Excess Mortality and Loss of Life Expectancy After Myocardial Infarction: A Registry-Based Matched Cohort Study.

BACKGROUND: The effect of myocardial infarction (MI) on life expectancy is difficult to study because the prevalence of MI hinders direct comparison with the life expectancy of the general population. We sought to assess this in relation to age, sex, and left ventricular ejection fraction (LVEF) by comparing individuals with MI with matched comparators without previous MI. METHODS: We included patients with a first MI between 1991 and 2022 from the nationwide SWEDEHEART registry (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies), each matched with up to 5 comparators on age, sex, and region of residence. Flexible parametric survival models were used to estimate excess mortality risk and mean loss of life expectancy (LOLE) depending on index year, age, sex, and LVEF, and adjusted for differences in characteristics. RESULTS: A total of 335 748 cases were matched to 1 625 396 comparators. A higher LOLE was observed in younger individuals, women, and those with reduced LVEF (<50%). In 2022, the unadjusted and adjusted mean LOLE spanned from 11.1 and 9.5 years in 50-year-old women with reduced LVEF to 5 and 3.7 months in 80-year-old men with preserved LVEF. Between 1992 and 2022, the adjusted mean LOLE decreased by 36% to 55%: from 4.4 to 2.0 years and from 3.3 to 1.9 years in 50-year-old women and men, respectively, and from 1.7 to 1.0 years and from 1.4 to 0.9 years in 80-year-old women and men, respectively. CONCLUSIONS: LOLE is higher in younger individuals, women, and those with reduced LVEF, but is attenuated when adjusting for comorbidities and risk factors. Advances in MI treatment during the past 30 years have almost halved LOLE, with no clear sign of leveling off to a plateau.

Vulvar cancer incidence and net survival in Sweden 1960 to 2019: A population-based national study.

INTRODUCTION: Vulvar cancer is a rare gynecological cancer affecting mostly older women. The aim of this population-based study was to investigate the incidence and net survival of vulvar cancer in Swedish women from 1960 to 2019. MATERIAL AND METHODS: Data were retrieved from the mandatory Swedish Cancer Registry consisting of all women diagnosed with vulvar cancer between 1960 and 2019. Only women with a morphologically verified diagnosis of vulvar cancer were included. The individuals were then further matched with the Swedish Death Registry up until May 31, 2020. RESULTS: In total, 8499 women were included with the following morphologies: squamous cell carcinoma 7250 (85.8%), malignant melanoma 539 (6.4%), adenocarcinoma 401 (4.8%) and other: 259 (3.1%). More than 50% of vulvar cancer cases occurred in women aged between 65 and 84 years of age. The 5-year age-standardized net survival increased from 53.0% (95% confidence interval [CI] 48.9-57.5) in 1960 to 72.1% (95% CI 68.8-75.5) in 2019. The proportion of adenocarcinoma among all cases increased from 2.0% to 8.7% between the 1960s and 2010s and an increase in age-standardized 5-year net survival was found for adenocarcinoma. CONCLUSIONS: The age-standardized incidence of vulvar cancer cases in Sweden was stable between 1960 and 2019. During the study period, an increase in adenocarcinoma and a decrease in malignant melanoma cases was found. Five-year net survival increased by 20 percent units during the study period. For squamous cell carcinoma, an increased age-specific 5-year net survival was observed for all age groups, apart for women aged ≥85.

Comparing the diagnostic accuracy, reading time, and inter-rater agreement of breast MRI abbreviated and full protocols: a multi-reader study.

