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PubMed | Tel Aviv Sourasky Medical Center, Wolfson Medical Center, Hasassha Medical Center, Sheba Medical Center and 4 more.
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2017

186 Background: Cabazitaxel (CAB) and abiraterone-acetate (AA) have been approved after docetaxel in castration resistant prostate cancer (CRPC). Both exhibit hormonal effects. AA depletes androgen in microenvironment; taxanes affect the microtubule-dependent trafficking of the androgen receptor. Recently, clinical cross-resistance has been suggested between AA and taxanes. This prompted evaluation of CAB following docetaxel and AA in CRPC.Over 13 months until December 2011, 130 CRPC patients received AA after docetaxel in compassionate programs. Of them, 24 (18.4%) subsequently received CAB. We retrospectively reviewed their data (PCWG2/RECIST and NCI toxicity criteria).Fourteen (58.3%) received CAB/prednisone at 20 mg/mLimited number of patients with CRPC received CAB following docetaxel and AA. In this selected population CAB was active. Response to prior docetaxel was associated with prolonged survival to CAB therapy.


PubMed | Roswell Park Cancer Institute, Soroka Medical Center, Wolfson Medical Center, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and 10 more.
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2017

458 Background: Geographic differences in the outcome of pts have been described in various cancers. The VEGFR inhibitor su is a standard treatment (tx) for mRCC. The effect of geographic differences on the outcome of su tx in mRCC is poorly defined. We aimed to study the effect of geographic differences on outcome of su tx in mRCC.We performed an international multicenter retrospective study of unselected cohort of 275 mRCC pts, who were treated with su from 2004 to 2012 in 7 centers across the United States and Middle East (ME; Israel). Clinicopathologic and prognostic factors, and tx outcome were compared between United States (n=133) and ME (n=142) pts. Chi-square and Fishers exact tests were used to compare categorical variables, and two-sample t-test was used to compare continuous endpoints. Progression free survival (PFS) and overall survival (OS) were determined by Cox regression.Median age was 61 (United States) vs. 65 (ME, p = 0.01). The groups were balanced regarding gender, Heng risk, past nephrectomy, RCC histology, presence of 2 metastatic sites, lung/liver/bone metastasis, use of angiotensin system inhibitors (ASI), prior cytokines/ targeted txt, su induced HTN, and su dose reduction/tx interruption secondary to side effects. The incidence of active smokers (28% vs. 15%, p =0.01), bisphosphonates users (23% vs. 13%, p = 0.03) and pts with pre-tx neutrophil to lymphocyte ratio (NLR) 3 (63% vs. 49%, p = 0.04) was higher among ME pts. In United States vs. ME pts, objective response was partial response/stable disease 77% (n=102) vs. 79% (n=112), and progressive disease at first imaging evaluation within the first 3 months (mos) 23% (n=31) vs. 21% (n=30) (p = 0.77, OR 1.1). Median PFS was 8 vs. 12 mos (HR=1.8, p < 0.0001), and median OS 21 vs. 22 mos (HR=0.94, p = 0.9) in United States vs ME pts. Factors associated with PFS in multivariate analysis of the entire cohort (n=275) were geographic location (United States vs. ME), Heng risk, RCC histology, su induced HTN, ASI use, pre-tx NLR, and smoking status.Geographic differences in clinicopathologic factors and PFS of pts with mRCC treated with su may exist. This should be further investigated, and if validated, applied in clinical practice and clinical trials.


PubMed | Roswell Park Cancer Institute, Soroka Medical Center, Wolfson Medical Center, Johns Hopkins University and 9 more.
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2017

