Dosimetric impact of adding non-coplanar arcs for scalp-avoidance whole-brain irradiation with volumetric-modulated arc radiotherapy on scalp dose reduction in pediatric patients with medulloblastomas.

PURPOSE: We performed scalp-avoidance whole-brain irradiation with volumetric-modulated arc therapy (SAWB-VMAT) as a component of craniospinal irradiation. In SAWB-VMAT with two coplanar arcs, radiation oncologists and medical physicists sometimes experience difficulty in reducing the dose to the scalp to below the cut-off equivalent dose in 2 Gy per fraction (assuming α/ß = 2) to 50% (EQD50%scalp ). To investigate the advantage of adding coplanar or non-coplanar arcs in reducing the dose to the scalp in SAWB-VMAT, we conducted a planning study to compare the EQD50%scalp , the dose to other organs at risk (OARs), and target coverage in VMAT with two coplanar arcs (Co2arcVMAT), VMAT with three coplanar arcs (Co3arcVMAT), and VMAT with two coplanar and two non-coplanar arcs (NcVMAT). METHODS: Co2arcVMAT, Co3arcVMAT, and NcVMAT plans were created for 10 pediatric patients with medulloblastoma. The planned target volume (PTV) included the regions of the whole brain, cervical spinal cord, cerebrospinal fluid space, and intervertebral foramen. The EQD50%scalp was evaluated separately for four areas (top, back, left, and right) in each case. The prescribed dose for the PTV was 35.2 Gy in 22 fractions. RESULTS: The median EQD50%scalp of the top area was 21.9 , 22.1 , and 18.3 Gy for Co2arcVMAT, Co3arcVMAT, and NcVMAT, respectively. The EQD50%scalp of the top area was significantly reduced in NcVMAT compared to those in Co2arcVMAT and Co3arcVMAT (p < 0.05). The median EQD50%scalp of the top area for NcVMAT was < 19.9 Gy, which is the cut-off dose for severe permanent alopecia. There were no significant differences in EQD50%scalp in the three other areas, the dose to other OARs, or the dose coverage of PTV among the three techniques. CONCLUSION: NcVMAT could reduce the EQD50%scalp of the top area below the cut-off dose of 19.9 Gy. NcVMAT appears to be a promising treatment technique for SAWB-VMAT.

Novel Strategy Involving High-Dose Chemotherapy with Stem Cell Rescue Followed by Intrathecal Topotecan Maintenance Therapy without Whole-Brain Irradiation for Atypical Teratoid/Rhabdoid Tumors.

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare aggressive central nervous system tumor that typically affects children under three years old and has poor survival with a high risk for neurologic deficits. The primary purpose of this study was to successfully treat the disease and delay or avoid whole-brain radiotherapy for children with AT/RT. A retrospective analysis was performed for six children diagnosed with AT/RT and treated with multimodal treatment at a single institute between 2014 and 2020. Furthermore, germline SMARCB1 aberrations and MGMT methylation status of the tumors were analyzed. One patient who did not receive a modified IRS-III regimen replaced with ifosphamide, carboplatin, and etoposide (ICE) in induction chemotherapy was excluded from this analysis. Five patients who received ICE therapy were under three years old. After a surgical approach, they received intensive chemotherapy and high-dose chemotherapy with autologous peripheral blood stem cell transplantation (HDCT/autoPBSCT) followed by intrathecal topotecan maintenance therapy. Three patients underwent single HDCT/autoPBSCT, and the other two received sequential treatment. Two patients with germline SMARCB1 aberrations and metastases died of progressive AT/RT or therapy-related malignancy, while 3 with localized tumors without germline SMARCB1 aberrations remained alive. One survivor received local radiotherapy only, while the other two did not undergo radiotherapy. All three surviving patients were able to avoid whole-brain radiotherapy. Our results suggest that AT/RT patients with localized tumors without germline SMARCB1 aberrations can be rescued with multimodal therapy, including induction therapy containing ICE followed by HDCT/autoPBSCT and intrathecal topotecan maintenance therapy without radiotherapy. Further large-scale studies are necessary to confirm this hypothesis.

