Israel National Cancer Registry Research Articles

Bias in Evaluating Trends of Thyroid Cancer Incidence between Rural and Urban Populations

Abstract Background Diagnosis of thyroid cancer is based on fine needle aspiration cytology of thyroid nodules, based on nodules’ sonographic appearance and size. The American Thyroid Association published new guidelines for management of thyroid nodules in 2009 and 2015, where in some cases, only follow-up of thyroid nodules without any other procedure is recommended. This may lead to a decrease in diagnosed thyroid cancer cases. We studied thyroid cancer trends in Israel between the Arab population who are more likely to be living in rural areas, and the Jewish population who predominantly living in urban areas, and assesses whether these guidelines were reflected in the trends. Methods Data on new thyroid cancer cases were retrieved for Jews and Arabs separately from the Israel National Cancer Registry. Trends in age standardized incidence rates between 1996-2019 were evaluated for the two population groups using joinpoint regression model. Population group was included in the regression models to compare the trends between the two groups. We also studied trends in treatment of thyroid cancer at Rambam Health Care Campus. Results In both populations, age standardized thyroid cancer incidence rate increased between 1996 and 2013. However, between 2013-2019, Annual Percentage Change continuously increased in Arabs, but decreased in Jews. In the hospital study, we found that the Arab patients were 30% more likely to have surgery for small tumors. Conclusions The decrease in thyroid cancer incidence in the Jewish population compared with the Arab population may be related to differences in implementing the 2009 guidelines, which do not recommend fine needle aspiration cytology for very small tumors. We have found evidence that these guidelines were not followed to the same extent among Arab community clinics. This may explain the persisting increasing trend among Arabs, and could be one of the possible explanations for the differences in trends between the two groups. Key messages • Updated Guidelines regarding thyroid cancer diagnosis may be differently implemented by rural and urban populations. • Trends assessment may be biased due to differences in guidelines implementation.

Mapping the patient journey and treatment patterns in early-stage (stage I-III) non-small cell lung cancer

IntroductionWe map the patient journey from symptom onset to intervention and describe primary treatment in a retrospective population-based cohort study of patients in a large healthcare-provider. MethodsNewly diagnosed adult patients diagnosed with stages I-III non-small cell lung cancer (NSCLC) between 2016 and 2019 were identified from the Israel National Cancer Registry and chart review was performed to extract de-identified data. The following timelines were constructed: from symptom onset to imaging, imaging to biopsy, and biopsy to primary treatment initiation. Cutoff: 31st December 2021. The initial symptom was captured up to one year prior to biopsy. ResultsAmong 302 patients (41 % female, 70 % >=65 years, 79 % former or current smoking, 62 % adenocarcinoma), 34.1 % stage I, 10.3 % stage II, 42.1 % stage III and 13.6 % unknown (AJCC ver. 8). In the baseline year, 80.5 % of patients reported at least one symptom to their physician, and 12.3 % reported four or more symptoms. The most common symptoms reported were cough (29.8 %), pneumonia (24.2 %), chest pain (18.5 %), bronchitis (17.5 %) and wheezing (17.2 %). For patients with an initial symptom (n=243) median time from symptom onset to imaging was 5.5 months (95% CI:4.8–6.3), and time from imaging to primary treatment initiation was 2.6 (2.3–2.9) months in all patients. Total duration from symptom to intervention was 8.5 months (7.6–9.3). Over 93 % of stage I patients underwent surgery and 4.9 % received definitive radiation. Over 83 % of stage II patients underwent surgery; of these, 54.8 % received adjuvant/neoadjuvant chemotherapy. Of stage III patients, 68.5 % received definitive chemoradiation (half received durvalumab), and the remaining underwent surgery with adjuvant/neoadjuvant treatment. ConclusionA total of 80.5 % of patients were symptomatic and the median duration from symptom onset to treatment initiation was 8.5 month long. Improving patient and physician awareness to lung cancer symptoms, and the introduction of screening programs are essential for reducing those delays.

Greenness Exposure and Mortality Risk in a Cardio-Oncologic Population.

