Bayesian hidden Markov model for overdiagnosis in colorectal cancer screening

Thanks to modern medical advances, humans have developed tools for detecting diseases so early, that a patient would be better off had the disease gone undetected. This is called overdiagnosis. Overdiagnosisisaproblemespeciallycommoninacts,wherethetargetpopulationofanintervention consists of mostly healthy people. Colorectal cancer (CRC) is a relatively rare disease. Thus screening for CRC affects mostly cancerfree population. In this thesis I evaluate overdiagnosis in guaiac faecal occult blood test (gFOBT) based CRC screening programme. In gFOBT CRC screening there are two goals: to detect known predecessors of cancers called adenomas and to remove them (cancer prevention), and to detect malign CRCs early enough to be still treatable (early detection). Overdiagnosis can happen when detecting adenomas, but also when detecting cancers. This thesis focuses on overdiagnosis due to detection of adenomas that are non-progressive in their nature. Since there is no clinical means to make distinction between progressive and non-progressive adenomas, statistical methods must be applied. Classical methods to estimate overdiagnosis fail in quantifying this type of overdiagnosis for couple of reasons: incidence data of adenomas is not available, and adenoma removal results in lowering cancer incidence in screened population. While the latter is a desired effect of screening, it makes it impossible to estimate overdiagnosis by just comparing cancer incidences among screened and control populations. In this thesis a Bayesian Hidden Markov model using HMC NUTS algorithm via software Stan is fitted to simulate the natural progression of colorectal cancer. The five states included in the model were healthy (1), progressive adenoma (2), screen-detectable CRC (3), clinically apparent CRC (4) and non-progressive adenoma (5). Possible transitions are from 1 to 2, 1 to 5, 2 to 3 and 3 to 4. The possible observations are screen-negative (1), detected adenoma (2), screen-detected CRC (3), clinically manifested CRC (3). Three relevant estimands for evaluating this type of overdiagnosis with a natural history model are presented. Then the methods are applied to estimate overdiagnosis proportion in guaiac faecal occult blood test (gFOBT) based CRC screening programme conducted in Finland between 2004 and 2016. The resulting mean overdiagnosis probability for all the patients that had an adenoma detected for programme is 0.48 (0.38, 0.56, 95-percent credible interval). Different estimates for overdiagnosis in sex and age-specific stratas of the screened population are also provided. In addition to these findings, the natural history model can be used to gain more insight about natural progression of colorectal cancer

Subsequent malignant neoplasms after primary hematological malignancy in adult patients

Patients with primary hematological malignancy (HM) are at an elevated risk of subsequent malignant neoplasms (SMNs), which is a common concern after treatment of primary cancer. We identified 45,533 patients aged ≥20 years and diagnosed with primary HM in Finland from 1992 to 2019 from the Finnish Cancer Registry and estimated standardized incidence ratios (SIR) and excess absolute risks per 1000 person-years (EAR) for SMNs. A total of 6076 SMNs were found (4604 solid and 1472 hematological SMNs). The SIRs were higher for hematological SMNs (SIR 4.9, 95% confidence interval [CI] 4.7–5.2) compared to solid SMNs (SIR 1.5, 95% CI 1.4–1.5). The SIRs for hematological SMNs were highest in the young HM patients aged 20–39 years (SIR 9.2, 95% CI 6.8–12.2 in males and SIR 10.5, 95% CI 7.2–14.7 in females) and decreased by age of first primary HM. However, EARs for hematological SMNs were highest in the older patients, aged 60–79 years at their first primary HM (EAR 5.7/1000 and 4.7/1000 in male and female patients, respectively). In conclusion, the incidence of both hematological and solid SMNs were increased in hematological cancer patients. The relative risk (SIR) was highest among younger HM patients with hematological SMNs. The absolute second cancer burden reflected by high EAR arises from solid malignancies in older patients. Our results accentuate the need for vigilance in the surveillance of HM patients.Peer reviewe

Deltagandet i första inbjudan till screening för livmoderhalscancer bland före detta cancerpatienter i barndom och ungdom i Finland

