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  • Fallara, G., et al. (författare)
  • Time on treatment with abiraterone and enzalutamide in the Patient-overview Prostate Cancer in The National Prostate Cancer Register of Sweden
  • 2021
  • Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 60:12, s. 1589-1596
  • Tidskriftsartikel (refereegranskat)abstract
    • Background There are little and inconsistent data from clinical practice on time on treatment with the androgen receptor-targeted drugs (ART) abiraterone and enzalutamide in men with metastatic castration-resistant prostate cancer (mCRPC). We assessed time on treatment with ART and investigated predictors of time on treatment. Material and methods Time on treatment with ART in men with mCRPC in the patient-overview prostate cancer (PPC), a subregister of the National Prostate Cancer Register (NPCR) of Sweden, was assessed by use of Kaplan-Meier plots and Cox regression. To assess the representativity of PPC for time on treatment, a comparison was made with all men in NPCR who had a filling for ART in the Prescribed Drug Registry. Results 2038 men in PPC received ART between 2015 and 2019. Median time on treatment in chemo-naive men was 10.8 (95% confidence interval 9.1-13.1) months for abiraterone and 14.1 (13.5-15.5) for enzalutamide. After the use of docetaxel, time on treatment was 8.2 (6.5-12.4) months for abiraterone and 11.1 (9.8-12.6) for enzalutamide. Predictors of a long time on treatment with ART were long duration of ADT prior to ART, low serum levels of PSA at start of ART, absence of visceral metastasis, good performance status, and no prior use of docetaxel. PPC captured 2522/6337 (40%) of all men in NPCR who had filled a prescription for ART. Based on fillings in the Prescribed Drug Registry, men in PPC had a slightly longer median time on treatment with ART compared to all men in NPCR, 9.6 (9.1-10.3) vs. 8.6 (6.3-9.1) months. Conclusions Time on treatment in clinical practice was similar or shorter than that in published RCTs, due to older age, poorer performance status and more comorbidities.
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  • Ahlberg, M., et al. (författare)
  • Time without PSA recurrence after radical prostatectomy as a predictor of prostate cancer death
  • 2022
  • Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 81:Suppl. 1, s. S286-S286
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Introduction & Objectives: Although surveillance after radical prostatectomy routinely includes repeated Prostate Specific Antigen (PSA)-testing for many years, biochemical recurrence often occurs without further clinical progression. We therefore hypothesised that follow-up can be shortened for many patients without increasing the risk for prostate cancer death. We investigated the long-term probabilities of PSA recurrence, metastases and prostate cancer death in patients without biochemical recurrence 5 and 10 years after radical prostatectomy.Materials & Methods: Between 1989 and 1998, 14 urological centres in Scandinavia randomized patients to the Scandinavian Prostate Cancer Group study number 4 (SPCG-4) trial. Data was collected prospectively. All 306 patients from the SPCG-4 trial who underwent radical prostatectomy within 1 year from inclusion were eligible in our cohort. 4 patients were excluded due to surgery-related death (n=1) or salvage radiotherapy or hormonal treatment within 6 weeks from surgery (n=3). We stratified by Gleason score (≤3+4=7 or ≥4+3=7), pathological tumour stage (pT2 or ≥pT3), and negative or positive surgical margins. We analysed the cumulative incidences and absolute differences in metastatic disease and prostate cancer death.Results: We analysed 302 patients with complete follow-up during a median of 18 years. Median preoperative PSA was 9.8 ng/ml and median age at inclusion was 65 years. For patients without biochemical recurrence 5 years after radical prostatectomy the 20-year probability of biochemical recurrence was 25% among men with Gleason score ≤3+4=7 and 57% among men with Gleason score ≥4+3=7; the probabilities for metastases were 0.8% and 17%; and for prostate cancer death 0.8% and 12% respectively. The long-term probabilities were higher for pT≥3 vs. pT2 and for positive vs. negative surgical margins.Conclusions: Following radical prostatectomy, patients with Gleason score ≤3+4=7 without biochemical recurrence 5 years after radical prostatectomy had low risk of metastases and prostate cancer death independent of pT-stage and surgical margins. The risk of clinical progression decreased drastically the first 3 years after radical prostatectomy and after 10 years without biochemical recurrence, no patient was diagnosed with metastases or died from prostate cancer. Our study indicates that men with favourable histopathology without biochemical recurrence 5 years after radical prostatectomy can stop follow-up earlier than 10 years after radical prostatectomy while men with adverse pathology should continue with at least 10 years follow-up
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  • George, G., et al. (författare)
  • Risk of cardiovascular events in men on abiraterone or enzalutamide combined with GnRH agonists: nation-wide, population-based cohort study in Sweden
  • 2021
  • Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 60:4, s. 459-465
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Men with prostate cancer (PCa) on gonadotropin-releasing hormone agonists (GnRH) have an increased risk of cardiovascular disease (CVD) compared to men with PCa not on GnRH as well as compared with PCa-free men. Whether the addition of androgen receptor targeted (ART) drugs to GnRH further increases CVD risk, remains to be fully elucidated. Material and methods We investigated risk of CVD for men with castration resistant PCa (CRPC) on GnRH plus ART; abiraterone or enzalutamide vs 5,127 and 12,079 respective matched comparator men on GnRH in Prostate Cancer data Base Sweden (PCBaSeTraject) 4.1 between 1 June 2015 and 31 December 2018. PCBaSeTraject links National Prostate Cancer Register of Sweden to other healthcare registries and demographic databases. We conducted multivariable Cox proportional hazard models adjusting for PCa risk category, Charlson comorbidity index (CCI), insulin or statin use, civil status, level of education, history of CVD events and number of CVD drugs, with any incident or fatal CVD as the outcome. Results and conclusion 1,310 men were treated with abiraterone and 3,579 with enzalutamide. In multivariable analysis, CVD risk was increased in men on abiraterone (hazard ratio (HR): 1.19; 95% confidence interval (CI): 1.03-1.38) and in men on enzalutamide (HR: 1.10; 95% CI: 1.01-1.20). Men with a recent CVD (<12 months) including both men on ART as well as comparators had a much higher probability of a new CVD vs men with no prior CVD. CVD risk was mildly increased in men with PCa on GnRH plus abiraterone or enzalutamide vs comparator men on GnRH. Residual confounding and detection bias may at least partly explain this association.