453 Background: Several studies have suggested the existence of a trial effect, in which for a given treatment, participation in a clinical trial is associated with a better outcome of cancer patients. The VEGFR inhibitor sunitinib is a standard treatment for mRCC. The effect of clinical trial participation on the outcome of sunitinib treatment in mRCC is poorly defined. We aimed to study the effect of clinical trial participation on outcome of mRCC patients treated with sunitinib.Records from 275 mRCC patients treated with sunitinib from 2004 to 2012 in 7 centers across 2 countries were reviewed. We compared the response rate, progression free survival, and overall survival, between clinical trial participants (n=49) and a matched cohort of non participants (n=49) who received standard therapy. Each patient participating in a clinical trial was individually matched with a non-participant by clinicopathologic factors. Progression free survival and overall survival were determined by Cox regression.The groups were matched by age (median 64), gender (male 67%), Heng risk (favorable 24%, intermediate 60%, poor 16%), ECOG performance status (0-1 92%), prior nephrectomy (92%), renal cell carcinoma histology (clear cell 80%), sunitinib induced hypertension (56%), and sunitinib dose reduction/treatment interruption (41%). In clinical trial participants vs. non participants, objective response was partial response/stable disease 80% (n=39) vs. 73% (n=36), and progressive disease at first imaging evaluation within the first 3 months (mos) 20% (n=10) vs. 27% (n=13) (p = 0.63, OR 1.2). Median progression free survival was 10 vs. 11 mos (HR=0.96, p = 0.84), and median overall survival 23 vs. 24 mos (HR=0.97, p=0.89).In mRCC patient treated with sunitinib, the outcome of clinical trial participants was similar to matched non participants who received standard therapy.


Yahalom G.,The Chaim Sheba Medical Center | Kivity S.,The unit of Rheumatology | Lidar M.,The Chaim Sheba Medical Center | Lidar M.,Tel Aviv University | And 6 more authors.
European Journal of Neurology | Year: 2011

Background and purpose: To describe and characterize the association between familial Mediterranean fever (FMF) and multiple sclerosis (MS). Methods: The patient registry of The National Center for FMF was screened for the coexistence of FMF and MS. Tel-Hashomer criteria were used for the diagnosis of FMF, and FMF severity was evaluated, using the simplified FMF severity scale. McDonald criteria were used for the diagnosis of MS, and neurologic disability was measured using the expanded disability status scale (EDSS). Results: We identified nine patients, affected with both FMF and MS. The onset of the FMF averaged 15.6 (3-37) years. Most patients suffered from abdominal and joint attacks, and 50% of the patients sustained a moderate to severe FMF. The onset of the MS was at an average age of 31.6 (17-50) years. Neurologic manifestations varied individually, without a dominant deficit, and the course was in a relapsing-remitting pattern in most. The median EDSS was in general of low score (3.0), apart from the patients who were homozygous for the M694V mutation, in whom the MS was more severe. Based on our case series, the frequency of MS in our FMF population is 0.075%, twice higher the expected rate in the general population (P=0.0057). Conclusions: Multiple sclerosis is more common in FMF than in the general Israeli population. Homozygosity for the M694V MEFV mutation may aggravate the phenotype of MS and predispose FMF patients to develop MS. © 2011 The Author(s). European Journal of Neurology © 2011 EFNS.


Peer A.,Rambam Medical Center | Gottfried M.,Meir Medical Center | Sinibaldi V.,Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Carducci M.A.,Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | And 5 more authors.
Prostate | Year: 2014

BACKGROUND: Abiraterone, a potent CYP 17 inhibitor, is standard treatment in docetaxel refractory, metastatic castrate resistant prostate cancer (mCRPC). However, in countries where abiraterone has not been approved yet, or for patients who cannot afford it, ketoconazole is used as an alternative CYP 17 inhibitor. Although preclinical data suggests that ketoconazole is a less potent inhibitor of CYP 17, there are limited clinical data comparing both agents. We aimed to compare the clinical effectiveness of abiraterone versus ketoconazole in docetaxel refractory mCRPC. METHODS: Records from mCRPC patients treated with ketoconazole (international multicenter database, n = 162) were reviewed retrospectively. Twenty-six patients treated post docetaxel were individually matched by clinicopathologic factors to patients treated with abiraterone (national multicenter database, n=140). We compared the PSA response, biochemical and radiological progression free survival (PFS), and overall survival (OS) between the groups. PFS and OS were determined by Cox regression. RESULTS: The groups were matched by Gleason score, pre-treatment disease extent, ECOG PS, pre-treatment risk category (Keizman, Oncologist 2012). Furthermore, they were balanced regarding other known confounding risk factors. In the groups of abiraterone versus ketoconazole, PSA response was 46% versus 19% (OR 4.3, P=0.04), median biochemical PFS 7 versus 2 months (HR 1.54, P=0.02), median radiological PFS 8 versus 2.5 months (HR 1.8, P=0.043), median OS 19 versus 11 months (HR 0.53, P=0.79), and treatment interruption d/t severe adverse events 8% (n=2) versus 31% (n=8) (0R 0.6, P=0.023). CONCLUSIONS: In docetaxel refractory mCRPC, the outcome of abiraterone treatment may be superior to ketoconazole. Prostate 74:433-440, 2014. © 2013 Wiley Periodicals, Inc.


