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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.
    Aglund, Kristina
    et al.
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Rauvala, Marita
    Puistola, Ulla
    Ångström, Tord
    Umeå University, Faculty of Medicine, Medical Biosciences.
    Turpeenniemi-Hujanen, Taina
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Stendahl, Ulf
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Gelatinases A and B (MMP-2 and MMP-9) in endometrial cancer-MMP-9 correlates to the grade and the stage2004In: Gynecol Oncol, ISSN 0090-8258, Vol. 94, no 3, p. 699-704Article in journal (Refereed)
  • 3. Ahlqvist-Rastad, Jane
    et al.
    Albertsson, Maria
    Bergh, Jonas
    Birgegård, Gunnar
    Johansson, Peter
    Jonsson, Bertil
    Kjellén, Elisabeth
    Påhlman, Sven
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Österborg, Anders
    Erythropoietin therapy and cancer related anaemia: updated Swedish recommendations.2007In: Med Oncol, ISSN 1357-0560, Vol. 24, no 3, p. 267-272Article in journal (Refereed)
  • 4. Ask, Anders
    et al.
    Björk-Eriksson, Thomas
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Blomquist, Erik
    Glimelius, Bengt
    The potential of proton beam radiation therapy in head and neck cancer.2005In: Acta Oncol, ISSN 0284-186X, Vol. 44, no 8, p. 876-880Article in journal (Refereed)
  • 5.
    Brynolfsson, Patrik
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Holmberg, August
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Jonsson, Joakim
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Goldhaber, David
    Jian, Yiqiang
    Illerstam, Fredrik
    Engström, Mathias
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Technical note: adapting a GE SIGNA PET/MR scanner for radiotherapy2018In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 45, no 8, p. 3546-3550Article in journal (Refereed)
    Abstract [en]

    Purpose: Simultaneous collection of PET and MR data for radiotherapy purposes are useful for, for example, target definition and dose escalations. However, a prerequisite for using PET/MR in the radiotherapy workflow is the ability to image the patient in treatment position. The aim of this work was to adapt a GE SIGNA PET/MR scanner to image patients for radiotherapy treatment planning and evaluate the impact on signal-to-noise (SNR) of the MR images, and the accuracy of the PET attenuation correction. Method: A flat tabletop and a coil holder were developed to image patients in the treatment position, avoid patient contour deformation, and facilitate attenuation correction of flex coils. Attenuation corrections for the developed hardware and an anterior array flex coil were also measured and implemented to the PET/MR system to minimize PET quantitation errors. The reduction of SNR in the MR images due to the added distance between the coils and the patient was evaluated using a large homogenous saline-doped water phantom, and the activity quantitation errors in PET imaging were evaluated with and without the developed attenuation corrections. Result: We showed that the activity quantitation errors in PET imaging were within ±5% when correcting for attenuation of the flat tabletop, coil holder, and flex coil. The SNR of the MRI images were reduced to 74% using the tabletop, and 66% using the tabletop and coil holders. Conclusion: We present a tabletop and coil holder for an anterior array coil to be used with a GE SIGNA PET/MR scanner, for scanning patients in the radiotherapy work flow. Implementing attenuation correction of the added hardware from the radiotherapy setup leads to acceptable PET image quantitation. The drop in SNR in MR images may require adjustment of the imaging protocols.

  • 6. Glimelius, Bengt
    et al.
    Ask, Anders
    Bjelkengren, Göran
    Björk-Eriksson, Thomas
    Blomquist, Erik
    Johansson, Bengt
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Number of patients potentially eligible for proton therapy2005In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 44, no 8, p. 836-849Article in journal (Refereed)
    Abstract [en]

    A group of Swedish radiation oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy in a facility where one of the principal aims is to facilitate randomized and other studies in which the advantage of protons can be shown and the magnitude of the differences compared with optimally administered conventional radiation treatment, also including intensity-modulated radiation therapy (IMRT) and brachytherapy, can be shown. The estimations have been based on current statistics of tumour incidence in Sweden, number of patients potentially eligible for radiation treatment, scientific support from clinical trials and model dose planning studies and knowledge of the dose-response relations of different tumours together with information on normal tissue complication rates. In Sweden, it is assessed that between 2200 and 2500 patients annually are eligible for proton beam therapy, and that for these patients the potential therapeutic benefit is so great as to justify the additional expense of proton therapy. This constitutes between 14- 15% of all irradiated patients annually.

  • 7. Johansson, Karl-Axel
    et al.
    Nilsson, Per
    Zackrisson, Björn
    Ohlson, Birgitta
    Kjellén, Elisabeth
    Mercke, Claes
    Alvarez-Fonseca, Mauricio
    Billström, Anette
    Björk-Eriksson, Thomas
    Björ, Ove
    Ekberg, Lars
    Friesland, Signe
    Karlsson, Magnus
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Lagerlund, Magnus
    Lundkvist, Lena
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Löfroth, Per-Olov
    Löfvander-Thapper, Kerstin
    Nilsson, Alla
    Nyman, Jan
    Persson, Essie
    Reizenstein, Johan
    Rosenbrand, Hans-Olov
    Wiklund, Fredrik
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wittgren, Lena
    The quality assurance process for the ARTSCAN head and neck study - A practical interactive approach for QA in 3DCRT and IMRT2008In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 87, no 2, p. 290-299Article in journal (Refereed)
    Abstract [en]

    AIM: This paper describes the quality assurance (QA) work performed in the Swedish multicenter ARTSCAN (Accelerated RadioTherapy of Squamous cell CArcinomas in the head and Neck) trial to guarantee high quality in a multicenter study which involved modern radiotherapy such as 3DCRT or IMRT.

    MATERIALS AND METHODS: The study was closed in June 2006 with 750 randomised patients. Radiation therapy-related data for every patient were sent by each participating centre to the QA office where all trial data were reviewed, analysed and stored. In case of any deviation from the protocol, an interactive process was started between the QA office and the local responsible clinician and/or physicist to increase the compliance to the protocol for future randomised patients. Meetings and workshops were held on a regular basis for discussions on various trial-related issues and for the QA office to report on updated results.

    RESULTS AND DISCUSSION: This review covers the 734 patients out of a total of 750 who had entered the study. Deviations early in the study were corrected so that the overall compliance to the protocol was very high. There were only negligible variations in doses and dose distributions to target volumes for each specific site and stage. The quality of the treatments was high. Furthermore, an extensive database of treatment parameters was accumulated for future dose-volume vs. endpoint evaluations.

    CONCLUSIONS: This comprehensive QA programme increased the probability to draw firm conclusions from our study and may serve as a concept for QA work in future radiotherapy trials where comparatively small effects are searched for in a heterogeneous tumour population.

