Swedish Cancer Registry Research Articles

Association Between Proton Pump Inhibitor Use and Biliary Tract Cancer Risk: A Swedish Population-Based Cohort Study.

Biliary tract cancer is a group of highly aggressive malignant disorders, yet risk factors are poorly understood. In this study, we aim to assess whether prolonged use of proton pump inhibitors (PPIs) increases the risk of incident biliary tract carcinoma in a nation-wide population-based cohort in Sweden. Using nation-wide registries, we identified all adults who received maintenance PPIs (≥180days) according to the Swedish Prescribed Drug Register from 2005 through 2012. Data on incident biliary tract cancer were retrieved from the Swedish Cancer, Death and Outpatient Registers. Risk of biliary tract cancer in persons who received PPI treatment was compared with the general population of the corresponding age, sex, and calendar year yielding standardized incidence ratios (SIRs) with 95% CIs. Of 738,881 PPI users (median follow-up of 5.3years), 206 (0.03%) developed gallbladder cancer and 265 (0.04%) extrahepatic and 131 (0.02%) intrahepatic bile duct cancer corresponding to SIRs of 1.58 (95% CI, 1.37-1.81), 1.77 (95% CI, 1.56-2.00), and 1.88 (95% CI, 1.57-2.23), respectively. In sensitivity analyses restricted to persons without a history of gallstones or chronic liver or pancreatic diseases, SIRs were 1.36 (95% CI, 1.17-1.57) and 1.47 (95% CI, 1.19-1.80) for extra- and intrahepatic duct cancer, respectively. The risk remained higher than the corresponding general population with ≥5years of PPIs use, ruling out confounding by indication. In this study, long-term use of PPIs was associated with an increased risk of gallbladder, intrahepatic, and extrahepatic bile duct cancer compared with the general population.

Is Cadmium a Risk Factor for Breast Cancer - Results from a Nested Case-Control Study Using Data from the Malmö Diet and Cancer Study.

Some studies have shown that cadmium (Cd) is associated with breast cancer risk. One hypothesis is that Cd has estrogen-like properties. This case-control study investigated the association between breast cancer risk and blood Cd (BCd) levels. All breast cancers in the Malmö Diet and Cancer cohort were identified through linkage to the Swedish Cancer Registry, baseline (1991-1996) through 2014. Two controls per case were selected from the same cohort. BCd was analyzed at baseline. Associations were analyzed using logistic regression. Mean BCd was 0.51 μg/L among 1,274 cases and 0.46 among 2,572 controls. There was an overall increased risk of breast cancer [OR, 1.18; 95% confidence interval (CI), 1.05-1.36] per μg/L of BCd. An increased risk was, however, only found at high BCd [OR, 1.34 (95% CI, 1.05-1.73)] for BCd more than 1.20 μg/L. The group with the highest BCd was mainly smokers. A spline indicated that at BCd less than 1.0 μg/L, the OR was not increased. The association with BCd was stronger in current smokers and at body mass index (BMI) above 25, while no modification due to receptor status was found. The results indicated increased risk of breast cancer only for high Cd exposure, which occurred mainly among smokers. This made it difficult to disentangle the effects of smoking and Cd, despite inclusion of smoking habits in the models. This study provides support for reducing Cd exposure through smoking cessation and dietary choice. On the population level, preventive measures against Cd pollution are warranted.

Cardiac risk stratification in emergency resection for colonic tumours.

BackgroundDespite advances in perioperative care, the postoperative mortality rate after emergency oncological colonic resection remains high. Risk stratification may allow targeted perioperative optimization and cardiac risk stratification. This study aimed to test the hypothesis that the Revised Cardiac Risk Index (RCRI), a user-friendly tool, could identify patients who would benefit most from perioperative cardiac risk mitigation.MethodsPatients who underwent emergency resection for colonic cancer from 2007 to 2017 and registered in the Swedish Colorectal Cancer Registry (SCRCR) were analysed retrospectively. These patients were cross-referenced by social security number to the Swedish National Board of Health and Welfare data set, a government registry of mortality, and co-morbidity data. RCRI scores were calculated for each patient and correlated with 90-day postoperative mortality risk, using Poisson regression with robust error of variance.ResultsSome 5703 patients met the study inclusion criteria. A linear increase in crude 90-day postoperative mortality was detected with increasing RCRI score (37.3 versus 11.3 per cent for RCRI 4 or more versus RCRI 1; P < 0.001). The adjusted 90-day all-cause mortality risk was also significantly increased (RCRI 4 or more versus RCRI 1: adjusted incidence rate ratio 2.07, 95 per cent c.i. 1.49 to 2.89; P < 0.001).ConclusionThis study documented an association between increasing cardiac risk and 90-day postoperative mortality. Those undergoing emergency colorectal surgery for cancer with a raised RCRI score should be considered high-risk patients who would most likely benefit from enhanced postoperative monitoring and critical care expertise.

