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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

Cohen YC, Zuckerman T, Yeshurun M, et al.
Efficacy and safety of autologous hematopoietic cell transplantation in elderly patients with multiple myeloma: a retrospective national multi-site cohort study.
Ann Hematol. 2017; 96(2):271-278 [PubMed] Related Publications
We aimed to test the efficacy and toxicity of autologous hematopoietic cell transplant (HCT) in Multiple Myeloma (MM) patients aged ≥65 years compared to patients aged 60-64. Two hundred twenty consecutive patients (age ≥65, n = 87) with MM aged 60 and above, who underwent HCT as part of an upfront MM treatment, at four Israeli centers between 2000 and 2014 were included. A melphalan dose of 200 mg/m(2) was more frequent in the 60-64 age group vs. the ≥65 age group (77 vs. 57%, p = 0.002). There were no differences between groups in median day of neutrophil engraftment, incidence of infections, grades 3-4 mucositis, cardiovascular events, or non-relapse mortality at 100 days post HCT (4.7, vs. 5%, p = 0.9). A similar rate of improvement in response level was observed (36, vs. 35%, p = 0.87). At 3 years post HCT progression-free survival (PFS) was higher in the 60-64 age group (42 vs. 29%, p = 0.04); however, it was no longer so after adjustment for disease status prior to HCT (p = 0.49). In a Multivariate analysis, melphalan doses and age did not predict PFS. There was no difference in overall survival (OS) between age groups (p = 0.2). We conclude that toxicity profile, response, PFS, and OS of HCT in aged ≥65 patients with myeloma is similar to patients aged 60-64.

Odelia A, Erel J, Chava P, et al.
Continuing dilemmas in the management of lymphoma during pregnancy: review of a 10-point case-based questionnaire.
Int J Clin Oncol. 2017; 22(1):190-199 [PubMed] Related Publications
INTRODUCTION: Due to the rarity of lymphoma during pregnancy, management guidelines are based upon evidence from retrospective studies and case reports. Here, we review the major dilemmas in the field and examine the approach of hemato-oncologists in Israel to the management of lymphoma in pregnancy.
METHODOLOGY: We performed a literature search on the PubMed database using keywords for all papers on the subject from 1990-2014. The papers were reviewed by an expert panel who devised a questionnaire covering the main dilemmas. Sixty questionnaires were sent out.
RESULTS: Non-contrast magnetic resonance imaging was the staging modality of choice. Chemoimmunotherapy was considered relatively safe beyond the first trimester except methotrexate (completed postpartum). Steroids or vinblastine were suggested by most as a reasonable 'bridging therapy' until the second trimester in Hodgkin lymphoma. The dosage of chemoimmunotherapy employed during pregnancy remained debatable; the majority recommended dosage according to actual pregnancy weight. Optimal timing for delivery was considered by most to be >35 weeks. Regarding approach to next pregnancy for patients in complete remission from diffuse large B-cell lymphoma, 69 % advised waiting 2 years but the majority advised 6-12 months for follicular lymphoma.
DISCUSSION: Despite consensus regarding the safety of chemotherapy post first trimester, optimal dosage, central nervous system therapy, timing of delivery and approach to future pregnancies remain controversial, indicating a need for further collaborative research in this field.

Agranat S, Baris H, Kedar I, et al.
Earlier Age of Breast Cancer Onset in Israeli BRCA Carriers-Is it a Real Phenomenon?
Breast J. 2016; 22(6):662-666 [PubMed] Related Publications
Data on genetic anticipation in breast cancer are sparse. We sought to evaluate age at diagnosis of breast cancer in daughters with a BRCA mutation and their mothers. A review of all carriers of the BRCA mutation diagnosed with breast cancer at the Genetics Institute of a tertiary medical center in 2000-2013 yielded 80 women who could be paired with a mother with breast cancer who was either a carrier of the BRCA mutation or an obligate carrier according to pedigree analysis. Age at diagnosis, type of mutation (BRCA1, BRCA2), year of birth, and ethnicity were recorded. Paired t-test was used to analyze differences in age at cancer diagnosis between groups and subgroups. Mean age at diagnosis of breast cancer was 50.74 years (range 22-88) in the mothers and 43.85 years (range 24-75) in the daughters. The difference was statistically significant (p < 0.001). These findings were consistent regardless of type of BRCA mutation, ethnicity, or mother's year of birth. However, on separate analysis of pairs in which the mother was diagnosed before the age of 50 years, there was no significant difference in mean age at diagnosis between mothers and daughters (~42 years for both). Daughters who carry a BRCA mutation are diagnosed with breast cancer at an earlier age than their carrier mothers, with the exception of pairs in which the mother was diagnosed before the age of 50 years. Future breast-screening guidelines may need to target specific subpopulations of BRCA mutation carriers.

Smirnov M, Lazarev I, Perry ZH, et al.
Colorectal cancer in southern Israel: Comparison between Bedouin Arab and Jewish patients.
Int J Surg. 2016; 33 Pt A:109-16 [PubMed] Related Publications
PURPOSE: Colorectal cancer (CRC) is the second most common malignancy and the third leading cause of cancer deaths in Israel; it is less common among the Arab than the Jewish population. This study compares the clinico-pathologic features, treatment, and prognosis between Bedouin-Arab (BA) and Jewish CRC patients treated at our medical centre.
METHODS: The medical records of 56 BA patients with CRC were compared retrospectively to 115 Jewish patients. Collected data included age, gender, history of smoking, family history of cancer, presenting symptoms, laboratory tests, previous malignancy, tumor characteristics, surgery type, stoma formation and closure, types of adjuvant treatment, and outcome.
RESULTS: BA patients were younger (mean age 68 versus 57 years, p < 0.001), showed a higher incidence in females (p = 0.045), and had a lower frequency of a family history of cancer (p = 0.005) compared to Jewish patients. BA patients had a higher presentation of rectal bleeding and a lower rate of anemia at tumor diagnosis (p = 0.05 and p = 0.004, respectively) with a more distal location of the tumor (p = 0.003). BA patients more often received chemotherapy and radiotherapy (p = 0.02 and p = 0.04, respectively). Disease-free survival was shorter among BA patients (p = 0.023); overall survival was similar in both groups.
CONCLUSIONS: CRC in BAs is characterized by a higher proportion of female, younger age, and higher proportion of distal location compared to Jewish patients. These differences in biology may be related to differences in past lifestyles and diet of BA compared to Jewish patients, and are expected to decrease in the following years as the BA population continues to undergo "westernization" changes.

