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Cancer Statistics
Population in 2012: 7.7m
People newly diagnosed with cancer (excluding NMSC) / yr: 29,200
Age-standardised rate, incidence per 100,000 people/yr: 283.2
Risk of getting cancer before age 75:28.1%
People dying from cancer /yr: 10,900
Data from IARC GlobalCan (2012)
Israel Cancer Organisations and Resources
Latest Research Publications Related to Israel

Israel Cancer Organisations and Resources (7 links)

Latest Research Publications Related to Israel

Makarov M, Peled N, Shochat T, et al.
Circulating Tumor DNA T790M Testing as a Predictor of Osimertinib Efficacy in Epidermal Growth Factor Receptor Mutant Non-small Cell Lung Cancer: A Single Center Experience.
Isr Med Assoc J. 2019; 21(6):394-398 [PubMed] Related Publications
BACKGROUND: The main acquired resistance mechanism to first- and second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR mutant non-small cell lung cancer (NSCLC) is the propagation of T790M clones, which can be detected in circulating tumor DNA (ctDNA).
OBJECTIVES: To analyze osimertinib outcomes according to T790M testing method.
METHODS: The study comprised 33 consecutive patients with advanced EGFR mutant NSCLC who were diagnosed with a T790M mutation after progression on first- or second-generation EGFR TKIs and treated with osimertinib. The patients were divided into groups A (diagnosed by tumor testing) and B (by ctDNA testing). Osimertinib outcomes were compared between the groups.
RESULTS: Objective response rate with osimertinib comprised 54% and 62% in groups A and B, respectively (P = 0.58). Median progression-free survival (PFS) with osimertinib was 8.9 months (95% confidence interval [95%CI] 1.8-17.5) and 9.1 months (95%Cl 5.3-12.6) in groups A and B, respectively (log-rank test 0.12, P = 0.73). Median overall survival (OS) was 13.8 months (95%CI 4.9-25.5) and 13.8 months (95%Cl 7.7-27.7) in groups A and B, respectively (log-rank test 0.09, P = 0.75). T790M testing technique did not affect PFS (hazard ratio [HR] 1.16, 95%CI 0.50-2.69, P = 0.73) or OS (HR = 1.16, 95%CI 0.45-3.01, P = 0.76). The proportion of patients diagnosed by ctDNA grew from 56% in 2015 to 67% in 2016-2017.
CONCLUSIONS: Our study provides a ctDNA validation for the purpose of T790M testing in EGFR mutant NSCLC.

Kobo OM, Vainer Evgrafov E, Cohen Y, et al.
Non-ST-Elevation Myocardial Infarction with Non-significant Coronary Artery Disease as a Symptom of Occult or New Malignancy.
Isr Med Assoc J. 2019; 21(6):381-385 [PubMed] Related Publications
BACKGROUND: Malignancy is a known risk factor for venous thromboembolism; however, the association with arterial thromboembolic events remains unclear.
OBJECTIVES: To examine the association between non-ST-elevation myocardial infarction (NSTEMI) and non-significant coronary artery disease (CAD) and the presence of new or occult malignancy.
METHODS: An observational cohort, single-center study was performed 2010-2015. Adult patients with NSTEMI, who underwent coronary angiography and had no significant coronary lesion, were included. Using propensity score matching, we created a 2:1 matched control group of adults with NSTEMI, and significant coronary artery disease. Risk factors for new or occult malignancy were assessed using multivariate backward stepwise logistic regression analysis. The primary outcome was new or occult malignancy, defined as any malignancy diagnosed in the 3 months prior and 6 months following the myocardial infarction (MI).
RESULTS: During the study period, 174 patients who presented with MI with non-obstructive coronary arteries were identified. The matched control group included 348 patients. There was no significant difference in the group demographics, past medical history, or clinical presentation. The incidence of new or occult malignancy in the study group was significantly higher (7/174, 4% vs. 3/348, 0.9%, P = 0.019). NSTEMI with non-significant CAD was an independent risk factor for occult malignancy (odds ratio [OR] 4.6, 95% confidence interval [95%CI] 1.1-18.7). Other risk factors included active smoking (OR 11.2, 95%CI 2.5-49.1) and age (OR 1.1, 95%CI 1.03-1.17).
CONCLUSIONS: NSTEMI with non-significant CAD may be a presenting or early marker of malignancy and warrants further investigation.

Twito O, Grozinsky-Glasberg S, Levy S, et al.
Clinico-pathologic and dynamic prognostic factors in sporadic and familial medullary thyroid carcinoma: an Israeli multi-center study.
Eur J Endocrinol. 2019; 181(1):13-21 [PubMed] Related Publications
Objective: Multiple clinical, pathological and biochemical variables, including the response to initial treatment, are associated with medullary thyroid carcinoma (MTC) prognosis. Studies that include separate analyses of familial and sporadic MTC patients followed for long period are scarce. This study evaluated the association between baseline clinico-pathologic variables and response to initial treatment and short- and long-term disease outcomes in sporadic and familial MTC.
Methods: Patients treated for MTC at four tertiary medical centers were retrospectively analyzed. Clinical and pathological data were collected. The outcomes measured included disease persistence 1 year after diagnosis, disease persistence at last follow-up, disease-related mortality (DRM) and all-cause mortality.
Results: The study enrolled 193 patients (mean age: 48.9 ± 18.7, 44.7% males), of whom 18.1% were familial cases. The mean follow-up period was 10.1 ± 9.4 years (8.5 ± 8.1 in sporadic and 16.9 ± 11.6 in familial MTC). Disease persistence 1-year after diagnosis and at last follow-up was detected in 56.1 and 60.4% patients, respectively. All-cause and DRM were 28.5 and 12.6%, respectively. Extra-thyroidal extension (ETE) and distant metastases (DM) were associated with disease persistence at last follow-up. ETE and DM were also significantly associated with DRM. Complete remission 1 year after diagnosis had high correlation with no evidence of disease at last follow-up (Cramer's V measure of association 0.884, P < 0.001) and with 100% disease-specific survival (Cramer's V measure of association 0.38, P < 0.001).
Conclusions: Apart from clinico-pathologic parameters, close correlation was found between 1-year status and long-term prognosis. These results underscore the importance of combining classical and dynamic factors for both sporadic and familial MTC prognostication and treatment decision making.