Second Primary Cancers After Gastric Cancer, and Gastric Cancer as Second Primary Cancer.

BackgroundSecond primary cancers (SPCs) are increasing, which may negatively influence patient survival. Gastric cancer (GC) has poor survival and when it is diagnosed as SPC it is often the cause of death. We wanted to analyze the risk of SPCs after GC and the risk of GC as SPC after any cancer. Such bidirectional analysis is important in relation to fatal cancers because SPCs may be under-reported in the short-term survival period.MethodsCancers were obtained from the Swedish Cancer Registry from years 1990 through 2015. Standardized incidence ratios (SIRs) were used to estimate bidirectional relative.ResultsWe identified 23,137 GC patients who developed 1042 SPCs (4.5%); 2158 patients had GC as SPC. While the risk for three SPCs was increased after GC, seven first primary cancers were followed by an increased risk of GC as SPC, including esophageal, colorectal, bladder, squamous cell skin and breast cancers and non-Hodgkin lymphoma. Breast cancer, which was followed by a diagnosis of second GC, showed an excess of lobular histology.ConclusionMultiple primary cancers in the same individuals may signal genetic predisposition. Accordingly, the association of GC with breast cancer may be related to mutations in the CDH1 gene, and clustering of colorectal, small intestinal and bladder cancers could be related to Lynch syndrome. The third line of findings supports a contribution of immune dysfunction on the increased risk of GC as SPC after skin cancer and non-Hodgkin lymphoma. Early detection of GC in the risk groups could save lives.

Diagnostic codes of cancer in Sk\xe5ne healthcare register: a validation study using individual-level data in southern Sweden

BackgroundThe Swedish healthcare is decentralised to 21 regions. Detailed information on all delivered care in the southernmost region, Skåne, is prospectively collected in the Skåne Healthcare Register (SHR). The data is updated daily and hence a good source for epidemiological studies. However, the diagnostic codes used to identify cancer patients in SHR have not yet been validated.MethodsWe conducted a validation study including 1,473,204 residents in Skåne region during 2005–2014, with at least one physical consultation in SHR. Newly diagnosed cancer from the Swedish Cancer Register was considered the ‘gold standard’ reference. We estimated the positive predictive value (PPV), sensitivity, and area under the curve (AUC) of a cancer diagnosis based on SHR by level of consultation, for any cancer, and for different cancer types.ResultsThere were 61,693 cancers from the Swedish Cancer Register, and 87,650 cancers from SHR. The PPV of SHR-based diagnosis of any cancer was 63.76% (95% confidence interval (CI): 63.44–64.08%) with a sensitivity of 90.58% (95% CI: 90.35–90.81%). The AUC was 0.94, for any cancer. The measures of PPV, sensitivity and AUC varied across levels of care and were higher in specialized care than in primary care. The highest PPV was observed for specialist inpatient care in SHR (89.17, 95% CI 88.89–89.45%) whereas the highest sensitivity was observed for specialized outpatient care in SHR (86.39, 95%CI 86.12–86.66%). Robust validity was noted among most cancers, except for cancers of soft tissues, central nervous system and eye, and endocrine glands.ConclusionsOur study supports that SHR is a valid and robust healthcare register for cancer diagnosis, with varying validities across levels of care and cancer types. This makes SHR a useful data source for cancer epidemiological studies, especially because the data covers the entire cancer care pathways without time lags for further linkage.

Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS) after Multiple Myeloma: Assessment of Risk Factors