Siegler E, Segev Y, Mackuli L, et al.
Vulvar and Vaginal Cancer, Vulvar Intraepithelial Neoplasia 3 and Vaginal Intraepithelial Neoplasia 3: Experience of a Referral Institute.
Isr Med Assoc J. 2016; 18(5):286-9 [PubMed] Related Publications
BACKGROUND: Vulvar and vaginal malignant and premalignant lesions are uncommon and are clinically heterogeneous diseases with two pathways of carcinogenesis: human papillomavirus (HPV) induced or non-HPV induced.
OBJECTIVES: To evaluate the demographic and clinical characteristics associated with vulvar or vaginal cancer and vulvar and vaginal intraepithelial neoplasia 3 (VIN3, VAIN3).
METHODS: We conducted a retrospective chart review of 148 women with vulvar and vaginal malignancy and pre-malignancy for the period October 2004 to October 2012, and identified 59 and 19 patients with vulvar and vaginal cancer respectively, and 57 and 13 patients with VIN3 and VAIN3 respectively
RESULTS: The median age of vulvar cancer patients was 30 years older than that of VIN3 patients. HPV was found in 60% and 66.6% of vulvar and vaginal cancer patients respectively, and in 82.3% and 84.6% of patients with VIN3 and VAIN3 respectively. A history of cervical intraepithelial neoplasia (CIN) or warts was observed in 10% and 10.5% of vulvar and vaginal cancer patients respectively, and in 57.9% and 46% of patients with VIN3 and VAIN3 respectively. In 52.6% of patients the vaginal cancer was metastases from other organs.
CONCLUSIONS: Most women with vulvar carcinoma are older than 70 years. VIN3 and VAIN3 are associated with HPV infection and the most prevalent type is HPV16. Almost half the vaginal cancers are associated with metastases from other organs and almost half of VAIN3 is associated with past cervical dysplasia or carcinoma.

Wiser I, Scope A, Azriel D, et al.
Head and Neck Cutaneous Squamous Cell Carcinoma Clinicopathological Risk Factors according to Age and Gender: A Population-based Study.
Isr Med Assoc J. 2016; 18(5):275-8 [PubMed] Related Publications
BACKGROUND: Clinicopathological risk factors for cutaneous squamous cell carcinoma of the head and neck (CSCCHN) are associated with local recurrence and metastasis.
OBJECTIVES: To compare the incidence and risk factors of CSCCHN by age and gender in order to help refine the clinical evaluation and treatment process.
METHODS: Clinical and pathological data of all patients diagnosed with CSCCHN during 2009-2011 were obtained from a central pathology laboratory in Israel. Estimated incidence rate calculation was standardized to the 2010 Israeli population. Independent risk factors for poorly differentiated CSCCHN were analyzed using logistic regression.
RESULTS: CSCCHN was diagnosed in 621 patients. Mean age was 75.2 years; mean tumor horizontal diameter was 11.1 ± 6.8 mm. The overall estimated incidence rate in males was higher than in females (106.2 vs. 54.3 per 1,000,000, P 0.001). Twenty cases (3.2%) had poorly differentiated CSCCHN. Scalp and ear anatomic locations were observed more often in males than in females (22.1% vs. 6.1% and 20.3% vs. 3.3%, respectively, P < 0.001). Per 1 mm increment, tumor horizontal diameter increased the risk for poorly differentiated CSCCHN by 6.7% (95% CI 1.3-12.4%, P = 0.014).
CONCLUSIONS: CSCCHN clinicopathological risk factors are not distributed evenly among different age and gender groups.

Livovsky DM, Pappo O, Skarzhinsky G, et al.
Gastric Polyp Growth during Endoscopic Surveillance for Esophageal Varices or Barrett's Esophagus.
Isr Med Assoc J. 2016; 18(5):267-71 [PubMed] Related Publications
BACKGROUND: We recently observed patients with chronic liver disease (CLD) or chronic reflux symptoms (CRS) who developed gastric polyps (GPs) while undergoing surveillance gastroscopies for the detection of esophageal varices or Barrett's esophagus, respectively.
OBJECTIVES: To identify risk factors for GP growth and estimate its growth rate.
METHODS: GP growth rate was defined as the number of days since the first gastroscopy (without polyps) in the surveillance program, until the gastroscopy when a GP was discovered.
RESULTS: Gastric polyp growth rates in CLD and CRS patients were similar. However, hyperplastic gastric polyps (HGPs) were detected more often (87.5% vs. 60.5%, P = 0.051) and at a higher number (2.57 ± 1.33 vs. 1.65 ± 0.93, P = 0.021) in the CLD patients. Subgroup analysis revealed the following findings only in CLD patients with HGPs: (i) a positive correlation between the GP growth rate and the patient's age; the older the patient, the higher the GP growth rate (r = 0.7, P = 0.004). (ii) A negative correlation between the patient's age and the Ki-67 proliferation index value; the older the patient, the lower the Ki-67 value (r = -0.64, P = 0.02). No correlation was detected between Ki-67 values of HGPs in CLD patients and the presence of portal hypertension, infection with Helicobacter pylori, or proton pump inhibitor use.
CONCLUSIONS: In comparison with CRS patients, CLD patients developed HGPs more often and at a greater number. Young CLD patients may have a tendency to develop HGPs at a faster rate than elderly CLD patients.

Bruwiere E, Van Roosbroeck S, Van Hal G, et al.
An exploration of attitudes towards breast cancer screening in orthodox Jewish women in Antwerp--Belgium.
Eur J Gynaecol Oncol. 2016; 37(3):384-7 [PubMed] Related Publications
OBJECTIVE: To explore determinants of participation in breast cancer screening in orthodox Jewish women living in Antwerp, Belgium, and to uncover their opinions and attitudes towards screening, and thereby to detect ways to optimize participation.
STUDY DESIGN: Focus group discussions were performed during the last months of 2011 and the first half of 2012 to explore motivation to participate or not in breast cancer screening. Groups consisted of five to seven women. Inclusion criteria were: being female, considering oneself as orthodox Jewish, aged between 50 and 69 years.
RESULTS: Three focus group discussions with in a total of 20 women had taken place. All participants in the focus group discussions had a screening mammography taken on a regular base. All participants agreed that the social cohesion between Jewish orthodox women and the importance that is given to healthcare within the Jewish tradition are important contributors to their participation in a breast cancer screening program. Pain, lack of information during the exam, lack of confidence in the quality of the exam, perceived problems when the examining doctor/technician is male, and fear of the results are mentioned as barriers. The participants, however, state that these were not important enough to result in non-participation. Barriers could be diminished by information sessions specifically aimed at orthodox Jewish women.
CONCLUSION: This qualitative research demonstrates a generally positive attitude of orthodox Jewish women living in Antwerp, Belgium, towards mammographic breast cancer screening. Increased and repeated structured information sessions are likely to improve breast cancer awareness in this population.

Bassal R, Schejter E, Bachar R, et al.
Risk Factors for Cervical Cancer and CIN3 in Jewish Women in Israel - Two Case Control Studies.
Asian Pac J Cancer Prev. 2016; 17(4):2067-73 [PubMed] Related Publications
PURPOSE: The aim of the study was to identify risk and protective factors/markers for cervical cancer and cervical intraepithelial neoplasia 3 (CIN3) in Israeli Jewish women in order to settle the discrepancy of low incidence rate of cervical cancer and relatively high incidence rate of CIN3.
MATERIALS AND METHODS: We conducted two case control studies, which examined the association between potential risk and protective factors/markers for cervical cancer or CIN3 using self administered detailed questionnaires.
RESULTS: For studying cervical cancer, 40 cases and 40 matched controls were interviewed. In the univariable and multivariable analyses older age, depression or anxiety and ever smoking seemed to act as independent risk factors/markers, while older age at first intercourse was protective. For studying CIN3, 99 cases and 79 controls were interviewed. Multivariable analysis has demonstrated that being born in Israel, depression or anxiety and ever smoking were independent risk factors/markers for CIN3.
CONCLUSIONS: The risk factors/markers studied, that were associated with cervical cancer or CIN3 among Jewish women in Israel, are similar to those reported in other parts of the world, and do not explain the observed discrepancy of high in-situ cervical cancer rates and low invasive cervical cancer incidence in Israel.