Lavie O, Chetrit A, Novikov I, et al.
Fifteen-year survival of invasive epithelial ovarian cancer in women with BRCA1/2 mutations - the National Israeli Study of Ovarian Cancer.
Gynecol Oncol. 2019; 153(2):320-325 [PubMed] Related Publications
OBJECTIVE: Compare 5, 10 and 15 year survival in invasive epithelial ovarian cancer, between patients with and without BRCA1/2 germ line mutation in a nonselective group of patients diagnosed during 1994-99.
METHODS: The analysis was based on 779 Jewish patients: 229 carriers to the Ashkenazi Jewish founder mutations in BRCA1 (185delAG; 5382insC) and BRCA2 (6174delT); and 550 non-carriers. Clinical characteristics were abstracted from the patients' medical records and vital status was updated through the National Population Registry up to 11/2015. The Kaplan-Meier method, log-rank tests, and Cox-regression model were used for survival analyses.
RESULTS: By the end of the follow-up period, (range 1-20 years), 629 (80.7%) deaths occurred. While considerably higher survival was observed during the first 5 years from diagnosis among carriers compared to non-carriers (46.7% vs. 36.2%, p = 0.0004), the survival rates at 15 years were 22.3% vs. 21.8% respectively (p = 0.04). The age-adjusted hazard ratio for all-cause mortality of carriers versus non-carriers was 0.74 (95%CI 0.60-0.91) in the first 5 years. For women who survived 5 and 10 years, the age-adjusted hazard ratios for mortality during 5 additional years, of carriers compared to non-carriers, were 1.38 (95%CI 0.93-2.04) and 1.08 (95%CI 0.61-1.92), respectively.
CONCLUSION: The results of this study, with up to 20 years follow-up, support studies with shorter follow-up that suggested that the advantage in survival observed among BRCA1/2 carriers during the first 5 years decreases over time. Clinically, this may have implications for follow-up and therapy, especially of new agents that are particularly effective in BRCA carriers.

Manchanda R, Burnell M, Gaba F, et al.
Attitude towards and factors affecting uptake of population-based BRCA testing in the Ashkenazi Jewish population: a cohort study.
BJOG. 2019; 126(6):784-794 [PubMed] Related Publications
OBJECTIVE: To evaluate factors affecting unselected population-based BRCA testing in Ashkenazi Jews (AJ).
DESIGN: Cohort-study set within recruitment to the GCaPPS trial (ISRCTN73338115).
SETTING: North London AJ population.
POPULATION OR SAMPLE: Ashkenazi Jews women/men >18 years, recruited through self-referral.
METHODS: Ashkenazi Jews women/men underwent pre-test counselling for BRCA testing through recruitment clinics (clusters). Consenting individuals provided blood samples for BRCA testing. Data were collected on socio-demographic/family history/knowledge/psychological well-being along with benefits/risks/cultural influences (18-item questionnaire measuring 'attitude'). Four-item Likert-scales analysed initial 'interest' and 'intention-to-test' pre-counselling. Uni- and multivariable logistic regression models evaluated factors affecting uptake/interest/intention to undergo BRCA testing. Statistical inference was based on cluster robust standard errors and joint Wald tests for significance. Item-Response Theory and graded-response models modelled responses to 18-item questionnaire.
MAIN OUTCOME MEASURES: Interest, intention, uptake, attitude towards BRCA testing.
RESULTS: A total of 935 individuals (women = 67%/men = 33%; mean age = 53.8 (SD = 15.02) years) underwent pre-test genetic-counselling. During the pre-counselling, 96% expressed interest in and 60% indicated a clear intention to undergo BRCA testing. Subsequently, 88% opted for BRCA testing. BRCA-related knowledge (P = 0.013) and degree-level education (P = 0.01) were positively and negatively (respectively) associated with intention-to-test. Being married/cohabiting had four-fold higher odds for BRCA testing uptake (P = 0.009). Perceived benefits were associated with higher pre-counselling odds for interest in and intention to undergo BRCA testing. Reduced uncertainty/reassurance were the most important factors contributing to decision-making. Increased importance/concern towards risks/limitations (confidentiality/insurance/emotional impact/inability to prevent cancer/marriage ability/ethnic focus/stigmatisation) were significantly associated with lower odds of uptake of BRCA testing, and discriminated between acceptors and decliners. Male gender/degree-level education (P = 0.001) had weaker correlations, whereas having children showed stronger (P = 0.005) associations with attitudes towards BRCA testing.
CONCLUSIONS: BRCA testing in the AJ population has high acceptability. Pre-test counselling increases awareness of disadvantages/limitations of BRCA testing, influencing final cost-benefit perception and decision-making on undergoing testing.
TWEETABLE ABSTRACT: BRCA testing in Ashkenazi Jews has high acceptability and uptake. Pre-test counselling facilitates informed decision-making.

Herishanu Y, Tadmor T, Braester A, et al.
Low-dose fludarabine and cyclophosphamide combined with standard dose rituximab (LD-FCR) is an effective and safe regimen for elderly untreated patients with chronic lymphocytic leukemia: The Israeli CLL study group experience.
Hematol Oncol. 2019; 37(2):185-192 [PubMed] Related Publications
Chronic lymphocytic leukemia (CLL) is a disease of elderly patients. The fludarabine, cyclophosphamide, and rituximab (FCR) regimen is considered the treatment of choice for young fit patients with CLL; however, this combination is toxic for older patients. At the time this study was first planned and initiated, there was no standard chemo-immunotherapy regimen regarded as standard therapy for the less fit elderly patient with CLL. Here, we conducted a single-arm, phase II trial to examine the efficacy and safety of lower-dose fludarabine and cyclophosphamide combined with a standard dose of rituximab (LD-FCR) in elderly patients with previously untreated CLL. Forty patients received LD-FCR and were included in the efficacy analysis. Two patients treated with FC alone were only included in the safety analysis. The median age was 72.7 years (range, 65.0 to 85.0). The overall response and complete response rates were 67.5% and 42.5%, respectively. Median progression-free survival (PFS) was 35.5 months (95% CI, 29.27-41.67). Two patients (4.8%) died during the study period. Hematological toxicities and infections were the most common complications encountered; grade 3 to 4 treatment-related neutropenia occurred in 20 (47.6%) patients. During the entire study follow-up, 26 patients (61.9%) had all grades of infection including six (14.3%) with neutropenic fever and eight (19%) with grade 3 to 4 non-neutropenic infections. In conclusion, LD-FCR is an effective and relatively safe regimen for previously untreated patients with CLL. It has the advantage of being both "time and cost limited" and, even in the era of novel agents, can still be considered when planning treatment for elderly patients without high-risk biomarkers. However, recent results in fit elderly patients using the combination of bendamustine and rituximab which have achieved longer PFS with good safety profile must be taken into consideration in this regard.

