Arie Figer - Academia.edu (original) (raw)

Papers by Arie Figer

Annals of Oncology, 2009

Background: Alkaline phosphatase (ALP) is a strong prognostic factor in patients with metastatic ... more Background: Alkaline phosphatase (ALP) is a strong prognostic factor in patients with metastatic colorectal cancer (MCRC). Patients with ALP more than three times the upper limit of normal (ULN) were excluded from our previous studies evaluating chemotherapy. An exploratory cohort of patients with ALP >3 ULN was included in the OPTIMOX1 study. Patients and methods: Previously untreated patients with MCRC were randomized to FOLFOX4 until progression (arm A) or FOLFOX7 for six cycles, maintenance without oxaliplatin for 12 cycles and reintroduction of FOLFOX7 (arm B). Patients were stratified according to ALP level £3 ULN versus 3-5 ULN. Results: Among the 620 patients in OPTIMOX1 study, 63 had ALP 3-5 ULN; 33 in arm A and 30 in arm B. The response rate in these patients was 56% versus 59% in patients with ALP £3 ULN. Median progression-free survival and overall survival were, respectively, 6.4 and 11.5 months in patients with ALP 3-5 ULN and 9.0 and 21.1 months in patients with ALP £3 ULN. Thirty-three percent of the patients in the cohort experienced grade 3/4 toxicity. Conclusion: Both FOLFOX regimens achieved high tumor response rates and offer good palliation in MCRC patients with a poor prognosis.

Genetic Testing, Jun 1, 2001

ABSTRACT A missense mutation within the APC gene, I1307K, was described in Ashkenazi individuals ... more ABSTRACT A missense mutation within the APC gene, I1307K, was described in Ashkenazi individuals at risk for colorectal cancer (CRC) and in the general population. The anecdotal reporting of the occurrence of this mutation in some non-Ashkenazi individuals led us to hypothesize that within the Jewish people, the I1307K polymorphism may reflect a founder mutation, and that the mutation is not restricted to ethnic Ashkenazis. To test that notion, and to establish the occurrence rate of the I1307K polymorphism in non-Ashkenazi Jewish populations, we screened Iraqi and Moroccan Jews and consecutive Jewish CRC patients and performed haplotype analysis with APC-linked markers in two I1307K carrier families. We analyzed Jewish individuals: 210 Moroccans, 160 Iraqis, 148 Ashkenazi, and 349 CRC patients (227 Ashkenazi and 122 non-Ashkenazi). The mutation detection scheme included PCR followed by denaturing gradient gel electrophoresis (DGGE) or modified restriction analysis (MRA). Haplotypes were assessed using three intragenic and three flanking markers. The I1307K polymorphism was detected in 29/227 Ashkenazi (12.8%), 2/122 (1.6%) non-Ashkenazi CRC patients, and in 2 individuals each (approximately 1%) within the Moroccan and Iraqi populations. Allelic pattern analysis in all our I1307K carriers, revealed a common haplotype for the three intragenic markers tested, in all mutation carriers, regardless of ethnic origin. The I1307K polymorphism, therefore, exists in all ethnic Jewish populations: Ashkenazi and non-Ashkenazi, with or without colon cancer. Jewish I1307K mutation carriers share a common allelic pattern with APC-linked markers. This strongly supports the notion of a founder mutation for I1307K.

Gastroenterology, Apr 1, 2000

Clinical Genetics, Oct 1, 2002

ABSTRACT Germline mutations in BRCA1 or BRCA2 account for the majority of inherited breast cancer... more ABSTRACT Germline mutations in BRCA1 or BRCA2 account for the majority of inherited breast cancer cases. Yet, in up to 40% of familial breast cancer cases, no mutations can be detected in either gene. Germline mutations in PTEN underlie two inherited syndromes: Cowden disease (CD) and Bannayan-Riley-Ruvalcaba syndrome (BRRS). The known association of CD with breast cancer risk made it plausible that germline mutations within PTEN may play a role in inherited predisposition to breast cancer. The nine coding exons of the PTEN gene were screened for harboring germline mutations using denaturing gradient gel electrophoresis (DGGE) complemented by sequencing, in two subsets of Israeli patients: 12 patients clinically diagnosed with BRRS, and 89 women with an apparent inherited predisposition to breast cancer, some with salient features of CD. Two of three familial BRRS patients exhibited novel germline mutations in PTEN: a missense mutation changing methionine to arginine at codon 134, and insertion of two nucleotides (CA) at cDNA position 1215 resulting in a frameshift at codon 61 and a premature stop at codon 99. Among 89 high-risk women, two missense mutations were detected in exon 4: A to C change at cDNA position 1279 resulting in a change of aspargine to threonine at codon 82 (N82T), and a G to an A alteration in 1269 which alters threonine to alanine at codon 78 (T78A), a non-conservative missense mutation. This study suggests that PTEN does not play a major role in predisposing to hereditary breast cancer in Israeli women, and that detection of PTEN mutations in BRRS patients is more likely in familial cases.