Risk factors for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) in patients with multiple myeloma (MM) are not well understood. We have previously shown that monoclonal gammopathy of undetermined significance (MGUS) is associated with an excess risk of AML/MDS, indicating an inherent excess risk of AML/MDS in plasma cell disorders. In addition, randomized studies have shown that lenalidomide maintenance is associated with increased relative risk of AML/MDS. The excess risk of AML/MDS in lenalidomide treated patients has been found to be most prominent in patients that also receive alkylating agents. A recent randomized clinical study shows that delayed autologous transplant has the same overall survival as upfront autologous transplant with high dose melphalan at 3 years of follow-up; also emerging data shows that minimal residual disease (MRD) negativity has very similar progression free survival independent of therapy. Thus, patients treated with modern combination therapy who obtain MRD negativity might not have additional benefit from upfront autologous transplant. We were motivated to better define the role of alkylating therapy in relation to subsequent risk of secondary malignancies.All patients diagnosed with MM from January 1, 1958 to December 31, 2011 were identified from the Swedish Cancer Registry. Information was obtained regarding all subsequent hematologic malignancies among patients in the MM cohort. Each patient with MM and a subsequent AML/MDS diagnosis (i.e., cases) was matched to another MM patient without AML/MDS for year of birth, sex, and date of MM diagnosis (i.e., control group). Detailed information on baseline characteristics at diagnosis and treatment was collected from medical records. Patients with MM and AML/MDS were also compared to MM patients that developed lymphoproliferative malignancies. Characteristics at MM diagnosis, radiation therapy, and ASCT were compared between groups with Kruskal-Wallis and Chi-square tests. Cumulative chemotherapy doses were analyzed with one way ANOVA. Post hoc analysis with Fisher´s LSD was performed.A total of 26,627 patients were diagnosed with MM in Sweden during the study period. Of these, 224 patients developed hematological malignancies. Data was found for 89 MM and subsequent AML/MDS patients and they were matched to 89 controls. Preliminary results from the first 12 controls were available for analysis, number of controls will be updated as more data has been reviewed. A total of 100 patients had lymphoproliferative malignancies and 1/3 of them were randomly selected. The demographic and clinical characteristics for all groups are listed in Table. The median age at MM diagnosis was 67 years (39 females and 50 males) for cases, 72 years (7 females and 5 males) for controls and 70 years (10 females and 23 males) for patients with lymphoproliferative malignancies. The median time from MM diagnosis to AML/MDS diagnosis was 3.8 (range 0.4-17.1) years and 3.4 (range 0.4-29.4) years for patients who developed lymphoproliferative malignancies. The mean cumulative melphalan dose was 1,318 mg (SD ± 1,159 mg) for cases, 704 mg (SD ± 588 mg) for the controls and 967 mg (SD ± 978 mg) for patients who developed lymphoproliferative malignancies. There was a statistically significant difference of mean cumulative melphalan dose between groups (F (2,123) = 3.14, p= 0.047). Post hoc analysis confirmed that cases had a statistically significant higher mean cumulative melphalan dose compared to controls, p <0.05.The preliminary results from this large nationwide population based study including almost 27,000 MM patients in Sweden over >50 years shows that the mean cumulative dose of melphalan was higher in MM patients who developed AML/MDS compared to MM patients who did not. With the average myeloma patient living over 10-15 years from diagnosis, strategies to avoid secondary complications is becoming more important. Our results showing that melphalan is associated with an increased risk of AML/MDS, call for studies using response driven (i.e. MRD based) therapy in myeloma; were high dose melphalan is rather offered to patients who are MRD positive. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Outcome of Patients with Chronic Lymphocytic Leukemia (CLL) Receiving First Line Therapy: A Swedish Nation-Wide Study on 1053 Consecutive Patients Treated between 2007 and 2013

