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  • 1.
    Adjeiwaah, Mary
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Bylund, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Lundman, Josef A.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Söderström, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Jonsson, Joakim H.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Garpebring, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Dosimetric Impact of MRI Distortions: A Study on Head and Neck Cancers2019In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 103, no 4, p. 994-1003Article in journal (Refereed)
    Abstract [en]

    Purpose: To evaluate the effect of magnetic resonance (MR) imaging (MRI) geometric distortions on head and neck radiation therapy treatment planning (RTP) for an MRI-only RTP. We also assessed the potential benefits of patient-specific shimming to reduce the magnitude of MR distortions for a 3-T scanner.

    Methods and Materials: Using an in-house Matlab algorithm, shimming within entire imaging volumes and user-defined regions of interest were simulated. We deformed 21 patient computed tomography (CT) images with MR distortion fields (gradient nonlinearity and patient-induced susceptibility effects) to create distorted CT (dCT) images using bandwidths of 122 and 488 Hz/mm at 3 T. Field parameters from volumetric modulated arc therapy plans initially optimized on dCT data sets were transferred to CT data to compute a new plan. Both plans were compared to determine the impact of distortions on dose distributions.

    Results: Shimming across entire patient volumes decreased the percentage of voxels with distortions of more than 2 mm from 15.4% to 2.0%. Using the user-defined region of interest (ROI) shimming strategy, (here the Planning target volume (PTV) was the chosen ROI volume) led to increased geometric for volumes outside the PTV, as such voxels within the spinal cord with geometric shifts above 2 mm increased from 11.5% to 32.3%. The worst phantom-measured residual system distortions after 3-dimensional gradient nonlinearity correction within a radial distance of 200 mm from the isocenter was 2.17 mm. For all patients, voxels with distortion shifts of more than 2 mm resulting from patient-induced susceptibility effects were 15.4% and 0.0% using bandwidths of 122 Hz/mm and 488 Hz/mm at 3 T. Dose differences between dCT and CT treatment plans in D-50 at the planning target volume were 0.4% +/- 0.6% and 0.3% +/- 0.5% at 122 and 488 Hz/mm, respectively.

    Conclusions: The overall effect of MRI geometric distortions on data used for RTP was minimal. Shimming over entire imaging volumes decreased distortions, but user-defined subvolume shimming introduced significant errors in nearby organs and should probably be avoided.

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  • 2.
    Bendsöe, Niels
    et al.
    Skåne University Hospital, Department of Dermatology and Venereology, Lund, Sweden.
    Paoli, John
    Department of Dermatology and Venereology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Region Västra Götaland, Sahlgrenska University Hospital, Department of Dermatology and Venereology, Gothenburg, Sweden.
    Söderkvist, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Persson, Bertil
    Skåne University Hospital, Department of Dermatology and Venereology, Lund, Sweden.
    Halldin, Christina
    Department of Dermatology and Venereology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Region Västra Götaland, Sahlgrenska University Hospital, Department of Dermatology and Venereology, Gothenburg, Sweden.
    Ihrlund, Linda
    Roche AB, Sweden.
    Wolodarski, Maria
    Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden; Theme Cancer, Patient Area Head and Neck, Lung, and Skin, Karolinska University Hospital Solna, Stockholm, Sweden.
    A Non-Interventional Study on Vismodegib for Basal Cell Carcinoma in Swedish Patients2023In: Dermatology Practical and Conceptual, E-ISSN 2160-9381, Vol. 13, no 2, article id e2023211Article in journal (Refereed)
    Abstract [en]

    Introduction: Real-life data on vismodegib in advanced basal cell carcinoma (aBCC) are limited. Optimal treatment duration is left to the discretion of the physician.

    Objectives: To assess the effectiveness, safety and treatment pattern for vismodegib in aBCC in clinical practice.

    Methods: In this multicenter, non-interventional, prospective study, 49 Swedish patients planned for vismodegib treatment were included. The treatment pattern observed was treatment until remission, allowing unlimited discontinuations/pauses.

    Results: The majority of patients (93.8%), discontinued at least once during the study. Compared to earlier studies there was a decrease of more than 2 months with actual drug intake, reducing the patients burden and costs, at the same time as a high number of responses were seen (87.8%). Median progression-free-survival was 16.7 months, and 90% of the patients were alive at 13.3 months. Ten patients were re-challenged with vismodegib at recurrence or progression, resulting in five partial remissions and three complete remissions.

    Conclusions: Clinical response rates with vismodegib for aBCC were comparable to those of similar trials despite a shorter and more intermittent treatment duration. The majority of re-challenges lead to partial or complete remissions.

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  • 3. Bergengren, Oskar
    et al.
    Belozerov, Alexej
    Bill-Axelson, Anna
    Garmo, Hans
    Hagberg, Oskar
    Aljabery, Firas
    Gårdmark, Truls
    Jahnson, Staffan
    Jerlström, Tomas
    Malmström, Per-Uno
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Ströck, Viveka
    Söderkvist, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ullén, Anders
    Holmberg, Lars
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Liedberg, Fredrik
    Short term outcomes after robot assisted and open cystectomy: A nation-wide population-based study2023In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 49, no 4, p. 868-874Article in journal (Refereed)
    Abstract [en]

    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 outcomes 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 multivariable 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.

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  • 4.
    Björeland, Ulrika
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Notstam, Kristina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Fransson, Per
    Umeå University, Faculty of Medicine, Department of Nursing.
    Söderkvist, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Beckman, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Jonsson, Joakim
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    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.
    Hyaluronic acid spacer in prostate cancer radiotherapy: dosimetric effects, spacer stability and long-term toxicity and PRO in a phase II study2023In: Radiation Oncology, E-ISSN 1748-717X, Vol. 18, no 1, article id 1Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Perirectal spacers may be beneficial to reduce rectal side effects from radiotherapy (RT). Here, we present the impact of a hyaluronic acid (HA) perirectal spacer on rectal dose as well as spacer stability, long-term gastrointestinal (GI) and genitourinary (GU) toxicity and patient-reported outcome (PRO).

    METHODS: In this phase II study 81 patients with low- and intermediate-risk prostate cancer received transrectal injections with HA before external beam RT (78 Gy in 39 fractions). The HA spacer was evaluated with MRI four times; before (MR0) and after HA-injection (MR1), at the middle (MR2) and at the end (MR3) of RT. GI and GU toxicity was assessed by physician for up to five years according to the RTOG scale. PROs were collected using the Swedish National Prostate Cancer Registry and Prostate cancer symptom scale questionnaires.

    RESULTS: There was a significant reduction in rectal V70% (54.6 Gy) and V90% (70.2 Gy) between MR0 and MR1, as well as between MR0 to MR2 and MR3. From MR1 to MR2/MR3, HA thickness decreased with 28%/32% and CTV-rectum space with 19%/17% in the middle level. The cumulative late grade ≥ 2 GI toxicity at 5 years was 5% and the proportion of PRO moderate or severe overall bowel problems at 5 years follow-up was 12%. Cumulative late grade ≥ 2 GU toxicity at 5 years was 12% and moderate or severe overall urinary problems at 5 years were 10%.

    CONCLUSION: We show that the HA spacer reduced rectal dose and long-term toxicity.

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  • 5.
    Björeland, Ulrika
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Strandberg, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Söderkvist, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Jonsson, Joakim
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Skorpil, Mikael
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Blomqvist, Lennart
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Beckman, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Thellenberg-Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Diffusion-weighted MRI and 11C-acetate-PET/CT imaging in high-risk/very high-risk prostate cancerManuscript (preprint) (Other academic)
  • 6.
    Flygare, Lennart
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Erdogan, Secil Telli
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Söderkvist, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    PET/MR versus PET/CT for locoregional staging of oropharyngeal squamous cell cancer2023In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 64, no 5, p. 1865-1872Article in journal (Refereed)
    Abstract [en]

    Background: The value of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for TN staging in head and neck cancer (HNC) has been proven in numerous studies. A few studies have investigated the value of FDG-PET/magnetic resonance imaging (MRI) in the staging of HNC; the combined results indicate potential for FDG-PET/MRI, but the scientific evidence remains weak.

    Purpose: To compare performance of FDG-PET/CT and FDG-PET/MRI for locoregional staging in patients with oropharyngeal carcinomas.

    Material and Methods: Two radiologists independently of each other retrospectively reviewed primary pre-therapeutic FDG-PET/CT and FDG-PET/MRI examinations from 40 individuals with oropharyngeal carcinomas. TN stage and primary tumor size were noted. The results were compared between observers and modalities and against TN stage set at a multidisciplinary conference.

    Results: For nodal staging, PET/MRI had slightly higher specificity and accuracy than PET/CT for the most experienced observer. Both methods demonstrated excellent sensitivity (≥ 0.97 and 1.00, respectively), as well as high negative predictive values (≥ 0.95 and 1.00, respectively). No significant differences were found for tumor staging or measurement of maximum tumor diameter. There was a weak agreement (κ = 0.35–0.49) between PET/CT and PET/MRI for T and N stages for both observers. Inter-observer agreement was higher for PET/MRI than for PET/CT, both for tumor staging (κ = 0.57 vs. 0.35) and nodal staging (κ = 0.69 vs. 0.55). The agreement between observers was comparable to the agreement between methods.

    Conclusion: PET/MRI may be a viable alternative to PET/CT for locoregional staging (TN staging) and assessment of maximal tumor diameter in oropharyngeal squamous cell cancer.

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  • 7. Gebre-Medhin, Maria
    et al.
    Brun, Eva
    Engström, Per
    Haugen Cange, Hedda
    Hammarstedt-Nordenvall, Lalle
    Reizenstein, Johan
    Nyman, Jan
    Abel, Edvard
    Friesland, Signe
    Sjödin, Helena
    Carlsson, Henrik
    Söderkvist, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Thomasson, Marcus
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nilsson, Per
    ARTSCAN III: A Randomized Phase III Study Comparing Chemoradiotherapy With Cisplatin Versus Cetuximab in Patients With Locoregionally Advanced Head and Neck Squamous Cell Cancer2021In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 39, no 1, p. 38-47Article in journal (Refereed)
    Abstract [en]

    PURPOSE: We performed an open-label randomized controlled phase III study comparing treatment outcome and toxicity between radiotherapy (RT) with concomitant cisplatin versus concomitant cetuximab in patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC; stage III-IV according to the Union for International Cancer Control TNM classification, 7th edition).

    MATERIALS AND METHODS: Eligible patients were randomly assigned 1:1 to receive either intravenous cetuximab 400 mg/m2 1 week before start of RT followed by 250 mg/m2/wk, or weekly intravenous cisplatin 40 mg/m2, during RT. RT was conventionally fractionated. Patients with T3-T4 tumors underwent a second random assignment 1:1 between standard RT dose 68.0 Gy to the primary tumor or dose escalation to 73.1 Gy. Primary end point was overall survival (OS) evaluated using adjusted Cox regression analysis. Secondary end points were locoregional control, local control with dose-escalated RT, pattern of failure, and adverse effects.

