scholarly journals Combination ipilimumab and radiosurgery for brain metastases: tumor, edema, and adverse radiation effects

2018 ◽  
Vol 129 (6) ◽  
pp. 1397-1406 ◽  
Author(s):  
Kevin Diao ◽  
Shelly X. Bian ◽  
David M. Routman ◽  
Cheng Yu ◽  
Paul E. Kim ◽  
...  

OBJECTIVETumor and edema volume changes of brain metastases after stereotactic radiosurgery (SRS) and ipilimumab are not well described, and there is concern regarding the safety of combination treatment. The authors evaluated tumor, edema, and adverse radiation-induced changes after SRS with and without ipilimumab and identified associated risk factors.METHODSThis single-institution retrospective study included 72 patients with melanoma brain metastases treated consecutively with upfront SRS from 2006 to 2015. Concurrent ipilimumab was defined as ipilimumab treatment within 4 weeks of SRS. At baseline and during each follow-up, tumor and edema were measured in 3 orthogonal planes. The (length × width × height/2) formula was used to estimate tumor and edema volumes and was validated in the present study for estimation of edema volume. Tumor and edema volume changes from baseline were compared using the Kruskal-Wallis test. Local failure, lesion hemorrhage, and treatment-related imaging changes (TRICs) were analyzed with the Cox proportional hazards model.RESULTSOf 310 analyzed lesions, 91 were not treated with ipilimumab, 59 were treated with concurrent ipilimumab, and 160 were treated with nonconcurrent ipilimumab. Of 106 randomly selected lesions with measurable peritumoral edema, the mean edema volume by manual contouring was 7.45 cm3 and the mean volume by (length × width × height)/2 formula estimation was 7.79 cm3 with R2 = 0.99 and slope of 1.08 on line of best fit. At 6 months after SRS, the ipilimumab groups had greater tumor (p = 0.001) and edema (p = 0.005) volume reduction than the control group. The concurrent ipilimumab group had the highest rate of lesion response and lowest rate of lesion progression (p = 0.002). Within the concurrent ipilimumab group, SRS dose ≥ 20 Gy was associated with significantly greater median tumor volume reduction at 3 months (p = 0.01) and 6 months (p = 0.02). The concurrent ipilimumab group also had the highest rate of lesion hemorrhage (p = 0.01). Any ipilimumab was associated with higher incidence of symptomatic TRICs (p = 0.005). The overall incidence of pathologically confirmed radiation necrosis (RN) was 2%. In multivariate analysis, tumor and edema response at 3 months were the strongest predictors of local failure (HR 0.131 and HR 0.125) and lesion hemorrhage (HR 0.225 and HR 0.262). Tumor and edema response at 1.5 months were the strongest predictors of TRICs (HR 0.144 and HR 0.297).CONCLUSIONSThe addition of ipilimumab improved tumor and edema volume reduction but was associated with a higher incidence of lesion hemorrhage and symptomatic TRICs. There may be a radiation dose-response relationship between SRS and ipilimumab when administered concurrently. Early tumor and edema response were excellent predictors of subsequent local failure, lesion hemorrhage, and TRICs. The incidence of pathologically proven RN was low, supporting the relative safety of ipilimumab in radiosurgery treatment.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21740-e21740
Author(s):  
Salma Ait Batahar