Background: The incidence of chronic lymphocytic leukemia (CLL) in Sweden is about 500/year. Previous US data suggest that region and type of institution/hospital where patients were treated may affect outcome. Swedish results may differ as almost all CLL patients are treated within public health care, most treatment decisions are taken at therapy conferences and we have a widespread usage of yearly updated national CLL guidelines.This study investigates the outcome following 1st line CLL therapy in a well-defined population of consecutive patients in a region with complete follow-up: such data may be used as quality assurance for healthcare providers and serve as real-world control for clinical trials, selecting patients based on inclusion/exclusion criteria. The Swedish Cancer Registry and the Information Network for Cancer (INCA) gives us a unique opportunity to identify all patients diagnosed within a defined time period, thus providing a possibility to obtain data on various therapies and outcome on a nation-wide basis.Methods: This is a retrospective study on all Swedish CLL patients who received 1st line therapy due to progressive, symptomatic CLL. The time period 2007-2013 was selected to obtain sufficient follow-up. In-depth analysis of all individual patient files was performed. Cross-checked, computerized data were subject to statistical analysis. Endpoints were clinical response (IWCLL criteria), PFS, OS and safety. Type of treating hospital (local/regional/university) and geographical region was recorded. Whether choice of 1st line therapy was compliant to the national CLL guidelines was also recorded. A multivariate cox proportional hazards model was used to explore risk factors on outcome.Results: Between 2007 and 2013, all 1st line treated patients (n=1053) were identified. At 1st line treatment initiation median age was 71 years (range 31- 96) and 34% were females. Rai stages (0-I, II-IV) were 45 and 53%. Regarding performance status (PS) 96% were grade 0-2 and only 2% had grade 3-4. FISH was not introduced in routine healthcare until late in the period and was excluded in the first analysis. IGHV mutational status analysis was not compulsory. Most frequently used treatments were chlorambucil (CLB) (39%), FCR (27%) and FC (16%). Bendamustine (B) was not introduced until end of the study period thus only 6% (n=63) had received B or BR. Other regimens included for example alemtuzumab (5%), CHOP/CVP +/-R (3%) and rituximab (R) single (2%). Dosing intensity was similar across geographical regions and type of institutions.The ORR was 64% (15% CR); with CLB 43% FCR 84%, FC 75% and B/BR 75%. ORR was significantly associated with type of treatment and age but not with sex, Rai stage (p=0.051) or bulky disease.Median PFS was 19 months and at a median follow-up of 5 years, 49% of all patients remained alive. PFS and OS were both significantly associated with type of treatment (Fig 1 and 2); CLB-treated patients had a median PFS and OS of only 9 and 33 months. Usage of CLB declined during the study period, but still 1/3 of all patients (in some regions up to 44%) received 1st line CLB as late as 2013.Age, Rai stage, PS and adherence to treatment guidelines were also significantly associated with PFS and OS by univariate analyses.There was no clearcut impact on PFS and OS by type of health care institution/hospital.Multivariate analysis revealed that age, PS, treatment (all p=0.00001), Rai stage (p=0.003) and sex (p=0.02) were all significantly associated with OS, whereas adherence to guidelines was no longer significant.Infections ≥ grade III were significantly associated with type of treatment (p=0.006); CLB 19% vs FCR 30%. Richter transformation occurred in 5% of the patients. 15 % of the patients were diagnosed with a secondary malignancy equally distrubuted between types of 1st line therapy.Conclusion:This is the largest retrospective cohort of consecutive 1st line treated CLL patients from a well defined geographical region (Sweden) with a complete follow-up. All patients were identified and data were subject to in-depth analysis of every individual patient file, ensuring high quality data. We demonstrate that single-agent CLB resulted in a poor outcome and conclude that alternative modern, effective 1st line treatment alternatives must be offered to elderly patients. This study also highlights the importance of updated evidence-based guidelines and their usage across all levels of health care. [Display omitted] DisclosuresKimby:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Celgene: Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria; Abbvie: Membership on an entity's Board of Directors or advisory committees. Andersson:Janssen-Cilag: Honoraria; Abbvie: Honoraria, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; roche: Speakers Bureau; GSK: Speakers Bureau. Karlsson:Abbvie: Honoraria; Janssen-Cilag: Honoraria. Mattsson:Janssen-Cilag: Honoraria; Gilead: Honoraria; Abbvie: Honoraria; Roche: Honoraria. Österborg:Pfizer: Honoraria; Abbvie: Honoraria; Celgene: Research Funding; Janssen-Cilag: Honoraria, Research Funding; Gilead: Honoraria, Research Funding. Hansson:Abbvie: Honoraria; Gilead: Honoraria, Research Funding; Janssen-Cilag: Honoraria, Research Funding.

Bladder and upper urinary tract cancers as first and second primary cancers.

BackgroundPrevious population‐based studies on second primary cancers (SPCs) in urothelial cancers have focused on known risk factors in bladder cancer patients without data on other urothelial sites of the renal pelvis or ureter.AimsTo estimate sex‐specific risks for any SPCs after urothelial cancers, and in reverse order, for urothelial cancers as SPCs after any cancer. Such two‐way analysis may help interpret the results.MethodsWe employed standardized incidence ratios (SIRs) to estimate bidirectional relative risks of subsequent cancer associated with urothelial cancers. Patient data were obtained from the Swedish Cancer Registry from years 1990 through 2015.ResultsWe identified 46 234 urinary bladder cancers (75% male), 940 ureteral cancers (60% male), and 2410 renal pelvic cancers (57% male). After male bladder cancer, SIRs significantly increased for 9 SPCs, most for ureteral (SIR 41.9) and renal pelvic (17.2) cancers. In the reversed order (bladder cancer as SPC), 10 individual FPCs were associated with an increased risk; highest associations were noted after renal pelvic (21.0) and ureteral (20.9) cancers. After female bladder cancer, SIRs of four SPCs were significantly increased, most for ureteral (87.8) and pelvic (35.7) cancers. Female bladder, ureteral, and pelvic cancers associated are with endometrial cancer.ConclusionsThe risks of recurrent urothelial cancers were very high, and, at most sites, female risks were twice over the male risks. Risks persisted often to follow‐up periods of >5 years, motivating an extended patient follow‐up. Lynch syndrome‐related cancers were associated with particularly female urothelial cancers, calling for clinical vigilance.

Trend Shifts in Age-Specific Incidence for In Situ and Invasive Cutaneous Melanoma in Sweden.