Keizman D.,Tel Aviv University | Gottfried M.,Tel Aviv University | Ish-Shalom M.,Tel Aviv University | Maimon N.,Tel Aviv University | And 10 more authors.
Oncologist | Year: 2012

Background. The neutrophil-to-lymphocyte ratio (NLR), an inflammation marker, is prognostic in several cancers. We assessed the association between the pretreatment NLR and outcome of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with the CYP17 inhibitor ketoconazole. Methods. This was an international, retrospective study of 156 mCRPC patients treated with ketoconazole. The independent effect of the pretreatment NLR and factors associated with treatment outcome were determined by multivariate analysis. Results. Seventy-eight patients (50%) had a ≥50% decline in prostate-specific antigen (PSA). The median progression-free survival (PFS) time was 8 months. Excluded from the analysis were 23 patients without available data on their NLR and those with a recent health event or treatment associated with a blood count change. Sixty-two patients (47%) had a pretreatment NLR >3. Risk factors associated with the PFS outcome were a pretreatment NLR >3 and PSA doubling time (PSADT) <3 months and a prior response to a gonadotropin-releasing hormone agonist of <24 months or to an antiandrogen of <6 months. The number of risk factors was used to form a predictive nomogram by patient categorization into favorable (zero or one factor), intermediate (two factors), and poor (three or four factors) risk groups. Conclusions. In mCRPC patients treated with ketoconazole, the pretreatment NLR and PSADT, and prior response to androgen-deprivation therapy, may be associated with the PFS time and used to form a risk stratification predictive nomogram. ©AlphaMed Press.


PubMed | The Johns Hopkins Medical Institutions, Roswell Park Cancer Institute, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Princess Margaret Hospital and 7 more.
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2017

146 Background: Abi is a standard treatment (tx) in pts with mCRPC refractory to deocetaxel. It is a potent and selective CYP 17 inhibitor that blocks the synthesis of androgens in the testis, adrenal glands, and prostate. However, in many countries where abi has not been approved yet, keto is used as an alternative CYP 17 inhibitor. Although preclinical data suggests that keto is a less specific and potent inhibitor of CYP 17, there are limited clinical data comparing both agents. We aimed to compare the clinical effectiveness of abi vs keto in pts with mCRPC refractory to D.Records from 156 mCRPC pts treated with keto 200 - 400 mg 3x day, in 4 centers across the US and Israel, were reviewed retrospectively. 26 pts treated post D were individually matched by clinicopathologic factors to pts treated with abi (selected from a multicenter Israeli database, n=120). We compared the PSA response (decrease 50% from baseline), biochemical and radiological progression free survival, and overall survival between the groups. Progression free survival and overall survival were determined by Cox regression.The groups were matched by Gleason score, pre-tx disease extent (limited-axial skeleton and/or nodal vs extensive- appendicular skeleton and/or visceral), ECOG PS, pre-tx risk category (favorable, intermediate, poor; Keizman, Oncologist 2012). Furthermore, they were balanced regarding median age (71 abi vs 69 keto), time from primary tx to disease relapse, time to progression on prior GnRH-a and antiandrogen, PSA response and time to progression on prior D, pre-tx pain score/alkaline phosphatase/hemoglobin/ neutrophil to lymphocyte ratio/PSADT/PSA. In the groups of abi vs keto, PSA response was 46% vs 19% (OR 4.4, p=0.043), median biochemical PFS 7 vs 2 months (HR 0.65, p=0.02), median radiological PFS 6 vs 2.5 months (HR 0.63, p=0.016), median overall survival 17 vs 12 months (HR 0.53, p=0.79), and tx interruption d/t adverse events 12% vs 23% (0R 0.6, p=0.023).In mCRPC refractory to D, the outcome of pts treated with abiraterone was superior to ketoconazole.