Ayalon R, Bachner YG
Medical, social, and personal factors as correlates of quality of life among older cancer patients with permanent stoma.
Eur J Oncol Nurs. 2019; 38:50-56 [PubMed] Related Publications
PURPOSE: The vast majority of cancer patients experience a substantial reduction in their quality of life (QOL) following a stoma procedure. There is a paucity of studies that examine QOL of patients with stoma and only a small percentage of these studies focuses on older patients. This study assesses the level of QOL of older patients with a permanent stoma; and examines the associations between three categories of variables -personal, medical, and social -and QOL.
METHODS: This was a cross-sectional study. Seventy-five older cancer patients (M = 75.1 SD = 8.6) with permanent stoma participated in the study. Participants were recruited by their physicians from hospitals and clinics in the central region of Israel. All study measures were valid and reliable.
RESULTS: Participants reported a moderate mean level of QOL. Men's QOL scores were higher than those of women. Positive correlations were found between perceived body image, self-care, self-efficacy, social support and QOL. A negative correlation was found between anxiety and QOL. Three variables emerged as significant predictors of QOL: self-efficacy (β = 0.41, P < .001), perceived body image (β = 0.41, P < .001), and gender (β = -0.14, P < .05). The model explained a variance of 73.6%.
CONCLUSIONS: Self-efficacy, perceived body image, and gender are the most important factors for QOL of older patients with stoma in this study. These three personal variables are more significant to QOL than either the medical or the social variables. The personal variables need to be considered by nurses when developing intervention programs aimed at increasing QOL among older cancer patients with permanent stoma.

Azulay R, Valinsky L, Hershkowitz F, Magnezi R
CRC Screening Results: Patient Comprehension and Follow-up.
Cancer Control. 2019 Jan-Dec; 26(1):1073274819825828 [PubMed] Free Access to Full Article Related Publications
BACKGROUND:: Fecal occult blood tests are recommended for colorectal cancer screening, but are only effective if colonoscopy follows positive results. Patients with positive results often do not complete follow-up. This study examined the association between patient comprehension and adherence to colonoscopy after positive FIT (Fecal Immunochemical Test).
METHODS:: Five hundred twenty-two patients completed a telephone questionnaire regarding the FIT and its implications 120 days after a positive result. Patients were asked whether they had the test, received the results, and required follow-up. These questions were used to identify the degree to which patients understood medical information. A participant who answered "no" to any question was defined as having "low comprehension" regarding the FIT, and participants who answered "yes" to all 3 questions, as having "high comprehension".
RESULTS:: Comprehension and colonoscopy adherence were significantly associated. Adherence to colonoscopy was significantly higher among participants with high comprehension, after adjusting for gender, age, education, ethnicity, and socio-economic status.
CONCLUSIONS:: This study demonstrates a link between health comprehension and patient follow-up after positive FIT and contributes to understanding the implications of health comprehension in terms of health promotion. We recommend patients undergoing screening tests receive clear explanations regarding need for follow-up of positive results thus reducing health disparities associated with health comprehension.

Ben Natan M, Abu Husayn A, Haj Muhamad R
Intention to undergo faecal occult blood testing in an ethnic minority.
Int J Nurs Pract. 2019; 25(2):e12721 [PubMed] Related Publications
AIM: To explore factors associated with the intention of an ethnic minority of Israeli Arabs to undergo faecal occult blood testing using the Health Belief Model.
METHODS: This was a quantitative correlational study that utilized a questionnaire constructed based on the Health Belief Model. The questionnaire was administered to a convenience sample of 200 Israeli Arabs aged 50 and over. Data were collected during January to March 2018.
FINDINGS: The research findings show that respondents had a high intention to undergo faecal occult blood testing in the future, although only 66.5% of the respondents had ever undergone it in the past. Physicians and nurses were the most significant sources of information regarding the faecal occult blood testing. The Health Belief Model explained 46% of variance in the intention to undergo the faecal occult blood testing among Israeli Arabs, with perceived benefits of testing being the most significant predictor of this intention.
CONCLUSION: The Health Belief Model can serve as a basis for planning intervention programmes to be implemented by health care professionals to raise the intention of ethnic minorities to undergo faecal occult blood testing.

Rottenberg Y, Zick A, Levine H
Temporal trends of geographic variation in mortality following cancer diagnosis: a population-based study.
BMC Public Health. 2019; 19(1):22 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Inequalities among the western population, combined with the introduction of new treatment options for cancer, have challenged endeavors to provide equal care to patients with cancer. Israel's highly developed healthcare system and mandatory National Health Insurance afforded an opportunity to study geographic variation over time in mortality following cancer diagnosis.
METHODS: This historical prospective cohort study included a nationally representative cohort that was assessed by the Israeli Central Bureau of Statistics 1995 census and followed until 2011. The cancer incidence (1995-2009) was ascertained by the Israel National Cancer Registry. We analyzed the effect on patient outcome of living in a given district, according to the Israeli Central Bureau of Statistics classification. Patients were stratified by the year of diagnosis (1995-1997, 1998-2000, etc.), and associations were adjusted for age, ethnicity, and districts. We excluded patients with malignancies associated with screening program (breast, prostate, colon, and cervical cancers).
RESULTS: This study included 26,173 patients living in 13 residential districts. During the last years (2007-2009) of the study, the hazard ratio (HR) for risk of death was high in 8/13 districts (61.5%), compared to 4/13 (30.7%) during 2004-2006, and 0/13 (0%) during 2001-2003. Districts that were less likely to be associated with increased risk of death were located in the center of Israel and in metropolitan areas, compared to the peripheral regions. Furthermore, HRs were substantially higher in the last years of the study (2007-2009, HRs rose to 1.69, 95%CI: 1.38-2.08) compared to the earlier years (2004-2006, HRs rose to 1.35, 95%CI: 1.13-1.62).
CONCLUSION: Our findings suggested that geographic variation for mortality following cancer diagnosis have increased over time. Our results provide policy makers with vital information regarding the need for targeted interventions, mainly in peripheral regions.

Leader A, Ten Cate V, Ten Cate-Hoek AJ, et al.
Managing Anti-Platelet Therapy in Thrombocytopaenic Patients with Haematological Malignancy: A Multinational Clinical Vignette-Based Experiment.
Thromb Haemost. 2019; 119(1):163-174 [PubMed] Related Publications
Data on anti-platelet therapy (APT) for prevention of atherothrombotic events in thrombocytopaenic cancer patients is lacking. We aimed to identify patient and physician characteristics associated with APT management in thrombocytopaenic patients with haematological malignancy. A clinical vignette-based experiment was designed. Eleven haematologists were interviewed, identifying five variable categories. Next, 18 hypothetical vignettes were generated. Each physician received three vignettes and chose to: hold all APT; continue APT without platelet transfusion support; or continue APT with platelet transfusion support. The survey was distributed to haematologists and thrombosis specialists in three countries. Multivariate cluster robust Poisson regression models were used to calculate relative risks (RRs) of using one management option (over the other) for each variable in comparison to a reference variable. A total of 145 physicians answered 434 cases. Clinicians were more likely to hold APT in case of 20,000/µL platelets (vs. 40,000/µL; RR for continuing: 0.82 [95% confidence interval: 0.75-0.91]), recent major gastrointestinal bleeding (vs. none; RR 0.81 [0.72-0.92]) and when the physician worked at a university-affiliated community hospital (vs. non-academic community hospital; RR 0.84 [0.72-0.98]). Clinicians were more likely to continue APT in ST elevation myocardial infarction with dual APT (vs. unstable angina with single APT; RR 1.31 [1.18-1.45]) and when there were institutional protocols guiding management (vs. none; RR 1.15 [1.03-1.27]). When APT was continued, increased platelet transfusion targets were used in 34%. In summary, the decision process is complex and affected by multiple patient and physician characteristics. Platelet transfusions were frequently chosen to support APT, although no evidence supports this practice.