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  • Glimelius, Bengt, et al. (författare)
  • A randomized phase III multicenter trial comparing irinotecan in combination with the Nordic bolus 5-FU and folinic acid schedule or the bolus/infused de Gramont schedule (Lv5FU2) in patients with metastatic colorectal cancer
  • 2008
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 19:5, s. 909-914
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: To compare irinotecan with the Nordic 5-fluorouracil (5-FU) and folinic acid (FA) bolus schedule [irinotecan 180 mg/m2 on day 1, 5-FU 500 mg/m2 and FA 60 mg/m2 on day 1 and 2 (FLIRI)] or the Lv5FU2 schedule [irinotecan 180 mg/m2 on day 1, FA 200 mg/m2, 5-FU bolus 400 mg/m2 and infused 5-FU 600 mg/m2 on day 1 and 2 (Lv5FU2-IRI)] due to uncertainties about how to administrate 5-FU with irinotecan. Patients and methods: Patients (n = 567) with metastatic colorectal cancer were randomly assigned to receive FLIRI or Lv5FU2-IRI. Primary end point was progression-free survival (PFS). Results: Patient characteristics were well balanced. PFS did not differ between groups (median 9 months, P = 0.22). Overall survival (OS) was also similar (median 19 months, P = 0.9). Fewer objective responses were seen in the FLIRI group (35% versus 49%, P = 0.001) but the metastatic resection rate did not differ (4% versus 6%, P = 0.3). Grade 3/4 neutropenia (11% versus 5%, P = 0.01) and grade 2 alopecia (18% versus 9%, P = 0.002) were more common in the FLIRI group. The 60-day mortality was 2.4% versus 2.1%. Conclusions: Irinotecan with the bolus Nordic schedule (FLIRI) is a convenient treatment with PFS and OS comparable to irinotecan with the Lv5FU2 schedule. Neutropenia and alopecia are more prevalent, but both regimens are equally well tolerated. © The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
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  • Kontos, Michalis, et al. (författare)
  • Follow-up may not be beneficial after treatment of grade 1 breast cancer
  • 2009
  • Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 96:9, s. 999-1004
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Identification of women treated for breast cancer who have a low risk of locoregional recurrence or contralateral breast cancer, and who can be discharged safely from follow-up, would lower costs without compromising prognosis. This study investigated the risk of locoregional recurrence and contralateral breast cancer in women treated for grade 1 breast cancer. METHODS: Some 1143 women who had surgery for breast cancer were followed, and the rate of locoregional recurrence or contralateral breast cancer was determined. The risk was compared to the tumour grade. RESULTS: At a mean follow-up of 9.1 years, 10-year estimates of the cumulative risk of locoregional recurrence or contralateral breast cancer for grade 1, 2 and 3 breast cancer were 0.03 (95 per cent confidence interval (c.i.) 0.01 to 0.08), 0.12 (0.09 to 0.15) and 0.16 (0.13 to 0.20) respectively. Grade 1 tumours had a risk of locoregional recurrence or contralateral breast cancer of 285 (95 per cent c.i. 93 to 670) per 100,000 person-years. CONCLUSION: Women treated for grade 1 breast cancer could be discharged from follow-up after completion of the primary treatment, without compromising their quality of care.
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  • Ringberg, Anita, et al. (författare)
  • Histopathological risk factors for ipsilateral breast events after breast conserving treatment for ductal carcinoma in situ of the breast--results from the Swedish randomised trial.
