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  • 1.
    Adjeiwaah, Mary
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Bylund, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Lundman, Josef A.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Thellenberg Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Jonsson, Joakim H.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Medical Radiation Physics, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Quantifying the effect of 3T MRI residual system and patient-induced susceptibility distortions on radiotherapy treatment planning for prostate cancer2018In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 100, no 2, p. 317-324Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate the effect of magnetic resonance system- and patient-induced susceptibility distortions from a 3T scanner on dose distributions for prostate cancers.

    Methods and Materials: Combined displacement fields from the residual system and patient-induced susceptibility distortions were used to distort 17 prostate patient CT images. VMAT dose plans were initially optimized on distorted CT images and the plan parameters transferred to the original patient CT images to calculate a new dose distribution.

    Results: Maximum residual mean distortions of 3.19 mm at a radial distance of 25 cm and maximum mean patient-induced susceptibility shifts of 5.8 mm were found using the lowest bandwidth of 122 Hz per pixel. There was a dose difference of <0.5% between distorted and undistorted treatment plans. The 90% confidence intervals of the mean difference between the dCT and CT treatment plans were all within an equivalence interval of (−0.5, 0.5) for all investigated plan quality measures.

    Conclusions: Patient-induced susceptibility distortions at high field strengths in closed bore magnetic resonance scanners are larger than residual system distortions after using vendor-supplied 3-dimensional correction for the delineated regions studied. However, errors in dose due to disturbed patient outline and shifts caused by patient-induced susceptibility effects are below 0.5%.

  • 2.
    Alexeyev, Oleg
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Bergh, Johanna
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Marklund, Ingrid
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Thellenberg Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wiklund, Fredrik
    Grönberg, Henrik
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Association between the presence of bacterial 16S RNA in prostate specimens taken during transurethral resection of prostate and subsequent risk of prostate cancer (Sweden)2006In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 17, no 9, p. 1127-1133Article in journal (Refereed)
    Abstract [en]

    Objective: To study bacterial 16S RNA in archival prostate samples from 352 patients with benign prostate hyperplasia (BPH) and evaluate whether the presence of bacterial DNA was different in those who later developed prostate cancer (n = 171) and in the matched controls that did not progress to cancer (n = 181).

    Methods: 16S DNA PCR followed by cloning and sequencing the positive samples.

    Results: In 96/352 (27%) of the prostate tissue specimens 16S RNA were detected. Sequence analysis revealed Propionibacterium acnes as the predominant microorganism (23% of 16S RNA positive patients). The second most frequent isolate—Escherichia coli was found in 12 (12%) patients. The other isolates included Pseudomonas sp. (3 patients), Actinomyces sp. (2), Streptococcus mutans (1), Corynebacterium sp. (2),Nocardioides sp. (1), Rhodococcus sp. (1) Veillonella sp. (2). In P. acnes positive samples 62% exhibited severe histological inflammation versus 50% in the bacteria-negative group (p = 0.602). The presence of P. acnes in the prostate was associated with prostate cancer development (OR 2.17, 95% CI 0.77–6.95).

    Conclusions: This study has revealed P. acnes as the most common bacteria in the prostate in BPH. Further studies are needed to clarify its role in contributing to the development of prostatic inflammation and prostate cancer.

  • 3. Andren, O.
    et al.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Falt, A.
    Ulvskog, E.
    Davidsson, S.
    Thellenberg Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hjalm-Eriksson, M.
    Cabazitaxel followed by androgen deprivation therapy (ADT) significantly improves time to progression in patients with newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC): A randomized, open label, phase III, multicenter trial2017In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 28Article in journal (Other academic)
  • 4.
    Björeland, Ulrika
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Jonsson, Joakim
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Alm, Magnus
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Beckman, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Thellenberg-Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Inter-fraction movements of the prostate and pelvic lymph nodes during IGRT2018In: Journal of radiation oncology, ISSN 1948-7894, Vol. 7, no 4, p. 357-366Article in journal (Refereed)
    Abstract [en]

    Objectivities: The aim of this study was to evaluate inter-fraction movements of lymph node regions that are commonly included in the pelvic clinical target volume (CTV) for high-risk prostate cancer patients. We also aimed to evaluate if the movements affect the planning target volumes. Methods: Ten prostate cancer patients were included. The patients underwent six MRI scans, from treatment planning to near end of treatment. The CTV movements were analyzed with deformable registration technique with the CTV divided into sections. The validity of the deformable registration was assessed by comparing the results for individual lymph nodes that were possible to identify in all scans. Results: Using repetitive MRI, measurements showed that areas inside the CTV (lymph nodes) in some extreme cases were as mobile as the prostate and not fixed to the bones. The lymph node volumes closest to the prostate did not tend to follow the prostate motion. The more cranial lymph node volumes moved less, but still independently, and they were not necessarily fixed to the pelvic bones. In 95% of the cases, the lymph node motion in the R-L direction was 2-4mm, in the A-P direction 2-7mm, and in the C-C direction 2-5mm depending on the CTV section. Conclusion: Lymph nodes and prostate were most mobile in the A-P direction, followed by the C-C and R-L directions. This movement should be taken into account when deciding the margins for the planning target volumes (PTV).