Lifshitz G, Gruber M, Ronen O
Occult malignancy in pediatric tonsil and adenoid surgeries - A national survey.
Int J Pediatr Otorhinolaryngol. 2019; 117:171-174 [PubMed] Related Publications
OBJECTIVE: To evaluate the incidence of tonsil and adenoid malignancy in pediatric patients in Israel compared to the known literature and to revisit the common practice of routine histopathologic examination of tonsils and adenoids.
METHODS: Analysis of the Israel National Cancer Registry data on pediatric tonsil and adenoid malignancies between the years 2005 and 2015, and a systematic literature review of all relevant articles that reported on malignancies amongst pediatric patients who underwent tonsillectomy with or without adenoidectomy.
RESULTS: Only seven cases of tonsillar malignancies were documented out of 152,352 (0.0052%) surgeries in the pediatric population. All malignancies were lymphoproliferative and mainly Burkitt's lymphoma. In our medical center no malignancy was found in 2165 patients in the same age groups and time period. We found the incidence of tonsillar malignancy in Israel to be significantly lower (p = 0.013) compared to the previously described literature.
CONCLUSION: The incidence of malignancy in routine histopathological examination of tonsils and adenoids is Israel is very low when compared to the known literature. According to these results, we suggest that routine histopathological examination of all such samples is not clinically justified.

Leibovici A, Sharon R, Azoulay D
BDNF Val66Met is Associated with Pre-existing but not with Paclitaxel-induced Peripheral Neuropathy in an Israeli Cohort of Breast Cancer Patients.
Isr Med Assoc J. 2018; 20(12):746-748 [PubMed] Related Publications
BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a neuronal growth factor that is important for the development, maintenance, and repair of the peripheral nervous system. The BDNF gene commonly carries a single nucleotide polymorphism (Val66Met-SNP), which affects the cellular distribution and activity-dependent secretion of BDNF in neuronal cells.
OBJECTIVES: To check the association between BDNF Val66Met-SNP as a predisposition that enhances the development of chemotherapy-induced peripheral neuropathy in an Israeli cohort of patients with breast cancer who were treated with paclitaxel.
METHODS: Peripheral neuropathy symptoms were assessed and graded at baseline, before beginning treatment, and during the treatment protocol in 35 patients, using the reduced version of the Total Neuropathy Score (TNSr). Allelic discrimination of BDNF polymorphism was determined in the patients' peripheral blood by established polymerase chain reaction and Sanger sequencing.
RESULTS: We found Val/Val in 20 patients (57.14%), Val/Met in 15 patients (42.86%), and Met/Met in none of the patients (0%). Baseline TNSr scores were higher in Met-BDNF patients compared to Val-BDNF patients. The maximal TNSr scores that developed during the follow-up in Met-BDNF patients were higher than in Val-BDNF patients. However, exclusion of patients with pre-existing peripheral neuropathy from the analysis resulted in equivalent maximal TNSr scores in Met-BDNF and Val-BDNF patients.
CONCLUSIONS: These observations suggest that BDNF Val66met-SNP has no detectable effect on the peripheral neuropathy that is induced by paclitaxel. The significance of BDNF Val66Met-SNP in pre-existing peripheral neuropathy-related conditions, such as diabetes, should be further investigated.

Bernstein-Molho R, Laitman Y, Schayek H, et al.
The rate of the recurrent MSH6 mutations in Ashkenazi Jewish breast cancer patients.
Cancer Causes Control. 2019; 30(1):97-101 [PubMed] Related Publications
BACKGROUND: Whether breast cancer (BC) should be considered within the spectrum of tumors in Lynch syndrome (LS) is unsettled. Recently, MSH6 and PMS2 germline mutations have reportedly been associated with an increased BC risk and with hereditary breast and ovarian cancer (HBOC) phenotype. We assessed the rates of the recurring Ashkenazi Jewish (AJ) mutations in the MSH6 gene (c.3984_3987dupGTCA and c.3959_3962delCAAG) in AJ cases with seemingly sporadic BC or HBOC phenotype, who were negative for the founder AJ BRCA1/2 mutations.
METHODS: All AJ individuals, affected with BC ≤ 70 years and/or ovarian cancer at any age who were counseled, genotyped and tested negative for the BRCA1/2 founder mutations between January 2010 and February 2018 at the Oncogenetics unit, Sheba Medical Center, were genotyped for the AJ mutations in MSH6.
RESULTS: Of 1016 genotyped participants (815 BC cases, 132 ovarian cancer cases, and 69 with more than one cancer), five carriers (0.49%) of the recurring AJ mutations in MSH6 were identified. All had BC, and two had personal history of additional cancers (pancreatic, endometrial, colorectal). The rate of MSH6 mutations was 0.93% (4/429) when considering only cases with a personal or first-degree relative with LS-related cancer, and 0.17% (1/587) of cases with second-degree relative or no family history of LS-related cancers (p = 0.087).
CONCLUSIONS: Our data suggest the spectrum of genotyped mutations in AJ BC patients with a personal or family history of LS-related cancers should be expanded. These data should be validated in other populations with a similar phenotype.

Hayek S, Dichtiar R, Shohat T, et al.
Risk of second primary neoplasm and mortality in childhood cancer survivors based on a national registry database.
Cancer Epidemiol. 2018; 57:127-133 [PubMed] Related Publications
OBJECTIVE: Although overall childhood cancer survival has improved, survivors may still have an elevated risk for second primary neoplasm (SPN) and excess mortality. The aim of the current study was to estimate the risks for SPN and mortality in childhood cancer survivors in Israel as compared to the general population.
METHODS: All children aged 0-19 diagnosed with primary neoplasm between 1980-2007 who survived at least 5 years following diagnosis were included in the study. Follow-up continued until December 31st, 2013, or diagnosis of SPN, or death due to any cause (the earliest of these events). Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) were calculated. Cox proportional hazards regression was employed to assess predictors of SPN and mortality.
RESULTS: The cohort consisted of 6637 childhood cancer survivors. A total of 244 all-site SPN cases were observed. Compared to the general population, the risks for SPN and for mortality were significantly increased (SIR = 5.48; 95%CI: 4.82-6.22 and SMR = 13.99; 95%CI = 12.54-15.56, respectively). Factors predicting SPN were sex (female), older age at first diagnosis, and initial cancer diagnosis (lymphomas). Factors predicting mortality were older age at first diagnosis, initial cancer diagnosis (myeloproliferative diseases) and earlier years, according to calendar period of initial diagnosis.
CONCLUSIONS: Although 5-year childhood cancer survival is high, survivors are at elevated risk for SPN and mortality, and the risks are associated with baseline characteristics of the patients. The increased risks should be considered when planning treatment, follow-up and surveillance of the survivors.