Knowledge is lacking on the relationship between greenness and mortality in cancer survivors who experience coronary artery disease (CAD), a cardio-oncologic population. We aimed to investigate the association between residential greenness exposure and all-cause mortality in a cardio-oncologic population. Cancer survivors undergoing percutaneous coronary intervention at the Rabin Medical Center in Israel between 2004 and 2014 were included in the study. Clinical data were collected from medical records during index hospitalization and from the Israeli National Cancer Registry. Residential greenness was estimated by the normalized difference vegetation index (NDVI), a satellite-based index derived from Landsat imagery at a 30-meter spatial resolution, with larger values indicating higher levels of vegetative density (ranging between -1 to 1). Mortality follow-up data were obtained through the end of 2021. Cox models were used to assess the hazard ratios (HRs) for all-cause mortality per 1SD increase in NDVI. Among 1,331 patients analyzed [mean (SD) age, 75.6 (10.2) years, 373 (28%) females], the mean (SD) NDVI within a 300-meter radius was 0.12 (0.03). During a median follow-up period of 12.0 (IQR 9.2-14.7) years, 883 (66%) participants died. After adjustment for potential confounding factors, including residential socioeconomic status, air pollution, and smoking, NDVI was inversely associated with mortality hazard [HR (95% CI) = 0.93 (0.86, 0.99); p=.042]. The association was stronger among individuals with more recently (<10 years) diagnosed cancer [HR (95% CI) = 0.89 (0.81, 0.98); p=.019]. In a cohort of cardio-oncologic patients, greenness was independently associated with lower mortality.

The Use of National Cancer Registry Data for Breast Cancer Family History Assessment in Premenopausal Women.

Background: Population-based cancer registries are the best source of information to measure cancer burden. However, little is done to use this information for individual cancer risk assessment. In this study, we aimed at identifying women at high risk of breast and ovarian cancer using data on family history of cancer from the Israel national cancer registry. Methods: We used the family history assessment tool (FHAT) to score all females, 26 to 45 years of age, in a 2.6-million-member health provider in Israel (Maccabi Healthcare Services). Data on breast, ovarian, prostate, and pancreatic cancer history among the participants and their parents (identified using the national census) were retrieved from the national cancer registry. These data were used to calculate individual FHAT scores. Results: A total of 377,931 eligible women were included in the analysis. A relevant family history of cancer was detected in 20,386 (5.4%), with FHAT scores ranging from 1 to 16. FHAT score was higher in older women and among those with a history of breast cancer. Among women aged 35-39, an FHAT score of 10 or above was associated with an OR of 15.23 (95%CI: 7.41-28.19) for breast cancer compared to women with an FHAT of 0. Conclusions: Using individual-level data from national cancer registries may assist in detecting women with a relevant family history of cancer.

Associations of Adolescence Exposure to Industrial Air Pollution with Cancer in Young Adults.

There is substantial public concern about the health risks of proximity to petrochemical industries. In the Haifa Bay Area (HBA), which contains Israel's densest industrial area, these concerns have been strengthened by elevated cancer mortality rates since the late 1960s. We studied the association between adolescent exposure to industrial air pollution in the HBA and adult-onset cancer. This is a historical cohort study. The study population comprised 2,187,317 subjects, using the Israeli medical corps data linked to the Israel National Cancer Registry with follow-up of up to 45 years. Exposure assessments were estimated by a spatial kriging interpolation model of SO2, serving as a marker for the dispersion of air pollution emitted from the complex during the study period. We found increased crude (HR = 1.23, 95%CI= 1.17 to 1.29) and adjusted (HR = 1.16, 95%CI = 1.10 to 1.21) risk of cancer with increased exposure to air pollution in HBA. The associations remained robust in analyses stratified by decade and socio-economic status. We found evidence of monotonically increased risk in five of 13 cancer categories (leukemia, melanoma, female breast, central nervous system, and thyroid tumors). Our findings strengthen the hypothesis that this exposure posed a carcinogenic risk during the study period.

Varicocoele in adolescence and testicular cancer in young adulthood.

