Familial Risks and Proportions Describing Population Landscape of Familial Cancer

Background: Familial cancer can be defined through the occurrence of the same cancer in two or more family members. We describe a nationwide landscape of familial cancer, including its frequency and the risk that it conveys, by using the largest family database in the world with complete family structures and medically confirmed cancers. Patients/methods: We employed standardized incidence ratios (SIRs) to estimate familial risks for concordant cancer among first-degree relatives using the Swedish Cancer Registry from years 1958 through 2016. Results: Cancer risks in a 20–84 year old population conferred by affected parents or siblings were about two-fold compared to the risk for individuals with unaffected relatives. For small intestinal, testicular, thyroid and bone cancers and Hodgkin disease, risks were higher, five-to-eight-fold. Novel familial associations included adult bone, lip, pharyngeal, and connective tissue cancers. Familial cancers were found in 13.2% of families with cancer; for prostate cancer, the proportion was 26.4%. High-risk families accounted for 6.6% of all cancer families. Discussion/Conclusion: High-risk family history should be exceedingly considered for management, including targeted genetic testing. For the major proportion of familial clustering, where genetic testing may not be feasible, medical and behavioral intervention should be indicated for the patient and their family members, including screening recommendations and avoidance of carcinogenic exposure.

Five-year survival in patients with Glioblastoma is overestimated in registry data - A nationwide population-based Swedish survey during 1958 - 1999

Background Some glioblastoma (GBM) patients survive more than five years with hitherto no clearly established epidemiological or molecular causes. Since varying rates of GBM five-year survival have been reported our aim was to assess the true prevalence of five-year survivors in Sweden from 1958 to 1999, before the introduction of concomitant temozolomide treatment.Methods After screening the Swedish Cancer Registry and the Cause of Death Register 736 out of 12765 patients with high-grade glioma were defined as five-year survivors. The full text pathology report was reviewed in 585 patients. Data on epidemiology and treatment were retrieved from the medical records of 556 patients.Results 77 five-year survivors with primary GBM were identified which corresponded to 0.60 % of the initial population. During 1990 to 1999 GBM five-year survival was 0. 90%. Younger age, Karnofsky score > 70 and non-eloquent tumour location were found in most but not all five-year survivors.Conclusion GBM five-year survival was exceedingly rare in Sweden until 2004, comprising less than 1 % of registered HGGs. Relying on registry data without reviewing the pathology report will overestimate the accurate number of five-year survivors. To our knowledge, this is the only nationwide population-based study of five-year survival in GBM patients.

Burden of Treatment-Induced Peripheral Neuropathy in Patients with Multiple Myeloma in Sweden

Introduction: Treatment-induced peripheral neuropathy (TIPN) is a complication of multiple myeloma (MM) treatment. Objective: This real-world, retrospective study used electronic medical record (EMR) data from 3 Swedish clinics to assess the occurrence and economic burden of TIPN in patients with MM. Methods: Eligible patients had an MM diagnosis in the Swedish Cancer Registry between 2006 and 2015 and initiated treatment during that period. Follow-up was until last EMR visit, death, or study end (April 2017). The current analyses included patients receiving bortezomib, lenalidomide, carfilzomib, or thalidomide at any treatment line. To discern healthcare resource utilization (HCRU) and costs associated with TIPN from other causes, patients with TIPN were matched with those without on baseline characteristics, treatment, and line of therapy. All analyses were descriptive. Results: Overall, 457 patients were included; 102 (22%) experienced TIPN. Patients experiencing TIPN during first-line treatment mostly received bortezomib-based regimens (n = 48/57 [84%]); those with TIPN during second- and third/fourth-line treatment mostly received lenalidomide/thalidomide-based regimens (19/31 [61%], 8/14 [57%], respectively). Patients with TIPN had higher HCRU/costs than those without TIPN (mean differences in hospital outpatient visits: 5.2, p = 0.0031; total costs per patient-year: EUR 17,183, p = 0.0007). Conclusions: Effective MM treatments associated with a reduced incidence of TIPN could result in decreased healthcare expenditure.

