The Israeli Society for Clinical Oncology and Radiotherapy requested that experts in breast cance... more The Israeli Society for Clinical Oncology and Radiotherapy requested that experts in breast cancer therapy assess the Society's policy regarding the use of hormone replacement therapy (HRT) in breast cancer survivors. The following recommendations are based on updated literature, which is limited since it summarizes only retrospective data. There is currently no evidence of an increased risk of breast cancer recurrence, death attributable to cancer, or overall mortality among breast cancer survivors who use HRT. We therefore recommend that there is no need to avoid HRT in women with menopausal symptoms who are interested in receiving such treatment, as long as ovarian ablation does not play a major role in their adjuvant therapy. Women should be informed about the limitations of available data. There are some concerns regarding the use of HRT in patients whose tumors developed while undergoing HRT and in such cases treatment should be reserved only for those with severe menopausal symptoms. For women with milder symptoms or those who are not interested in HRT, other treatment options should be outlined. The policy should be updated according to future publication of results from ongoing randomized prospective studies.
American Journal of Clinical Oncology, Feb 1, 1999
A phase II study of carboplatin and etoposide as salvage polychemotherapy in metastatic, infiltra... more A phase II study of carboplatin and etoposide as salvage polychemotherapy in metastatic, infiltrating breast carcinoma was carried out with 25 multiply pretreated patients. Six of 25 patients (24%) had a partial response that lasted an average of 3.5 months; of the six responders, four had undergone either four or five previous chemotherapeutic treatments. Eight of 25 patients (32%) had stable disease, and 11 (44%) manifested disease progression. The median survival from time of entry to the salvage protocol was 8 months. There were treatment responses in lung, chest wall, liver, and skeleton. The most common side effects were leukopenia (68% of 25 patients), thrombocytopenia (56%), anemia (40%), fever (28%), and weakness (16%). Carboplatin combined with etoposide may be an effective and tolerable salvage regimen in advanced breast cancer.
International Journal of Occupational and Environmental Health, Oct 1, 1999
Three cases of fatal extrapulmonary neoplasms among asbestos-exposed power plant workers are desc... more Three cases of fatal extrapulmonary neoplasms among asbestos-exposed power plant workers are described. These cases add to the growing evidence for a causal relationship between asbestos exposures and extrapulmonary neoplasms.
Purpose: Diarrhea (with or without colitis) is an immune-related adverse event (irAE) associated ... more Purpose: Diarrhea (with or without colitis) is an immune-related adverse event (irAE) associated with ipilimumab. A randomized, double-blind, placebo-controlled, multicenter, multinational phase II trial was conducted to determine whether prophylactic budesonide (Entocort EC), a nonabsorbed oral steroid, reduced the rate of grade ≥2 diarrhea in ipilimumab-treated patients with advanced melanoma.Experimental Design: Previously treated and treatment-naïve patients (N = 115) with unresectable stage III or IV melanoma received open-label ipilimumab (10 mg/kg every 3 weeks for four doses) with daily blinded budesonide (group A) or placebo (group B) through week 16. The first scheduled tumor evaluation was at week 12; eligible patients received maintenance treatment starting at week 24. Diarrhea was assessed using Common Terminology Criteria for Adverse Events (CTCAE) 3.0. Patients kept a diary describing their bowel habits.Results: Budesonide did not affect the rate of grade ≥2 diarrhea, which occurred in 32.7% and 35.0% of patients in groups A and B, respectively. There were no bowel perforations or treatment-related deaths. Best overall response rates were 12.1% in group A and 15.8% in group B, with a median overall survival of 17.7 and 19.3 months, respectively. Within each group, the disease control rate was higher in patients with grade 3 to 4 irAEs than in patients with grade 0 to 2 irAEs, although many patients with grade 1 to 2 irAEs experienced clinical benefit. Novel patterns of response to ipilimumab were observed.Conclusions: Ipilimumab shows activity in advanced melanoma, with encouraging survival and manageable adverse events. Budesonide should not be used prophylactically for grade ≥2 diarrhea associated with ipilimumab therapy. (Clin Cancer Res 2009;15(17):5591–8)