Soyfer V, Corn BW, Bickels J, Merimsky O
Primary high-grade soft-tissue sarcoma of the buttock: a rare but distinct clinical entity.
Br J Radiol. 2016; 89(1062):20151017 [PubMed] Article available free on PMC after 01/06/2017 Related Publications
OBJECTIVE: Sarcoma arising in the region of the buttocks is a rare entity and therefore no consensus regarding management exists in the literature.
METHODS: 16 patients diagnosed with localized, non-metastatic primary soft-tissue sarcoma (STS) in the buttock area, who were consecutively treated between 2005 and 2013, were retrospectively evaluated for the rate of local control, distant metastases and overall survival.
RESULTS: Most tumours were classified as high grade (87.5%). The average time between the appearances of symptoms to diagnosis of sarcoma was 4.5 months. At the end of the observation period, 7 (44%) patients were alive without signs of progressive disease, 37.5% patients died as the disease progressed, 13 patients were free of disease and 3 (19%) patients were alive with signs of progressive disease. Seven (44%) patients developed local recurrence. Six (37.5%) patients developed distant metastases. The lung was the most common site of distant failure (four patients); other sites were the liver as well as the adrenal gland and kidney (one patient). Four patients had both distant and local progression, three patients experienced isolated local recurrence and two patients developed isolated distant metastases. 5-year local recurrence-free survival was 58% and 5-year distant metastases-free survival was 63%.
CONCLUSION: It is unclear whether to subsume STS of the buttock under the rubric of pelvic tumours or tumours of the lower extremity. Either way, STS of the buttock seems to be characterized by local control, freedom from distant relapse and survival, which is inferior to accepted standards for either pelvic or lower extremity sarcomas. To improve this poor outcome, oncologists are encouraged to regard sarcoma of the buttock as a distinct clinical entity and to devise innovative therapeutic strategies accordingly.
ADVANCES IN KNOWLEDGE: Sarcoma of the buttock area should possibly be regarded as a distinct entity.

Orenstein L, Chetrit A, Dankner R
Healthy Lifestyle Pattern is Protective Against 30-Yr Cancer Incidence in Men and Women: A Cohort Study.
Nutr Cancer. 2016; 68(3):410-9 [PubMed] Related Publications
OBJECTIVES: Investigate associations of healthier behaviors with 30-yr cancer incidence.
SUBJECTS/METHODS: In 1982, 632 healthy men and women (ages 40-70) were interviewed for nutritional habits using a Food Frequency Questionnaire and a 24-h physical activity questionnaire. Blood pressure, weight, and height were measured, and blood was drawn for biochemical profiles. Thirteen and four subjects were excluded due to cancer diagnosis ≤1 yr from recruitment and extreme values of reported total daily calorie intake, respectively.
RESULTS: During a mean follow-up of 24.2 yr, 146 cancer incident patients (23.7%) were documented. Total cancer risk was 38% lower in the medium vegetable intake tertile [adjusted hazards ratio (HR) = 0.62, 95%confidence interval (CI): 0.40-0.95], and 66% higher in the medium fruit intake tertile (adjusted HR = 1.66, 95%CI: 1.08-2.55) compared to the lowest tertile. The risk of gastrointestinal cancers was 3 times greater for the highest, compared to the lowest, dairy consumption tertile (HR = 3.06, 95%CI: 1.01-9.23). "Healthy lifestyle" (normal BMI, never smoked, consuming high levels of dietary fiber and vegetables, and more physically active) reduced overall cancer risk (adjusted HR = 0.63, 95%CI: 0.44-0.91) as compared to the rest of the cohort.
CONCLUSIONS: Our findings reinforce the importance of lifestyle-related factors, which are relatively low-cost and may contribute to reduction in the burden of malignant diseases.

Leiba M, Leiba A, Keinan-Boker L, et al.
Adolescent weight and height are predictors of specific non-Hodgkin lymphoma subtypes among a cohort of 2,352,988 individuals aged 16 to 19 years.
Cancer. 2016; 122(7):1068-77 [PubMed] Related Publications
BACKGROUND: The age-adjusted annual incidence of non-Hodgkin lymphoma (NHL) has risen worldwide. This trend may be affected by the secular increase in height and the sharp upswing in adolescent overweight; these drive increased insulinlike growth factor 1 and chronic inflammation, which may play an etiologic role. This study examined the association of the body mass index (BMI) and height of adolescents with NHL subtypes, which have been insufficiently evaluated.
METHODS: Health-related data on 2,352,988 Israeli adolescents, aged 16 to 19 years, who were examined between 1967 and 2011 were linked to the Israel National Cancer Registry to derive the NHL incidence up to December 31, 2012 (4021 cases). Cox proportional hazards modeling was used to estimate the multivariate-adjusted hazard ratio (HR) for NHL subtypes associated with the BMI and height of adolescents.
RESULTS: Adolescent overweight and obesity were associated with an HR of 1.25 (95% confidence interval [CI], 1.13-1.37; P = 1.14 × 10(-5) ) for NHL in comparison with normal weight. There was a graded association of height with NHL (P = 4.29 × 10(-9) ), with the tallest adolescents (≥ 95th percentile vs 25th to < 50th percentiles [US Centers for Disease Control and Prevention]) exhibiting an HR of 1.28 (95% CI, 1.04-1.56). Marginal zone lymphoma, primary cutaneous lymphoma (PCL), and diffuse large B-cell lymphoma (DLBCL) showed the strongest associations for overweight/obesity, and DLBCL and PCL showed the strongest associations for height.
CONCLUSIONS: The findings of this large cohort study add to the growing body of evidence showing that higher body weight and taller stature during adolescence are associated with an increased risk of NHL and may modestly contribute to its increasing incidence. Further studies are needed to elucidate the mechanisms linking anthropometric measures and NHL risk.