Previously diagnosed multiple primary malignancies in patients with breast carcinoma in Western Sweden between 2007 and 2018

Purpose Multiple primary malignancies (MPMs) caused by breast cancer treatment are well described, but only few studies to date describe which other previous primary malignancies (OPPMs) occur before breast cancer. The purpose of the present study was to evaluate the prevalence of OPPMs in patients with breast cancer between 2007 and 2018 in Western Sweden. Methods Patient selection was performed using both pathology reports at Sahlgrenska University Hospital (Sweden) and the Swedish Cancer Registry. All newly diagnosed breast cancer patients were screened for presence of OPPM. Results In total, 8031 breast cancer patients were diagnosed at Sahlgrenska University Hospital between 2007 and 2018. The prevalence of breast cancer patients with OPPMs (n = 414) increased from on average 2.6% to 8.2% during this 12-year period and ranged from 17 to 59 patients annually. The most striking increase in prevalence was found among the gynecological tumors (endometrium and ovarian adenocarcinomas), malignant melanomas and gastrointestinal malignancies. These findings were validated using data of the Swedish Cancer Registry. Conclusions The overall survival rates for cancer patients have improved tremendously during the past 40 years, in part due to individually tailored therapies and screening programs. Our study revealed an increasing trend of OPPMs in breast cancer patients.

MON-330 Cancer Incidence in 1,296 Patients with Acromegaly Is Not Increased: A Nationwide Population-Based Study

Background: Single- and multi-center studies have shown an increased incidence of malignancies in patients with acromegaly. These findings may be affected by selection bias. Our aim was therefore to investigate the incidence of malignancies in a nationwide unselected cohort of patients with acromegaly. Methods: Adult patients diagnosed with acromegaly due to a pituitary tumor between 1987 and 2017 were identified in the Swedish National Patient Registry. All malignancies following the diagnosis of acromegaly were identified in the Swedish Cancer Registry that has a coverage of over 96%. Standardized incidence ratios (SIRs) for malignancies, with 95% confidence intervals (CI), were calculated by using the Swedish general population as a reference. Incidence of malignancies was also analyzed in sub-groups of patients treated with radiotherapy and in those having diabetes mellitus and hypopituitarism. Results: A total of 1,296 patients with acromegaly were included (621 men, 675 women). The mean age (±SD) at diagnosis was 51.6±14.7 years. The mean follow-up was 12.7±8.3 years, with a total of 16,395 person years at risk. Pituitary surgery was performed in 842 (65%) patients and radiation therapy in 152 (12%) patients. The diagnosis of hypopituitarism and diabetes mellitus was recorded in 29% and 16% of patients, respectively. Overall, 186 malignancies were identified in patients with acromegaly as compared to 179 expected malignancies in the general population (SIR 1.04; 95% CI 0.90-1.20). Incidence of malignancies was similar in men and women [SIR 1.08 (95% CI 0.88-1.32) vs 1.00 (95% CI 0.80-1.23)]. Incidence of colorectal cancer (SIR 1.12; 95% CI 0.75-1.62) or malignancies of the respiratory system (SIR 1.22; 95% CI 0.76-1.84) was not increased. Incidence of kidney and ureter cancer (n=17) was, however, increased (SIR 3.81; 95% CI 2.22-6.11). In the entire study cohort, only three cases of thyroid cancer were recorded. SIR for malignancies in patients treated with radiotherapy (1.12; 95% CI 0.56-2.01) and in patients with hypopituitarism (SIR 0.91; 95% CI 0.68-1.18) or diabetes (SIR 1.08; 95% CI 0.78-1.45) did not differ from the general population. Conclusions: This large nationwide population-based study showed that the overall incidence of malignancies in patients with acromegaly was not different from the general population. In particular, incidence of colorectal and thyroid cancer was not increased. Incidence of malignancies of the urinary tract was, however, increased.