Ejc Supplements, Sep 1, 2003

Fathers reported higher mental wellbeing than mothers and more mothers than fathers reported symp... more Fathers reported higher mental wellbeing than mothers and more mothers than fathers reported symptoms of depression. Within the same family, mothers (n=70) reported lower mental wellbeing and more depression, gastrointestinal, urinary and metabolic symptoms than fathers (n=70). Parents of children on treatment (n=92) reported lower social and mental wellbeing and more symptoms of depression than parents with children off treatment (n=iOi). Conclusion: The findings suggest that fathers experience a better quality of life than mothers and that parents of children off cancer treatment enjoy a better quality of life than parents of children on treatment.

Digestive Diseases and Sciences, 2005

International Journal of Radiation Oncology Biology Physics, Oct 1, 2007

The current standard of adjuvant treatment for gastric cancer after curative resection is concurr... more The current standard of adjuvant treatment for gastric cancer after curative resection is concurrent administration of radiotherapy and 5-fluorouracil-based chemotherapy. The radiation fields are often arranged as anterioposterior-posteroanterior opposed parallel fields with general recommendations for sparing at least two-thirds of one kidney. We investigated whether a better radiation distribution would be achievable with three-dimensional conformal approaches compared with the classic anterioposterior-posteroanterior fields. A total of 19 patients with adenocarcinoma of the stomach were treated with adjuvant chemoradiotherapy using a non-coplanar four-field arrangement. In each case, parallel planning using an anterioposterior-posteroanterior arrangement and a four-field "box" was performed, and the generated plans were subsequently compared for coverage of target volumes and doses to irradiated organs next to the tumor bed. A separate analysis was performed for kidneys exposed to greater and lower doses in each patient. The mean radiation dose and percentage of kidney volume receiving a dose >20 Gy were registered. Statistical analysis was performed using the two-tailed t test. The clinical target volume was adequately covered in all three plans. In the greater-dose kidney group, all the differences were statistically significant with a benefit for the three-dimensional plan. In the lower-dose kidney group, the differences in the mean radiation dose did not reach the level of statistical significance, and the differences in the kidney volume receiving a dose >20 Gy showed a statistically significant benefit for the three-dimensional plan. Non-coplanar three-dimensional-based conformal planning for postoperative radiotherapy for gastric cancer provided the best results regarding kidney and spinal cord exposure with adequate clinical target volume coverage. This technique was readily implemented in clinical practice.

Clinical Genetics, Feb 22, 2005

Journal of Clinical Oncology, 2007

15145 Background: The Current standard of adjuvant treatment for gastric cancer following curativ... more 15145 Background: The Current standard of adjuvant treatment for gastric cancer following curative resection is concurrent administration of radiation and 5FU-based chemotherapy (INT0116). Radiation fields are often arranged as AP-PA opposed parallel fields with general recommendations for sparing at least two thirds of one kidney. In the current trial we investigated whether a better radiation distribution is achievable with 3-D conformal approaches as opposed to classical AP-PA fields. Methods: Nineteen patients with adenocarcinoma of stomach were treated by adjuvant chemoradiotherapy using a non-coplanar four field arrangement. In each case parallel planning by AP-PA arrangement and four fields “box was carried out and the generated plans were subsequently compared with dose volume histograms (DVH). Adequate coverage of the CTV was the basis for a comparison between other planning parameters. Separate analysis was performed not for right and left kidney but rather for kidneys exp...

Journal of Clinical Oncology, 2004

8197 Background: The term ‘World assumptions’ (WA) refers to beliefs by which one defines his/her... more 8197 Background: The term ‘World assumptions’ (WA) refers to beliefs by which one defines his/her own identity and coping strategies. Psychologists have been interested in the association between depression, anxiety and WA. It was even suggested that anxiety and depression can be treated by mainly focusing on altering dysfunctional beliefs. The aim of the current study was to investigate which beliefs are associated with anxiety and depression amongst cancer patients. Methods: We conducted a convenience sampling with 69 female breast cancer patients, and 68 colorectal cancer patients (33 males, 35 females), aged 35–85, treated in 3 urban medical centers in Israel. Measurements were made using the world assumptions scale and the brief symptoms index. Results: In our sample, anxiety and depression were both found to be significantly more severe among breast cancer patients than in colorectal patients. Breast cancer patients also reported more dysfunctional world assumptions. A Pearson correlation procedure ...