  • 5.
    Bovinder Ylitalo, Erik
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Thysell, Elin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Thellenberg-Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lundholm, Marie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Josefsson, Andreas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Brattsand, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Excellent cabazitaxel response in prostate cancer xenografts expressing androgen receptor variant 7 and reversion of resistance development by anti-androgensManuscript (preprint) (Other academic)
  • 6.
    Brynolfsson, Patrik
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nilsson, David
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Torheim, Turid
    Asklund, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Thellenberg Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Garpebring, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Haralick texture features from apparent diffusion coefficient (ADC) MRI images depend on imaging and pre-processing parameters2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 4041Article in journal (Refereed)
    Abstract [en]

    In recent years, texture analysis of medical images has become increasingly popular in studies investigating diagnosis, classification and treatment response assessment of cancerous disease. Despite numerous applications in oncology and medical imaging in general, there is no consensus regarding texture analysis workflow, or reporting of parameter settings crucial for replication of results. The aim of this study was to assess how sensitive Haralick texture features of apparent diffusion coefficient (ADC) MR images are to changes in five parameters related to image acquisition and pre-processing: noise, resolution, how the ADC map is constructed, the choice of quantization method, and the number of gray levels in the quantized image. We found that noise, resolution, choice of quantization method and the number of gray levels in the quantized images had a significant influence on most texture features, and that the effect size varied between different features. Different methods for constructing the ADC maps did not have an impact on any texture feature. Based on our results, we recommend using images with similar resolutions and noise levels, using one quantization method, and the same number of gray levels in all quantized images, to make meaningful comparisons of texture feature results between different subjects.

  • 7.
    Fransson, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing.
    Olofsson, Sebastian
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Thellenberg Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Patient-reported gastrointestinal and genitourinary toxicity after prostate cancer treatment: A comparison between radiotherapy including pelvic nodes and prostate-only radiotherapy2015In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 33, no 7 SArticle in journal (Other academic)
    Abstract [en]

    Background: To evaluate side effects of radiotherapy (RT) including the pelvic nodes in patients with prostate cancer. Methods: 143 patients with high risk prostate cancer (Pca) receiving whole pelvic radiotherapy (WPRT) was matched to a group of 142 patients receiving RT towards the prostate and seminal vesicles only (PORT). Both groups were given 78 Gy towards the prostate and 50 Gy towards the seminal vesicles. The WPRT group also received 50 Gy towards the pelvic nodes. WPRT was given with intensity modulated RT or volumetric modulated arc therapy technique and the group treated towards the prostate and seminal vesicles only was treated with 3-dimensional conformal RT. Gastrointestinal (GI) and genitourinary (GU) side effects were evaluated with patient-reported questionnaires and with the RTOG scale, scored by treating physician, at baseline and one-year after RT. Results: Overall the side effects were mild. At one-year follow up there were significant differences regarding morning urgency, mucus- and blood in stool between the two groups (Table 1). The WPRT group expressed lesser complications in all of these cases. In the RTOG GU and GI scores there were no differences between the groups. About 20% had RTOG grade 2 GU score and 2%/1% had RTOG grade 3 score in the PORT and WPRT groups, respectively. The numbers for RTOG grade 2 GI scores were 11% and 5% in the PORT and WPRT groups, respectively. None of the groups reported RTOG grade 3 GI symptoms. Conclusions: Whole pelvic RT can be done with a very satisfying profile of side effects. Sometimes even lesser gastrointestinal reported side effects are seen with the newer techniques compared to prostate only radiotherapy with older techniques.

  • 8.
    Fridriksson, Jón O.
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Folkvaljon, Yasin
    Nilsson, Per
    Robinson, David
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Urology, Ryhov Hospital, J€onk€oping, Sweden.
    Franck-Lissbrant, Ingela
    Ehdaie, Behfar
    Eastham, James A.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Karlsson, Camilla T.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Long-term adverse effects after curative radiotherapy and radical prostatectomy: population-based nationwide register study2016In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 50, no 5, p. 338-345Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to assess the risk of serious adverse effects after radiotherapy (RT) with curative intention and radical prostatectomy (RP).

    Materials and methods: Men who were diagnosed with prostate cancer between 1997 and 2012 and underwent curative treatment were selected from the Prostate Cancer data Base Sweden. For each included man, five prostate cancer-free controls, matched for birth year and county of residency, were randomly selected. In total, 12,534 men underwent RT, 24,886 underwent RP and 186,624 were controls. Adverse effects were defined according to surgical and diagnostic codes in the National Patient Registry. The relative risk (RR) of adverse effects up to 12 years after treatment was compared to controls and the risk was subsequently compared between RT and RP in multivariable analyses.

    Results: Men with intermediate- and localized high-risk cancer who underwent curative treatment had an increased risk of adverse effects during the full study period compared to controls: the RR of undergoing a procedures after RT was 2.64 [95% confidence interval (CI) 2.56–2.73] and after RP 2.05 (95% CI 2.00–2.10). The risk remained elevated 10–12 years after treatment. For all risk categories of prostate cancer, the risk of surgical procedures for urinary incontinence was higher after RP (RR 23.64, 95% CI 11.71–47.74), whereas risk of other procedures on the lower urinary tract and gastrointestinal tract or abdominal wall was higher after RT (RR 1.67, 95% CI 1.44–1.94, and RR 1.86, 95% CI 1.70–2.02, respectively).

    Conclusion: The risk of serious adverse effects after curative treatment for prostate cancer remained significantly elevated up to 12 years after treatment.

  • 9. Glimelius, Bengt
    et al.
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Enblad, Gunilla
    Alafuzoff, Irina
    Beskow, Anna
    Ahlström, Håkan
    Bill-Axelson, Anna
    Birgisson, Helgi
    Björ, Ove
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Edqvist, Per-Henrik
    Hansson, Tony
    Helleday, Thomas
    Hellman, Per
    Henriksson, Kerstin
    Hesselager, Göran
    Hultdin, Magnus
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Häggman, Michael
    Höglund, Martin
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Larsson, Chatarina
    Lindman, Henrik
    Ljuslinder, Ingrid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Mindus, Stephanie
    Nygren, Peter
    Pontén, Fredrik
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Rosenquist, Richard
    Sandin, Fredrik
    Schwenk, Jochen M.
    Stenling, Roger
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Stålberg, Karin
    Stålberg, Peter
    Sundström, Christer
    Thellenberg Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Westermark, Bengt
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Claesson-Welsh, Lena
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Sjöblom, Tobias
    U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden2018In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 2, p. 187-194Article in journal (Refereed)
    Abstract [en]

    Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umea Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population.

    Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data.

    Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort.

    Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.

  • 10. Gronlund, Eric
    et al.
    Johansson, Silvia
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Thellenberg, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Ahnesjo, Anders
    Dose painting of prostate cancer based on Gleason score correlations with apparent diffusion coefficients2018In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 5, p. 574-581Article in journal (Refereed)
    Abstract [en]

    Background: Gleason scores for prostate cancer correlates with an increased recurrence risk after radiotherapy (RT). Furthermore, higher Gleason scores correlates with decreasing apparent diffusion coefficient (ADC) data from diffusion weighted MRI (DWI-MRI). Based on these observations, we present a formalism for dose painting prescriptions of prostate volumes based on ADC images mapped to Gleason score driven dose-responses.

    Methods: The Gleason score driven dose-responses were derived from a learning data set consisting of pre-RT biopsy data and post-RT outcomes for 122 patients treated with a homogeneous dose to the prostate. For a test data set of 18 prostate cancer patients with pre-RT ADC images, we mapped the ADC data to the Gleason driven dose-responses by using probability distributions constructed from published Gleason score correlations with ADC data. We used the Gleason driven dose-responses to optimize dose painting prescriptions that maximize the tumor control probability (TCP) with equal average dose as for the learning sets homogeneous treatment dose.

    Results: The dose painting prescriptions increased the estimated TCP compared to the homogeneous dose by 0–51% for the learning set and by 4–30% for the test set. The potential for individual TCP gains with dose painting correlated with increasing Gleason score spread and larger prostate volumes. The TCP gains were also found to be larger for patients with a low expected TCP for the homogeneous dose prescription.

    Conclusions: We have from retrospective treatment data demonstrated a formalism that yield ADC driven dose painting prescriptions for prostate volumes that potentially can yield significant TCP increases without increasing dose burdens as compared to a homogeneous treatment dose. This motivates further development of the approach to consider more accurate ADC to Gleason mappings, issues with delivery robustness of heterogeneous dose distributions, and patient selection criteria for design of clinical trials.

  • 11. Gunnlaugsson, Adalsteinn
    et al.
    Kjellen, Elisabeth
    Hagberg, Oskar
    Thellenberg-Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nilsson, Per
    Change in prostate volume during extreme hypo-fractionation analysed with MRI2014In: Radiation Oncology, ISSN 1748-717X, E-ISSN 1748-717X, Vol. 9, p. 22-Article in journal (Refereed)
    Abstract [en]

    Background: Hypo-fractionated external beam radiotherapy with narrow CTV-PTV margins is increasingly applied for prostate cancer. This demands a precise target definition and knowledge on target location and extension during treatment. It is unclear how increase in fraction size affects changes in prostate volume during treatment. Our aim was to study prostate volume changes during extreme hypo-fractionation (7 x 6.1 Gy) by using sequential MRIs. Methods: Twenty patients treated with extreme hypo-fractionation were recruited from an on-going prospective randomized phase III trial. An MRI scan was done before start of treatment, at mid treatment and at the end of radiotherapy. The prostate was delineated at each MRI and the volume and maximum extension in left-right, anterior-posterior and cranial-caudal directions were measured. Results: There was a significant increase in mean prostate volume (14%) at mid treatment as compared to baseline. The prostate volume remained enlarged (9%) at the end of radiotherapy. Prostate swelling was most pronounced in the anterior-posterior and cranial-caudal directions. Conclusions: Extreme hypo-fractionation induced a significant prostate swelling during treatment that was still present at the time of last treatment fraction. Our results indicate that prostate swelling is an important factor to take into account when applying treatment margins during short extreme hypo-fractionation, and that tight margins should be applied with caution.

  • 12.
    Karlsson Thellenberg, Camilla
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wiklund, Fredrik
    Grönberg, Henrik
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Risk of prostate cancer after trans urethral resection of BPH: a cohort and nested case-control study2011In: Cancers, ISSN 2072-6694, Vol. 3, no 4, p. 4127-4138Article in journal (Refereed)
    Abstract [en]

    Epidemiological and experimental evidence suggests that inflammation plays a role in both prostate cancer (PCa) and benign prostate hyperplasia (BPH). This study evaluates the risk of PC after transurethral resection (TURP) for BPH and estimates the PCa risk related to presence of inflammation in the resected material. The Pathology Department at the University Hospital of Umea (Umea, Sweden) identified BPH cases (n = 7,901) that underwent TURP between 1982 and 1997. Using these pathological specimens, we compared the incidence of PCa in the cohort to the population and calculated the standardized incidence and mortality ratios (SIR and SMR). Inflammation, the androgen receptor (AR), and p53 were evaluated in a nested case-control study of 201 cases and controls. Inflammation was graded severe or mild-moderate. In the follow-up period after TURP, cases developed prostate cancer and the controls did not. After TURP, SIR for prostate cancer increased [1.26, CI 95% (1.17–1.35)], whereas SMR decreased [0.59, CI 95% (0.47–0.73)]. Presence of inflammation at the time of TURP did not differ between cases and controls nor were there differences in p53 or AR staining. The data suggest a small increased risk of PCa after TURP and decreased PCa mortality. Inflammation at the time of TURP is not associated with PCa risk in this material. The increased PCa risk may be attributed to increased surveillance and PSA screening.

