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  • 1. Baumann, Pia
    et al.
    Nyman, Jan
    Hoyer, Morten
    Gagliardi, Giovanna
    Lax, Ingmar
    Wennberg, Berit
    Drugge, Ninni
    Ekberg, Lars
    Friesland, Signe
    Johansson, Karl-Axel
    Lund, Jo-Smund
    Morhed, Elisabeth
    Nilsson, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Levin, Nina
    Paludan, Merete
    Sederholm, Christer
    Traberg, Anders
    Wittgren, Lena
    Lewensohn, Rolf
    Stereotactic body radiotherapy for medically inoperable patients with stage I non-small cell lung cancer: a first report of toxicity related to COPD/CVD in a non-randomized prospective phase II study2008In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 88, no 3, p. 359-67Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: In a retrospective study using stereotactic body radiotherapy (SBRT) in medically inoperable patients with stage I NSCLC we previously reported a local control rate of 88% utilizing a median dose of 15Gyx3. This report records the toxicity encountered in a prospective phase II trial, and its relation to coexisting chronic obstructive pulmonary disease (COPD) and cardio vascular disease (CVD). MATERIAL AND METHODS: Sixty patients were entered in the study between August 2003 and September 2005. Fifty-seven patients (T1 65%, T2 35%) with a median age of 75 years (59-87 years) were evaluable. The baseline mean FEV1% was 64% and median Karnofsky index was 80. A total dose of 45Gy was delivered in three fractions at the 67% isodose of the PTV. Clinical, pulmonary and radiological evaluations were made at 6 weeks, 3, 6, 9, 12, 18, and 36 months post-SBRT. Toxicity was graded according to CTC v2.0 and performance status was graded according to the Karnofsky scale. RESULTS: At a median follow-up of 23 months, 2 patients had relapsed locally. No grade 4 or 5 toxicity was reported. Grade 3 toxicity was seen in 12 patients (21%). There was no significant decline of FEV1% during follow-up. Low grade pneumonitis developed to the same extent in the CVD 3/17 (18%) and COPD 7/40 (18%) groups. The incidence of fibrosis was 9/17 (53%) and pleural effusions was 8/17 (47%) in the CVD group compared with 13/40 (33%) and 5/40 (13%) in the COPD group. CONCLUSION: SBRT for stage I NSCLC patients who are medically inoperable because of COPD and CVD results in a favourable local control rate with a low incidence of grade 3 and no grade 4 or 5 toxicity.

  • 2. Bentzen, Søren M.
    et al.
    Heeren, Germaine
    Cottier, Brian
    Slotman, Ben
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Lievens, Yolande
    van den Bogaert, Walter
    Towards evidence-based guidelines for radiotherapy infrastructure and staffing needs in Europe: the ESTRO QUARTS project2005In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 75, no 3, p. 355-65Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Adequate and equitable access to radiotherapy (RT) must be a reasonable health care goal for the EU. However, there are large variations among the EU countries and even regional variations within countries in the provision of RT. In this report, we combine the best available evidence on the indications for RT with national epidemiological data to arrive at estimates for the appropriate level of RT infrastructure in the 25 EU countries. PATIENTS AND METHODS: Data from three systematic overviews of the best available evidence for the indication for RT in 23 main cancer types are combined with epidemiological data from the EUCAN and GLOBOCAN databases on the crude incidence of each of these cancers in the 25 EU countries. Together with published benchmarks for accelerator throughput this allows estimation of the number of linear accelerators per million people required to facilitate appropriate RT utilization rates in each country. Where possible, the estimates are compared with the detailed data available from Sweden. RESULTS: The crude incidence of the main cancer types shows large variation among the 25 EU countries. This reflects in part differences in exposure to aetiological risk factors and partly differences among the countries in population age structure. Correspondingly, the estimate of the required number of linear accelerators per million people showed considerable variation: ranging from 4.0 in Cyprus to 8.1 in Hungary. The average for the 25 countries was 5.9 per million people. These estimates were compared with available national guidelines and actual data on RT infrastructure and large shortfalls were found in many countries. Implications for health economics and capacity planning are briefly discussed. CONCLUSIONS: The QUARTS project has developed a model that establishes a direct and transparent link between epidemiological data and indications for RT based on the best available evidence. Comparison of the model estimates with current levels of RT infrastructure has revealed major inequalities in provision of RT in the 25 EU countries. Continuation of this study is recommended as a way of improving RT provision on rational grounds throughout the European community and as a model for health care planning in the EU.

