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  • 1.
    Ahnesjö, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Hårdemark, Björn
    Isacsson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Montelius, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    The IMRT information process-mastering the degrees of freedom in external beam therapy2006In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 51, no 13, p. R381-402Article in journal (Refereed)
    Abstract [en]

    The techniques and procedures for intensity-modulated radiation therapy (IMRT) are reviewed in the context of the information process central to treatment planning and delivery of IMRT. A presentation is given of the evolution of the information based radiotherapy workflow and dose delivery techniques, as well as the volume and planning concepts for relating the dose information to image based patient representations. The formulation of the dose shaping process as an optimization problem is described. The different steps in the calculation flow for determination of machine parameters for dose delivery are described starting from the formulation of optimization objectives over dose calculation to optimization procedures. Finally, the main elements of the quality assurance procedure necessary for implementing IMRT clinically are reviewed.

  • 2. Benedek, Hunor
    et al.
    Isacsson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Olevik-Dunder, Maria
    Westermark, Mathias
    Hallstrom, Per
    Olofsson, Jorgen
    Gustafsson, Magnus
    Strategies for quality assurance of intensity modulated radiation therapy2015In: 8TH INTERNATIONAL CONFERENCE ON 3D RADIATION DOSIMETRY (IC3DDOSE), 2015, Vol. 573, p. 012015-, article id 012015Conference paper (Refereed)
    Abstract [en]

    In late 2011 The Swedish Society of Radiation Physics formed a working group to concentrate on the Quality Assurance of modern radiation therapy techniques. The given task was to identify and summarise the different QA strategies in Sweden and also the international recommendations. This was used to formulate recommendations for practical guidelines within Sweden. In this paper a brief summery of the group's work is presented. All the Swedish radiation therapy centres do a pre treatment verification measurement as QA for every new IMRT and VMAT plan. Physicists do it and they believe it to be time consuming. A general standpoint from all the centres was that new guidelines and legislation is needed to allow QA that does not require a measurement. Based on various international publications and recommendations the working group has presented two strategies, one where all new plans are checked through measurement and one where no measurement is needed. The measurement-based strategy is basically the same as the one used today with an extended machine QA part. The other presented strategy is process oriented where all the different parts of the treatment chain are checked separately. The final report can be found in Swedish on http://www.radiofysik.org.

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  • 3.
    Blomquist, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Ronne Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Borota, Ljubisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Gál, Gyula
    Nilsson, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Montelius, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Grusell, Erik
    Isacsson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Positive correlation between occlusion rate and nidus size of proton beam treated brain arteriovenous malformations (AVMs)2016In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 1, p. 105-112Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Proton beam radiotherapy of arteriovenous malformations (AVM) in the brain has been performed in Uppsala since 1991. An earlier study based on the first 26 patients concluded that proton beam can be used for treating large and medium sized AVMs that were considered difficult to treat with photons due to the risk of side effects. In the present study we analyzed the result from treating the subsequent 65 patients.

    MATERIAL AND METHODS: A retrospective review of the patients' medical records, treatment protocols and radiological results was done. Information about gender, age, presenting symptoms, clinical course, the size of AVM nidus and rate of occlusion was collected. Outcome parameters were the occlusion of the AVM, clinical outcome and side effects.

    RESULTS: The rate of total occlusion was overall 68%. For target volume 0-2cm(3) it was 77%, for 3-10 cm(3) 80%, for 11-15 cm(3) 50% and for 16-51 cm(3) 20%. Those with total regress of the AVM had significantly smaller target volumes (p < 0.009) higher fraction dose (p < 0.001) as well as total dose (p < 0.004) compared to the rest. The target volume was an independent predictor of total occlusion (p = 0.03). There was no difference between those with and without total occlusion regarding mean age, gender distribution or symptoms at diagnosis. Forty-one patients developed a mild radiation-induced brain edema and this was more common in those that had total occlusion of the AVM. Two patients had brain hemorrhages after treatment. One of these had no effect and the other only partial occlusion from proton beams. Two thirds of those presenting with seizures reported an improved seizure situation after treatment.

