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PURPOSE Few data are available regarding the influence of adjuvant capecitabine on long-term survival of patients with early breast cancer. METHODS The Finland Capecitabine Trial (FinXX) is a randomized, open-label, multicenter trial that evaluates integration of capecitabine to an adjuvant chemotherapy regimen containing a taxane and an anthracycline for the treatment of early breast cancer. Between January 27, 2004, and May 29, 2007, 1,500 patients with axillary node-positive or high-risk node-negative early breast cancer were accrued. The patients were randomly allocated to either TX-CEX, consisting of three cycles of docetaxel (T) plus capecitabine (X) followed by three cycles of cyclophosphamide, epirubicin, and capecitabine (CEX, 753 patients), or to T-CEF, consisting of three cycles of docetaxel followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil (CEF, 747 patients). We performed a protocol-scheduled analysis of overall survival on the basis of approximately 15-year follow-up of the patients. RESULTS The data collection was locked on December 31, 2020. By this date, the median follow-up time of the patients alive was 15.3 years (interquartile range, 14.5-16.1 years) in the TX-CEX group and 15.4 years (interquartile range, 14.8-16.0 years) in the T-CEF group. Patients assigned to TX-CEX survived longer than those assigned to T-CEF (hazard ratio 0.81; 95% CI, 0.66 to 0.99; P = .037). The 15-year survival rate was 77.6% in the TX-CEX group and 73.3% in the T-CEF group. In exploratory subgroup analyses, patients with estrogen receptor–negative cancer and those with triple-negative cancer treated with TX-CEX tended to live longer than those treated with T-CEF. CONCLUSION Addition of capecitabine to a chemotherapy regimen that contained docetaxel, epirubicin, and cyclophosphamide prolonged the survival of patients with early breast cancer.

Supplementary Figure 3 from ST14 Gene Variant and Decreased Matriptase Protein Expression Predict Poor Breast Cancer Survival

PDF file, 70K, Availability of information on tumor morphology and receptor status for Europeans, by each included BCAC study.

Background: Matriptase plays a role in carcinogenesis, but the role of its genetic variation or that of the hepatocyte growth factor activator inhibitor-1 (HAI-1) has not been evaluated. This study aimed to examine the genetic variation of matriptase (ST14 gene) and HAI-1 (SPINT1 gene) in breast cancer risk and prognosis, to assess matriptase and HAI-1 gene and protein expression in breast tumors, and to identify their clinicopathologic correlations and prognostic significance.Methods: Five single nucleotide polymorphisms in ST14 and three in SPINT1 were genotyped in 470 invasive breast cancer cases and 446 healthy controls. Gene expression analysis was done for 40 breast cancer samples. Protein expression was assessed by immunohistochemical analyses in 377 invasive breast tumors. The statistical significance of the associations among genotypes, clinicopathologic variables, and prognosis was assessed.Results: The ST14 single nucleotide polymorphism rs704624 independently predicted breast cancer survival, a poor outcome associated with the minor allele (P = 0.001; risk ratio, 2.221; 95% confidence interval, 1.382-3.568). Moreover, ST14 gene expression levels were lower among the minor allele carriers (P = 0.009), and negative/low matriptase protein expression was independently predictive of poorer survival (P = 0.046; risk ratio, 1.554; 95% confidence interval, 1.008-2.396).Conclusions: The ST14 variant rs704624 and protein expression of matriptase have prognostic significance in breast cancer. This study adds to the evidence for the role of matriptase in breast cancer and has found new evidence for the genotypes having an impact in breast cancer.Impact: This is the first study showing that genetic variation in matriptase has clinical importance. The results encourage further study on the genetic variation affecting protein levels and function in type II transmembrane serine proteases. Cancer Epidemiol Biomarkers Prev; 19(9); 2133–42. ©2010 AACR.