  • 3.
    Chen, Lingjing
    et al.
    Karolinska Inst, Dept Med Solna, Div Clin Epidemiol, Stockholm, Sweden.
    Eloranta, Sandra
    Karolinska Inst, Dept Med Solna, Div Clin Epidemiol, Stockholm, Sweden.
    Martling, Anna
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Glimelius, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Karolinska Inst, Dept Med Solna, Div Clin Epidemiol, Stockholm, Sweden.
    Neovius, Martin
    Karolinska Inst, Dept Med Solna, Div Clin Epidemiol, Stockholm, Sweden.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Smedby, Karin E.
    Karolinska Inst, Dept Med Solna, Div Clin Epidemiol, Stockholm, Sweden.
    Short- and long-term risks of cardiovascular disease following radiotherapy in rectal cancer in four randomized controlled trials and a population-based register2018In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 126, no 3, p. 424-430Article in journal (Refereed)
    Abstract [en]

    Aim: A population-based cohort and four randomized trials enriched with long-term register data were used to clarify if radiotherapy in combination with rectal cancer surgery is associated with increased risks of cardiovascular disease (CVD). Methods: We identified 14,901 rectal cancer patients diagnosed 1995-2009 in Swedish nationwide registers, of whom 9227 were treated with preoperative radiotherapy. Also, we investigated 2675 patients with rectal cancer previously randomized to preoperative radiotherapy or not followed by surgery in trials conducted 1980-1999. Risks of CVD overall and subtypes were estimated based on prospectively recorded hospital visits during relapse-free follow-up using multivariable Cox regression. Maximum follow-up was 18 and 33 years in the register and trials, respectively. Results: We found no association between preoperative radiotherapy and overall CVD risk in the register (Incidence Rate Ratio, IRR = 0.99, 95% confidence interval (CI) 0.92-1.06) or in the pooled trials (IRR = 1.07, 95% CI 0.93-1.24). We noted an increased risk of venous thromboembolism among irradiated patients in both cohorts (lRR(register) = 1.41, 95% CI 1.15-2.72; IRRtrials = 1.41, 95% CI 0.97-2.04), that remained during the first 6 months following surgery among patients treated 2006-2009, after the introduction of antithrombotic treatment (IRR6 (months) = 2.30, 95% CI 1.01-5.21). However, the absolute rate difference of venous thromboembolism attributed to RT was low (10 cases per 1000 patients and year). Discussion: Preoperative radiotherapy did not affect rectal cancer patients' risk of CVD overall. Although an excess risk of short-term venous thromboembolism was noted, the small increase in absolute numbers does not call for general changes in routine prophylactic treatment, but might do so for patients already at high risk of venous thromboembolism. (C) 2017 Elsevier B.V. All rights reserved.

  • 4. Fokstuen, Tone
    et al.
    Holm, Torbjörn
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Postoperative morbidity and mortality in relation to leukocyte counts and time to surgery after short-course preoperative radiotherapy for rectal cancer2009In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 93, no 2, p. 293-297Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Preoperative radiotherapy for rectal cancer decreases local recurrence rates, but increases postoperative complications. Impaired postoperative leukocyte reaction after preoperative short-course radiotherapy has been reported. The aim was to assess postoperative morbidity and mortality in relation to leukocyte reaction and the time interval between radiotherapy and surgery. MATERIALS AND METHODS: A retrospective analysis of patients included in the Stockholm I and II trials, randomising patients to surgery alone or to 5 x 5 Gy with immediate surgery, identified pre- and postoperative leukocyte values for 274 patients. RESULTS: In the surgery alone group (n=144), all but three patients (2%) reacted with leukocytosis (ratio post/preoperative >1.0) on day 1 and all but 9 (6%) on day 5. In the radiotherapy group (n=130), 40 (31%) became leukopenic (<4 x 10(9) cells/L) after radiotherapy, 29 (22%) reacted abnormally (leukopenia or ratio < or =1.0) on day 1 and 66 (51%) on day 5 (all p<0.001). Preoperative leukocyte counts did not influence postoperative morbidity, but a poor response on day 1 increased the risk of sepsis (p<0.05) and mortality (6/29 (21%) vs. 6/101 (6%), p<0.05). An interval of 10 days or more between the start of radiotherapy and surgery also had an impact on mortality; 6/17 (35%) vs. 6/113 (5%), p=0.001. In a logistic regression analysis, the time interval and age were independent predictors of mortality. CONCLUSIONS: Impaired postoperative leukocyte reaction is frequent after short-course radiotherapy and increases the risk of postoperative complications and death. A longer than recommended radiotherapy-surgery interval also appears to be detrimental for postoperative death, independently of leukocyte response.