    CONCLUSION: Our observations agree with earlier results and show that proton beam irradiation is a treatment alternative for brain AVMs since it has a high occlusion rate even in larger AVMs.

  • 4. Hellman, Björn
    et al.
    Brodin, David
    Andersson, Maria
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Dahlman-Wright, Karin
    Isacsson, Ulf
    Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Onkologi.
    Brattstrom, Daniel
    Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Onkologi.
    Bergqvist, Michael
    Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Onkologi.
    Radiation-induced DNA-damage and gene expression profiles in human lung cancer cells with different radiosensitivity.2005In: Exp Oncol, ISSN 1812-9269, Vol. 27, no 2, p. 102-7Article in journal (Refereed)
  • 5.
    Johansson, Andreas K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Lennernäs, Bo
    Isacsson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Neurovascular Bundle Infiltration Can Explain Local Relapses Using Conformal Radiotherapy of Prostate Cancer.2017In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 37, no 4, p. 1825-1830Article in journal (Refereed)
    Abstract [en]

    AIM: To quantify the impact of decreased margins for two treatment techniques, three-dimensional conformal radiotherapy (3D-CRT) and volumetric-modulated arc therapy (VMAT), on local control in curative treatment of prostate cancer.

    MATERIALS AND METHODS: The planning target volume (PTV) margins were decreased in steps of 1 mm from 10 to 1 mm. Treatment plans using 3D-CRT and VMAT technique were produced for all margin sizes and the dose to the neuro vascular bundles (NVB), that was not included in the PTV, was investigated.

    RESULTS: Due to the more conformal dose delivery using VMAT, the dose to the NVB decreased more rapidly by VMAT compared to the 3D-CRT plans. The dose difference was significant for margins from 1-7 mm.

    CONCLUSION: One should be very cautious before clinical routines are changed, bearing in mind whether the change means more conformal treatment technique, smaller margins or target segmentation in different imaging modalities.

  • 6.
    Johansson, Jonas
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enheten för onkologi.
    Blomquist, Erik
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enheten för onkologi.
    Montelius, Anders
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enheten för onkologi.
    Isacsson, Ulf
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enheten för onkologi.
    Glimelius, Bengt
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enheten för onkologi.
    Potential outcomes of modalities and techniques in radiotherapy for patients with hypopharyngeal carcinoma.2004In: Radiother Oncol, ISSN 0167-8140, Vol. 72, no 2, p. 129-38Article in journal (Other scientific)
  • 7.
    Johansson, Silvia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Isacsson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Sandin, Fredrik
    Reg Canc Ctr, S-75185 Uppsala, Sweden.
    Turesson, Ingela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    High efficacy of hypofractionated proton therapy with 4 fractions of 5 Gy as a boost to 50 Gy photon therapy for localized prostate cancer2019In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 141, p. 164-173Article in journal (Refereed)
    Abstract [en]

    Purpose: We report the outcome of hypofractionated proton boost as an alternative to high dose-rate brachytherapy boost, aimed at an equivalent dose exceeding 86 Gy in 2 Gy fractions, for patients with localized prostate cancer and all risk groups.

    Methods: Proton boost of 20 Gy given in 4 daily fractions to the prostate was followed after a one-week rest by photon therapy to 50 Gy in 2 Gy fractions. Outcomes are presented per risk group according to both NCCN and ISUP classifications. Advanced imaging was performed for adequate staging, and at an early stage of rising PSA, to identify the relapse site. Endpoints were PSA relapse-free-, locoregional relapse-free-, and distant metastasis-free- survival. Prostate cancer-specific-, metastasis-free-, and overall survival were also estimated. Genitourinary (GU) and gastrointestinal (GI) toxicity were based on patients' questionnaires and physicians' records.