Simple SummaryThe incidence of invasive cutaneous melanoma (CM) is increasing in Sweden. The aim was to present age- and sex-specific trends of the age-standardised incidence and the average annual percentage change (AAPC) for in situ and invasive CM by analysing data obtained from the Swedish Melanoma Register and the Swedish Cancer registry for 35,350 in situ tumours and 59,932 CM. Trend shifts in age-specific incidence for in situ and invasive CM reflect a rise among both sexes since the 2000s and could be a result of more effective secondary prevention efforts and a higher awareness of CM.Background: The incidence of invasive cutaneous melanoma (CM) is increasing in Sweden. The aim was to present age- and sex-specific trends of the age-standardised incidence and the average annual percentage change (AAPC) for in situ and invasive CM. Methods: Joinpoint regression models were used to analyse data from the Swedish Cancer Register and the Swedish Melanoma Registry 1997–2018 (N = 35,350 in situ CM; 59,932 CM). Results: The AAPC of CM for women was 4.5 (4.1–5.0; p < 0.001) for the period 1997–2018. For men, the APCC was 4.2 (3.0–5.4; p < 0.001), with a significantly higher annual percentage change (APC) for the period 2000–2018 (5.0; 4.6–5.4; p < 0.001) compared to 1997–1999. An increasing annual incidence of CM ≤ 0.6 mm and 0.7 mm Breslow tumour thickness was found for men with a significant incidence shift for the period 2006–2015, respectively. Similarly for women, with a significantly higher APC for CM ≤ 0.6 mm from 2005. The incidence of intermediate thick CM (2.1–4.0 mm) has not increased since 2011. The incidence of CM > 4.0 mm has been increasing among both sexes, with a significantly lower APC among women from 2005. Conclusions: The incidence of in situ and low-risk CM ≤ 1.0 mm in tumour thickness has been rising among both sexes since the 2000s.

ICU Admission in Children With Acute Lymphoblastic Leukemia in Sweden: Prevalence, Outcome, and Risk Factors.

Despite progress in the treatment of childhood acute lymphoblastic leukemia, severe complications are common, and the need of supportive care is high. We explored the cumulative prevalence, clinical risk factors, and outcomes of children with acute lymphoblastic leukemia, on first-line leukemia treatment in the ICUs in Sweden. A nationwide prospective register and retrospective chart review study. Children with acute lymphoblastic leukemia were identified, and demographic and clinical data were obtained from the Swedish Childhood Cancer Registry. Data on intensive care were collected from the Swedish Intensive Care Registry. Data on patients with registered ICU admission in the Swedish Childhood Cancer Registry were supplemented through questionnaires to the pediatric oncology centers. All 637 children 0-17.9 years old with acute lymphoblastic leukemia diagnosed between June 2008 and December 2016 in Sweden were included. None. Twenty-eight percent of the children (178/637) were admitted to an ICU at least once. The Swedish Intensive Care Registry data were available for 96% of admissions (241/252). An ICU admission was associated with poor overall survival (hazard ratio, 3.25; 95% CI, 1.97-5.36; p ≤ 0.0001). ICU admissions occurred often during early treatment; 48% (85/178) were admitted to the ICU before the end of the first month of acute lymphoblastic leukemia treatment (induction therapy). Children with T-cell acute lymphoblastic leukemia or CNS leukemia had a higher risk of being admitted to the ICU in multivariable analyses, both for early admissions before the end of induction therapy and for all admissions during the study period. The need for intensive care in children with acute lymphoblastic leukemia, especially for children with T cell acute lymphoblastic leukemia and CNS leukemia, is high with most admissions occurring during early treatment.

Epidural analgesia and mortality after colorectal cancer surgery: A retrospective cohort study

BackgroundEpidural analgesia (EA) has been the standard of care after major abdominal surgery for many years. This study aimed to correlate EA with postoperative complications, short- and long-term mortality in patients with and without EA after open surgery (OS) and minimally invasive surgery (MIS) for colorectal cancer. MethodsPatient, clinical and outcome data were obtained from the Swedish Colorectal Cancer Registry and the Swedish Perioperative Registry. All adult patients diagnosed with colorectal cancer without metastases who underwent elective curative MIS or OS for colorectal cancer between January 2016 and December 2018 and who had data recorded in both registries, were included in the study. Data were analyzed for OS and MIS procedures separately. A Poisson regression model was used to investigate the association between EA and the outcomes of interest. ResultsFive thousand seven hundred sixty-two patients were included in the study, 2712 in the MIS and 3050 patients in the OS group. After adjusting for patient specific and clinically relevant variables in the regression model, no statistically significant difference in risk for complications; 30-day, 90-day, and up to 3-year mortality following either MIS or OS could be detected between the EA+ and EA-cohorts. ConclusionsIn this large study cohort, EA as part of the comprehensive care provided was not associated with a reduction in postoperative complications risk or improved 30-day, 90-day, or 3-year survival after MIS or OS for colorectal cancer.