  • 5. Georg, Dietmar
    et al.
    Nyholm, Tufve
    Olofsson, Jörgen
    Kjær-Kristoffersen, Flemming
    Schnekenburger, Bruno
    Winkler, Peter
    Nyström, Håkan
    Ahnesjö, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Karlsson, Mikael
    Clinical evaluation of monitor unit software and the application of action levels2007In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 85, no 2, p. 306-315Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The aim of this study was the clinical evaluation of an independent dose and monitor unit verification (MUV) software which is based on sophisticated semi-analytical modelling. The software was developed within the framework of an ESTRO project. Finally, consistent handling of dose calculation deviations applying individual action levels is discussed.

    MATERIALS AND METHODS: A Matlab-based software (&quot;MUV&quot;) was distributed to five well-established treatment centres in Europe (Vienna, Graz, Basel, Copenhagen, and Umeå) and evaluated as a quality assurance (QA) tool in clinical routine. Results were acquired for 226 individual treatment plans including a total of 815 radiation fields. About 150 beam verification measurements were performed for a portion of the individual treatment plans, mainly with time variable fluence patterns. The deviations between dose calculations performed with a treatment planning system (TPS) and the MUV software were scored with respect to treatment area, treatment technique, geometrical depth, radiological depth, etc.

    RESULTS: In general good agreement was found between calculations performed with the different TPSs and MUV, with a mean deviation per field of 0.2+/-3.5% (1 SD) and mean deviations of 0.2+/-2.2% for composite treatment plans. For pelvic treatments less than 10% of all fields showed deviations larger than 3%. In general, when using the radiological depth for verification calculations the results and the spread in the results improved significantly, especially for head-and-neck and for thorax treatments. For IMRT head-and-neck beams, mean deviations between MUV and the local TPS were -1.0+/-7.3% for dynamic, and -1.3+/-3.2% for step-and-shoot IMRT delivery. For dynamic IMRT beams in the pelvis good agreement was obtained between MUV and the local TPS (mean: -1.6+/-1.5%). Treatment site and treatment technique dependent action levels between +/-3% and +/-5% seem to be clinically realistic if a radiological depth correction is performed, even for dynamic wedges and IMRT.

    CONCLUSION: The software MUV is well suited for patient specific treatment plan QA applications and can handle all currently available treatment techniques that can be applied with standard linear accelerators. The highly sophisticated dose calculation model implemented in MUV allows investigation of systematic TPS deviations by performing calculations in homogeneous conditions

  • 6.
    Glimelius, Bengt
    et al.
    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.
    Proton beam therapy - do we need the randomised trials and can we do them?2007In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 83, no 2, p. 105-109Article in journal (Refereed)
  • 7.
    Glimelius, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Myklebust, Tor Åge
    Canc Registry Norway, Dept Registrat, Oslo, Norway..
    Lundqvist, Kristina
    Umea Univ, Dept Radiat Sci, Oncol, S-90187 Umea, Sweden..
    Wibe, Arne
    Norwegian Univ Sci & Technol, Dept Canc Res & Mol Med, Trondheim, Norway..
    Guren, Marianne G.
    Oslo Univ Hosp, Dept Oncol, N-0450 Oslo, Norway.;Oslo Univ Hosp, KG Jebsen Colorectal Canc Res Ctr, N-0450 Oslo, Norway..
    Two countries - Two treatment strategies for rectal cancer2016In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 121, no 3, p. 357-363Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Trials in rectal cancer have shown that radiotherapy (RT) decreases local recurrence rates, whereas the effects on survival are uncertain. Swedish and Norwegian oncologists have had different treatment recommendations. The aim was to evaluate local recurrence rates and survival in the two countries. Patients and methods: Between 1995 and 2012 rectal cancer patients registered in Sweden and Norway were analyzed, presenting population-based "real world" data. Results: Totally 29,029 Swedish and 15,456 Norwegian patients were analyzed. Resection for cure was performed in two-thirds of the patients. RT was given to 49% of Swedish patients, mainly short-course RT and to 26% of Norwegian patients, predominantly chemoradiotherapy (CRT). In Sweden, the proportion irradiated was stable whereas in Norway, an increase from 10% to 40% was seen. Local 5-year recurrence rates were initially higher in Norway (12%) than in Sweden (8%), whereas they were equally low (4%) during the latter time. No survival differences were seen, however, survival improved with time in both countries. Conclusions: Two entirely different approaches to preoperative therapy resulted in similar survival with initially higher local recurrence rates in Norway, but similarly low rates in later years. This raises questions about optimal RT rates and regimens.