Screening of small molecular biomarker candidates using untargeted metabolomics strategy in peripheral blood from rats with neuroinflammatory injury induced by whole-brain irradiation.

Neuroinflammatory injury is one of the typical brain injuries after the body is exposed to radiation. It is mainly characterized by the release of inflammatory factors by activated microglia and peripherally invading lymphocytes. To provide early warning for nerve injury and early diagnosis of neurodegenerative diseases, it is of great significance to explore the biomarker candidates of neuroinflammatory injury. This study focused on the screening of small molecular biomarker candidates in peripheral blood from rats with neuroinflammatory injury induced by whole-brain irradiation. The rats were exposed to 0, 10, 10 × 3, and 30 Gy of cobalt-60 γ-rays. Serum was collected on the 30th day after exposure and analyzed using reversed-phase liquid chromatography and hydrophilic interaction liquid chromatography coupled with high-resolution mass spectrometry based on untargeted metabolomics. Biomarker candidates were investigated by comparing the 0-Gy group and three irradiation groups using univariate statistical analysis, principal component analysis, and orthogonal partial least squares discriminant analysis. Eleven biomarker candidates were putatively identified, and four major altered metabolic pathways were found. The screened small molecular biomarker candidates could be used as a useful supplement to traditional biomacromolecule markers and may be valuable for radiation protection, target therapy of inflammatory injury, and discovery of new target drugs for the prevention and cure of related neurodegenerative diseases.

A matched-pair study comparing whole-brain irradiation alone to radiosurgery or fractionated stereotactic radiotherapy alone in patients irradiated for up to three brain metastases.

BACKGROUND: This matched-pair study was initiated to validate the results of a retrospective study of 186 patients published in 2007 that compared whole-brain irradiation (WBI) alone and radiosurgery (RS) alone for up to three brain metastases. METHODS: One-hundred-fifty-two patients receiving WBI alone for up to three brain metastases were matched with 152 patients treated with RS of fractionated stereotactic radiotherapy (FSRT) alone 1:1 for each of eight factors (age, gender, Eastern Oncology Cooperative Group (ECOG)-performance score, nature of tumor, brain metastases number, extra-cerebral spread, period from cancer detection to irradiation of brain metastases, and recursive partitioning analysis (RPA)-class. Groups were analyzed regarding intracerebral control (IC) and overall survival (OS). RESULTS: On univariate analysis of IC, type of irradiation did not significantly affect outcomes (p = 0.84). On Cox regression, brain metastases number (p < 0.001), nature of tumor (p < 0.001) and period from cancer detection to irradiation of brain metastases (p = 0.013) were significantly associated with IC. On univariate analysis of OS, type of irradiation showed no significant association with outcomes (p = 0.63). On multivariate analyses, OS was significantly associated with ECOG performance score (p = 0.011), nature of tumor (p = 0.035), brain metastases number (p = 0.048), extra-cerebral spread (p = 0.002) and RPA-class (p < 0.001). CONCLUSION: In this matched-pair study, RS/FSRT alone was not superior to WBI alone regarding IC and OS. These results can be considered a revision of the findings from our retrospective previous study without matched-pair design, where RS alone resulted in significantly better IC than WBI alone on multivariate analysis.

[A modern strategy of combined surgical and radiation treatment in patients with brain metastases]. / Sovremennaia strategiia kombinatsii khirurgicheskogo i luchevogo lecheniia u patsientov s metastazami v golovnom mozge.