    RESULTS: Study inclusion was prematurely closed after an unplanned interim analysis when 298 patients had been randomly assigned. At 3 years, OS was 88% (95% CI, 83% to 94%) and 78% (95% CI, 71% to 85%) in the cisplatin and cetuximab groups, respectively (adjusted hazard ratio, 1.63; 95% CI, 0.93 to 2.86; P = .086). The cumulative incidence of locoregional failures at 3 years was 23% (95% CI, 16% to 31%) compared with 9% (95% CI, 4% to 14%) in the cetuximab versus the cisplatin group (Gray’s test P = .0036). The cumulative incidence of distant failures did not differ between the treatment groups. Dose escalation in T3-T4 tumors did not increase local control.

    CONCLUSION: Cetuximab is inferior to cisplatin regarding locoregional control for concomitant treatment with RT in patients with locoregionally advanced HNSCC. Additional studies are needed to identify possible subgroups that still may benefit from concomitant cetuximab treatment.

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  • 8.
    Grefve, Josefine
    et al.
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Söderkvist, Karin
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Gunnlaugsson, Adalsteinn
    Department of Hematology, Oncology and Radiation Physics, Skane University Hospital, Lund University, Lund, Sweden.
    Sandgren, Kristina
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Jonsson, Joakim
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Keeratijarut Lindberg, Angsana
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nilsson, Erik
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Moreau, Mathieu
    Department of Hematology, Oncology and Radiation Physics, Skane University Hospital, Lund University, Lund, Sweden.
    Thellenberg-Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Olsson, Lars.E.
    Department of Translational Medicine, Medical Radiation Physics, Lund University, Malmö, Sweden.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Blomqvist, Lennart
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Berg Loegager, Vibeke
    Department of Radiology, Copenhagen University Hospital in Herlev, Herlev, Denmark.
    Strandberg, Sara
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Histopathology-validated gross tumor volume delineations of intraprostatic lesions using PSMA-positron emission tomography/multiparametric magnetic resonance imaging2024In: Physics and Imaging in Radiation Oncology, E-ISSN 2405-6316, Vol. 31, article id 100633Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Dose escalation in external radiotherapy of prostate cancer shows promising results in terms of biochemical disease-free survival. Boost volume delineation guidelines are sparse which may cause high interobserver variability. The aim of this research was to characterize gross tumor volume (GTV) delineations based on multiparametric magnetic resonance imaging (mpMRI) and prostate specific membrane antigen-positron emission tomography (PSMA-PET) in relation to histopathology-validated Gleason grade 4 and 5 regions.

    Material and methods: The study participants were examined with [68Ga]PSMA-PET/mpMRI prior to radical prostatectomy. Four radiation oncologists delineated GTVs in 15 study participants, on four different image types; T2-weighted (T2w), diffusion weighted imaging (DWI), dynamic contrast enhanced (DCE) and PSMA-PET scans separately. The simultaneous truth and performance level estimation (STAPLE) algorithm was used to generate combined GTVs. GTVs were subsequently compared to histopathology. We analysed how Dice similarity coefficient (DSC) and lesion coverage are affected by using single versus multiple image types as well as by adding a clinical target volume (CTV) margin.

    Results: Median DSC (STAPLE) for different GTVs varied between 0.33 and 0.52. GTVPSMA-PET/mpMRI generated the highest median lesion coverage at 0.66. Combining different image types achieved similar lesion coverage as adding a CTV margin to contours from a single image type, while reducing non-malignant tissue inclusion within the target volume.

    Conclusion: The combined use of mpMRI or PSMA-PET/mpMRI shows promise, achieving higher DSC and lesion coverage while minimizing non-malignant tissue inclusion, in comparison to the use of a single image type with an added CTV margin.

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  • 9. Holmberg, Lars
    et al.
    Hagberg, Oskar
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Department of surgical Sciences, Uppsala, University, Uppsala, Sweden.
    Gårdmark, Truls
    Ströck, Viveka
    Aljabery, Firas
    Jahnson, Staffan
    Hosseini, Abolfazl
    Jerlström, Tomas
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Söderkvist, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ullén, Anders
    Enlund, Mats
    Liedberg, Fredrik
    Malmström, Per-Uno
    Number of transurethral procedures after non-muscle-invasive bladder cancer and survival in causes other than bladder cancer2022In: PLOS ONE, E-ISSN 1932-6203, Vol. 17, no 9, article id e0274859Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Previous research has associated repeated transurethral procedures after a diagnosis of non-muscle invasive bladder cancer (NMIBC) with increased risk of death of causes other than bladder cancer.

    AIM: We investigated the overall and disease-specific risk of death in patients with NMIBC compared to a background population sample.

    METHODS: We utilized the database BladderBaSe 2.0 containing tumor-specific, health-related and socio-demographic information for 38,547 patients with NMIBC not primarily treated with radical cystectomy and 192,733 individuals in a comparison cohort, matched on age, gender, and county of residence. The cohorts were compared using Kaplan-Meier curves and Hazard ratios (HR) from a Cox regression models. In the NMIBC cohort, we analyzed the association between number of transurethral procedures and death conditioned on surviving two or five years.

    RESULTS: Overall survival and survival from causes other than bladder cancer estimated with Kaplan-Meier curves was 9.3% (95% confidence interval (CI) (8.6%-10.0%)) and 1.4% (95% CI 0.7%-2.1%) lower respectively for the NMIBC cohort compared to the comparison cohort at ten years. In a Cox model adjusted for prognostic group, educational level and comorbidity, the HR was 1.03 (95% CI 1.01-1.05) for death from causes other than bladder cancer comparing the NMIBC cohort to the comparison cohort. Among the NMIBC patients, there was no discernible association between number of transurethral procedures and deaths of causes other than bladder cancer after adjustment. The number of procedures were, however, associated with risk of dying from bladder cancer HR 3.56 (95% CI 3.43-3.68) for four or more resections versus one within two years of follow-up.

    CONCLUSION: The results indicate that repeated diagnostic or therapeutic transurethral procedures under follow-up do not increase of risk dying from causes other than bladder cancer. The modestly raised risk for NMIBC patients dying from causes other than bladder cancer is likely explained by residual confounding.

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  • 10. Holmberg, Lars
    et al.
    Skogmar, Sten
    Garmo, Hans
    Hagberg, Oskar
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Department of Surgical Sciences, Uppsala University, Uppsala; Northern Register Centre, Umeå universitet, Umeå, Sverige.
    Gårdmark, Truls
    Ströck, Viveka
    Aljabery, Firas
    Jahnson, Staffan
    Hosseini, Abolfazl
    Jerlström, Tomas
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Söderkvist, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Ullén, Anders
    Malmström, Per-Uno
    Liedberg, Fredrik
    Cumulative incidence of and risk factors for BCG infection after adjuvant BCG instillations2024In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 134, no 2, p. 229-238Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To investigate the cumulative incidence proportion of disseminated or local Bacillus Calmette-Guérin (BCG) infections after adjuvant BCG instillations in patients with non-muscle-invasive bladder cancer (NMIBC).

    PATIENTS AND METHODS: We analysed the timing and occurrence of BCG infections and absolute and relative risk in relation to patient characteristics available in the Swedish nationwide database 'BladderBaSe 2.0'. The cumulative incidence proportion of a BCG infection was indicated by a reported diagnosis of tuberculosis (TB) in the patient registry or filing a prescription for tuberculostatic drugs.

    RESULTS: The cumulative incidence proportion was 1.1% at the 5-year follow-up in 5033 patients exposed to adjuvant BCG instillations. The incidence rate was highest during the first 2 years after start of BCG instillations. Women had a lower risk than men (hazard ratio 0.23, 95% confidence interval 0.07-0.74). Age and calendar time at diagnosis, comorbidity, tumour risk group, previous medication with corticosteroids, immunosuppressive drugs, or time between transurethral resection of the bladder tumour and commencing the adjuvant BCG instillation were not associated with risk.

    CONCLUSIONS: These data further supports that the overall risk of a BCG infection after BCG-instillation treatment for NMIBC is low. The great majority of infections occur in the first 2 years, calling for an awareness of the diverse symptoms of BCG infection during this period. We provide evidence for male sex as a risk factor; however, the statistical precision is low and with a risk of selection bias, making it difficult to rule out the other suggested risk factors without further studies with different approaches.

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  • 11.
    Häggström, Christel
    et al.
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Garmo, Hans
    de Luna, Xavier
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Van Hemelrijck, Mieke
    Söderkvist, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Aljabery, Firas
    Ströck, Viveka
    Hosseini, Abolfazl
    Gårdmark, Truls
    Malmström, Per-Uno
    Jahnson, Staffan
    Liedberg, Fredrik
    Holmberg, Lars
    Survival after radiotherapy versus radical cystectomy for primary muscle-invasive bladder cancer: A Swedish nationwide population-based cohort study2019In: Cancer Medicine, E-ISSN 2045-7634, Vol. 8, no 5, p. 2196-2204Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Studies of survival comparing radical cystectomy (RC) and radiotherapy for muscle-invasive bladder cancer have provided inconsistent results and have methodological limitations. The aim of the study was to investigate risk of death after radiotherapy as compared to RC.

    METHODS: We selected patients with muscle-invasive urothelial carcinoma without distant metastases, treated with radiotherapy or RC from 1997 to 2014 in the Bladder Cancer Data Base Sweden (BladderBaSe) and estimated absolute and relative risk of bladder cancer death and all-cause death. In a group of patients, theoretically eligible for a trial comparing radiotherapy and RC, we calculated risk difference in an instrumental variable analysis. We have not investigated chemoradiotherapy as this treatment was not used in the study time period.

    RESULTS: The study included 3 309 patients, of those 17% were treated with radiotherapy and 83% with RC. Patients treated with radiotherapy were older, had more advanced comorbidity, and had a higher risk of death as compared to patients treated with RC (relative risks of 1.5-1.6). In the "trial population," all-cause death risk difference was 6 per 100 patients lower after radiotherapy at 5 years of follow-up, 95% confidence interval -41 to 29.

    CONCLUSION(S): Patient selection between the treatments make it difficult to evaluate results from conventionally adjusted and propensity-score matched survival analysis. When taking into account unmeasured confounding by instrumental variable analysis, no differences in survival was found between the treatments for a selected group of patients. Further clinical studies are needed to characterize this group of patients, which can serve as a basis for future comparison studies for treatment recommendations.

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  • 12.
    Häggström, Christel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Hagberg, Oskar
    Department of Translational Medicine, Lund University, Lund, Sweden.
    Gårdmark, Truls
    Department of Clinical Sciences, Karolinska Institute, Danderyd Hospital, Stockholm, Sweden.
    Aljabery, Firas
    Department of Clinical and Experimental Medicine, Division of Urology, Linköping University, Linköping, Sweden.
    Ströck, Viveka
    Department of Urology, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
    Hosseini, Abolfazl
    Department of Urology, Karolinska University Hospital, Stockholm, Sweden.
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Malmstrom, Per-Uno
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Söderkvist, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ullén, Anders
    Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden; Department of Pelvic Cancer, Genitourinary Oncology and Urology unit, Karolinska University Hospital, Stockholm, Sweden.
    Jerlström, Tomas
    School of Medical Sciences, Örebro University, Sweden.
    Jahnson, Staffan
    Department of Clinical and Experimental Medicine, Division of Urology, Linköping University, Linköping, Sweden.
    Liedberg, Fredrik
    Department of Translational Medicine, Lund University, Lund, Sweden; Department of Urology, Skåne University Hospital, Malmö, Sweden.
    Holmberg, Lars
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King's College London, London, United Kingdom.
    Cohort profile: Bladder Cancer Data Base Sweden (BladderBaSe) 2.02022In: BMJ Open, E-ISSN 2044-6055, Vol. 12, no 12, article id e064898Article in journal (Refereed)
    Abstract [en]

    PURPOSE: We constructed Bladder Cancer Data Base Sweden (BladderBaSe) 2.0 to expand studies in BladderBaSe on incidence, treatment outcomes, side effects, survival and health economic aspects of men and women with cancer in the urinary bladder, upper tract urothelial carcinoma (UTUC) (renal pelvis and ureter) and urethral carcinoma.