BACKGROUND: Earlier studies have shown that abbreviated protocol magnetic resonance imaging (AB-MRI) has similar diagnostic accuracy as the full protocol (Full MRI). PURPOSE: To compare the diagnostic accuracy, reading time, and inter-rater agreement of AB-MRI to Full MRI among women without known increased familial risk of breast cancer or prior biopsy. MATERIAL AND METHODS: In total, 395 MRI examinations were included in this study. Three readers were blinded to all patient information. The AB-MRI and Full MRI were read separately and in a different random order for each of the readers. Scores 1-2 were considered test negative while scores 3-5 were test positive. A positive reference test was the diagnosis of malignancy; a negative reference test was the absence of a diagnosis of breast cancer within a two-year follow-up. We used a generalized estimating equations approach to compare sensitivity and specificity between the two protocols. We used t-tests to compare the average reading time and Krippendorff's alpha to compare inter-rater agreement. RESULTS: MRI examinations of 395 women (median age=56 years) were evaluated. For AB-MRI and Full MRI, respectively, the sensitivity was 93.0% (95% CI=90.6-95.0) vs. 92.0% (95% CI=89.4-94.1), the specificity was 91.7% (95% CI=90.3-92.9) vs. 94.3% (95% CI=93.2-95.3), average reading time was 67 vs. 126 s, and the inter-rater agreement 0.79 vs. 0.83. The difference in sensitivity was not statistically significant (P=0.840), but the difference in specificity was significant (P=0.003). CONCLUSION: AB-MRI has similar sensitivity, but somewhat lower specificity. The average reading time for the abbreviated protocol is lower, as is inter-rater agreement.

Improving communication of cancer survival statistics-feasibility of implementing model-based algorithms in routine publications.

BACKGROUND: Routine reporting of cancer patient survival is important, both to monitor the effectiveness of health care and to inform about prognosis following a cancer diagnosis. A range of different survival measures exist, each serving different purposes and targeting different audiences. It is important that routine publications expand on current practice and provide estimates on a wider range of survival measures. We examine the feasibility of automated production of such statistics. METHODS: We used data on 23 cancer sites obtained from the Cancer Registry of Norway (CRN). We propose an automated way of estimating flexible parametric relative survival models and calculating estimates of net survival, crude probabilities, and loss in life expectancy across many cancer sites and subgroups of patients. RESULTS: For 21 of 23 cancer sites, we were able to estimate survival models without assuming proportional hazards. Reliable estimates of all desired measures were obtained for all cancer sites. DISCUSSION: It may be challenging to implement new survival measures in routine publications as it can require the application of modeling techniques. We propose a way of automating the production of such statistics and show that we can obtain reliable estimates across a range of measures and subgroups of patients.

Current clinical practice in the management of phyllodes tumors of the breast: an international cross-sectional study among surgeons and oncologists.

PURPOSE: Phyllodes tumors of the breast are rare fibroepithelial lesions that are classified as benign, borderline or malignant. There is little consensus on best practice for the work-up, management, and follow-up of patients with phyllodes tumors of the breast, and evidence-based guidelines are lacking. METHODS: We conducted a cross-sectional survey of surgeons and oncologists with the aim to describe current clinical practice in the management of phyllodes tumors. The survey was constructed in REDCap and distributed between July 2021 and February 2022 through international collaborators in sixteen countries across four continents. RESULTS: A total of 419 responses were collected and analyzed. The majority of respondents were experienced and worked in a university hospital. Most agreed to recommend a tumor-free excision margin for benign tumors, increasing margins for borderline and malignant tumors. The multidisciplinary team meeting plays a major role in the treatment plan and follow-up. The vast majority did not consider axillary surgery. There were mixed opinions on adjuvant treatment, with a trend towards more liberal regiments in patients with locally advanced tumors. Most respondents preferred a five-year follow-up period for all phyllodes tumor types. CONCLUSIONS: This study shows considerable variation in clinical practice managing phyllodes tumors. This suggests the potential for overtreatment of many patients and the need for education and further research targeting appropriate surgical margins, follow-up time and a multidisciplinary approach. There is a need to develop guidelines that recognize the heterogeneity of phyllodes tumors.

Survival in Swedish patients with systemic sclerosis: a nationwide population-based matched cohort study.