The treatment standards for patients with brain metastases have been developed for several decades. An important element in the evolution of approaches to the treatment of these patients is the development of microsurgery, stereotactic radiotherapy, and targeted therapy and introduction of these techniques into clinical practice. Surgery is an effective treatment option in patients having single brain metastases and/or occuring in life-threatening clinical situations. Irradiation of the whole brain after surgical treatment is a necessary step in achieving satisfactory local control of intracranial metastatic foci, but the development of neurocognitive disorders and deterioration of life quality after this irradiation necessitate the search for alternative radiotherapy techniques in this clinical situation. Currently, an alternative to postoperative irradiation of the whole brain is stereotactic radiotherapy, which is used before or after surgical treatment. Stereotactic radiotherapy improves local control of intracranial metastatic foci and reduces the risk of neurotoxicity. In this review, we analyze the literature data on outcomes of stereotactic irradiation as a component of combined treatment of patients with metastatic brain lesions.

Colony-stimulating factor 1 receptor blockade prevents fractionated whole-brain irradiation-induced memory deficits.

BACKGROUND: Primary central nervous system (CNS) neoplasms and brain metastases are routinely treated with whole-brain radiation. Long-term survival occurs in many patients, but their quality of life is severely affected by the development of cognitive deficits, and there is no treatment to prevent these adverse effects. Neuroinflammation, associated with activation of brain-resident microglia and infiltrating monocytes, plays a pivotal role in loss of neurological function and has been shown to be associated with acute and long-term effects of brain irradiation. Colony-stimulating factor 1 receptor (CSF-1R) signaling is essential for the survival and differentiation of microglia and monocytes. Here, we tested the effects of CSF-1R blockade by PLX5622 on cognitive function in mice treated with three fractions of 3.3 Gy whole-brain irradiation. METHODS: Young adult C57BL/6J mice were given three fractions of 3.3 Gy whole-brain irradiation while they were on diet supplemented with PLX5622, and the effects on periphery monocyte accumulation, microglia numbers, and neuronal functions were assessed. RESULTS: The mice developed hippocampal-dependent cognitive deficits at 1 and 3 months after they received fractionated whole-brain irradiation. The impaired cognitive function correlated with increased number of periphery monocyte accumulation in the CNS and decreased dendritic spine density in hippocampal granule neurons. PLX5622 treatment caused temporary reduction of microglia numbers, inhibited monocyte accumulation in the brain, and prevented radiation-induced cognitive deficits. CONCLUSIONS: Blockade of CSF-1R by PLX5622 prevents fractionated whole-brain irradiation-induced memory deficits. Therapeutic targeting of CSF-1R may provide a new avenue for protection from radiation-induced memory deficits.

Involved-Site Radiation Therapy Enables Effective Disease Control in Parenchymal Low-Grade Primary Cerebral Lymphoma.

BACKGROUND: Primary lymphoma of the central nervous system (PCNSL) encompasses a variety of lymphoma subtypes, with the majority being diffuse large B-cell lymphomas, which require aggressive systemic treatment. In contrast, low-grade lymphomas are reported infrequently and are mostly limited to dural manifestations. Very rarely, parenchymal low-grade PCNSL is diagnosed, and the cases documented in the literature show a wide variety of treatment approaches. METHODS: We screened all cases of PCNSL treated at our department (a tertiary hematooncology and neurooncology center) in the last 15 years and conducted a comprehensive literature research in the PubMed database. RESULTS: Overall, two cases of low-grade primary parenchymal PCNSL treated with irradiation were identified. The dose prescriptions ranged from 30.6 to 36 Gy for the involved site, with sparing of the hippocampal structures. Both patients had an excellent response to the treatment with a mean follow-up of 20 months. No clinical or radiological signs of treatment toxicity were detected. CONCLUSIONS: Our analysis corroborates the results from the literature and demonstrates that parenchymal low-grade PCNSL shows a good response to localized radiation treatment, enabling a favorable outcome while avoiding long-term treatment toxicity.

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

BACKGROUND: Approximately 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. METHODS: We 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. RESULTS: Blood-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. CONCLUSIONS: The immune response plays a role in the magnitude of blood-brain barrier disruption following irradiation in a time- and size-dependent manner.

Stereotactic Radiotherapy or Whole-Brain Irradiation Plus Simultaneous Integrated Boost After Resection of Brain Metastases.

