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Umeå, Sweden

Nilsson S.,Karolinska University Hospital | Strang P.,Karolinska Institutet | Aksnes A.K.,Algeta ASA | Franzn L.,Lanssjukhuset | And 7 more authors.
European Journal of Cancer | Year: 2012

Purpose: To investigate the dose-response relationship and pain-relieving effect of radium-223, a highly bone-targeted alpha-pharmaceutical. Methods: One hundred patients with castration-resistant prostate cancer (CRPC) and painful bone metastases were randomized to a single intravenous dose of 5, 25, 50 or 100 kBq/kg radium-223. The primary end-point was pain index (visual analogue scale [VAS] and analgesic use), also used to classify patients as responders or non-responders. Results: A significant dose response for pain index was seen at week 2 (P =.035). At week 8 there were 40%, 63%, 56% and 71% pain responders (reduced pain and stable analgesic consumption) in the 5, 25, 50 and 100 kBq/kg groups, respectively. On the daily VAS, at week 8, pain decreased by a mean of -30, -31, -27 and -28 mm, respectively (P =.008, P =.0005, P =.002, and P <.0001) in these responders (post-hoc analysis). There was also a significant improvement in the brief pain inventory functional index for all dose-groups (P =.04,.01,.002 and.02, Wilcoxon signed rank test). Furthermore, a decrease in bone alkaline phosphatase in the highest dose-group was demonstrated (P =.0067). All doses were safe and well tolerated. Conclusion: Pain response was seen in up to 71% of the patients with a dose response observed 2 weeks after administration. The highly tolerable side-effect profile of radium-223 previously reported was confirmed. © 2011 Elsevier Ltd. All rights reserved.

Sun A.,Uppsala University Hospital | Sun A.,Ume University Hospital | Johansson S.,Uppsala University Hospital | Turesson I.,Uppsala University Hospital | And 2 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2012

Background: A growing body of in vitro evidence links alterations of the intermediary metabolism in cancer to treatment outcome. This study aimed to characterize tumor oxidative metabolism and perfusion in vivo using dynamic positron emission tomography (PET) with 1- [ 11C]-acetate (ACE) during radiotherapy. Methods and Materials: Nine patients with head-and-neck cancer were studied. Oxidative metabolic rate (k mono) and perfusion (rF) of the primary tumors were assessed by dynamic ACE-PET at baseline and after 15, 30, and 55 Gy was delivered. Tumor glucose uptake (Tglu) was evaluated with [ 18F]-fluorodeoxyglucose PET at baseline. Patients were grouped into complete (CR, n = 6) and partial responders (PR, n = 3) to radiotherapy. Results: The 3 PR patients died within a median follow-up period of 33 months. Baseline k mono was almost twice as high in CR as in PR (p = 0.02) and Tglu was lower in CR than in PR (p = 0.04). k mono increased during radiotherapy in PR (p = 0.004) but remained unchanged in CR. There were no differences in rF between CR and PR at any dosage. k mono and rF were coupled in CR (p = 0.001), but not in PR. Conclusions: This study shows that radiosensitive tumors might rely predominantly on oxidative metabolism for their bioenergetic needs. The impairment of oxidative metabolism in radioresistant tumors is potentially reversible, suggesting that therapies targeting the intermediary metabolism might improve treatment outcome. © 2012 Elsevier Inc.

Budaus L.,University of Hamburg | Bolla M.,Center Hospitalier University | Bossi A.,Institute Gustave Roussy | Cozzarini C.,San Raffaele Scientific Institute | And 3 more authors.
European Urology | Year: 2012