Elevated intrascrotal temperature has been suggested as a risk factor for testicular cancer, which is the most common neoplasm among young men. Varicocoele was linked to increased intrascrotal temperature, but whether it is associated with testicular cancer is unclear. To explore the possible association between varicocoele at adolescence and the incidence of testicular cancer at adulthood. This nationwide, population-based, historical cohort study includes 1,521,661 Israeli male adolescents (mean age 17.5±0.4years), who were screened for varicocoele during the years 1967-2012, as part of their medical assessment prior to compulsory military service. The mean follow-up was 18±4.2years. The diagnosis of testicular cancer was ascertained from linkage of records to the the Israeli National Cancer Registry. Survival analysis was applied. In total, 53,210 adolescents were diagnosed with varicocoele stages 2 and 3 prior to military service. Of 1988 (0.13% of the total cohort) men who were diagnosed with testicular cancer during follow-up, 54 (0.1%) had varicocoele prior to military service, while 1934 (99.9%) did not; p=0.213. The age at cancer diagnosis and the distribution of seminomas versus non-seminomas did not differ significantly between those with and without varicocoele in adolescence. In a multivariable analysis controlling for sociodemographic factors, varicocoele was not associated with testicular cancer; odds ratio=0.816 (CI: 0.615-1.083). Varicocoele in adolescents was not found to be associated with testicular cancer in young adults. In light of the theoretical association between varicocoele and testicular cancer, we conducted this large population study. We found no association between varicocoele in young adulthood and testicular cancer later in life.

Preventable Cancer in Israel.

Background: The cancer burden in Israel is substantial. Recently calculated population attributable fractions (PAFs) for modifiable cancer risk factors in the US and the UK have indicated much room for prevention. Our aim was to estimate PAFs for selected modifiable cancer risk factors in Israel. Methods: Exposure data on selected modifiable risk factors were based on national health surveys conducted in 2013–2015. Data on invasive cancer incidence in 2015 were retrieved from the Israel National Cancer Registry (INCR). Relative risks (RRs) for specific cancer sites were retrieved from the scientific literature. PAFs were calculated for selected modifiable risk factors using an approximate formula. Results: In 2015, 21% of all invasive cancer cases in Israel were attributed to smoking, 9% to excess body weight, and 1.5% to alcohol intake. Moreover, 32% of all invasive cancer cases were attributed to all modifiable risk factors (combined) included in our study. Conclusions: Quantifying the contribution of modifiable risk factors to the incidence of certain cancer types in Israel offers an opportunity for primary prevention and enables informed decision-making with respect to the prioritization of interventions.

Persistent Asymptomatic Isolated Microscopic Hematuria in Adolescents is not Associated With an Increased Risk for Early Onset Urinary Tract Cancer

ObjectiveTo elucidate the association between adolescent microscopic hematuria and early onset urothelial carcinoma and renal cell carcinoma. MethodsNationwide, population-based, retrospective cohort study using medical data of 970,366 adolescents aged 16 through 19 years (58.6% male) examined for fitness for military service between 1980 and 1997. Diagnoses of persistent isolated microscopic hematuria were given after thorough work up process excluding any other renal abnormalities. Incident cases of urothelial carcinoma and renal cell carcinoma diagnosed during the years of 1982-2012 were retrieved from the Israeli National Cancer Registry. Cox proportional hazards models were used to estimate the hazard ratio (HR) separately for urothelial carcinoma and renal cell carcinoma. ResultsDuring a cumulative follow-up of 22,115,629 person-years (median follow-up, 22.8), persistent isolated microscopic hematuria was diagnosed among 5509 (0.6%) adolescents. Urothelial carcinoma and renal cell carcinoma developed in 332 (3 among those with persistent isolated microscopic hematuria) and 292 (2) individuals, respectively. The adjusted HR for incident urothelial carcinoma among adolescents with isolated microscopic hematuria was 1.17 (95% CI, 0.38-3.66) and the adjusted HR for renal cell carcinoma was 1.02 (95% CI, 0.25-4.12). ConclusionPersistent asymptomatic isolated microscopic hematuria at adolescence was not associated with increased risk for urothelial carcinoma nor renal cell carcinoma.

Secondary cancer after meningioma diagnosis: an Israeli national study.