Abir R, Ben-Aharon I, Garor R, et al.
Cryopreservation of in vitro matured oocytes in addition to ovarian tissue freezing for fertility preservation in paediatric female cancer patients before and after cancer therapy.
Hum Reprod. 2016; 31(4):750-62 [PubMed] Related Publications
STUDY QUESTION: Is a protocol that combines in vitro maturation of germinal vesicle-stage oocytes and their vitrification with freezing of cortical ovarian tissue feasible for use in fertility preservation for both chemotherapy-naive paediatric patients as well as patients after initiation of cancer therapy?
SUMMARY ANSWER: Follicle-containing ovarian tissue as well as oocytes that can undergo maturation in vitro can be obtained from paediatric patients (including prepubertal girls) both before and after cancer therapy.
WHAT IS KNOWN ALREADY: Anticancer therapy reduces the number of follicles/oocytes but this effect is less severe in young patients, particularly the paediatric age group. Autotransplantation of ovarian tissue has yielded to date 60 live births, including one from tissue that was cryostored in adolescence. However, it is assumed that autografting cryopreserved-thawed ovarian cortical tissue poses a risk of reseeding the malignancy. Immature oocytes can be collected from very young girls without hormonal stimulation and then matured in vitro and vitrified. We have previously shown that there is no difference in the number of ovarian cortical follicles between paediatric patients before and after chemotherapy.
STUDY DESIGN, SIZE, DURATION: A prospective study was conducted in a cohort of 42 paediatric females with cancer (before and after therapy initiation) who underwent fertility preservation procedures in 2007-2014 at a single tertiary medical centre.
PARTICIPANTS/MATERIALS, SETTING, METHODS: The study group included girls and adolescent females with cancer: 22 before and 20 after chemotherapy. Following partial or complete oophorectomy, immature oocytes were either aspirated manually ex vivo from visible small antral follicles or filtered from spent media. Oocytes were incubated in oocyte maturation medium, and those that matured at 24 or 48 h were vitrified. Ovarian cortical tissue was cut and prepared for slow-gradual cryopreservation. Anti-Mullerian hormone (AMH) levels were measured in serum before and after oophorectomy.
MAIN RESULTS AND ROLE OF CHANCE: Ovarian tissue was successfully collected from 78.7% of the 42 patients. Oocytes were obtained from 20 patients before chemotherapy and 13 after chemotherapy. The youngest patients from whom oocytes were retrieved were aged 2 years (two atretic follicles) and 3 years. Of the 395 oocytes collected, ∼30% were atretic (29.6% in the pre-chemotherapy group, 37% in the post-chemotherapy group). One hundred twenty-one oocytes (31%) were matured in vitro and vitrified: 67.8% from patients before chemotherapy, the rest after chemotherapy. Mature oocytes suitable for vitrification were obtained from 16/20 patients before chemotherapy and from 12/13 patients after chemotherapy (maturation rate, 32 and 26.4%, respectively). There were significant correlations of the number of vitrified oocytes with patient age (more matured oocytes with older age) (P = 0.001) and with pre-oophorectomy AMH levels (P = 0.038 pre-chemotherapy group, P = 0.029 post-chemotherapy group). Oocytes suitable for vitrification were obtained both by manual aspiration of antral follicles (45%) and from rinse solutions after dissection. There were significantly more matured oocytes in the pre-chemotherapy group from aspiration than in the post-chemotherapy group after both aspiration (P < 0.033) and retrieval from rinsing fluids (P < 0.044). The number of pre-antral follicles per histological section did not differ in the pre- versus post-chemotherapy. AMH levels dropped by approximately 50% after ovarian removal in both groups, with a significant correlation between pre- and post-oophorectomy levels (P = 0.002 pre-chemotherapy group, P = 0.001 post-chemotherapy group).
LIMITATIONS, REASONS FOR CAUTION: There were no patients between 5 years and 10 years old in the post-chemotherapy group, which might have affected some results and correlations. Oocytes from patients soon after chemotherapy might be damaged, and caution is advised when using them for fertility-restoration purposes. The viability, development capability and fertilization potential of oocytes from paediatric patients, especially prepubertal and after chemotherapy, are unknown, in particular oocytes recovered from the media after the tissue dissection step.
WIDER IMPLICATIONS OF THE FINDINGS: Although more oocytes were collected and matured from chemotherapy-naïve paediatric patients, ovarian tissue and immature oocytes were also retrieved from young girls in whom cancer therapy has already been initiated. Our centre has established a protocol for potential maximal fertility preservation in paediatric female patients with cancer. Vitrified-in vitro-matured oocytes may serve as an important gamete source in paediatric female patients with cancer because the risk of reseeding the disease is avoided. Further studies are needed on the fertility-restoring potential of oocytes from paediatric and prepubertal patients, especially after exposure to chemotherapy.
STUDY FUNDING/COMPETING INTERESTS: The study was conducted as part of the routine procedures for fertility preservation at our IVF unit. No funding outside of the IVF laboratory was received. Funding for the AMH measurements was obtained by a research grant from the Israel Science Foundation (to B.-A.I., ISF 13-1873). None of the authors have competing interests.

Schorr L, Burger A, Hochner H, et al.
Mortality, cancer incidence, and survival in parents after bereavement.
Ann Epidemiol. 2016; 26(2):115-21 [PubMed] Related Publications
PURPOSE: The study objective was to investigate whether child loss is related to mortality, cancer incidence, and cancer survival in parents.
METHODS: We used a population-based birth cohort (1964-1976) in Jerusalem and ascertained mortality (average follow-up of 39.1 years) and any cancer (average follow-up of 35.6 years) among parents who lost a child (2838 mothers and 2532 fathers) and among nonbereaved parents (38,212 mothers and 36,433 fathers). We also assessed mortality among parents with cancer. Time-dependent Cox models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs).
RESULTS: Overall mortality rates among bereaved parents were modestly increased when compared with nonbereaved parents (HR = 1.18, 95% CI: 1.05-1.32 in mothers; HR = 1.10, 95% CI: 1.01-1.20 in fathers). Hazard models indicated a significant relationship between bereavement and deaths from coronary heart disease in mothers (HR = 1.90, 95% CI: 1.23-2.95) and circulatory causes in both parents (HR = 1.69; 95% CI: 1.22-2.34 in mothers and HR = 1.25; 95% CI: 1.02-1.54 in fathers). Bereavement was not associated with parental risk of cancer disease and with survival from cancer. The association between bereavement and parental overall mortality was similar in the different parental sociodemographic characteristics. We observed a decrease in HRs for parental mortality associated with bereavement, with increasing time since the death of the child (HRs = 9-10, 0-3 years; HRs = 0.9-1.0, 9+ years; P(heterogeneity) ≤ 3 × 10(-32)). A similar decrease in HRs was observed for parental survival from cancer (HRs = 6.7-8.7, 0-3 years; HRs = 0.9-1.0, 9+ years).
CONCLUSIONS: Our study suggests that child loss was associated with slightly increased risk of all-cause and circulatory mortality in parents but not with incidence of cancer and cancer survival. The considerable increased parental mortality during a short period after child loss support the involvement of pathways related to psychological stress.