Inbar M, Herishanu Y, Goldschmidt N, et al.
Hairy Cell Leukemia: Retrospective Analysis of Demographic Data and Outcome of 203 Patients from 12 Medical Centers in Israel.
Anticancer Res. 2018; 38(11):6423-6429 [PubMed] Related Publications
BACKGROUND/AIM: In this retrospective study, we summarized the national Israeli experience with hairy cell leukemia (HCL) in a large cohort of patients with a long follow-up.
PATIENTS AND METHODS: Demographic data, and relevant laboratory and clinical parameters were analyzed, emphasizing the outcome after first-line treatment with cladribine.
RESULTS: Data on 203 patients was collected from 12 medical centers during 1985-2015. Mean and median follow-up were 7.5 years and 5.18 years (interquartile range=0.1-40 years), and 5- and 10-year survival were 96% and 90.62%, respectively. The median age of diagnosis was 55.5 years for Jews and 49 years for Arabs (p=0.021), and most patients were males (81.77%); 52.2% were Ashkenazi Jews, 36.1% Sephardic Jews and 11.7% were Arab, Druze or other ethnicity. Cladribine was given to 159 patients (80.7%%) and most (62%) received intravenous (i.v.) and 38% received subcutaneous (s.c.) therapy. Overall survival and time to next treatment were not significantly different between the two schedules (i.v., s.c.). In univariate analysis of a variety of factors, only age >65 years had a negative impact on outcome, with shorter overall survival. It is of interest that Arab patients with HCL were diagnosed at an earlier age, but had a similar clinical course and outcome to both Ashkenazi and Sephardic Jews.

Dotan G, Qureshi HM, Toledano-Alhadef H, et al.
Prevalence of Strabismus Among Children With Neurofibromatosis Type 1 Disease With and Without Optic Pathway Glioma.
J Pediatr Ophthalmol Strabismus. 2019; 56(1):19-22 [PubMed] Related Publications
PURPOSE: To evaluate the prevalence of strabismus in neurofibromatosis type 1 (NF-1) by comparing children with normal neuroimaging to those with optic pathway glioma.
METHODS: A retrospective data collection of all children with NF-1 with neuroimaging studies examined at a single medical center between 2000 and 2016.
RESULTS: Of the 198 children with NF-1 reviewed, 109 (55%) were male, 121 (61%) had normal neuroimaging, and 77 (39%) had an optic pathway glioma. Mean age at presentation was 6.3 ± 4.7 years and mean follow-up was 4.8 ± 3.1 years. Strabismus was present in 29 (15%) children and was significantly more prevalent in children with NF-1 with optic pathway glioma (21 of 77 [27%]) than in those with normal neuroimaging (8 of 121 [7%], P < .001). Sensory strabismus was only found in children with optic pathway glioma, accounting for most cases (12 of 21 [57%]). A strong association between strabismus and optic pathway glioma is demonstrated by an odds ratio of 5.29 (P < .001). Children with NF-1 with optic pathway glioma have a 4.13 times higher relative risk of developing strabismus than children with NF-1 without it (P = .001). The direction of ocular misalignment in children with NF-1 with optic pathway glioma was not significantly different than that observed in children without optic pathway glioma (P = .197, Fisher's exact test). Only 5 (17%) children with NF-1 with strabismus (3 with optic pathway glioma) underwent corrective surgery to align their eyes.
CONCLUSIONS: Optic pathway glioma in children with NF-1 is associated with an increased risk of strabismus that is often sensory. Although exotropia is the most common ocular misalignment associated with optic pathway glioma, the direction of strabismus cannot be used as an accurate predictor for its presence. [J Pediatr Ophthalmol Strabismus. 2019;56(1):19-22.].

Shitara K, Doi T, Dvorkin M, et al.
Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial.
Lancet Oncol. 2018; 19(11):1437-1448 [PubMed] Related Publications
BACKGROUND: Trifluridine/tipiracil showed activity and was well tolerated in a phase 2 study of pretreated patients with advanced gastric cancer done in Japan. We investigated whether the treatment was efficacious compared with placebo in a global population.
METHODS: TAGS was a randomised, double-blind, placebo-controlled, phase 3 trial done in 110 academic hospitals in 17 countries. Patients aged 18 years or older with histologically confirmed, non-resectable, metastatic gastric adenocarcinoma (including adenocarcinoma of the gastroesophageal junction) as defined by the American Joint Committee on Cancer staging classification (7th edition) who had received at least two previous chemotherapy regimens and had experienced radiological disease progression were eligible for inclusion. Patients were randomly assigned (2:1) via dynamic randomisation from a centralised interactive voice-response system to receive either oral trifluridine/tipiracil (35 mg/m
FINDINGS: Between Feb 24, 2016, and Jan 5, 2018, 507 patients were enrolled and randomly assigned, 337 to the trifluridine/tipiracil group and 170 to the placebo group. Median overall survival was 5·7 months (95% CI 4·8-6·2) in the trifluridine/tipiracil group and 3·6 months (3·1-4·1) in the placebo group (hazard ratio 0·69 [95% CI 0·56-0·85]; one-sided p=0·00029, two-sided p=0·00058). Grade 3 or worse adverse events of any cause occurred in 267 (80%) patients in the trifluridine/tipiracil group and 97 (58%) in the placebo group. The most frequent grade 3 or worse adverse events of any cause were neutropenia (n=114 [34%]) and anaemia (n=64 [19%]) in the trifluridine/tipiracil group and abdominal pain (n=15 [9%]) and general deterioration of physical health (n=15 [9%]) in the placebo group. Serious adverse events of any cause were reported in 143 (43%) patients in the trifluridine/tipiracil group and 70 (42%) in the placebo group. One treatment-related death was reported in each group (because of cardiopulmonary arrest in the trifluridine/tipiracil group and because of toxic hepatitis in the placebo group).
INTERPRETATION: Trifluridine/tipiracil significantly improved overall survival compared with placebo and was well tolerated in this heavily pretreated population of patients with advanced gastric cancer. Trifluridine/tipiracil could be a new treatment option in this population who represent a high unmet medical need.
FUNDING: Taiho Oncology and Taiho Pharmaceutical.