e21740 Background: Lung cancer is the first cause of death by cancer worldwide. Brain metastases in lung cancer are associated to an even poorer prognosis of this cancer. Identifying patients with a higher risk of developing brain cancer may help their prognosis by including systematic brain radiotherapy to their treatment. But what are risk factors of brain metastasis occurrence in lung cancer patients? Methods: To answer this question, we conducted a case control study comparing two groups of lung cancer patients. The cases group included 35 lung cancer patients with brain metastasis at the moment of diagnosis while the control group was made of 49 lung cancer patient with no brain metastasis at the moment of diagnosis. Many parameters were compared between the two groups such as: professional exposure, type and duration of smoking, medical history, clinical and radiological presentation as well as the histological type of the carcinoma. Results: The mean age was 56 for the cases group and 61 for the control group. Nonsmokers represented 14% in the cases group and 4% in the control group. The average smoking was 34 pack-year for the cases group and 31 pack-year for the control group and in both groups 51% of patients smoked a mixture of tobacco and Cannabis. 36% of the control group patients had an exposure to a professional carcinogen while 48% of the cases group patients had one. Digital clubbing was found in 62% of cases group patients and in 51% of the control group patients. 17% of the cases group patients had two more metastases outside the lungs and other than the brain ones while this rate was only 6% for the control group patients. The mean level of LDH (Lactate Dehydrogenase) was 340 U/L for the cases group and 342 U/L for the control group while the CRP (C- reactive protein) one was 78 mg/L for the cases group and 59 mg/L for the control group. The main histological type found in both groups was Adenocarcinoma (25% in the cases group and 18% in the control group) followed by the poorly differentiated carcinoma in the cases group and the squamous cell carcinoma in the control group. Small cell carcinoma was found in 5% of the patients with brain metastases and in 8% of the patients without brain metastases. Conclusions: Patients with brain metastases have a higher professional carcinogens exposure, a higher percentage of nonsmokers, more digital clubbing, and higher CRP levels than patients with no brain metastases. They also have more than one metastasis at the moment of the diagnosis and the predominant histological types are Adenocarcinoma and poorly differentiated carcinoma.


2020 ◽  
Vol 38 (5) ◽  
pp. 385-393
Author(s):  
Jin-Xia Cao ◽  
Li Liu ◽  
Yun-Tao Sun ◽  
Qing-Hong Zeng ◽  
Zhen-Dong Yang ◽  
...  

Background: Escitalopram is one of the most commonly used SSRIs at present, which has the characteristics of quick onset, less interactions with other drugs, and relative safety. Objective: This study aims to investigate the effects of escitalopram on neural functional prognoses and endothelial dysfunction after acute ischemic stroke. Methods: One hundred eligible patients afflicted with acute ischemic stroke were randomized into two groups: control and treatment groups. Patients in the treatment group received escitalopram in addition to the basic therapies in the control group over a period of 90 days. Neurological deficits were quantified using the National Institutes of Health Stroke Scale (NIHSS) score and Barthel index (BI) score, cognitive impairment was determined using the Mini-Mental State Examination (MMSE) score, depressive symptoms were measured using the 17-item Hamilton Depression Rating Scale (HAMD). Furthermore, post-stroke depression (PSD) was defined based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition), with a HAMD score ≥17. Flow-mediated vascular dilatation (FMD) of the brachial artery was use as a surrogate indicator for endothelial dysfunction assessment with ultrasound. Results: The mean NIHSS and HAMD scores on day 90 after treatment were significantly lower in the treatment group than in the control group (2.17±0.36 vs. 4.24±0.85; 5.81±1.35 vs. 10.43±4.91; P < 0.01), while the mean BI score and FMD were significantly higher in the treatment group (93.08±6.23 vs. 79.64±7.56, P < 0.01; 8.71±2.35 vs. 5.83±1.21, P < 0.05) than in the control group. The improvement in MMSE score was not significantly different between the two groups. Conclusions: Treatment with escitalopram early after ischemic stroke can improve neural functional prognoses and endothelial dysfunction. Escitalopram had less side effects, which is worthy of clinical prophylactic application.


2019 ◽  
Vol 128 (8) ◽  
pp. 749-754 ◽  
Author(s):  
Helena Wichova ◽  
Sameer Alvi ◽  
Christine Boatright ◽  
Luke Ledbetter ◽  
Hinrich Staecker ◽  
...  

Objectives: The cochlear aqueduct is a bony duct connecting the scala tympani with the subarachnoid space. Given the pathophysiology of otosclerosis, including bone resorption and new bone deposition, we hypothesize that the cochlear aqueduct in otosclerotic ears is narrowed. Methods: A retrospective review of patients with otosclerosis who have undergone high-resolution computed tomography (HRCT) of the temporal bone was completed. The control cohort included 20 patients with the diagnosis of noise-induced hearing loss, without the diagnosis of otosclerosis. Uniform measurements of cochlear aqueduct dimensions were performed using the axial plane. Results: The otosclerosis cohort included 25 males and 52 females with mean age of 52.2 ± 17.6 years. The control group included 10 males and 10 females with mean age of 64.0 ± 18.5 years. The mean cochlear aqueduct length, width mid canal, aperture base, aperture widest diameter, and funnel diameter in millimeters were 12.19 ± 1.66, 0.68 ± 0.28, 4.21 ± 1.67, 3.23 ± 1.47, and 2.70 ± 1.05 in the ears with otosclerotic foci and 11.57 ± 1.66, 0.69 ± 0.29, 2.56 ± 1.59, 2.77 ± 1.67, and 2.58 ± 1.03 in control group, respectively. Statistical difference was seen in length of cochlear aqueduct, aperture base, and aperture widest diameters ( P = .017, <.001, .007). Conclusions: The length of the cochlear aqueduct and the funnel width are statistically longer in the otosclerotic population compared to control. The width of the cochlear aqueduct is not statistically different.