Joshua B.-Z.,Ben - Gurion University of the Negev | Sachs O.,Ben - Gurion University of the Negev | Shelef I.,Soroka University Medical Center | Vardy-Sion N.,Soroka University Medical Center | And 3 more authors.
Otolaryngology - Head and Neck Surgery (United States) | Year: 2013

Objectives. To evaluate bone changes demonstrated by computed tomography (CT) as a predictor of the severity of chronic rhinosinusitis. Study Design. Cross-sectional study. Settings. Tertiary referral university medical center. Subjects and Methods. Thirty-eight patients diagnosed with unilateral chronic maxillary sinusitis underwent endoscopic sinus surgery from 2003 to 2009. Preoperative CTs of all patients were reviewed by a single radiologist blinded to the pathologic diagnosis. Bone density was evaluated and expressed in Hounsfield units (HU). Sinus wall thickness (WT) was also measured and compared with the contralateral side. All the histopathologic specimens were reviewed. A database was constructed containing demographic data, clinical symptoms, CT measurements, and histopathologic findings. Results. Average age was 44.07 years, with 22 women (57.9%) and 16 men (42.1%). The average wall density (WD) was 828.7 HU, and no correlation was found between the density of the diseased maxillary sinus bony walls and the severity of the histopathologic inflammatory process of the soft tissue (P = .474). The average wall thickness of the diseased sinuses was 2.6 mm, and a correlation was found between inflammation severity and wall thickness (P = .018). Wall thickening was found in 97.3% of the cases and an increase in density in 78.9% without correlation between WD and WT. Conclusion. Wall thickness but not WD obtained from CT scans may be a simple index for evaluation of unilateral chronic rhinosinusitis and its severity. Further studies confirming these results and comparing them with clinical correlates are indicated. © American Academy of Otolaryngology-Head and Neck Surgery Foundation 2013.


Jacob T.,Ariel University | Shapira A.,Asaf Harofe Medical Center
Journal of Rehabilitation Medicine | Year: 2010

Objective: To evaluate the perceptions of health and quality of life among a group of polio survivors in Israel and to identify potential activities for improving their quality of life. Design: An observational study. Subjects: The sample consisted of 101 polio survivors who sought treatment at 2 post-polio clinics in Israel. The majority of participants were between the ages of 45 and 65 years, and approximately 25% were wheelchair-bound. Methods: Participants were invited to attend a seminar, where they were invited to complete a questionnaire on demographic variables, mobility, perceptions of and satisfaction with health status and quality of life, and the potential contribution of 16 activities to improve their quality of life. Results: Participants had low physical scores and normative mental scores. Mean scores on the Short-Form-12 questionnaire for physical and mental components were 32.9 and 50.3, respectively. Approximately 70% expressed the belief that exposure to up-to-date information about post-polio, as well as participation in social activities, might improve their quality of life. Conclusion: Information about the physical and mental components of polio survivors, as well as the desire to partake in specific activities for polio survivors, may serve as a basis for the operations and prioritization of service providers © 2010 Foundation of Rehabilitation Information.


PubMed | Asaf Harofe Medical Center and Tel Aviv University
Type: Journal Article | Journal: Journal of the American Academy of Audiology | Year: 2016

Increased metabolism in the left auditory cortex has been reported in tinnitus patients. However, gender difference has not been addressed.To assess the differences in Positron emission tomography-computed tomography (PET-CT) results between the genders in tinnitus patients.Retrospective cohort.Included were patients referred to our clinic between January 2011 and August 2013 who complained of tinnitus and underwent fluorodeoxyglucose (FDG)-PET to assess brain metabolism.Univariate and multivariate nominal logistic regressions were used to evaluate the association between upper temporal gyrus (UTG; right and left) and gender.Included were 140 patients (87 males) with an average age of 52.5 yr (median = 53.1). Bilateral tinnitus was found in 85 patients (60.7%), left sided in 30 (21.4%), and right sided in 21(15%). Increased uptake in the UTG was found in 60% of the patients on either side. Males had a statistically significant increased uptake in the UTG in those with unilateral tinnitus and in the entire population.We present the largest study reported so far on tinnitus patients who have undergone FDG-PET-CT. We found a statistically significant difference between the genders in FDG uptake by the UTG. Further investigations should be undertaken to reveal the etiologies for these differences and to assess different therapeutic protocols according to gender.

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