Genetic Testing, 2001

A missense mutation within the APC gene, I1307K, was described in Ashkenazi individuals at risk f... more A missense mutation within the APC gene, I1307K, was described in Ashkenazi individuals at risk for colorectal cancer (CRC) and in the general population. The anecdotal reporting of the occurrence of this mutation in some non-Ashkenazi individuals led us to hypothesize that within the Jewish people, the I1307K polymorphism may reflect a founder mutation, and that the mutation is not restricted to ethnic Ashkenazis. To test that notion, and to establish the occurrence rate of the I1307K polymorphism in non-Ashkenazi Jewish populations, we screened Iraqi and Moroccan Jews and consecutive Jewish CRC patients and performed haplotype analysis with APC-linked markers in two I1307K carrier families. We analyzed Jewish individuals: 210 Moroccans, 160 Iraqis, 148 Ashkenazi, and 349 CRC patients (227 Ashkenazi and 122 non-Ashkenazi). The mutation detection scheme included PCR followed by denaturing gradient gel electrophoresis (DGGE) or modified restriction analysis (MRA). Haplotypes were assessed using three intragenic and three flanking markers. The I1307K polymorphism was detected in 29/227 Ashkenazi (12.8%), 2/122 (1.6%) non-Ashkenazi CRC patients, and in 2 individuals each (, 1%) within the Moroccan and Iraqi populations. Allelic pattern analysis in all our I1307K carriers, revealed a common haplotype for the three intragenic markers tested, in all mutation carriers, regardless of ethnic origin. The I1307K polymorphism, therefore, exists in all ethnic Jewish populations: Ashkenazi and non-Ashkenazi, with or without colon cancer. Jewish I1307K mutation carriers share a common allelic pattern with APC-linked markers. This strongly supports the notion of a founder mutation for I1307K.

European Journal of Gastroenterology & Hepatology, 1999

British Journal of Cancer, 2000

The frequency of the APC I1307K mutation and its association with disease pattern was examined in... more The frequency of the APC I1307K mutation and its association with disease pattern was examined in 996 Ashkenazi women consisting of individuals with either sporadic (n = 382) or hereditary (n = 143) breast and/or ovarian cancer; asymptomatic BRCA1/2 mutation carriers (185delAG, 5382insC and 6174delT) (n = 53) and healthy controls (n = 418). The I1307K allele was equally distributed among women with sporadic (17/382; 4.6%) and inherited (10/143; 7%) breast and/or ovarian cancer irrespective of their being diagnosed before or after 42 years of age and among asymptomatic (7/53; 13.2%) and cancer manifesting BRCA1/2 carriers (10/143; 7%). Taken together, the prevalence of the I1307K allele was significantly higher in BRCA1/2 carriers compared to non-BRCA1/2 carriers (17/196; 8.7% and 40/800, 5%; respectively). The high prevalence of the I1307K allele among BRCA1/2 carriers is not associated with increased cancer risk but seems to be genetically connected because of Jewish ancestry.

British Journal of Cancer, 2001

Women with a history of BC were found to have an increased risk for developing subsequent CRC (Ro... more Women with a history of BC were found to have an increased risk for developing subsequent CRC (Rozen et al, 1986; Schoen et al, 1994). Such an association between BC and CRC could arise due to a genetic predisposition (Slattery and Kerber, 1994; Stoll, 1998). Several lines of evidence point to a possible contribution of mutations within the inherited BC susceptibility gene, BRCA1, to CRC pathogenesis: allelic losses at the BRCA1 locus, putatively targeting this tumour suppressor gene, have been detected in almost 50% of sporadic CRCs (Garcia-Patino et al, 1998); Individuals within BRCA1-linked families have an increased risk for developing CRC-the relative risk of BRCA1 mutation carriers (by haplotype analysis) for CRC was found to be 4.11 (Ford et al, 1994) and the risk for developing CRC in relatives of familial BC patients is increased over that of the general population (Phipps and Perry, 1989; Slattery and Kerber, 1994; Burke et al, 1997; Olsen et al, 1999). However, the increased risk for developing CRC in patients with familial BC is not uniformly reported by all investigators (Anderson and Badzioch, 1993; Lin et al, 1999). A high carrier rate of BRCA1/2 families in a defined population permits a comparison of mutation frequencies between affected CRC individuals and the general population. Among Ashkenazi (East European) Jews, three mutations in the BRCA1 and BRCA2 genes, account for the majority of inherited BC predisposition: 185delAG and 5382insC (BRCA1) and 6174delT (BRCA2). Furthermore, these mutations occur at a rate of about 2.5% among the general Jewish Ashkenazi population