  • 13. 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.

  • 14.
    Lundman, Josef Axel
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Bylund, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Garpebring, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Thellenberg Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Patient-induced susceptibility effects simulation in magnetic resonance imaging2017In: Physics and Imaging in Radiation Oncology, ISSN 2405-6316, Vol. 1, p. 41-45Article in journal (Refereed)
    Abstract [en]

    Background and purpose A fundamental requirement for safe use of magnetic resonance imaging (MRI) in radiotherapy is geometrical accuracy. One factor that can introduce geometrical distortion is patient-induced susceptibility effects. This work aims at developing a method for simulating these distortions. The specific goal being to help objectively identifying a balanced acquisition bandwidth, keeping these distortions within acceptable limits for radiotherapy.

    Materials and methods A simulation algorithm was implemented in Medical Interactive Creative Environment (MICE). The algorithm was validated by comparison between simulations and analytical solutions for a cylinder and a sphere. Simulations were performed for four body regions; neck, lungs, thorax with the lungs excluded, and the pelvic region. This was done using digital phantoms created from patient CT images, after converting the CT Hounsfield units to magnetic susceptibility values through interpolation between known values.

    Results The simulations showed good agreement with analytical solutions, with only small discrepancies due to pixelation of the phantoms. The calculated distortions in digital phantoms based on patient CT data showed maximal 95th percentile distortions of 39%, 32%, 28%, and 25% of the fat-water shift for the neck, lungs, thorax with the lungs excluded, and pelvic region, respectively.

    Conclusions The presented results show the expected pixel distortions for various body parts, and how they scale with bandwidth and field strength. This information can be used to determine which bandwidth is required to keep the patient-induced susceptibility distortions within an acceptable range for a given field strength.

  • 15. Nilsson, Sten
    et al.
    Lindberg, Henriette
    Thellenberg-Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nyman, Claes
    Marquez, Marcela
    Lennartsson, Lena
    Blom, Rene
    Castellanos, Enrique
    Holmberg, Anders R
    Efficacy of a novel cytotoxic polybisphosphonate for treatment of bone metastasis in castration-resistant prostate cancer (CRPC)2015In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 33, no 15, suppl., article id e16065Article in journal (Other academic)
  • 16. Nilsson, Sten
    et al.
    Lindberg, Henriette
    Thellenberg-Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nyman, Claes
    Marquez, Marcela
    Lennartsson, Lena
    Blom, Rene
    Castellanos, Enrique
    Holmberg, Anders R.
    Efficacy of a novel cytotoxic polybisphosphonate for treatment of bone metastasis in castration-resistant prostate cancer (CRPC)2015In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 33, no 7 SArticle in journal (Other academic)
  • 17.
    Sandgren, Kristina
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Westerlinck, Philippe
    Jonsson, Joakim H
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Blomqvist, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Thellenberg Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Department of Immunology, Genetics, and Pathology, Medical Radiation Science, Uppsala University, Uppsala, Sweden.
    Dirix, Piet
    Imaging for the Detection of Locoregional Recurrences in Biochemical Progression After Radical Prostatectomy: A Systematic Review2017In: European Urology Focus, ISSN 2405-4569Article, review/survey (Refereed)
    Abstract [en]

    Context: Local and regional recurrence after radical prostatectomy (RP) can be treated using salvage radiotherapy (SRT). If the recurrence can be delineated on diagnostic imaging, this could allow for increasingly individualized SRT.

    Objective: This systematic review aimed at evaluating the evidence regarding the usefulness of positron emission tomography (PET) and magnetic resonance imaging (MRI) in identifying local and regional recurrences, with the aim to further individualize the SRT treatment.

    Evidence acquisition: A systematic PubMed/Medline search was conducted in December 2015. Studies included were imaging studies of post-RP patients focusing on local and/or regional recurrence where sensitivity and specificity of MRI or PET were the primary end points. Only studies using biopsy, other histological analysis, and/or treatment follow-up as reference standard were included. Quality Assessment of Diagnostic Accuracy Studies-2 was used to score the study quality. Twenty-five articles were deemed of sufficient quality and included in the review.

    Evidence synthesis: [11C]Acetate had the highest pooled sensitivity (92%), while [11C]choline and [18F]choline had pooled sensitivities of 71% and 84%, respectively. The PET tracer with highest pooled specificity was [11C]choline (86%). Regarding MRI, MR spectroscopy combined with dynamic contrast enhanced (DCE) MRI showed the highest pooled sensitivity (89%). High pooled sensitivities were also seen using multiparametric MRI (84%), diffusion-weighted MRI combined with T2-weigthed (T2w) imaging (82%), and DCE MRI combined with T2w imaging (82%). These also showed high pooled specificities (85%, 89%, and 92%, respectively).

    Conclusions: Both MRI and PET have adequate sensitivity and specificity for the detection of prostate cancer recurrences post-RP. Multiparametric MRI, using diffusion-weighted and/or DCE imaging, and the choline-labeled tracers showed high pooled sensitivity and specificity, although their ranges were broad.

    Patient summary: After reviewing imaging studies of recurrent prostate cancer after prostatectomy, we concluded that choline positron emission tomography and diffusion-weighted magnetic resonance imaging can be proposed as the current standard, with high sensitivity and specificity.