  • 2007
  • Ingår i: European journal of cancer (Oxford, England : 1990). - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 43:2, s. 291-8
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: The primary aims were to study risk factors for an ipsilateral breast event (IBE) after sector resection for ductal carcinoma in situ of the breast (DCIS) in a trial comparing adjuvant radiotherapy to no therapy and to assess predictive factors for response to radiotherapy. Secondary aims were to analyse reproducibility of the histopathological evaluation and to estimate correctness of diagnosis in the trial. SETTING: A randomised trial in Sweden (the SweDCIS trial), including 1046 women with a median of 5.2 years of follow-up in a population, offered routine mammographic screening. METHODS: A case-cohort design with a total of 161 cases of IBE (42 of those being members of the subcohort) and 284 sampled for the sub-cohort. Ninety five percent of the participants' slides could be retrieved and were re-evaluated by three experienced pathologists. RESULTS: Low nuclear grade (NG 1-2) and absence of necrosis halves the risk of IBE in both irradiated and non-irradiated patients. Lesion size, margins of excision and age at diagnosis did not modify these associations. The presence of necrosis modified the effect of radiotherapy: relative risk was 0.40 with necrosis present and 0.07 with necrosis absent (p-value for interaction 0.068). In all subsets of prognostic factors, radiotherapy conferred a substantial benefit. The risk factors for in situ and invasive IBE were similar. The agreement between pathologists was moderate (kappa=0.486). Correctness of diagnosis in the subcohort of SweDCIS was 84.8%. CONCLUSION: Although nuclear grade and necrosis carry prognostic information, we could not define a group with very low risk after sector resection alone. Radiotherapy has a protective effect in all substrata of risk factors studied. The interaction between the presence of necrosis and radiotherapy is a clinically and biologically relevant research area.
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  • Wulaningsih, W., et al. (författare)
  • A competing risks analysis of the association between prediagnostic serum glucose and lipids and breast cancer survival
  • 2016
  • Ingår i: Cancer Research. - Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London WC2R 2LS, England. Kings Coll London, Inst Math & Mol Biomed, London WC2R 2LS, England. Uppsala Univ, Uppsala, Sweden. Reg Canc Ctr, Uppsala, Sweden. Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. Karolinska Inst, S-10401 Stockholm, Sweden. AstraZeneca R&D, Mlndal, Switzerland. CALAB Res, Madrid, Spain.. - 0008-5472 .- 1538-7445. ; 76
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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  • Andrén, Ove, et al. (författare)
  • Incidence and mortality of incidental prostate cancer : a Swedish register-based study
  • 2009
  • Ingår i: British Journal of Cancer. - London : Nature publishing group. - 0007-0920 .- 1532-1827. ; 100:1, s. 170-173
  • Tidskriftsartikel (refereegranskat)abstract
    • In a national register-based study of incidence trends and mortality of incidental prostate cancer in Sweden, we found that a significant proportion (26.6%) of affected men diagnosed died of their disease, which challenges earlier descriptions of incidental prostate cancer as a non-lethal disease.
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  • Arthur, R., et al. (författare)
  • Serum inflammatory markers in relation to prostate cancer severity and death in the Swedish AMORIS study
  • 2018
  • Ingår i: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 142:11, s. 2254-2262
  • Tidskriftsartikel (refereegranskat)abstract
    • Inflammation is a well-documented driver of cancer development and progression. However, little is known about its role in prostate carcinogenesis. Thus, we examined the association of C-reactive protein (CRP), haptoglobin, albumin and white blood cells (WBC) with prostate cancer (PCa) severity (defined by PCa risk category and clinicopathological characteristics) and progression (defined by PCa death). We selected 8,471 Swedish men with newly diagnosed PCa who had exposure measurements taken approximately 14 years prior to diagnosis. We calculated odds ratio (OR) and 95% confidence interval (CI) for the associations between the inflammatory markers and PCa severity using logistic regression, while Cox proportional hazard regression was used for the associations with overall and PCa death. Serum CRP levels were associated with increased odds of high risk and metastatic PCa, and high PSA levels (20 mu g/L) (OR: 1.29; 95% CI: 1.06-1.56, 1.32; 1.05-1.65 and 1.51; 1.26-1.81, respectively). Similarly, higher haptoglobin levels were associated with increased odds of metastatic PCa, high PSA level and possibly high grade PCa (1.38; 1.10-1.74, 1.50; 1.17-1.93 and 1.25; 1.00-1.56, respectively). Albumin was positively associated with Gleason 4+3 tumour (1.38; 1.02-1.86) and overall death (HRunit increase in log: 1.60; 95% CI: 1.11-2.30), but inversely associated with high risk PCa and high PSA levels (20 mu g/L) (0.71; 0.56-0.89 and 0.72; 0.5 9-0.90). WBC was associated with increased odds of T3-T4 PCa. Except for albumin, none of these markers were associated with PCa death or overall death. Systemic inflammation as early as 14 years prior to diagnosis may influence prostate cancer severity. What's new? High levels of C-reactive protein can presage a particularly malignant prostate cancer, new results show. Cancers certainly arise in the wake of chronic inflammation, but it's not known exactly how markers of inflammation initiate prostate cancer. Here, the authors show that systemic inflammation can worsen the severity of the cancer, even if it occurred long before the cancer's onset. High levels of CRP and haptoglobin, they found, were associated with prostate cancer with high PSA and metastasis. The question remains whether inflammation pushes cancer cells into a more malignant mode, or selects for the more dangerous cells early on.