Lavie O, Moskoviz MG, Auslender R, et al.
Clinical and Pathological Characteristics of Incidental Diagnostic Early Occult Malignancy After Risk-Reducing Salpingo-Oophorectomy in BRCA Mutation Carriers.
Int J Gynecol Cancer. 2016; 26(2):233-9 [PubMed] Related Publications
OBJECTIVE: Carriers of familial BRCA mutations are at high risk of early development of ovarian tubal or peritoneal cancers. The definite preventative treatment for these cases is early, risk-reducing, bilateral salpingo-oophorectomy (BSO). The aims of the study were to describe the incidence and source of early occult malignancy after risk-reducing salpingo-oophorectomy in carriers of Ashkenazi Jewish BRCA mutations and to characterize the clinical and pathological features of this unique population.
METHODS: Data were collected retrospectively regarding women who underwent BSO in our gynecologic oncology unit from January 2002 through July 2012, after a positive test for a BRCA1 or BRCA2 mutation.
RESULTS: The following 92 cases of BRCA mutations were included: 53 BRCA1, 37 BRCA2, and 2 with both mutations. After risk-reducing salpingo-oophorectomy, 5 (5.4%) of the patients were found to have early occult adnexal malignancy upon pathology study. All 5 had the BRCA1 185 del-AG mutation. Three of the 5 malignancies originated from the ovaries and 2 in the fallopian tubes with no involvement of the ovaries.
CONCLUSIONS: A 5.4% incidence of early occult malignancy in adnexal pathology of BSO was found in carriers of Ashkenazi Jewish BRCA mutations. Two cases with malignant origins within the fallopian tube, while sparing the ovaries in their entirety, support the fallopian tubes as the originating organ for some ovarian or peritoneal malignancies in BRCA mutation carriers.

Yablonski-Peretz T, Paluch-Shimon S, Gutman LS, et al.
Screening for germline mutations in breast/ovarian cancer susceptibility genes in high-risk families in Israel.
Breast Cancer Res Treat. 2016; 155(1):133-8 [PubMed] Related Publications
We evaluated the clinical utility of screening for mutations in 34 breast/ovarian cancer susceptibility genes in high-risk families in Israel. Participants were recruited from 12, 2012 to 6, 2015 from 8 medical centers. All participants had high breast/ovarian cancer risk based on personal and family history. Genotyping was performed with the InVitae™ platform. The study was approved by the ethics committees of the participating centers; all participants gave a written informed consent before entering the study. Overall, 282 individuals participated in the study: 149 (53 %) of Ashkenazi descent, 80 (28 %) Jewish non-Ashkenazi descent, 22 (8 %) of mixed Ashkenazi/non-Ashkenazi origin, 21 (7 %) were non-Jewish Caucasians, and the remaining patients (n = 10-3.5 %) were of Christian Arabs/Druze/unknown ethnicity. For breast cancer patients (n = 165), the median (range) age at diagnosis was 46 (22-90) years and for ovarian cancer (n = 15) 54 (38-69) years. Overall, 30 cases (10.6 %) were found to carry a pathogenic actionable mutation in the tested genes: 10 BRCA1 (3 non-founder mutations), 9 BRCA2 (8 non-founder mutations), and one each in the RAD51C and CHEK2 genes. Furthermore, actionable mutations were detected in 9 more cases in 4 additional genes (MSH2, RET, MSH6, and APC). No pathogenic mutations were detected in the other genotyped genes. In this high-risk population, 10.6 % harbored an actionable pathogenic mutation, including non-founder mutations in BRCA1/2 and in additional cancer susceptibility genes, suggesting that high-risk families should be genotyped and be assigned a genotype-based cancer risk.

Kadmon I, Noy S, Billig A, Tzur T
Decision-Making Styles and Levels of Involvement Concerning Breast Reconstructive Surgery: An Israeli Study.
Oncol Nurs Forum. 2016; 43(1):E1-7 [PubMed] Related Publications
PURPOSE/OBJECTIVES: To address decision-making styles among breast cancer survivors considering breast reconstruction.
DESIGN: A primary analysis of a cross-sectional sample among survivors who chose to have breast reconstruction to examine correlations among patient age, decision-making style, and the level of involvement of decision making.
SETTING: Hadassah Medical Center in Jerusalem, Israel.
SAMPLE: 70 women who had undergone breast reconstruction surgery in the past five years.
METHODS: Participants completed decision-making style and demographic questionnaires and an assessment of their level of involvement in the decision-making process. 
MAIN RESEARCH VARIABLES: Level of involvement in decision making, decision-making model between provider and patient, and decision-making styles were examined.
FINDINGS: No correlation was found between four main decision-making styles and patient age or the extent of patient decision-making involvement and age. A statistically significant correlation was found between the level of involvement in decision making and the decision-making style of the patient.
CONCLUSIONS: Nurses should assess patient decision-making styles to ensure maximum patient involvement in the decision-making process based on personal desires regardless of age.
IMPLICATIONS FOR NURSING: Nurses working in breast cancer care must address the decision-making process of patients diagnosed with breast cancer, including the choice to undergo breast reconstruction after mastectomy. Nurses should understand the complex factors that influence a woman's decision-making style to best help with the decision.

Stupp R, Taillibert S, Kanner AA, et al.
Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma: A Randomized Clinical Trial.
JAMA. 2015; 314(23):2535-43 [PubMed] Related Publications
IMPORTANCE: Glioblastoma is the most devastating primary malignancy of the central nervous system in adults. Most patients die within 1 to 2 years of diagnosis. Tumor-treating fields (TTFields) are a locoregionally delivered antimitotic treatment that interferes with cell division and organelle assembly.
OBJECTIVE: To evaluate the efficacy and safety of TTFields used in combination with temozolomide maintenance treatment after chemoradiation therapy for patients with glioblastoma.
DESIGN, SETTING, AND PARTICIPANTS: After completion of chemoradiotherapy, patients with glioblastoma were randomized (2:1) to receive maintenance treatment with either TTFields plus temozolomide (n = 466) or temozolomide alone (n = 229) (median time from diagnosis to randomization, 3.8 months in both groups). The study enrolled 695 of the planned 700 patients between July 2009 and November 2014 at 83 centers in the United States, Canada, Europe, Israel, and South Korea. The trial was terminated based on the results of this planned interim analysis.
INTERVENTIONS: Treatment with TTFields was delivered continuously (>18 hours/day) via 4 transducer arrays placed on the shaved scalp and connected to a portable medical device. Temozolomide (150-200 mg/m2/d) was given for 5 days of each 28-day cycle.
MAIN OUTCOMES AND MEASURES: The primary end point was progression-free survival in the intent-to-treat population (significance threshold of .01) with overall survival in the per-protocol population (n = 280) as a powered secondary end point (significance threshold of .006). This prespecified interim analysis was to be conducted on the first 315 patients after at least 18 months of follow-up.
RESULTS: The interim analysis included 210 patients randomized to TTFields plus temozolomide and 105 randomized to temozolomide alone, and was conducted at a median follow-up of 38 months (range, 18-60 months). Median progression-free survival in the intent-to-treat population was 7.1 months (95% CI, 5.9-8.2 months) in the TTFields plus temozolomide group and 4.0 months (95% CI, 3.3-5.2 months) in the temozolomide alone group (hazard ratio [HR], 0.62 [98.7% CI, 0.43-0.89]; P = .001). Median overall survival in the per-protocol population was 20.5 months (95% CI, 16.7-25.0 months) in the TTFields plus temozolomide group (n = 196) and 15.6 months (95% CI, 13.3-19.1 months) in the temozolomide alone group (n = 84) (HR, 0.64 [99.4% CI, 0.42-0.98]; P = .004).
CONCLUSIONS AND RELEVANCE: In this interim analysis of 315 patients with glioblastoma who had completed standard chemoradiation therapy, adding TTFields to maintenance temozolomide chemotherapy significantly prolonged progression-free and overall survival.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00916409.