OBJECTIVES: To conduct the first-ever nationwide, population-based cohort study investigating survival patterns of all patients with incident SSc in Sweden compared with matched individuals from the Swedish general population. METHODS: We used the National Patient Register to identify patients with incident SSc diagnosed between 2004 and 2015 and the Total Population Register to identify comparators (1:5), matched on sex, birth year and residential area. We followed them until death, emigration or the end of 2016. Follow-up of the general population comparators started the same date as their matched patients were included. We estimated all-cause survival using the Kaplan-Meier method, crude mortality rates and hazard ratios (HRs) using flexible parametric models. RESULTS: We identified 1139 incident patients with SSc and 5613 matched comparators. The median follow-up was 5.0 years in patients with SSc and 6.0 years for their comparators. During follow-up, 268 deaths occurred in patients with SSc and 554 in their comparators. The 5-year survival was 79.8% and the 10-year survival was 67.7% among patients with SSc vs 92.9% and 84.8%, respectively, for the comparators (P < 0.0001). The mortality rate in patients with SSc was 42.1 per 1000 person-years and 15.8 per 1000 person-years in their comparators, corresponding to an HR of 3.7 (95% CI 2.9, 4.7) at the end of the first year of follow-up and 2.0 (95% CI 1.4, 2.8) at the end of the follow-up period. CONCLUSION: Despite advances in understanding the disease and in diagnostic methods over the past decades, survival is still severely impacted in Swedish patients diagnosed with SSc between 2004 and 2015.

Increased incidence and improved survival in endometrial cancer in Sweden 1960-2014: a population-based registry survey.

BACKGROUND: An investigation of trends of incidence and net survival (NS) for endometrial cancer in Sweden. METHODS: Morphologically verified endometrial carcinoma diagnosed 1960 to 2014 were collected from the nation-wide Swedish Cancer Registry. Endometrial cancer patients were assessed with regards to time trends for incidence and 54,825 cases remained for survival analyses. Cases diagnosed 1995 to 2014 were categorized according to detailed morphology and from 2005 to 2014 FIGO stage was also categorized. RESULTS: There was a trend of increasing incidence of endometrial carcinoma for women above 55 years of age. NS was improved at 5- and 10-year follow-up. The 5-year net survival in 2010-2014 was 86%. The most prominent improvement in NS was found in the elderly women above 75 years of age. CONCLUSIONS: This study observed increased incidence of endometrial cancer in Sweden from 1960 to 2014. The progress in diagnostics and treatment, seem to have improved the net survival, especially in elderly women.

Survival, causes of death, and the prognostic role of comorbidities in chronic lymphocytic leukemia in the pre-ibrutinib era: A population-based study.

OBJECTIVE: To evaluate temporal trends in survival and causes of death in patients with chronic lymphocytic leukemia (CLL) in a nationwide study. METHODS: The cohort consisted of 13,009 Swedish CLL patients diagnosed 1982-2013. Relative survival (RS) and excess mortality rate ratios (EMRR) with 95% confidence intervals (95% CIs) were estimated using flexible parametric survival models. Cause-specific hazard ratios (HRs) were estimated for the linear effect of 10-year increase in year of diagnosis. RESULTS: The excess mortality decreased comparing 2003-2013 to 1982-1992 (EMRR = 0.53, 95% CI 0.48-0.58). The 5-year RS increased between 1982 and 2012 for patients >51 years at diagnosis and improved for patients ≤51 years after 2002. The rate of CLL-specific deaths decreased over time (HR = 0.78, 95% CI 0.75-0.81). Compared to patients with no comorbidity, patients with 1 and 2+ Charlson Comorbidity Index points had HR = 1.35 (95% CI 1.25-1.45) and HR = 1.47 (95% CI 1.37-1.57) for CLL-related mortality, respectively. CONCLUSION: Survival in CLL patients improved in the era of chemoimmunotherapy, and this was largely explained by reduced CLL-related mortality. The increased rate of CLL-related mortality in patients with comorbidities emphasizes the importance of the newer and better tolerated targeted therapy.