  • 8.
    Grönlund, Eric
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science. Uppsala Univ, Med Radiat Sci, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Johansson, Silvia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Montelius, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Ahnesjö, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Dose painting by numbers based on retrospectively determined recurrence probabilities2017In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 122, no 2, p. 236-241Article in journal (Refereed)
    Abstract [en]

    Background and purpose: The aim of this study is to derive "dose painting by numbers" prescriptions from retrospectively observed recurrence volumes in a patient group treated with conventional radiotherapy for head and neck squamous cell carcinoma. Materials and methods: The spatial relation between retrospectively observed recurrence volumes and pre-treatment standardized uptake values (SUV) from fluorodeoxyglucose positron emission tomography (FDG-PET) imaging was determined. Based on this information we derived SUV driven dose-response functions and used these to optimize ideal dose redistributions under the constraint of equal average dose to the tumor volumes as for a conventional treatment. The response functions were also implemented into a treatment planning system for realistic dose optimization. Results: The calculated tumor control probabilities (TCP) increased between 0.1-14.6% by the ideal dose redistributions for all included patients, where patients with larger and more heterogeneous tumors got greater increases than smaller and more homogeneous tumors. Conclusions: Dose painting prescriptions can be derived from retrospectively observed recurrence volumes spatial relation to pre-treatment FDG-PET image data. The ideal dose redistributions could significantly increase the TCP for patients with large tumor volumes and large spread in SUV from FDG-PET. The results yield a basis for prospective studies to determine the clinical value for dose painting of head and neck squamous cell carcinomas.

  • 9. Gunnlaugsson, Adalsteinn
    et al.
    Anderson, Harald
    Lind, Pehr
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Johnsson, Anders
    Multicentre phase I-II trial of capecitabine and oxaliplatin in combination with radiotherapy for unresectable pancreatic and biliary tract cancer: The CORGI-U study2010In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 95, no 3, p. 292-297Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: In this multicentre phase I-II trial we evaluated the feasibility and efficacy of capecitabine and oxaliplatin followed by the combination of these two drugs with radiotherapy in patients with locally advanced pancreatic or biliary tract cancer. MATERIAL AND METHODS: Thirty-nine patients with inextirpable adenocarcinoma of the pancreas, gallbladder or extrahepatic bile ducts were included. Two cycles of XELOX (capecitabine 1000mg/m(2) bid d1-14+oxaliplatin 130mg/m(2) d1, q3w) were followed by XELOX-RT (radiotherapy (50.4Gy), combined with capecitabine 750-675mg/m(2) bid every radiotherapy day and oxaliplatin 40-30mg/m(2) once weekly). Primary end-points were tolerance (phase I) and objective response (phase II). RESULTS: The maximum tolerated doses of oxaliplatin and capecitabine to combine with irradiation were 30mg/m(2) and 675mg/m(2), respectively. Twenty-one percent (95% CI: 9-38%) of evaluable patients achieved partial response. Five patients went through surgery (three R0 resections). Two-year survival was 28%, and estimated local tumour control rate at 2 years was 72%. The most common grade 3-4 toxicity was nausea and vomiting. CONCLUSIONS: XELOX-RT (30mg/m(2) oxaliplatin/675mg/m(2) capecitabine in combination with 50.4Gy/28 fractions) was well tolerated and effective for locally advanced pancreatic and biliary tract cancer.