Paltiel O, Tajuddin SM, Polanker Y, et al.
Grand multiparity and reproductive cancer in the Jerusalem Perinatal Study Cohort.
Cancer Causes Control. 2016; 27(2):237-47 [PubMed] Related Publications
OBJECTIVES: Grand multiparity is associated with reduced mortality from reproductive cancers. We aimed to separate the components of mortality, by measuring incidence of and survival after reproductive cancer onset in grand multiparous compared to other parous women.
STUDY DESIGN: We linked data from the population-based Jerusalem Perinatal Study Cohort, which included women aged 13-55 who delivered 1964-1976, with Israel's National Cancer Registry. We compared breast and gynecologic cancer risk and all-cause survival following a cancer diagnosis, among grand multiparae (GMPs = parity 5+, n = 8,246) versus women with parity 1-4 (n = 19,703), adjusting for reproductive and demographic variables.
RESULTS: Grand multiparae were at significantly lower risk of breast cancer than others (adjusted hazard ratio (HRadj) = 0.62, 95 % confidence interval (CI) 0.54-0.71), after controlling for age at first birth, education, and other covariates. This reduction was greater among GMPs whose first birth occurred after age 30 (p-interaction = 0.0001) and for cancer occurring before age 50 years (p = 0.002). In contrast, GMPs were at greater risk of death than women with parity <5, following a breast cancer diagnosis (HRadj = 1.69, CI 1.39-2.1). Ovarian, uterine, and cervical cancer incidence did not differ between the groups, but survival was reduced for GMPs with uterine cancer (HRadj = 2.48, CI 1.22-5.03).
CONCLUSION: Reduced reproductive cancer mortality reported among GMPs masks two opposing phenomena: decreased breast cancer risk and poorer survival after breast and uterine cancers. The latter unfavorable outcome suggests that tumors in GMPs may be particularly aggressive, having perhaps escaped protective mechanisms conferred by parity. This finding calls for heightened clinical attention in this group.

Goldberg M, Calderon-Margalit R, Paltiel O, et al.
Socioeconomic disparities in breast cancer incidence and survival among parous women: findings from a population-based cohort, 1964-2008.
BMC Cancer. 2015; 15:921 [PubMed] Article available free on PMC after 01/06/2017 Related Publications
BACKGROUND: Socioeconomic position (SEP) has been associated with breast cancer incidence and survival. We examined the associations between two socioeconomic indicators and long-term breast cancer incidence and survival in a population-based cohort of parous women.
METHODS: Residents of Jerusalem who gave birth between 1964-1976 (n = 40,586) were linked to the Israel Cancer Registry and Israel Population Registry to determine breast cancer incidence and vital status through mid-2008. SEP was assessed by husband's occupation and the woman's education. We used log ranks tests to compare incidence and survival curves by SEP, and Cox proportional hazard models to adjust for demographic, reproductive and diagnostic factors and assess effect modification by ethnic origin.
RESULTS: In multivariable models, women of high SEP had a greater risk of breast cancer compared to women of low SEP (Occupation: HR 1.18, 95 % CI 1.03-1.35; Education: HR 1.39, 95 % CI 1.21-1.60) and women of low SEP had a greater risk of mortality after a breast cancer diagnosis (Occupation: HR 1.33, 95 % CI 1.04-1.70; Education: HR 1.37, 95 % CI 1.06-1.76). The association between education and survival was modified by ethnic origin, with a gradient effect observed only among women of European origin. Women of Asian, North African and Israeli origin showed no such trend.
CONCLUSIONS: SEP was associated with long-term breast cancer incidence and survival among Israeli Jews. Education had a stronger effect on breast cancer outcomes than occupation, suggesting that a behavioral mechanism may underlie disparities. More research is needed to explain the difference in the effect of education on survival among European women compared to women of other ethnicities.

Feitelson DG
Data on the distribution of cancer incidence and death across age and sex groups visualized using multilevel spie charts.
J Clin Epidemiol. 2016; 72:90-7 [PubMed] Related Publications
Cancer incidence and death statistics are typically recorded for multiple age and sex brackets, leading to large data tables which are difficult to digest. Effective visualizations of this data would allow practitioners, policy makers, and the general public to comprehend the data more readily and act on it appropriately. We introduce multilevel spie charts to create a combined visualization of cancer incidence and death statistics. Spie charts combine multiple pie charts, where the base pie chart (representing the general population) is used to set the angles of slices, and the superimposed ones use variable radii to portray the cancer data. Spie charts of cancer incidence and death statistics from Israel for 2009-2011 are used as an illustration. These charts clearly show various patterns of how cancer incidence and death distribute across age and sex groups, illustrating (1) absolute numbers and (2) rates per 100,000 population for different age and sex brackets. In addition, drawing separate charts for different cancer types illustrates relative mortality, both (3) across cancer types and (4) mortality relative to incidence. Naturally, this graphical depiction can be used for other diseases as well.

Shepshelovich D, Goldvaser H, Edel Y, et al.
High Lung Cancer Incidence in Heavy Smokers Following Hospitalization due to Pneumonia.
Am J Med. 2016; 129(3):332-8 [PubMed] Related Publications
INTRODUCTION: The rate of lung cancer incidence following pneumonia in heavy smokers is unknown. Heavy smokers hospitalized due to community-acquired pneumonia might be at high risk for subsequent lung cancer. The primary objective of this study was to determine lung cancer incidence in this high-risk population.
PATIENTS AND METHODS: This was a single-center, retrospective cohort study that included heavy smokers hospitalized due to community-acquired pneumonia between January 1, 2007 and December 31, 2011 in Beilinson hospital, a large community hospital and tertiary center. Patients were identified by International Classification of Diseases, Ninth Revision coding from the hospital's registry. Two physicians reviewed every patient's medical file for patient demographics, smoking history, lung cancer risk factors, and anatomical location of pneumonia. Data were cross-checked with the database at the national cancer registry for new diagnoses of cancer.
RESULTS: There were 381 admissions for community-acquired pneumonia included in the final analysis. Thirty-one cases (8.14%; 95% confidence interval [CI], 5.9%-11.2%) of lung cancer were diagnosed during the first year after hospitalization. Lung cancer incidence was significantly higher in patients who had upper-lobe pneumonia (23.8%; 95% CI, 14.9%-40%). Lung cancer was located within the lobe involved by the pneumonia in 75.8% of patients.
CONCLUSIONS: A high lung cancer rate was found in heavy smokers admitted due to community-acquired pneumonia. The association was especially strong for patients with upper-lobe pneumonia. Screening with chest computed tomography should be strongly considered for these patients.