Modelling multiple time-scales with flexible parametric survival models.

BACKGROUND: There are situations when we need to model multiple time-scales in survival analysis. A usual approach in this setting would involve fitting Cox or Poisson models to a time-split dataset. However, this leads to large datasets and can be computationally intensive when model fitting, especially if interest lies in displaying how the estimated hazard rate or survival change along multiple time-scales continuously. METHODS: We propose to use flexible parametric survival models on the log hazard scale as an alternative method when modelling data with multiple time-scales. By choosing one of the time-scales as reference, and rewriting other time-scales as a function of this reference time-scale, users can avoid time-splitting of the data. RESULT: Through case-studies we demonstrate the usefulness of this method and provide examples of graphical representations of estimated hazard rates and survival proportions. The model gives nearly identical results to using a Poisson model, without requiring time-splitting. CONCLUSION: Flexible parametric survival models are a powerful tool for modelling multiple time-scales. This method does not require splitting the data into small time-intervals, and therefore saves time, helps avoid technological limitations and reduces room for error.

Reproductive history, as measured by parity, age at first birth and sex of offspring, and cancer-specific survival after a haematological malignancy.

BACKGROUND: Overall, women have better cancer-specific survival than men following haematological malignancies. The effect of reproductive factors on prognosis in women remains unknown and population-based studies are needed. MATERIAL AND METHODS: A nationwide cohort of 21,237 Swedish women with a recorded haematological malignancy at ages 18-69 years was identified in the Swedish Cancer Register 1970-2018. Pre-diagnosis childbirths for each woman were linked to the Swedish Multigeneration Register. Net survival and excess hazard ratios for parity, age at first birth, time since the latest birth, and sex of offspring were estimated using flexible parametric models adjusted for age, year, and educational level. RESULTS: In unadjusted analyses, parity (p = 0.0012) and high age at first birth (p < 0.0001) were associated with better survival. After co-adjustments for reproductive factors and confounders, the associations were attenuated. The adjusted association with parity was mainly observed among women aged above 40 years at diagnosis (p = 0.0033). The associations with reproductive factors were non-significant across subtypes of haematological malignancy. There was a tendency of higher excess mortality for an increasing number of boys compared to girls, although only significant for women with three or more children (p = 0.0126). CONCLUSION: Reproductive factors were in part associated with survival following diagnosis of a haematological malignancy. However, the effect sizes were small with inconsistent association patterns, and thus reproductive factors may only partly contribute to the survival advantage of women over men.

Comparison of Relative Survival and Cause-Specific Survival in Men With Prostate Cancer According to Age and Risk Category: A Nationwide, Population-Based Study.

Net survival, estimated in a relative survival (RS) or cause-specific survival (CSS) framework, is a key measure of the effectiveness of cancer management. We compared RS and CSS in men with prostate cancer (PCa) according to age and risk category, using Prostate Cancer data Base Sweden, including 168,793 men younger than age 90 years, diagnosed 1998-2016 with PCa. RS and CSS were compared according to age and risk category based on TNM (tumor, nodes, and metastases) stage, Gleason score, and prostate-specific antigen level. Each framework requires assumptions that are unlikely to be appropriate for PCa. Ten-year RS was substantially higher than CSS in men aged 80-89 with low-risk PCa: 125% (95% confidence interval: 113, 138) versus 85% (95% confidence interval: 82, 88). In contrast, RS and CSS were similar for men under age 70 and for all men with regional or distant metastases. Both RS and CSS produce biased estimates of net survival for men with low- and intermediate-risk PCa, in particular for men over 80. Due to biases, net survival is overestimated in analysis of RS but underestimated in analysis of CSS. These results highlight the importance of evaluating the underlying assumptions for each method, because the "true" net survival is expected to lie between the limits of RS and CSS.

Incidence and survival of epithelial ovarian, fallopian tube, peritoneal, and undesignated abdominal/pelvic cancers in Sweden 1960-2014: A population-based cohort study.