5141 Background: Five years survival of patients with advanced epithelial ovarian cancer (EOC) is... more 5141 Background: Five years survival of patients with advanced epithelial ovarian cancer (EOC) is 25-40% and once the disease recurs, treatment is mainly palliative. We would like to give that treatment with the longest time to progression (TTP) together with the best quality of life. Our objectives in this study were to evaluate the safety and to determine the TTP of monotherapy Gemcitabine in heavily pretreated patients with recurrent or persistent EOC. METHODS nineteen heavily pretreated patients with recurrent or persistent EOC were treated with single agent Gemcitabine during 1995-2003 in the Oncology Division in Tel Aviv Sourasky Medical Center. Fifteen of them were retrospectively evaluated (4 had died and received the drug for =< 1.5 months - less than two cycles). All patients were previously treated with cisplatin combinations and had received a median of 3 prior chemotherapy regimens (range 2-6). Seven (47%) patients were considered platinum sensitive and 8(53%) platinum resistant. Median age was 64(43-78) years. Protocol schedule was Gemcitabine 1000mg/m2 over one hour administration days 1, 8 and 15 every 28 days. RESULTS Fifteen patients are evaluable for response by CA-125 reduction or stability and clinical improvement (pain, ascites etc). Patients were not on preplanned protocols and for that, follow-up CT's were not done routinely. Clinical benefit (PR or SD by CA-125 and symptom relief) was noted in 12 out of 15(80%) patients. Median TTP was 4 months (range 2-14). Median OS was 6 months (range 3-28) and 5 patients are still alive. Toxicities: Grade III-IV toxicity was found in 4(27%) patients with anemia, 4(27%) with thrombocytopenia, 1(6%) with fatigue and 2(13%) with leg edema. CONCLUSIONS Gemcitabine is an active drug in heavily pretreated patients with EOC and has a very favorable toxicity profile. It's use as a monotherapy and in combination with platinum salts drugs should be studied. No significant financial relationships to disclose.
Background. There is an urgent need to develop new treatment strategies and drugs for pancreatic ... more Background. There is an urgent need to develop new treatment strategies and drugs for pancreatic cancer that is highly resistant to radio-chemotherapy. Aesculus hippocastanum (the horse chestnut) known in Chinese medicine as a plant with anti-inflammatory, antiedema, antianalgesic, and antipyretic activities. The main active compound of this plant is Escin (C54H84O23). Objective. To evaluate the effect of Escin alone and combined with chemotherapy on pancreatic cancer cell survival and to unravel mechanism(s) of Escin anticancer activity. Methods. Cell survival was measured by XTT colorimetric assay. Synergistic effect of combined therapy was determined by CalcuSyn software. Cell cycle and induction of apoptosis were evaluated by FACS analysis. Expression of NF- κ B-related proteins (p65, I κ Bα, and p-I κ Bα) and cyclin D was evaluated by western blot analysis. Results. Escin decreased the survival of pancreatic cancer cells with IC50 = 10-20 M. Escin combined with gemcitabine show...
The Israel Medical Association journal : IMAJ, 2008
Over 75% of postmenopausal patients with metastatic breast cancer have hormone receptor-positive ... more Over 75% of postmenopausal patients with metastatic breast cancer have hormone receptor-positive tumors. Endocrine therapy, with its more favorable toxicity profile than chemotherapy, is the preferred treatment modality for these patients. To assess our experience with fulvestrant, an antiestrogen, in an advanced phase of treatment, after progression on the classical anti-estrogen (tamoxifen) and aromatase inhibitors The study group comprised 46 patients with metastatic breast cancer treated with fulvestrant during the years 2002-2006. Fulvestrant was given monthly until disease progression or unacceptable toxicity. The median number of fulvestrant cycles was 4.14 (range 1-32). Four patients are still on the treatment. The reasons for treatment discontinuation include disease progression (n=40), refusal (n=1), and allergic reaction (n=1). Ten patients (22%) achieved partial response and 22 (47%) had stable disease. Fourteen (30%) had disease progression with a response rate of 22% a...
This work presents survival data of 42 melanoma patients at high risk for disease recurrence who ... more This work presents survival data of 42 melanoma patients at high risk for disease recurrence who received an allogeneic melanoma vaccine composed of three cell lines, each matching at least one allele of the recipient's human leukocyte antigen (HLA)‐A and ‐B loci. The 5‐year overall survival (OS) rate and disease‐free survival (DFS) compared favorably with the standard interferon‐α regimen. Interestingly, patients bearing HLA‐B35 had significantly better OS and DFS (OS of 100% and DFS of 90% for HLA‐B35 vs 56% and 23%, for the non‐B35 patients). In contrast, patients expressing HLA‐B07 did not fare well with the vaccine. Although the data include a relatively small cohort of patients, it strongly hints toward a correlation between HLA types and potential benefit from anticancer immunotherapy.