Baris HN, Barnes-Kedar I, Toledano H, et al.
Constitutional Mismatch Repair Deficiency in Israel: High Proportion of Founder Mutations in MMR Genes and Consanguinity.
Pediatr Blood Cancer. 2016; 63(3):418-27 [PubMed] Related Publications
BACKGROUND: Heterozygous germline mutations in any of the mismatch repair (MMR) genes, MLH1, MSH2, MSH6, and PMS2, cause Lynch syndrome (LS), an autosomal dominant cancer predisposition syndrome conferring a high risk of colorectal, endometrial, and other cancers in adulthood. Offspring of couples where both spouses have LS have a 1:4 risk of inheriting biallelic MMR gene mutations. These cause constitutional MMR deficiency (CMMRD) syndrome, a severe recessively inherited cancer syndrome with a broad tumor spectrum including mainly hematological malignancies, brain tumors, and colon cancer in childhood and adolescence. Many CMMRD children also present with café au lait spots and axillary freckling mimicking neurofibromatosis type 1.
PROCEDURE: We describe our experience in seven CMMRD families demonstrating the role and importance of founder mutations and consanguinity on its prevalence. Clinical presentations included brain tumors, colon cancer, lymphoma, and small bowel cancer.
RESULTS: In children from two nonconsanguineous Ashkenazi Jewish (AJ) families, the common Ashkenazi founder mutations were detected; these were homozygous in one family and compound heterozygous in the other. In four consanguineous families of various ancestries, different homozygous mutations were identified. In a nonconsanguineous Caucasus/AJ family, lack of PMS2 was demonstrated in tumor and normal tissues; however, mutations were not identified.
CONCLUSIONS: CMMRD is rare, but, especially in areas where founder mutations for LS and consanguinity are common, pediatricians should be aware of it since they are the first to encounter these children. Early diagnosis will enable tailored cancer surveillance in the entire family and a discussion regarding prenatal genetic diagnosis.

Shoshani A, Mifano K, Czamanski-Cohen J
The effects of the Make a Wish intervention on psychiatric symptoms and health-related quality of life of children with cancer: a randomised controlled trial.
Qual Life Res. 2016; 25(5):1209-18 [PubMed] Article available free on PMC after 01/05/2017 Related Publications
OBJECTIVE: Children with life-threatening medical conditions frequently undergo invasive medical procedures that may elicit anxiety and distress. However, there are few empirically validated interventions that reduce mental health symptoms and increase the resilience of children during the acute stages of illness. This study aimed to evaluate the efficacy of the Make a Wish intervention for children with life-threatening cancer.
METHODS: The design was a wait-list-controlled trial with two parallel groups. Sixty-six children aged 5-12 with an initial diagnosis of life-threatening cancer were identified and randomly assigned to the Make a Wish intervention (n = 32) or a wait-list control group (n = 34). Children completed measures of psychiatric and health-related symptoms, positive and negative affect, hope, and optimism pre-intervention and post-intervention. After baseline data collection, children were interviewed and made an authentic wish that they wanted to come true. These wishes were made possible 5-6 months after baseline data collection, to fuel anticipation and excitement over the wish-fulfillment event. The post-intervention assessment point was 5 weeks after wish fulfillment (approximately 7 months after baseline data collection).
RESULTS: Children in the intervention group exhibited a significant reduction in general distress (d = 0.54), depression (d = 0.70), and anxiety symptoms (d = 0.41), improved health-related quality of life (d = 0.59), hope (d = 0.71), and positive affect (d = 0.80) compared to decrease in positive affect and no significant changes in the other measures in the control group.
CONCLUSIONS: These findings emphasize the role of hope and positive emotions in fostering the well-being of children who suffer from serious illnesses.

Rottenberg Y, Ratzon NZ, Jacobs JM, et al.
Unemployment risk and income change after testicular cancer diagnosis: A population-based study.
Urol Oncol. 2016; 34(1):5.e27-33 [PubMed] Related Publications
BACKGROUND: Among patients with cancer, returning to full working may serve as an indicator for return to normal lifestyle following illness, as opposed to unemployment or shifting to part-time work. The aim of the project was to clarify the association between unemployment risk and decreased income at 4 years after the diagnosis of testicular cancer (TC).
PARTICIPANTS AND METHODS: A case control in a cohort study includes baseline measurement of people participating in the Israeli Central Bureau of Statistics 1995 National Census, and follow-up until 2011. Cancer incidence, employment status, and income level were ascertained through the Israel Cancer Registry and Tax Authority, respectively. A matched group was sampled from the population in the census. Binary logistic regression analyses were used to assess odds ratios (ORs) for study׳s outcomes, while controlling for age, ethnicity, education, and socioeconomic and employment status at 2 years before diagnosis.
RESULTS: A total of 113 cases of TC and 468 persons in the matched group were included in the study after excluding persons who died during the study period. No association was found between TC and subsequent risk after the 4 years of unemployment (OR = 1.12, 95% CI: 0.65-1.95) or decreased income (OR = 1.41, 95% CI: 0.84-2.36). Predictors of subsequent unemployment were unemployment 2 years before diagnosis (OR = 6.91, 95% CI: 4.39-10.86) and increasing age (OR = 1.03 per year, 95% CI: 1.01-1.06).
CONCLUSION: TC survivorship is not associated with subsequent unemployment or decreased income at 4 years after diagnosis.

Leshno A, Shapira S, Liberman E, et al.
The APC I1307K allele conveys a significant increased risk for cancer.
Int J Cancer. 2016; 138(6):1361-7 [PubMed] Related Publications
This study is the first attempt to evaluate the association between the APC I1307K variant and overall cancer risk. It is unique in both its large sample size and in the reliability of data in the control group. The findings described in this article have major implications in terms of identifying asymptomatic individuals who are at increased risk to harbor cancer and therefore targeted to be enrolled in specific early detection and prevention programs. The prevalence of the APC I1307K missense mutation among Ashkenazi Jews is ∼ 6%. Carriers are at an increased risk for colorectal neoplasia. In this study, we examined the association of this variant with non-colorectal cancers. Consecutive 13,013 healthy subjects who underwent screening at the Integrated Cancer Prevention Center between 2006 and 2014 were enrolled. This population was supplemented with 1,611 cancer patients from the same institution. Demographics, medical history, and pathological data were recorded. Mortality data were obtained from the Ministry of Health's registry. The prevalence of APC I1307K in cancer patients and healthy subjects was compared. The APC I1307K variant was detected in 189 (11.8%) cancer patients compared to 614 (4.7%) healthy subjects, reflecting an adjusted age and sex odds ratio (OR) of 2.53 (p < 0.0001). History of two or more cancer types was associated with a positive carrier prevalence (OR = 4.38 p < 0.0001). Males had significantly increased carrier prevalence in lung, urologic, pancreatic, and skin cancers. The carrier prevalence among females was significantly higher only in breast and skin cancers. Female carriers developed cancer at a significantly older age compared to non-carriers (average 62.7 years vs. 57.8, respectively, p = 0.027), had better survival rates (HR = 0.58, p = 0.022) and overall increased longevity (average age of death 78.8 vs. 70.4 years, respectively, p = 0.003). In conclusion, the APC I1307K variant is a reliable marker for overall cancer risk (OR 2.53). Further studies are needed to evaluate its use for specific cancer types-particularly in males. Female carriers have better prognosis and increased lifespan.