    PARTICIPANTS: BladderBaSe 2.0 includes 53 298 patients with cancer in the urinary bladder, diagnosed from 1 January 1997 to 31 December 2019, and 961 patients with UTUC in the renal pelvis and 792 in the ureter, and 146 patients with urethral urothelial carcinoma, diagnosed from 1 January 2015 to 31 December 2019, and in total 275 816 participants in reference groups, free of cancer in the urinary tract, matched 1:5 on sex, age and county.

    FINDINGS TO DATE: To date, 18 published studies based on data from the BladderBaSe have investigated calendar time trends in survival; impact of gender, socioeconomic factors, tumour aggressiveness and hospital volume for radical cystectomy on prognosis; survival after radical cystectomy compared with radical radiotherapy; risk factors for complications and side effects after radical cystectomy such as thromboembolism, strictures of ureteroenterostomies and incisional hernia.

    FUTURE PLANS: The BladderBaSe initiators are currently investigating gender-dependent detection delays due to urinary tract infections; survival after non-muscle invasive bladder cancer with respect to the number of transurethral resections; short-term outcomes comparing open and robot-assisted radical cystectomy; studies on risk for intravesical recurrence after different diagnostic measures in UTUC, and suicide risk after bladder cancer diagnosis. The BladderBaSe project group is open for collaborations with national and international colleagues.

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  • 13.
    Högmo, Anders
    et al.
    Regional Cancer Centre West, Region Västra Götaland, Gothenburg, Sweden.
    Holmberg, Erik
    Regional Cancer Centre West, Region Västra Götaland, Gothenburg, Sweden; Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden.
    Haugen Cange, Hedda
    Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.
    Reizenstein, Johan
    Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Wennerberg, Johan
    Otolaryngology/H&N Surgery, Department of Clinical Sciences, Lund University and University Hospital of Scania, Lund, Sweden.
    Beran, Martin
    Department of ENT and Maxillofacial Surgery, NAL Medical Center Hospital, Trollhättan, Sweden.
    Söderkvist, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Cancercentre, Umeå University Hospital, Umeå, Sweden.
    Hammerlid, Eva
    Department of Otorhinolaryngology, Head and Neck Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Sjödin, Helena
    Department of Oncology, Theme Cancer, Karolinska University Hospital, Stockholm, Sweden.
    Farnebo, Lovisa
    Department of Otorhinolaryngology–Head and Neck Surgery in Östergötland, and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    Sandström, Karl
    Otolaryngology, Department of Surgical Sciences, Uppsala University and University Hospital, Uppsala, Sweden.
    Hammarstedt-Nordenvall, Lalle
    Division of Ear, Nose, and Throat Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
    Zborayova, Katarina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology. Umeå University Hospital, Umeå, Sweden.
    Brun, Eva
    Oncology, Department of Clinical Sciences, Lund University and University Hospital of Scania, Lund, Sweden.
    Base of tongue squamous cell carcinomas, outcome depending on treatment strategy and p16 status. A population-based study from the Swedish Head and Neck Cancer Register2022In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 61, no 4, p. 433-440Article in journal (Refereed)
    Abstract [en]

    Background: The base of tongue squamous cell carcinoma (BOTSCC) is mainly an HPV-related tumor. Radiotherapy (EBRT) ± concomitant chemotherapy (CT) is the backbone of the curatively intended treatment, with brachytherapy (BT) boost as an option. With four different treatment strategies in Sweden, a retrospective study based on the population-based Swedish Head and Neck Cancer Register (SweHNCR) was initiated.

    Material and methods: Data on tumors, treatment and outcomes in patients with BOTSCC treated between 2008 and 2014 were validated through medical records and updated as needed. Data on p16 status were updated or completed with immunohistochemical analysis of archived tumor material. Tumors were reclassified according to the UICC 8th edition.

    Results: Treatment was EBRT, EBRT + CT, EBRT + BT or EBRT + CT + BT in 151, 145, 82 and 167 patients respectively (n = 545). A p16 analysis was available in 414 cases; 338 were p16+ and 76 p16−. 5-year overall survival (OS) was 68% (95% CI: 64–72%), with76% and 37% for p16+ patients and p16− patients, respectively. An increase in OS was found with the addition of CT to EBRT for patients with p16+ tumors, stages II–III, but for patients with tumor stage I, p16+ (UICC 8) none of the treatment strategies was superior to EBRT alone.

    Conclusion: In the present retrospective population-based study of BOTSCC brachytherapy was found to be of no beneficial value in curatively intended treatment. An increase in survival was found for EBRT + CT compared to EBRT alone in patients with advanced cases, stages II and III (UICC 8), but none of the regimes was significantly superior to EBRT as a single treatment modality for stage I (UICC 8), provided there was p16 positivity in the tumor. In the small group of patients with p16− tumors, a poorer prognosis was found, but the small sample size did not allow any comparisons between different treatment strategies.

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  • 14.
    Jahnson, Staffan
    et al.
    Department of Clinical and Experimental Medicine, Division of Urology, Linkoping University, Linkoping, Sweden.
    Gårdmark, Truls
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.
    Hosseini, Abolfazl
    Department of Pelvic Surgery, Karolinska University Hospital, Stockholm, Sweden.
    Jerlström, Tomas
    Department of Urology, School of Medical Sciences, Faculty of Medicine and Health, Orebro University, Orebro, Sweden.
    Liedberg, Fredrik
    Department of Urology, Skane University Hospital, Malmo, Sweden; Institution of Translational Medicine, Lund University, Malmo, Sweden.
    Malmström, Per-Uno
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Hagberg, Oskar
    Institution of Translational Medicine, Lund University, Malmo, Sweden.
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Ströck, Viveka
    Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Region Vastra Gotaland, Sahlgrenska University Hospital, Department of Urology, Gothenburg, Sweden.
    Söderström, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ullen, Anders
    Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden; Patient Area Pelvic Cancer, Theme Cancer, Karolinska University Hospital, Solna, Sweden.
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Holmberg, Lars
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Translational Oncology Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King's College London, London, United Kingdom.
    Aljabery, Firas
    Department of Clinical and Experimental Medicine, Division of Urology, Linkoping University, Linkoping, Sweden.
    Thromboembolism in Muscle-Invasive Bladder Cancer. A Population-based Nationwide Study2021In: Bladder Cancer, ISSN 2352-3727, Vol. 7, no 2, p. 161-171Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Routine VTE prophylaxis within 30 days of radical cystectomy (RC) for urinary bladder cancer (UBC) is used to protect from venous thromboembolism (VTE). However, randomized studies and nationwide population-based studies are lacking.

    OBJECTIVE: To study VTE and risk factors for VTE in muscle-invasive UBC in a nationwide population-based series, with a focus on the association with RC with and without chemotherapy.

    MATERIALS AND METHODS: We studied all patients with clinical stage T2-T4 UBC diagnosed 1997 to 2014 in the Bladder Cancer Data Base Sweden (BladderBaSe). Previous VTE events and risk factors for VTE were registered from 1987. Cox regression analyses and Kaplan-Meier curves were performed to study risk factors for VTE and cumulative incidence of VTE.

    RESULTS: In 9720 patients (71%males) with a median age of 74 years 546 (5.6%) had VTE after diagnosis. In Cox analyses controlling for patient's and tumour characteristics, and risk factors for VTE, VTE after diagnosis and first treatment date were associated with chemotherapy with or without RC. Cumulative incidence of VTE increased during 24 months after diagnosis and first treatment date. VTE were less common in patients with previous cardiovascular disease.

    CONCLUSIONS: VTE was commonly observed after 30 days from diagnosis and from first treatment date in patients with T2-T4 UBC, particularly after chemotherapy. The findings suggest that long-term intervention studies of benefit and possible harms of VTE prophylaxis after UBC should be undertaken.

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  • 15.
    Jonsson, Joakim H
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Brynolfsson, Patrik
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Garpebring, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Söderström, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Registration accuracy for MR images of the prostate using a subvolume based registration protocol2011In: Radiation Oncology, E-ISSN 1748-717X, Vol. 6, no 1, p. 73-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In recent years, there has been a considerable research effort concerning the integration of magnetic resonance imaging (MRI) into the external radiotherapy workflow motivated by the superior soft tissue contrast as compared to computed tomography. Image registration is a necessary step in many applications, e.g. in patient positioning and therapy response assessment with repeated imaging. In this study, we investigate the dependence between the registration accuracy and the size of the registration volume for a subvolume based rigid registration protocol for MR images of the prostate.

    METHODS: Ten patients were imaged four times each over the course of radiotherapy treatment using a T2 weighted sequence. The images were registered to each other using a mean square distance metric and a step gradient optimizer for registration volumes of different sizes. The precision of the registrations was evaluated using the center of mass distance between the manually defined prostates in the registered images. The optimal size of the registration volume was determined by minimizing the standard deviation of these distances.

    RESULTS: We found that prostate position was most uncertain in the anterior-posterior (AP) direction using traditional full volume registration. The improvement in standard deviation of the mean center of mass distance between the prostate volumes using a registration volume optimized to the prostate was 3.9 mm (p < 0.001) in the AP direction. The optimum registration volume size was 0 mm margin added to the prostate gland as outlined in the first image series.

    CONCLUSIONS: Repeated MR imaging of the prostate for therapy set-up or therapy assessment will both require high precision tissue registration. With a subvolume based registration the prostate registration uncertainty can be reduced down to the order of 1 mm (1 SD) compared to several millimeters for registration based on the whole pelvis.

  • 16.
    Jonsson, Joakim
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Johansson, Adam
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Söderström, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Asklund, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Treatment planning of intracranial targets on MRI derived substitute CT data2013In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 108, no 1, p. 118-122Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The use of magnetic resonance imaging (MRI) as a complement to computed tomography (CT) in the target definition procedure for radiotherapy is increasing. To eliminate systematic uncertainties due to image registration, a workflow based entirely on MRI may be preferable. In the present pilot study, we investigate dose calculation accuracy for automatically generated substitute CT (s-CT) images of the head based on MRI. We also produce digitally reconstructed radiographs (DRRs) from s-CT data to evaluate the feasibility of patient positioning based on MR images. METHODS AND MATERIALS: Five patients were included in the study. The dose calculation was performed on CT, s-CT, s-CT data without inhomogeneity correction and bulk density assigned MRI images. Evaluation of the results was performed using point dose and dose volume histogram (DVH) comparisons, and gamma index evaluation. RESULTS: The results demonstrate that the s-CT images improves the dose calculation accuracy compared to the method of non-inhomogeneity corrected dose calculations (mean improvement 2.0 percentage points) and that it performs almost identically to the method of bulk density assignment. The s-CT based DRRs appear to be adequate for patient positioning of intra-cranial targets, although further investigation is needed on this subject. CONCLUSIONS: The s-CT method is very fast and yields data that can be used for treatment planning without sacrificing accuracy.