Preoperative multidisciplinary team assessment is associated with improved survival in patients with locally advanced colon cancer; a nationwide cohort study in 3157 patients

IntroductionMultidisciplinary team (MDT) assessment is associated with improved survival in locally advanced rectal cancer, but the effect of an MDT assessment on survival in locally advanced colon cancer has not been reported. The aim of this national population-based cohort study was to establish if preoperative MDT assessment affects prognosis in patients with primary locally advanced colon cancer. Material and methodsAll patients in Sweden with locally advanced colon cancer, without metastatic disease, who underwent an elective colon resection between 2010 and 2017 were identified through the Swedish Colorectal Cancer Registry (SCRCR), and the cohort was linked to national registers. Data on patient characteristics, preoperative staging, surgical procedures, recurrence and survival were collected from SCRCR. The association between MDT assessment and colon cancer-specific survival was evaluated using Kaplan-Meier survival curves and Cox proportional hazards models. The multivariable analysis was adjusted for sex, age, ASA grade, CCI, time period, pN, region and preoperative MDT. ResultsMDT assessment was performed in 2663 patients (84.4%) of 3157 eligible patients. The 3-year colon cancer-specific survival was higher following MDT, compared with no MDT assessment (80% versus 68%). MDT assessment was independently associated with reduced colon cancer-specific mortality (HR 0.70, 0.57–0.84 95% CI). ConclusionPreoperative MDT assessment is associated with an improved long-term survival in patients with locally advanced colon cancer and should be mandatory in patients with suspected locally advanced colon cancer.

Association between one-time prostate-specific antigen (PSA) test with free/total PSA ratio and prostate cancer mortality: A 30-year prospective cohort study.

To explore if there is a long-term association between baseline prostate-specific antigen (PSA), including free/total PSA ratio and long-term (30-year) risk for prostate cancer death. In all, 1782 men were screened for prostate cancer through PSA analysis. Some years later, frozen plasma samples were used to calculate the ratio of free to total PSA (f/t PSA). At 30-year follow-up, baseline PSA and f/t PSA were compared with recent data extracts from the Swedish Cause of Death Registry and Swedish Cancer Registry. PSA values and f/t PSA values were treated as continuous variables in a multivariable analysis and also stratified according to their distribution and useful clinical thresholds. Risk of death from prostate cancer after 30years of follow-up was significantly increased with a higher baseline PSA level, with the hazard ratio being 1.04 (95% confidence interval 1.03-1.09) per increase of one unit of PSA. Adding f/t PSA increased the model's ability to discriminate (concordance index 0.84-0.88). Men with PSA levels <1.0ng/mL had a very low long-term risk of prostate cancer death (1.2% risk). An f/t PSA ≥ 0.25 extended the low-risk range to PSA < 2.0ng/mL (1.5% risk). Prostate-specific antigen testing can be carried out less frequently or can be discontinued in men aged 55-70years if their PSA levels are <2.0ng/mL and the f/t PSA is ≥0.25.

Age is the most important predictor of survival in diffuse large B‐cell lymphoma patients achieving event‐free survival at 24 months: a Swedish population‐based study

SummaryRoutine follow‐up for diffuse large B‐cell lymphoma have been shortened to 2 years when event‐free survival at 24 months (EFS24) emerged as a new milestone. In the present study, we aimed to determine whether the achievement of this milestone affected overall survival (OS). We compared OS to that of an age‐ and sex‐matched population, analysed other factors governing OS, and reviewed the causes of death. Data were collected from the Swedish Cancer Registry and from individual patient’s records. We included 1169 adult patients from five counties between the years 2001 and 2014. The median (range) age was 64·6 (18–91) years, 56·6% were men and the median follow‐up was 82·3 months. For early stages, the achievement of EFS12 did not improve OS. More than two‐thirds of the patients (n = 837, 71·6%) achieved EFS24, of which 190 (22·7%) died during follow‐up. Lymphoma (20%), cardiovascular disease (22·4%) and malignancies (16%) contributed to causes of death. Patients aged <60 years had an OS that matched the standard population. In multivariate analysis, only age >60 years significantly affected OS after EFS24 compared with the standard population. We concluded that follow‐up beyond EFS24 should be considered for patients aged >60 years.

Family history of any cancer for childhood leukemia patients in Sweden.