Mahlab-Guri K, Asher I, Allweis T, et al.
Granulomatous Lobular Mastitis.
Isr Med Assoc J. 2015; 17(8):476-80 [PubMed] Related Publications
BACKGROUND: Granulomatous lobular mastitis (GLM) is a rare disorder that can clinically mimic breast carcinoma. The recommendation for diagnosis and treatment of GLM has not yet been established.
OBJECTIVES: To assess a series of GLM patients, including their clinical presentation, diagnosis, treatment and outcome.
METHODS: We retrospectively analyzed the clinical data and treatment of 17 female patients with biopsy-proven GLM. Breast tissue was obtained by a core needle biopsy (15 patients) or open biopsy (2 patients). Images were reviewed by an experienced radiologist.
RESULTS: The mean age of the patients at diagnosis was 44.6 ± 12.6 years. Five patients (29%) presented with bilateral disease, and seven (41%) presented with a mass, suggesting the initial diagnosis of breast carcinoma. Treatment comprised observation alone (23%), antibiotics (58.8%) and/or corticosteroids (with or without methotrexate) (35%). At the end of the study 70.6% of the patients demonstrated complete remission. None of the patients developed any systemic (granulomatous) disease or breast carcinoma during the follow-up period (4.7 ± 3.8 years).
CONCLUSIONS: Core needle biopsy is mandatory for the diagnosis of GLM and the exclusion of breast carcinoma. The recommended treatment modalities are observation alone or corticosteroids; surgery should be avoided. GLM is a benign disease with a high rate of resolution and complete remission.

Hammerman A, Greenberg-Dotan S, Feldhamer I, et al.
Second-Line Treatment of Her2-Positive Metastatic Breast Cancer: Trastuzumab beyond Progression or Lapatinib? A Population Based Cohort Study.
PLoS One. 2015; 10(9):e0138229 [PubMed] Article available free on PMC after 01/05/2017 Related Publications
BACKGROUND: The relative efficacy of lapatinib vs. continuing trastuzumab beyond progression (TBP) in HER2-positive metastatic breast cancer (MBC) patients, who progressed on first-line trastuzumab, is still unclear. The objective of this population based cohort study was to compare outcomes of lapatinib vs. TBP in daily practice.
METHODS: All HER2-positive MBC patients who began second-line anti HER2 therapy between 1st January 2010 and 30th August 2013 were selected from Clalit Health Services' (CHS) electronic database. Available data on patient and disease characteristics and treatments were analyzed. The primary endpoint was overall survival (OS). Outcomes were compared using the Kaplan-Meier (log-rank) method and Cox proportional hazards model.
RESULTS: 64 patients received second-line lapatinib and 93 TBP. The two treatment groups were similar in age and co-morbidity rates, but differed in proportion of prior adjuvant trastuzumab (lapatinib: 29.7%, TBP: 16.1%, P = 0.043) and rates of prior brain metastases (lapatinib: 32.8%, TBP: 10.8%, P = 0.01). Lapatinib median OS was 13.0 months (95% CI: 9.5-16.5) vs. 31.0 for TBP (95% CI: 20.6-41.4), P<0.001. On multivariate analysis, longer OS was preserved for TBP, after controlling for differences in age, adjuvant trastuzumab, duration of first-line trastuzumab therapy, brain metastases, visceral metastases and hormonal treatment [Hazard Ratio (HR) = 0.63, 95% CI: 0.40-0.99, P = 0.045].
CONCLUSION: In this comparative cohort study, OS of HER2-positive MBC patients treated with TBP was significantly longer than with lapatinib. These results might be especially relevant in settings where ado-trastuzumab-emtansine (TDM-1), the current preferred agent in this setting, is not available yet for patients.

Atrash F, Kaidar-Person O, Billan S
Toxicity of Treatment for Anal Carcinoma: 2D versus 3D Planning.
Isr Med Assoc J. 2015; 17(7):414-7 [PubMed] Related Publications
BACKGROUND: Anal cancer is a relatively uncommon disease, accounting for only 4% of cancers of the lower gastrointestinal tract.
OBJECTIVES: To summarize a single-center experience in the treatment of anal carcinoma using various radiation techniques.
METHODS: We conducted a retrospective chart review of consecutive patients who were treated for anal cancer between the years 2002 and 2011. The data extracted included demographics, type of radiation technique, treatment-associated acute toxicity, and patterns of failure and survival. For statistical analysis purposes, the patients were divided into two groups according to radiotherapy technique: 2D (group A) and 3D (group B).
RESULTS: A total of 42 patients--25 (59.5%) females and 17 males (40.5%)--underwent definitive chemo-radiation treatment (CRT) for anal cancer. Group A comprised 26 patients and group B 14 patients. Toxicity did not differ significantly between the groups; only in grade 1-2 skin toxicity which was more common in group B. There were significant differences in the unplanned interruptions in treatment, in both the number of patients who needed a treatment break and the number of days needed (more in group A). There were no differences in treatment response and patterns of failure between these two techniques, or in overall survival between the two groups.
CONCLUSIONS: Our study results are consistent with reported large randomized trials, indicating that current treatments for anal carcinomas are associated with high grade acute toxicity that may result in significant treatment interruptions. The 2D technique was associated with significantly more treatment interruptions but did not differ from 3D with regard to treatment efficacy.

Kessous R, Davidson E, Meirovitz M, et al.
The risk of female malignancies after fertility treatments: a cohort study with 25-year follow-up.
J Cancer Res Clin Oncol. 2016; 142(1):287-93 [PubMed] Related Publications
OBJECTIVE: To investigate whether an association exists between a history of fertility treatments and future risk of female malignancies.
STUDY DESIGN: A population-based study compared the incidence of long-term female malignancies in a cohort of women with and without a history of fertility treatments including in vitro fertilization (IVF) and ovulation induction (OI). Deliveries occurred between the years 1988-2013, with a mean follow-up duration of 12 years. Excluded from the study were women with known genetic predisposition for malignancies or known malignancies prior to the index pregnancy. Female malignancies were divided into specific types including ovarian, uterine, breast and cervix. Kaplan-Meier survival curve was used to estimate cumulative incidence of malignancies. Cox proportional hazard models were used to estimate the adjusted hazard ratios (HRs) for female malignancy.
RESULTS: During the study period, 106,031 women met the inclusion criteria; 4.1 % (n = 4363) occurred in patients following fertility treatments. During the follow-up period, patients with a history of IVF treatments had a significantly increased risk of being diagnosed with ovarian and uterine cancer as compared to patients after OI and patients with no history of fertility treatments. Cox proportional hazard models were constructed for ovarian and uterine cancer separately, controlling for confounders such as maternal age and obesity. A history of IVF treatment remained independently associated with ovarian and uterine cancer (adjusted HR 3.9; 95 % CI 1.2-12.6; P = 0.022 and adjusted HR 4.6; 95 % CI 1.4-14.9; P = 0.011; respectively).
CONCLUSION: IVF treatments pose a significant risk of subsequent long-term ovarian and uterine cancer.

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