  • 17.
    Jonsson, Joakim
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Söderkvist, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    The rationale for MR-only treatment planning for external radiotherapy2019In: Clinical and Translational Radiation Oncology, E-ISSN 2405-6308, Vol. 18, p. 60-65Article, review/survey (Refereed)
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  • 18.
    Leffler, Klara
    et al.
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Tommaso Luppino, Luigi
    Department Physics and Technology, UiT The Arctic University of Norway, Tromsø, Norway.
    Kuttner, Samuel
    University Hospital of North Norway, Tromsø, Norway; Physics and Technology, UiT The Arctic University of Norway, Tromsø, Norway; Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
    Söderkvist, Karin
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention.
    Filling of incomplete sinograms from sparse PET detector configurations using a residual U-NetManuscript (preprint) (Other academic)
  • 19.
    Liedberg, Fredrik
    et al.
    Department of Urology, Skåne University Hospital, Malmö, Sweden; Institution of Translational Medicine, Lund University, Malmö, Sweden.
    Hagberg, Oskar
    Institution of Translational Medicine, Lund University, Malmö, Sweden; Regional Cancer Centre South, Region Skåne, Lund, Sweden.
    Aljabery, Firas
    Department of Clinical and Experimental Medicine, Division of Urology, Linköping University, Linköping, Sweden.
    Gårdmark, Truls
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.
    Hosseini, Abolfazl
    Department of Molecular Medicine and Surgery, Karolinska Institute and Department of Pelvic Cancer, Karolinska University Hospital, Stockholm, Sweden.
    Jahnson, Staffan
    Department of Clinical and Experimental Medicine, Division of Urology, Linköping University, Linköping, Sweden.
    Jerlström, Tomas
    Department of Urology, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Malmström, Per-Uno
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Söderkvist, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ströck, Viveka
    Department of Urology, Sahlgrenska University Hospital and Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Ullén, Anders
    Department of Oncology-Pathology, Karolinska Institute, and Department of Pelvic Cancer, Karolinska University Hospital, Stockholm, Sweden.
    Häggström, Christel
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Holmberg, Lars
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; School of Cancer and Pharmaceutical Sciences, King’s College London, London, United Kingdom.
    Survival after radical cystectomy during holiday periods2021In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 55, no 4, p. 276-280Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: For patients undergoing radical cystectomy for bladder cancer, a procedure requiring complex urinary tract reconstruction prone to major postoperative complications, the timing and quality of the surgery have been associated with outcomes.

    PATIENTS AND METHODS: This study investigated if radical cystectomy for bladder cancer performed during holiday periods had worse disease-specific (DSS) and overall survival (OS), higher 90-day mortality and risk of readmissions. All patients operated on with radical cystectomy for primary bladder cancer during 1997-2014 with holiday periods as exposure (with one narrow (7 weeks) and one wider (14 weeks) definition) in the Swedish population-based bladder cancer research-database (BladderBaSe) were studied. DSS and OS after radical cystectomy during holiday periods were analysed with Cox regression models adjusted for sex, age, comorbidity, marital status, T-stage and nodal metastases, neoadjuvant chemotherapy, hospital volume and year of cystectomy.

    RESULTS: Surgery during the holiday periods (narrow and wide definitions) were not associated with DSS (Hazard ratio [HR] = 1.05, 95% confidence interval [95% CI] = 0.90-1.21 and HR = 1.04, 95% CI = 0.91-1.17), respectively. HRs for OS were similar, and no associations between radical cystectomy during any of the holiday period definitions and 90-day mortality and readmission were found.

    CONCLUSION: Survival after radical cystectomy in Sweden is similar during holiday and non-holiday periods.

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  • 20.
    Liedberg, Fredrik
    et al.
    Department of Urology Skåne University Hospital, Malmö, Sweden; Institution of Translational Medicine, Lund University, Malmö, Sweden.
    Hagberg, Oskar
    Institution of Translational Medicine, Lund University, Malmö, Sweden.
    Aljabery, Firas
    Department of Clinical and Experimental Medicine, Division of Urology, Linköping University, Linköping, Sweden.
    Gårdmark, Truls
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.
    Jahnson, Staffan
    Department of Clinical and Experimental Medicine, Division of Urology, Linköping University, Linköping, Sweden.
    Jerlström, Tomas
    Department of Urology, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Sweden.
    Ströck, Viveka
    Department of Urology, Sahlgrenska University Hospital and Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Söderkvist, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Ullén, Anders
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Department of Pelvic Cancer, Genitourinary Oncology and Urology unit, Karolinska University Hospital, Stockholm, Sweden.
    Bobjer, Johannes
    Department of Urology Skåne University Hospital, Malmö, Sweden; Institution of Translational Medicine, Lund University, Malmö, Sweden.
    Diagnostic pathways and treatment strategies in upper tract urothelial carcinoma in Sweden between 2015 and 2021: a population-based survey2024In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 59, p. 19-25Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To report national data on diagnostics and treatment of upper tract urothelial carcinoma (UTUC) from the Swedish National Registry of Urinary Bladder Cancer (SNRUBC).

    PATIENTS AND METHODS: Data from 2015 to 2021 were retrieved, and descriptive analyses were performed regarding incidence, diagnostic modalities, preoperative tumor staging, quality indicators for treatment including the use of standardized care pathways (SCP) and multidisciplinary tumor boards (MDTB). Time trends were explored for the study period.

    RESULTS: Registrations included 1,213 patients with renal pelvic cancer and 911 patients with ureteric cancer with a median age of 74 (interquartile range [IQR] 70-77) and 75 (IQR 71-78) years, respectively. Incidence rates of UTUC were stable, as were proportions of curative treatment intent. Median number of days from referral to treatment was 76 (IQR 57-99) and 90 (IQR 72-118) days, respectively, for tumors of the renal pelvis and ureter, which remained unchanged after introduction of SCP in 2016. Noticeable trends included stable use of kidney-sparing surgery and increased use of MDTB. For radical nephroureterectomy (RNU), robot-assisted technique usage increased even for non-organ-confined tumors (cT3-4) and in one out of three patients undergoing RNU a bladder cuff excision was not registered.

    CONCLUSIONS: The population-based SNRUBC with high coverage contributes to the knowledge about UTUC with granular and generalizable data. The present study reveals a high proportion of patients not subjected to curatively intended treatment and suggests unmet needs to shorten lead times to treatment and use of bladder cuff excision when performing radical surgery for UTUC in Sweden.

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  • 21.
    Liedberg, Fredrik
    et al.
    Department of Urology, Skåne University Hospital, Malmö, Sweden; Institution of Translational Medicine, Lund University, Malmö, Sweden.
    Hagberg, Oskar
    Institution of Translational Medicine, Lund University, Malmö, Sweden.
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Aljabery, Firas
    Division of Urology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Gårdmark, Truls
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.
    Hosseini, Abolfazl
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Jahnson, Staffan
    Division of Urology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Jerlström, Tomas
    Department of Urology, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Ströck, Viveka
    Department of Urology, Sahlgrenska University Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Söderkvist, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Ullén, Anders
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Department of Pelvic Cancer, Genitourinary Oncology and Urology Unit, Karolinska University Hospital, Stockholm, Sweden.
    Holmberg, Lars
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; School of Cancer and Pharmaceutical Sciences, King’s College London, London, United Kingdom.
    Bobjer, Johannes
    Department of Urology, Skåne University Hospital, Malmö, Sweden; Institution of Translational Medicine, Lund University, Malmö, Sweden.
    Preoperative upper tract invasive diagnostic modalities are associated with intravesical recurrence following surgery for upper tract urothelial carcinoma: A population-based study2023In: PLOS ONE, E-ISSN 1932-6203, Vol. 18, no 2 February, article id e0281304Article in journal (Refereed)
    Abstract [en]

    Background: Intravesical recurrence (IVR) after surgery for upper tract urothelial carcinoma (UTUC) is a clinical problem. We investigated if preoperative invasive diagnostic modalities (IDM) such as antegrade/retrograde uretero-pyelography and/or selective urine cytology/barbotage, and URS with or without concomitant biopsy are associated with IVR after radical surgery for UTUC. Risk of death from urothelial cancer and all causes was investigated as secondary outcomes.

    Methods: We investigated a population-based cohort of 1038 consecutive patients subjected to radical surgery for UTUC 2015–2019 in Sweden, using the Bladder Cancer Data Base Sweden (BladderBaSe 2.0), comprising all patients in the Swedish National Registry of Urinary Bladder Cancer. Risk estimates of IVR, death from urothelial cancer, and all causes was assessed using multivariable Cox regression models.

    Results: The study included 536 cases with and 502 without preoperative IDM. IDM was associated with increased risk of IVR (HR 1.24, 95% CI 1.03–1.52) and risk of urothelial cancer death (HR 1.56, CI 1.12–2.18), compared to no IDM after a median follow-up of 1.3 yrs. Stratified analysis for tumor location showed that IDM was associated with risk of IVR in ureteric cancer (HR 1.66, 95% CI 1.21–2.28) but not in renal pelvic cancer (HR 1.07, 95% CI 0.81–1.41). Limitations included the observational setting and the lack of variables such as tumour grade, multifocality and preoperative hydronephrosis.

    Conclusions: Worse outcomes for patients subjected to preoperative IDM highlight the need for carefully considering diagnostic decisions for UTUC patients, specifically in tumours located in the ureter.

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  • 22. Liedberg, Fredrik
    et al.
    Kjellström, Sofia
    Lind, Anna-Karin
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Söderkvist, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Falkman, Karin
    Thulin, Helena
    Aljabery, Firas
    Papantonio, Dimitrious
    Ströck, Viveka
    Öfverholm, Elisabeth
    Jerlström, Tomas
    Sandzen, Johan
    Verbiene, Ingrida
    Ullén, Anders
    Swedish National Guidelines on Urothelial Carcinoma: 2021 update on non-muscle invasive bladder cancer and upper tract urothelial carcinoma2022In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 56, no 2, p. 137-146Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To overview the updated Swedish National Guidelines on Urothelial Carcinoma 2021, with emphasis on non-muscle-invasive bladder cancer (NMIBC) and upper tract urothelial carcinoma (UTUC).

    METHODS: A narrative review of the updated version of the Swedish National Guidelines on Urothelial Carcinoma 2021 and highlighting new treatment recommendations, with comparison to the European Association of Urology (EAU) guidelines and current literature.

    RESULTS: For NMIBC the new EAU 2021 risk group stratification has been introduced for non-muscle invasive bladder cancer to predict risk of progression and the web-based application has been translated to Swedish (https://nmibc.net.). For patients with non-BCG -responsive disease treatment recommendations have been pinpointed, to guide patient counselling in this clinical situation. A new recommendation in the current version of the guidelines is the introduction of four courses of adjuvant platinum-based chemotherapy to patients with advanced disease in the nephroureterectomy specimen (pT2 or higher and/or N+). Patients with papillary urothelial neoplasms with low malignant potential (PUNLMP) can be discharged from follow-up already after 3 years based on a very low subsequent risk of further recurrences.