The American Journal of Human Genetics, 2002

Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by mutations in the mismatch-repair g... more Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by mutations in the mismatch-repair genes. We report here the identification and characterization of a founder mutation in MSH2 in the Ashkenazi Jewish population. We identified a nucleotide substitution, MSH2*1906GrC, which results in a substitution of proline for alanine at codon 636 in the MSH2 protein. This allele was identified in 15 unrelated Ashkenazi Jewish families with HNPCC, most of which meet the Amsterdam criteria. Genotype analysis of 18 polymorphic loci within and flanking MSH2 suggested a single origin for the mutation. All colorectal cancers tested showed microsatellite instability and absence of MSH2 protein, by immunohistochemical analysis. In an analysis of a population-based incident series of 686 Ashkenazi Jews from Israel who have colorectal cancer, we identified 3 (0.44%) mutation carriers. Persons with a family history of colorectal or endometrial cancer were more likely to carry the mutation than were those without such a family history (), and those with colorectal cancer who carried the mutation P p .042 were, on average, younger than affected individuals who did not carry it (). The mutation was not detected P p .033 in either 566 unaffected Ashkenazi Jews from Israel or 1,022 control individuals from New York. In hospital-based series, the 1906C allele was identified in 5/463 Ashkenazi Jews with colorectal cancer, in 2/197 with endometrial cancer, and in 0/83 with ovarian cancer. When families identified by family history and in case series are included, 25 apparently unrelated Ashkenazi Jewish families have been found to harbor this mutation. Although this pathogenic mutation is not frequent in the Ashkenazi Jewish population (accounting for 2%-3% of colorectal cancer in those whose age at diagnosis is !60 years), it is highly penetrant and accounts for approximately one-third of HNPCC in Ashkenazi Jewish families that fulfill the Amsterdam criteria.

Journal of Clinical Oncology, 2007

Purpose In the OPTIMOX1 trial, previously untreated patients with advanced colorectal cancer were... more Purpose In the OPTIMOX1 trial, previously untreated patients with advanced colorectal cancer were randomly assigned to two different schedules of leucovorin, fluorouracil, and oxaliplatin that were administered until progression in the control arm or in a stop-and-go fashion in the experimental arm. The randomly assigned treatment groups did not differ significantly in terms of response rate, progression-free survival, and overall survival (OS). However, the impact of oxaliplatin reintroduction on OS was potentially masked by the fact that a large number of patients did not receive the planned oxaliplatin reintroduction or received oxaliplatin after second-line therapy in both treatment groups. Patients and Methods A Cox model was fitted with all significant baseline factors plus time-dependent variables reflecting tumor progression, reintroduction of oxaliplatin, and use of second-line irinotecan. A shared frailty model was fitted with all significant baseline factors plus the numb...

Targeted Oncology, Jan 20, 2018

Background Precision treatment of cancer uses biomarker-driven therapy to individualize and optim... more Background Precision treatment of cancer uses biomarker-driven therapy to individualize and optimize patient care. Objective To evaluate real-life clinical experience with biomarker-driven therapy in metastatic gastric and esophageal cancer in Israel. Patients and Methods This multicenter retrospective cohort study included patients with metastatic gastric or esophageal cancer who were treated in the participating institutions and underwent biomarker-driven therapy. Treatment was considered to have a benefit if the ratio between the longest progression-free survival (PFS) post biomarker-driven therapy and the last PFS before the biomarker-driven therapy was ≥1.3. The null hypothesis was that ≤15% of patients gain such benefit. Results The analysis included 46 patients (61% men; median age, 58 years; 57% with poorly-differentiated tumors). At least one actionable (i.e., predictive of response to a specific therapy) biomarker was identified for each patient. Immunohistochemistry was performed on all samples and identified 1-8 (median: 3) biomarkers per patient (most commonly: low TS, high TOPO1, high TOP2A). Twenty-eight patients received therapy after the biomarker analysis (1-4 lines). In the 1st line after biomarker analysis, five patients (18%) achieved a partial response and five (18%) stable disease; the median (range) PFS was 129 (12-1155) days. Twenty-four patients were evaluable for PFS ratio analysis; in seven (29.2%), the ratio was ≥1.3. In a one-sided exact binomial test vs. the null hypothesis, p = 0.019; therefore, the null hypothesis was rejected. Conclusions Our findings demonstrated that implementing biomarker-driven analysis is feasible and could provide clinical benefit for a considerable proportion (~30%) of patients with metastatic gastric or esophageal cancer.

Gastroenterology, Apr 1, 2008

combinations of KS organ involvement found were less frequent. There was no difference between H+... more combinations of KS organ involvement found were less frequent. There was no difference between H+ and H-patients concerning SK GI distribution. CONCLUSIONS: Patients with cutaneous KS and low CD4 cell count have shown a very high frequency of KS GI involvement. It was independent of HAART use. Stomach was the most often affected organ. Since a diagnosis of visceral KS may dictate a change toward systemic therapy, our results may suggest an upper endoscopy to be done in all patients with cutaneous KS and low CD4 cell count, irrespective of HAART.