  • 8.
    Karlsson, Mikael
    et al.
    Umeå University, Faculty of Medicine, Radiation Sciences, Radiation Physics.
    Björk-Eriksson, Thomas
    Mattsson, Olof
    Mattsson, Sören
    Montelius, Anders
    Nilsson, Per
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Distributed proton radiation therapy - A new concept for advance competence support2006In: Acta Oncologica, ISSN 0284-186X, Vol. 45, no 8, p. 1094-1101Article in journal (Refereed)
  • 9.
    Karlsson, Mikael
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Björk-Eriksson, Thomas
    Mattsson, Olof
    Mattsson, Sören
    Montelius, Anders
    Nilsson, Per
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    "Distributed proton radiation therapy'': a new concept for advanced competence support2006In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 45, no 8, p. 1094-1101Article in journal (Refereed)
    Abstract [en]

    The increased interest in high precision radiation therapy is to a large extent driven by the potential of modern imaging technology. The aim of this project was to analyse how an expensive proton facility best could support a multi-centre health care system. We have developed a model for distributed expert collaboration where all clinical experts will work close to their patients in regional centres. Patients who are candidates for proton therapy will be examined and dose-planned at their regional clinic, discussed in a fully information supported video conference and digitally made available at the proton treatment facility. The proton facility itself will be placed near a communication centre easily reached by all patients where they will be treated under full responsibility of their own physician at the home clinic. This concept has been analysed in detail both with respect to the overall functionality and with respect to possible weaknesses. It was found that the concept of distributed radiation therapy, as proposed here, will offer a stable clinical solution for advanced radiation therapy. It will support the spread of knowledge, serve as a fully developed backup system and the concept will further serve as an efficient base for clinical research.

  • 10.
    Karlsson, Mikael
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Karlsson, Magnus G
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Amies, Christopher
    Siemens Medical Systems, Oncology Care Systems Group, Concord, California.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Dedicated magnetic resonance imaging in the radiotherapy clinic2009In: International journal of radiation oncology, biology, physics, ISSN 1879-355X, Vol. 74, no 2, p. 644-651Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To introduce a novel technology arrangement in an integrated environment and outline the logistics model needed to incorporate dedicated magnetic resonance (MR) imaging in the radiotherapy workflow. An initial attempt was made to analyze the value and feasibility of MR-only imaging compared to computed tomography (CT) imaging, testing the assumption that MR is a better choice for target and healthy tissue delineation in radiotherapy. METHODS AND MATERIALS: A 1.5-T MR unit with a 70-cm-bore size was installed close to a linear accelerator, and a special trolley was developed for transporting patients who were fixated in advance between the MR unit and the accelerator. New MR-based workflow procedures were developed and evaluated. RESULTS: MR-only treatment planning has been facilitated, thus avoiding all registration errors between CT and MR scans, but several new aspects of MR imaging must be considered. Electron density information must be obtained by other methods. Generation of digitally reconstructed radiographs (DRR) for x-ray setup verification is not straight forward, and reliable corrections of geometrical distortions must be applied. The feasibility of MR imaging virtual simulation has been demonstrated, but a key challenge to overcome is correct determination of the skeleton, which is often needed for the traditional approach of beam modeling. The trolley solution allows for a highly precise setup for soft tissue tumors without the invasive handling of radiopaque markers. CONCLUSIONS: The new logistics model with an integrated MR unit is efficient and will allow for improved tumor definition and geometrical precision without a significant loss of dosimetric accuracy. The most significant development needed is improved bone imaging.

  • 11.
    Karlsson, Mikael
    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.
    Karlsson, Magnus G
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    MR-only procedures for improved overall precision in radiotherapy2009In: International Journal of Radiation Oncology Biology Physics: Proceedings of the American Society for Radiation Oncology 51st Annual Meeting, 51st Annual Meeting of the American Society for Radiation Oncology, 2009, p. S656-S656Conference paper (Refereed)
    Abstract [en]

     Purpose/Objective(s)

    To reduce the overall geometrical uncertainty in radiotherapy by introducing a novel technology arrangement based on a dedicated MR in an integrated workflow. A new logistics model needed to incorporate MR in this way was developed and clinically evaluated. Testing the assumption that MR is a better choice for target and healthy tissue delineation in radiotherapy, the suggested procedure was analyzed with respect to feasibility and precision of MR-only imaging compared to CT. The focus of the present study was on the geometrical uncertainty which is connected to the required margins between PTV and CTV.

     

    Materials/Methods

    A 1.5-T “open bore” MR unit with a 70-cm-bore size, Siemens Espree, was installed in close proximity to a treatment unit. A new MR-based workflow procedure was developed where all target drawing and treatment planning was performed on MR-data only. For non-fixed soft tissue targets, e.g. prostate, a special trolley was developed for transporting patients, who were immobilized, between the MR unit and the accelerator. The geometrical uncertainty using the transport solution was added to the uncertainty originating from the target definition process and compared with the total uncertainty in a more conventional CT based workflow.

    Results

    MR-only treatment planning has been facilitated, thus avoiding all registration errors between CT and MR data, but several new aspects of MR imaging must be considered. Reliable corrections of geometrical distortions must be applied and electron density information must be obtained by other methods. The feasibility of MR virtual simulation has previously been demonstrated. However, a key challenge is improve the visualization of skeletal structures, which is often needed for the traditional approach of set-up verification. The trolley solution allows for a highly precise setup of soft tissue targets without the invasive handling of fiducial markers. In the overall analyses of geometrical uncertainties it was shown that the combined uncertainty is reduced with the MR based workflow, mostly because of reduced systematic uncertainties when the CT-image registration is avoided.

    Conclusions

    The new logistics model is efficient and will allow for improved tumor definition and geometrical precision without a significant loss of dosimetric accuracy. Treatment planning directly on MR images is a way to reduce the geometrical uncertainty for e.g. prostate treatments. MR aided patient positioning does not require implanted fiducial markers and will be facilitated by rigid MR-MR registration. Less precise soft tissue CT-CT or CT-MR registrations will thus be avoided.

  • 12.
    Karlsson, Mikael
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Exploration of new treatment modalities offered by high energy (up to 50 MeV) electrons and photons1997In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 43, no 3, p. 303-309Article in journal (Refereed)
    Abstract [en]

    Background and purpose: A number of deep seated tumours are difficult to treat conformally with photon beams mainly dub to the almost exponential dose decrease with depth.

    Materials and methods: In order to improve the conformity of these treatments a number of useful characteristics of high energy (above 20 MeV) electron beams of the MM50 Racetrack Microtron have been systematically investigated and clinically applied.

    Results: A typical characteristic of electron beams with energies up to 20 MeV is the sharp dose fall-off with depth. At higher energies this effect is less pronounced but may be improved by adding a small fraction of photons with a matching dose gradient (wedge). With this technique, high energy electrons can be used close to sensitive organs down to 17 cm depth. Another physical characteristic of high energy electrons is the sharp penumbra at depths down to 4-5 cm and the possibility to use opposed electron beams in order to enhance the dose centrally or near the centre of a body. Skin sparing by delivering a part of the absorbed dose with photons through the same beam portal as the electrons has also been systematically studied. These characteristics of the high-energy electron beams have been utilised in the optimisation of some clinical treatments.

    Conclusions: Electron beams in this high energy region give increased possibilities to achieve dose conformity. Enhanced conformity can be obtained especially if electrons and photons are combined to augment some specific characteristics of the electron beams.