BACKGROUND/AIM: Most patients with resected brain metastases receive post-operative radiotherapy. This study investigated outcomes of fractionated stereotactic radiotherapy (FSRT) alone or whole-brain irradiation plus simultaneous integrated boost (WBI+SIB) in the post-operative setting. PATIENTS AND METHODS: Forty-four patients receiving FSRT alone (n=32) or WBI+SIB (n=12) after resection of 1-3 brain metastases from 2014-2022 were analyzed. Twelve factors were evaluated for local control (LC), distant brain control (DBC), and overall survival (OS). RESULTS: On univariate and multivariate analyses, single brain metastasis was associated with improved LC and DBC. Longer interval between tumor diagnosis and radiotherapy, single brain metastasis, and Karnofsky performance score >80 were associated with improved OS. WBI+SIB showed a trend towards better DBC. CONCLUSION: Several independent predictors of outcomes after FSRT or WBI+SIB following resection of brain metastases were identified. Given similar survival in the post-operative setting between FSRT and WBI+SIB, potential toxicity remains a significant factor in treatment recommendations.

Semiautomatic Treatment Planning for the Field-in-field Technique in Whole Brain Irradiation.

Objectives: In radiation therapy, the field-in-field (FIF) technique is used to prevent the administration of unnecessarily high doses to reduce toxicity. Recently, the FIF technique has been used for whole brain irradiation (WBI). Using the FIF technique, the volume that receives a higher than prescribed dose (hotspot) can be largely reduced; however, the treatment planning requires time. Therefore, to reduce the burden on the treatment planners, we propose a semiautomatic treatment planning method for the FIF technique. Methods: In the semiautomatic FIF technique, hotspot regions in a treatment plan without the FIF technique are identified three-dimensionally, and beams with blocks that cover the hotspot regions using a multileaf collimator (sub-beams) are automatically created. The sub-beams are added to the original plan, and weights are assigned based on the maximum dose of the original plan to decrease the doses in the hotspot regions. This method was applied to 22 patients previously treated with WBI, wherein treatment plans were originally created without the FIF technique. Results: In the semiautomatic FIF plans, the hotspots almost disappeared. The dose to 95% of the volume and the volume receiving at least 95% of the prescribed dose in the planning target volume decreased by only 0.3% ± 0.2% and 0.0% ± 0.1%, respectively, on average compared with those in the original plan. The average semiautomatic FIF processing time was 28 ± 4 s. Conclusions: The proposed method reduced the hotspot regions with a slight change in the target coverage.

Anatomic and metabolic alterations in the rodent frontal cortex caused by clinically relevant fractionated whole-brain irradiation.

Radiation-induced brain injury (RII) is a harmful side-effect occurring after conventional radiation therapy (usually fractionated whole-brain irradiation/fWBI) of patients with cerebral tumors and metastases. An important role in the quality of patients' lives plays cognitive, executive, and emotional functions, regulation on which are involved in frontal cortices pathways. This study assessed the morphologic and metabolic alterations in the rodent frontal cortex caused by fWBI with the total dose of 32 Gy in 4 fractions performed by linear accelerator Clinac iX. Nine male Wistar rats underwent radiation procedures, whereas the other nine rats were investigated as a sham-irradiated group. All eighteen animals were examined using magnetic resonance (MR) in three intervals - before, on 2nd, and 70th day after sham/irradiation. After ten weeks of surviving, all rats underwent histopathological analysis determined by image analysis of immunofluorescent stained sections in the frontal cortex. MR examination was performed on 7T MR scanner Bruker BioSpec 70/20 and consisted of MR-volumetry, T2 relaxometry, and single-voxel proton-1 MR spectroscopy localized in the frontal cortex. Both tissue volume and T2 relaxation time of the frontal cortex were significantly lower in animals after 2 and 70 days of exposure than in controls; however, there were no differences between irradiated groups. Similarly, in animals' frontal cortex after fWBI, increased levels of myoinositol and glutamate/glutamine ratios were observed. Ratios of N-acetyl-aspartate, choline, and peaks of lactate and lipids did not change between groups. The histopathological analysis of the frontal cortex showed increased signs of neurodegeneration and a slight increase in astrocytes and microglia in exposed animals. Early (2 days, 10 weeks) after clinically relevant fWBI were in the frontal cortices of exposed rodents confirmed morphologic and metabolic changes indicating neurodegenerative changes, initializing cerebral atrophy, and evident signs of endothelial disruption and dysregulated neurotransmission that may cause a wide range of functional as well as cognitive deficits.