Annals of Oncology, 2009

Background: Alkaline phosphatase (ALP) is a strong prognostic factor in patients with metastatic ... more Background: Alkaline phosphatase (ALP) is a strong prognostic factor in patients with metastatic colorectal cancer (MCRC). Patients with ALP more than three times the upper limit of normal (ULN) were excluded from our previous studies evaluating chemotherapy. An exploratory cohort of patients with ALP >3 ULN was included in the OPTIMOX1 study. Patients and methods: Previously untreated patients with MCRC were randomized to FOLFOX4 until progression (arm A) or FOLFOX7 for six cycles, maintenance without oxaliplatin for 12 cycles and reintroduction of FOLFOX7 (arm B). Patients were stratified according to ALP level £3 ULN versus 3-5 ULN. Results: Among the 620 patients in OPTIMOX1 study, 63 had ALP 3-5 ULN; 33 in arm A and 30 in arm B. The response rate in these patients was 56% versus 59% in patients with ALP £3 ULN. Median progression-free survival and overall survival were, respectively, 6.4 and 11.5 months in patients with ALP 3-5 ULN and 9.0 and 21.1 months in patients with ALP £3 ULN. Thirty-three percent of the patients in the cohort experienced grade 3/4 toxicity. Conclusion: Both FOLFOX regimens achieved high tumor response rates and offer good palliation in MCRC patients with a poor prognosis.

Genetic Testing, Jun 1, 2001

ABSTRACT A missense mutation within the APC gene, I1307K, was described in Ashkenazi individuals ... more ABSTRACT A missense mutation within the APC gene, I1307K, was described in Ashkenazi individuals at risk for colorectal cancer (CRC) and in the general population. The anecdotal reporting of the occurrence of this mutation in some non-Ashkenazi individuals led us to hypothesize that within the Jewish people, the I1307K polymorphism may reflect a founder mutation, and that the mutation is not restricted to ethnic Ashkenazis. To test that notion, and to establish the occurrence rate of the I1307K polymorphism in non-Ashkenazi Jewish populations, we screened Iraqi and Moroccan Jews and consecutive Jewish CRC patients and performed haplotype analysis with APC-linked markers in two I1307K carrier families. We analyzed Jewish individuals: 210 Moroccans, 160 Iraqis, 148 Ashkenazi, and 349 CRC patients (227 Ashkenazi and 122 non-Ashkenazi). The mutation detection scheme included PCR followed by denaturing gradient gel electrophoresis (DGGE) or modified restriction analysis (MRA). Haplotypes were assessed using three intragenic and three flanking markers. The I1307K polymorphism was detected in 29/227 Ashkenazi (12.8%), 2/122 (1.6%) non-Ashkenazi CRC patients, and in 2 individuals each (approximately 1%) within the Moroccan and Iraqi populations. Allelic pattern analysis in all our I1307K carriers, revealed a common haplotype for the three intragenic markers tested, in all mutation carriers, regardless of ethnic origin. The I1307K polymorphism, therefore, exists in all ethnic Jewish populations: Ashkenazi and non-Ashkenazi, with or without colon cancer. Jewish I1307K mutation carriers share a common allelic pattern with APC-linked markers. This strongly supports the notion of a founder mutation for I1307K.

Gastroenterology, Apr 1, 2000

Clinical Genetics, Oct 1, 2002

ABSTRACT Germline mutations in BRCA1 or BRCA2 account for the majority of inherited breast cancer... more ABSTRACT Germline mutations in BRCA1 or BRCA2 account for the majority of inherited breast cancer cases. Yet, in up to 40% of familial breast cancer cases, no mutations can be detected in either gene. Germline mutations in PTEN underlie two inherited syndromes: Cowden disease (CD) and Bannayan-Riley-Ruvalcaba syndrome (BRRS). The known association of CD with breast cancer risk made it plausible that germline mutations within PTEN may play a role in inherited predisposition to breast cancer. The nine coding exons of the PTEN gene were screened for harboring germline mutations using denaturing gradient gel electrophoresis (DGGE) complemented by sequencing, in two subsets of Israeli patients: 12 patients clinically diagnosed with BRRS, and 89 women with an apparent inherited predisposition to breast cancer, some with salient features of CD. Two of three familial BRRS patients exhibited novel germline mutations in PTEN: a missense mutation changing methionine to arginine at codon 134, and insertion of two nucleotides (CA) at cDNA position 1215 resulting in a frameshift at codon 61 and a premature stop at codon 99. Among 89 high-risk women, two missense mutations were detected in exon 4: A to C change at cDNA position 1279 resulting in a change of aspargine to threonine at codon 82 (N82T), and a G to an A alteration in 1269 which alters threonine to alanine at codon 78 (T78A), a non-conservative missense mutation. This study suggests that PTEN does not play a major role in predisposing to hereditary breast cancer in Israeli women, and that detection of PTEN mutations in BRRS patients is more likely in familial cases.