    CONCLUSIONS: The current version of the Swedish national guidelines introduces a new risk-stratification model and follow-up recommendation for NMIBC and adjuvant chemotherapy after radical surgery for UTUC.

  • 23.
    Magnusson, Jenny
    et al.
    Department of Urology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Hagberg, Oskar
    Department of Translational Medicine, Lund University, Malmö, Sweden.
    Aljabery, Firas
    Division of Urology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Hosseini, Abolfazl
    Department of Molecular Medicine and Surgery, Karolinska Institutet and Department of Pelvic Surgery, Karolinska University Hospital, Stockholm, Sweden.
    Jahnson, Staffan
    Division of Urology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Jerlström, Tomas
    Department of Urology, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Söderström, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ströck, Viveka
    Department of Urology, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Ullén, Anders
    Genitourinary Oncology and Urology Unit, Department of Oncology-Pathology, Karolinska Institutet, and Department of Pelvic Cancer, Karolinska University Hospital, Stockholm, Sweden.
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; .
    Holmberg, Lars
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Translational Oncology and Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King’s College London, London, United Kingdom.
    Kjölhede, Henrik
    Department of Urology, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Cumulative incidence of ureteroenteric strictures after radical cystectomy in a population-based Swedish cohort2021In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 55, no 5, p. 361-365Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The incidence of benign ureteroenteric strictures following radical cystectomy (RC) for urinary bladder cancer (UBC) is investigated mainly in single-centre studies from high-volume centres. The aim of this study was to evaluate the cumulative incidence of strictures and risk factors in a population-based cohort.

    PATIENTS AND METHODS: Data was collected from Bladder Cancer Data Base Sweden (BladderBaSe). The primary endpoint was stricture with intervention. Secondary endpoint included hydronephrosis both with/without intervention.

    RESULTS: In total, 5,816 patients were registered as having had RC due to UBC between 1997 and 2014. After a median follow-up of 23.5 months (IQR = 9.0-63.1 months; range = 0.0-214.0 months), we found that 515 (8.9%) patients underwent intervention for stricture. Seven hundred and sixty-one (13.1%) patients were diagnosed with hydronephrosis without intervention. The cumulative incidence of strictures with intervention was 19.7% (95% CI = 16.7-23.1%) during the 17 years of follow-up. In the first year, the cumulative incidence of strictures was 5.6% (95% CI = 5.0-6.2%), and in the first 2 years 8.4% (95% CI = 7.6-9.3%). For the secondary endpoint, the cumulative incidence was 30.4% (95% CI = 26.7-33.1%) after 17 years. Only the year of RC was associated with stricture incidence in Cox regression analysis, whereas hospital cystectomy volume, patient age and patient sex were not.

    CONCLUSION: Ureteroenteric strictures requiring intervention may be more common than previously reported, affecting nearly one fifth of patients who have undergone RC for UBC. The annual incidence was highest in the first 2 years after surgery but the cumulative incidence increased continuously during 17 years of follow-up.

  • 24. Mäkitie, A.
    et al.
    Ruuskanen, M.
    Bentzen, J.
    Brun, E.
    Gebre-Medhin, M.
    Friesland, S.
    Marsk, E.
    Hammarstedt-Nordenvall, L.
    Gille, E.
    Reizenstein, J.
    Adell, G.
    Farnebo, L.
    Rzepecki, J.
    Haugen, H.
    Söderström, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergström, S.
    Lödén, B.
    Cederblad, L.
    Laurell, G.
    Smeland, E.
    Evensen, J. Folkvard
    Lund, J. Å.
    Tøndel, H.
    Karlsdottir, Å.
    Jóhannsson, J.
    Johansen, J.
    Kristensen, C. A.
    Jensen, K.
    Andersen, L. J.
    Koivunen, P.
    Korpela, M.
    Voutilainen, L.
    Wigren, T.
    Minn, H.
    Joensuu, H.
    Overgaard, J.
    Saarilahti, K.
    The management and survival outcomes of nasopharyngeal cancer in the Nordic countries2018In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 4, p. 557-560Article in journal (Refereed)
  • 25.
    Nilsson, Erik
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Sandgren, Kristina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Grefve, Josefine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Jonsson, Joakim
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Keeratijarut Lindberg, Angsana
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Söderkvist, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    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.
    Blomqvist, Lennart
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Sweden.
    Strandberg, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    The grade of individual prostate cancer lesions predicted by magnetic resonance imaging and positron emission tomography2023In: Communications Medicine, E-ISSN 2730-664X, Vol. 3, no 1, article id 164Article in journal (Refereed)
    Abstract [en]

    Background: Multiparametric magnetic resonance imaging (mpMRI) and positron emission tomography (PET) are widely used for the management of prostate cancer (PCa). However, how these modalities complement each other in PCa risk stratification is still largely unknown. We aim to provide insights into the potential of mpMRI and PET for PCa risk stratification.

    Methods: We analyzed data from 55 consecutive patients with elevated prostate-specific antigen and biopsy-proven PCa enrolled in a prospective study between December 2016 and December 2019. [68Ga]PSMA-11 PET (PSMA-PET), [11C]Acetate PET (Acetate-PET) and mpMRI were co-registered with whole-mount histopathology. Lower- and higher-grade lesions were defined by International Society of Urological Pathology (ISUP) grade groups (IGG). We used PET and mpMRI data to differentiate between grades in two cases: IGG 3 vs. IGG 2 (case 1) and IGG ≥ 3 vs. IGG ≤ 2 (case 2). The performance was evaluated by receiver operating characteristic (ROC) analysis.

    Results: We find that the maximum standardized uptake value (SUVmax) for PSMA-PET achieves the highest area under the ROC curve (AUC), with AUCs of 0.72 (case 1) and 0.79 (case 2). Combining the volume transfer constant, apparent diffusion coefficient and T2-weighted images (each normalized to non-malignant prostatic tissue) results in AUCs of 0.70 (case 1) and 0.70 (case 2). Adding PSMA-SUVmax increases the AUCs by 0.09 (p < 0.01) and 0.12 (p < 0.01), respectively.

    Conclusions: By co-registering whole-mount histopathology and in-vivo imaging we show that mpMRI and PET can distinguish between lower- and higher-grade prostate cancer, using partially discriminative cut-off values.

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  • 26.
    Nyholm, Tufve
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Jonsson, Joakim
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Söderström, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergström, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Carlberg, Andreas
    Frykholm, Gunilla
    Behrens, Claus F.
    Geertsen, Poul Flemming
    Trepiakas, Redas
    Hanvey, Scott
    Sadozye, Azmat
    Ansari, Jawaher
    McCallum, Hazel
    Frew, John
    McMenemin, Rhona
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Variability in prostate and seminal vesicle delineations defined on magnetic resonance images, a multi-observer, -center and -sequence study2013In: Radiation Oncology, E-ISSN 1748-717X, Vol. 8, p. 126-Article in journal (Refereed)
    Abstract [en]

    Background: The use of magnetic resonance (MR) imaging as a part of preparation for radiotherapy is increasing. For delineation of the prostate several publications have shown decreased delineation variability using MR compared to computed tomography (CT). The purpose of the present work was to investigate the intra- and inter-physician delineation variability for prostate and seminal vesicles, and to investigate the influence of different MR sequence settings used clinically at the five centers participating in the study.

    Methods: MR series from five centers, each providing five patients, were used. Two physicians from each center delineated the prostate and the seminal vesicles on each of the 25 image sets. The variability between the delineations was analyzed with respect to overall, intra-and inter-physician variability, and dependence between variability and origin of the MR images, i.e. the MR sequence used to acquire the data.

    Results: The intra-physician variability in different directions was between 1.3 - 1.9 mm and 3 - 4 mm for the prostate and seminal vesicles respectively (1 std). The inter-physician variability for different directions were between 0.7 - 1.7 mm and approximately equal for the prostate and seminal vesicles. Large differences in variability were observed for individual patients, and also for individual imaging sequences used at the different centers. There was however no indication of decreased variability with higher field strength.

    Conclusion: The overall delineation variability is larger for the seminal vesicles compared to the prostate, due to a larger intra-physician variability. The imaging sequence appears to have a large influence on the variability, even for different variants of the T2-weighted spin-echo based sequences, which were used by all centers in the study.

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    Variability in prostate and seminal vesicle delineations defined on magnetic resonance images, a multi-observer, -center and -sequence study
  • 27.
    Nyholm, Tufve
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Medical Radiation Physics, Department of Immunology, Genetics and Pathology, Uppsala University.
    Olsson, Caroline
    Agrup, Måns
    Björk, Peter
    Björk-Eriksson, Thomas
    Gagliardi, Giovanna
    Grinaker, Hanne
    Gunnlaugsson, Adalsteinn
    Gustafsson, Anders
    Gustafsson, Magnus
    Johansson, Bengt
    Johnsson, Stefan
    Karlsson, Magnus
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Kristensen, Ingrid
    Nilsson, Per
    Nyström, Leif
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Onjukka, Eva
    Reizenstein, Johan
    Skönevik, Johan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Söderström, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Valdman, Alexander
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Montelius, Anders
    A national approach for automated collection of standardized and population-based radiation therapy data in Sweden2016In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 119, no 2, p. 344-350Article in journal (Refereed)
    Abstract [en]

    Purpose: To develop an infrastructure for structured and automated collection of interoperable radiation therapy (RT) data into a national clinical quality registry.

    Materials and methods: The present study was initiated in 2012 with the participation of seven of the 15 hospital departments delivering RT in Sweden. A national RT nomenclature and a database for structured unified storage of RT data at each site (Medical Information Quality Archive, MIQA) have been developed. Aggregated data from the MIQA databases are sent to a national RT registry located on the same IT platform (INCA) as the national clinical cancer registries.

    Results: The suggested naming convention has to date been integrated into the clinical workflow at 12 of 15 sites, and MIQA is installed at six of these. Involvement of the remaining 3/15 RT departments is ongoing, and they are expected to be part of the infrastructure by 2016. RT data collection from ARIA (R), Mosaiq (R), Eclipse (TM), and Oncentra (R) is supported. Manual curation of RT-structure information is needed for approximately 10% of target volumes, but rarely for normal tissue structures, demonstrating a good compliance to the RT nomenclature. Aggregated dose/volume descriptors are calculated based on the information in MIQA and sent to INCA using a dedicated service (MIQA2INCA). Correct linkage of data for each patient to the clinical cancer registries on the INCA platform is assured by the unique Swedish personal identity number.

    Conclusions: An infrastructure for structured and automated prospective collection of syntactically inter operable RT data into a national clinical quality registry for RT data is under implementation. Future developments include adapting MIQA to other treatment modalities (e.g. proton therapy and brachytherapy) and finding strategies to harmonize structure delineations. How the RT registry should comply with domain-specific ontologies such as the Radiation Oncology Ontology (ROO) is under discussion. 