    Results: We treated 531 patients between 2002 and 2015; 504 had localized disease. The cohort included 180 patients with T3/T4 disease (36%). The majority of the 50% with high-/very high-risk disease received ADT, 9-24 months; 92 had adjuvant pelvic node treatment. Median follow-up was 113 months (43-193). For low-, intermediate-, high-, and very high-risk patients, the 5-year PSA relapse-free survival was 100%, 94%, 82%, and 72%, respectively. Prolonged ADT improved biochemical control and nodal treatment regional control. The NCCN classification had higher predictive discrimination than the ISUP classification. The 5-year prevalence grade 3+ was 2% for GU and 0% for GI toxicity in pre-treatment symptom-free patients, and not worsened by nodal treatment.

    Conclusion: Dose escalation with hypofractionated proton boost was as effective as reported with high dose-rate brachytherapy boost, and the GU and GI toxicity profile was very similar. The proton boost was also appropriate for patients with larger prostate volume, higher T-stage, and high-risk disease encompassing elective regional node photon therapy. 

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  • 8.
    Johansson, Silvia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Åström, Lennart
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Sandin, Fredrik
    Isacsson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Montelius, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Turesson, Ingela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Hypofractionated proton boost combined with external beam radiotherapy for treatment of localized prostate cancer2012In: Prostate Cancer, ISSN 2090-3111, E-ISSN 2090-312X, Vol. 2012, article id 654861Article in journal (Refereed)
    Abstract [en]

    Proton boost of 20 Gy in daily 5 Gy fractions followed by external beam radiotherapy (EBRT) of 50 Gy in daily 2 Gy fractions were given to 278 patients with prostate cancer with T1b to T4N0M0 disease. Fifty-three percent of the patients received neoadjuvant androgen deprivation therapy (N-ADT). The medium followup was 57 months. The 5-year PSA progression-free survival was 100%, 95%, and 74% for low-, intermediate-, and high-risk patients, respectively. The toxicity evaluation was supported by a patient-reported questionnaire before every consultant visit. Cumulative probability and actuarial prevalence of genitourinary (GU) and gastrointestinal (GI) toxicities are presented according to the RTOG classification. N-ADT did not influence curability. Mild pretreatment GU-symptoms were found to be a strong predictive factor for GU-toxicity attributable to treatment. The actuarial prevalence declined over 3 to 5 years for both GU and GI toxicities, indicating slow resolution of epithelial damage to the genitourinary and gastrointestinal tract. Bladder toxicities rather than gastrointestinal toxicities seem to be dose limiting. More than 5-year followup is necessary to reveal any sign of true progressive late side effects of the given treatment. Hypofractionated proton-boost combined with EBRT is associated with excellent curability of localized PC and acceptable frequencies of treatment toxicity.

  • 9. Lennernas, Bo
    et al.
    Majumder, Khairul
    Damber, Jan-Erik
    Albertsson, Per
    Holmberg, Erik
    Brandberg, Yvonne
    Isacsson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Ljung, Gunilla
    Damm, Ole
    Nilsson, Sten
    Radical prostatectomy versus high-dose irradiation in localized/locally advanced prostate cancer: A Swedish multicenter randomized trial with patient-reported outcomes2015In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 54, no 6, p. 875-881Article in journal (Refereed)
    Abstract [en]

    Background. Treatment of localized prostate cancer (PC) is controversial. This is the first randomized study comparing an open surgery procedure (radical prostatectomy) with a combination of high-dose rate brachytherapy (2 x 10 Gy) and external beam radiotherapy (25 x 2 Gy) in PC patients in Sweden 1996-2001. The two randomization arms were compared regarding differences in patients-reported outcomes, such as complications and health-related quality of life (HRQoL). Material and methods. The patients had localized/locally advanced PC, clinical category T1b-T3a, N0, M0 and PSA <= 50 ng/ml. All underwent total androgen blockade (six months). Self-reported HRQoL and symptoms including urinary, bowel, and sexual side effects were investigated prospectively before randomization and 12 and 24 months after randomization. A total of 89 patients were randomized and completed the EORTC QLQ C-33 and EORTC PR-25 questionnaires. Results. Over the study period, there were no discernible differences in HRQoL, or complications between the two groups. Emotional functioning, however, improved statistically significantly over time, whereas Social functioning decreased, and financial difficulties increased. No statistically signifi cant differences in group-by-time interactions were found. The survival rate was 76%. Only eight patients (9%) died of PC. Conclusion. Open radical prostatectomy and the combined high-dose rate brachytherapy with external beam radiation appeared to be comparable in the measured outcomes. It was not possible to draw any conclusion on the efficacy of the two treatments due to insufficient power of the study.