American Journal of Clinical Oncology, Oct 1, 2002
A multicenter phase III randomized study comparing the efficacies of two adjuvant polychemotherap... more A multicenter phase III randomized study comparing the efficacies of two adjuvant polychemotherapeutic regimens in 145 patients with stage II node-positive breast cancer: the standard chemotherapy combination, CMF (cyclophosphamide, methotrexate, 5-fluorouracil), and an experimental protocol, CNF (cyclophosphamide, mitoxantrone [Novantrone], 5-fluorouracil) in which mitoxantrone replaced methotrexate. The finding of a significant advantage (p ϭ 0.04) in the disease-free survival for those receiving mitoxantrone (mean survival 4.4 years for CNF versus 2.7 years for CMF) led the authors to break the data down in subpopulations to determine exactly which groups of women responded more favorably to CNF than CMF. An advantage in disease-free survival was found, most notable in four subgroups: Sephardic women, women less than 45 years of age, premenopausal women, and women with 4 to 10 positive axillary lymph nodes. Although the small numbers of women in each of these subgroups rule out drawing definitive conclusions, the trend merits further study to confirm these observations.
Disagreement persists on the necessity of axillary lymph node dissection for small T1 stage unila... more Disagreement persists on the necessity of axillary lymph node dissection for small T1 stage unilateral breast cancers. In this study of 120 women with T1 primary tumors who underwent extensive dissection, better de nition of pathological factors that can predict axillary node metastases might have spared 88 (73.3%) who were node negative. We assessed age, tumor size, histology, grade and hormone receptor status as possible indicators of lymph node involvement. As expected, tumor size was a strong predictor of the likelihood of node involvement (p ¾ 0.026 in univariate and p ¾ 0.0024 in multivariate analyses). Progesterone receptor status also correlated signi cantly (p ¾ 0.0008 in univariate and p ¾ 0.017 in multivariate analyses) with axillary positivity. Tumor grade was found to be signi cant (p ¾ 0.018) only in univariate analysis. These ndings contribute to the ongoing search for con dent selection of subgroups of patients who will undergo lumpectomy but can safely be spared axillary node dissection.
Many bacterial strains exhibit beautiful branching patterns during colonial development. Much eff... more Many bacterial strains exhibit beautiful branching patterns during colonial development. Much effort is devoted to the search for basic principles of self-organization (growth, communication, regulation and control) on the cellular and multi-cellular levels. Our approach is to use the successful conceptual framework for branching growth patterns in non-living systems as a tool to understand their significantly more complex biological counterparts.
To assess activity and toxicity of gemcitabine treatment in heavily pretreated epithelial ovarian... more To assess activity and toxicity of gemcitabine treatment in heavily pretreated epithelial ovarian cancer (EOC) patients and compare the outcome between platinum-sensitive and platinum-resistant patients. We conducted a retrospective analysis of 43 women with EOC treated with gemcitabine on Days 1, 8 and 15 every 28 days. Response was evaluated by physical examination and serial CA 125 measurements. The patients (median age 62 years, range 29-87) were previously exposed to a median of 3 (2-8) chemotherapy regimens. A median of 3.5 (1-14) gemcitabine cycles were administered. Eleven (25.6%) patients showed partial response, 19 (44.2%) had stable disease and 13 (30.2%) progressed. Among 22 platinum-sensitive and 21 platinum-resistant patients, the response rate was 45.5% and 4.7% respectively (p = 0.001), and the median time to progression was 5.0 and 2.8 months, respectively (p = 0.0006). The respective median survival was 16.5 and 6.3 months (p = 0.0001). Grade III-IV hematological toxicities included anemia in four (9.3%) patients, thrombocytopenia in four (9.3%) and leucopenia in two (4.7%). The main non-hematological toxicities were grade III fatigue in two patients (4.7%) and nausea and vomiting in two (4.7%). Single agent gemcitabine is an attractive option for heavily pretreated EOC patients. The significant difference between platinum-sensitive and resistant patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; warrants further investigation.