BACKGROUND: Despite 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. METHODS: A 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. RESULTS: Overall 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. CONCLUSIONS: Survival 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.

Frequent platelet donation is associated with lymphopenia and risk of infections: A nationwide cohort study.

BACKGROUND: Recently, plateletpheresis donations using a widely used leukoreduction system (LRS) chamber have been associated with T-cell lymphopenia. However, clinical health consequences of plateletpheresis-associated lymphopenia are still unknown. STUDY DESIGN AND METHODS: A nationwide cohort study using the SCANDAT3-S database was conducted with all platelet- and plasmapheresis donors in Sweden between 1996 and 2017. A Cox proportional hazards model, using donations as time-dependent exposures, was used to assess the risk of infections associated with plateletpheresis donations using an LRS chamber. RESULTS: A total of 74 408 apheresis donors were included. Among donors with the same donation frequency, plateletpheresis donors using an LRS chamber were at an increased risk of immunosuppression-related infections and common bacterial infections in a dose-dependent manner. While very frequent donors and infections were rare in absolute terms resulting in wide confidence intervals (CIs), the increased risk was significant starting at one-third or less of the allowed donation frequency in a 10-year exposure window, with hazard ratios reaching 10 or more. No plateletpheresis donors that used an LRS chamber experienced a Pneumocystis jirovecii, aspergillus, disseminated mycobacterial, or cryptococcal infection. In a subcohort (n = 42), donations with LRS were associated with low CD4+ T-cell counts (Pearson's R = -0.41; 95% CI, - 0.63 to -0.12). CONCLUSION: Frequent plateletpheresis donation using an LRS chamber was associated with CD4+ T-cell lymphopenia and an increased risk of infections. These findings suggest a need to monitor T-lymphocyte counts in frequent platelet donors and to conduct future investigations of long-term donor health and for regulators to consider steps to mitigate lymphodepletion in donors.

A multistate model incorporating estimation of excess hazards and multiple time scales.

As cancer patient survival improves, late effects from treatment are becoming the next clinical challenge. Chemotherapy and radiotherapy, for example, potentially increase the risk of both morbidity and mortality from second malignancies and cardiovascular disease. To provide clinically relevant population-level measures of late effects, it is of importance to (1) simultaneously estimate the risks of both morbidity and mortality, (2) partition these risks into the component expected in the absence of cancer and the component due to the cancer and its treatment, and (3) incorporate the multiple time scales of attained age, calendar time, and time since diagnosis. Multistate models provide a framework for simultaneously studying morbidity and mortality, but do not solve the problem of partitioning the risks. However, this partitioning can be achieved by applying a relative survival framework, allowing us to directly quantify the excess risk. This article proposes a combination of these two frameworks, providing one approach to address (1) to (3). Using recently developed methods in multistate modeling, we incorporate estimation of excess hazards into a multistate model. Both intermediate and absorbing state risks can be partitioned and different transitions are allowed to have different and/or multiple time scales. We illustrate our approach using data on Hodgkin lymphoma patients and excess risk of diseases of the circulatory system, and provide user-friendly Stata software with accompanying example code.

Conditional Survival and Cure of Patients With Colon or Rectal Cancer: A Population-Based Study.