  • 10.
    Lennernäs, Bo
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Isacsson, Ulf
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Nilsson, Sten
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    The use of artificial intelligence neural networks in the evaluation of treatment plans for external beam radiotherapy1995In: Oncol. Reports, Vol. 2Article in journal (Refereed)
  • 11.
    Radu, Calin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Norrlid, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Braendengen, Morten
    Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden; Department of Oncology, Oslo University Hospital, Oslo, Norway.
    Hansson, Karl
    Department of Diagnostic Radiology, Karolinska University Hospital, Solna, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Isacsson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Integrated peripheral boost in preoperative radiotherapy for the locally most advanced non-resectable rectal cancer patients2013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 3, p. 528-537Article in journal (Refereed)
    Abstract [en]

    Background and Purpose.

    Few studies have explored the potential clinical advantages of dose escalation and integrated boosts for patients with non-resectable locally advanced rectal cancer. The possibility of escalating dose to non-resectable regions in these patients was the aim of this study.

    Patients and methods.

    Seven patients with locally very advanced rectal tumours (sacrum overgrowth or growth into pelvic side walls) were evaluated. Intensity modulated photon and pencil beam scanning proton plans with simultaneously integrated boosts (45 Gy to elective lymph nodes, 50 Gy to tumour and 62.5 Gy to boost area in 25 fractions) were compared.

    Results.

    Target coverage was achieved with both photon and proton plans. Estimated risks of acute side effects put the two patients with the largest tumours at unacceptable risk for intestinal toxicity, regardless of modality. The remaining five patients had beneficial sparing of dose to the small intestine with protons.

    Conclusions.

    Adding boost to areas where rectal tumours infiltrate adjacent non-resectable organs is an attractive option which appears possible using both photon and proton irradiation. Proton plans reduced dose to organs at risk. Integrated peripheral boosts should be considered more frequently in these very advanced tumours.

  • 12.
    Silander, Hans
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Neurokirurgi.
    Pellettieri, Luigi
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Neurokirurgi.
    Enblad, Per
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Neurokirurgi.
    Montelius, Anders
    Department of Oncology, Radiology and Clinical Immunology.
    Grusell, Erik
    Vallhagen-Dahlgren, C
    Department of Oncology, Radiology and Clinical Immunology.
    Isacsson, U
    Nyberg, Gunnar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Neurokirurgi.
    Moström, Ulf
    Lilja, Anders
    Gal, Guyla
    Department of Oncology, Radiology and Clinical Immunology.
    Blomquist, Erik
    Department of Oncology, Radiology and Clinical Immunology.
    Fractionated, stereotactic proton beam treatment of cerebral arterionvenous malformations.2004In: Acta Neurol Scand, Vol. 109, no 2, p. 85-90Article in journal (Refereed)
  • 13.
    Tilly, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Johansson, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Isacsson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Medin, Joakim
    Blomquist, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Grusell, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    The influence of RBE variations in a clinical proton treatment plan for a hypopharynx cancer2005In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 50, no 12, p. 2765-2777Article in journal (Refereed)
    Abstract [en]