Brain Metastasis from Prostate Carcinoma Antemortem Recognition and Outcome after Treatment W e r... more Brain Metastasis from Prostate Carcinoma Antemortem Recognition and Outcome after Treatment W e read with interest the article on brain metastasis from prostate carcinoma (CaP) by McCutcheon et al. 1 published in Cancer. For the benefit of the readers, we would like to update and refine the data regarding solitary brain metastasis from CaP. Using the MEDLINE database, we reviewed the data concerning brain metastasis and prostate carcinoma in living patients from 1960 to 1999. We excluded patients who lacked a negative metastatic survey and a brain biopsy consistent with CaP. We found a total of eight patients who met our criteria. Sites of single metastasis included pons alone (one patient), pons at the cerebellar-pontine angle (one patient), pons and cerebral peduncle (one patient), pons and cerebellar peduncle (one patient), pons and midbrain (one patient), the parietal lobe (one patient), the temporal lobe (one patient), and the frontoparietal lobe (one patient). Brain biopsy yielded seven patients with CaP and one patient with papillary adenocarcinoma. Brain histology included poorly differentiated (two patients), moderately differentiated (one patient), and well differentiated (four patients) CaP. The rate of incidence of brain metastasis from CaP in the recent study by McCutcheon et al. was 0.7%. 1 One study proposes four reasons for the low incidence rate of clinically suspect solitary brain metastasis from CaP: 1) lower detection rate of tumor spread to brain (even in autopsy data), 2) late occurrence of brain involvement in the course of the disease, 3) clinically silent growth related to the most common site of tumor involvement, and 4) rare and nonspecific symptoms due to brain metastasis from CaP. 2,3 Another hypothesis for the rarity of solitary brain metastases in patients with CaP is that the brain parenchyma does not represent "fertile soil" for CaP cells, just as, conversely, the skeleton provides a preferential milieu for these cells. 4 We believe our review shows the highest percentage of prostate metastasis to the pons Ϯ cerebrum, cerebellum, and midbrain reported to date. McCutcheon et al.'s large series included only three patients who had metastatic disease solely to the brain. One patient had metastases specifically to the hypothalamus and the right temporal lobe. The other two patients had multiple frontal metastases. Their review also included seven additional patients who presented with a solitary brain metastasis. To our knowledge the study by Gupta et al. was the only analysis that met the criteria for our study. 5 The number of solitary brain metastasis from CaP may indeed be higher than previously thought. McCutcheon et al. were correct to speculate that given the obscuring effect of bone artifact in the posterior fossa on computed tomography (CT) scans of the brain, tumor in this location actually may be underreported when CT is the primary method used. The fact that magnetic resonance imaging diagnosed all the patients with a solitary brain metastasis to the pons lends support to their theory.
... 7. Shojaei F, et al Cancer Res. ... Taiwan University Hospital, Taipei), WC Su (National Chen... more ... 7. Shojaei F, et al Cancer Res. ... Taiwan University Hospital, Taipei), WC Su (National Cheng Kung University Hospital, Tainan), CJ Tsao (Chi Mei Hospital, Yung-Kang City), TS Yang (Chang Gung Memorial Hospital LinKou, Tao-Yuan) US: H Burris (Sarah Cannon Research ...
European Journal of Integrative Medicine, Dec 1, 2013
Introduction: "The work" meditation technique was developed by Byron Katie in 1986 and has been p... more Introduction: "The work" meditation technique was developed by Byron Katie in 1986 and has been practiced worldwide. To date, there has been no empirical evaluation of its efficacy among cancer survivors. Cancer diagnoses and treatments may have short and long term negative effects on individuals' health status and wellbeing. This study assessed the feasibility and effectiveness of "The work" meditative technique in improving psychological and physical wellbeing in breast cancer survivors. Methods: Twenty-nine breast cancer survivors participated in a prospective pilot clinical trial of "The work" intervention. Sleep quality, level of fatigue and breast cancer health-related quality of life assessment was conducted before and after the intervention. The intervention consisted of 12 weekly 3.5 h group sessions in addition to individual practice for a minimum of 60 min per week. Results: A total of 24 women (82.75%) completed the program with no adverse effects reported at any time suggesting that the technique can be implemented in this population of survivors of breast cancer. Sleep quality, levels of fatigue as well as physical, social, familial, emotional and functional wellbeing improved significantly after the intervention. The sense of coherence scores were not affected by the intervention. Conclusions: The physical and mental health of these breast cancer survivors was improved after the practice of "The work" meditation technique. The encouraging results of this pilot study highlight the potentially beneficial effects of this intervention for this population and warrant further investigation in randomized controlled trials.