There are limited data on whether primary diagnosis of meningioma may be associated with development of secondary primary cancer (SPC). All meningioma cases (ICD-O-3 morphology codes 9530/0-9539/3) diagnosed in Jewish Israelis ≥ 20years 1990 through 2015 registered in the Israel National Cancer Registry (INCR) were retrieved. All subsequent cancers occurring more than 6 months after meningioma diagnosis were identified. Risk of secondary cancer (SPC) was compared to cancer risk in the general population through the calculation of standardized incidence ratios (SIRs) and excess absolute risks (EARs). SIRs were stratified by type of second cancer, sex, and age group. Cox regression models were used to estimate hazard ratios of developing SPC. Overall, 8044 meningioma cases were identified: mean age at diagnosis was 64.0 ± 14.1years. Of these, 927 (11.5%) were diagnosed with SPC (SIR 1.6, 95% CI 1.5-1.7). SPC risk was elevated in men (SIR 1.6, 95% CI 1.5-1.9) and women (SIR 1.6, 95% CI 1.5-1.8) diagnosed with meningioma in univariable analyses. Cancers most commonly encountered in the studied population were breast (17.6%), colorectal (13.4%), lung (8.1%), prostate (5%), and bladder (4.6%) cancer. In multivariable analyses, 10+ year increment in age at meningioma diagnosis was significantly associated with higher risk for SPC in individuals diagnosed with meningioma between 20 and 64years, with an inverse association in the older age group (65+ years). Meningioma diagnosis is associated with an increased risk for developing secondary cancers. This risk should be discussed with patients treated for meningioma.

Cancer‐associated venous thromboembolism in Israel: Incidence, risk factors, treatment, and health care utilization in a population based cohort study

BackgroundRecent international guidelines recommend thromboprophylaxis in patients with cancer at intermediate‐high venous thromboembolism (VTE) risk. ObjectivesWe aimed to assess the current incidence, risk factors and management of cancer‐associated VTE and associated health care resource utilization in a 2.5‐million‐member state‐mandated health service in Israel. MethodsPatients aged ≥18 years with newly diagnosed cancer, initiating systemic anticancer treatment from 2010 through 2018 were identified from the Israel National Cancer Registry. The index date was fixed as the first day of systemic anticancer treatment. The cumulative VTE incidence from the first day of systemic anticancer treatment and the respective hazard ratios for VTE risk factors were calculated at 12 months of follow‐up. Health care resource utilization (primary care physician, emergency room, and hospital visits) during the study period was compared between patients with and without VTE. ResultsA total of 15 388 patients were included, and 338 had VTE with a 12‐month cumulative incidence of 2.2% (95% confidence interval, 1.96%‐2.43%). In a multivariable model, older age, higher comorbidity index, intermediate‐high‐risk Khorana score, certain malignancy types, and chemotherapy were significantly associated with an increased VTE risk in the year after initiating anticancer treatment. Compared with matched controls, the VTE subcohort were more likely to be hospitalized (81.4% vs 35.2%), have longer hospital stays (20.1 days vs 13.1 days), have an emergency room visit (41.5% vs 19.3%), and have a larger number of primary care physician visits (17.6 vs 12.5). ConclusionSeveral risk factors, including the Khorana score, were associated with VTE incidence. VTE was associated with long‐term use of anticoagulation. Health care utilization was higher in patients with VTE.

Previously undiagnosed cancer in patients with arterial thrombotic events – A population‐based cohort study