  • 13.
    Karlsson, Mikael
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Matching of electron and photon beams with a multi-leaf collimator1993In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 29, no 3, p. 317-326Article in journal (Refereed)
    Abstract [en]

    Multi-leaf collimators (MLCs) are offered as an accessory to many accelerators for radiation therapy. However, beam edges generated with these collimators are not as smooth as can be achieved with individually made blocks. The clinical drawbacks and benefits of this ripple were evaluated both for single field treatments and for combined adjacent fields of different beam qualities. In this investigation the MLC-collimated beams of the MM50 racetrack microtron were studied. The distance between the field edge and the 90% isodose was measured at the reference depth for four beam qualities (20 MV photons and 10, 20 and 50 MeV electrons). This distance was found to vary from approximately 6 mm for straight beam edges (i.e., all collimator leaves aligned) to approximately 2 mm from the tip of the leaves for a saw-tooth shaped beam edge. The over- and under-dosage in the joint between combined adjacent fields was found to be typically +/- 10% in small volumes. Improved clinical techniques using adjacent photon and electron fields with the same isocentre and source position (without moving the gantry) have been developed. For treatments of the breast, including the mammary chain, a uniform dose distribution was created with special attention given to the irradiation of the heart and lung outside the target volume. A method for head and neck treatments was optimised to give uniform dose distribution in the joint between the photon and electron fields and a method of treating the mediastinum, including the chest wall in front of the left lung, was analysed with respect to dose uniformity in the tumour and shielding of the lung.

  • 14. Kjellén, Elisabeth
    et al.
    Sasaki, Yutaka
    Kjellström, Johan
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Wennerberg, Johan
    Recombinant erythropoietin beta enhances growth of xenografted human squamous cell carcinoma of the head and neck after surgical trauma2006In: Acta Otolaryngol, ISSN 0001-6489, Vol. 126, no 5, p. 545-547Article in journal (Refereed)
  • 15. Lacas, Benjamin
    et al.
    Bourhis, Jean
    Overgaard, Jens
    Zhang, Qiang
    Gregoire, Vincent
    Nankivell, Matthew
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Szutkowski, Zbigniew
    Suwinski, Rafal
    Poulsen, Michael
    O'Sullivan, Brian
    Corvo, Renzo
    Laskar, Sarbani Ghosh
    Fallai, Carlo
    Yamazaki, Hideya
    Dobrowsky, Werner
    Cho, Kwan Ho
    Garden, Adam S.
    Langendijk, Johannes A.
    Viegas, Celia Maria Pais
    Hay, John
    Lotayef, Mohamed
    Parmar, Mahesh K. B.
    Auperin, Anne
    van Herpen, Carla
    Maingon, Philippe
    Trotti, Andy M.
    Grau, Cai
    Pignon, Jean-Pierre
    Blanchard, Pierre
    Role of radiotherapy fractionation in head and neck cancers (MARCH): an updated meta-analysis2017In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 18, no 9, p. 1221-1237Article in journal (Refereed)
    Abstract [en]

    Background: The Meta-Analysis of Radiotherapy in squamous cell Carcinomas of Head and neck(MARCH) showed that altered fractionation radiotherapy is associated with improved overall and progression-free survival compared with conventional radiotherapy, with hyperfractionated radiotherapy showing the greatest benefit. This update aims to confirm and explain the superiority of hyperfractionated radiotherapy over other altered fractionation radiotherapy regimens and to assess the benefit of altered fractionation within the context of concomitant chemotherapy with the inclusion of new trials.

    Methods: For this updated meta-analysis, we searched bibliography databases, trials registries, and meeting proceedings for published or unpublished randomised trials done between Jan 1, 2009, and July 15, 2015, comparing primary or postoperative conventional fractionation radiotherapy versus altered fractionation radiotherapy (comparison 1) or conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone (comparison 2). Eligible trials had to start randomisation on or after Jan 1, 1970, and completed accrual before Dec 31, 2010; had to have been randomised in a way that precluded prior knowledge of treatment assignment; and had to include patients with non-metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx undergoing first-line curative treatment. Trials including a non-conventional radiotherapy control group, investigating hypofractionated radiotherapy, or including mostly nasopharyngeal carcinomas were excluded. Trials were grouped in three types of altered fractionation: hyperfractionated, moderately accelerated, and very accelerated. Individual patient data were collected and combined with a fixed-effects model based on the intention-to-treat principle. The primary endpoint was overall survival.

    Findings: Comparison 1 (conventional fractionation radiotherapy vs altered fractionation radiotherapy) included 33 trials and 11 423 patients. Altered fractionation radiotherapy was associated with a significant benefit on overall survival (hazard ratio [HR] 0·94, 95% CI 0·90–0·98; p=0·0033), with an absolute difference at 5 years of 3·1% (95% CI 1·3–4·9) and at 10 years of 1·2% (−0·8 to 3·2). We found a significant interaction (p=0·051) between type of fractionation and treatment effect, the overall survival benefit being restricted to the hyperfractionated group (HR 0·83, 0·74–0·92), with absolute differences at 5 years of 8·1% (3·4 to 12·8) and at 10 years of 3·9% (−0·6 to 8·4). Comparison 2 (conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone) included five trials and 986 patients. Overall survival was significantly worse with altered fractionation radiotherapy compared with concomitant chemoradiotherapy (HR 1·22, 1·05–1·42; p=0·0098), with absolute differences at 5 years of −5·8% (−11·9 to 0·3) and at 10 years of −5·1% (−13·0 to 2·8).

    Interpretation: This update confirms, with more patients and a longer follow-up than the first version of MARCH, that hyperfractionated radiotherapy is, along with concomitant chemoradiotherapy, a standard of care for the treatment of locally advanced head and neck squamous cell cancers. The comparison between hyperfractionated radiotherapy and concomitant chemoradiotherapy remains to be specifically tested.

  • 16. Lassen, P.
    et al.
    Lacas, B.
    Pignon, J. P.
    Trotti, A.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Zhang, Q.
    Overgaard, J.
    Blanchard, P.
    Prognostic Impact of HPV-Associated p16 Expression and Smoking Status on Outcomes Following Radiation Therapy for Oropharyngeal Cancer: the MARCH-HPV Project2018In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 100, no 5, p. 1332-1332Article in journal (Other academic)
  • 17. Lassen, Pernille
    et al.
    Lacas, Benjamin
    Pignon, Jean-Pierre
    Trotti, Andy
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Zhang, Qiang
    Overgaard, Jens
    Blanchard, Pierre
    Prognostic impact of HPV-associated p16-expression and smoking status on outcomes following radiotherapy for oropharyngeal cancer: the MARCH-HPV project2018In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 126, no 1, p. 107-115Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Evaluate the prognostic and predictive impact of HPV-associated p16 -expression and assess the combined prognostic impact of p16 and smoking on altered fractionated radiotherapy (AFRT) for oropharyngeal cancer (OPC) within the frames of the update of the Meta-Analysis of Radiotherapy in Carcinomas of Head and neck (MARCH). Materials and methods: Patients with OPC, known tumor p16-status and smoking history were identified from the MARCH update, resulting in a dataset of 815 patients from four randomized trials (RTOG9003, DAHANCA6&7, RTOG0129, ARTSCAN). Analysis was performed using a Cox model stratified by trial and adjusted on gender, age, T-stage, N-stage, type of radiotherapy fractionation, p16, smoking. Primary end-point was progression-free survival (PFS). Results: In total, 465 patients (57%) had p16-positive tumors and 350 (43%) p16-negative. Compared to p16-negative, p16-positive patients had significantly better PFS (HR = 0.42 [95% CI: 0.34-0.51], 28.9% absolute increase at 10 years) and OS (HR = 0.40 [0.32-0.49], 32.1% absolute increase at 10 years). No interaction between p16-status and fractionation schedule was detected. Smoking negatively impacted outcome; in the p16-positive subgroup, never smokers had significantly better PFS than former/current smokers (HR = 0.49 [0.33-0.75], 24.2% survival benefit at 10 years). Conclusions: No predictive impact of p16-status on response to AFRT could be detected but the strong prognostic impact of p16-status was confirmed and especially p16-positive never smoking patients have superior outcome after RT. 