Fully automated planning and delivery of hippocampal-sparing whole brain irradiation.

The goal of this study is to fully automate the treatment planning and delivery process of hippocampal-sparing whole brain irradiation (HS-WBRT) by combining a RapidPlan (RP) knowledge-based planning model and HyperArc (HA) technology. Additionally, this study compares the dosimetric performance of RapidPlan-HyperArc (RP-HA) treatment plans with RP plans and volumetric modulated arc therapy (VMAT) plans. Ten patients previously treated with HS-WBRT using conventional VMAT were re-planned using RP-HA technique and RP model for HS-WBRT. Treatment plans were generated for 30Gy in 3Gy fractions using 6MV photon beam on a TrueBeam linear accelerator (Varian Medical Systems, Palo Alto, CA) equipped with high definition multileaf collimator (HDMLC). Target coverage, homogeneity index (HI), Paddick Conformity index (CI), dose to organs-at-risk (OARs) provided by the 3 planning modalities were compared, and a paired t-test was performed. Total number of monitor units (MU), effective planning time and beam-on-time time were reported and evaluated for each plan. RP-HA plans achieved on average a 4% increase in D98% of PTV, a 26% improvement in HI, a 2.3% increase in CI, when compared to RP plans. Furthermore, RP-HA plans provided on average 11% decrease in D100% of hippocampi when compared to VMAT plans. All RP-HA plans were generated in less than 30 minutes while RP plans took 40 minutes and VMAT plans required on average 9 hours to complete. Regarding beam-on-time time, it was estimated that RP-HA plans take on average 5 minutes to deliver while RP and VMAT plans require 6.5 and 10 minutes, respectively. RP-HA method provides fully automated planning and delivery for HS-WBRT. The auto-generated plans together with automated treatment delivery allow standardization of plan quality, increased efficiency and ultimately improved patient care.

Reproducible abscopal effect in a patient with lung cancer who underwent whole-brain irradiation and atezolizumab administration.

Due to the emergence of immune checkpoint inhibitors, the abscopal effect has gained more attention. We report a case of extracranial abscopal effect after whole-brain irradiation therapy due to brain metastasis. After the initial abscopal effect was confirmed, a second abscopal effect was confirmed following radiation therapy for bone metastases. This case confirms the reproducibility of the abscopal effect. Moreover, the abscopal effect was not observed in metastatic lesions with low immunogenicity, even in the same patient.

Effect of fractionated whole-brain irradiation on brain and plasma in a rat model: Metabolic, volumetric and histopathological changes.

In the present study, we investigated the correlation between histopathological, metabolic, and volumetric changes in the brain and plasma under experimental conditions. Adult male Wistar rats received fractionated whole-brain irradiation (fWBI) with a total dose of 32 Gy delivered in 4 fractions (dose 8 Gy per fraction) once a week on the same day for 4 consecutive weeks. Proton magnetic resonance spectroscopy (1H MRS) and imaging were used to detect metabolic and volumetric changes in the brain and plasma. Histopathological changes in the brain were determined by image analysis of immunofluorescent stained sections. Metabolic changes in the brain measured by 1H MRS before, 48 h, and 9 weeks after the end of fWBI showed a significant decrease in the ratio of total N-acetylaspartate to total creatine (tNAA/tCr) in the corpus striatum. We found a significant decrease in glutamine + glutamate/tCr (Glx/tCr) and, conversely, an increase in gamma-aminobutyric acid to tCr (GABA/tCr) in olfactory bulb (OB). The ratio of astrocyte marker myoinositol/tCr (mIns/tCr) significantly increased in almost all evaluated areas. Magnetic resonance imaging (MRI)-based brain volumetry showed a significant increase in volume, and a concomitant increase in the T2 relaxation time of the hippocampus. Proton nuclear magnetic resonance (1H NMR) plasma metabolomics displayed a significant decrease in the level of glucose and glycolytic intermediates and an increase in ketone bodies. The histomorphological analysis showed a decrease to elimination of neuroblasts, increased astrocyte proliferation, and a mild microglia response. The results of the study clearly reflect early subacute changes 9-11 weeks after fWBI with strong manifestations of brain edema, astrogliosis, and ongoing ketosis.