Costs per Treatment Phase for AML Patients Receiving High-Dose Chemoterapy in Sweden

Introduction: AML affects all ages with an incidence rate of 5 per 100,000, but is much more frequent in older population. The overall lifetime risk of AML is estimated to be 0.5-1%. Long-term overall survival in younger (age < 60 years) is about 50%, but much worse among older population. Although AML therapy is one of the most resource-intensive cancer treatments, there are few estimates of the resource use and economic burden by treatment phase. Methods: This study was a retrospective database study performed on Swedish national data. Adult patients (age ≥18 years) diagnosed with AML in Sweden between 2007 and 2015 were identified in the Swedish Cancer Registry, along with vital status. Data on resource use were collected from national registers for inpatient- and outpatient specialized care and prescribed drugs. Information on diagnostics and treatment was accessed from the Swedish national AML Registry (SwAMLR). Data on sick leave (SL) and early retirement (ER) came from the Swedish Social Insurance Agency (absent days costed with the mean salary in Sweden). Hospital care resource use was costed using diagnosis-related group (DRG) remunerations, and include cost of inpatient drugs. The mean cost from the defined start of the treatment phase until the end of the treatment phase was divided by the mean number of days for the corresponding treatment phase to estimate the mean cost per day. The defined treatment phases were restricted to a maximum of 5 years. All costs are represented in US$. Results: Of the 2,954 patients identified in the Swedish Cancer Registry, 1,772 patients with a median age of 64 years were identified in the SwAMLR as fit for receiving high-dose chemotherapy . Of these, 1,243 were recorded with both curative intent of treatment and dates for achieving complete remission. Mean costs from the first AML-related hospital admission until the date of complete remission amount to $27,244. The mean number of days for the corresponding period were 45.16, resulting in a mean cost per day of $603 from first admission to first complete remission. The corresponding cost per day for patients recorded with curative intent but no complete remission (n=428) are $494. Time was counted from first AML-related admission until 90 days after first admission, or SCT or death, whichever occurred first. Costs after complete remission to either relapse, SCT, death or re-induction (n=1,237) amount to $50,793 for a mean of 438.63 days ($116/day). This treatment phase includes long-term survivors, whereas the costs from SCT, relapse or re-induction are not included. From relapse to death, the total cost is almost twofold for patients with re-induction (n=350) compared to palliative treatment (n=254). Cost per day amount to $179 for patients with palliative treatment and $256 for patients with re-induction treatment, respectively. The cost per day from date of SCT to death (n=511) is estimated to $192, incurred over a long period of time (mean number of days 844.02). The age of transplant recipients ranged between 18-71 years, with a median of 52 years. Conclusions: Costs of AML up to remission are feasible to estimate through DRG-costing methods, and studies have shown these costs are intense. Indeed this study shows that the highest cost per day is observed from first admission to complete remission. In addition results from our study show that there are high costs incurred also in the long-term, i.e. after remission. Of the included treatment phases the total cost from date of SCT to death is the largest, amounting to over $160,000. Approximately 20% are due to SL/ER, which is the second largest cost component after inpatient costs accounting for 60% of the total costs. Table. Disclosures Hernlund: ICON: Employment. Redig:ICON: Employment. Paulsson:Novartis: Employment. Vertuani:Novartis: Employment.

Investigating the risk of breast cancer among women exposed to chemicals: a nested case–control study using improved exposure estimates

Purpose The aim of this study was to examine if exposures to chemicals at the workplace were associated with an increased risk of postmenopausal breast cancer, using improved exposure estimates. Methods The design is a case–control study, nested within a cohort of women from the Malmö Diet and Cancer Study. The study comprised 2400 women, 731 cases and 1669 matched controls, born 1923–1950 and living in Malmö, Sweden between 1991 and 1996. An occupational hygienist reclassified the probability for exposure given by a job-exposure matrix, using individual data on work tasks. First-time diagnoses of invasive breast cancer were identified through the Swedish Cancer Registry. Results Women exposed to chemicals in their occupational environment had a statistically significantly increased risk (OR 1.59, 95% CI 1.11–2.29) of breast cancer, and the risk correlated positively with duration of exposure but not with exposure intensity. Women exposed to chlorinated hydrocarbon solvents for more than 10 years had a significant higher risk of breast cancer (OR 3.06, 95% CI 1.18–7.96) as well as women exposed to oil mist for more than 10 years (OR 3.08, 95% CI 1.12–8.49). Conclusions This study gives some support to the hypothesis that exposure to organic solvents as well as oil mist is associated with increased risk of breast cancer.