Context: Prostate cancer (PCa) patients have many options within the realms of surgery or radiation therapy (RT). Technical advancements in RT planning and delivery have yielded different approaches, such as external beam, brachytherapy, and newer approaches such as image-guided tomotherapy or volumetric-modulated arc therapy. The selection of the optimal RT treatment for the individual is still a point of discussion, and the debate centres on two important outcomes - namely, cancer control and reduction of side-effects. Objective: To critically review and summarise the available literature on functional outcomes and rectal sequelae following RT for PCa treatment. Evidence acquisition: A review of the literature published between 1999 and 2010 was performed using Medline and Scopus search. Relevant reports were identified using the terms prostate cancer, radiotherapy, functional outcomes, external beam radiation, brachytherapy, IMRT, quality of life, and tomotherapy and were critically reviewed and summarised. Evidence synthesis: Related to nonuniform definition of their assessed functional end points and uneven standards of reporting, only a minority of series retrieved could be selected for analyses. Moreover, patterns of patient selection for different types of RT, inherent differences in the RT modalities, and the presence or absence of hormonal treatment also limit the ability to synthesise results from different publications or perform meta-analyses across the different treatment types. Nonetheless, several studies agree that recent technical improvements in the field of RT planning and delivery enable the administration of higher doses with equal or less toxicity. Regardless of the type of RT, the most frequently considered functional end points in the published analyses are gastrointestinal (GI) complications and rectal bleeding. Established risk factors for acute or late toxicities after RT include advanced age, larger rectal volume, a history of prior abdominal surgery, the concomitant use of androgen deprivation, preexisting diabetes mellitus, haemorrhoids, and inflammatory bowel disease (IBD). Similarly, mild acute irritative urinary symptoms are reported in several studies, whereas total urinary incontinence and other severe urinary symptoms are rare. Pretreatment genitourinary complaints, prior transurethral resection of the prostate (TURP), and the presence of acute genitourinary toxicity are suggested as contributing to long-term urinary morbidity. Erectile dysfunction (ED) is not an immediate side-effect of RT, and the occurrence of spontaneous erections before treatment is the best predictor for preserving erections sufficient for intercourse. In addition, the use of magnetic resonance imaging (MRI) permits a reduction in the dose delivered to vascular structures critical for erectile function. Conclusions: In the future, further improvement in RT planning and delivery will decrease side-effects and permit administration of higher doses. Related to the anatomy of the prostate, these higher doses may favour rectal sparing while not readily sparing the urethra and bladder neck. As a consequence, there may be a future shift from dose-limiting long-term rectal morbidity towards long-term urinary morbidity. In the absence of prospective randomised trials comparing different types of surgical and RT-based treatments in PCa, the introduction of validated tools for reporting functional and clinical outcomes is crucial for evaluating and identifying each individual's best treatment choice. © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Isaksson S.,Uppsala University | Skoog Svanberg A.,Uppsala University | Sydsjo G.,Linkoping University | Thurin-Kjellberg A.,Sahlgrenska Academy | And 4 more authors.
Human Reproduction | Year: 2011

Background Two decades after the introduction of Swedish legislation that allows children born as a result of gamete donation access to identifying information about the donor, a nationwide multicentre study on the psychosocial consequences of this legislation for recipients and donors of gametes was initiated in 2005. The aim of the present study was to investigate recipient couples' attitudes and behaviour regarding disclosure to offspring and others, attitudes towards genetic parenthood and perceptions of information regarding parenthood after donation.Methods The present study is part of the prospective longitudinal 'Swedish study on gamete donation, including all fertility clinics performing donation treatment in Sweden. A consecutive cohort of 152 heterosexual recipient couples of donated oocytes (72 response) and 127 heterosexual recipient couples of donated sperm (81 response) accepted participation in the study. In connection with the donation treatment, male and female participants individually completed two questionnaires with study-specific instruments concerning disclosure, genetic parenthood and informational aspects.Results About 90 of participants (in couples receiving anonymous donated gametes) supported disclosure and openness to the offspring concerning his/her genetic origin. Only 6 of all participants had not told other people about their donation treatment. Between 26 and 40 of participants wanted additional information/support about parenthood following donation treatment. Conclusions Two decades after the Swedish legislation of identifiable gamete donors, recipient couples of anonymously donated sperm and oocytes are relatively open about their treatment and support disclosure to offspring. Recipient couples may benefit from more information and support regarding parenthood after gamete donation. Further studies are required to follow-up on the future parents' actual disclosure behaviour directed to offspring. © 2011 The Author.

Sorbe B.,Orebro University | Horvath G.,Sahlgrenska University Hospital | Andersson H.,Sahlgrenska University Hospital | Boman K.,Ume University Hospital | And 2 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2012

Purpose: To evaluate the value of adjuvant external beam pelvic radiotherapy as adjunct to vaginal brachytherapy (VBT) in medium-risk endometrial carcinoma, with regard to locoregional tumor control, recurrences, survival, and toxicity. Methods and Materials: Consecutive series of 527 evaluable patients were included in this randomized trial. Median follow-up for patients alive was 62 months. The primary study endpoints were locoregional recurrences and overall survival. Secondary endpoints were recurrence-free survival, recurrence-free interval, cancer-specific survival, and toxicity. Results: Five-year locoregional relapse rates were 1.5% after external beam radiotherapy (EBRT) plus VBT and 5% after vaginal irradiation alone (p = 0.013), and 5-year overall survival rates were 89% and 90%, respectively (p = 0.548). Endometrial cancer-related death rates were 3.8% after EBRT plus VBT and 6.8% after VBT (p = 0.118). Pelvic recurrences (exclusively vaginal recurrence) were reduced by 93% by the addition of EBRT to VBT. Deep myometrial infiltration was a significant prognostic factor in this medium-risk group of endometrioid carcinomas but not International Federation of Gynecology and Obstetrics grade or DNA ploidy. Combined radiotherapy was well tolerated, with serious (Grade 3) late side effects of less than 2%. However, there was a significant difference in favor of VBT alone. Conclusions: Despite a significant locoregional control benefit with combined radiotherapy, no survival improvement was recorded, but increased late toxicity was noted in the intestine, bladder, and vagina. Combined RT should probably be reserved for high-risk cases with two or more high-risk factors. VBT alone should be the adjuvant treatment option for purely medium-risk cases. © 2012 Elsevier Inc.

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