Best Supportive Care Versus Whole-Brain Irradiation, Chemotherapy Alone, or WBRT Plus Chemotherapy in Patients With Brain Metastases From Small-Cell Lung Cancer: A Case-Controlled Analysis.

BACKGROUND: WBRT and systemic chemotherapy are the mainstay treatments for small-cell lung cancer (SCLC) brain metastases (BM). However, current recommendations are mainly based on evidence from retrospective analyses. A recent randomized trial found no benefits from WBRT compared with best supportive care (BSC) in patients with more than three BM from non-small-cell lung cancer (NSCLC). Herein, we aimed to evaluate the roles of WBRT and chemotherapy further in the management of BM from SCLC. MATERIALS AND METHODS: There were 698 patients with BM from SCLC included. Of these, 580 received anti cancer treatment (Group 1), including 178 who received WBRT only (Group 1a), 129 who received chemotherapy only (Group 1b), and 273 who received WBRT plus chemotherapy (Group 1c). The other 118 received BSC (Group 2). Propensity score matching (PSM) analysis was used to compare Group 2 with each of the other groups. RESULTS: After PSM, compared with Group 2 (n = 118), patients in Group 1 (n = 440) had a prolonged overall survival (OS) in both univariate and multivariate tests, with a median survival time of 10 months (95% CI = 9-11) in Group 1 and 3.5 months (95% CI = 2-7) in Group 2 (p < 0.001). In subgroup analyses, patients who received WBRT plus chemotherapy were more likely to benefit from treatment (p < 0.001). Chemotherapy alone or WBRT alone did not show survival benefits. CONCLUSION: WBRT plus chemotherapy improved OS in patients with BM from SCLC as compared to BSC. Chemotherapy alone and WBRT alone did not show survival benefits. This retrospective study suggests that SCLC patients with BM who receive WBRT combined with chemotherapy have a better outcome than those receiving BSC alone.

Clinical outcome after CyberKnife® radiosurgery re-irradiation for recurrent brain metastases.

PURPOSE: The objective of this study was to elucidate the impact on clinical outcomes resulting from re-irradiation for locally recurrent (LR) brain metastases (BM) using CyberKnife® stereotactic radiosurgery (SRS). MATERIALS AND METHODS: Seventy-seven patients with 254 LR BM lesions treated using SRS re-irradiation between January 2014 and December 2018 were analysed in this retrospective study. The local control (LC), overall survival (OS) rates, and adverse events were assessed. The adverse events were classified according to the Common terminology for adverse event (CTCAE) v5.0. RESULTS: The median follow-up duration was 8.9 months. The median age of the patients was 55 years (IQR: 47-62). The 3, 6, and 9-month LC and OS rates were 92.2%, 73.4%, and 73.4% and 79.2%, 61.0%, and 48.1%, respectively. On multivariate analysis the gender (male vs. female; HR, 1.79; 95% CI, 1.06-3.01; P=0.028), type of first brain radiation (WBI vs. SRS) followed by re-irradiation using SRS (HR, 9.32; 95% CI, 2.77-15.27; P<0.001) tumour volume (>12cc vs. ≤12cc; HR, 1.84; 95% CI, 1.10-3.11; P=0.02), and recursive partitioning analysis (RPA) (I vs. II & III; HR, 0.38; 95% CI, 0.19-0.70; P=0.001) were independent predictive factor for OS. Radionecrosis was reported in 3 patients. CONCLUSION: With acceptable toxicity, SRS re-irradiation for LR BM showed a favourable rate for LC and OS and reported better OS for the female gender, a patient undergoing first brain radiation with SRS, tumour volume ≤12cc, and RPA-I. This result needs to be further evaluated in future clinical studies.