BackgroundEmerging data suggest increased arterial thrombosis risk in the months preceding a cancer diagnosis. ObjectivesTo assess whether patients without documented vascular risk factors or pre‐existing cardiovascular disease have a higher relative risk of cancer 12 months after arterial thrombotic events (ATE), compared to unselected patients. Patients/MethodsA population‐based cohort study of Clalit Health Services (CHS) database included CHS members ≥25 years without prior cancer or ATE (n = 2 804 584). An iterative matching process selected 10 potential controls chronologically for each consecutive exposed, age‐ and sex‐matched (actual controls drawn 1:1 from a lot). Study exposure, ATE, was defined as ischemic stroke, transient ischemic attack, myocardial infarction or systemic arterial thromboembolism during hospitalization. The outcome was newly‐diagnosed cancer within 12 months, based on Israeli national cancer registry. Cox proportional hazards multivariate regression calculated hazard ratio (HR) for outcomes, adjusted for cancer risk factors. Analysis also performed for three subgroups: age ≤50 years; no cardiovascular risk factors; no prior cardiovascular disease. ResultsThe full ATE and matched control cohorts included 43 108 patients. The 12‐month cumulative incidence of cancer (95% confidence interval) was 0.020 (0.019–0.022) in the ATE cohort and 0.012 (0.011–0.013) in controls, corresponding to an adjusted HR of 1.665 (1.489–1.862). The relative risk of cancer was high in all subgroups up to a HR of 3.754 (1.912–7.372) in patients without cardiovascular risk factors. ConclusionThere is an increased risk of previously undiagnosed cancer at 12 months after ATE, especially in patients without documented vascular risk factors or pre‐existent cardiovascular disease.

Validation of the Enriching New-Onset Diabetes for Pancreatic Cancer Model: A Retrospective Cohort Study Using Real-World Data.

The Enriching New-onset Diabetes for Pancreatic Cancer (END-PAC) model identified patients at high-risk for pancreatic ductal adenocarcinoma (PDAC) more than 6 months before diagnosis. The current study aimed to validate the END-PAC model using a large, state-mandated health care provider database. A retrospective cohort study of patients older than 50 years that had a diagnosis of new-onset diabetes (NOD) between 2006 and 2015. A risk score was assigned according to the END-PAC model. Patients who developed PDAC over the 3-year period after NOD diagnosis were identified using the Israeli National Cancer Registry. Twenty-three percent (1245/5408) of NOD patients were classified as high-risk, of them 32 (2.6%) developed PDAC. Median follow-up time from NOD detection to PDAC diagnosis was 609 days (interquartile range, 367-997). The hazard ratio for PDAC diagnosis among individuals at the high-risk group compared with the low-risk group was 5.70 (95% confidence interval, 2.93-11.06). Using the high-risk group as the screening threshold, the sensitivity, specificity, positive predictive value and negative predictive value of the model were 54.2%, 76.98%, 2.57%, and 99.4%, respectively. Area under the curve of the model was 0.69. Our findings support the robustness, generalizability and clinical applicability of the END-PAC model.

Pre-diagnosis thyroid hormone dysfunction is associated with cancer mortality.

Research on the association between thyroid hormone levels and cancer mortality remains limited and inconclusive. We determined the relation of thyroid stimulating hormone (TSH), free T4 (FT4), and free T3 (FT3) levels with mortality in overall cancer and specific tumor types. Thyroid hormone levels 1-5 years prior to cancer diagnosis, as well as multiple clinical and demographic parameters, were retrospectively collected for 10,325 Israeli cancer patients, diagnosed between 2000 and 2016. Patients treated with thyroid altering medications were excluded. Cancer diagnosis was determined via the Israel National Cancer Registry. Multivariate-adjusted Cox proportional hazards model was used to assess the hazard ratios (HRs) based on thyroid hormone function for cancer mortality. A total of 5265 patients died during the follow-up period (median of 4.4 years). TSH, FT4, and FT3 levels in the hypothyroid range were associated with increase in overall mortality (adjusted HR 1.20, 1.74, 1.87, respectively). We further analyzed the association between TSH and mortality in 14 cancer subgroups. Specifically, TSH in both the hyperthyroid and hypothyroid range was associated with melanoma mortality (adjusted HR 2.20, 4.47, respectively). In conclusion, pre-diagnosis of thyroid dysfunction is associated with increased cancer mortality, a relation likely driven by specific cancer types. These findings suggest that thyroid hormones may potentially serve as prognostic markers in cancer.

Excess Body Weight and Long-Term Incidence of Lung and Colon Cancer in Men; Follow-Up Study of 43 Years.