Acute lymphoblastic leukemia (ALL) is the most common childhood leukemia, while the other types, acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), and chronic myeloid leukemia (CML) are much rarer. While data on familial risks for childhood ALL have been emerging, such data for the other childhood leukemias are hardly available. We aim to fill in the gap of knowledge by assessing familial clustering of each childhood leukemia with childhood and adult leukemia and with any cancer. We identified 4461 childhood leukemias from the Swedish Cancer Registry and obtained their family members from the Multigeneration Register. Standardized incidence ratios (SIRs) were 3.34 for singleton siblings both diagnosed with ALL before age 20 years and 1.64 for those who had a family member diagnosed with ALL in adult age. Other childhood leukemias showed no familial risk, but childhood ALL risk was increased to 1.40 when adult family members were diagnosed with CLL. Childhood ALL was associated with endometrial cancer, and female ALL patients showed increased risk when family members were diagnosed with testicular cancer, melanoma, and skin squamous cell carcinoma. Childhood CLL was associated with rectal cancer, and childhood AML was associated with pancreatic and bladder cancers. As most of these associations are reported for the first time, there is a need to replicate the findings from independent sources.

Gestational diabetes mellitus and risks of gynecologic cancers: Results from a nationwide Swedish twin study

BackgroundType 2 diabetes has been associated with increased risk of gynecologic cancers, yet the effect of gestational diabetes mellitus (GDM) on gynecologic cancers is unclear. ObjectivesTo examine associations between GDM history and subsequent gynecologic cancers in parous women, and to explore whether gestational hypertension (GH) plays a role in the associations. Study designThe population-based cohort study included 15,941 individuals from the Swedish Twin Registry. The history of GDM and GH was ascertained based on self-reports. Incident cases of gynecologic cancers (including cancers of the cervix, uterus, ovaries and other female genitalia) were obtained from the National Patients Registry and the Swedish Cancer Registry. Generalized estimating equation models were applied to analyze associations between GDM and gynecologic cancers. Stratified analysis was used to explore whether associations between GDM and gynecologic cancers differed by GH. Additive and multiplicative interactions were calculated between GDM and GH. ResultsOf all participants, 350 (2.2%) had GDM, and 1762 (11.1%) had incident gynecologic cancers. No statistically significant associations were found between GDM and risks of any gynecologic cancers. However, GDM was associated with an increased risk of ovarian cancer (OR = 5.29, 95% CI: 1.63–17.19) in women with GH. Interactions between GDM and GH were observed on the additive scale (Attributable proportion due to interaction: 0.86, 95% CI 0.42–1.30, P < 0.001). ConclusionsThe associations between GDM and risks of gynecologic cancers were not evident, but the effect of GDM on the risk of ovarian cancer was modified by GH. Further validation in larger cohorts is warranted.

Cancer Risk in Patients With Autoimmune Hepatitis: A Nationwide Population-Based Cohort Study With Histopathology.

We aimed to determine the risk of incident cancer in autoimmune hepatitis (AIH) compared with the general population and siblings. AIH was defined by the presence of a medical diagnosis of AIH and results of examination of a liver biopsy specimen in a nationwide Swedish population-based cohort study. We identified 5,268 adults with AIH diagnosed during 1969-2016 and 22,996 matched, general population, reference individuals and 4,170 sibling comparators. Using Cox regression, hazard ratios were determined for any incident cancer, and subtypes were determined from the Swedish Cancer Register. During follow-up, a cancer diagnosis was made in 1,119 individuals with AIH (17.2 per 1,000 person-years) and 4,450 reference individuals (12.0 per 1,000 person-years). This corresponded to a hazard ratio of 1.53 (95% confidence interval: 1.42, 1.66). Cancer risk was highest in those with cirrhosis. There was a 29.18-fold increased risk of hepatocellular carcinoma (HCC) (95% confidence interval: 17.52, 48.61). The annual incidence risk of HCC in individuals with AIH who had cirrhosis was 1.1% per year. AIH was also linked to nonmelanoma skin cancer (hazard ratio (HR)=2.69) and lymphoma (HR=1.89). Sibling analyses yielded similar risk estimates for any cancer (HR=1.84) and HCC (HR=23.10). AIH is associated with an increased risk of any cancer, in particular, HCC and extrahepatic malignancies. The highest risk for cancer, especially HCC, is in patients with cirrhosis.

