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  • 1.
    Adjeiwaah, Mary
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Bylund, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Lundman, Josef A.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Söderström, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Jonsson, Joakim H.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Garpebring, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    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.

  • 2.
    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, ISSN 1748-717X, 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.

  • 3.
    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.

  • 4.
    Jonsson, Joakim
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Söderkvist, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    The rationale for MR-only treatment planning for external radiotherapy2019In: Clinical and Translational Radiation Oncology, ISSN 2405-6308, Vol. 18, p. 60-65Article, review/survey (Refereed)
  • 5.
    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, ISSN 1748-717X, 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.

  • 6.
    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. 

  • 7.
    Nyholm, Tufve
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Svensson, Stina
    Andersson, Sebastian
    Jonsson, Joakim
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Sohlin, Maja
    Gustafsson, Christian
    Kjellén, Elisabeth
    Söderström, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Albertsson, Per
    Blomqvist, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    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.

  • 8.
    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.

  • 9.
    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, ISSN 1748-717X, 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.

  • 10.
    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.

  • 11.
    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.

  • 12.
    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, ISSN 1748-717X, 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.

  • 13.
    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.

  • 14. 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.

  • 15.
    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.

  • 16.
    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.
    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)
1 - 16 of 16
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