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  • Beckmann, K., et al. (författare)
  • Radical radiotherapy for prostate cancer: patterns of care in Sweden 1998-2016
  • 2020
  • Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 59:5, s. 549-557
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Radiotherapy is an established treatment option for prostate cancer (PCa), both as primary treatment and secondary treatment after radical prostatectomy (RP). Since 1998, detailed data on radiotherapy delivered to Swedish men with PCa (e.g. treatment modalities, absorbed doses, fractionation) have been collated within PCa data Base Sweden (PCBaSe). This study reports patterns of radical radiotherapy for PCa in Sweden over the past two decades. Materials and methods: All men with non-metastatic PCa (1998-2016) who received external beam radiotherapy (EBRT) or high or low dose-rate brachytherapy (HDR-BT/LDR-BT) were identified in PCBaSe. Analyses included: trends in radiation techniques, fractionation patterns and total doses over time; PCa-specific survival comparing treatment in 2007-2017 with 1998-2006; and regional variation in type of primary radiotherapy. Results: About 20,876 men underwent primary radiotherapy. The main treatment modalities include conventionally fractionated (2.0 Gy/fraction) EBRT (51%), EBRT with HDR-BT boost (27%) and hypofractionated (>2.4 Gy/fraction) EBRT (11%). EBRT with photon or proton boost and HDR-BT and LDR-BT monotherapies were each used minimally. Use of dose-escalated EBRT (>74 Gy) and moderate hypofractionation increased over time, while use of HDR-BT declined. Considerable regional variation in treatment modalities was apparent. Risk of PCa death following primary radiotherapy had declined for intermediate-risk (HR: 0.60; 95%CI 0.47-0.87) and high-risk PCa (HR: 0.72; 95%CI 0.61-0.86). Discussion: Increased use of dose escalation and hypofractionated EBRT has occurred in Sweden over the past two decades, reflecting current evidence and practice guidelines. Disease-specific outcomes have also improved. Data collected in PCBaSe provide an excellent resource for further research into RT use in PCa management.
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  • Bergengren, Oskar, et al. (författare)
  • Determinants for choosing and adhering to active surveillance for localised prostate cancer: A nationwide population-based study
  • 2019
  • Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 9:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Knowledge about factors influencing choice of and adherence to active surveillance (AS) for prostate cancer (PC) is scarce. We aim to identify which factors most affected choosing and adhering to AS and to quantify their relative importance. Design, setting and participants In 2015, we sent a questionnaire to all Swedish men aged ≤70 years registered in the National Prostate Cancer Register of Sweden who were diagnosed in 2008 with low-risk PC and had undergone prostatectomy, radiotherapy or started on AS. Outcome measurements and statistical analysis Logistic regression was used to calculate ORs with 95% CIs for factors potentially affecting choice and adherence to AS. Results 1288 out of 1720 men (75%) responded, 451 (35%) chose AS and 837 (65%) underwent curative treatment. Of those starting on AS, 238 (53%) diverted to treatment within 7years. Most men (83%) choose AS because ‘My doctor recommended AS’. Factors associated with choosing AS over treatment were older age (OR 1.81, 95%CI 1.29 to 2.54), a Charlson Comorbidity Index >2 (OR 1.50, 95%CI 1.06 to 2.13), being unaccompanied when notified of the cancer diagnosis (OR 1.45, 95%CI 1.11 to 1.89). Men with a higher prostate-specific antigen (PSA) at the time of diagnosis were less likely to adhere to AS (OR 0.26, 95%CI 0.10 to 0.63). The reason for having treatment after initial AS was ‘the PSA level was rising’ in 55% and biopsy findings in 36%. Conclusions A doctor’s recommendation strongly affects which treatment is chosen for men with low-risk PC. Rising PSA values were the main factor for initiating treatment for men on AS. These findings need be considered by healthcare providers who wish to increase the uptake of and adherence to AS.
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  • Bergengren, Oskar, et al. (författare)
  • Satisfaction with Care Among Men with Localised Prostate Cancer: A Nationwide Population-based Study
  • 2018
  • Ingår i: European Urology Oncology. - : Elsevier BV. - 2588-9311. ; 1:1, s. 37-45
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Information about how men with prostate cancer (PC) experience their medical care and factors associated with their overall satisfaction with care (OSC) is limited. Objective: To investigate OSC and factors associated with OSC among men with low-risk PC. Design, setting, and participants: Men registered in the National Prostate Cancer Register of Sweden as diagnosed in 2008 with low-risk PC at the age of ≤70 yr who had undergone radical prostatectomy (RP), radiotherapy (RT), or started on active surveillance (AS) were invited in 2015 to participate in this nationwide population-based survey (n = 1720). Outcome measurements and statistical analysis: OSC data were analysed using ordinal logistic regression. Odds ratios (ORs) were calculated for comparisons between the highest and lowest possible response categories. Results and limitations: A total of 1288 men (74.9%) responded. High OSC was reported by 958 (74.4%). Factors associated with high OSC were high participation in decision-making (OR 4.18, 95% confidence interval [CI] 2.61–6.69), receiving more information (OR 11.1, 95% CI 7.97–15.6), high-quality information (OR 7.85, 95% CI 5.46–11.3), access to a nurse navigator (OR 1.80, 95% CI 1.44–2.26), and better functional outcomes (defined as 25 points higher on the EPIC-26 questionnaire; OR 1.34, 95% CI 1.21–1.48). OSC was not affected by whether a doctor or specialist nurse conducted follow-up (OR 0.84, 95% CI 0.66–1.07). These findings were similar