Ejc Supplements, Sep 1, 2003

Fathers reported higher mental wellbeing than mothers and more mothers than fathers reported symp... more Fathers reported higher mental wellbeing than mothers and more mothers than fathers reported symptoms of depression. Within the same family, mothers (n=70) reported lower mental wellbeing and more depression, gastrointestinal, urinary and metabolic symptoms than fathers (n=70). Parents of children on treatment (n=92) reported lower social and mental wellbeing and more symptoms of depression than parents with children off treatment (n=iOi). Conclusion: The findings suggest that fathers experience a better quality of life than mothers and that parents of children off cancer treatment enjoy a better quality of life than parents of children on treatment.

Digestive Diseases and Sciences, 2005

International Journal of Radiation Oncology Biology Physics, Oct 1, 2007

The current standard of adjuvant treatment for gastric cancer after curative resection is concurr... more The current standard of adjuvant treatment for gastric cancer after curative resection is concurrent administration of radiotherapy and 5-fluorouracil-based chemotherapy. The radiation fields are often arranged as anterioposterior-posteroanterior opposed parallel fields with general recommendations for sparing at least two-thirds of one kidney. We investigated whether a better radiation distribution would be achievable with three-dimensional conformal approaches compared with the classic anterioposterior-posteroanterior fields. A total of 19 patients with adenocarcinoma of the stomach were treated with adjuvant chemoradiotherapy using a non-coplanar four-field arrangement. In each case, parallel planning using an anterioposterior-posteroanterior arrangement and a four-field "box" was performed, and the generated plans were subsequently compared for coverage of target volumes and doses to irradiated organs next to the tumor bed. A separate analysis was performed for kidneys exposed to greater and lower doses in each patient. The mean radiation dose and percentage of kidney volume receiving a dose >20 Gy were registered. Statistical analysis was performed using the two-tailed t test. The clinical target volume was adequately covered in all three plans. In the greater-dose kidney group, all the differences were statistically significant with a benefit for the three-dimensional plan. In the lower-dose kidney group, the differences in the mean radiation dose did not reach the level of statistical significance, and the differences in the kidney volume receiving a dose >20 Gy showed a statistically significant benefit for the three-dimensional plan. Non-coplanar three-dimensional-based conformal planning for postoperative radiotherapy for gastric cancer provided the best results regarding kidney and spinal cord exposure with adequate clinical target volume coverage. This technique was readily implemented in clinical practice.

Clinical Genetics, Feb 22, 2005

Journal of Clinical Oncology, 2007

15145 Background: The Current standard of adjuvant treatment for gastric cancer following curativ... more 15145 Background: The Current standard of adjuvant treatment for gastric cancer following curative resection is concurrent administration of radiation and 5FU-based chemotherapy (INT0116). Radiation fields are often arranged as AP-PA opposed parallel fields with general recommendations for sparing at least two thirds of one kidney. In the current trial we investigated whether a better radiation distribution is achievable with 3-D conformal approaches as opposed to classical AP-PA fields. Methods: Nineteen patients with adenocarcinoma of stomach were treated by adjuvant chemoradiotherapy using a non-coplanar four field arrangement. In each case parallel planning by AP-PA arrangement and four fields “box was carried out and the generated plans were subsequently compared with dose volume histograms (DVH). Adequate coverage of the CTV was the basis for a comparison between other planning parameters. Separate analysis was performed not for right and left kidney but rather for kidneys exp...

Journal of Clinical Oncology, 2004

8197 Background: The term ‘World assumptions’ (WA) refers to beliefs by which one defines his/her... more 8197 Background: The term ‘World assumptions’ (WA) refers to beliefs by which one defines his/her own identity and coping strategies. Psychologists have been interested in the association between depression, anxiety and WA. It was even suggested that anxiety and depression can be treated by mainly focusing on altering dysfunctional beliefs. The aim of the current study was to investigate which beliefs are associated with anxiety and depression amongst cancer patients. Methods: We conducted a convenience sampling with 69 female breast cancer patients, and 68 colorectal cancer patients (33 males, 35 females), aged 35–85, treated in 3 urban medical centers in Israel. Measurements were made using the world assumptions scale and the brief symptoms index. Results: In our sample, anxiety and depression were both found to be significantly more severe among breast cancer patients than in colorectal patients. Breast cancer patients also reported more dysfunctional world assumptions. A Pearson correlation procedure ...