Supplementary Data from Molecular Subtypes of Breast Cancers Detected in Mammography Screening and Outside of Screening

Supplementary Figure Legends from ST14 Gene Variant and Decreased Matriptase Protein Expression Predict Poor Breast Cancer Survival

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Background: The single-nucleotide polymorphism (SNP) 5p12-rs10941679 has been found to be associated with risk of breast cancer, particularly estrogen receptor (ER)-positive disease. We aimed to further explore this association overall, and by tumor histopathology, in the Breast Cancer Association Consortium.Methods: Data were combined from 37 studies, including 40,972 invasive cases, 1,398 cases of ductal carcinoma in situ (DCIS), and 46,334 controls, all of white European ancestry, as well as 3,007 invasive cases and 2,337 controls of Asian ancestry. Associations overall and by tumor invasiveness and histopathology were assessed using logistic regression.Results: For white Europeans, the per-allele OR associated with 5p12-rs10941679 was 1.11 (95% CI = 1.08–1.14, P = 7 × 10−18) for invasive breast cancer and 1.10 (95% CI = 1.01–1.21, P = 0.03) for DCIS. For Asian women, the estimated OR for invasive disease was similar (OR = 1.07, 95%CI = 0.99–1.15, P = 0.09). Further analyses suggested that the association in white Europeans was largely limited to progesterone receptor (PR)-positive disease (per-allele OR = 1.16, 95% CI = 1.12–1.20, P = 1 × 10−18 vs. OR = 1.03, 95% CI = 0.99–1.07, P = 0.2 for PR-negative disease; Pheterogeneity = 2 × 10−7); heterogeneity by ER status was not observed (P = 0.2) once PR status was accounted for. The association was also stronger for lower grade tumors [per-allele OR (95% CI) = 1.20 (1.14–1.25), 1.13 (1.09–1.16), and 1.04 (0.99–1.08) for grade 1, 2, and 3/4, respectively; Ptrend = 5 × 10−7].Conclusion: 5p12 is a breast cancer susceptibility locus for PR-positive, lower grade breast cancer.Impact: Multicenter fine-mapping studies of this region are needed as a first step to identifying the causal variant or variants. Cancer Epidemiol Biomarkers Prev; 20(10); 2222–31. ©2011 AACR.

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PDF file, 57K, Genotyping characteristics of each BCAC participating study.

Background: Our recent genome-wide association study identified a novel breast cancer susceptibility locus at 9q31.2 (rs865686).Methods: To further investigate the rs865686–breast cancer association, we conducted a replication study within the Breast Cancer Association Consortium, which comprises 37 case–control studies (48,394 cases, 50,836 controls).Results: This replication study provides additional strong evidence of an inverse association between rs865686 and breast cancer risk [study-adjusted per G-allele OR, 0.90; 95% confidence interval (CI), 0.88; 0.91, P = 2.01 × 10−29] among women of European ancestry. There were ethnic differences in the estimated minor (G)-allele frequency among controls [0.09, 0.30, and 0.38 among, respectively, Asians, Eastern Europeans, and other Europeans; P for heterogeneity (Phet) = 1.3 × 10−143], but no evidence of ethnic differences in per allele OR (Phet = 0.43). rs865686 was associated with estrogen receptor–positive (ER+) disease (per G-allele OR, 0.89; 95% CI, 0.86–0.91; P = 3.13 × 10−22) but less strongly, if at all, with ER-negative (ER−) disease (OR, 0.98; 95% CI, 0.94–1.02; P = 0.26; Phet = 1.16 × 10−6), with no evidence of independent heterogeneity by progesterone receptor or HER2 status. The strength of the breast cancer association decreased with increasing age at diagnosis, with case-only analysis showing a trend in the number of copies of the G allele with increasing age at diagnosis (P for linear trend = 0.0095), but only among women with ER+ tumors.Conclusions: This study is the first to show that rs865686 is a susceptibility marker for ER+ breast cancer.Impact: The findings further support the view that genetic susceptibility varies according to tumor subtype. Cancer Epidemiol Biomarkers Prev; 21(10); 1783–. ©2012 AACR.

Supplementary Figure 2A from ST14 Gene Variant and Decreased Matriptase Protein Expression Predict Poor Breast Cancer Survival