2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 82-89 ◽  
Author(s):  
Chung Ping Yu ◽  
Joel Yiu Chung Cheung ◽  
Samuel Leung ◽  
Robert Ho

Object. The purpose of this study was to confirm, by using a sequential volume mapping (SVM) technique, that gamma knife radiosurgery (GKS) induces negative growth in vestibular schwannomas (VS). Methods. Over a period of 5 years, 126 small- to medium-sized (< 15 cm3) VSs were treated using microradiosurgical techniques within a standard protocol. All patient data were collected prospectively. Sequential magnetic resonance imaging was performed every 6 months to assess the volume of the tumor, based on specially developed GammaPlan software. The mean follow-up duration was 22 months. At least three SVM measurements were obtained in 91 patients and at least four were obtained in 62 patients. The mean number of SVM measurements for each patient was 2.54. After GKS, the following patterns of volume change were seen: 1) 57 VSs showed transient increase in volume with a peak at 6 months, followed by shrinkage. Four VSs exhibited prolonged swelling beyond 24 months. Transient swelling and eventual shrinkage were independent of the initial VS volume; 2) 29 VSs showed direct volume shri6nkage without swelling; and 3) five VSs showed persistent volume increase. All volume changes were greater than 10%. The overall mean volume reduction was 46.8% at 30 months. Conclusions. Sequential volume mapping appears to be superior to conventional two-dimensional measurements in monitoring volume changes in VS after GKS. It confirms that transient swelling is common. Ninety-two percent of tumors responded by showing significant volume shrinkage (mean 46.8%). It would seem that GKS can induce volume reduction in VS.


Neurosurgery ◽  
2011 ◽  
Vol 68 (3) ◽  
pp. 682-690 ◽  
Author(s):  
Huai-che Yang ◽  
Hideyuki Kano ◽  
L Dade Lunsford ◽  
Ajay Niranjan ◽  
John C Flickinger ◽  
...  

Abstract BACKGROUND: Approximately 20 to 40% of patients with systemic malignancies develop brain metastases. OBJECTIVE: To assess the potential role of stereotactic radiosurgery (SRS) for larger metastatic brain tumors, we reviewed our recent experience. METHODS: Between 2004 and 2008, 70 patients with a metastatic brain tumor larger than 3 cm in maximum diameter underwent Gamma knife SRS. Thirty-three patients had received previous whole brain radiation therapy (WBRT) and 37 received only SRS. RESULTS: The overall median follow-up was 8.1 months. At the first planned imaging follow-up at 2 months, 29 (41%) tumors had &gt;50% volume reduction, 22 (31%) had 10 to 50% volume reduction, and 19 (28%) were stable or larger. We also evaluated brain edema using MRI T2 images. In 11 patients (16%) the peritumoral edema volume was reduced by more than 50%, in 25 (36%) it was reduced by 10 to 50%, in 21 (30%) it was stable, and in 13 (19%) it was increased. Twenty (36%) discontinued corticosteroids by the time of first imaging follow-up. Because of persistent symptoms, 7 patients (10%) required a craniotomy to remove the tumor. Tumor volume reduction (&gt;50%) was associated with a single metastasis (P = .012), no previous WBRT (P = .002), and a tumor volume &lt;16 cm3 (P = .002). The better peritumoral edema volume reduction (&gt;50%) was associated with a single metastasis (P = .024), no previous WBRT (P = .05), and breast cancer histology (P = .044). CONCLUSION: Surgical resection remains the primary approach for larger brain metastases if feasible. Tumor volume is a better indicator than maximum diameter. Tumor volume and edema responded better in patients who underwent SRS alone.