The Israeli Society for Clinical Oncology and Radiotherapy requested that experts in breast cance... more The Israeli Society for Clinical Oncology and Radiotherapy requested that experts in breast cancer therapy assess the Society's policy regarding the use of hormone replacement therapy (HRT) in breast cancer survivors. The following recommendations are based on updated literature, which is limited since it summarizes only retrospective data. There is currently no evidence of an increased risk of breast cancer recurrence, death attributable to cancer, or overall mortality among breast cancer survivors who use HRT. We therefore recommend that there is no need to avoid HRT in women with menopausal symptoms who are interested in receiving such treatment, as long as ovarian ablation does not play a major role in their adjuvant therapy. Women should be informed about the limitations of available data. There are some concerns regarding the use of HRT in patients whose tumors developed while undergoing HRT and in such cases treatment should be reserved only for those with severe menopausal symptoms. For women with milder symptoms or those who are not interested in HRT, other treatment options should be outlined. The policy should be updated according to future publication of results from ongoing randomized prospective studies.
American Journal of Clinical Oncology, Feb 1, 1999
A phase II study of carboplatin and etoposide as salvage polychemotherapy in metastatic, infiltra... more A phase II study of carboplatin and etoposide as salvage polychemotherapy in metastatic, infiltrating breast carcinoma was carried out with 25 multiply pretreated patients. Six of 25 patients (24%) had a partial response that lasted an average of 3.5 months; of the six responders, four had undergone either four or five previous chemotherapeutic treatments. Eight of 25 patients (32%) had stable disease, and 11 (44%) manifested disease progression. The median survival from time of entry to the salvage protocol was 8 months. There were treatment responses in lung, chest wall, liver, and skeleton. The most common side effects were leukopenia (68% of 25 patients), thrombocytopenia (56%), anemia (40%), fever (28%), and weakness (16%). Carboplatin combined with etoposide may be an effective and tolerable salvage regimen in advanced breast cancer.
International Journal of Occupational and Environmental Health, Oct 1, 1999
Three cases of fatal extrapulmonary neoplasms among asbestos-exposed power plant workers are desc... more Three cases of fatal extrapulmonary neoplasms among asbestos-exposed power plant workers are described. These cases add to the growing evidence for a causal relationship between asbestos exposures and extrapulmonary neoplasms.
Purpose: Diarrhea (with or without colitis) is an immune-related adverse event (irAE) associated ... more Purpose: Diarrhea (with or without colitis) is an immune-related adverse event (irAE) associated with ipilimumab. A randomized, double-blind, placebo-controlled, multicenter, multinational phase II trial was conducted to determine whether prophylactic budesonide (Entocort EC), a nonabsorbed oral steroid, reduced the rate of grade ≥2 diarrhea in ipilimumab-treated patients with advanced melanoma.Experimental Design: Previously treated and treatment-naïve patients (N = 115) with unresectable stage III or IV melanoma received open-label ipilimumab (10 mg/kg every 3 weeks for four doses) with daily blinded budesonide (group A) or placebo (group B) through week 16. The first scheduled tumor evaluation was at week 12; eligible patients received maintenance treatment starting at week 24. Diarrhea was assessed using Common Terminology Criteria for Adverse Events (CTCAE) 3.0. Patients kept a diary describing their bowel habits.Results: Budesonide did not affect the rate of grade ≥2 diarrhea, which occurred in 32.7% and 35.0% of patients in groups A and B, respectively. There were no bowel perforations or treatment-related deaths. Best overall response rates were 12.1% in group A and 15.8% in group B, with a median overall survival of 17.7 and 19.3 months, respectively. Within each group, the disease control rate was higher in patients with grade 3 to 4 irAEs than in patients with grade 0 to 2 irAEs, although many patients with grade 1 to 2 irAEs experienced clinical benefit. Novel patterns of response to ipilimumab were observed.Conclusions: Ipilimumab shows activity in advanced melanoma, with encouraging survival and manageable adverse events. Budesonide should not be used prophylactically for grade ≥2 diarrhea associated with ipilimumab therapy. (Clin Cancer Res 2009;15(17):5591–8)