Purpose: The frequency and significance of gene expression profile-derived molecular subtypes of breast cancers found in mammography screening are unknown.Experimental Design: We identified breast cancers diagnosed in women of any age living in defined geographic regions in Finland in 1991 to 1992 and collected clinical and pathologic data. Surrogates for the molecular subtypes were determined for 247 cancers found in organized mammography screening and 989 cancers detected outside of screening using immunohistochemistry or in situ hybridization. Molecular subtypes were defined as luminal A [estrogen receptor (ER) positive and/or progesterone receptor (PR) positive, HER2-], luminal B (ER+ and/or PR+, HER2+), basal-like (ER-, PR-, HER2-, cytokeratin 5+, and/or HER1+), HER2+/ER- (ER-, PR-, and HER2+), and unclassified. The median follow-up time was 9.4 years.Results: The luminal type A was common (73.7%) and the HER2+/ER- type is rare (5.7%) in screen-detected cancer, and only 16% were HER2 positive. Women with cancer diagnosed in screening at ages 50 to 69 years had similar molecular subtype distribution as women whose cancer was found outside of screening at age >69 years. In a multivariate model, cancer detection at screening independently predicted favorable distant disease-free survival when the molecular subtype was included as a covariate in addition to age, histologic grade, and cancer size. Women with small (pT1N0M0) HER2-positive cancer had similar outcome regardless of the method of detection.Conclusions: Molecular subtype distribution of screen-detected breast cancer differs from that of cancers found outside of screening and accounts in part for the better outcome of screen-detected cancer.

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PDF file, 107K, Summary characteristics of the participating BCAC case-control studies.

Background Chemotherapy cycle prescription is generally carried out through a manual process. ICT tools with data analytics could streamline this process and limit human errors. Methods A one-arm multicenter prospective clinical trial ECHO 7/2019-1/2021 (NCT04081558) investigated the use of a novel Kaiku Health ePRO tool in cancer care. The most important patient inclusion criteria were colorectal cancer (CRC) planned to be treated with oxaliplatin-based chemotherapy as an adjuvant therapy or in the first or second line setting of advanced disease, age ≥18 years, ECOG performance score of 0-2, and internet access. A decision support tool consisting of a digital symptom monitoring, laboratory value interface, and treatment schedule integration for a semi-automatized chemotherapy cycle prescribing was created for the trial. Results The dataset included CRC patients (n=43) treated with doublet or triplet chemotherapy in adjuvant or metastatic setting, and 339 prescribed chemotherapy cycles. For the 77% of the new chemotherapy cycles, ePRO questionnaire data was available. 65% of cycles had symptom questionnaires grading at ≤ 1 while 67% of the cycles had laboratory values at pre-set range. The recommendation by the tool for a new chemotherapy cycle was (green/go) in 42.8%, two (yellow/evaluate) in 24.5%, and three (red/hold) 32.7% of the cycles. HCPs valued the improved workflow, faster patient evaluation, and direct messaging option the most. Conclusions In this study, we investigated the feasibility of a decision support system in chemotherapy cycle pre-evaluation and prescription. The study shows that the functionalities of the investigated tool were feasible, and an automated approach to chemotherapy cycle prescription was possible for nearly half of the cycles. Trial registration: NCT04081558 9th Sep 2019

Purpose Electronic (e) patient-reported outcomes (PROs) have been shown to improve the quality of life and survival in chemotherapy treated advanced cancer patients. We hypothesized that multidimensional ePRO centered approach could improve symptom management, streamline patient flow, and optimize the use of healthcare resources. Methods In this multicenter trial (NCT04081558), colorectal cancer (CRC) patients receiving oxaliplatin-based chemotherapy as adjuvant or in the first- or second-line setting in advanced disease were included in the prospective ePRO cohort, while a comparative retrospective cohort was collected from the same institutes. The investigated tool consisted of a weekly e-symptom questionnaire integrated to an urgency algorithm and laboratory value interface, which generated semi-automated decision support for chemotherapy cycle prescription and individualized symptom management. Results Recruitment to the ePRO cohort occurred 1/2019–1/2021 (n = 43). The comparator group (n = 194) consisted of patients treated in the same institutes 1–7/2017. The analysis was limited to adjuvant treated (n = 36 and n = 35). The feasibility of the ePRO follow-up was good with 98% reporting easy usage and 86% improved care, while health care personnel valued the easy use and logical workflow. In the ePRO cohort, 42% needed a phone call before planned chemotherapy cycles, while this was 100% in the retrospective cohort (p = 1.4e−8). Peripheral sensory neuropathy was detected significantly earlier with ePRO followed (p = 1e−5) but did not translate to earlier dose reduction, delays, or unplanned therapy termination compared to the retrospective cohort. Conclusion The results suggest that the investigated approach is feasible and streamlines workflow. Earlier symptom detection may improve the quality in cancer care.