2015 ◽  
Vol 123 (5) ◽  
pp. 1261-1267 ◽  
Author(s):  
Jessica M. Frakes ◽  
Nicholas D. Figura ◽  
Kamran A. Ahmed ◽  
Tzu-Hua Juan ◽  
Neha Patel ◽  
...  

OBJECT Linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) is a treatment option for patients with melanoma in whom brain metastases have developed. Very limited data are available on treating patients with ≥ 5 lesions. The authors sought to determine the effectiveness of SRS in patients with ≥ 5 melanoma brain metastases. METHODS A retrospective analysis of metastatic melanoma treated with SRS in a single treatment session for ≥ 5 lesions was performed. Magnetic resonance imaging studies were reviewed post-SRS to evaluate local control (LC). Disease progression on imaging was defined using the 2009 Response Evaluation Criteria in Solid Tumors (RECIST). Survival curves were calculated from the date of brain metastases diagnosis or the date of SRS by using the Kaplan-Meier (KM) method. Univariate and multivariate analysis (UVA and MVA, respectively) were performed using the Cox proportional-hazards model. RESULTS The authors identified 149 metastatic brain lesions treated in 28 patients. The median patient age was 60.5 years (range 38–83 years), and the majority of patients (24 [85.7%]) had extracranial metastases. Four patients (14.3%) had received previous whole-brain radiotherapy (WBRT), and 11 (39.3%) had undergone previous SRS. The median planning target volume (PTV) was 0.34 cm3 (range 0.01–12.5 cm3). Median follow-up was 6.3 months (range 1–46 months). At the time of treatment, 7% of patients were categorized as recursive partitioning analysis (RPA) Class I, 89% as RPA Class II, and 4% as RPA Class III. The rate of local failure was 11.4%. Kaplan-Meier LC estimates at 6 and 12 months were 91.3% and 82.2%, respectively. A PTV volume ≥ 0.34 cm3 was a significant predictor of local failure on UVA (HR 16.1, 95% CI 3.2–292.6, p < 0.0001) and MVA (HR 14.8, 95% CI 3.0–268.5, p = 0.0002). Sixteen patients (57.1%) were noted to have distant failure in the brain with a median time to failure of 3 months (range 1–15 months). Nine patients with distant failures received WBRT, and 7 received additional SRS. Median overall survival (OS) was 9.4 and 7.6 months from the date of brain metastases diagnosis and the date of SRS, respectively. The KM OS estimates at 6 and 12 months were 57.8% and 28.2%, respectively, from the time of SRS treatment. The RPA class was a significant predictor of KM OS estimates from the date of treatment (p = 0.02). Patients who did not receive WBRT after SRS treatment had decreased OS on MVA (HR 3.5, 95% CI 1.1–12.0, p = 0.03), and patients who did not receive WBRT prior to SRS had improved OS (HR 0.11, 95% CI 0.02–0.53, p = 0.007). CONCLUSIONS Stereotactic radiosurgery for ≥ 5 lesions appears to be effective for selected patients with metastatic melanoma, offering excellent LC. This is particularly important for patients as new targeted systemic agents are improving outcomes but still have limited efficacy within the central nervous system.


2016 ◽  
Vol 86 (1-2) ◽  
pp. 9-17 ◽  
Author(s):  
Bekir Ucan ◽  
Mustafa Sahin ◽  
Muyesser Sayki Arslan ◽  
Nujen Colak Bozkurt ◽  
Muhammed Kizilgul ◽  
...  