Levin D, Grinfeld G, Greenberg V, et al.
Real-time Online Matching in High Dose-per-Fraction Treatments: Do Radiation Therapists Perform as Well as Physicians?
Pract Radiat Oncol. 2019; 9(2):e236-e241 [PubMed] Related Publications
PURPOSE: In our department, for high dose-per-fraction treatments such as stereotactic body radiation therapy, we require a physician to perform the pretreatment on-board imaging match. The purpose of this study was to determine whether patient-matching positioning performed by radiation therapists (RTTs) is as accurate as that performed by physicians.
METHODS AND MATERIALS: Sixteen RTTs and 5 physicians participated in this study. Data were collected from 113 patients, totaling 324 measurements. A total of 60 patients were treated for bone lesions and 53 for soft-tissue lesions, such as lung and liver. Matching was performed using kV-kV imaging for bones and cone beam computed tomography for soft tissue. All treatments were delivered on Varian linear accelerators. The initial match was performed by the RTTs, and the shifts were noted. Subsequently, the match was reset, and the physician performed an independent match blinded to the RTT match. Physician shifts were applied for treatment. We used the Wilcoxon rank sum test to determine the statistical significance between RTT and physician shifts.
RESULTS: The differences in patient shifts between physicians and RTTs were calculated in 3 translational 1 one rotational axis. The average vector shift was 0.88 ± 0.57 cm versus 0.91 ± 0.57 cm for RTTs versus physicians, respectively. Neither the average vector nor the individual axis shifts were statistically significantly different (P > .2). There was no significant difference when testing for bony or soft lesion matches separately.
CONCLUSIONS: RTT on-board imaging matching is as accurate as physician matching for both bone and soft tissue lesions. On the basis of these results, RTTs are as qualified as physicians to perform a pretreatment match. Thus, it may be feasible for the RTTs to perform the match and the physician to review it offline after treatment without being present at the machine during treatment. Our results show that this approach does not compromise patient safety.

Peer M, Azzam S, Gofman V, et al.
Robotic Mediastinal Surgery in Patients with Suspected Thymic Neoplasms: First Israeli Experience.
Isr Med Assoc J. 2018; 20(10):637-641 [PubMed] Related Publications
BACKGROUND: Thymectomy is a reliable surgical method for treating patients with myasthenia gravis (MG) and benign tumors of the thymus. Despite the advantages of minimally invasive surgical approaches for resection of thymic neoplasms, there are still controversies regarding the superiority of one type of surgery over another.
OBJECTIVES: To report the results of our initial Israeli experience with robotic thymectomy in 22 patients with MG and suspected benign thymic tumors.
METHODS: We retrospectively analyzed 22 patients (10 men, 12 women) who underwent robotic thymectomy by a left-sided (16) or right-sided approach (6) using the da Vinci robotic system at Assaf Harofeh Medical Center. Seven patients were diagnosed with MG before surgery and 14 had suspected benign thymic neoplasms.
RESULTS: Average operative time was 90 minutes. There were no deaths or intraoperative complications. Postoperative complications occurred in two patients (dyspnea and pleural effusion). Median blood loss was 12.3 cc (range 5-35 cc), median hospital stay 2.9 days (range 2-5 days), and mean weight of resected thymus 32.1 grams. Seven patients had thymic hyperplasia, six a lipothymoma, one a thymic cyst. Seven each had thymomas in different stages and one had a cavernous hemangioma.
CONCLUSIONS: Robotic thymectomy is a safe, technically effective surgical method for resection of thymic neoplasms. The advantages of this technique are safety, short hospitalization period, little blood loss, and low complications. We have included this surgical procedure in our thoracic surgery residency program and recommend a learning curve program of 10 to 12 procedures during residency.

Turner MC, Gracia-Lavedan E, Momoli F, et al.
Nonparticipation Selection Bias in the MOBI-Kids Study.
Epidemiology. 2019; 30(1):145-153 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: MOBI-Kids is a 14-country case-control study designed to investigate the potential effects of electromagnetic field exposure from mobile telecommunications devices on brain tumor risk in children and young adults conducted from 2010 to 2016. This work describes differences in cellular telephone use and personal characteristics among interviewed participants and refusers responding to a brief nonrespondent questionnaire. It also assesses the potential impact of nonparticipation selection bias on study findings.
METHODS: We compared nonrespondent questionnaires completed by 77 cases and 498 control refusers with responses from 683 interviewed cases and 1501 controls (suspected appendicitis patients) in six countries (France, Germany, Israel, Italy, Japan, and Spain). We derived selection bias factors and estimated inverse probability of selection weights for use in analysis of MOBI-Kids data.
RESULTS: The prevalence of ever-regular use was somewhat higher among interviewed participants than nonrespondent questionnaire respondents 10-14 years of age (68% vs. 62% controls, 63% vs. 48% cases); in those 20-24 years, the prevalence was ≥97%. Interviewed controls and cases in the 15- to 19- and 20- to 24-year-old age groups were more likely to have a time since start of use of 5+ years. Selection bias factors generally indicated a small underestimation in cellular telephone odds ratios (ORs) ranging from 0.96 to 0.97 for ever-regular use and 0.92 to 0.94 for time since start of use (5+ years), but varied in alternative hypothetical scenarios considered.
CONCLUSIONS: Although limited by small numbers of nonrespondent questionnaire respondents, findings generally indicated a small underestimation in cellular telephone ORs due to selective nonparticipation.

Itskoviz D, Tamary H, Krasnov T, et al.
Endoscopic findings and esophageal cancer incidence among Fanconi Anemia patients participating in an endoscopic surveillance program.
Dig Liver Dis. 2019; 51(2):242-246 [PubMed] Related Publications
BACKGROUND AND AIMS: The primary clinical characteristics of Fanconi Anemia (FA) include typical physical features, progressive bone marrow failure, and an increased incidence of neoplasms, including esophageal carcinoma. Currently, there are no data regarding endoscopic findings or the interval time to malignancy in these patients. Data about the contribution of Human Papilloma Virus (HPV) to esophageal carcinoma is conflicting. Our objective is to document the upper gastrointestinal (GI) findings at baseline, document cancer incidence, and evaluate the role of HPV among these cancers.
METHODS: We reviewed endoscopic and clinical data of FA subjects who participated in active surveillance before cancer diagnosis. Incident esophageal cancers were stained for HPV
RESULTS: Eight FA patients were included (men 62.5%; median age at first endoscopy 20 years, median endoscopies number: 5.5). At baseline, 8/8 had endoscopic evidence for reflux esophagitis. In 3/8 the reflux esophagitis was mild and in 5/8 it was moderate or severe. During the follow up time (median time 4.5 years 2/8 developed Barrett's esophagus and 2/8 patients had incident esophageal squamous cell carcinoma during follow up, at intervals of eight and eighteen months from the previous upper endoscopy. Both cancers stained negative for HPV
CONCLUSIONS: FA subjects have both an extremely high risk for esophageal cancer within short intervals and a very high prevalence of reflux esophagitis with various severities. Active surveillance programs in specialized centers including annual upper endoscopies should be considered in these patients.