  • 10. Henriksson, Roger
    et al.
    Capala, Jacek
    Michanek, Annika
    Lindahl, Sten-Åke
    Salford, Leif G.
    Franzén, Lars
    Blomquist, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Westlin, Jan-Erik
    Bergenheim, A. Tommy
    Boron neutron capture therapy (BNCT) for glioblastoma multiforme: a phase II study evaluating a prolonged high-dose of boronophenylalanine (BPA)2008In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 88, no 2, p. 183-91Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: To evaluate the efficacy and safety of boron neutron capture therapy (BNCT) for glioblastoma multiforme (GBM) using a novel protocol for the boronophenylalanine-fructose (BPA-F) infusion. PATIENT AND METHODS: This phase II study included 30 patients, 26-69 years old, with a good performance status of which 27 have undergone debulking surgery. BPA-F (900 mg BPA/kg body weight) was given i.v. over 6h. Neutron irradiation started 2h after the completion of the infusion. Follow-up reports were monitored by an independent clinical research institute. RESULTS: The boron-blood concentration during irradiation was 15.2-33.7 microg/g. The average weighted absorbed dose to normal brain was 3.2-6.1 Gy (W). The minimum dose to the tumour volume ranged from 15.4 to 54.3 Gy (W). Seven patients suffered from seizures, 8 from skin/mucous problem, 5 patients were stricken by thromboembolism and 4 from abdominal disturbances in close relation to BNCT. Four patients displayed 9 episodes of grade 3-4 events (WHO). At the time for follow-up, minimum ten months, 23 out of the 29 evaluable patients were dead. The median time from BNCT treatment to tumour progression was 5.8 months and the median survival time after BNCT was 14.2 months. Following progression, 13 patients were given temozolomide, two patients were re-irradiated, and two were re-operated. Patients treated with temozolomide lived considerably longer (17.7 vs. 11.6 months). The quality of life analysis demonstrated a progressive deterioration after BNCT. CONCLUSION: Although, the efficacy of BNCT in the present protocol seems to be comparable with conventional radiotherapy and the treatment time is shorter, the observed side effects and the requirement of complex infrastructure and higher resources emphasize the need of further phase I and II studies, especially directed to improve the accumulation of (10)B in tumour cells.

  • 11. La Tessa, C.
    et al.
    Berger, T.
    Kaderka, R.
    Schardt, D.
    Körner, C.
    Ramm, U.
    Licher, J.
    Matsufuji, N.
    Dahlgren, Christina Vallhagen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Medical Physics.
    Lomax, T.
    Reitz, G.
    Durante, M.
    Out-of-field dose studies with an anthropomorphic phantom: Comparison of X-rays and particle therapy treatments2012In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 105, no 1, p. 133-138Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Characterization of the out-of-field dose profile following irradiation of the target with a 3D treatment plan delivered with modern techniques. Methods: An anthropomorphic RANDO phantom was irradiated with a treatment plan designed for a simulated 5×2×5cm 3 tumor volume located in the center of the head. The experiment was repeated with all most common radiation treatment types (photons, protons and carbon ions) and delivery techniques (Intensity Modulated Radiation Therapy, passive modulation and spot scanning). The measurements were performed with active diamond detector and passive thermoluminescence (TLD) detectors to investigate the out-of-field dose both inside and outside the phantom. Results: The highest out-of-field dose values both on the surface and inside the phantom were measured during the treatment with 25 MV photons. In the proximity of the Planned Target Volume (PTV), the lowest lateral dose profile was observed for passively modulated protons mainly because of the presence of the collimator in combination with the chosen volume shape. In the far out-of-field region (above 100 mm from the PTV), passively modulated ions were characterized by a less pronounced dose fall-off in comparison with scanned beams. Overall, the treatment with scanned carbon ions delivered the lowest dose outside the target volume. Conclusions: For the selected PTV, the use of the collimator in proton therapy drastically reduced the dose deposited by ions or photons nearby the tumor. Scanning modulation represents the optimal technique for achieving the highest dose reduction far-out-of-field.

