.27 to 1.39; P = 0.24; moderate-certainty evidence). For overall brain control at one year, the HR was 0.39 (95% CI 0.25 to 0.60; P < 0.0001; high-certainty evidence) favouring the WBRT and radiosurgery boost group.Radiosurgery alone versus radiosurgery and WBRTThe HR for local brain control was 2.73 (95% CI 1.87 to 3.99; P < 0.00001; high-certainty evidence)favouring the addition of WBRT to radiosurgery. The HR for distant brain control was 2.34 (95% CI 1.73 to 3.18; P < 0.00001; high-certainty evidence) favouring WBRT and radiosurgery. The HR for OS was 1.00 (95% CI 0.80 to 1.25; P = 0.99; moderate-certainty evidence). Two trials reported worse neurocognitive outcomes and one trial reported worse quality of life outcomes when WBRT was added to radiosurgery.We could not pool data from trials related to chemotherapy, optimal supportive care (OSC), molecular targeted agents, neurocognitive protective agents, and hippocampal sparing WBRT. However, one trial reported no differences in quality-adjusted life-years for selected participants with brain metastases from non-small-cell lung cancer randomised to OSC and WBRT versus OSC alone. None of the trials with altered higher biological WBRT dose-fractionation schemes reported benefit for OS, NFI, or symptom control compared with standard care. However, OS and NFI were worse for lower biological WBRT dose-fractionation schemes than for standard dose schedules.The addition of WBRT to radiosurgery improved local and distant brain control in selected people with brain metastases, but data show worse neurocognitive outcomes and no differences in OS.Selected people with multiple brain metastases from non-small-cell lung cancer may show no difference in OS when OSC is given and WBRT is omitted.Use of radiosensitisers, chemotherapy, or molecular targeted agents in conjunction with WBRT remains experimental.Further trials are needed to evaluate the use of neurocognitive protective agents and hippocampal sparing with WBRT. As well, future trials should examine homogeneous participants with brain metastases with focus on prognostic features and molecular markers.

Bevacizumab and gefitinib enhanced whole-brain radiation therapy for brain metastases due to non-small-cell lung cancer.

Non-small-cell lung cancer (NSCLC) patients who experience brain metastases are usually associated with poor prognostic outcomes. This retrospective study proposed to assess whether bevacizumab or gefitinib can be used to improve the effectiveness of whole brain radiotherapy (WBRT) in managing patients with brain metastases. A total of 218 NSCLC patients with multiple brain metastases were retrospectively included in this study and were randomly allocated to bevacizumab-gefitinib-WBRT group (n=76), gefitinib-WBRT group (n=77) and WBRT group (n=75). Then, tumor responses were evaluated every 2 months based on Response Evaluation Criteria in Solid Tumors version 1.0. Karnofsky performance status and neurologic examination were documented every 6 months after the treatment. Compared to the standard WBRT, bevacizumab and gefitinib could significantly enhance response rate (RR) and disease control rate (DCR) of WBRT (P<0.001). At the same time, RR and DCR of patients who received bevacizumab-gefitinib-WBRT were higher than those who received gefitinib-WBRT. The overall survival (OS) rates and progression-free survival (PFS) rates also differed significantly among the bevacizumab-gefitinib-WBRT (48.6 and 29.8%), gefitinib-WBRT (36.7 and 29.6%) and WBRT (9.8 and 14.6%) groups (P<0.05). Although bevacizumab-gefitinib-WBRT was slightly more toxic than gefitinib-WBRT, the toxicity was tolerable. As suggested by prolonged PFS and OS status, bevacizumab substantially improved the overall efficacy of WBRT in the management of patients with NSCLC.