  • 18.
    Lindblom, Ulrika
    et al.
    Department of Clinical Sciences, Otorhinolaryngology, Lund University, Lund, Sweden ; Department of Otorhinolaryngology, Kirkenes Hospital, Kirkenes , Norway Correspondence: P. Nilsson, Department of Oncology and Radiation Physics, Skåne University Hospital, Lund University, Lund, Sweden.
    Gärskog, Ola
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Kjellén, Elisabeth
    Department of Oncology and Radiation Physics, Skåne University Hospital, Lund University, Lund, Sweden.
    Laurell, Göran
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Levring Jäghagen, Eva
    Umeå University, Faculty of Medicine, Department of Odontology.
    Wahlberg, Peter
    Department of Clinical Sciences, Otorhinolaryngology, Lund University, Lund, Sweden.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nilsson, Per
    Department of Oncology and Radiation Physics, Skåne University Hospital, Lund University, Lund, Sweden.
    Radiation-induced trismus in the ARTSCAN head and neck trial2014In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, no 5, p. 620-627Article in journal (Refereed)
    Abstract [en]

    Trismus, a well-known sequelae after treatment of head and neck cancer, decreases a patient's oral function and quality of life. The main objectives of this study were to: 1) investigate the long-term prevalence of radiation-induced trismus in patients treated for head and neck cancer according to two different fractionation schedules; and 2) model a dose-response relationship for trismus. MATERIAL AND METHODS: Patients were recruited from the Swedish ARTSCAN trial, a prospective randomised multicentre study comparing conventional and accelerated fractionation. A total of 124 patients agreed to a clinical ENT examination 21-127 months (median 66 months) after beginning radiation therapy. Trismus-related scores were assessed using the EORTC H&N35 Quality of Life questionnaire. The TheraBite(®) range of motion scale was used to measure maximal interincisal distance. The dose-response relationship for structures important for mastication and the temporomandibular joints was investigated by normal tissue complication probability modelling. RESULTS: No significant differences in patient-reported trismus or maximal interincisal distance were found between the two trial arms. Patient-reported moderate to high scores regarding trismus increased from 3% at the start of radiation therapy to 25% at the long-term follow-up. Maximal interincisal distance correlated significantly with patient-reported scores of trismus. The best dose-response fit to the endpoint data was found for the dose to the ipsilateral masseter. CONCLUSIONS: Trismus is a persistent complication after radiotherapy with 3D-conformal radiation therapy. We found no difference between the severity and prevalence of trismus between conventional and accelerated fractionation, but a significant correlation between the absorbed dose to the mastication structures and opening of the mouth. Further prospective studies may determine whether a reduced dose to structures important for mastication using intensity-modulated radiation therapy will reduce problems with trismus.

  • 19. Lindblom, Ulrika
    et al.
    Nilsson, Per
    Gärskog, Ola
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Kjellen, Elisabeth
    Laurell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Wahlberg, Peter
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Levring Jäghagen, Eva
    Umeå University, Faculty of Medicine, Department of Odontology.
    Aspiration as a late complication after accelerated versus conventional radiotherapy in patients with head and neck cancer2016In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 136, no 3, p. 304-311Article in journal (Refereed)
    Abstract [en]

    Conclusion Neck dissection after radiotherapy increased the risk of aspiration as a late effect in a sub-sample of patients treated for head and neck cancer in the ARTSCAN study. Patients treated with accelerated fractionation (AF) developed aspiration, with or without coughing, more frequently than patients treated with conventional fractionation (CF). Objectives A long-term follow-up study was conducted to determine the frequency of aspiration as a late effect in patients with head and neck cancer treated with AF or CF. Method One-hundred and eight patients were recruited from two centres of the Swedish multi-centre study, ARTSCAN, where AF and CF were compared. Patients with positive lymph nodes were treated with neck dissection after completing radiotherapy. The follow-up was performed at a median of 65 months after initiation of radiotherapy and included an ENT and a videofluoroscopic examination. Results Aspiration was found in 51/108 (47%) and silent aspiration in 34/96 (35%) patients. Neck dissection (n = 47 patients) was significantly associated with both aspiration and silent aspiration. Aspiration was more common among patients treated with AF (34/61; 56%) compared to CF (17/47; 36%; p = 0.053). Silent aspiration was also more common after AF (24/54; 44%) than after CF (10/42; 24%; p = 0.052).

  • 20.
    Mu, Xiangkui
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Björk-Eriksson, Thomas
    Nill, Simeon
    Oelfke, Uwe
    Johansson, Karl-Axel
    Gagliardi, Giovanna
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Does electron and proton therapy reduce the risk of radiation induced cancer after spinal irradiation for childhood medulloblastoma? A comparative treatment planning study2005In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 44, no 6, p. 554-562Article in journal (Refereed)
    Abstract [en]

    The aim of this treatment planning comparison study was to explore different spinal irradiation techniques with respect to the risk of late side-effects, particularly radiation-induced cancer. The radiotherapy techniques compared were conventional photon therapy, intensity modulated x-ray therapy (IMXT), conventional electron therapy, intensity/energy modulated electron therapy (IMET) and proton therapy (IMPT).CT images for radiotherapy use from five children, median age 8 and diagnosed with medulloblastoma, were selected for this study. Target volumes and organs at risk were defined in 3-D. Treatment plans using conventional photon therapy, IMXT, conventional electron therapy, IMET and IMPT were set up. The probability of normal tissue complication (NTCP) and the risk of cancer induction were calculated using models with parameters-sets taken from published data for the general population; dose data were taken from dose volume histograms (DVH). Similar dose distributions in the targets were achieved with all techniques but the absorbed doses in the organs-at-risk varied significantly between the different techniques. The NTCP models based on available data predicted very low probabilities for side-effects in all cases. However, the effective mean doses outside the target volumes, and thus the predicted risk of cancer induction, varied significantly between the techniques. The highest lifetime risk of secondary cancers was estimated for IMXT (30%). The lowest risk was found with IMPT (4%). The risks associated with conventional photon therapy, electron therapy and IMET were 20%, 21% and 15%, respectively. This model study shows that spinal irradiation of young children with photon and electron techniques results in a substantial risk of radiation-induced secondary cancers. Multiple beam IMXT seems to be associated with a particularly high risk of secondary cancer induction. To minimise this risk, IMPT should be the treatment of choice. If proton therapy is not available, advanced electron therapy may provide a better alternative.