5141 Background: Five years survival of patients with advanced epithelial ovarian cancer (EOC) is... more 5141 Background: Five years survival of patients with advanced epithelial ovarian cancer (EOC) is 25-40% and once the disease recurs, treatment is mainly palliative. We would like to give that treatment with the longest time to progression (TTP) together with the best quality of life. Our objectives in this study were to evaluate the safety and to determine the TTP of monotherapy Gemcitabine in heavily pretreated patients with recurrent or persistent EOC. METHODS nineteen heavily pretreated patients with recurrent or persistent EOC were treated with single agent Gemcitabine during 1995-2003 in the Oncology Division in Tel Aviv Sourasky Medical Center. Fifteen of them were retrospectively evaluated (4 had died and received the drug for =< 1.5 months - less than two cycles). All patients were previously treated with cisplatin combinations and had received a median of 3 prior chemotherapy regimens (range 2-6). Seven (47%) patients were considered platinum sensitive and 8(53%) platinum resistant. Median age was 64(43-78) years. Protocol schedule was Gemcitabine 1000mg/m2 over one hour administration days 1, 8 and 15 every 28 days. RESULTS Fifteen patients are evaluable for response by CA-125 reduction or stability and clinical improvement (pain, ascites etc). Patients were not on preplanned protocols and for that, follow-up CT's were not done routinely. Clinical benefit (PR or SD by CA-125 and symptom relief) was noted in 12 out of 15(80%) patients. Median TTP was 4 months (range 2-14). Median OS was 6 months (range 3-28) and 5 patients are still alive. Toxicities: Grade III-IV toxicity was found in 4(27%) patients with anemia, 4(27%) with thrombocytopenia, 1(6%) with fatigue and 2(13%) with leg edema. CONCLUSIONS Gemcitabine is an active drug in heavily pretreated patients with EOC and has a very favorable toxicity profile. It's use as a monotherapy and in combination with platinum salts drugs should be studied. No significant financial relationships to disclose.
Background. There is an urgent need to develop new treatment strategies and drugs for pancreatic ... more Background. There is an urgent need to develop new treatment strategies and drugs for pancreatic cancer that is highly resistant to radio-chemotherapy. Aesculus hippocastanum (the horse chestnut) known in Chinese medicine as a plant with anti-inflammatory, antiedema, antianalgesic, and antipyretic activities. The main active compound of this plant is Escin (C54H84O23). Objective. To evaluate the effect of Escin alone and combined with chemotherapy on pancreatic cancer cell survival and to unravel mechanism(s) of Escin anticancer activity. Methods. Cell survival was measured by XTT colorimetric assay. Synergistic effect of combined therapy was determined by CalcuSyn software. Cell cycle and induction of apoptosis were evaluated by FACS analysis. Expression of NF- κ B-related proteins (p65, I κ Bα, and p-I κ Bα) and cyclin D was evaluated by western blot analysis. Results. Escin decreased the survival of pancreatic cancer cells with IC50 = 10-20 M. Escin combined with gemcitabine show...
The Israel Medical Association journal : IMAJ, 2008
Over 75% of postmenopausal patients with metastatic breast cancer have hormone receptor-positive ... more Over 75% of postmenopausal patients with metastatic breast cancer have hormone receptor-positive tumors. Endocrine therapy, with its more favorable toxicity profile than chemotherapy, is the preferred treatment modality for these patients. To assess our experience with fulvestrant, an antiestrogen, in an advanced phase of treatment, after progression on the classical anti-estrogen (tamoxifen) and aromatase inhibitors The study group comprised 46 patients with metastatic breast cancer treated with fulvestrant during the years 2002-2006. Fulvestrant was given monthly until disease progression or unacceptable toxicity. The median number of fulvestrant cycles was 4.14 (range 1-32). Four patients are still on the treatment. The reasons for treatment discontinuation include disease progression (n=40), refusal (n=1), and allergic reaction (n=1). Ten patients (22%) achieved partial response and 22 (47%) had stable disease. Fourteen (30%) had disease progression with a response rate of 22% a...
This work presents survival data of 42 melanoma patients at high risk for disease recurrence who ... more This work presents survival data of 42 melanoma patients at high risk for disease recurrence who received an allogeneic melanoma vaccine composed of three cell lines, each matching at least one allele of the recipient's human leukocyte antigen (HLA)‐A and ‐B loci. The 5‐year overall survival (OS) rate and disease‐free survival (DFS) compared favorably with the standard interferon‐α regimen. Interestingly, patients bearing HLA‐B35 had significantly better OS and DFS (OS of 100% and DFS of 90% for HLA‐B35 vs 56% and 23%, for the non‐B35 patients). In contrast, patients expressing HLA‐B07 did not fare well with the vaccine. Although the data include a relatively small cohort of patients, it strongly hints toward a correlation between HLA types and potential benefit from anticancer immunotherapy.