Most evidence for an association between excess body weight and cancer risk has been derived from studies of relatively short duration with little reference to the effect on tumor site. This study was designed to evaluate the association between categories of body mass index (BMI: <20, 20–25, 25–30, and >30 kg/m2) and the incidence of colon and lung cancer over 43 years of follow-up (1963–2006), in 10,043 men from the Israeli Ischemic Heart Disease (IIHD) prospective cohort (mean age at baseline 49.3 years, mean BMI 25.7 kg/m2). Data from the Israel National Cancer Registry was linked with the IIHD, and the Cox proportional hazards regression model was applied to analyze the relative risks for lung and colon cancer across BMI categories at baseline. Three hundred cases of lung cancer (2.9%) and 328 cases of colon cancer (3.3%) were diagnosed in the total population. Applying a multivariate model adjusted for age, smoking intensity, and total cholesterol, higher BMI category was associated with an increased risk of colon cancer [HR = 1.22 (95% CI 1.02–1.45)], and with a decreased risk for lung cancer [HR = 0.66 (95% CI 0.56–0.77)]. In this long-term follow-up study over four decades, we observed a consistent dose-response pattern between BMI and increased risk for colon cancer, but decreased risk for lung cancer. Specific associations between excess body weight and cancer risk may suggest different patterns of body fat and cancer incidence at a given site.

Increased incidence with improved survival of gynecologic carcinosarcoma: A population-based study

ObjectiveTo evaluate trends in the incidence and survival of gynecologic carcinosarcoma over the last 35 years and to explore ethnic disparities. Study designUsing the Israeli National Cancer Registry database, all cases of gynecologic carcinosarcoma were included (1980–2014). Age at diagnosis, patient’s ethnicity and anatomical site were extracted. Age-standardized incidence rates (ASRs) were calculated for 3 time periods (1980–1994, 1995–2004 and 2005–2014). Relative survival was calculated using the Pohar-Perme method. ResultsOverall, 935 cases of gynecologic carcinosarcomas were diagnosed during 1980–2014. The most common gynecologic anatomical site was the uterus (83.4%). Most cases (66%) were diagnosed at ages 60–80, with median age of 69 years.There was a steady increase in ASRs from 5.6 to 8.2 per million women. Throughout 1980–1994 and 2005–2014, ASRs were significantly higher in the Jewish compared to the Arab population (5.8 vs. 3.1, p = 0.02 and 8.5 vs. 5.2, p = 0.002, respectively).Relative survival rates increased throughout the study period. No significant differences were noted in relative survival between the Jewish and Arab populations (p = 0.18). ConclusionThe incidence of gynecologic carcinosarcoma increased significantly from 1980 through 2014. Nevertheless, survival rates increased during this time, with no difference in survival between the Jewish and Arab populations.

Cancer diagnosis among women with recurrent pregnancy loss: a retrospective cohort study

Research questionWhat is relationship between unexplained recurrent pregnancy loss (RPL) and risk of cancer morbidity? DesignA retrospective observational cohort study was conducted, based on data from a tertiary medical centre. RPL cases (exposed) were defined as women presenting with three or more unexplained confirmed pregnancy losses at 5–24 weeks, whose first visit to the RPL clinic was between 1990 and 2010. The unexposed group included women giving birth who were not RPL patients; these were matched by age and year of giving birth/admission (1:5 ratio). Data from the RPL and the live birth registries were cross-linked to the Israeli national cancer registry according to the unique ID number and merged into one database. ResultsThe study group comprised 937 RPL patients who were matched by maternal age (P = 1.0) and admission date (P = 0.84) to 4685 women achieving a live birth. There was no difference in overall cancer incidence between groups (adjusted odds ratio [OR] 0.76, 95% confidence interval [CI] 0.55–1.03; P = 0.08). The secondary RPL group showed a trend towards decreased cancer morbidity incidence compared with primary RPL (adjusted OR 0.65, 95% CI 0.41–1.03; P = 0.07). Analysis by cancer type showed a similar risk for breast cancer among women with RPL compared with live birth, but a significantly lower risk for gynaecological cancers among women with RPL (adjusted OR 0.25, 95% CI 0.08–0.79; P = 0.018). ConclusionsUnexplained RPL may be related to a lower risk of gynaecological cancers, possibly explained by hyper-responsive immunological mechanisms involving uterine natural killer cells.