Abstract.The relationship between Hashimoto’s thyroiditis and vitamin D has been demonstrated in several studies. The aim of the present study was to evaluate vitamin D concentrations in patients with Hashimoto’s thyroiditis, the effect of vitamin D therapy on the course of disease, and to determine changes in thyroid autoantibody status and cardiovascular risk after vitamin D therapy. We included 75 patients with Hashimoto’s thyroiditis and 43 healthy individuals. Vitamin D deficiency is defined as a 25-hydroxy vitamin D (25(OH)D3) concentration less than 20ng/mL. Vitamin D deficient patients were given 50.000 units of 25(OH)D3 weekly for eight weeks in accordance with the Endocrine Society guidelines. All evaluations were repeated after 2 months of treatment. Patients with Hashimoto’s thyroiditis had significantly lower vitamin D concentrations compared with the controls (9.37±0.69 ng/mL vs 11.95±1.01 ng/mL, p < 0.05, respectively). Thyroid autoantibodies were significantly decreased by vitamin D replacement treatment in patients with euthyroid Hashimoto’s thyroiditis. Also, HDL cholesterol concentrations improved in the euthyroid Hashimoto group after treatment. The mean free thyroxine (fT4) concentrations were 0.89±0.02 ng/dL in patients with Hashimoto’s thyroiditis and 1.07±0.03 ng/dL in the healthy control group (p < 0.001). The mean thyroid volumes were 7.71±0.44 mL in patients with Hashimoto’s thyroiditis and 5.46±0.63 mL in the healthy control group (p < 0.01). Vitamin D deficiency is frequent in Hashimoto’s thyroiditis and treatment of patients with this condition with Vitamin D may slow down the course of development of hypothyroidism and also decrease cardiovascular risks in these patients. Vitamin D measurement and replacement may be critical in these patients.


2010 ◽  
Vol 69 (3) ◽  
pp. 131-139 ◽  
Author(s):  
Félix Neto

This study investigated mental health problems and their predictors among adolescents from returned immigrant families. The sample consisted of 360 returned adolescents (mean age = 16.8 years; SD = 1.9). The mean duration of a sojourn in Portugal for the sample was 8.2 years (SD = 4.5). A control group of 217 Portuguese youths were also included in the study. Adolescents from immigrant families reported mental health levels similar to those of Portuguese adolescents who have never migrated. Girls showed more mental health problems than boys. Younger adolescents showed fewer mental health problems than older adolescents. Adaptation variables contributed to mental health outcomes even after acculturation variables were accounted for. Implications of the study for counselors are discussed.


Author(s):  
J. Santoantonio ◽  
L. Yazigi ◽  
E. I. Sato

The purpose of this study was to investigate the personality characteristics in adolescents with SLE. The research design is a case-control study by means of the Rorschach Method and the Wechsler Intelligence Scale. Study group: 30 female adolescents with lupus, 12–17 years of age. The SLE Disease Activity Index was administered during the period of psychological evaluation. Control group: 32 nonpatient adolescents were matched for age, sex, and socioeconomic level. In the Wechsler Intelligence Scale the mean IQ of the experimental group was significantly lower than that of the control group (77 and 98, respectively, p < .001). In the Rorschach, the lupus patients showed greater difficulty in interpersonal interactions, although they displayed the resources to process affect and to cope with stressful situations. A positive moderate correlation (p = .069) between the activity index of the disease and the affect constriction proportion of the Rorschach was observed: the higher the SLEDAI score, the lower the capacity to process affect. There is a negative correlation between the activity index of the disease and the IQ (p = .001): with a higher activity index of the disease, less intellectual resources are available.


1987 ◽  
Vol 57 (01) ◽  
pp. 55-58 ◽  
Author(s):  
J F Martin ◽  
T D Daniel ◽  
E A Trowbridge

SummaryPatients undergoing surgery for coronary artery bypass graft or heart valve replacement had their platelet count and mean volume measured pre-operatively, immediately post-operatively and serially for up to 48 days after the surgical procedure. The mean pre-operative platelet count of 1.95 ± 0.11 × 1011/1 (n = 26) fell significantly to 1.35 ± 0.09 × 1011/1 immediately post-operatively (p <0.001) (n = 22), without a significant alteration in the mean platelet volume. The average platelet count rose to a maximum of 5.07 ± 0.66 × 1011/1 between days 14 and 17 after surgery while the average mean platelet volume fell from preparative and post-operative values of 7.25 ± 0.14 and 7.20 ± 0.14 fl respectively to a minimum of 6.16 ± 0.16 fl by day 20. Seven patients were followed for 32 days or longer after the operation. By this time they had achieved steady state thrombopoiesis and their average platelet count was 2.44 ± 0.33 × 1011/1, significantly higher than the pre-operative value (p <0.05), while their average mean platelet volume was 6.63 ± 0.21 fl, significantly lower than before surgery (p <0.001). The pre-operative values for the platelet volume and counts of these patients were significantly different from a control group of 32 young males, while the chronic post-operative values were not. These long term changes in platelet volume and count may reflect changes in the thrombopoietic control system secondary to the corrective surgery.


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