  • 18. Sartor, O.
    et al.
    Heinrich, D.
    Mariados, N.
    Mendez Vidal, M. J.
    Keizman, D.
    Thellenberg Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Peer, A.
    Procopio, G.
    Frank, S. J.
    Pulkkanen, K.
    Rosenbaum, E.
    Severi, S.
    Trigo Perez, J. M.
    Wagner, V.
    Li, R.
    Nordquist, L. T.
    Re-treatment with radium-223: first experience from an international, open-label, phase I/II study in patients with castration-resistant prostate cancer and bone metastases2017In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 28, no 10, p. 2464-2471Article in journal (Refereed)
    Abstract [en]

    Background: Six radium-223 injections at 4-week intervals is indicated for patients with castration-resistant prostate cancer and symptomatic bone metastases. However, patients usually develop disease progression after initial treatment. This prospective phase I/II study assessed re-treatment safety and efficacy of up to six additional radium-223 injections. Patients and methods: Patients had castration-resistant prostate cancer and bone metastases and six initial radium-223 injections with no on-treatment bone progression; all had subsequent radiologic or clinical progression. Concomitant agents were allowed at investigator discretion, excluding chemotherapy and initiation of new abiraterone or enzalutamide. The primary endpoint was safety; additional exploratory endpoints included time to radiographic bone progression, time to total alkaline phosphatase and prostate-specific antigen progression, radiographic progression-free survival, overall survival, time to first symptomatic skeletal event (SSE), SSE-free survival, and time to pain progression. Results: Among 44 patients, 29 (66%) received all six re-treatment injections. Median time from end of initial radium-223 treatment was 6 months. Forty-one (93%) reported >= 1 treatment-emergent adverse event. No grade 4-5 hematologic treatment-emergent adverse events occurred. Only one (2%) patient had radiographic bone progression; eight (18%) had radiographic soft tissue tumor progression (three lymph node and five visceral metastases). Median times to total alkaline phosphatase and prostate-specific antigen progression were not reached and 2.2 months, respectively. Median radiographic progression-free survival was 9.9 months (12.8-month maximum follow-up). Five (11%) patients died and eight (18%) experienced first SSEs. Median overall survival, time to first SSE, and SSE-free survival were not reached. Five (14%) of 36 evaluable patients (baseline worst pain score <= 7) had pain progression. After 2 years of follow-up, 28 (64%) patients died, and the median overall survival was 24.4 months. Conclusions: Re-treatment with a second course of six radium-223 injections after disease progression is well tolerated, with minimal hematologic toxicity and low radiographic bone progression rates in this small study with limited follow-up. Favorable safety and early effects on disease progression indicate that radium-223 re-treatment is feasible and warrants further evaluation in larger prospective trials.

  • 19. Schwartz, A.
    et al.
    Sartor, O.
    Mariados, N.
    Casas, J. A. Vallejo
    Thellenberg Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Peer, A.
    Procopio, G.
    Frank, S. J.
    Pulkkanen, K.
    Severi, S.
    Perez, J. M. Trigo
    Li, R.
    Garcia-Vargas, J.
    Keizman, D.
    Re-treatment of Radium-223 From an International, Multicenter, Prospective, Single-Arm Trial in Patients With Castration-Resistant Prostate Cancer and Bone Metastases2016In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 43, p. S104-S104Article in journal (Refereed)
  • 20.
    Strandberg, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Karlsson, Camilla Thellenberg
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sundström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Ögren, Mattias
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Ögren, Margareta
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    11C-acetate PET/CT in pre-therapeutic lymph node staging in high-risk prostate cancer patients and its influence on disease management: a retrospective study2014In: EJNMMI Research, ISSN 2191-219X, E-ISSN 2191-219X, Vol. 4, no 55, p. 1-9Article in journal (Refereed)
    Abstract [en]

    Background: Radiation treatment with simultaneous integrated boost against suspected lymph node metastases may be a curative therapeutic option in patients with high-risk prostate cancer (> 15% estimated risk of pelvic lymph node metastases according to the Cagiannos nomogram). C-11-acetate positron emission tomography/computed tomography (PET/CT) can be used for primary staging as well as for detection of suspected relapse of prostate cancer. The aims of this study were to evaluate the association between positive C-11-acetate PET/CT findings and the estimated risk of pelvic lymph node metastases and to assess the impact of C-11-acetate PET/CT on patient management in high-risk prostate cancer patients. Methods: Fifty consecutive prostate cancer patients referred for primary staging with C-11-acetate PET/CT prior to radiotherapy with curative intention were enrolled in this retrospective study. Results: All patients showed increased C-11-acetate uptake in the prostate. Pelvic lymph node uptake was seen in 42% (21/50) of the patients, with positive external iliac lymph nodes in 71% (15/21) of these. The overall observed proportion of PET/CT-positive pelvic lymph nodes at patient level was higher than the average estimated risk, especially in low-risk groups (< 15%). There was a significant association between observed proportion and estimated risk of pelvic lymph node metastases in groups with <= 45 and >45% estimated risk. Treatment strategy was altered due to C-11-acetate PET/CT findings in 43% (20/47) of the patients. Conclusions: The observed proportion of C-11-acetate PET/CT findings suggestive of locoregional metastases was higher than the estimated risk, suggesting that the Cagiannos nomogram underestimates the risk for metastases. The imaging results with C-11-acetate PET/CT have a considerable impact on patient management.