    Currently, most clinical range-modulated proton beams are assumed to have a fixed overall relative biological effectiveness (RBE) of 1.1. However, it is well known that the RBE increases with depth in the spread-out Bragg peak (SOBP) and becomes about 10% higher than mid-SOBP RBE at 2 mm from the distal edge (Paganetti 2003 Technol. Cancer Res. Treat. 2 413-26) and can reach values of 1.3-1.4 in vitro at the distal edge (Robertson et al 1975 Cancer 35 1664-77, Courdi et al 1994 Br. J. Radiol. 67 800-4). We present a fast method for applying a variable RBE correction with linear energy transfer (LET) dependent tissue-specific parameters based on the alpharef/betaref ratios suitable for implementation in a treatment planning system. The influence of applying this variable RBE correction on a clinical multiple beam proton dose plan is presented here. The treatment plan is evaluated by RBE weighted dose volume histograms (DVHs) and the calculation of tumour control probability (TCP) and normal tissue complication probability (NTCP) values. The variable RBE correction yields DVHs for the clinical target volumes (CTVs), a primary advanced hypopharynx cancer and subclinical disease in the lymph nodes, that are slightly higher than those achieved by multiplying the absorbed dose with RBE=1.1. Although, more importantly, the RBE weighted DVH for an organ at risk, the spinal cord is considerably increased for the variable RBE. As the spinal cord in this particular case is located 8 mm behind the planning target volume (PTV) and hence receives only low total doses, the NTCP values are zero in spite of the significant increase in the RBE weighted DVHs for the variable RBE. However, high NTCP values for the non-target normal tissue were obtained when applying the variable RBE correction. As RBE variations tend to be smaller for in vivo systems, this study-based on in vitro data since human tissue RBE values are scarce and have large uncertainties-can be interpreted as showing the upper limits of the possible effects of utilizing a variable RBE correction. In conclusion, the results obtained here still indicate a significant difference in introducing a variable RBE compared to applying a generic RBE of 1.1, suggesting it is worth considering such a correction in clinical proton therapy planning, especially when risk organs are located immediately behind the target volume.

  • 14. Vatnitsky, S
    et al.
    Siebers, J
    Miller, D
    Moyers, M
    Schaefer, M
    Jones, D
    Vynckier, S
    Hayakawa, Y
    Delacroix, S
    Isacsson, Ulf
    Uppsala University, The Svedberg Laboratory.
    Medin, Joakim
    Uppsala University, The Svedberg Laboratory.
    Kacperek, A
    Lomax, A
    Coray, A
    Kluge, H
    Heese, J
    Verhey, L
    Daftari, I
    Gall, K
    Lam, G
    Beck, T
    Hartmann, G
    Proton dosimetry intercomparison1996In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 41, no 2, p. 169-77Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Methods for determining absorbed dose in clinical proton beams are based on dosimetry protocols provided by the AAPM and the ECHED. Both groups recommend the use of air-filled ionization chambers calibrated in terms of exposure or air kerma in a 60Co beam when a calorimeter or Faraday cup dosimeter is not available. The set of input data used in the AAPM and the ECHED protocols, especially proton stopping powers and w-value is different. In order to verify inter-institutional uniformity of proton beam calibration, the AAPM and the ECHED recommend periodic dosimetry intercomparisons. In this paper we report the results of an international proton dosimetry intercomparison which was held at Loma Linda University Medical Center. The goal of the intercomparison was two-fold: first, to estimate the consistency of absorbed dose delivered to patients among the participating facilities, and second, to evaluate the differences in absorbed dose determination due to differences in 60Co-based ionization chamber calibration protocols.

    MATERIALS AND METHODS: Thirteen institutions participated in an international proton dosimetry intercomparison. The measurements were performed in a 15-cm square field at a depth of 10 cm in both an unmodulated beam (nominal accelerator energy of 250 MeV) and a 6-cm modulated beam (nominal accelerator energy of 155 MeV), and also in a circular field of diameter 2.6 cm at a depth of 1.14 cm in a beam with 2.4 cm modulation (nominal accelerator energy of 100 MeV).

    RESULTS: The results of the intercomparison have shown that using ionization chambers with 60Co calibration factors traceable to standard laboratories, and institution-specific conversion factors and dose protocols, the absorbed dose specified to the patient would fall within 3% of the mean value. A single measurement using an ionization chamber with a proton chamber factor determined with a Faraday cup calibration differed from the mean by 8%.