Incidence and survival of epithelial ovarian, fallopian tube, peritoneal, and undesignated abdominal/pelvic cancers in Sweden 1960\u20132014: A population-based cohort study

BackgroundDespite improved surgical and oncological treatment, ovarian cancer continues to be the most lethal of the gynecologic malignancies. We aimed to analyze survival trends in epithelial ovarian cancer with regard to age, tumor site, and morphology in Sweden 1960 to 2014.MethodsA nationwide population-based study was conducted using data from the Swedish Cancer Registry on 46,350 women aged 18 or older with a diagnosis of epithelial ovarian, fallopian tube, peritoneal, or undesignated abdominal/pelvic cancer 1960 to 2014. Analyses of age-standardized incidence and relative survival (RS) were performed and time trends modelled according to age, tumor site, and morphology.ResultsOverall incidence of ovarian, tubal, peritoneal, and undesignated abdominal/pelvic cancers declined since 1980. Median age at diagnosis increased. Serous carcinoma increased in incidence. RS at 1, 2 and 5 years from diagnosis improved since 1960, although not for the youngest and the oldest patients. Ten-year RS did not improve. The best RS was found for fallopian tube cancer and the worst RS for undesignated abdominal/pelvic cancer. Among the morphologic subgroups, endometrioid carcinoma had the best RS.ConclusionsSurvival in epithelial ovarian, tubal, peritoneal, and undesignated abdominal/pelvic cancers in Sweden has improved over the last six decades. Advances in epithelial ovarian cancer treatment have extended life for the first 5 years from diagnosis but 10-year survival remains poor.

Risk of second HPV-associated cancers in men with penile cancer

Purpose The aim of this study was to examine the risk of HPV-associated oral cavity, oropharyngeal or anal cancer in men with penile cancer to test the hypothesis of an increased risk to develop a second HPV-associated cancer later in life. Material and methods We conducted a population-based register study including all men in Sweden diagnosed with penile cancer between 2000 and 2012. For each patient, six men without penile cancer were matched based on age and county of residence. Data were retrieved from Swedish cancer and population registers, to assess the risk of oral cavity, oropharyngeal or anal cancer in patients with penile cancer. Cox proportional hazard models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Risks in men with penile cancer were also compared with the background Swedish male population by use of standardized incidence ratios. Results In total, 1634 men with and 9804 without penile cancer were included in the study. Among men with penile cancer, four men were subsequently diagnosed with oral cavity cancer, one with oropharyngeal cancer and one with anal cancer. Corresponding numbers among the penile cancer-free men were ten, two and three, respectively. There was evidence of an increased risks of all three cancers under study with an HR of 2.84 (95% CI 0.89–9.06) for oral cavity cancer, 3.66 (95% CI 0.33–40.39) for oropharyngeal cancer and 2.34 (95% CI 0.24–22.47) for anal cancer. When comparing the incidence of these malignancies between penile cancer patients and the background population, the patterns of association were similar. Conclusions Our findings indicate that men with penile cancer are at an increased risk of a second HPV-associated cancer of the oral cavity, oropharynx and anal canal. Considering that our study was based on small numbers reflecting the rarity of these cancers, larger studies are needed to confirm our findings.

Menopausal hormone therapies and risk of colorectal cancer: a Swedish matched-cohort study.

Menopausal hormone therapy (MHT) has been associated with various malignancies. To investigate the association of various MHT regimens with the risk of colorectal cancer (CRC). All MHT ever-users (n=290186) were included through the Swedish Prescribed Drug Registry, with a 1:3 group-level matching to non-users. Ever-users were defined as women who received ≥1 dispensed prescription of systemic MHT during 2005-2012 in Sweden. All CRC cases after drug initiation were extracted from the Swedish Cancer Registry. The association was assessed by multivariable conditional logistic and Cox regression models, presented as odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs) considering different regimens, duration and age at treatment initiation. Compared with non-users, MHT users had an overall reduced odds for colon (OR=0.67, 95% CI 0.63-0.72) and rectal adenocarcinoma (OR=0.66, 95% CI 0.60-0.73), especially among women aged 40-60years. Current users of oestrogen-only preparations (E-MHT) showed a reduced odds (colon OR=0.73, 95% CI 0.65-0.82; rectal OR=0.76, 95% CI 0.64-0.90) compared to non-users, particularly with oestradiol and oestriol. Past E-MHT use showed stronger odds reductions (colon OR=0.49, 95% CI 0.43-0.56; rectal OR=0.36, 95% CI 0.28-0.45). Current use of oestrogen combined progestin therapy (EP-MHT) indicated a less prominent odds reduction (colon adenocarcinoma OR 0.62, 95% CI 0.54-0.72; rectal adenocarcinoma OR=0.60, 95% CI 0.49-0.74) than past users. Tibolone showed an increased risk of left-sided colorectal adenocarcinoma. Oral and cutaneous MHT usage showed similar patterns. MHT use may decrease colorectal adenocarcinoma risk, for both E-MHT and EP-MHT, and especially in past users.