Secondary Cancer after Meningioma Diagnosis – an Israeli National Study

Background: There are limited data on whether primary diagnosis of meningioma may be associated with development of secondary primary cancer (SPC). Methods: All meningioma cases (ICD-O-3 morphology codes 9530/0-9539/3) diagnosed in Jewish Israelis ages 20 and over between 1990 to 2015 were located in the database of the Israel National Cancer Registry (INCR). All subsequent cancers occurring more than six months after meningioma diagnosis were identified. Risk of secondary cancer (SPC) was compared to cancer risk in the general population through the calculation of standardized incidence ratios (SIRs) and excess absolute risks (EARs). SIRs were stratified by type of second cancer, sex, and age group. Cox regression models were used to estimate hazard ratios of developing SPC. Findings: Overall, 8044 eligible meningioma cases were identified: mean age at diagnosis was 64.0 years (standard deviation=14.1). Of these, 927 (11.5%) were diagnosed with SPC (SIR 1.6, 95% Confidence Interval, CI 1.5–1.7). Secondary cancer risk was found to be elevated in both men (SIR 1.6, 95% CI 1.5–1.9) and women (SIR 1.6, 95%CI 1.5–1.8) diagnosed with meningioma. Cancers most commonly encountered as secondary cancers in persons previously diagnosed with meningioma were breast (17.6%), colorectal (13.4%), lung (8.1%), prostate (5%), and bladder (4.6%) cancer. Interpretation: Meningioma diagnosis is associated with an increased risk for developing secondary cancers. This risk should be discussed with patients treated for meningioma. Funding: There was no funding for this research project. Declaration of Interest: None to declare. Ethical Approval: The study was approved by the Sheba Medical Center ethics committee.

The Risk of Developing Tuberculosis in Cancer Patients Is Greatest in Lymphoma: A Large Population-Based Study

Introduction: Patients with cancer, especially those diagnosed with hematological malignancies, are considered at higher risk for tuberculosis (TB). Several studies reported that Hodgkin lymphoma (HL) patients have the highest risk for TB among patients with hematological malignancies. These data are relatively old and based mostly on series of patients with malignancies or with TB but often lack statistical rigor and not based on large population-based studies.According to the Israeli regulations, every new diagnosis of cancer must be reported to the Israel National Cancer Registry (INCR) and every new diagnosis of TB to the Israel National Tuberculosis Registry (INTR). We combined both databases and studied epidemiological features of TB among patients with cancer in Israel, in which the incidence of TB in the general population is relatively low. The study objectives were to examine whether patients with hematological malignancies are at increased risk to develop active TB, compared to patients with solid tumors, and to examine whether patients with HL have a higher risk of active TB than patients with other hematological malignancies.Methods: The study population consists of all newly diagnosed cancer cases reported to the INCR from 1993-2013. These data were linked with data from the INTR for the same period. HIV patients were excluded from both databases. Hematologic malignancies were categorized into 5 groups: acute leukemia, HL, non-Hodgkin lymphoma (NHL), myelodysplastic syndrome/myeloproliferative neoplasm and plasma cell dyscrasia. Incidence rates per 100,000 person-years were calculated. Logistic regression was used to analyze the risk of TB following cancer diagnosis among patients with different malignancies.Results: Of 465,429 patients who were diagnosed with cancer during 1993-2013, 676 patients were notified to have TB but in only 321 patients the diagnosis of TB followed cancer diagnosis. The cumulative incidence of TB following cancer diagnosis was 14.4 per 100,000 person-years (PY). The rate of TB incidence following cancer diagnosis was 27.2/100,000 PY for persons diagnosed with hematological malignancies, and 12.7/100,000 PY among those with non-hematological malignancies (p<0.001). The highest TB incidence was found among patients with lymphoma (30.1 TB cases per 100,000 PY). Among lymphoma patients, a higher incidence rate was found in NHL patients than among HL patients, however the difference was not significant (32.1 vs . 21.6, respectively, p=0.378). Accounting for sex, age at diagnosis and ethnicity in logistic regression, the risk of TB among lymphoma patients is significantly higher than in other malignancies (Odds ratio 2.61, p=0.002) and there is no added significant risk for patients with HL (Odds ratio 1.33, p=0.464).Conclusions: 1) In this population-based study of more than 450,000 patients diagnosed with cancer, the incidence of TB following a cancer diagnosis is higher among patients with hematological malignancies than in patients with solid tumors. 2) Lymphoma patients have the highest risk to develop TB. 3) In contrast to common perception, we did not find that patients with HL are at increased risk to develop TB relative to NHL patients. 4) These data suggest for a heightened awareness for latent TB among newly diagnosed patients with lymphoma and for active TB among patients with a background of lymphoma who present with fever or respiratory complains. DisclosuresNo relevant conflicts of interest to declare.