  • 21.
    Mu, Xiangkui
    et al.
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Löfroth, Per-Olov
    Umeå University, Faculty of Medicine, Radiation Sciences, Radiation Physics.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Radiation Sciences, Radiation Physics.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Reply to letter by Tomé, Welsh and Fowler: Letter to the Editor2004In: Radioth Oncol, Vol. 72, p. 114-115Article in journal (Refereed)
  • 22.
    Mu, Xiangkui
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Löfroth, Per-Olov
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    The effect of fraction time in intensity modulated radiotherapy: theoretical and experimental evaluation of an optimisation problem.2003In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 68, no 2, p. 181-187Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: In intensity modulated radiotherapy (IMRT), the complexity and the number of treatment fields have expanded. This may imply that the delivery time for each fraction becomes prolonged. In a number of IMRT techniques used in the clinic, the delivery time per fraction is usually 10-15 min, sometimes more than 15 min. In studies on human skin, prolonged delivery time is shown to cause significant reduction of radiation effects compared with acute irradiation. In this paper the effect of changes in fraction delivery time was studied by in vitro irradiation of mammalian cells. MATERIAL AND METHODS: Chinese hamster fibroblasts (V79-379-A) were used for simulating clinical situations. Most experiments were performed with 2Gy/fraction with 4-h intervals in 40-60 replicates. Each fraction was divided into different subfractions, simulating the delivery of a complicated treatment. The effect of changing the delivery time for each fraction was studied. Parameters for the cell survival curve and repair kinetics were determined experimentally. The same methods were also used for large fraction sizes (8Gy). The validity of the most widely used models in the literature, all derived from linear-quadratic formalism, were tested against the experimental results. RESULTS: The effect of prolonging the fraction time for 2-Gy fractions was underestimated by the biological models. The experiments showed that 10-min prolonged delivery time gave a ratio between surviving fractions at 2Gy (S-ratio) of 1.054 with a 95% confidence interval (CI) 1.030-1.080, while the models predicted 1.007 and 1.009. Extending the fraction time to 20 min gave an S-ratio of 1.063 with CI of 1.045-1.080, while the models predicted 1.012 and 1.014. For 8-Gy fractions, there was a good agreement between predications and experimental results. The ratio between surviving fractions at 8Gy is 1.370 with CI of 1.300-1.440, while the models predicated 1.37 and 1.35. CONCLUSIONS: The effect of prolonging fraction time at conventional dose/fraction is underestimated by biological models. Prolonging the fraction time will spare tissues with a fast DNA repair. There is a risk for sparing tumours. This should be considered when IMRT technique is implemented in the clinic.

  • 23.
    Mu, Xiangkui
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Olofsson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Sjögren, Rickard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Can photon IMRT be improved by combination with mixed electron and photon techniques?2004In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 43, no 8, p. 727-735Article in journal (Refereed)
    Abstract [en]

    Conformal radiotherapy or intensity modulated radiotherapy (IMRT) commonly leads to a large integral dose in the patient. Electrons would reduce the integral dose but are not suitable for treating deep-seated tumours, owing to their limited penetration. By combining electron and photon beams, the dose distributions may be improved. In this study, the possibility is explored of using a mixture of electron and photon beams for a deep-seated target volume in the head and neck region. Treatment plans were made for five simulated head and neck cancer cases. Mixed electron and photon beam plans (MB) were constructed using a manual iterative procedure. Photon IMRT plans were optimized automatically. Both electron and photon beams were collimated by a computer controlled multi-leaf collimator (MLC). Both methods were able to produce clinically acceptable plans. Criteria for the target dose were met similarly by both as were the criteria for critical organs. The integral dose outside the planning target volume (PTV) showed a tendency to be lower with MB plans compared with photon IMRT plans. A mixed electron and photon technique has the potential to treat deep-seated tumours. It is reasonable to expect that if computerized optimization tools were coupled with the mixed electron and photon beam technique, treatment goals would be more readily achieved than if using solely pure photon IMRT.

  • 24.
    Mullaney, Tara
    et al.
    Umeå University, Faculty of Science and Technology, Umeå Institute of Design.
    Olausson, Kristina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sharp, Lena
    Karolinska Institute, Department of Learning, Informatics, Management and Ethics.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Edvardsson, David
    Umeå University, Faculty of Medicine, Department of Nursing.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    The influence of a department's psychosocial climate and treatment environment on cancer patients' anxiety during radiotherapy2016In: European Journal of Oncology Nursing, ISSN 1462-3889, E-ISSN 1532-2122, Vol. 20, p. 113-118Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The objective of this study is to determine whether there is a relationship between cancer patients' perceptions of the person-centeredness of their treatment experience and their anxiety levels during treatment.

    METHOD: A questionnaire was distributed to adult cancer patients going through external beam radiotherapy (RT) with curative intent at a university hospital in Sweden (n = 892), which included two surveys, the State Trait Anxiety Inventory-state specific questions (STAI-S), and the Patient-centered Climate Questionnaire (PCQ) and additional treatment-specific questions. Eligible patients were provided with the questionnaire on their seventh day of RT by an RT-nurse.

    RESULTS: Statistical analysis showed a significant negative relationship between STAI-S scores and PCQ scores, and a significant positive relationship between the Treatment Environment questions and the STAI-S scores. Multivariate regression modeling found the PCQ subscale of safety to have the strongest negative association with STAI-S scores, showing that a climate of safety can significantly decrease patient situational anxiety levels. On the other hand, difficulty tolerating the overall treatment experience, worry about the treatment equipment, or feelings of isolation or claustrophobia within the treatment room all significantly factor into increases in patient-reported situational anxiety levels.

    CONCLUSION: Both the treatment environment and the psychosocial climate of the RT clinic significantly impact cancer patient state anxiety levels. These findings suggest that actively employing a person-centered approach during RT, and designing the treatment environment to be more attentive to the patient experience can both play a significant role in decreasing patient situational anxiety during treatment.

  • 25. 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, K.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    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)
  • 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, 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.

  • 27.
    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.
    Mullaney, Tara
    Umeå University, Faculty of Science and Technology, Umeå Institute of Design.
    Olsson, L. E.
    Finnilä, Kristina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    MRI in radiotherapy - Is it time to rethink the current radiotherapy fixation solutions?2014In: Journal of Applied Clinical Medical Physics, ISSN 1526-9914, E-ISSN 1526-9914, Vol. 15, no 6, p. 360-361Article in journal (Refereed)
  • 28.
    Nyholm, Tufve
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Olsson, C.
    Skönevik, Johan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Gunnlaugsson, A.
    Valdman, A.
    Johnsson, S.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nationwide Collection of Structured RT Data in Sweden2017In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 44, no 6, p. 3241-3241Article in journal (Other academic)
  • 29.
    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. 

  • 30.
    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.

  • 31.
    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.

  • 32.
    Olausson, Kristina
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Holst Hansson, Annette
    Department of Care Sciences, Faculty of Health and Society, Malmö, Sweden.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Edvardsson, David
    Umeå University, Faculty of Medicine, Department of Nursing. La Trobe University/Austin Health Clinical School of Nursing, Melbourne, Australia.
    Östlund, Ulrika
    Centre for Research & Development, Uppsala University/Region Gävleborg, Sweden.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Development and psychometric testing of an instrument to measure the patient’s experience of external radiotherapy: The Radiotherapy Experience Questionnaire (RTEQ)2017In: Technical Innovations & Patient Support in Radiation Oncology, ISSN 2405-6324, Vol. 3-4, p. 7-12Article in journal (Refereed)
    Abstract [en]

    Background

    The patient’s perception of external radiotherapy (RT) procedures and equipment is important to evaluate as a complement to endpoints such as treatment outcome and reproducibility. There is a lack of a proper, psychometrically robust instrument to evaluate the patient’s comfort and experience of the external RT procedure. Hence, this study aimed to develop and test an instrument to measure the patient’s experience during external RT.