American Journal of Clinical Oncology, Oct 1, 2002
A multicenter phase III randomized study comparing the efficacies of two adjuvant polychemotherap... more A multicenter phase III randomized study comparing the efficacies of two adjuvant polychemotherapeutic regimens in 145 patients with stage II node-positive breast cancer: the standard chemotherapy combination, CMF (cyclophosphamide, methotrexate, 5-fluorouracil), and an experimental protocol, CNF (cyclophosphamide, mitoxantrone [Novantrone], 5-fluorouracil) in which mitoxantrone replaced methotrexate. The finding of a significant advantage (p ϭ 0.04) in the disease-free survival for those receiving mitoxantrone (mean survival 4.4 years for CNF versus 2.7 years for CMF) led the authors to break the data down in subpopulations to determine exactly which groups of women responded more favorably to CNF than CMF. An advantage in disease-free survival was found, most notable in four subgroups: Sephardic women, women less than 45 years of age, premenopausal women, and women with 4 to 10 positive axillary lymph nodes. Although the small numbers of women in each of these subgroups rule out drawing definitive conclusions, the trend merits further study to confirm these observations.
Disagreement persists on the necessity of axillary lymph node dissection for small T1 stage unila... more Disagreement persists on the necessity of axillary lymph node dissection for small T1 stage unilateral breast cancers. In this study of 120 women with T1 primary tumors who underwent extensive dissection, better de nition of pathological factors that can predict axillary node metastases might have spared 88 (73.3%) who were node negative. We assessed age, tumor size, histology, grade and hormone receptor status as possible indicators of lymph node involvement. As expected, tumor size was a strong predictor of the likelihood of node involvement (p ¾ 0.026 in univariate and p ¾ 0.0024 in multivariate analyses). Progesterone receptor status also correlated signi cantly (p ¾ 0.0008 in univariate and p ¾ 0.017 in multivariate analyses) with axillary positivity. Tumor grade was found to be signi cant (p ¾ 0.018) only in univariate analysis. These ndings contribute to the ongoing search for con dent selection of subgroups of patients who will undergo lumpectomy but can safely be spared axillary node dissection.
Many bacterial strains exhibit beautiful branching patterns during colonial development. Much eff... more Many bacterial strains exhibit beautiful branching patterns during colonial development. Much effort is devoted to the search for basic principles of self-organization (growth, communication, regulation and control) on the cellular and multi-cellular levels. Our approach is to use the successful conceptual framework for branching growth patterns in non-living systems as a tool to understand their significantly more complex biological counterparts.
To assess activity and toxicity of gemcitabine treatment in heavily pretreated epithelial ovarian... more To assess activity and toxicity of gemcitabine treatment in heavily pretreated epithelial ovarian cancer (EOC) patients and compare the outcome between platinum-sensitive and platinum-resistant patients. We conducted a retrospective analysis of 43 women with EOC treated with gemcitabine on Days 1, 8 and 15 every 28 days. Response was evaluated by physical examination and serial CA 125 measurements. The patients (median age 62 years, range 29-87) were previously exposed to a median of 3 (2-8) chemotherapy regimens. A median of 3.5 (1-14) gemcitabine cycles were administered. Eleven (25.6%) patients showed partial response, 19 (44.2%) had stable disease and 13 (30.2%) progressed. Among 22 platinum-sensitive and 21 platinum-resistant patients, the response rate was 45.5% and 4.7% respectively (p = 0.001), and the median time to progression was 5.0 and 2.8 months, respectively (p = 0.0006). The respective median survival was 16.5 and 6.3 months (p = 0.0001). Grade III-IV hematological toxicities included anemia in four (9.3%) patients, thrombocytopenia in four (9.3%) and leucopenia in two (4.7%). The main non-hematological toxicities were grade III fatigue in two patients (4.7%) and nausea and vomiting in two (4.7%). Single agent gemcitabine is an attractive option for heavily pretreated EOC patients. The significant difference between platinum-sensitive and resistant patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; warrants further investigation.