The need for high quality palliative care at end-of-life has been increasingly recognized while regional differences exist in its quality and availability. Basic palliative care is given by oncologists at any stage of the disease, but this does not cover the high need for specialized palliative care. The aim of this study was to assess the trends in end-of-life decisions among patients dying in a university hospital oncology ward before and after the implementation of a palliative outpatient clinic. The study population consists of all patients who died in the Kuopio University Hospital oncology ward between 1.1.2010–31.10.2011 and 1.1.2012–31.12.2018. The palliative outpatient clinic was established and set up in November - December 2011. Data on inpatient stays, cancer treatments, treatment decisions, and some background factors were retrieved from electronic records. The study population totaled 644 patients dying in the oncology ward at KUH (57.8% males; 42.2% females). The deaths comprise 17.2% (191/1108) of all cancer deaths in 2010–2011 and 11.1% (461/4049) in 2012–2018 in the KUH catchment area (North-Savo Health Care District). In years 2012–2018, 14.1% of patients treated at KUH oncology clinic visited the palliative outpatient clinic. The percentage of DNR (do-not-resuscitate), palliative care, and end-of-life (EOL) care decisions increased significantly in the later period. The decisions were mainly made during the last week of life. The proportion of patients receiving chemotherapy during the last two weeks of life remained stable. The proportion of patients receiving DNR, palliative care and EOL care decisions increased after the implementation of the palliative outpatient clinic, but the decisions were still made rather late, mainly during the last days of life.

Background The use of stereotactic body radiotherapy (SBRT) as the primary treatment modality in clinically localized prostate cancer (PCa) is emerging. The aim of the study was to analyze the long-term results of PCa patients treated with SBRT. Methods This non-selected, real-life patient cohort included 213 patients with localized PCa treated with a robotic SBRT device during 2012–2015. Results The median follow-up was 64 months (range, 10–85 months), and all risk-groups were represented as 47 (22.1%), 56 (26.3%) and 110 (51.6%) patients were classified into D’Amico risk stratification of low, intermediate and high-risk groups, respectively. Androgen deprivation therapy (ADT) was administered to 64.3% of the patients. At cut-off, the biochemical relapse-free survival (bRFS) was 100, 87.5 and 80.0% for patients at low, intermediate and high-risk (p = 0.004), and 92.5, 84.2 and 66.7% for patients with Gleason score ≤ 6, 7 and ≥ 8, respectively (p = 0.001). The actuarial 5-year overall survival (OS) rates were 97.9, 96.4 and 88.6% in the low, intermediate and high-risk groups, respectively, and at the cut-off, the disease-specific survival (DSS) rate of the whole cohort was high (99.1%), as only two high-risk patients died due to PCa. Conclusion Our present results of SBRT delivered with CyberKnife produced excellent long-term bRFS, OS and DSS outcomes among patients with localized PCa. We conclude that SBRT provides an efficient and convenient treatment option for patients with localized PCa, irrespective of the risk-group.

Background As aging is the most significant risk factor for cancer development, long-term prostate cancer (PCa) survivors have an evident risk of developing subsequent primary cancers (SPCs). Radiotherapy itself is an additional risk factor for cancer development and the SPCs appearing beyond 5 years after radiotherapy in the original treatment field can be considered as radiation-induced subsequent primary cancers (RISPCs). Methods During the years 1999-2008, 241 patients with localized PCa who underwent low dose-rate brachytherapy (LDR-BT) with I125 and were followed-up in Kuopio University Hospital, were included in this study. In this study the incidences and types of SPCs and RISPCs with a very long follow-up time after LDR-BT were evaluated. Results During the median follow-up time of 11.4 years, a total of 34 (14.1%) patients developed a metachronous SPC. The most abundant SPCs were lung and colorectal cancers, each diagnosed in six patients (16.7% out of all SPCs). The crude incidence rate of RISPC was 1.7% (n = 4). Half of the SPC cases (50%) were diagnosed during the latter half of the follow-up time as the risk to develop an SPC continued throughout the whole follow-up time with the actuarial 10-year SPC rate of 7.0%. The crude death rates due to metachronous out-of-field SPCs and RISPCs were 50 and 50%, respectively. Conclusion The crude rate of SPC was in line with previously published data and the incidence of RISPC was very low. These results support the role of LDR-BT as a safe treatment option for patients with localized PCa.