    Material and Methods

    A preliminary 34-item questionnaire was generated from research literature, expert consultations and patient interviews, and it was distributed to patients (n = 825) at 8 RT units in Sweden. The answers were subjected to item analysis and reduction by using exploratory factor analysis. The reliability of the final questionnaire was evaluated using Cronbach’s alpha. Mean scale scores were compared across gender, length of RT and treatment area.

    Results

    Most items were highly skewed towards positive responses. Scree plot analyses of the 34-item correlation matrix identified six underlying themes explaining 68% of the total variance. After item reduction, the 6 themes explained 73% of the variance in a 23-item questionnaire. Cronbach’s alpha was satisfactory for all themes (between 0.79 and 0.9). Significant differences between treatment areas were found for two scales: situational unease and situational repose.

    Conclusion

    The RT Experience Questionnaire is a tentatively valid and reliable instrument to measure how patients experience the external RT session process and the environment in the treatment room.

  • 33.
    Olofsson, Lennart
    et al.
    Umeå University, Faculty of Medicine, Radiation Sciences, Radiation Physics.
    Mu, Xiangkui
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Nill, Simeon
    Oelfke, Uwe
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Radiation Sciences, Radiation Physics.
    Intensity modulated radiation therapy with electrons using algorithm based energy/range selection methods.2004In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 73, no 2, p. 223-231Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: In recent years photon intensity modulated radiation therapy (IMRT) has gained attention due to its ability to improve conformity of dose distributions. A potential advantage of electron-IMRT is that the dose fall off in the depth dose curve makes it possible to modulate the dose distribution in the direction of the beam by selecting different electron energies. This paper examines the use of a computer based energy selection in combination with the IMRT technique to optimise the electron dose distribution. MATERIALS AND METHODS: One centimetre square electron beamlets ranging from 2.5 to 50 MeV were pre-calculated in water using Monte Carlo methods. A modified IMRT optimisation tool was then used to find an optimum mix of electron energies and intensities. The main principles used are illustrated in some simple geometries and tested on two clinical cases of post-operated ca. mam. RESULTS: It is clearly illustrated that the energy optimisation procedure lowers the dose to lung and heart and makes the dose in the target more homogeneous. Increasing the energy at steep gradients compensates for lack of target coverage at beam edges and steep gradients. Comparison with a clinically acceptable four segment plan indicates the advantage of the used electron IMRT technique. CONCLUSIONS: Using an intensity optimised mix of computer selected electron energies has the potential to improve electron treatments for mastectomy patients with good target coverage and reduced dose to normal tissue such as lung and heart.

  • 34.
    Ottosson, Sandra
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Lindblom, Ulrika
    Lunds universitet.
    Wahlberg, Peter
    Lunds universitet.
    Nilsson, Per
    Lunds universitet.
    Kjellén, Elisabeth
    Lunds universitet.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Levring Jäghagen, Eva
    Umeå University, Faculty of Medicine, Department of Odontology.
    Laurell, Göran
    Uppsala universitet.
    Weight loss and Body Mass Index in relation to aspiration in patients treated for head and neck cancer: a long-term follow-up2014In: Supportive Care in Cancer, ISSN 0941-4355, E-ISSN 1433-7339, Vol. 22, no 9, p. 2361-2369Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Persistent severe swallowing dysfunction with aspiration is a common and sometimes overlooked sequelae after treatment for squamous cell carcinoma of the head and neck (SCCHN) and may impact food intake and nutritional status. More knowledge is needed to increase the understanding of severe swallowing dysfunction as a risk factor for persistent nutritional deteriorations in SCCHN survivors. The purpose of the study was to investigate weight loss and body mass index (BMI) in relation to pharyngeal swallowing function in a long-term perspective in patients after SCCHN treatment.

    METHODS: Data from 101 patients were available for the analyses. Swallowing function was assessed by videofluoroscopy at a mean of 71.6 months after the start of radiotherapy (RT). Percent weight change (calculated with weight at the start of RT as the reference) and BMI at follow-up were the primary nutritional measures.

    RESULTS: Aspiration was present in 48 of 101 patients (48 %). Patients with aspiration had a significantly higher mean weight loss and a lower BMI (-10.9 % and 23.1, respectively) at follow-up compared with patients without aspiration (-2.8 % and 26.0, respectively). Patients with aspiration were unable to gain weight after 23 months. Only ten of 101 patients (10 %) were underweight at follow-up.

    CONCLUSIONS: Swallowing dysfunction with aspiration was related to long-term weight loss and reduced BMI. Few patients were underweight despite the high prevalence of swallowing dysfunction.

  • 35.
    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.

  • 36.
    Ottosson, Sandra
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Kjellén, Elisabeth
    Lunds Universitet, Klinisk vetenskap.
    Nilsson, Per
    Lunds Universitet, Klinisk vetenskap.
    Laurell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Weight loss in patients with head and neck cancer during and after conventional and accelerated radiotherapy2013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 4, p. 711-718Article in journal (Refereed)
    Abstract [en]

    Background. Weight loss is common among patients with squamous cell carcinoma of the head and neck (SCCHN) and is mainly due to tumor and treatment related factors. The aim of the present study was to evaluate weight loss in patients with SCCHN undergoing two different radiotherapy (RT) schedules.

    Material and methods. Nutritional data were analyzed from the ARTSCAN study, a controlled randomized prospective Swedish multicenter study conducted with the aim of comparing conventional fractionation (2.0 Gy per day, total 68 Gy during 7 weeks) and accelerated fractionation (1.1 + 2.0 Gy per day, total 68 Gy during 4.5 weeks). Seven hundred and fifty patients were randomized and 712 patients were followed from the start of RT in the present nutritional study.

    Results. The patients had a weight loss of 11.3% (± 8.6%) during the acute phase (start of RT up to five months after the termination of RT). No difference in weight loss was seen between the two RT fractionation schedules (p = 0.839). Three factors were significantly predictive for weight loss during the acute phase, i.e. tumor site, overweight/obesity or lack of tube feeding at the start of RT. Moreover, the nadir point of weight loss occurred at five months after the termination of RT.

    Conclusion. The results of the present study showed no difference in weight loss between the two RT fractionation schedules and also highlight that weight loss in SCCHN is a multifactorial problem. Moreover, the nadir of weight loss occurred at five months after the termination of treatment which calls for more intense nutritional interventions during the period after treatment.

  • 37. Persson, Emilia
    et al.
    Gustafsson, Christian
    Nordström, Fredrik
    Sohlin, Maja
    Gunnlaugsson, Adalsteinn
    Petruson, Karin
    Rintelä, Niina
    Hed, Kristoffer
    Blomqvist, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Olsson, Lars E.
    Siversson, Carl
    Jonsson, Joakim
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    MR-OPERA: a multicenter/multivendor validation of magnetic resonance imaging–only prostate treatment planning using synthetic computed tomography images2017In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 99, no 3, p. 692-700Article in journal (Refereed)
    Abstract [en]

    Purpose: To validate the dosimetric accuracy and clinical robustness of a commercially available software for magnetic resonance (MR) to synthetic computed tomography (sCT) conversion, in an MR imaging–only workflow for 170 prostate cancer patients.