    CONCLUSION: The adoption of a single ionization chamber dosimetry protocol and uniform conversion factors will establish agreement on proton absorbed dose to approximately 1.5%, consistent with that which has been observed in high-energy photon and electron dosimetry.

  • 15.
    Vlachogiannis, Pavlos
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Gudjonsson, Olafur
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Montelius, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Grusell, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Isacsson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Nilsson, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Blomquist, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Hypofractionated high-energy proton-beam irradiation is an alternative treatment for WHO grade I meningiomas2017In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 159, no 12, p. 2391-2400Article in journal (Refereed)
    Abstract [en]

    Radiation treatment is commonly employed in the treatment of meningiomas. The aim of this study was to evaluate the effectiveness and safety of hypofractionated high-energy proton therapy as adjuvant or primary treatment for WHO grade I meningiomas. A total of 170 patients who received irradiation with protons for grade I meningiomas between 1994 and 2007 were included in the study. The majority of the tumours were located at the skull base (n = 155). Eighty-four patients were treated post subtotal resection, 42 at tumour relapse and 44 with upfront radiotherapy after diagnosis based on the typical radiological image. Irradiation was given in a hypofractionated fashion (3-8 fractions, usually 5 or 6 Gy) with a mean dose of 21.9 Gy (range, 14-46 Gy). All patients were planned for follow-up with clinical controls and magnetic resonance imaging scans at 6 months and 1, 2, 3, 5, 7 and 10 years after treatment. The median follow-up time was 84 months. Age, gender, tumour location, Simpson resection grade and target volume were assessed as possible prognostic factors for post-irradiation tumour progression and radiation related complications. The actuarial 5- and 10-year progression-free survival rates were 93% and 85% respectively. Overall mortality rate was 13.5%, while disease-specific mortality was 1.7% (3/170 patients). Older patients and patients with tumours located in the middle cranial fossa had a lower risk for tumour progression. Radiation-related complications were seen in 16 patients (9.4%), with pituitary insufficiency being the most common. Tumour location in the anterior cranial fossa was the only factor that significantly increased the risk of complications. Hypofractionated proton-beam radiation therapy may be used particularly in the treatment of larger World Health Organisation grade I meningiomas not amenable to total surgical resection. Treatment is associated with high rates of long-term tumour growth control and acceptable risk for complications.

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  • 16.
    Wennstig, A. K.
    et al.
    Umea Univ, Sundsvall Hosp, Dept Oncol, Dept Surg & Perioperat Sci Surg, Sundsvall, Sweden..
    Garmo, H.
    Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.;Reg Canc Ctr, SE-75185 Uppsala, Sweden..
    Isacsson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Gagliardi, G.
    Karolinska Univ Hosp, Dept Med Radiat Phys & Nucl Med, SE-17176 Stockholm, Sweden..
    Rintela, N.
    Karolinska Univ Hosp, Dept Med Radiat Phys & Nucl Med, SE-17176 Stockholm, Sweden..
    Lagerqvist, B.
    Uppsala Univ, Dept Med Sci, SE-75185 Uppsala, Sweden..
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England..
    Blomqvist, C.
    Orebro Univ, Univ Hosp, Dept Oncol, SE-70182 Orebro, Sweden..
    Sund, M.
    Umea Univ, Dept Surg & Perioperat Sci Surg, SE-90185 Umea, Sweden..
    Nilsson, G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    The relationship between radiation doses to coronary arteries and later intervention requiring coronary stenosis in breast cancer2018In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 92, p. S61-S62Article in journal (Other academic)
  • 17.
    Wennstig, Anna-Karin
    et al.
    Umea Univ, Dept Surg & Perioperat Sci, Surg, SE-90185 Umea, Sweden;Sundsvall Hosp, Dept Oncol, SE-85186 Sundsvall, Sweden.
    Garmo, Hans
    Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England;Reg Canc Ctr, SE-75185 Uppsala, Sweden.
    Isacsson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Gagliardi, Giovanna
    Karolinska Univ Hosp, Dept Med Radiat Phys & Nucl Med, SE-17176 Stockholm, Sweden.
    Rintelä, Niina
    Karolinska Univ Hosp, Dept Med Radiat Phys & Nucl Med, SE-17176 Stockholm, Sweden.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.
    Blomqvist, Carl
    Orebro Univ, Univ Hosp, Dept Oncol, SE-70182 Orebro, Sweden.
    Sund, Malin
    Umea Univ, Dept Surg & Perioperat Sci, Surg, SE-90185 Umea, Sweden.
    Nilsson, Greger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Gavle Cent Hosp, Dept Oncol, SE-80107 Gavle, Sweden;Visby Hosp, Dept Oncol, SE-62184 Visby, Sweden.
    The relationship between radiation doses to coronary arteries and location of coronary stenosis requiring intervention in breast cancer survivors2019In: Radiation Oncology, ISSN 1748-717X, E-ISSN 1748-717X, Vol. 14, article id 40Article in journal (Refereed)
    Abstract [en]