Clozapine is the most efficacious treatment for schizophrenia and is associated with lower overall mortality than are other antipsychotic drugs, despite the risk of agranulocytosis. Preliminary reports over the past 10 years suggest a possible risk of haematological malignancies, but the issue has remained unsettled. We aimed to study the risk of haematological malignancies associated with use of clozapine and other antipsychotics.We did a nationwide case-control (and cohort) study of people with schizophrenia, using prospectively gathered data from Finnish national registers. A nested case-control study was constructed by individually matching cases of lymphoid and haematopoietic tissue malignancy with up to ten controls without cancer by age, sex, and time since first schizophrenia diagnosis. For the case-control study, we restricted inclusion criteria to malignancies diagnosed on a histological basis, and excluded individuals outside of the age range 18-85 years, and any patients that had a previous malignancy. Analyses were done using conditional logistic regression adjusting for comorbid conditions.For the case-control study 516 patients with a first-time diagnosis of lymphoid and haematopoietic tissue malignancy during years 2000-17 and diagnosed after their first diagnosis of schizophrenia were identified. 102 patients were excluded due to diagnosis that was without a histological basis, five patients were excluded because of their age, and 34 were excluded for a previous malignancy, resulting in 375 patients being matched to controls. We selected up to ten controls without cancer (3734 in total) for each case from the base cohort of people with schizophrenia. For the cohort study, data for 55 949 people were included for analysis. Cumulative incidence of haematological malignancies during the mean follow-up of 12·3 years (SD 6·5) was 102 (0·7%) cases among 13 712 patients who had used clozapine (corresponding to event rate of 61 cases per 100 000 person-years), and during mean follow-up of 12·9 years (SD 7·2) was 235 (0·5%) malignancies among 44 171 patients having used other antipsychotic medication than clozapine (corresponding to 41 cases per 100 000 person-years). Of the 375 individuals with haematological malignancies (305 lymphomas, 42 leukaemia, 22 myelomas, 6 unspecified) observed from 2000-17, 208 (55%) were males and 167 (45%) were female. Ethnicity data were not available. Compared with non-use of clozapine (most had used other antipsychotics and a few had used no antipsychotics), clozapine use was associated with increased odds of haematological malignancies in a dose-response manner (adjusted odds ratio 3·35, [95% CI 2·22-5·05] for ≥5000 defined daily dose cumulative exposure, p0·0001). Exposure to other antipsychotic drugs was not associated with increased odds. A complementary analysis showed that the clozapine-related risk increase was specific for haematological malignancies, because no such finding was observed for other malignancies. Over 17 years of follow-up of the base cohort, 37 deaths occurred due to haematological malignancy among patients exposed to clozapine (26 with ongoing use at time of haematological malignancy diagnosis, and 11 in patients who did not use clozapine at the exact time of their cancer diagnosis), whereas only three deaths occurred due to agranulocytosis.Unlike other antipsychotics, long-term clozapine use is associated with increased odds of haematological malignancies. Long-term clozapine use has a higher effect on mortality due to lymphoma and leukaemia than due to agranulocytosis. However, acknowledging that the absolute risk is small compared with the previously observed absolute risk reduction in all-cause mortality is important. Our results suggest that patients and caregivers should be informed about warning signs of haematological malignancies, and mental health clinicians should be vigilant for signs and symptoms of haematological malignancy in patients treated with clozapine.The Finnish Ministry of Social Affairs and Health and Academy of Finland.

Purpose The purpose of this study was to evaluate the incidence of late severe (≥Grade 3) urinary toxicity and the long-term efficacy after low-dose-rate brachytherapy (LDR-BT) in patients with localized prostate cancer (PCa). Methods and Materials During the years 1999–2008, 241 patients with PCa who underwent LDR-BT with I 125 and were followed up in Kuopio University Hospital were included to this analysis. The incidence of late severe (Grade 3) urinary toxicity and the long-term efficacy results were analyzed. Results All D'Amico risk groups were represented, as 58.9%, 35.3%, and 5.8% of the patients were classified as low-, intermediate-, and high-risk patients, respectively. With a median followup of 11.4 years after implantation, the incidence of severe urinary toxicity increased throughout the followup period. The risk of Grade 3 urinary toxicity was highest among patients with higher Gleason scores ( p = 0.016) and higher initial urine residual volumes ( p = 0.017) and the cumulative incidence of severe urinary toxicity was 10.0%. The crude rate for transurethral prostatic resection was 5.8%. The relapse-free survival, the cause-specific survival, and the overall survival were 79.3%, 95.0%, and 66.4%, respectively. Conclusions The treatment was well tolerated as 90% of patients avoided any Grade 3 urinary toxicity. LDR-BT for localized PCa achieved high and durable efficacy. These results support the role of LDR-BT monotherapy as one of the valid primary treatment options for low-risk and favorable intermediate-risk patients.