Genetic Testing, 2001

A missense mutation within the APC gene, I1307K, was described in Ashkenazi individuals at risk f... more A missense mutation within the APC gene, I1307K, was described in Ashkenazi individuals at risk for colorectal cancer (CRC) and in the general population. The anecdotal reporting of the occurrence of this mutation in some non-Ashkenazi individuals led us to hypothesize that within the Jewish people, the I1307K polymorphism may reflect a founder mutation, and that the mutation is not restricted to ethnic Ashkenazis. To test that notion, and to establish the occurrence rate of the I1307K polymorphism in non-Ashkenazi Jewish populations, we screened Iraqi and Moroccan Jews and consecutive Jewish CRC patients and performed haplotype analysis with APC-linked markers in two I1307K carrier families. We analyzed Jewish individuals: 210 Moroccans, 160 Iraqis, 148 Ashkenazi, and 349 CRC patients (227 Ashkenazi and 122 non-Ashkenazi). The mutation detection scheme included PCR followed by denaturing gradient gel electrophoresis (DGGE) or modified restriction analysis (MRA). Haplotypes were assessed using three intragenic and three flanking markers. The I1307K polymorphism was detected in 29/227 Ashkenazi (12.8%), 2/122 (1.6%) non-Ashkenazi CRC patients, and in 2 individuals each (, 1%) within the Moroccan and Iraqi populations. Allelic pattern analysis in all our I1307K carriers, revealed a common haplotype for the three intragenic markers tested, in all mutation carriers, regardless of ethnic origin. The I1307K polymorphism, therefore, exists in all ethnic Jewish populations: Ashkenazi and non-Ashkenazi, with or without colon cancer. Jewish I1307K mutation carriers share a common allelic pattern with APC-linked markers. This strongly supports the notion of a founder mutation for I1307K.

European Journal of Gastroenterology & Hepatology, 1999

British Journal of Cancer, 2000

The frequency of the APC I1307K mutation and its association with disease pattern was examined in... more The frequency of the APC I1307K mutation and its association with disease pattern was examined in 996 Ashkenazi women consisting of individuals with either sporadic (n = 382) or hereditary (n = 143) breast and/or ovarian cancer; asymptomatic BRCA1/2 mutation carriers (185delAG, 5382insC and 6174delT) (n = 53) and healthy controls (n = 418). The I1307K allele was equally distributed among women with sporadic (17/382; 4.6%) and inherited (10/143; 7%) breast and/or ovarian cancer irrespective of their being diagnosed before or after 42 years of age and among asymptomatic (7/53; 13.2%) and cancer manifesting BRCA1/2 carriers (10/143; 7%). Taken together, the prevalence of the I1307K allele was significantly higher in BRCA1/2 carriers compared to non-BRCA1/2 carriers (17/196; 8.7% and 40/800, 5%; respectively). The high prevalence of the I1307K allele among BRCA1/2 carriers is not associated with increased cancer risk but seems to be genetically connected because of Jewish ancestry.

British Journal of Cancer, 2001

Women with a history of BC were found to have an increased risk for developing subsequent CRC (Ro... more Women with a history of BC were found to have an increased risk for developing subsequent CRC (Rozen et al, 1986; Schoen et al, 1994). Such an association between BC and CRC could arise due to a genetic predisposition (Slattery and Kerber, 1994; Stoll, 1998). Several lines of evidence point to a possible contribution of mutations within the inherited BC susceptibility gene, BRCA1, to CRC pathogenesis: allelic losses at the BRCA1 locus, putatively targeting this tumour suppressor gene, have been detected in almost 50% of sporadic CRCs (Garcia-Patino et al, 1998); Individuals within BRCA1-linked families have an increased risk for developing CRC-the relative risk of BRCA1 mutation carriers (by haplotype analysis) for CRC was found to be 4.11 (Ford et al, 1994) and the risk for developing CRC in relatives of familial BC patients is increased over that of the general population (Phipps and Perry, 1989; Slattery and Kerber, 1994; Burke et al, 1997; Olsen et al, 1999). However, the increased risk for developing CRC in patients with familial BC is not uniformly reported by all investigators (Anderson and Badzioch, 1993; Lin et al, 1999). A high carrier rate of BRCA1/2 families in a defined population permits a comparison of mutation frequencies between affected CRC individuals and the general population. Among Ashkenazi (East European) Jews, three mutations in the BRCA1 and BRCA2 genes, account for the majority of inherited BC predisposition: 185delAG and 5382insC (BRCA1) and 6174delT (BRCA2). Furthermore, these mutations occur at a rate of about 2.5% among the general Jewish Ashkenazi population