    Methods and Materials: The 4 participating centers had MriPlanner (Spectronic Medical), an atlas-based sCT generation software, installed as a cloud-based service. A T2-weighted MR sequence, covering the body contour, was added to the clinical protocol. The MR images were sent from the MR scanner workstation to the MriPlanner platform. The sCT was automatically returned to the treatment planning system. Four MR scanners and 2 magnetic field strengths were included in the study. For each patient, a CT-treatment plan was created and approved according to clinical practice. The sCT was rigidly registered to the CT, and the clinical treatment plan was recalculated on the sCT. The dose distributions from the CT plan and the sCT plan were compared according to a set of dose-volume histogram parameters and gamma evaluation. Treatment techniques included volumetric modulated arc therapy, intensity modulated radiation therapy, and conventional treatment using 2 treatment planning systems and different dose calculation algorithms.

    Results: The overall (multicenter/multivendor) mean dose differences between sCT and CT dose distributions were below 0.3% for all evaluated organs and targets. Gamma evaluation showed a mean pass rate of 99.12% (0.63%, 1 SD) in the complete body volume and 99.97% (0.13%, 1 SD) in the planning target volume using a 2%/2-mm global gamma criteria.

    Conclusions: Results of the study show that the sCT conversion method can be used clinically, with minimal differences between sCT and CT dose distributions for target and relevant organs at risk. The small differences seen are consistent between centers, indicating that an MR imaging–only workflow using MriPlanner is robust for a variety of field strengths, vendors, and treatment techniques.

  • 38. Petit, C.
    et al.
    Pignon, J. P.
    Landais, C.
    Trotti, A.
    Gregoire, V.
    Overgaard, J.
    Tobias, J.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Parmar, M. K.
    Lee, J. W.
    Ghi, M. G.
    Corvo, R.
    Janot, F.
    O'Sullivan, B.
    Horiuchi, M.
    Zhang, Q.
    Fortpied, C.
    Grau, C.
    Bourhis, J.
    Blanchard, P.
    What is the most effective treatment for head and neck squamous cell carcinoma?: An individual patient data network meta-analysis from the MACH-NC and MARCH collaborative groups2017In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 72, p. S101-S102Article in journal (Other academic)
  • 39. Skripcak, Tomas
    et al.
    Belka, Claus
    Bosch, Walter
    Brink, Carsten
    Brunner, Thomas
    Budach, Volker
    Buettner, Daniel
    Debus, Juergen
    Dekker, Andre
    Grau, Cai
    Gulliford, Sarah
    Hurkmans, Coen
    Just, Uwe
    Krause, Mechthild
    Lambin, Philippe
    Langendijk, Johannes A.
    Lewensohn, Rolf
    Luehr, Armin
    Maingon, Philippe
    Masucci, Michele
    Niyazi, Maximilian
    Poortmans, Philip
    Simon, Monique
    Schmidberger, Heinz
    Spezi, Emiliano
    Stuschke, Martin
    Valentini, Vincenzo
    Verheij, Marcel
    Whitfield, Gillian
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Zips, Daniel
    Baumann, Michael
    Creating a data exchange strategy for radiotherapy research: Towards federated databases and anonymised public datasets2014In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 113, no 3, p. 303-309Article in journal (Refereed)
    Abstract [en]

    Disconnected cancer research data management and lack of information exchange about planned and ongoing research are complicating the utilisation of internationally collected medical information for improving cancer patient care. Rapidly collecting/pooling data can accelerate 'translational research in radiation therapy and oncology. The exchange of study data is one of the fundamental principles behind data aggregation and data mining. The possibilities of reproducing the original study results, performing further analyses on existing research data to generate new hypotheses or developing computational models to support medical decisions (e.g. risk/benefit analysis of treatment options) represent just a fraction of the potential benefits of medical data-pooling. Distributed machine learning and knowledge exchange from federated databases can be considered as one beyond other attractive approaches for knowledge generation within "Big Data". Data interoperability between research institutions should be the major concern behind a wider collaboration. Information captured in electronic patient records (EPRs) and study case report forms (eCRFs), linked together with medical imaging and treatment planning data, are deemed to be fundamental elements for large multi-centre studies in the field of radiation therapy and oncology. To fully utilise the captured medical information, the study data have to be more than just an electronic version of a traditional (un-modifiable) paper CRF. Challenges that have to be addressed are data interoperability, utilisation of standards, data quality and privacy concerns, data ownership, rights to publish, data pooling architecture and storage. This paper discusses a framework for conceptual packages of ideas focused on a strategic development for international research data exchange in the field of radiation therapy and oncology.

  • 40.
    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.

  • 41.
    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.

  • 42.
    Widmark, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Gunnlaugsson, Adalsteinn
    Beckman, Lars
    Thellenberg-Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hoyer, Morten
    Lagerlund, Magnus
    Kindblom, Jon
    Ginman, Claes
    Johansson, Bengt
    Björnlinger, Kirsten
    Seke, Mihajl
    Agrup, Måns
    Fransson, Per
    Umeå University, Faculty of Medicine, Department of Nursing.
    Tavelin, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Norman, David
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Anderson, Harald
    Kjellén, Elisabeth
    Franzén, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nilsson, Per
    Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial2019In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 394, no 10196, p. 385-395Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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

  • 43.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation biology.
    Biological effects of high energy radiation and ultra high dose rates1991Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Recently a powerful electron accelerator, 50 MeV race-track microtron, has been taken into clinical use. This gives the opportunity to treat patients with higher x-ray and electron energies than before. Furthermore, treatments can be performed were the entire fractional dose can be delivered in parts of a second.

    The relative biological effectiveness (RBE) of high energy photons (up to 50 MV) was studied in vitro and in vivo. Oxygen enhancement ratio (OER) of 50 MV photons and RBE of 50 MeV electrons were investigated in vitro. Single-fraction experiments, in vitro, using V-79 Chinese hamster fibroblasts showed an RBE for 50 MV x-rays of approximately 1.1 at surviving fraction 0.01, with reference to the response to 4 MV x- rays. No significant difference in OER could be demonstrated. Fractionation experiments were carried out to establish the RBE at the clinically relevant dose level, 2 Gy. The RBE calculated for the 2 Gy/fraction experiments was 1.17. The RBEs for 20 MV x-rays and 50 MeV electrons were equal to one. In order to investigate the validity of these results, the jejunal crypt microcolony assay in mice was used to determine the RBE of 50 MV x-rays. The RBE for 50 MV x-rays in this case was estimated to be 1.06 at crypt surviving fraction 0.1. Photonuclear processes are proposed as one possible explanation to the higher RBE for 50 MV x-rays.

    Several studies of biological response to ionizing radiation of high absorbed dose rates have been performed, often with conflicting results. With the aim of investigating whether a difference in effect between irradiation at high dose rates and at conventional dose rates could be verified, pulsed 50 MeV electrons from a clinical accelerator were used for experiments with ultra high dose rates (mean dose rate: 3.8 x 10^ Gy/s) in comparison to conventional (mean dose rate: 9.6 x 10"^ Gy/s). V-79 cells were irradiated in vitro under both oxic and anoxic conditions. No significant difference in relative biological effectiveness (RBE) or oxygen enhancement ratio (OER) was observed for ultra high dose rates compared to conventional dose rates.