across treatment groups. Men who had undergone RP or RT reported high OSC more often than men on AS (78.2% vs 84.0% vs 72.6%), high participation in decision-making (70.5% vs 64.5% vs 49.2%), and having received more information (40.5% vs 45.8% vs 28.6%), and were less likely to believe they would die from PC (3.8% vs 3.9% vs 8.0%). Limitations include the nonrandomised retrospective design and potential recall bias. Conclusions: Information and participation in decision-making, as well as access to a nurse navigator, are key factors for OSC, regardless of treatment. Men on AS need more information about their treatment and need to participate more in decision-making. OSC was as high among men who had nurse-led follow-up as among men who had doctor-led follow-up. Patient summary: Information about how men with low-risk prostate cancer experience their medical care is limited. In this nationwide population-based study we found that information and participation in decision-making as well as access to a nurse navigator are key factors for satisfaction regardless of treatment. Men who are being closely watched for prostate cancer without immediate curative treatment need more information than they now receive and need to participate more in decision-making than they currently do. Information and participation in decision-making are key factors for satisfaction with care among men with localised prostate cancer. Men under active surveillance need more information about their treatment and need to participate more in decision-making. © 2018 European Association of Urology
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  • Bergengren, Oskar, et al. (författare)
  • Short term outcomes after robot assisted and open cystectomy- A nation-wide population-based study
  • 2023
  • Ingår i: Ejso. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 49:4, s. 868-874
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: We aimed to compare short term outcomes after robot assisted radical cystectomy (RARC) and open radical cystectomy (ORC) for urinary bladder cancer in a large population.Materials and methods: We included all patients without distant metastases who underwent either RARC or ORC with ileal conduit between 2011 and 2019 registered in the Bladder cancer data Base Sweden (BladderBaSe) 2.0. Primary outcome was unplanned readmissions within 90 days, and secondary out-comes within 90 days of surgery were reoperations, Clavien 3-5 complications, total days alive and out of hospital, and mortality. The analysis was carried out using multivariate regression models.Results: Out of 2905 patients, 832 were operated with RARC and 2073 with ORC. Robotic procedures were to a larger extent performed during later years, at high volume centers (47% vs 17%), more often for organ-confined disease (82% vs. 72%) and more frequently in patients with high socioeconomic status (26% vs. 21%). Patients operated with RARC were more commonly readmitted (29% vs. 25%). In multi -variable analysis RARC was associated with decreased risk of Clavien 3-5 complications (OR 0.58, 95% CI 0.47-0.72), reoperations (OR 0.53, 95% CI 0.39-0.71) and had more days alive and out of hospital (mean difference 3.7 days, 95% CI 2.4-5.0).Conclusion: This study illustrates the "real-world" effects of a gradual and nation-wide introduction of RARC. Patients operated with RARC had fewer major complications and reoperations but were more frequently readmitted compared to ORC. The observed differences were largely due to more wound related complications among patients treated with ORC.(c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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  • Bill-Axelson, Anna, et al. (författare)
  • Radical Prostatectomy or Watchful Waiting in Prostate Cancer-29-Year Follow-up
  • 2018
  • Ingår i: New England Journal of Medicine. - : Massachussetts Medical Society. - 0028-4793 .- 1533-4406. ; 379:24, s. 2319-2329
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND Radical prostatectomy reduces mortality among men with clinically detected localized prostate cancer, but evidence from randomized trials with long-term followup is sparse. METHODS We randomly assigned 695 men with localized prostate cancer to watchful waiting or radical prostatectomy from October 1989 through February 1999 and collected follow-up data through 2017. Cumulative incidence and relative risks with 95% confidence intervals for death from any cause, death from prostate cancer, and metastasis were estimated in intention-to-treat and per-protocol analyses, and numbers of years of life gained were estimated. We evaluated the prognostic value of histopathological measures with a Cox proportional-hazards model. RESULTS By December 31, 2017, a total of 261 of the 347 men in the radical-prostatectomy group and 292 of the 348 men in the watchful-waiting group had died; 71 deaths in the radical-prostatectomy group and 110 in the watchful-waiting group were due to prostate cancer (relative risk, 0.55; 95% confidence interval [CI], 0.41 to 0.74; P<0.001; absolute difference in risk, 11.7 percentage points; 95% CI, 5.2 to 18.2). The number needed to treat to avert one death from any cause was 8.4. At 23 years, a mean of 2.9 extra years of life were gained with radical prostatectomy. Among the men who underwent radical prostatectomy, extracapsular extension was associated with a risk of death from prostate cancer that was 5 times as high as that among men without extracapsular extension, and a Gleason score higher than 7 was associated with a risk that was 10 times as high as that with a score of 6 or lower (scores range from 2 to 10, with higher scores indicating more aggressive cancer). CONCLUSIONS Men with clinically detected, localized prostate cancer and a long life expectancy benefited from radical prostatectomy, with a mean of 2.9 years of life gained. A high Gleason score and the presence of extracapsular extension in the radical prostatectomy specimens were highly predictive of death from prostate cancer.