Predictors of death at home among cancer patients in Israel: a population-based study

BackgroundMost cancer patients prefer to die at home; however, many die in hospital. The aim of the current study is to elucidate the association between dying at home and various personal factors in the Israeli population of cancer patients.MethodsData on cancer incidence (2008–2015) and death (2008–2017) was provided by the Israeli Central Bureau of Statistics and the Israel National Cancer Registry. Binary logistic regression analyses were performed to assess odds ratios for death at home following cancer diagnosis while controlling for age, sex, ethnicity, years of education, residential socioeconomic score, and time from diagnosis. We also assessed the relation between place of death and specific cancer sites, as well as the time trend from 2008 to 2017.ResultsAbout one quarter (26.7%) of the study population died at home. Death at home was most frequent among patients diagnosed with brain tumors (37.0%), while it was the lowest among patients with hematologic malignancies (lymphoma and leukemia, 20.3 and 20.0%, respectively). Rates of dying at home among patients with residential socioeconomic scores of 1, 2–9, and 10 were about 15, 30, and 42.9%, respectively. In patients from the 4th to the 7th decades of life, rates of death at home increased at a linear rate that increased exponentially from the 8th decade onwards. After controlling for potential confounders, predictive variables for death at home included age (OR = 1.020 per year, 95% CI 1.017–1.024), male sex (OR = 1.18, 95% CI 1.077–1.294), years of education (OR = 1.029 per year, 95% CI 1.018–1.040), and time from diagnosis (OR = 1.003 per month, 95% CI 1.001–1.005 all p < 0.001). No trend was seen from 2008 to 2013, while from 2014 to 2017 a slight increase in the rate of death at home was seen each year.ConclusionsThese results indicate wide variability in death at home exists among patients of different ages, sex, education, socioeconomic status and time from diagnosis. These findings stress the importance of delivering quality palliative care at home, mainly for patients with hematologic malignancies, younger patients, and patients of very low socioeconomic status. Understanding the complex mechanisms whereby patient preferences and the above variables may determine the preferred place of death remains an important research priority.

Height in adolescence as a risk factor for glioma subtypes: a nationwide retrospective cohort study of 2.2 million subjects.

Gliomas manifest in a variety of histological phenotypes with varying aggressiveness. The etiology of glioma remains largely unknown. Taller stature in adulthood has been linked with glioma risk. The aim of this study was to discern whether this association can be detected in adolescence. The cohort included 2 223 168 adolescents between the ages of 16 and 19 years. Anthropometric measurements were collected at baseline. Incident cases of glioma were extracted from the Israel National Cancer Registry over a follow-up period spanning 47 635 745 person-years. Cox proportional hazard models were used to estimate the hazard ratio (HR) for glioma and glioma subtypes according to height, body mass index (BMI), and sex. A total of 1195 patients were diagnosed with glioma during the study period. Mean (SD) age at diagnosis was 38.1 (11.7) years. Taller adolescent height (per 10-cm increase) was positively associated with the risk for glioma of any type (HR: 1.15; P = .002). The association was retained in subgroup analyses for low-grade glioma (HR: 1.17; P = .031), high-grade glioma (HR: 1.15; P = .025), oligodendroglioma (HR: 1.31; P = .015), astrocytoma (HR: 1.12; P = .049), and a category of presumed IDH-mutated glioma (HR: 1.17; P = .013). There was a trend toward a positive association between height and glioblastoma, however this had borderline statistical significance (HR: 1.15; P = .07). After stratification of the cohort by sex, height remained a risk factor for men but not for women. The previously established association between taller stature in adulthood and glioma risk can be traced back to adolescence. The magnitude of association differs by glioma subtype.