  • 21.
    Strandberg, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Karlsson, Camilla Thellenberg
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Ögren, Mattias
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    C-11-Acetate-PET/CT Compared to Tc-99m-HDP Bone Scintigraphy in Primary Staging of High-risk Prostate Cancer2016In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 36, no 12, p. 6475-6479Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of this study was to evaluate the detection rate of bone metastases and the added value of C-11-acetate (ACE) positron-emission tomography/computed tomography (PET/CT) compared to bone scintigraphy (BS) in high-risk prostate cancer (PC). Materials and Methods: A total of 66 untreated patients with high-risk PC with ACE-PET/CT and planar BS findings within 3 months of each other were retrospectively enrolled. Findings were compared and verified with follow-up data after an average of 26 months. Results: The rate of detection of bone metastases was superior with ACE-PET/CT compared to BS (p<0.01). Agreement between the methods and between BS and follow-up was moderate (Cohen's kappa coefficient of 0.64 and 0.66, respectively). Agreement between ACE-PET/CT and follow-up was excellent (kappa coefficient of 0.95). Therapy was changed in 11% of patients due to ACE-PET/CT results. Conclusion: ACE-PET/CT performed better than planar BS in detection of bone metastases in high-risk PC. ACE-PET/CT findings influenced clinical management.

  • 22.
    Strandberg, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Thellenberg Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Åhlström Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Unexpected Findings in C-11-acetate-PET/CT in Prostate Cancer Patients2014In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 41, no suppl 2, p. S386-S386, article id P099Article in journal (Other academic)
  • 23.
    Thellenberg Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Prostate cancer: epidemiological studies of risk factors2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In spite of the fact that prostate cancer is the most common male cancer in both Sweden and many other countries in the developed world, little is known of risk factors and predisposing conditions. The only well recognized risk factors are age, race and familial aggregation. More knowledge about risk factors could lead to better preventive measures together with better treatments.

    One way to evaluate this is to study second primary cancers; the connection between two different cancers can give valuable insight in etiology or clues to shared risk factors. This thesis aims at evaluating risk factors for prostate cancer.

    We constructed a cohort of 135,713 men diagnosed with prostate cancer and reported to the Swedish Cancer Registry 1958-1996. The cohort was followed for second primary cancers and a doubled risk of male breast cancer was found. We also noted increased risks for small intestine cancers and melanoma.

    As a follow-up on the increased risk of male breast cancer, we performed a nested case – control study. Included cases were men with first prostate and then breast cancer (n = 41) matched to men with only prostate cancer (n =81). For these men, we collected medical records and extracted data regarding treatment. Furthermore, all men diagnosed with both prostate and breast cancer irrespective which came first (n = 83) were used as probands. To both these sets of cases with breast and prostate cancer, we identified first degree relatives and grandchildren from parish offices throughout Sweden. Linking to the Cancer Registry retrieved all cancer diagnoses amongst relatives. Results from this study show a relation between estrogen treatment of prostate cancer and the risk of developing breast cancer. We also found that a small part of the cases with both cancers appeared in families with inheritance patterns possibly attributed to BRCA2.

    As estrogen treatment seemed involved in increased risk of breast cancer after prostate cancer, we wanted to investigate the newly discovered Estrogen receptor β and the relation to prostate cancer risk. Previous reports have shown that ERβ acts as a negative regulator of proliferation. ERβ expression occurs mainly in prostatic epithelial cells and the expression gradually diminishes when cancer develops and aggravates. We used a single nucleotide polymorphism (SNP) association study approach to evaluate genetic variation in ERβ as a risk factor for prostate cancer. One SNP, located in the promoter region associated with a small increased risk of prostate cancer whereas variation in the rest of the gene did not.

    In the last paper, we investigated trans-urethral resection (TURP) of the prostate due to benign prostate hyperplasia (BPH) as a risk factor for later development of prostate cancer. Evidence has gathered that both BPH and prostate cancer are associated to inflammation. By comparing incidence and mortality in a cohort of 7,901 men with the general population there appeared to be an increased risk of prostate cancer but decreased mortality. Analyzing this increased risk further, we conducted a nested case - control study with men extracted from the cohort. Cases had a TURP and later developed prostate cancer and controls just had a TURP. We then evaluated the specimens from TURP regarding extent of inflammation, degree of androgen receptor down regulation and expression of p53, all factors previous associated with prostate cancer. None of these parameters differed between cases and controls and they can therefore not explain the increased risk. Decreased mortality but increased risk might be explained by surveillance bias, which means more medical attention to these patients, resulting in diagnosing clinically non-significant cancers.

    In summary, our results show a doubled risk of male breast cancer following prostate cancer. A risk that can be attributed to the use of estrogen to treat prostate cancer or to some extent a possible mutation in BRCA2. We also propose that a SNP change in the ERβ promoter confer a small increased risk of prostate cancer. A small risk elevation of prostate cancer following TURP most probable could depend on surveillance bias.

  • 24.
    Thellenberg Karlsson, Camilla
    et al.
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology. Onkologi.
    Lindström, Sara
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology. Onkologi.
    Malmer, Beatrice
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology. Onkologi.
    Wiklund, Fredrik
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology. Onkologi.
    Augustsson-Bälter, Katarina
    Adami, Hans-Olov
    Stattin, Pär
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Urology and Andrology. Urologi och andrologi.
    Nilsson, Maria
    Dahlman-Wright, Karin
    Gustafsson, Jan-Åke
    Grönberg, Henrik
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology. Onkologi.
    Estrogen receptor beta polymorphism is associated with prostate cancer risk2006In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 12, no 6, p. 1936-1941Article in journal (Refereed)
  • 25.
    Thellenberg Karlsson, Camilla
    et al.
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology. Onkologi.
    Malmer, Beatrice
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology. Onkologi.
    Wiklund, Fredrik
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology. Onkologi.
    Grönberg, Henrik
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology. Onkologi.
    Breast cancer as a second primary in patients with prostate cancer: estrogen treatment or association with family history of cancer?2006In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 176, no 2, p. 538-543Article in journal (Refereed)
  • 26.
    Thellenberg-Karlsson, Camilla
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Fridriksson, Jon
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Folkvaljon, Yasin
    Nilsson, Per
    Robinson, David
    Lissbrant, Ingela Franck
    Ehdaie, Behdar
    Eastham, James Andrew
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Lag time to adverse events after radical prostatectomy and curative radiotherapy2015In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 33, no 7 SArticle in journal (Other academic)
  • 27.
    Thellenberg-Karlsson, Camilla
    et al.
    Norrlands University Hospital, Umeå, Sweden.
    Nyman, Claes
    Nilsson, Sten
    Blom, René
    Márquez, Marcela
    Castellanos, Enrique
    Holmberg, Anders R
    Bone-targeted Novel Cytotoxic Polybisphosphonate Conjugate in Castration-resistant Prostate Cancer: A Multicenter Phase 1 Study2016In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 36, no 12, p. 6499-6504Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Osteodex (ODX) is a cytotoxic bone-targeting polybisphosphonate, intended for treatment of bone metastasis from castration-resistant prostate cancer (CRPC). The primary objective of this study was to describe the tolerability and toxicity of such treatment by defining its maximum tolerated dose (MTD) and dose-limiting toxicity (DLT).