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  • Bill-Axelson, Anna, et al. (författare)
  • Radical prostatectomy versus watchful waiting in localized prostate cancer : the Scandinavian prostate cancer group-4 randomized trial
  • 2008
  • Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 100:16, s. 1144-1154
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The benefit of radical prostatectomy in patients with early prostate cancer has been assessed in only one randomized trial. In 2005, we reported that radical prostatectomy improved prostate cancer survival compared with watchful waiting after a median of 8.2 years of follow-up. We now report results after 3 more years of follow-up.METHODS: From October 1, 1989, through February 28, 1999, 695 men with clinically localized prostate cancer were randomly assigned to radical prostatectomy (n = 347) or watchful waiting (n = 348). Follow-up was complete through December 31, 2006, with histopathologic review and blinded evaluation of causes of death. Relative risks (RRs) were estimated using the Cox proportional hazards model. Statistical tests were two-sided.RESULTS: During a median of 10.8 years of follow-up (range = 3 weeks to 17.2 years), 137 men in the surgery group and 156 in the watchful waiting group died (P = .09). For 47 of the 347 men (13.5%) who were randomly assigned to surgery and 68 of the 348 men (19.5%) who were not, death was due to prostate cancer. The difference in cumulative incidence of death due to prostate cancer remained stable after about 10 years of follow-up. At 12 years, 12.5% of the surgery group and 17.9% of the watchful waiting group had died of prostate cancer (difference = 5.4%, 95% confidence interval [CI] = 0.2 to 11.1%), for a relative risk of 0.65 (95% CI = 0.45 to 0.94; P = .03). The difference in cumulative incidence of distant metastases did not increase beyond 10 years of follow-up. At 12 years, 19.3% of men in the surgery group and 26% of men in the watchful waiting group had been diagnosed with distant metastases (difference = 6.7%, 95% CI = 0.2 to 13.2%), for a relative risk of 0.65 (95% CI = 0.47 to 0.88; P = .006). Among men who underwent radical prostatectomy, those with extracapsular tumor growth had 14 times the risk of prostate cancer death as those without it (RR = 14.2, 95% CI = 3.3 to 61.8; P < .001).CONCLUSION: Radical prostatectomy reduces prostate cancer mortality and risk of metastases with little or no further increase in benefit 10 or more years after surgery. 
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33.
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34.
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35.
  • Eriksson, John, et al. (författare)
  • Primary small intestinal neuroendocrine tumors are highly prevalent and often multiple before metastatic disease develops
  • 2021
  • Ingår i: Scandinavian Journal of Surgery. - : Sage Publications. - 1457-4969 .- 1799-7267. ; 110:1, s. 44-50
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Small intestinal neuroendocrine tumors are the most common of small bowel malignancies with a clinical incidence of about 1 per 100,000 persons per year. There has been a threefold increase in the incidence of small intestinal neuroendocrine tumor during later decades, but there are no studies that clarify whether this is due to a true higher incidence or if the rise is a mere product of, for instance, improved diagnostic modalities. The aim of this study was to investigate the incidence of clinical as well as subclinical small intestinal neuroendocrine tumors found at autopsy as well as describing the frequency of concomitant malignancies in patients with small intestinal neuroendocrine tumor. Materials and methods: An autopsy registry from the Malmo county population from 1970 to 1982 with an 87% autopsy rate was used. The clinical autopsy reports for patients coded for the existence of "carcinoid tumor" were scrutinized for the presence of small intestinal neuroendocrine tumor, metastatic disease, and concomitant malignancies. Details of patients with clinically diagnosed small intestinal neuroendocrine tumor during this time period were gathered from the Swedish Cancer Registry. Results: The mean annual incidence of small intestinal neuroendocrine tumor during this period was 5.33 per 100,000 individuals, and the mean annual prevalence was 581 per 100,000. The cause of death in the majority of cases was not due to small intestinal neuroendocrine tumor. In total, 48% of the people with small intestinal neuroendocrine tumor had at least one other malignancy, most commonly colorectal cancer. Conclusion: Most small intestinal neuroendocrine tumors are subclinical, and persons living with them will often die due to other causes. There was a high rate of multiple primary tumors (40%), suggesting that multiple tumors seem to arise before the advent of metastatic disease. Moreover, a comparably high rate of associated colorectal carcinoma was found.
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36.
  • Eriksson, John, et al. (författare)
  • Prognostic factors for death after surgery for small intestinal neuroendocrine tumours.
  • 2018
  • Ingår i: BJS Open. - : Oxford University Press (OUP). - 2474-9842. ; 2:5, s. 345-352
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Neuroendocrine tumours of the small intestine (SI-NETs) are rare gastrointestinal neoplasms with an annual incidence of about one per 100 000. Patients with apparently similar tumours have variable outcomes. The aim of this study was to identify postoperative prognostic factors identifiable after initial surgery.Methods: This was a nested case-control study of patients with SI-NETs who were treated between 1961 and 2001. Data were retrieved from the Swedish Cancer Registry. Patients who died from the SI-NET and corresponding controls (who outlived cases by at least 1 month), matched by age at diagnosis and calendar period, were included. Sex, postoperative symptoms, postoperative 5-hydroxyindoleacetic acid (5-HIAA) values, European Neuroendocrine Tumor Society (ENETS) stage, insufficiency of the tricuspid valve, radical secondary surgery and secondary malignancy were studied as potential prognostic factors.Results: In total, 1122 patients were included (561 cases, 561 controls). Postoperative factors of prognostic importance included hormone-related symptoms, stage IV disease, raised levels of 5-HIAA, insufficiency of the tricuspid valve, secondary surgery not being macroscopically radical and a second malignancy.Conclusion: Stage and symptomatic disease are important prognostic factors in SI-NET.
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37.