Objectives Few studies have focused on the association between childhood and young adulthood cancers and cancer screening attendance. Our aim was to assess the effect of cancer diagnosed before the age of 30 years on first-time cervical screening attendance. Methods Using the nation-wide and population-based Finnish Cancer Registry and the Mass Screening Registry, we identified 4,491 cancer patients born between years 1961 and 1988 and diagnosed with cancer before age 30 and alive at the time of first cervical cancer screening invitation at age 25 or 30 years. Attendance probability to screening was compared between individuals with and without a prior cancer diagnosis. Results Compared to women with no previous cancer (attendance probability of 58% in study period), difference in attendance to first-time screening invitation was observed among women with previous cervical cancer (24%), other malignant gynaecologic cancer (43%) and borderline ovarian tumours (48%). Attendance among women with other previous cancer types did not differ from women with no previous cancer. Differences in the attendance probability of cancer survivors and cancer free individuals also varied between catchment areas. Conclusions The low cervical cancer screening attendance among survivors of previous gynecologic cancers and borderline ovarian tumors calls for further exploration on the reasons. As attendance probability differed among survivors of gynecological and other types of cancer significantly only if the invitation came <5 years after the cancer diagnosis, one likely explanation is ongoing oncologic follow-up. Regional differences underline the importance of national guidelines.Endast ett fåtal tidigare studier har undersökt sambandet mellan fall av cancer i barndomen och deltagande i nationella cancerscreening programmet. Studiens mål var att undersöka sambandet mellan att ha insjuknat i cancer före 30-års åldern och deltagandet i första inbjudan till det nationella screeningprogrammet för livmoderhalscancer. Med hjälp av Finlands cancerregister och massundersökningsregistret identifierade vi 4 491 cancerpatienter födda mellan 1961 och 1988 som diagnostiserats med cancer före 30 års åldern och som var vid liv för sin första livmoderhalscancerscreenings inbjudan. Andelen deltagare i sitt livs första screening för livmoderhalscancer jämfördes mellan dessa individer och resten av befolkningen Vi kom fram till att jämfört med resten av befolkningen hade patienter med tidigare livmoderhalscancer, andra gynekologiska maligniteter samt semimaligna ovarietumörer en signifikant lägre andel deltagare i den första screeningen för livmoderhalscancer. Det fanns även regionala skillnader i deltagningsandelen. Individer med en tidigare livmoderhalscancerdiagnos hade en speciellt signifikant lägre deltagningsprocent jämfört med resten av befolkningen (24% emot 58%). Det vore viktigt att kartlägga vad detta beror på. En möjlig förklaring är att dessa individer uppföljs ännu i specialsjukvården. Faktumet, att skillnaden i andelen deltagare är endast markant för de 5 första åren efter diagnos stöder denna hypotes

Accurate pattern-based extraction of complex Gleason score expressions from pathology reports

Purpose: The Gleason score is an important grading factor of prostate cancer. Gleason scores can be extracted from pathology report texts using regular expressions, but previously developed programmes have targeted only relatively simple Gleason score expressions. We developed a programme capable of extracting also complex expressions. The programme is relatively easy to adapt to other languages and datasets. Methods: We developed and evaluated our regular expression-based programme using manually processed pathology reports of prostate cancer cases diagnosed in Finland in 2016-2017. Both simple and complex Gleason score expressions were targeted. We measured the performance of our programme using recall, precision, and the F1. The proportion of complex Gleason score expressions was estimated as the complement of the recall when only addition expressions (e.g. "Gleason 3 + 4") were targeted. Results: The detection of values (scores and score components) is based on mandatory keywords before or after the value. The programme favours precision over recall by primarily allowing for lists of optional expressions between keyword-value pairs and only secondarily allowing for arbitrary expressions. The programme is straightforward to adapt to new datasets by modifying the lists of mandatory and optional expressions. The full and addition-only programmes had 92% (95% CI: [90%, 95%]) and 65% ([61%, 70%]) recall and high precision (98% [97%, 99%] and 100% [99%, 100%]), respectively. The estimated proportion of complex Gleason score expressions was 100-65 = 35%. Conclusions: Even complex Gleason score expressions can be extracted with high recall and precision using regular expressions. We recommend implementing automated Gleason score extraction where possible by adapting our validated programme.Peer reviewe

Decreasing trend and changing indications of hysterectomy in Finland

Introduction: Hysterectomy has been one of the most common surgical procedures in women in Finland. We studied the population-based trends of hysterectomy and its indications from 1986 to 2017. Material and methods: A retrospective population-based cohort was created from the Care Register for Health Care by identifying women who had a hysterectomy from 1986 to 2017 and calculating the number of women from the Digital and Population Data Services Agency. We estimated the number and incidence of hysterectomy by period and age as well as by indication. We considered the primary diagnosis at the time of surgery as the indication of hysterectomy. Results: The number of hysterectomies increased from 7492 procedures in 1986 to 12 404 procedures in 1998, and reduced substantially after that to 5971 procedures in 2017, the turning point being in 1999. The incidence rate of hysterectomy has decreased on average by 2.5% annually from 432.6 per 100 000 women in 1998–2001 to 224.5 per 100 000 women in 2014–2017. The median age at the time of hysterectomy has increased from 51 years in 1998–2001 to 55 years in 2014–2017. The cumulative burden of hysterectomy by age of 60 years has nearly halved from the first 4-year period (23%) to the last (12%). After 2010, the most common indication has been genital prolapse and incontinence, whereas earlier it was uterine fibroids. Conclusions: The number and incidence of hysterectomies have fluctuated during the observation period 1986–2017 and decreased considerably during the past 17 years in Finland. This is probably a result of the availability of hormonal and other conservative treatment options for bleeding disorders and uterine fibroids. As hysterectomy practically removes the risk for endometrial cancer, the change in hysterectomy incidence over time emphasizes the importance of correcting endometrial cancer incidence according to hysterectomy incidence.publishedVersionPeer reviewe