  • 12. Lundkvist, Jonas
    et al.
    Ekman, Mattias
    Ericsson, Suzanne Rehn
    Isacsson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Jönsson, Bengt
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Economic evaluation of proton radiation therapy in the treatment of breast cancer2005In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 75, no 2, p. 179-85Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Proton beam therapy offers potential clinical advantages compared with conventional radiation therapy for many cancer patients. The benefits are mainly a result of a more favourable dose distribution. The treatment cost with proton radiation is higher than for conventional radiation, mainly due to the large investment cost of building a proton therapy facility. It is therefore important to evaluate whether the medical benefits of proton therapy are large enough to justify the higher treatment costs, compared with conventional radiation therapy. PATIENTS AND METHODS: The cost-effectiveness of proton therapy in the treatment of 55-year old women with left-sided breast cancer was assessed. A Markov cohort simulation model was used to simulate the life of patients diagnosed with breast cancers and treated with radiation. Cost and quality adjusted life years (QALYs) were the primary outcome measures. RESULTS: The study found a cost per QALY gained of 67,000 Euro for the base case analysis of an average breast cancer patient. The cost per QALY gained would, however, be considerably lower if a population with high-risk of developing cardiac disease was treated. Sensitivity analyses showed that the results were stable and that the risk of cardiac disease was the most important parameter. CONCLUSIONS: The results indicate that proton therapy for breast cancer can be cost-effective if appropriate risk groups are chosen as targets for the therapy.

  • 13.
    Nilsson, Cecilia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Valachis, Antonis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    The role of boost and hypofractionation as adjuvant radiotherapy in patients with DCIS: A meta-analysis of observational studies2015In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 114, no 1, p. 50-55Article, review/survey (Refereed)
    Abstract [en]

    Purpose: The purpose of this meta-analysis is to summarize the current evidence on the role of boost and the efficacy of hypofractionated radiotherapy in patients with ductal cancer in situ (DCIS) after surgery and grade the quality of evidence. Materials and methods: A comprehensive systematic electronic search through MEDLINE and the Cochrane Library as well as through the major international congresses' proceedings was conducted. Studies were considered eligible if they investigated the efficacy of hypofractionated vs. standard radiotherapy or the efficacy of boost vs. no boost in patients with DCIS. The outcome of interest was the number of local recurrences. Pooled estimates were calculated by using standard meta-analytic procedures. Results: Thirteen trials were considered eligible and were further analyzed. No difference in the risk of local recurrence was observed between the patients that received boost vs. no boost in the general cohort (12 studies, 6943 patients; Odds Ratio (OR): 0.91, 95% confidence interval (CI): 0.77-1.08, very low level of evidence). However, we found a reduced risk for local recurrence when boost was administered in patients with positive margins compared to no boost (6 studies, 811 patients; OR: 0.56, 95% Cl: 0.36-0.87, very low level of evidence). No difference in local recurrence rate between patients who received hypofractionated versus standard radiotherapy was observed (4 studies, 2534 patients; OR: 0.78, 95% CI: 0.58-1.03, low level of evidence). Conclusion: Hypofractionated radiotherapy seems to be a safe option in patients with DCIS after breast-conserving surgery while the addition of boost reduces the risk for local recurrence in the presence of positive margins. However, the level of evidence for these observations ranges between very low and low and the results of the ongoing randomized trials are necessary to confirm the results with higher level of evidence.

  • 14. Nyholm, Tufve
    et al.
    Olofsson, Jörgen
    Ahnesjö, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Section of Medical Physics.
    Karlsson, Mikael
    Photon pencil kernel parameterisation based on beam quality index2006In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 78, no 3, p. 347-351Article in journal (Refereed)
    Abstract [en]

    Background and purpose

    New treatment techniques in radiotherapy employ increasing dose calculation complexity in treatment planning. For an adequate check of the results coming from a modern treatment planning system, clinical tools with almost the same degree of generality and accuracy as the planning system itself are needed. To fulfil this need we propose a photon pencil kernel parameterization based on a minimum of input data that can be used for phantom scatter calculations. Through scatter integration the pencil kernel model can calculate common parameters, such as TPR or phantom scatter factors, used in various dosimetric QA (quality assurance) procedures.

    Material and methods

    The proposed model originates from an already published radially parameterized pencil kernel. A depth parameterization of the pencil kernel parameters has been introduced, based on a large database containing commissioned beam data for a commercial treatment planning system. The entire pencil kernel model demands only one photon beam quality index, TPR20,10, as input.

    Results

    By comparing the dose calculation results to the extensive experimental data set in the database, it has been possible to make a thorough analysis of the resulting accuracy. The errors in calculated doses, normalized to the reference geometry, are in most cases smaller than 2%.