  • Franck-Lissbrant, Ingela, 1969, et al. (författare)
  • Population-based study on use of chemotherapy in men with castration resistant prostate cancer
  • 2013
  • Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 52:8, s. 1593-1601
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Chemotherapy prolongs life and relieves symptoms in men with castration resistant prostate cancer (CRPC). There is limited information on a population level on the use of chemotherapy for CRPC. Material and methods. To assess the use of chemotherapy in men with CRPC we conducted a register-based nationwide population-based study in Prostate Cancer data Base Sweden (PCBaSe) and a nationwide in-patient drug register (SALT database) between May 2009 and December 2010. We assumed that men who died of prostate cancer (PCa) underwent a period of CRPC before they died. Results. Among the 2677 men who died from PCa during the study inclusion period, 556 (21%) had received chemotherapy (intravenous or per oral) detectable within the observation period in SALT database. Specifically, 239 (61%) of men <70 years had received chemotherapy, 246 (30%) of men between 70 and 79 years and 71 (5%) men older than 80 years. The majority of men 465/556 (84%) had received a docetaxel-containing regimen. Among chemotherapy treated men, 283/556 (51%) received their last dose of chemotherapy during the last six months prior to death. Treatment with chemotherapy was more common among men with little comorbidity and high educational level, as well as in men who had received curatively intended primary treatment. Conclusion. A majority of men younger than 70 years with CRPC were treated with chemotherapy in contrast to men between 70 and 79 years of whom half as many received chemotherapy. Chemotherapy treatment was often administered shortly prior to death. The low uptake of chemotherapy in older men with CRPC may be caused by concerns about tolerability of treatment, as well as treatment decisions based on chronological age rather than global health status.
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38.
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39.
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40.
  • Garmo, H (författare)
  • Asymptotic properties of the connectivity number of random railways
  • 1999
  • Ingår i: ADVANCES IN APPLIED PROBABILITY. - : APPLIED PROBABILITY TRUST. - 0001-8678. ; 31:3, s. 720-741
  • Tidskriftsartikel (refereegranskat)abstract
    • In a cubic multigraph certain restrictions on the paths are made to define what is called a railway. On the tracks in the railway ledges in the multigraph) an equivalence relation is defined. The number of equivalence classes induced by this relation is i
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41.
  • Garmo, H (författare)
  • Random railways modeled as random 3-regular graphs
  • 1996
  • Ingår i: RANDOM STRUCTURES & ALGORITHMS. - : JOHN WILEY & SONS LTD. ; 9:1-2, s. 113-136
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • In a cubic multigraph certain restrictions on the paths are made. Due to these restrictions a special kind of connectivity is defined. The asymptotic probability of this connectivity is calculated in a random cubic multigraph and is shown to be 1/3. (C) 1
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42.
  • Garmo, H (författare)
  • The asymptotic distribution of long cycles in random regular graphs
  • 1999
  • Ingår i: RANDOM STRUCTURES & ALGORITHMS. - : JOHN WILEY & SONS LTD. ; 15:1, s. 43-92
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • The asymptotic distribution of the number of cycles of length l in a random r-regular graph is determined. The length of the cycles is defined as a function of the number of vertices n, thus l = l(n), and the length satisfies l(n) --> infinity as n --> in
  •  
43.
  • Glimelius, Bengt, et al. (författare)
  • Prediction of irinotecan and 5-fluorouracil toxicity and response in patients with advanced colorectal cancer
  • 2011
  • Ingår i: The Pharmacogenomics Journal. - : Springer Science and Business Media LLC. - 1470-269X .- 1473-1150. ; 11:1, s. 61-71
  • Tidskriftsartikel (refereegranskat)abstract
    • Irinotecan and 5-fluorouracil (5-FU) are used to treat metastatic colorectal cancer. Irinotecan's active metabolite is inactivated by UDP-glucuronosyltransferase 1A1 (UGT1A1), which is deficient in Gilbert's syndrome. Irinotecan and metabolites are transported by P-glycoprotein, encoded by ABCB1. 5-FU targets folate metabolism through inhibition of thymidylate synthase (TYMS). Methylenetetrahydrofolate reductase (MTHFR) generates active folate necessary for haematopoiesis. We retrospectively genotyped 140 Swedish and Norwegian irinotecan and 5-FU-treated colorectal cancer patients from the Nordic VI clinical trial for selected variants of UGT1A1, ABCB1, TYMS and MTHFR. We found an increased risk of clinically relevant early toxicity in patients carrying the ABCB1 3435 T/T genotype, Odds ratio (OR)=3.79 (95% confidence interval (CI)=1.09-13.2), and in patients carrying the UGT1A1(*)28/(*)28 genotype, OR=4.43 (95% CI=1.30-15.2). Patients with UGT1A1(*)28/(*)28 had an especially high risk of neutropenia, OR=6.87 (95% CI=1.70-27.7). Patients who had reacted with toxicity during the first two cycles were in total treated with fewer cycles (P<0.001), and less often responded to treatment (P<0.001). Genetic variation in ABCB1 was associated with both early toxicity and lower response to treatment. Carriers of the ABCB1 1236T-2677T-3435T haplotype responded to treatment less frequently (43 vs 67%, P=0.027), and survived shorter time, OR=1.56 (95% CI=1.01-2.45).
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44.