    Background: To assess the relationship between radiation doses to the coronary arteries (CAs) and location of a coronary stenosis that required intervention after three-dimensional conformal radiotherapy (3DCRT) for breast cancer (BC).

    Methods: The study population consisted of 182 women treated for BC in Sweden between 1992 and 2012. All women received 3DCRT and subsequently underwent coronary angiography due to a suspected coronary event. CA segments were delineated in the patient's original planning-CT and radiation doses were recalculated based on the dose distribution of the original radiotherapy (RT) plan. The location of the CA stenosis that required intervention was identified from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). Logistic regression analysis was used to assess the relationship between CA radiation doses and risk of a later coronary intervention at this specific location.

    Results: The odds ratio (OR) varied by radiation dose to the mid left anterior descending artery (LAD) (p=0.005). Women receiving mean doses of 1-5 Gray (Gy) to the mid LAD had an adjusted OR of 0.90 (95% CI 0.47-1.74) for a later coronary intervention compared to women receiving mean doses of 0-1Gy to the mid LAD. In women receiving mean doses of 5-20Gy to the mid LAD, an adjusted OR of 1.24 (95% CI 0.52-2.95) was observed, which increased to an OR of 5.23 (95% CI 2.01-13.6) for mean doses over 20Gy, when compared to women receiving mean doses of 0-1Gy to the mid LAD.

    Conclusions: In women receiving conventional 3DCRT for BC between 1992 and 2012, radiation doses to the LAD remained high and were associated with an increased requirement of coronary intervention in mid LAD. The results support that the LAD radiation dose should be considered in RT treatment planning and that the dose should be kept as low as possible. Minimising the dose to LAD is expected to diminish the risk of later radiation-induced stenosis.

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  • 18.
    Wikström, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Isacsson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Bengt, Johansson
    Örebro University Hospital, Department of Oncology.
    Lennernäs, Bo
    Örebro University Hospital, Department of Oncology.
    Magnetic Resonance Compatibility of a Transponder Aimed for Radiotherapy Positioning – A Phantom Study2017In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 37, no 9, p. 4993-4996Article in journal (Refereed)
    Abstract [en]

    Background/Aim: Electromagnetic Positioning Systems (EMP) is a new position-ing technique in four-dimensional radiotherapy. Patients with implanted transponders may be referred for magnetic resonance imaging (MRI) making it important to establish the MR safety.

    Materials and Methods: Oranges were prepared with transponders and imaged on a 3T MR scanner with different sequences. Computed tomography (CT) was performed as comparison. MR artifacts were assessed. An estimation of the maximum transponder de-flection force and heating was made.

    Results: The mean measured displacement of transponders was 0.1 mm (range=0.03-0.3 mm). Artifacts were observed adjacent to transponders using all sequences. The deflection force on the transponder in the gantry was less than 38 mN. No heating was observed.

    Conclusion: The absence of any substantial movement, the weak measured deflection force and absence of observed heating speaks for the safe use of MR imaging with transponder 3T. Local artefacts makes evaluation impossible adjacent to transponders.