    A central issue in clinical radiobiological research is the prediction of responses to different radiation qualities. The choice of cell survival and dose response model greatly influences the results. In this context the relationship between theory and model is emphasized. Generally, the interpretations of experimental data are dependent on the model. Cell survival models are systematized with respect to their relations to radiobiological theories of cell kill. The growing knowledge of biological, physical, and chemical mechanisms is reflected in the formulation of new models. This study shows that recent modelling has been more oriented towards the stochastic fluctuations connected to radiation energy deposition. This implies that the traditional cell survival models ought to be complemented by models of stochastic energy deposition processes at the intracellular level.

  • 44.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation biology.
    Radiobiological Cell-survival Models: a Methodological Overview1992In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 31, no 4, p. 433-441Article in journal (Refereed)
    Abstract [en]

    A central issue in clinical radiobiological research is the prediction of responses to different radiation qualities. The, choice of cell survival and dose-response model greatly influences the results. In this context the relationship between theory and model is emphasized. Generally, the interpretations of experimental data depend on the model. Cell survival models are systematized with respect to their relations to radiobiological theories of cell kill. The growing knowledge of biological, physical, and chemical mechanisms is reflected in the formulation of new models. The present overview shows that recent modelling has been more oriented towards the stochastic fluctuations connected to radiation energy deposition. This implies that the traditional cell survival models ought to be complemented by models of stochastic energy deposition processes and repair processes at the intracellular level.

  • 45.
    Zackrisson, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation biology.
    Johansson, B.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Östbergh, Peter
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Relative Biological Effectiveness and Oxygen Enhancement Ratio of 50 MV X-rays1989In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 28, no 4, p. 529-535Article in journal (Refereed)
  • 46.
    Zackrisson, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation biology.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Östbergh, Peter
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Relative Biological Effectiveness of High-energy Photons (up tO 50-MV) and Electrons (50-MeV)1991In: Radiation Research, ISSN 0033-7587, E-ISSN 1938-5404, Vol. 128, no 2, p. 192-196Article in journal (Refereed)
  • 47.
    Zackrisson, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Matching of electron beams for conformal therapy of target volumes at moderate depths1996In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 39, no 3, p. 261-270Article in journal (Refereed)
    Abstract [en]

    The basic requirements for conformal electron therapy are an accelerator with a wide range of energies and field shapes. The beams should be well characterised in a full 3-D dose planning system which has been verified for the geometries of the current application. Differences in the basic design of treatment units have been shown to have a large influence on beam quality and dosimetry. Modern equipment can deliver electron beams of good quality with a high degree of accuracy. A race-track microtron with minimised electron scattering and a multi-leaf collimator (MLC) for electron collimating will facilitate the isocentric technique as a general treatment technique for electrons. This will improve the possibility of performing combined electron field techniques in order to conform the dose distribution with no or minimal use of a bolus. Furthermore, the isocentric technique will facilitate multiple field arrangements that decrease the problems with distortion of the dose distribution due to inhomogeneities, etc. These situations are demonstrated by clinical examples where isocentric, matched electron fields for treatment of the nose, thyroid and thoracic wall have been used.

  • 48.
    Zackrisson, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation biology.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Relative biological effectiveness of 50-MV X-rays on jejunal crypt survival in vivo1992In: Radiation Research, ISSN 0033-7587, E-ISSN 1938-5404, Vol. 132, no 1, p. 112-114Article in journal (Refereed)
    Abstract [en]

    Earlier in vitro studies of relative biological effectiveness (RBE) of 50-MV X rays show an RBE of approximately 1.1 compared to 4 MV. No difference in RBE has been found for 20-MV X rays or 50-MeV electrons. The higher RBE for 50 MV can be explained to some extent by the small high linear energy transfer contribution from photonuclear reactions at high X-ray energies. To investigate the validity of the results in vitro, a study of the RBE of 50-MV X rays has been performed in vivo using the jejunal crypt microcolony assay in mice. The reference radiation used in this case was 20-MV X rays. The results confirm the earlier in vitro studies. The RBE for 50-MV X rays was estimated to be 1.06, calculated as the ratio between the slopes of the response curves.

  • 49.
    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.

  • 50.
    Zackrisson, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nilsson, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Kjellén, Elisabeth
    Skåne University Hospital, Lund and Malmö, Sweden.
    Johansson, Karl-Axel
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Modig, Hans
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Brun, Eva
    Skåne University Hospital, Lund and Malmö, Sweden.
    Nyman, Jan
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Friesland, Signe
    Karolinska University Hospital, Stockholm, Sweden.
    Reizenstein, Johan
    Örebro University Hospital, Örebro, Sweden.
    Sjödin, Helena
    Karolinska University Hospital, Stockholm, Sweden.
    Ekberg, Lars
    Skåne University Hospital, Lund and Malmö, Sweden.
    Lödén, Britta
    Karlstad Central Hospital, Karlstad, Sweden.
    Mercke, Claes
    Karolinska University Hospital, Stockholm, Sweden.
    Fernberg, Jan-Olof
    Karolinska University Hospital, Stockholm, Sweden.
    Franzén, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ask, Anders
    Skåne University Hospital, Lund and Malmö, Sweden.
    Persson, Essie
    Örebro University Hospital, Örebro, Sweden.
    Wickart-Johansson, Gun
    Karolinska University Hospital, Stockholm, Sweden.
    Lewin, Freddi
    Karolinska University Hospital, Stockholm, Sweden.
    Wittgren, Lena
    Skåne University Hospital, Lund and Malmö, Sweden.
    Björ, Ove
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Björk-Eriksson, Thomas
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Two-year results from a Swedish study on conventional versus accelerated radiotherapy in head and neck squamous cell carcinoma - The ARTSCAN study2011In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 100, no 1, p. 41-48Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Studies on accelerated fractionation (AF) in head and neck cancer have shown increased local control and survival compared with conventional fractionation (CF), while others have been non-conclusive. In 1998 a national Swedish group decided to perform a randomised controlled clinical study of AF.

    Materials and methods: Patients with verified squamous cell carcinoma of the oral cavity, oropharynx, larynx (except glottic T1-T2, N0) and hypopharynx were included. Patients with prior chemotherapy or surgery were excluded. Patients were randomised to either CF (2Gy/day, 5days/week for 7 weeks, total dose 68Gy) or to AF (1.1Gy+2.0Gy/day, 5days/week for 4.5weeks, total dose 68Gy). An extensive quality assurance protocol was followed throughout the study. The primary end point was loco-regional tumour control (LRC) at two years after treatment. RESULTS: The study was closed in 2006 when 750 patients had been randomised. Eighty-three percent of the patients had stages III-IV disease. Forty eight percent had oropharyngeal, 21% laryngeal, 17% hypopharyngeal and 14% oral cancers. There were no significant differences regarding overall survival (OS) or LRC between the two regimens. The OS at two years was 68% for AF and 67% for CF. The corresponding figures for LRC were 71% and 67%, respectively. There was a trend towards improved LRC for oral cancers treated (p=0.07) and for large tumours (T3-T4) (p=0.07) treated with AF. The AF group had significantly worse acute reactions, while there was no significant increase in late effects.

    Conclusion: Overall the AF regimen did not prove to be more efficacious than CF. However, the trend towards improved results in AF for oral cancers needs to be further investigated.

     

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