An Instrument to Guide Physicians when Estimating the Survival of Elderly Patients With Brain Metastasis from Gynecological Cancer.

BACKGROUND/AIM: For treatment personalization in elderly cancer patients, survival prognoses should be considered. We developed an instrument to estimate survival of elderly patients with brain metastasis from gynecological cancer. PATIENTS AND METHODS: In 15 patients, whole-brain radiotherapy regimen, tumor site, age, Karnofsky performance score (KPS), number of brain metastases, extra-cerebral metastases and interval from diagnosis of gynecological cancer until radiotherapy were retrospectively evaluated for survival. Characteristics found significant on multivariate analysis were used for the instrument. RESULTS: In the multivariate analysis, KPS ≥70% (hazard ratio=3.71, p=0.0499) and an interval ≥28 months (hazard ratio=3.71, p=0.030) were significantly associated with better survival. Based on these characteristics, patients received 0 (n=6), 1 (n=3) or 2 points (n=6). Six-month survival rates of the groups 0-1 and 2 points were 0% and 50%, respectively (p=0.007). CONCLUSION: This instrument helps estimating survival in elderly patients with brain metastases from gynecological cancer and contributes to personalization of their treatment.

Seizures Prior to Whole-brain Irradiation for Metastatic Disease: Prevalence, Risk Factors and Association With Survival.

BACKGROUND/AIM: Seizures are a serious condition for patients with brain metastases. Prevalence, risk factors and a potential association of seizures with survival prior to whole-brain irradiation (WBI) for cerebral metastases were retrospectively investigated. PATIENTS AND METHODS: In 1,934 patients, the prevalence of pre-treatment seizures (pre-WBI) was determined. Seven pre-treatment characteristics were evaluated for associations with seizures. Ten characteristics including pre-treatment symptoms (none vs. seizures only vs. seizures+others vs. others only) and seizures (yes vs. no) were analyzed for survival. RESULTS: In 251 patients (13.0%), pre-treatment seizures were documented. The occurrence of seizures was significantly associated with 1-3 brain metastases and lack of extra-cerebral spread. On multivariate analysis, age, gender, performance score, number of metastases and extra-cerebral spread were significantly associated with survival; pre-treatment symptoms and seizures showed associations on univariate but not on multivariate analyses. CONCLUSION: Few brain metastases and lack of extra-cerebral spread were independent risk factors for pre-treatment seizures. Seizures appeared positively associated with survival.

Pre-operative Seizures in Patients With Single Brain Metastasis Treated With Resection Plus Whole-Brain Irradiation and a Boost.

BACKGROUND/AIM: Seizures can be the initial symptom of brain metastases. This study investigated pre-treatment seizures in patients with a single lesion. PATIENTS AND METHODS: Pre-operative seizures were analyzed in 104 patients with a single brain metastasis receiving resection plus whole-brain irradiation and a boost. Prevalence of seizures, risk factors and associations with survival (OS) were evaluated. RESULTS: Thirty patients (34.6%) had seizures prior to neurosurgery. Significant associations between seizures and investigated characteristics were not found. However, age ≤61 years showed a trend (p=0.117) for increased incidence of seizures. Time from diagnosis of malignancy until neurosurgery >12 months was significantly associated with improved OS on univariate analysis (p=0.003). Trends for a positive association with OS were found for no seizures (p=0.054), female gender (p=0.066) and breast cancer (p=0.098). On multivariate analysis, time until neurosurgery >12 months was independently associated (p=0.019) with better OS, and seizures showed a trend (p=0.119) for improved OS. CONCLUSIONS: Considering the high prevalence of seizures in this cohort, regular screening and monitoring of these patients appears reasonable. This applies particularly to patients aged ≤61 years.