Background/Aim: Our phase III trial showed that biweekly docetaxel (D) is better tolerated than triweekly D in metastatic castration-resistant prostate cancer (mCRPC). The safety of biweekly cabazitaxel (CBZ) post-docetaxel was studied in mCRPC. Patients and Methods: Altogether, 60 patients received CBZ 16 mg/m2 i.v. on day 1 and day 14 of a 4-week cycle. The mean serum PSA levels were 305 ng/ml, and the mean age 67 years. The primary endpoint was safety according to CTCAEv4.0. Results: A total of 255 4-week cycles of CBZ were administered. The most common grade 3/4 adverse events were neutropenia (16.7%), pain (13.3%), fatigue (10.0%), anemia (5.0%) and non-neutropenic infection (10.0%). PSA responses occurred in 10 patients (16.7%). Clinical benefit rate was 38.3% and median survival 10 months. Conclusion: Biweekly CBZ is a well-tolerated treatment resulting in meaningful benefits for heavily pretreated mCRPC patients.

Generally, screen-detected cancers have more favourable tumour characteristics than clinically detected or symptomatic cancers. Less is known, whether the tumour characteristics of breast cancer have changed over time into more favourable in general and whether the changes have been similar in all ages.The aim of this study was to explore the change of breast cancer characteristics in parallel to the implementation of modern diagnostic methods in three age groups over four 5-year time periods between 1992 and 2011. The data from 942 primary breast cancers in one university hospital district in Finland were combined with data from the Finnish Cancer Registry and the Mass Screening Registry. The association of favourable tumour characteristics with time period, age group and diagnostic methods was explored.The most discernible secular change was the increase in oestrogen (ER)-positive cancers in every consecutive time period. The risk for ER positivity in the second, third and fourth period was 2- to 2.71-fold compared to the first period. An increase in small tumours and node-negative tumours was detected during the most recent years of data collection. The secular changes were observed in all age groups; however, overall ER positivity was most frequent among women beyond screening age and small tumours among screening-aged women. The increase in small and node-negative tumours could partly be explained by the implementation of new radiological methods.This study detected a secular change of tumour characteristics into more favourable irrespective of age group. If the trend continues, it seems that we are going to have a breast cancer population of mainly small ER-positive breast cancers in the future forcing to rethink the therapeutic approach.

The cost of cancer and outcomes of cancer care have been discussed a lot since cancer represents 3-6% of total healthcare costs and cost estimations have indicated growing costs. There are studies considering the cost of all cancers, but studies focusing on the cost of disease and outcomes in most common cancer sites are limited. The objective of this study was to analyze the development of the costs and outcomes in Finland between 2009 and 2014 per cancer site.The National cost, episode and outcomes data were obtained from the National register databases based on International Statistical Classification of Diseases (ICD)-10 diagnosis codes. Cost data included both the direct and indirect costs. Two hospitals were used to validate the costs of care. The outcome measures included relative survival rate, mortality, sick leave days per patient and number of new disability pensions.The outcomes of cancer care in most common cancer sites have improved in Finland between 2009-2014. The real costs per new cancer patient decreased in seven out of ten most common cancer sites. The significance of different cost components differ significantly between the different cancer sites. The share of medication costs of the total cost of all cancers increased, but decreased for the five most common cancer sites.The changes in the cost components indicate that the length of stay has shortened in special care and treatment methods have developed towards outpatient care. This partially explains the decrease of costs. Also, at the same time outcomes improved, which indicates that decrease in costs did not come at the expense of treatment quality. As the survival rates increase, the relevance of mortality measures decreases and the relevance of other, patient-relevant outcome measures increases. In the future, the outcomes and costs of health care systems should be assessed routinely for the most common patient groups.