    PATIENTS AND METHODS: Twenty-eight patients with castration-resistant prostate cancer and confirmed bone metastasis were assigned to seven infusions of ODX every third week, divided in seven ascending dose cohorts.

    RESULTS: No DLT's were observed and as pre-specified, the highest dose administered was defined as MTD. In total, 206 adverse events (AE) were recorded and 13,6% were classified as treatment-related, while none were serious or severe (SAE). No cumulative toxicity and no renal toxicity were recorded.

    CONCLUSION: ODX was well tolerated, with few and mild side-effects and with apparent treatment efficacy in the highest dose cohort. Further clinical development is currently in progress.

  • 28.
    Tjon-Kon-Fat, Lee-Ann
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lundholm, Marie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Schröder, Mona
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wurdinger, Thomas
    Thellenberg-Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Nilsson, Rolf Jonas Andreas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Platelets harbor prostate cancer biomarkers and the ability to predict therapeutic response to abiraterone in castration resistant patients2018In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 78, no 1, p. 48-53Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Novel therapies for castration resistant prostate cancer (CRPC) have been introduced in the clinic with possibilities for individualized treatment plans. Best practice of those expensive drugs requires predictive biomarker monitoring. This study used circulating biomarker analysis to follow cancer-derived transcripts implicated in therapy resistance.

    METHOD: The isolated platelet population of blood samples and digital-PCR were used to identify selected biomarker transcripts in patients with CRPC prior chemo- or androgen synthesis inhibiting therapy.

    RESULTS: Fifty patients received either docetaxel (n = 24) or abiraterone (n = 26) therapy, with therapy response rates of 54% and 48%, respectively. Transcripts for the PC-associated biomarkers kallikrein-related peptidase-2 and -3 (KLK2, KLK3), folate hydrolase 1 (FOLH1), and neuropeptide-Y (NPY) were uniquely present within the platelet fraction of cancer patients and not detected in healthy controls (n = 15). In the abiraterone treated cohort, the biomarkers provided information on therapy outcome, demonstrating an association between detectable biomarkers and short progression free survival (PFS) (FOLH1, P < 0.01; KLK3, P < 0.05; and NPY, P < 0.05). Patients with biomarker-negative platelets had the best outcome, while FOLH1 (P < 0.05) and NPY (P = 0.05) biomarkers provided independent predictive information in a multivariate analysis regarding PFS. KLK2 (P < 0.01), KLK3 (P < 0.001), and FOLH1 (P < 0.05) biomarkers were associated with short overall survival (OS). Combining three biomarkers in a panel (KLK3, FOLH1, and NPY) made it possible to separate long-term responders from short-term responders with 87% sensitivity and 82% specificity.

    CONCLUSION: Analyzing tumor-derived biomarkers in platelets of CRPC patients enabled prediction of the outcome after abiraterone therapy with higher accuracy than baseline serum PSA or PSA response.

  • 29.
    Widmark, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Gunnlaugsson, A.
    Beckman, L.
    Thellenberg-Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hoyer, M.
    Lagerlund, M.
    Fransson, Per
    Umeå University, Faculty of Medicine, Department of Nursing.
    Kindblom, J.
    Ginman, C.
    Johansson, B.
    Seke, M.
    Björnlinger, K.
    Kjellén, E.
    Franzen, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nilsson, P.
    Extreme Hypofractionation versus Conventionally Fractionated Radiotherapy for Intermediate Risk Prostate Cancer: Early Toxicity Results from the Scandinavian Randomized Phase III Trial "HYPO-RT-PC"2016In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 96, no 5, p. 938-939Article in journal (Refereed)
  • 30.
    Widmark, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Gunnlaugsson, A.
    Beckman, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Dept Radiat Sci, Sundsvall, Sweden.
    Thellenberg-Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hoyer, M.
    Lagerlund, M.
    Fransson, P.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Tavelin, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Norman, D. B.
    Kindblom, J.
    Ginman, C.
    Johansson, B.
    Seke, M.
    Bjorlinger, K.
    Agrup, M.
    Kjellen, E.
    Franzén, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nilsson, P.
    Ultrahypofractionation for prostate cancer: Outcome from the Scandinavian phase 3 HYPO-RT-PC trial2018In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 127, p. S314-S314Article in journal (Other academic)
  • 31.
    Widmark, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Gunnlaugsson, Adalsteinn
    Beckman, Lars
    Thellenberg-Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hoyer, Morten
    Lagerlund, Magnus
    Kindblom, Jon
    Ginman, Claes
    Johansson, Bengt
    Björnlinger, Kirsten
    Seke, Mihajl
    Agrup, Måns
    Fransson, Per
    Umeå University, Faculty of Medicine, Department of Nursing.
    Tavelin, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Norman, David
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Anderson, Harald
    Kjellén, Elisabeth
    Franzén, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nilsson, Per
    Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial2019In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 394, no 10196, p. 385-395Article in journal (Refereed)
    Abstract [en]

    Background: Hypofractionated radiotherapy for prostate cancer has gained increased attention due to its proposed high radiation-fraction sensitivity. Recent reports from studies comparing moderately hypofractionated and conventionally fractionated radiotherapy support the clinical use of moderate hypofractionation. To date, there are no published randomised studies on ultra-hypofractionated radiotherapy. Here, we report the outcomes of the Scandinavian HYPO-RT-PC phase 3 trial with the aim to show non-inferiority of ultra-hypofractionation compared with conventional fractionation.