Klil-Drori AJ, Kleinstern G, Seir RA, et al.
Serum organochlorines and non-Hodgkin lymphoma: A case-control study in Israeli Jews and Palestinians.
Chemosphere. 2018; 213:395-402 [PubMed] Related Publications
Associations of organochlorine (OC) pesticides and polychlorinated biphenyls (PCBs) with non-Hodgkin lymphoma are controversial. We compared serum levels of 6 OC pesticides and 38 PCBs in Israeli Jews (IJ) and Palestinian Arabs (PA) and assessed possible associations with B-cell non-Hodgkin lymphoma (B-NHL). Ninety B-NHL cases (50 IJ and 40 PA) and 120 controls (65 IJ and 55 PA) were included. Median concentrations of analytes in controls were compared across ethnic groups using quantile regression, adjusting for age and sex. We used logistic regression to derive odds ratios (OR) and 95% confidence intervals (CI) for detectable analytes and B-NHL, adjusting for age, ethnic group, faming and body mass index. Median values of PCBs and dichlorodiphenyldichloroethylene (DDE) were higher in IJ vs PA controls (P = 0.0007), as were several PCBs (74, 99, 118, 138, 146, 153, 156, 163, 170, and 180). Overall, OC pesticide and PCB exposures were comparable with reports from high-income countries. B-NHL was associated with PCB 146 (OR 1.70, 95% CI: 1.02, 2.83), PCB 156 (OR 1.75, 95% CI: 1.06, 2.89), and high-chlorinated PCBs (OR 1.55, 95% CI: 1.00, 2.40) in all study subjects. These associations were robust in quantile as well as sensitivity analyses. An association of DDE with B-NHL was noted in PA (OR 1.72, 95% CI: 1.07, 2.77), but not in IJ (OR 0.87, 95% CI: 0.59, 1.27). Although high-chlorinated PCB concentrations did not indicate high exposure levels, our findings indicate that B-NHL may be associated with this exposure.

Vaiman M, Halevy A, Cohenpour M, et al.
Evaluation and management of thyroid incidentalomas detected prior to the parathyroid surgery.
Surg Oncol. 2018; 27(3):508-512 [PubMed] Related Publications
BACKGROUND: We investigated the management of thyroid incidentalomas associated with cases of parathyroid lesions in order to suggest a practical approach to their management from a surgical point of view.
METHODS: 639 patients underwent radiological and ultrasound investigation of the thyroid area because of parathyroid disorders and parathyroidectomy and had at least three years of follow-up. All follow-up data for these cases were investigated from the moment the lesion was detected and up to the last report.
RESULTS: Out of 639 cases, incidental or asymptomatic thyroid nodules were found in 179 patients (28%), of which, 22 patients were operated (parathyroidectomy + thyroidectomy) and 157 remained with the nodules. For these patients, the average period of follow-up was 7 years 5 mo. Following the results of the follow-up, 52 patients (33%) were suggested to have surgery of the thyroid gland and 49 were operated (16 total thyroidectomies and 33 hemithyroidectomies). The complications after the second surgery included recurrent laryngeal nerve palsy (n = 3), superior laryngeal nerve palsy (n = 1), permanent hypocalcaemia (n = 8), and surgical damage to the internal jugular vein (n = 1). All complications occurred at the previously operated side of the neck.
CONCLUSION: While surgery remains the management of choice for malignant thyroid incidentalomas, for benign cases, if an asymptomatic thyroid nodule was detected inside the thyroid lobe on the side of planned parathyroidectomy and if the size of the nodule is ˃1.5 cm we suggest combined parathyroidectomy + hemithyroidectomy.

Cox DM, Nelson KL, Clytone M, Collins DL
Hereditary cancer screening: Case reports and review of literature on ten Ashkenazi Jewish founder mutations.
Mol Genet Genomic Med. 2018; 6(6):1236-1242 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Historically, three founder mutations in the BRCA1/2 (OMIM 113705; OMIM 600185) genes have been the focus of cancer risks within the Ashkenazi Jewish (AJ) population. However, there are several additional mutations associated with increased susceptibility to cancer in individuals of AJ ancestry.
METHODS: We report three patients who exemplify the need to keep these additional founder mutations in mind when pursuing hereditary cancer genetic testing of individuals in this population. All gene sequences in this paper were aligned to reference sequences based on human genome build GRCh37/UCSC hg19.
RESULTS: review of the literature discusses that the combined risk is 12.36%-20.83% forhaving 1 of the 10 hereditary cancer AJ founder mutations in the BRCA1, BRCA2, CHEK2 (OMIM 604373), APC (OMIM 611731), MSH2 (OMIM 609309), MSH6 (OMIM 600678), and GREM1 (OMIM 603054) genes for individuals of AJ ancestry.
CONCLUSION: We recommend testing for all 10 of these AJ founder cancer susceptibility mutations for individuals within this population as standard screening in order to ensure appropriate cancer risk management and cascade testing.

Makhoul Khoury S, Ben-Zur H, Ben-Arush M
Mastery and social support moderate the effects of educational level on adjustment of Arab mothers of children diagnosed with cancer.
Eur J Cancer Care (Engl). 2018; 27(6):e12906 [PubMed] Related Publications
The study explored the adjustment of Arab mothers of children diagnosed with cancer, as shown by the mothers' distress and quality of life. The aim was twofold: to examine the associations between educational level, psychosocial resources and adjustment indices and to assess the moderating effects of psychosocial resources on the education and adjustment association. The sample consisted of 100 Arab mothers who completed questionnaires assessing demographic and illness variables, mastery, social support, psychological distress and quality of life. High levels of education and psychosocial resources contributed to low distress and high levels of quality of life. Mastery and social support moderated the effects of education on adjustment: Under low levels of education, higher mastery was related to lower distress and higher quality of life, and higher social support was related to lower distress. Education, mastery and social support are important resources in the context of adjustment to cancer. In addition, psychosocial resources are important factors for adjustment under low levels of education and should be taken into consideration when developing intervention programmes for Arab parents coping with their child's cancer.