Brain Metastasis from Prostate Carcinoma Antemortem Recognition and Outcome after Treatment W e r... more Brain Metastasis from Prostate Carcinoma Antemortem Recognition and Outcome after Treatment W e read with interest the article on brain metastasis from prostate carcinoma (CaP) by McCutcheon et al. 1 published in Cancer. For the benefit of the readers, we would like to update and refine the data regarding solitary brain metastasis from CaP. Using the MEDLINE database, we reviewed the data concerning brain metastasis and prostate carcinoma in living patients from 1960 to 1999. We excluded patients who lacked a negative metastatic survey and a brain biopsy consistent with CaP. We found a total of eight patients who met our criteria. Sites of single metastasis included pons alone (one patient), pons at the cerebellar-pontine angle (one patient), pons and cerebral peduncle (one patient), pons and cerebellar peduncle (one patient), pons and midbrain (one patient), the parietal lobe (one patient), the temporal lobe (one patient), and the frontoparietal lobe (one patient). Brain biopsy yielded seven patients with CaP and one patient with papillary adenocarcinoma. Brain histology included poorly differentiated (two patients), moderately differentiated (one patient), and well differentiated (four patients) CaP. The rate of incidence of brain metastasis from CaP in the recent study by McCutcheon et al. was 0.7%. 1 One study proposes four reasons for the low incidence rate of clinically suspect solitary brain metastasis from CaP: 1) lower detection rate of tumor spread to brain (even in autopsy data), 2) late occurrence of brain involvement in the course of the disease, 3) clinically silent growth related to the most common site of tumor involvement, and 4) rare and nonspecific symptoms due to brain metastasis from CaP. 2,3 Another hypothesis for the rarity of solitary brain metastases in patients with CaP is that the brain parenchyma does not represent "fertile soil" for CaP cells, just as, conversely, the skeleton provides a preferential milieu for these cells. 4 We believe our review shows the highest percentage of prostate metastasis to the pons Ϯ cerebrum, cerebellum, and midbrain reported to date. McCutcheon et al.'s large series included only three patients who had metastatic disease solely to the brain. One patient had metastases specifically to the hypothalamus and the right temporal lobe. The other two patients had multiple frontal metastases. Their review also included seven additional patients who presented with a solitary brain metastasis. To our knowledge the study by Gupta et al. was the only analysis that met the criteria for our study. 5 The number of solitary brain metastasis from CaP may indeed be higher than previously thought. McCutcheon et al. were correct to speculate that given the obscuring effect of bone artifact in the posterior fossa on computed tomography (CT) scans of the brain, tumor in this location actually may be underreported when CT is the primary method used. The fact that magnetic resonance imaging diagnosed all the patients with a solitary brain metastasis to the pons lends support to their theory.
... 7. Shojaei F, et al Cancer Res. ... Taiwan University Hospital, Taipei), WC Su (National Chen... more ... 7. Shojaei F, et al Cancer Res. ... Taiwan University Hospital, Taipei), WC Su (National Cheng Kung University Hospital, Tainan), CJ Tsao (Chi Mei Hospital, Yung-Kang City), TS Yang (Chang Gung Memorial Hospital LinKou, Tao-Yuan) US: H Burris (Sarah Cannon Research ...
European Journal of Integrative Medicine, Dec 1, 2013
Introduction: "The work" meditation technique was developed by Byron Katie in 1986 and has been p... more Introduction: "The work" meditation technique was developed by Byron Katie in 1986 and has been practiced worldwide. To date, there has been no empirical evaluation of its efficacy among cancer survivors. Cancer diagnoses and treatments may have short and long term negative effects on individuals' health status and wellbeing. This study assessed the feasibility and effectiveness of "The work" meditative technique in improving psychological and physical wellbeing in breast cancer survivors. Methods: Twenty-nine breast cancer survivors participated in a prospective pilot clinical trial of "The work" intervention. Sleep quality, level of fatigue and breast cancer health-related quality of life assessment was conducted before and after the intervention. The intervention consisted of 12 weekly 3.5 h group sessions in addition to individual practice for a minimum of 60 min per week. Results: A total of 24 women (82.75%) completed the program with no adverse effects reported at any time suggesting that the technique can be implemented in this population of survivors of breast cancer. Sleep quality, levels of fatigue as well as physical, social, familial, emotional and functional wellbeing improved significantly after the intervention. The sense of coherence scores were not affected by the intervention. Conclusions: The physical and mental health of these breast cancer survivors was improved after the practice of "The work" meditation technique. The encouraging results of this pilot study highlight the potentially beneficial effects of this intervention for this population and warrant further investigation in randomized controlled trials.
Uploads
Papers by Ilan Ron