Primary small intestinal neuroendocrine tumors are highly prevalent and often multiple before metastatic disease develops

Background: Small intestinal neuroendocrine tumors are the most common of small bowel malignancies with a clinical incidence of about 1 per 100,000 persons per year. There has been a threefold increase in the incidence of small intestinal neuroendocrine tumor during later decades, but there are no studies that clarify whether this is due to a true higher incidence or if the rise is a mere product of, for instance, improved diagnostic modalities. The aim of this study was to investigate the incidence of clinical as well as subclinical small intestinal neuroendocrine tumors found at autopsy as well as describing the frequency of concomitant malignancies in patients with small intestinal neuroendocrine tumor. Materials and methods: An autopsy registry from the Malmö county population from 1970 to 1982 with an 87% autopsy rate was used. The clinical autopsy reports for patients coded for the existence of “carcinoid tumor” were scrutinized for the presence of small intestinal neuroendocrine tumor, metastatic disease, and concomitant malignancies. Details of patients with clinically diagnosed small intestinal neuroendocrine tumor during this time period were gathered from the Swedish Cancer Registry. Results: The mean annual incidence of small intestinal neuroendocrine tumor during this period was 5.33 per 100,000 individuals, and the mean annual prevalence was 581 per 100,000. The cause of death in the majority of cases was not due to small intestinal neuroendocrine tumor. In total, 48% of the people with small intestinal neuroendocrine tumor had at least one other malignancy, most commonly colorectal cancer. Conclusion: Most small intestinal neuroendocrine tumors are subclinical, and persons living with them will often die due to other causes. There was a high rate of multiple primary tumors (40%), suggesting that multiple tumors seem to arise before the advent of metastatic disease. Moreover, a comparably high rate of associated colorectal carcinoma was found.

Helicobacter pylori eradication treatment and the risk of gastric adenocarcinoma in a Western population

ObjectiveGastric infection with Helicobacter pylori is a strong risk factor for non-cardia gastric adenocarcinoma. The aim of this study was to assess whether the risk of gastric adenocarcinoma and non-cardia gastric adenocarcinoma decreases after eradication treatment for H. pylori in a Western population.DesignThis was a nationwide, population-based cohort study in Sweden in 2005–2012. Data from the Swedish Prescribed Drug Registry provided information on H. pylori eradication treatment, whereas information concerning newly developed gastric adenocarcinoma was retrieved from the Swedish Cancer Registry. The risk of gastric adenocarcinoma and non-cardia gastric adenocarcinoma in individuals who had received H. pylori eradication treatment was compared with the background population of the corresponding age, sex and calendar year distribution, yielding standardised incidence ratios (SIRs) with 95% CIs.ResultsDuring the follow-up of 95 176 individuals who had received eradication treatment (351 018 person-years at risk), 75 (0.1%) developed gastric adenocarcinoma and 69 (0.1%) developed non-cardia gastric adenocarcinoma. The risk of gastric adenocarcinoma decreased over time after eradication treatment to levels below that of the corresponding background population. The SIRs were 8.65 (95% CI 6.37 to 11.46) for 1–3 years, 2.02 (95% CI 1.25 to 3.09) for 3–5 years and 0.31 (95% CI 0.11 to 0.67) for 5–7.5 years after eradication treatment. When restricted to non-cardia adenocarcinoma, the corresponding SIRs were 10.74 (95% CI 7.77 to 14.46), 2.67 (95% CI 1.63 to 4.13) and 0.43 (95% CI 0.16 to 0.93).ConclusionEradication treatment for H. pylori seems to counteract the development of gastric adenocarcinoma and non-cardia gastric adenocarcinoma in this Western population.