Bar-Sela G, Gruber R, Mitnik I, et al.
Attachment Orientation and Relationships With Physicians and Nurses Among Israeli Patients With Advanced Cancer.
Oncol Nurs Forum. 2018; 45(5):631-638 [PubMed] Related Publications
OBJECTIVES: To examine the association between attachment orientation and relationships with physicians and nurses among Israeli patients with advanced cancer.
SAMPLE & SETTING: 52 patients with advanced cancer during active oncologic treatment.
METHODS & VARIABLES: Eligible patients who agreed to participate in the study completed the Experience in Close Relationships Scale, Working Alliance Inventory-Short Revised, and a list of topics, which were defined by the research team as central and common to patients' coping.
RESULTS: A correlation was found between avoidant attachment orientation and working alliance with nurses. In addition, patients' attachment orientation was found to be correlated with the type of topics they chose to share with the staff.
IMPLICATIONS FOR NURSING: Knowledge regarding the theoretical concepts of attachment orientation may assist nurses in providing tailored and beneficial communication patterns with patients.

Michaan N, Park SY, Won YJ, Lim MC
Comparison of gynecologic cancer risk factors, incidence and mortality trends between South Korea and Israel, 1999-2013.
Jpn J Clin Oncol. 2018; 48(10):884-891 [PubMed] Related Publications
Objective: To discuss possible causes of disparities in incidence and mortality rates of ovarian cancer, uterine cancer and cervical cancer between two diverse populations from east and west Asia.
Methods: Incidence and mortality data from 1999 to 2013 were extracted from Korean and Israeli cancer registries. Age-standardized rates and annual percent changes were calculated. Trends were analyzed using Joinpoint analysis and discussed with respect to risk factor exposure.
Results: Age-standardized rate of ovarian cancer significantly increased in Korea (annual percent change 1.7%) but decreased among Jews (annual percent change -2.15%). Age-standardized rate of uterine cancer increased among both Koreans and Israeli Jews (annual percent changes 5.8 and 1.17%, respectively). Incidence of cervical cancer significantly decreased in Korea (annual percent change -3.8%) while remained stable on Israel. Mortality trends paralleled incidence trends with a significant increase in ovarian cancer and uterine cancer mortality in Korea (annual percent changes 1.2 and 4.6%, respectively) and a drop in cervical cancer mortality from 2002 (annual percent change -5.8%). Among Israeli Jews, uterine cancer mortality increased (annual percent change 1.01%), while ovarian cancer mortality decreased (annual percent change -0.58%). Uterine cancer mortality among Arabs declined (annual percent change -0.5%), while cervical cancer mortality remained unchanged.
Conclusions: Gynecologic malignancies show different incidence trends in Korea and Israel. Uterine cancer is rising in both countries and is correlated to changing trends in obesity and dietary habits. Ovarian cancer is rising in Korea but declining among Israeli Jews along with changes in parity, childbearing age, contraceptive use and increasing awareness to BRCA gene carriers and risk reduction salpingo-oophorectomy. Cervical cancer is declining in Korea along with an effective screening program implemented. Mortality trends follow incidence trends in both countries.

Rosner G, Gluck N, Carmi S, et al.
POLD1 and POLE Gene Mutations in Jewish Cohorts of Early-Onset Colorectal Cancer and of Multiple Colorectal Adenomas.
Dis Colon Rectum. 2018; 61(9):1073-1079 [PubMed] Related Publications
BACKGROUND: Germline mutations in the DNA polymerase genes POLD1 and POLE confer high risk for multiple colorectal adenomas and colorectal cancer. However, prevalence and the clinical phenotype of mutation carriers are still not fully characterized.
OBJECTIVE: The purpose of this study was to assess the prevalence of germline mutations and to describe the genotype-phenotype correlation in POLD1 and POLE genes in Jewish subjects with multiple colorectal adenomas and/or early-onset mismatch repair proficient colorectal cancers.
DESIGN: This study is a comparison of genetic and clinical data from affected and control groups.
SETTINGS: The study was conducted at a high-volume tertiary referral center.
PATIENTS: The study cohort included 132 subjects: 68 with multiple colorectal adenomas and 64 with early-onset mismatch repair proficient colorectal cancers. The control group included 5685 individuals having no colorectal cancer or colorectal adenomas.
MAIN OUTCOME MEASURES: Study and control subjects were tested for POLD1 and POLE mutations and a clinical correlation was assessed.
RESULTS: Eleven of the 132 study subjects (8.3%) carried either a POLD1 or a POLE mutation: 7 of 68 (10.3%) subjects with multiple colorectal adenomas and 4 of 64 (6.2%) subjects with early-onset mismatch repair proficient colorectal cancer. Three mutations were detected, showing statistical significance in frequency between study and control groups (p < 0.001). Eight of the 11 mutation carriers were Ashkenazi Jews carrying the same POLD1 mutation (V759I), implicating it as a possible low-to-moderate risk founder mutation. Phenotype of mutation carriers was notable for age under 50 at diagnosis, a propensity toward left-sided colorectal cancer, and extracolonic tumors (64%, 100%, and 27% of cases).
LIMITATIONS: The study cohort was limited by its relatively small size.
CONCLUSIONS: Germline mutations in POLD1 and POLE were found to be relatively frequent in our Jewish cohorts. Further studies are needed to clarify the importance of POLD1 and POLE mutations and to define the most suitable surveillance program for Jewish and other POLD1 and POLE mutation carriers. See Video Abstract at http://links.lww.com/DCR/A658.

Levy I, Vadasz Z, Polliack A, Tadmor T
The Frequency and Prognostic Value of Neutrophilia in Chronic Lymphocytic Leukemia.
Anticancer Res. 2018; 38(8):4731-4734 [PubMed] Related Publications
BACKGROUND/AIM: In chronic lymphocytic leukemia (CLL) the absolute neutrophil count (ANC) has generally been reported to be within normal limits and leukocytosis is due to absolute lymphocytosis. However, other cell types such as neutrophils and monocytes may also exceed the normal range in this disorder. The aim of this retrospective study was to evaluate the frequency and prognostic value of neutrophilia defined as an ANC>7×10
MATERIALS AND METHODS: We analyzed clinical and laboratory data from the records of patients with CLL followed in the Hematology unit of a tertiary hospital in Israel. Patients were categorized according to their ANC and AMC before treatment and their data compared.
RESULTS: In 24 (21%) patients, neutrophilia was present at diagnosis while 40 (35%) had monocytosis. We identified that 9% of cases had neutrophilia with normal AMC. This subgroup of patients had a better prognosis with lower mortality rate, longer time-to-treatment interval and a higher rate of complete or partial response to treatment compared to patients without neutrophilia or monocytosis.
CONCLUSION: The presence of neutrophilia without monocytosis before treatment appears to be associated with a more favorable prognosis in CLL. These observations still need to be confirmed and validated in a larger cohort of patients.

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