BACKGROUND: The increasing number of colorectal cancer (CRC) survivors need survival estimates that account for the time already survived. The aim of this population-based study was to determine conditional survival, cure proportions, and time-to-cure (TTC) of patients with colon or rectal cancer. MATERIALS AND METHODS: All patients with pathologic stage I-III CRC treated with endoscopy or surgery, diagnosed and registered in the Netherlands Cancer Registry between 1995 and 2016, and aged 18 to 99 years were included. Conditional survival was calculated for those diagnosed before and after 2007. Cure proportions were calculated using flexible parametric models. RESULTS: A total of 175,384 patients with pathologic stage I (25%), II (38%), or III disease (37%) were included. Conditional 5-year survival of patients with stage I, II, and III colon cancer having survived 5 years was 98%, 94%, and 92%, respectively. For patients with stage I-III rectal cancer, this was 96%, 89%, and 85%, respectively. Statistical cure in patients with colon cancer was reached directly after diagnosis (stage I) to 6 years (stage III) after diagnosis depending on age, sex, and disease stage. Patients with rectal cancer reached cure 0.5 years after diagnosis (stage I) to 9 years after diagnosis (stage III). In 1995, approximately 42% to 46% of patients with stage III colon or rectal cancer, respectively, were considered cured, whereas in 2016 this percentage increased to 73% to 78%, respectively. CONCLUSIONS: The number of patients with CRC reaching cure has increased substantially over the years. This study's results provide valuable insights into trends of CRC patient survival and are important for patients, clinicians, and policymakers.

The association between breast cancer risk factors and background parenchymal enhancement at dynamic contrast-enhanced breast MRI.

BACKGROUND: Background parenchymal enhancement (BPE) of normal tissue at breast magnetic resonance imaging is suggested to be an independent risk factor for breast cancer. Its association with established risk factors for breast cancer is not fully investigated. PURPOSE: To study the association between BPE and risk factors for breast cancer in a healthy, non-high-risk screening population. MATERIAL AND METHODS: We measured BPE and mammographic density and used data from self-reported questionnaires in 214 healthy women aged 43-74 years. We estimated odds ratios for the univariable association between BPE and risk factors. We then fitted an adjusted model using logistic regression to evaluate associations between BPE (high vs. low) and risk factors, including mammographic breast density. RESULTS: The majority of women had low BPE (84%). In a multivariable model, we found statistically significant associations between BPE and age (P = 0.002) and BMI (P = 0.03). We did find a significant association between systemic progesterone medication and BPE, but due to small numbers, the results should be interpreted with caution. The adjusted odds ratio for high BPE was 3.1 among women with density D (compared to B) and 2.1 for density C (compared to B). However, the association between high BPE and density was not statistically significant. We did not find statistically significant associations with any other risk factors. CONCLUSION: Our study confirmed the known association of BPE with age and BMI. Although our results show a higher likelihood for high BPE with increasing levels of mammographic density, the association was not statistically significant.

Temporal trends in treatment-related incidence of diseases of the circulatory system among Hodgkin lymphoma patients.

While Hodgkin lymphoma (HL) survival has improved, treatment-related complications remain a concern. As a measure of treatment-related diseases of the circulatory system (DCS) we report excess incidence of DCS and absolute risks among HL patients diagnosed in the modern treatment era. From the Swedish Cancer Register, we identified all HL patients diagnosed 1985 through 2013, at ages 18-80 years. Excess incidence rate ratios (EIRRs) with 95% confidence intervals (CIs) comparing excess DCS incidence between calendar periods were estimated overall, and at 5 and 10 years after diagnosis using flexible parametric models. Model-based predictions were used to obtain probabilities of being diagnosed with DCS, in the presence of competing risks. During follow-up, 726 (16%) of the 4,479 HL patients experienced DCS. Overall, the excess DCS incidence was lower during all calendar periods compared to the first (2009-2013 vs. 1985-1988: EIRR = 0.63, 95% CI: 0.42-0.95). The 5- and 10-year excess incidence of DCS decreased between 1985 and 1994 for 25-year-olds (5-year-EIRR1994 = 0.32, 95% CI: 0.12-0.92) and 60-year-olds (5-year-EIRR1994 = 0.45, 95% CI: 0.24-0.88), but remained stable thereafter. No improvements were observed among 75-year-olds. The probability of excess DCS remained the same throughout the study period. In 2009, the percentage of patients aged 25, 60 and 75 experiencing excess DCS within 5 years was 3.4, 15.0 and 17.0% (males) and 2.3, 10.8 and 12.6% (females). Treatment-related incidence of DCS has declined since the mid-1980s, but more recent improvements are absent and an excess risk remains. Continued efforts towards less toxic treatments are warranted, alongside primary prevention strategies.