    Methods: In this open-label, randomised, phase 3 non-inferiority trial done in 12 centres in Sweden and Denmark, we recruited men up to 75 years of age with intermediate-to-high-risk prostate cancer and a WHO performance status between 0 and 2. Patients were randomly assigned to ultra-hypofractionation (42·7 Gy in seven fractions, 3 days per week for 2·5 weeks) or conventional fractionated radiotherapy (78·0 Gy in 39 fractions, 5 days per week for 8 weeks). No androgen deprivation therapy was allowed. The primary endpoint was time to biochemical or clinical failure, analysed in the per-protocol population. The prespecified non-inferiority margin was 4% at 5 years, corresponding to a critical hazard ratio (HR) limit of 1·338. Physician-recorded toxicity was measured according to the Radiation Therapy Oncology Group (RTOG) morbidity scale and patient-reported outcome measurements with the Prostate Cancer Symptom Scale (PCSS) questionnaire. This trial is registered with the ISRCTN registry, number ISRCTN45905321.

    Findings: Between July 1, 2005, and Nov 4, 2015, 1200 patients were randomly assigned to conventional fractionation (n=602) or ultra-hypofractionation (n=598), of whom 1180 (591 conventional fractionation and 589 ultra-hypofractionation) constituted the per-protocol population. 1054 (89%) participants were intermediate risk and 126 (11%) were high risk. Median follow-up time was 5·0 years (IQR 3·1–7·0). The estimated failure-free survival at 5 years was 84% (95% CI 80–87) in both treatment groups, with an adjusted HR of 1·002 (95% CI 0·758–1·325; log-rank p=0·99). There was weak evidence of an increased frequency of acute physician-reported RTOG grade 2 or worse urinary toxicity in the ultra-hypofractionation group at end of radiotherapy (158 [28%] of 569 patients vs 132 [23%] of 578 patients; p=0·057). There were no significant differences in grade 2 or worse urinary or bowel late toxicity between the two treatment groups at any point after radiotherapy, except for an increase in urinary toxicity in the ultra-hypofractionation group compared to the conventional fractionation group at 1-year follow-up (32 [6%] of 528 patients vs 13 [2%] of 529 patients; (p=0·0037). We observed no differences between groups in frequencies at 5 years of RTOG grade 2 or worse urinary toxicity (11 [5%] of 243 patients for the ultra-hypofractionation group vs 12 [5%] of 249 for the conventional fractionation group; p=1·00) and bowel toxicity (three [1%] of 244 patients vs nine [4%] of 249 patients; p=0·14). Patient-reported outcomes revealed significantly higher levels of acute urinary and bowel symptoms in the ultra-hypofractionation group compared with the conventional fractionation group but no significant increases in late symptoms were found, except for increased urinary symptoms at 1-year follow-up, consistent with the physician-evaluated toxicity.

    Interpretation: Ultra-hypofractionated radiotherapy is non-inferior to conventionally fractionated radiotherapy for intermediate-to-high risk prostate cancer regarding failure-free survival. Early side-effects are more pronounced with ultra-hypofractionation compared with conventional fractionation whereas late toxicity is similar in both treatment groups. The results support the use of ultra-hypofractionation for radiotherapy of prostate cancer.

    Funding: The Nordic Cancer Union, the Swedish Cancer Society, and the Swedish Research Council.

  • 32.
    Widmark, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Karlsson Thellenberg, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hoppfullt om avancerad cancer, flera nya läkemedel är på väg2012In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, no 8, p. 416-419Article in journal (Refereed)
    Abstract [sv]

    Behandlingen av metastaserad kastrationsresistent pros­tatacancer befinner sig i en mycket stark utvecklingsfas, med flera nya godkända läkemedel.

    Mitoshämmaren docetaxel godkändes redan år 2004.

    Immunterapi enligt en ny princip, sipuleucel-T, godkändes 2010 men är ännu inte tillgänglig i Europa.

    Kabazitaxel har nyligen godkänts för andra linjens behandling efter docetaxel, med 2,4 månaders överlevnadsvinst jämfört med mitoxantron.

    Ett nytt antihormon, abirateron, som visats medföra 4,1 månaders överlevnadsvinst jämfört med prednisolon, god­kändes också under förra året.

  • 33. Wirth, M.
    et al.
    Saad, F.
    Keizman, D.
    O'Sullivan, J. M.
    Carles, J.
    Gillessen, S.
    Thellenberg Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Miller, K.
    Tucci, M.
    Paganelli, G.
    Procopio, G.
    Gratt, J.
    Seger, M.
    Nilsson, S.
    Heinrich, D.
    Analysis of overall survival by number of radium-223 injections received in an international expanded access program (iEAP)2017In: Oncology Research and Treatment, ISSN 2296-5270, Vol. 40, p. 320-320Article in journal (Other academic)
1 - 33 of 33
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