  • 28.
    Nyholm, Tufve
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Svensson, Stina
    Andersson, Sebastian
    Jonsson, Joakim
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Sohlin, Maja
    Gustafsson, Christian
    Kjellén, Elisabeth
    Söderström, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Albertsson, Per
    Blomqvist, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Olsson, Lars E.
    Gunnlaugsson, Adalsteinn
    MR and CT data with multiobserver delineations of organs in the pelvic area: Part of the Gold Atlas project2018In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 45, no 3, p. 1295-1300Article in journal (Refereed)
    Abstract [en]

    Purpose: We describe a public dataset with MR and CT images of patients performed in the same position with both multiobserver and expert consensus delineations of relevant organs in the male pelvic region. The purpose was to provide means for training and validation of segmentation algorithms and methods to convert MR to CT like data, i.e., so called synthetic CT (sCT).

    Acquisition and validation methods: T1- and T2-weighted MR images as well as CT data were collected for 19 patients at three different departments. Five experts delineated nine organs for each patient based on the T2-weighted MR images. An automatic method was used to fuse the delineations. Starting from each fused delineation, a consensus delineation was agreed upon by the five experts for each organ and patient. Segmentation overlap between user delineations with respect to the consensus delineations was measured to describe the spread of the collected data. Finally, an open-source software was used to create deformation vector fields describing the relation between MR and CT images to further increase the usability of the dataset.

    Data format and usage notes: The dataset has been made publically available to be used for academic purposes, and can be accessed from . Potential applicationsThe dataset provides a useful source for training and validation of segmentation algorithms as well as methods to convert MR to CT-like data (sCT). To give some examples: The T2-weighted MR images with their consensus delineations can directly be used as a template in an existing atlas-based segmentation engine; the expert delineations are useful to validate the performance of a segmentation algorithm as they provide a way to measure variability among users which can be compared with the result of an automatic segmentation; and the pairwise deformably registered MR and CT images can be a source for an atlas-based sCT algorithm or for validation of sCT algorithm.

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  • 29.
    Nyqvist, Johanna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology. Department of Otolaryngology and Head and Neck Surgery, Skåne University Hospital, Lund.
    Fransson, Per
    Umeå University, Faculty of Medicine, Department of Nursing.
    Laurell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology. Department of Otolaryngology and Head and Neck Surgery, Uppsala University Hospital.
    Hammerlid, Eva
    Kjellén, Elisabeth
    Franzén, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Söderström, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wickart-Johansson, Gun
    Friesland, Signe
    Sjödin, Helena
    Brun, Eva
    Ask, Anders
    Nilsson, Per
    Ekberg, Lars
    Björk-Eriksson, Thomas
    Nyman, Jan
    Lödén, Britta
    Lewin, Freddi
    Reizenstein, Johan
    Lundin, Erik
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Differences in health related quality of life in the randomised ARTSCAN study; accelerated vs. conventional radiotherapy for head and neck cancer: A five year follow up2016In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 118, no 2, p. 335-341Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Health related quality of life (HRQoL) was assessed in the randomised, prospective ARTSCAN study comparing conventional radiotherapy (CF) with accelerated radiotherapy (AF) for head and neck cancer.

    Material and methods: 750 patients with squamous cell carcinoma (of any grade and stage) in the oral cavity, oro-, or hypopharynx or larynx (except T1-2, NO glottic carcinoma) without distant metastases were randomised to either conventional fractionation (2 Gy/day, 5 days/week in 49 days, total dose 68 Gy) or accelerated fractionation (1.1 + 2.0 Gy/day, 5 days/week in 35 days, total dose 68 Gy). HRQoL was assessed with EORTC QLQ-C30, QLQ-H&N35 and HADS at baseline, at end of radiotherapy (eRT) and at 3 and 6 months and 1, 2 and 5 years after start of treatment.

    Results: The AF group reported HRQoL was significantly lower at eRT and at 3 months for most symptoms, scales and functions. Few significant differences were noted between the groups at 6 months and 5 years. Scores related to functional oral intake never reached baseline.

    Conclusion: In comparison to CF, AF has a stronger adverse effect on HRQoL in the acute phase.

  • 30.
    Ottosson, Sandra
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Söderström, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Kjellén, Elisabeth
    Lunds universitet.
    Nilsson, Per
    Lunds universitet.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Laurell, Göran
    Uppsala universitet.
    Weight and body mass index in relation to irradiated volume and to overall survival in patients with oropharyngeal cancer: a retrospective cohort study2014In: Radiation Oncology, E-ISSN 1748-717X, Vol. 9, p. 160-Article in journal (Refereed)
    Abstract [en]

    Background: Weight loss is a common problem in patients with Squamous Cell Carcinoma of the Head and Neck (SCCHN) treated with radiotherapy (RT). The aims of the present study were to determine if treated volume (TV), as a measure of the radiation dose burden, can predict weight loss in patients with oropharyngeal cancer and to analyze weight loss and body mass index (BMI) in the same patient group in relation to 5-year overall survival. Methods: The ARTSCAN trial is a prospective, randomized, multicenter trial in patients with SCCHN. Nutritional data from the ARTSCAN trial were analyzed retrospectively using univariate and multivariate statistical methods based on information on percentage weight loss from the start of RT up to five months after the termination of RT (study cohort 1, n = 232) and information on patients' BMI at the start of RT (study cohort 2, n = 203). TV was defined as the volume of the patient receiving at least 95% of the prescribed dose. TV64.6 (Gy) encompasses macroscopic tumor and TV43.7 (Gy) elective lymph nodes of the neck. Results: TV64.6 Gy and TV43.7 Gy were both significantly correlated with higher weight loss up to five months after the termination of RT in study cohort 1 (p < 0.001 for both). BMI at the start of RT was shown to be a prognostic factor for 5-year overall survival in study cohort 2 but weight loss was not. The hazard ratios and 95% confidence intervals were 3.78 (1.46-9.75) and 2.57 (1.43-4.62) in patients with underweight and normal weight, respectively. Conclusions: TV can predict weight loss during RT in patients with oropharyngeal cancer regardless of clinical stage. A high BMI (>25 kg/m(2)) at the start of RT is positively associated with survival in patients with oropharyngeal cancer.

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  • 31. Russell, Beth
    et al.
    Liedberg, Fredrik
    Hagberg, Oskar
    Ullén, Anders
    Söderkvist, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ströck, Viveka
    Aljabery, Firas
    Gårdmark, Truls
    Jerlström, Tomas
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Holmberg, Lars
    Bryan, Richard T.
    Enting, Deborah
    Van Hemelrijck, Mieke
    Risk of bladder cancer death in patients younger than 50 with non-muscle-invasive and muscle-invasive bladder cancer2022In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 56, no 1, p. 27-33Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION AND OBJECTIVES: Bladder cancer is primarily a disease of older age and little is known about the differences between patients diagnosed with bladder cancer at a younger versus older age. Our objectives were to compare bladder cancer specific survival in patients aged <50 versus those aged 50-70 at time of diagnosis.

    MATERIALS AND METHODS: The Swedish bladder cancer database provided data on patient demographics, clinical characteristics and treatments for this observational study. Cox proportional hazard regression models were adjusted for appropriate variables. All analyses were stratified by disease stage (non-muscle-invasive bladder cancer and muscle-invasive bladder cancer. Furthermore, we compared the frequency of lower urinary tract infections within 24 months prior to bladder cancer diagnosis by sex and age groups.

    RESULTS: The study included 15,452 newly-diagnosed BC patients (1997-2014); 1,207 (8%) patients were <50 whilst 14,245 (92%) were aged 50-70. Patients aged <50 at diagnosis were at a decreased risk of bladder cancer death (HR = 0.82, 95%CI: 0.68-0.99) compared to those aged 50-70. When stratified by non-muscle-invasive and muscle-invasive bladder cancer, this association remained in non-muscle-invasive patients only (<50, HR = 0.43, 95% CI: 0.28-0.64). The frequency of lower urinary tract infection diagnoses did not differ between younger and older patients in either men or women.

    CONCLUSIONS: Patients diagnosed with non-muscle-invasive bladder cancer when aged <50 are at decreased risk of bladder cancer-specific death when compared to their older (50-70) counterparts. These observations raise relevant research questions about age-related differences in diagnostic procedures, clinical decision-making and, not least, potential differences in tumour biology.

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  • 32.
    Sandgren, Kristina
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nilsson, Erik
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Keeratijarut Lindberg, Angsana
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Strandberg, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Blomqvist, Lennart
    Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Friedrich, Bengt
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Ögren, Margareta
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Ögren, Mattias
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    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.
    Söderström, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Jonsson, Joakim
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Registration of histopathology to magnetic resonance imaging of prostate cancer2021In: Physics and Imaging in Radiation Oncology, E-ISSN 2405-6316, Vol. 18, p. 19-25Article in journal (Refereed)
    Abstract [en]

    Background and purpose: The diagnostic accuracy of new imaging techniques requires validation, preferably by histopathological verification. The aim of this study was to develop and present a registration procedure between histopathology and in-vivo magnetic resonance imaging (MRI) of the prostate, to estimate its uncertainty and to evaluate the benefit of adding a contour-correcting registration.

    Materials and methods: For twenty-five prostate cancer patients, planned for radical prostatectomy, a 3D-printed prostate mold based on in-vivo MRI was created and an ex-vivo MRI of the specimen, placed inside the mold, was performed. Each histopathology slice was registered to its corresponding ex-vivo MRI slice using a 2D-affine registration. The ex-vivo MRI was rigidly registered to the in-vivo MRI and the resulting transform was applied to the histopathology stack. A 2D deformable registration was used to correct for specimen distortion concerning the specimen's fit inside the mold. We estimated the spatial uncertainty by comparing positions of landmarks in the in-vivo MRI and the corresponding registered histopathology stack.

    Results: Eighty-four landmarks were identified, located in the urethra (62%), prostatic cysts (33%), and the ejaculatory ducts (5%). The median number of landmarks was 3 per patient. We showed a median in-plane error of 1.8 mm before and 1.7 mm after the contour-correcting deformable registration. In patients with extraprostatic margins, the median in-plane error improved from 2.1 mm to 1.8 mm after the contour-correcting deformable registration.

    Conclusions: Our registration procedure accurately registers histopathology to in-vivo MRI, with low uncertainty. The contour-correcting registration was beneficial in patients with extraprostatic surgical margins.

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  • 33.
    Sandgren, Kristina
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Strandberg, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Jonsson, Joakim
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Grefve, Josefine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Keeratijarut Lindberg, Angsana
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nilsson, Erik
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Söderkvist, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Thellenberg-Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Friedrich, Bengt
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Blomqvist, Lennart
    Department of Molecular Medicine and Surgery, Karolinska Institute, Solna, Sweden.
    Loegager, Vibeke Berg
    Department of Radiology, Copenhagen University Hospital in Herlev, Herlev, Denmark.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    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.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Histopathology-validated lesion detection rates of clinically significant prostate cancer with mpMRI, [68Ga]PSMA-11-PET and [11C]Acetate-PET2023In: Nuclear medicine communications, ISSN 0143-3636, E-ISSN 1473-5628, Vol. 44, no 11, p. 997-1004Article in journal (Refereed)
    Abstract [en]

    Objective: PET/CT and multiparametric MRI (mpMRI) are important diagnostic tools in clinically significant prostate cancer (csPC). The aim of this study was to compare csPC detection rates with [68Ga]PSMA-11-PET (PSMA)-PET, [11C] Acetate (ACE)-PET, and mpMRI with histopathology as reference, to identify the most suitable imaging modalities for subsequent hybrid imaging. An additional aim was to compare inter-reader variability to assess reproducibility.