  • 19.
    Wikström, Kenneth
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Isacsson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Nilsson, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Ahnesjö, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Reproducibility of heart and thoracic wall positionin repeated deep inspiration breath holds forradiotherapy of left-sided breast cancer patients2018In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 10, p. 1318-1324Article in journal (Refereed)
    Abstract [en]

    Background: Deep inspiration breath hold (DIBH) for radiotherapy of left-sided breast cancer patientscan effectively move the heart away from the target and reduce the heart dose compared to treatmentsin free breathing. This study aims to investigate the positional reproducibility of heart edge(HE) and thoracic wall (TW) during repeated DIBHs.

    Material and methods: At three occasions, 11 left-sided breast cancer patients were CT imaged during6 minutes of repeated DIBHs with 60 cine CT series. The series were evenly distributed over threebed positions and for each bed position, the heart edge associated maximum heart distance (MHD)and thoracic wall-associated maximum lung distance (MLD) from a reference line were retrospectivelyanalyzed. The high temporal resolution of the CT series enabled intrinsic heart movements to beresolved from breath hold variations. A body surface laser scanning system continuously extracted thethorax height and displayed it in a pair of goggles for patient feedback. To check for ‘fake-breathing’movements, e.g. that the patient lifts its back from the couch to reach DIBH, the couch-to-spine distancewas also measured in all CT series.

    Results: The analysis was done for 1432 cine CTs captured during 292 breath holds. The DIBH movedthe heart on average 15mm in medial direction compared with free breathing. For the three bed positionsstudied, the mean value of the max range, across all patients, was between 11–13mm for theMHD and 4–8mm for the MLD. The MHD variation due to breath hold variation was twice as large asthe MHD variation due to intrinsic heart movement. The couch-to-spine distance varied less than3mm for all fractions, i.e., no fake-breathing was discovered.

    Conclusions: The heart edge and thoracic wall reproducibility was high in relation to the medial heartdisplacement induced by the DIBH.

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  • 20.
    Wikström, Kenneth
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Nilsson, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Isacsson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Ahnesjö, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    A comparison of patient position displacements from body surface laser scanning and cone beam CT bone registrations for radiotherapy of pelvic targets2014In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, no 2, p. 268-277Article in journal (Refereed)
    Abstract [en]

    Background and purpose

    Optical surface detection has attractive features as a mean in radiotherapy for patient positioning tasks such as set-up, monitoring and gating. To aid in hitting radiotherapy targets the correlation between detected surface displacements and internal structure displacements is crucial. In this study, we compare set-up displacements derived from a body surface laser scanning (BSLS) system to displacements derived from bone registrations with a cone beam computed tomography (CBCT) system in order to quantify the accuracy and applicability of BSLS for fractionated treatments in the pelvic region.

    Material and methods

    Displacements from concurrent BSLS and CBCT registrations were compared for 40 patients treated in the pelvic region for a total of 170 set-ups. Surface data captured by BSLS at the first treatment fraction (BSLSref) was used as main reference for the BSLS system, while bony structures from the planning CT were used as a reference for the CBCT method. As comparison, the patient outline extracted from the planning CT was used as BSLS reference (CTref). The displacements detected by the CBCT system (skin-marks-only) was also used for comparison.

    Results

    The mean differences (+/- 1 SD) between the BSLS and CBCT displacements were -0.01 (+0.17) cm, 0.00 (+0.21) cm and 0.01 (+0.17) cm in the lateral, longitudinal and vertical directions, respectively. The median length of the difference was 0.26 cm (0.24-0.29 cm, 95% CI). The median of the difference between CBCT and BSLS displacements based on CTref was 0.37 cm (0.30-0.39 cm) and the median for skin-marks-only was 0.38 cm (0.34-0.42 cm).

    Conclusions

    The BSLS system is a good supplement to the CBCT system for accurate set-up for fractions when no CBCT is deemed necessary for pelvic targets. Inter-fractional skin movement in relation to bone was estimated to be 0.2 cm in the lateral (X), longitudinal (Y) and vertical direction (Z), respectively.

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