  • Holmberg, Lars, et al. (författare)
  • Mammography casting-type calcification and risk of local recurrence in DCIS: analyses from a randomised study
  • 2013
  • Ingår i: British Journal of Cancer. - : Cancer Research UK. - 0007-0920 .- 1532-1827. ; 108:4, s. 812-819
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We studied the association between mammographic calcifications and local recurrence in the ipsilateral breast. less thanbrgreater than less thanbrgreater thanMethods: Case-cohort study within a randomised trial of radiotherapy in breast conservation for ductal cancer in situ of the breast (SweDCIS). We studied mammograms from cases with an ipsilateral breast event (IBE) and from a subcohort randomly sampled at baseline. Lesions were classified as a density without calcifications, architectural distortion, powdery, crushed stone-like or casting-type calcifications. less thanbrgreater than less thanbrgreater thanResults: Calcifications representing necrosis were found predominantly in younger women. Women with crushed stone or casting-type microcalcifications had higher histopathological grade and more extensive disease. The relative risk (RR) of a new IBE comparing those with casting-type calcifications to those without calcifications was 2.10 (95% confidence interval (Cl) 0.92-4.80). This risk was confined to in situ recurrences; the RR of an IBE associated with casting-type calcifications on the mammogram adjusted for age and disease extent was 16.4 (95% Cl 2.20-140). less thanbrgreater than less thanbrgreater thanConclusion: Mammographic appearance of ductal carcinoma in situ of the breast is prognostic for the risk of an in situ IBE and may also be an indicator of responsiveness to RT in younger women.
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45.
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46.
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47.
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48.
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49.
  • Lycken, M., et al. (författare)
  • Changes in Characteristics of Men with Lethal Prostate Cancer During the Past 25 Years: Description of Population-based Deaths
  • 2022
  • Ingår i: European Urology Open Science. - Nederländerna : Elsevier BV. - 2666-1691 .- 2666-1683. ; 41, s. 81-87
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Attempts to reduce prostate cancer (PC) mortality require an understanding of temporal changes in the characteristics of men with lethal PC. Objective: To describe the diagnostic characteristics of and time trends for a nationwide population-based cohort of Swedish men who died from PC between 1992 and 2016. Design, setting, and participants: Men with PC as the underlying cause of death from 1992 to 2016 according to the Swedish Cause of Death Register were included in the study. Characteristics at diagnosis were collected via links to other nationwide registries using personal identity numbers. Outcome measurements and statistical analysis: Data on disease duration, age at death, and risk category were analyzed. Missing data for risk categories for men with an early date of PC diagnosis were imputed according to the method of chained equations. Results and limitations: Between 1992 and 2016, age-standardized PC mortality decreased by 25%. Median PC disease duration increased from 3.3 yr (interquartile range [IQR] 1.6-6.3) to 5.9 yr (IQR 2.5-10.3) and the median age at death from PC increased from 78.9 yr (IQR 73.3-84.2) to 82.2 yr (IQR 75.2-87.5). The proportion of men with localized disease at diagnosis who died from PC increased from 34% to 48%, while the rate of distant metastases at diagnosis decreased from 56% to 42%. The rate of distant metastases at diagnosis was highest among the youngest men. Treatment trajectories could not be described owing to the large proportion of missing data before the start of registration in the National Prostate Cancer Registry. Conclusion: Age-standardized PC mortality has decreased substantially since 1992. However, there is still a high proportion of men who die from PC who had localized disease at diagnosis, which indicates that more attention is needed to identify the underlying causes to prevent disease progression. Since the proportion of men with distant metastases at diagnosis remains high, early detection of lethal tumors is essential to further reduce PC mortality. Patient summary: We investigated the characteristics of men who died from prostate cancer in Sweden between 1992 and 2016. We found that men with lethal prostate cancer live longer and are older when they die today in comparison to men who died at the beginning of the study period. However, the proportion of men with distant metastases at diagnosis remains high, which is why early detection of lethal tumors is essential to reduce mortality. (C) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology.
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50.
  • Lycken, Magdalena, et al. (författare)
  • The use of palliative medications before death from prostate cancer: Swedish population-based study with a comparative overview of European data
  • 2018
  • Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 88, s. 101-108
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Symptoms of terminal cancer have previously been reported as under-treated. The aim of this study was to assess the use of palliative medications before death from prostate cancer. Methods: This Swedish register study included men who died from 2009 to 2012 with prostate cancer as the underlying cause of death. We assessed the proportion who collected a prescription of androgen deprivation therapy, non-steroidal anti-inflammatory drugs, paracetamol, opioids, glucocorticoids, antidepressants, anxiolytics and sedative-hypnotics and the differences in treatment related to age, time since diagnosis, educational level, close relatives and comorbidities. Data were collected from 3 years before death from prostate cancer. Results: We included 8326 men. The proportion who received opioids increased from 30% to 72% during the last year of life, and 67% received a strong opioid at the time of death. Antidepressants increased from 13% to 22%, anxiolytics from 9% to 27% and sedative-hypnotics from 21% to 33%. Men without close relatives and older men had lower probability to receive opioids (odds ratio [OR]: 0.56, 95% confidence interval [CI]: 0.47-0.66 for > 85 years versus < 70 years) and (OR 0.78, 95% CI: 0.66-0.92 for unmarried without children versus married with children). Conclusion: Our results represent robust epidemiological data from Sweden for comparison of palliative care quality between countries. The findings indicate that men without close relatives and older men are disadvantaged with respect to the treatment of cancer pain and need closer attention from health care providers and highlight the importance to identify psychological distress in terminal prostate cancer. (C) 2017 Elsevier Ltd. All rights reserved.
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