    Methods: During 2016–2019, all study participants were examined with PSMA-PET/mpMRI and ACE-PET/CT prior to radical prostatectomy. PSMA-PET, ACE-PET and mpMRI were evaluated separately by two observers, and were compared with histopathology-defined csPC. Statistical analyses included two-sided McNemar test and index of specific agreement.

    Results: Fifty-five study participants were included, with 130 histopathological intraprostatic lesions >0.05 cc. Of these, 32% (42/130) were classified as csPC with ISUP grade ≥2 and volume >0.5 cc. PSMA-PET and mpMRI showed no difference in performance (P = 0.48), with mean csPC detection rate of 70% (29.5/42) and 74% (31/42), respectively, while with ACE-PET the mean csPC detection rate was 37% (15.5/42). Interobserver agreement was higher with PSMA-PET compared to mpMRI [79% (26/33) vs 67% (24/38)]. Including all detected lesions from each pair of observers, the detection rate increased to 90% (38/42) with mpMRI, and 79% (33/42) with PSMA-PET.

    Conclusion: PSMA-PET and mpMRI showed high csPC detection rates and superior performance compared to ACE-PET. The interobserver agreement indicates higher reproducibility with PSMA-PET. The combined result of all observers in both PSMA-PET and mpMRI showed the highest detection rate, suggesting an added value of a hybrid imaging approach.

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  • 34.
    Sorbe, Bengt
    et al.
    Univ Hosp, Dept Oncol, S-70185 Örebro, Sweden .
    Söderstrom, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Treatment of Vaginal Recurrences in Endometrial Carcinoma by High-dose-rate Brachytherapy2013In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 33, no 1, p. 241-247Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of the present study was to evaluate the efficacy and safety of high-dose-rate brachytherapy alone or in combination with external pelvic irradiation in treatment of vaginal recurrences in endometrial carcinomas. Predictive and prognostic factors were also evaluated. Patients and Methods: Between 1990 and 2005, forty patients were consecutively treated for vaginal recurrences with or without extravaginal tumoral spread from endometrial carcinoma of International Federation of Gynecology and Obstetrics (FIGO) stages IA-IIIA. Thirty-five patients were treated primarily with surgery and five patients with primary radiotherapy. Six patients were treated with adjuvant external beam irradiation and seven patients with vaginal brachytherapy upfront. The medium time from diagnosis to recurrence was 17 months. The recurrences were treated with a combination of high-dose-rate brachytherapy (mean 25.8 Gy) and external beam pelvic irradiation (mean 46.7 Gy) in 24 cases (60%) and with external therapy-alone or brachytherapy-alone in 12 cases. Results: The local control of vaginal recurrences treated with a combination of external beam therapy and brachytherapy was 92%. The local control rate was lower for external beam therapy-alone. In eleven patients (28%), a second recurrence occurred (five vaginal and six distant metastases). The overall 5-year survival rate was 50%. Age, FIGO grade and time from diagnosis to recurrence were the only independent and significant prognostic factors. Upfront external beam therapy was associated with a worse overall survival rate. Site of recurrence was significant only in univariate analysis. Late gastrointestinal toxicity (grade 3-4) was recorded in 11% of irradiated patients. Conclusion: Combined high-dose-rate brachytherapy and external beam therapy was an effective treatment for vaginal recurrences. Age, FIGO grade, and time-to-recurrence were significant and independent prognostic factors. Upfront radiotherapy was an unfavorable prognostic factor in univariate analysis.

  • 35.
    Strandberg, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Jonsson, Joakim
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Zarei, Maryam
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Aglund, Kristina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Blomqvist, Lennart
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Sweden.
    Söderkvist, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Baseline and early response 2-[18F]FDG-PET/MRI for prediction of radiotherapy outcome in uterine cervical squamous cell carcinoma: a prospective single-center observational cohort study2024In: EJNMMI Reports, E-ISSN 3005-074X, Vol. 8, no 1, article id 5Article in journal (Refereed)
    Abstract [en]

    Background: Should early response imaging predict tumor response to therapy, personalized treatment adaptations could be feasible to improve outcome or reduce the risk of adverse events. This prospective single-center observational study on 2-fluorine-18-fluoro-deoxy-glucose (2-[18F]FDG) positron-emission tomography/magnetic resonance imaging (PET/MRI) features aims to investigate the association between semantic 2-[18F]FDG-PET/MRI imaging parameters and outcome prediction in uterine cervical squamous cell carcinoma (CSCC) treated with radiotherapy.

    Results: Eleven study participants with previously untreated CSCC were examined with 2-[18F]FDG-PET/MRI at baseline and approximately one week after start of curative radiotherapy. All study participants had at least 24 months clinical follow-up. Two patients relapsed during the follow-up period. Reduced tumor size according to visual assessment was present in 9/11 participants (median change in sum of largest diameters (SLD) − 10.4%; range − 2.5 to − 24.6%). The size reduction was less pronounced in the relapse group compared to the no relapse group, with median change in SLD − 4.9%, versus − 10.4%. None of the reductions qualified as significantly reduced or increased in size according to RECIST 1.1., hence all participants were at this stage classified as non-responders/stable disease. Median baseline functional tumor volume (FTV) for the relapse group was 126 cm3, while for the no relapse group 9.3 cm3. Median delta FTV in the relapse group was 50.7 cm3, representing an actual increase in metabolically active volume, while median delta FTV in the no relapse group was − 2.0 cm3. Median delta apparent diffusion coefficient (ADC) was lower in the relapse group versus the no relapse group (− 3.5 mm2/s vs. 71 mm2/s).

    Conclusions: Early response assessment with 2-[18F]FDG-PET/MRI identified potentially predictive functional imaging biomarkers for prediction of radiotherapy outcome in CSCC, that could not be recognized with tumor measurements according to RECIST 1.1. These biomarkers (delta FTV and delta ADC) should be further evaluated.

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  • 36.
    Söderström, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Cancercentrum, VLL.
    Radiotherapy for head and neck cancer: costs and benefits of time, dose and volume2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background In the treatment of head and neck cancers (HNCs), radiotherapy (RT) has the advantage of organ preservation compared to surgery. However, treatment toxicities associated with RT can affect important functions for everyday life, both in the acute and late stage. RT to macroscopic tumour in HNC is commonly combined with elective RT to cervical lymph nodes at risk of microscopic involvement. The resulting risk reduction of the elective treatment based on dose-volume parameters is sparsely evaluated. So is the relationship between the elective treatment and treatment toxicity. The present thesis addresses these aspects.

    A strategy aimed at improving the outcome of RT is accelerated fractionation (AF). AF strives to shorten total treatment time to minimise proliferation of the tumour tissue during the RT period. We have investigated the impact of AF on both disease control and toxicity.

    Methods In the ARTSCAN study, 750 patients with localised HNC were randomised between AF (68 Gy in 4.5 weeks) and conventional fractionation (CF) (68 Gy in 7 weeks). The elective treatment volume was prescribed 46 Gy with CF in both treatment arms. The thesis is based on four individual papers, investigating the issues above in the whole study population or in sub-populations.

    Results No difference in disease control or late toxicity between CF and AF was observed at five years. However, there was an increased acute toxicity with AF. Weight loss was associated with treatment volume, independent of tumour stage. The elective treatment volume was found to be an independent risk factor for late aspiration, as well as mean dose to the pharyngeal constrictor muscles, neck dissection, and age at randomisation. There was a significant risk reduction for node relapses in volumes treated to an elective dose. Only a relapse in volumes treated to >60 Gy affected the survival.

    Conclusion The present thesis questions the benefit of AF in definitive RT as well as extensive elective treatment of the cervical nodes.

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  • 37.
    Söderström, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nilsson, Per
    Dalianis, Tina
    Kjellen, Elisabeth
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Regional recurrence of oropharyngeal cancer after definitive radiotherapy: a case control study2015In: Radiation Oncology, E-ISSN 1748-717X, Vol. 10, article id 117Article in journal (Refereed)
    Abstract [en]

    Background: Elective treatment of lymph nodes in oropharyngeal cancer (OPC) has impact on both regional recurrences (RR) and risk of late side effects. This study was performed to quantify the dose-dependent impact on RR and overall survival (OS) in a prospectively collected cohort of OPC from the ARTSCAN study with emphasis on elective treatment. Methods: ARTSCAN is a previously published prospective, randomized, multicentre study of altered radiotherapy (RT) fractionation in head and neck cancer. In ARTSCAN the elective treatment volume for node positive OPC varied significantly between centres due to local treatment principles. All patients with OPC in complete response after primary treatment were eligible for the present case-control study. Cases were patients with RR during five years follow-up. Patients with no recurrence were eligible as controls. Four controls per case were matched according to T-and N-stage. Mean (D-mean) and median (D-50%) dose for the lymph node level (LNL) of RR in the cases and the corresponding LNL in the controls were analysed with conditional logistic regression. OS was estimated with the Kaplan-Meier method and evaluated by multivariate Cox regression analysis. Results: There was a dose-dependent risk reduction for D-50% in the interval that represented elective treatment (40-50 Gy) (OR = 0.18, p < 0.05) and a trend in the same dose interval for D-mean (OR = 0.19, p = 0.07). OS rates at five years were 0.39 (0.24-0.65) for cases and 0.70 (0.62-0.81) for controls (p < 0.001). The Kaplan-Meier and the Cox regression analysis for cases categorised by delivered dose showed an inverse relationship between dose and survival. The cases with RR in a LNL outside planning target volume (PTV) (D-mean < 40 Gy) had an OS rate comparable to that of all patients, and those with RR in a LNL in PTVelective (D-mean 40-60 Gy) or PTVtumour (D-mean > 60 Gy) did significantly worse (p < 0.05). The same inverse relationship was also shown for a small subset of patient with known HPV-status, defined by over expression of p16 (p < 0.05). Conclusions: There was a significant risk reduction for RR of elective treatment. However the OS for patients with RR outside target volumes was not affected, with similar results for patients with HPV-positive OPC. This could be an argument for a prospective randomized study on limited elective target volumes in OPC.

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  • 38.
    Söderström, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nilsson, Per
    Laurell, Göran
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Levring Jäghagen, Eva
    Umeå University, Faculty of Medicine, Department of Odontology.
    Dysphagia - Results from multivariable predictive modelling on aspiration from a subset of the ARTSCAN trial2017In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 122, no 2, p. 192-199Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To establish predictive models for late objective aspiration and late patient-reported choking based on dose-volume parameters and baseline patient and treatment characteristics, for patients with head and neck cancer undergoing definitive radiotherapy (RT). The impact of electively treated volume on late aspiration was also investigated.

