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  • 1. FitzGerald, L. M.
    et al.
    Zhao, S.
    Leonardson, A.
    Geybels, M. S.
    Kolb, S.
    Lin, D. W.
    Wright, J. L.
    Eeles, R.
    Kote-Jarai, Z.
    Govindasami, K.
    Giles, G. G.
    Southey, M. C.
    Schleutker, J.
    Tammela, T. L.
    Sipeky, C.
    Penney, K. L.
    Stampfer, M. J.
    Gronberg, H.
    Wiklund, F.
    Stattin, P.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Hugosson, J.
    Karyadi, D. M.
    Ostrander, E. A.
    Feng, Z.
    Stanford, J. L.
    Germline variants in IL4, MGMT and AKT1 are associated with prostate cancer-specific mortality: an analysis of 12,082 prostate cancer cases2018In: Prostate Cancer and Prostatic Diseases, ISSN 1365-7852, E-ISSN 1476-5608, Vol. 21, no 2, p. 228-237Article in journal (Refereed)
    Abstract [en]

    Background Prostate cancer (PCa) is a leading cause of mortality and genetic factors can influence tumour aggressiveness. Several germline variants have been associated with PCa-specific mortality (PCSM), but further replication evidence is needed. Methods Twenty-two previously identified PCSM-associated genetic variants were genotyped in seven PCa cohorts (12,082 patients; 1544 PCa deaths). For each cohort, Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals for risk of PCSM associated with each variant. Data were then combined using a meta-analysis approach. Results Fifteen SNPs were associated with PCSM in at least one of the seven cohorts. In the meta-analysis, after adjustment for clinicopathological factors, variants in the MGMT (rs2308327; HR 0.90; p-value = 3.5 x 10(-2)) and IL4 (rs2070874; HR 1.22; p-value = 1.1 x 10(-3)) genes were confirmed to be associated with risk of PCSM. In analyses limited to men diagnosed with local or regional stage disease, a variant in AKT1, rs2494750, was also confirmed to be associated with PCSM risk (HR 0.81; p-value = 3.6 x 10(-2)). Conclusions This meta-analysis confirms the association of three genetic variants with risk of PCSM, providing further evidence that genetic background plays a role in PCa-specific survival. While these variants alone are not sufficient as prognostic biomarkers, these results may provide insights into the biological pathways modulating tumour aggressiveness.

  • 2. Jäderling, Fredrik
    et al.
    Akre, Olof
    Aly, Markus
    Björklund, Johan
    Olsson, Mats
    Adding, Christofer
    Öberg, Michael
    Blomqvist, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden Department of Urology, Karolinska University Hospital, Solna, Sweden.
    Nyberg, Tommy
    Wiklund, Peter
    Carlsson, Stefan
    Preoperative staging using magnetic resonance imaging and risk of positive surgical margins after prostate-cancer surgery2019In: Prostate Cancer and Prostatic Diseases, ISSN 1365-7852, E-ISSN 1476-5608, Vol. 22, no 3, p. 391-398Article in journal (Refereed)
    Abstract [en]

    Background: It is unclear whether preoperative staging using Magnetic Resonance Imaging (MRI) reduces the risk of positive margins in prostate cancer. We aimed to assess the effect on surgical margins and degree of nerve sparing of a pelvic MRI presented at a preoperative MRI conference. Methods: Single institution, observational cohort study including 1037 men that underwent robot assisted radical prostatectomy between October 2013 and June 2015. Of these, 557 underwent a preoperative MRI combined with a preoperative MRI conference and 410 did not. With whole-mount prostate specimen histopathology as gold standard we assessed the ability of MRI in finding the index tumor and the sensitivity and specificity for extra prostatic extension. We calculated relative risks for positive surgical margins and non-nerve sparing procedure, adjusting for preoperative risk factors using stabilized inverse-probability weighting. Results: MRI detected the index tumor in 80% of the cases. Non-organ confined disease (pT3) at histology was present in the MRI and the non-MRI group in 42% and 24%, respectively. Rate of positive surgical margins comparing the MRI and non-MRI groups was 26.7% and 33.7%, respectively, relative risk 0.79 [95% CI 0.65-0.96], weighted relative risk (wRR) 0.69 [95% CI 0.55-0.86]. The wRR of extensive positive surgical margins was 0.45 [95% CI 0.31-0.67]. Undergoing MRI was also associated with an increased risk of being operated with a non-nerve sparing technique (wRR, 1.84 [95% CI 1.11-3.03]). Conclusions: Our study suggests that preoperative prostate MRI in combination with a preoperative MRI conference affects the degree of nerve-sparing surgery and reduces positive surgical margins.

  • 3. Kellokumpu-Lehtinen, P-L
    et al.
    Hjalm-Eriksson, M.
    Thellenberg-Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Astrom, L.
    Franzen, L.
    Marttila, T.
    Seke, M.
    Taalikka, M.
    Ginman, C.
    Toxicity in patients receiving adjuvant docetaxel plus hormonal treatment after radical radiotherapy for intermediate or high-risk prostate cancer: a preplanned safety report of the SPCG-13 trial2012In: Prostate Cancer and Prostatic Diseases, ISSN 1365-7852, E-ISSN 1476-5608, Vol. 15, no 3, p. 303-307Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Radical radiotherapy (RD combined with androgen deprivation therapy is currently the standard treatment for elderly patients with localized intermediate- or high-risk prostate cancer (PC). To increase the recurrence-free and overall survival, we conducted an adjuvant, randomized trial using docetaxel (T) in PC patients (Scandinavian Prostate Cancer Group trial 13). METHODS: The inclusion criteria are the following: men > 18 and <= 75 years of age, WHO/ECOG performance status 0-1, histologically proven PC within 12 months before randomization and one of the following: T2, Gleason 7 (4 + 3), PSA > 10; T2, Gleason 8-10, any PSA; or any T3 tumors. Neoadjuvant/adjuvant hormone therapy is mandatory for all patients. The patients were randomized to receive six cycles of T (75 mg m(-2) d 1. cycle 21 d) or no docetaxel after radical RI (with a minimum tumor dose of 74 Gy). This study identifier number is NTC 006653848 (http://www.clinicaltrials.org). RESULTS: In this preplanned safety analysis of 100 patients, T treatment induced grade (G) 3 adverse events (AEs) in 15 patients (30%) and G4 AEs in 30 patients (60%), mainly due to bone marrow toxicity. Neutropenia G3-4 was observed in 72% of the patients, febrile neutropenia was found in 24% of patients, neutropenic infection in 10% of patients and G3 infection without neutropenia in 4% of patients. Nonhematological G3 AEs were rare: anorexia, diarrhea, mucositis, nausea, pain (1 patient each) and fatigue (5). Other severe serious AEs related to T were pulmonary embolism and renal failure. However, only three patients discontinued T before completing the planned six cycles. No deaths had occurred. No patients in the control arm experienced G3-4 toxicities at 12 weeks after the randomization. CONCLUSIONS: Adjuvant docetaxel chemotherapy after radiotherapy has a higher frequency of neutropenia than previous studies on patients with metastatic disease. Otherwise, the treatment was quite well tolerated.

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