The cost of cancer and outcomes of cancer care has been much debated, since cancer represents 3-6% of total healthcare costs. The objective of this study was to analyse the development of the costs and outcomes in Finland between 2004 and 2014.The national cost, episodes and outcomes data were obtained from the national register databases. Two hospitals were used to validate the costs of care. The outcome measures included relative survival rate, mortality, sick leave days per patient and number of new disability pensions.The total cost of cancer in 2014 was 927 million €. The real costs increased by 1.7% per year over the period studied, while the cost per new cancer patient decreased. The relative survival rate was enhanced by 7%, and the number of sick leave days and new disability pensions per cancer patient was reduced. The share occupied by cancer treatment in total healthcare costs decreased slightly from 3.7% to 3.6%, indicating that cancer care has not become more expensive compared to the treatment of other diseases.This is the first survey to analyse the change in actual cancer costs and outcomes in the population-level within a 10-year period. Since cancer care outcomes in Finland have been among the best in Europe, the progress in terms of the costs and the conversions in the cost distributions across categories are significant and valuable sources for international comparisons.

Background/aim Tyrosine kinase inhibitors are important in the treatment of metastatic renal cell cancer (mRCC). The aim of the study was to evaluate the costs and effects of sunitinib in mRCC. Patients and methods A total of 81 mRCC patients who received first-line sunitinib therapy between 2010 and 2014 were recruited. Drug doses, laboratory and imaging studies, outpatient visits and inpatient stays were recorded. Health-related quality of life (HRQoL) was measured (15D- and EQ-5D - 3L questionnaires). Results The cost of sunitinib (mean 22,268 €/patient range 274 € to 105,121 €) covered 73% of the total costs during the treatment period. The total treatment cost was 30,530 €/patient (range=1,661-111,516 €). The median overall survival was 17.9 months. HRQoL decreased during treatment. Conclusion The main cost during sunitinib treatment of mRCC was the drug itself (73% of the total costs). Drug costs and HRQoL should be considered when choosing treatment for mRCC.

Background: Luminal A breast cancer defined as hormone receptor positive and human epidermal growth factor receptor 2 (HER2) negative is known to be heterogeneous. Previous study showed that luminal A tumours with the expression of basal markers ((cytokeratin (CK) 5 or CK5/6) or epidermal growth factor receptor (EGFR)) were associated with poorer prognosis compared with those that stained negative for basal markers. Prompted by this study, we assessed whether tumour characteristics and risk factors differed by basal marker status within luminal A tumours.\ud \ud Methods: We pooled 5040 luminal A cases defined by immunohistochemistry (4490 basal-negative ((CK5 (or CK5/6))− and EGFR−) and 550 basal-positive ((CK5 (or CK5/6+)) or EGFR+)) from eight studies participating in the Breast Cancer Association Consortium. Case–case comparison was performed using unconditional logistic regression.\ud \ud Results: Tumour characteristics and risk factors did not vary significantly by the expression of basal markers, although results suggested that basal-positive luminal tumours tended to be smaller and node negative, and were more common in women with a positive family history and lower body mass index.\ud \ud Conclusions: Most established breast cancer risk factors were similar in basal-positive and basal-negative luminal A tumours. The non-significant but suggestive differences in tumour features and family history warrant further investigations.

e14058 Background: ICIs have introduced novel irAEs, arising from various organ systems without strong timely dependency on initiation and discontinuation of the therapy. Early detection of the irAEs could result in improved safety profile of the treatment and better quality of life for patients. Symptom data collected by ePROs could be used as an input for ML based prediction models for early detection of irAEs. Methods: The utilized dataset consisted of two data sources. The first dataset consisted of 16 540 reported symptoms from 33 ICI-treated cancer patients, including 18 monitored symptoms collected using Kaiku Health digital platform. The second dataset included prospectively collected irAE data, including initiation and end dates, CTCAE class, and severity of 26 irAEs (the longest irAE lasted 799 days, and the shortest two days while median duration was 61 days). Two ML models were built using extreme gradient boosting, a well-known classification algorithm. Using the ePRO data, the first model was trained to detect the presence and the second model to detect the onset (0-21 days prior to diagnosis) of irAEs. The dataset was split into training (70 % of the data) and test sets (30 % of the data) by random allocation. The test set was left out from the model training and tuning, and was used only to evaluate the model performance. Results: The model trained to predict the presence of irAEs had an excellent performance with the test dataset. The prediction of the irAE onset was more difficult, but the model performance was still at a very good level. The performance metrics for the ML models are presented in Table. Conclusions: Current study suggests that ML based prediction models, using ePRO data as input for the models, can predict the presence and onset of irAEs with high accuracy. Thus, it indicates that digital symptom monitoring combined with ML could enable the detection of irAEs in ICI-treated cancer patients. The results should be validated with a larger dataset from prospective clinical trials. Clinical trial information: NCT03928938. [Table: see text]