    METHODS AND MATERIAL: This prospective cohort is a subsample of 124 survivors from the ARTSCAN study. Late aspiration was identified with videofluoroscopy, at a minimum of 25months after the start of RT. Patient-reported choking was analysed at 12 and 60months post RT using the EORTC Quality of Life Module for Head and Neck Cancer 35. Univariable and multivariable analyses were performed to describe the association between clinical factors and dose-volume descriptors for organs at risk (OARs) and late dysphagia.

    RESULTS: Aspiration was found in 47% of the eligible patients. Mean dose to the middle pharyngeal constrictor (MPC), neck dissection post RT and age at randomisation in ARTSCAN were associated to late aspiration. Mean dose to the superior pharyngeal constrictor (SPC) and swallowing complaints at baseline were associated to patient reported choking at both time-points.

    CONCLUSIONS: Three separate risk groups for late aspiration, and two risk groups for late patient-reported choking were identified based on number of risk factors. The size of the electively treated volume could be used as a surrogate for individual OARs predicting late aspiration.

  • 39. Tandstad, T.
    et al.
    Ståhl, O.
    Håkansson, U.
    Dahl, O.
    Haugnes, H. S.
    Klepp, O. H.
    Langberg, C. W.
    Laurell, A.
    Oldenburg, J.
    Solberg, A.
    Söderström, Karin
    The Cancer Clinic, Norrland University Hospital, Umeå.
    Cavallin-Ståhl, E.
    Stierner, U.
    Wahlquist, R.
    Wall, N.
    Cohn-Cedermark, G.
    One course of adjuvant BEP in clinical stage I nonseminoma mature and expanded results from the SWENOTECA group2014In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 25, no 11, p. 2167-2172Article in journal (Refereed)
    Abstract [en]

    The SWENOTECA group treated 517 clinical stage I nonseminoma patients with one course of adjuvant BEP in a prospective study. The median follow-up is 7.9 years. One course of adjuvant BEP reduced the risk of relapse by over 90%. The relapse rates were 1.6% in low-risk disease and 3.2% in high-risk disease. One course of adjuvant BEP should be considered a standard adjuvant treatment option.SWENOTECA has since 1998 offered patients with clinical stage I (CS I) nonseminoma, adjuvant chemotherapy with one course of bleomycin, etoposide and cisplatin (BEP). The aim has been to reduce the risk of relapse, sparing patients the need of toxic salvage treatment. Initial results on 312 patients treated with one course of adjuvant BEP, with a median follow-up of 4.5 years, have been previously published. We now report mature and expanded results. In a prospective, binational, population-based risk-adapted treatment protocol, 517 Norwegian and Swedish patients with CS I nonseminoma received one course of adjuvant BEP. Patients with lymphovascular invasion (LVI) in the primary testicular tumor were recommended one course of adjuvant BEP. Patients without LVI could choose between surveillance and one course of adjuvant BEP. Data for patients receiving one course of BEP are presented in this study. At a median follow-up of 7.9 years, 12 relapses have occurred, all with IGCCC good prognosis. The latest relapse occurred 3.3 years after adjuvant treatment. The relapse rate at 5 years was 3.2% for patients with LVI and 1.6% for patients without LVI. Five-year cause-specific survival was 100%. The updated and expanded results confirm a low relapse rate following one course of adjuvant BEP in CS I nonseminoma. One course of adjuvant BEP should be considered a standard treatment in CS I nonseminoma with LVI. For patients with CS I nonseminoma without LVI, one course of adjuvant BEP is also a treatment option.

  • 40.
    Wennerberg, Johan
    et al.
    Department of ORL, Head & Neck Surgery, Skåne University Hospital, Lund University, Sweden.
    Gebre-Medhin, Maria
    Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund University, Sweden.
    Nilsson, Per
    Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund University, Sweden.
    Brun, Eva
    Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund University, Sweden.
    Kjellén, Elisabeth
    Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund University, Sweden.
    Carlwig, Kristin
    Department of ORL, Head & Neck Surgery, Skåne University Hospital, Lund University, Sweden.
    Reizenstein, Johan
    Department of Oncology, Örebro University Hospital, Sweden.
    Kristiansson, Stefan
    Department of Otolaryngology, Örebro University Hospital, Sweden.
    Söderkvist, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wahlgren, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Results from a prospective, randomised study on (accelerated) preoperative versus (conventional) postoperative radiotherapy in treatment of patients with resectable squamous cell carcinoma of the oral cavity: The ARTSCAN 2 study2022In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 166, p. 26-32Article in journal (Refereed)
    Abstract [en]

    Background and purpose: An earlier prospective randomised multicentre study (ARTSCAN) in head and neck cancer patients that compared conventionally fractionated radiotherapy (CF) with accelerated radiotherapy (AF) was inconclusive. In the subgroup of oral cavity squamous cell cancer (OCSCC) a large absolute, but not statistically significant, difference in local control was seen in favour of AF. This difference was more pronounced in resectable tumours. The finding raised the hypothesis that AF could be beneficial for OCSCC patients. In addition, the longstanding controversy on pre- or postoperative radiotherapy was addressed.

    Materials and methods: Patients with OCSCC, judged to withstand and likely benefit from combined therapy, were recruited. Subjects were randomised to either preoperative AF with 43 fractions given as a concomitant boost with two fractions/day to the tumour bearing volume to a total dose of 68 Gy in 4.5 weeks followed by surgery, or primary surgery with postoperative CF, total dose 60 or 66 Gy in 6–7 weeks. For patients whose tumours had high-risk features, 66 Gy and concomitant cisplatin was prescribed.

    Results: 250 patients were randomised. Median follow-up was 5 years for locoregional control (LRC) and 9 years for overall survival (OS). There were no statistically significant differences between the two treatment arms regarding LRC and OS. LRC at five years was 73% (95% CI, 65–82) in preoperative AF and 78% (95% CI, 70–85) in postoperative CF. Toxicity was more pronounced in preoperative AF.

    Conclusion: This study does not support that AF prior to surgery improves outcome in oral cavity cancer compared with postoperative CF.

  • 41.
    Zackrisson, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Kjellén, Elisabeth
    Söderström, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Brun, Eva
    Nyman, Jan
    Friesland, Signe
    Reizenstein, Johan
    Sjodin, Helena
    Ekberg, Lars
    Lödén, Britta
    Franzén, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ask, Anders
    Wickart-Johansson, Gun
    Lewin, Freddi
    Björk-Eriksson, Thomas
    Lundin, Erik
    Dalianis, Tina
    Wennerberg, Johan
    Johansson, Karl-Axel
    Nilsson, Per
    Mature results from a Swedish comparison study of conventional versus accelerated radiotherapy in head and neck squamous cell carcinoma - The ARTSCAN trial2015In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 117, no 1, p. 99-105Article in journal (Refereed)
    Abstract [en]

    Background and purpose: This report contains the mature five-year data from the Swedish ARTSCAN trial including information on the influence of p16 positivity (p16+) for oropharyngeal cancers. Material and methods: Patients with previously untreated squamous cell carcinoma without distant metastases of the oral cavity, oropharynx, larynx (except T1-2, NO glottic cancers) and hypopharynx were included. Patients were randomised between accelerated fractionation (AF) (1.1 Gy + 2 Gy per day, 5 days/week for 4.5 weeks, total dose 68 Gy) and conventional fractionation (CF) (2 Gy per day, 5 days/week for 7 weeks, total dose 68 Gy). Human papillomavirus (HPV)-associated p16-expression was assessed retrospectively in tumour tissues from patients with oropharyngeal carcinoma. Results: There was no significant difference in loco-regional control (LRC) between AF and CF (log-rank test p = 0.75). LRC at 5 years was 65.5% for AF and 64.9% for CF. Overall survival (OS) was similar in both arms (p = 0.99). The estimated cancer specific survival (CSS) at 5 years was 62.2% (AF) and 63.3% (CF) (p = 0.99). 206 specimens were analysed for p16 with 153 specimens (74%) identified as p16+. P16 status did not discriminate for response to AF vs. CF with regard to LRC, OS or CSS. Patients with p16+ tumours had a statistically significant better overall prognosis compared with p16 tumours. Conclusion: This update confirms the results of the 2-year report. We failed to identify a positive effect resulting from AF with regards to LRC, OS and CSS. The addition of information on the HPV-associated p16 overexpression did not explain this lack of effect.

  • 42.
    Zarei, Maryam
    et al.
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Wallstén, Elin
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Grefve, Josefine
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Söderkvist, Karin
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Gunnlaugsson, Adalsteinn
    Department of Hematology, Oncology and Radiation Physics, Skane University Hospital, Lund, Sweden.
    Sandgren, Kristina
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Jonsson, Joakim
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Keeratijarut Lindberg, Angsana
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Nilsson, Erik
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Moreau, Mathieu
    Department of Hematology, Oncology and Radiation Physics, Skane University Hospital, Lund, Sweden.
    Thellenberg-Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Olsson, Lars E.
    Department of Translational Medicine, Medical Radiation Physics, Lund University, Malmö, Sweden.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Blomqvist, Lennart
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Sweden.
    Berg Loegager, Vibeke
    Department of Radiology, Copenhagen University Hospital in Herlev, Herlev, Denmark.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Strandberg, Sara
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Accuracy of gross tumour volume delineation with [68Ga]-PSMA-PET compared to histopathology for high-risk prostate cancer2024In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 63, p. 503-510Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The delineation of intraprostatic lesions is vital for correct delivery of focal radiotherapy boost in patients with prostate cancer (PC). Errors in the delineation could translate into reduced tumour control and potentially increase the side effects. The purpose of this study is to compare PET-based delineation methods with histopathology.

    MATERIALS AND METHODS: The study population consisted of 15 patients with confirmed high-risk PC intended for prostatectomy. [68Ga]-PSMA-PET/MR was performed prior to surgery. Prostate lesions identified in histopathology were transferred to the in vivo [68Ga]-PSMA-PET/MR coordinate system. Four radiation oncologists manually delineated intraprostatic lesions based on PET data. Various semi-automatic segmentation methods were employed, including absolute and relative thresholds, adaptive threshold, and multi-level Otsu threshold.

    RESULTS: The gross tumour volumes (GTVs) delineated by the oncologists showed a moderate level of interobserver agreement with Dice similarity coefficient (DSC) of 0.68. In comparison with histopathology, manual delineations exhibited the highest median DSC and the lowest false discovery rate (FDR) among all approaches. Among semi-automatic approaches, GTVs generated using standardized uptake value (SUV) thresholds above 4 (SUV > 4) demonstrated the highest median DSC (0.41), with 0.51 median lesion coverage ratio, FDR of 0.66 and the 95th percentile of the Hausdorff distance (HD95%) of 8.22 mm.

    INTERPRETATION: Manual delineations showed a moderate level of interobserver agreement. Compared to histopathology, manual delineations and SUV > 4 exhibited the highest DSC and the lowest HD95% values. The methods that resulted in a high lesion coverage were associated with a large overestimation of the size of the lesions.

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  • 43.
    Zborayova, Katarina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Blomqvist, L.
    Flygare, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Gebre-Medhin, M.
    Jonsson, Joakim
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Söderkvist, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Early changes in multiparametric imaging parameters during radiotherapy of squamous carcinoma2019In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 132, p. 63-63Article in journal (Other academic)
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