The American Journal of Human Genetics, 2002

Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by mutations in the mismatch-repair g... more Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by mutations in the mismatch-repair genes. We report here the identification and characterization of a founder mutation in MSH2 in the Ashkenazi Jewish population. We identified a nucleotide substitution, MSH2*1906GrC, which results in a substitution of proline for alanine at codon 636 in the MSH2 protein. This allele was identified in 15 unrelated Ashkenazi Jewish families with HNPCC, most of which meet the Amsterdam criteria. Genotype analysis of 18 polymorphic loci within and flanking MSH2 suggested a single origin for the mutation. All colorectal cancers tested showed microsatellite instability and absence of MSH2 protein, by immunohistochemical analysis. In an analysis of a population-based incident series of 686 Ashkenazi Jews from Israel who have colorectal cancer, we identified 3 (0.44%) mutation carriers. Persons with a family history of colorectal or endometrial cancer were more likely to carry the mutation than were those without such a family history (), and those with colorectal cancer who carried the mutation P p .042 were, on average, younger than affected individuals who did not carry it (). The mutation was not detected P p .033 in either 566 unaffected Ashkenazi Jews from Israel or 1,022 control individuals from New York. In hospital-based series, the 1906C allele was identified in 5/463 Ashkenazi Jews with colorectal cancer, in 2/197 with endometrial cancer, and in 0/83 with ovarian cancer. When families identified by family history and in case series are included, 25 apparently unrelated Ashkenazi Jewish families have been found to harbor this mutation. Although this pathogenic mutation is not frequent in the Ashkenazi Jewish population (accounting for 2%-3% of colorectal cancer in those whose age at diagnosis is !60 years), it is highly penetrant and accounts for approximately one-third of HNPCC in Ashkenazi Jewish families that fulfill the Amsterdam criteria.

Journal of Clinical Oncology, 2007

Purpose In the OPTIMOX1 trial, previously untreated patients with advanced colorectal cancer were... more Purpose In the OPTIMOX1 trial, previously untreated patients with advanced colorectal cancer were randomly assigned to two different schedules of leucovorin, fluorouracil, and oxaliplatin that were administered until progression in the control arm or in a stop-and-go fashion in the experimental arm. The randomly assigned treatment groups did not differ significantly in terms of response rate, progression-free survival, and overall survival (OS). However, the impact of oxaliplatin reintroduction on OS was potentially masked by the fact that a large number of patients did not receive the planned oxaliplatin reintroduction or received oxaliplatin after second-line therapy in both treatment groups. Patients and Methods A Cox model was fitted with all significant baseline factors plus time-dependent variables reflecting tumor progression, reintroduction of oxaliplatin, and use of second-line irinotecan. A shared frailty model was fitted with all significant baseline factors plus the numb...

Targeted Oncology, Jan 20, 2018

Background Precision treatment of cancer uses biomarker-driven therapy to individualize and optim... more Background Precision treatment of cancer uses biomarker-driven therapy to individualize and optimize patient care. Objective To evaluate real-life clinical experience with biomarker-driven therapy in metastatic gastric and esophageal cancer in Israel. Patients and Methods This multicenter retrospective cohort study included patients with metastatic gastric or esophageal cancer who were treated in the participating institutions and underwent biomarker-driven therapy. Treatment was considered to have a benefit if the ratio between the longest progression-free survival (PFS) post biomarker-driven therapy and the last PFS before the biomarker-driven therapy was ≥1.3. The null hypothesis was that ≤15% of patients gain such benefit. Results The analysis included 46 patients (61% men; median age, 58 years; 57% with poorly-differentiated tumors). At least one actionable (i.e., predictive of response to a specific therapy) biomarker was identified for each patient. Immunohistochemistry was performed on all samples and identified 1-8 (median: 3) biomarkers per patient (most commonly: low TS, high TOPO1, high TOP2A). Twenty-eight patients received therapy after the biomarker analysis (1-4 lines). In the 1st line after biomarker analysis, five patients (18%) achieved a partial response and five (18%) stable disease; the median (range) PFS was 129 (12-1155) days. Twenty-four patients were evaluable for PFS ratio analysis; in seven (29.2%), the ratio was ≥1.3. In a one-sided exact binomial test vs. the null hypothesis, p = 0.019; therefore, the null hypothesis was rejected. Conclusions Our findings demonstrated that implementing biomarker-driven analysis is feasible and could provide clinical benefit for a considerable proportion (~30%) of patients with metastatic gastric or esophageal cancer.

Gastroenterology, Apr 1, 2008

combinations of KS organ involvement found were less frequent. There was no difference between H+... more combinations of KS organ involvement found were less frequent. There was no difference between H+ and H-patients concerning SK GI distribution. CONCLUSIONS: Patients with cutaneous KS and low CD4 cell count have shown a very high frequency of KS GI involvement. It was independent of HAART use. Stomach was the most often affected organ. Since a diagnosis of visceral KS may dictate a change toward systemic therapy, our results may suggest an upper endoscopy to be done in all patients with cutaneous KS and low CD4 cell count, irrespective of HAART.