Does three-dimensional functional infrared imaging improve breast cancer detection based on digital mammography in women with dense breasts?

PURPOSE: We aimed to estimate the incremental cancer detection rate achieved by adding three-dimensional functional infrared imaging (3DIRI) to digital mammography in women with dense breasts. MATERIALS AND METHODS: In this prospective study conducted between December 2014 and April 2016, 1727 women (median age 56) with percentage volumetric breast density > 6% were recruited at routine screening mammography to undergo additional 3DIRI. The 3DIRI findings were classified as negative or positive. Women with a negative mammography but positive 3DIRI were referred to dynamic contrast-enhanced MRI, whereas all other women underwent routine follow-up based on the mammography finding. Diagnosis of breast cancer was verified by histopathologic examination. The number of women diagnosed with a malignancy formed the basis of our statistical analysis. RESULTS: Mammography detected 7 cancers in 7 women. Of 1692 women with negative mammography, 222 women (13%) had a positive 3DIRI of which 219 underwent MRI. An additional 6 cancers were identified in 5 women, increasing the diagnostic yield from 7 of 1727 (0.41%) to 12 of 1727 (0.69%). The incremental cancer detection rate associated with using 3DIRI to select women for MRI was 5 of 222 (22.5 additional cancers per 1000). CONCLUSION: The use of 3DIRI to select women for an additional MRI can result in the detection of additional cancers in women with dense breasts, but at the expense of additional false positives and considerably lower positive predictive value of the combined examinations. Additional studies are necessary to evaluate the role of 3DIRI as an adjunct to mammography. KEY POINTS: • Use of three-dimensional functional infrared imaging to select women for an MRI in addition to screening mammography has the potential to improve breast cancer detection in women with dense breasts.

Risk for Arterial and Venous Thrombosis in Patients With Myeloproliferative Neoplasms: A Population-Based Cohort Study.

Background: Patients with myeloproliferative neoplasms (MPNs) are reported to be at increased risk for thrombotic events. However, no population-based study has estimated this excess risk compared with matched control participants. Objective: To assess risk for arterial and venous thrombosis in patients with MPNs compared with matched control participants. Design: Matched cohort study. Setting: Population-based setting in Sweden from 1987 to 2009, with follow-up to 2010. Patients: 9429 patients with MPNs and 35 820 matched control participants. Measurements: The primary outcomes were rates of arterial and venous thrombosis. Flexible parametric models were used to calculate hazard ratios (HRs) and cumulative incidence with 95% CIs. Results: The HRs for arterial thrombosis among patients with MPNs compared with control participants at 3 months, 1 year, and 5 years were 3.0 (95% CI, 2.7 to 3.4), 2.0 (CI, 1.8 to 2.2), and 1.5 (CI, 1.4 to 1.6), respectively. The corresponding HRs for venous thrombosis were 9.7 (CI, 7.8 to 12.0), 4.7 (CI, 4.0 to 5.4), and 3.2 (CI, 2.9 to 3.6). The rate was significantly elevated across all age groups and was similar among MPN subtypes. The 5-year cumulative incidence of thrombosis in patients with MPNs showed an initial rapid increase followed by gentler increases during follow-up. The HR for venous thrombosis decreased during more recent calendar periods. Limitation: No information on individual laboratory results or treatment. Conclusion: Patients with MPNs across all age groups have a significantly increased rate of arterial and venous thrombosis compared with matched control participants, with the highest rates at and shortly after diagnosis. Decreases in the rate of venous thrombosis over time likely reflect advances in clinical management. Primary Funding Source: The Cancer Research Foundations of Radiumhemmet, Blodcancerfonden, the Swedish Research Council, the regional agreement on medical training and clinical research between Stockholm County Council and Karolinska Institutet, the Adolf H. Lundin Charitable Foundation, and Memorial Sloan Kettering Cancer Center.