    Conclusions

    The investigation shows that a pencil kernel model based only on TPR20,10 can be used for dosimetric verification purposes in megavoltage photon beams at depths below the range of contaminating electrons.

  • 15.
    Nyholm, Tufve
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science. Umea Univ, Dept Radiat Sci, S-90187 Umea, Sweden..
    Olsson, Caroline
    Gothenburg Univ, Sahlgrenska Acad, Inst Clin Sci, Dept Radiat Phys, Gothenburg, Sweden.;Western Sweden Healthcare Reg, Reg Canc Ctr West, Gothenburg, Sweden..
    Agrup, Mans
    Linkoping Univ Hosp, Dept Oncol, Linkoping, Sweden..
    Bjork, Peter
    Malar Hosp, Dept Phys & Biomed Engn, Eskilstuna, Sweden..
    Bjork-Eriksson, Thomas
    Sahlgrens Univ Hosp, Dept Oncol, Gothenburg, Sweden..
    Gagliardi, Giovanna
    Karolinska Univ Hosp, Dept Med Phys, Stockholm, Sweden..
    Grinaker, Hanne
    Swedish Radiat Safety Author, Lund, Sweden..
    Gunnlaugsson, Adalsteinn
    Lund Univ, Skane Univ Hosp, Dept Oncol & Radiat Phys, S-22100 Lund, Sweden..
    Gustafsson, Anders
    Cureos AB, Uppsala, Sweden..
    Gustafsson, Magnus
    Sahlgrens Univ Hosp, Dept Phys & Biomed Engn, Gothenburg, Sweden..
    Johansson, Bengt
    Orebro Univ Hosp, Dept Oncol, Orebro, Sweden.;Univ Orebro, Orebro, Sweden..
    Johnsson, Stefan
    Kalmar Cty Hosp, Dept Radiat Phys, Kalmar, Sweden..
    Karlsson, Magnus
    Umea Univ, Dept Radiat Sci, S-90187 Umea, Sweden..
    Kristensen, Ingrid
    Lund Univ, Skane Univ Hosp, Dept Oncol & Radiat Phys, S-22100 Lund, Sweden..
    Nilsson, Per
    Lund Univ, Skane Univ Hosp, Dept Oncol & Radiat Phys, S-22100 Lund, Sweden..
    Nystrom, Leif
    Umea Univ, Dept Radiat Sci, S-90187 Umea, Sweden..
    Onjukka, Eva
    Karolinska Univ Hosp, Dept Med Phys, Stockholm, Sweden..
    Reizenstein, Johan
    Univ Orebro, Orebro, Sweden..
    Skonevik, Johan
    Umea Univ, Dept Radiat Sci, S-90187 Umea, Sweden.;Orebro Univ Hosp, Dept Oncol, Orebro, Sweden..
    Soderstrom, Karin
    Umea Univ, Dept Radiat Sci, S-90187 Umea, Sweden..
    Valdman, Alexander
    Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden..
    Zackrisson, Bjorn
    Umea Univ, Dept Radiat Sci, S-90187 Umea, Sweden..
    Montelius, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    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.

  • 16.
    Nyqvist, Johanna
    et al.
    Skane Univ Hosp, Dept Otolaryngol & Head & Neck Surg, Lund, Sweden.;Umea Univ, Dept Clin Sci Otolaryngol & Head & Neck Surg, S-90187 Umea, Sweden..
    Fransson, Per
    Umea Univ, Dept Nursing, S-90187 Umea, Sweden..
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery. Umea Univ, Dept Clin Sci Otolaryngol & Head & Neck Surg, S-90187 Umea, Sweden..
    Hammerlid, Eva
    Sahlgrens Univ Hosp, Dept Otolaryngol & Head & Neck Surg, Gothenburg, Sweden..
    Kjellen, Elisabeth
    Lund Univ, Skane Univ Hosp, Dept Oncol & Radiat Phys, S-22100 Lund, Sweden..
    Franzen, Lars
    Umea Univ, Dept Radiat Sci Oncol, S-90187 Umea, Sweden..
    Soderstrom, Karin
    Umea Univ, Dept Radiat Sci Oncol, S-90187 Umea, Sweden..
    Wickart-Johansson, Gun
    Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden..
    Friesland, Signe
    Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden..
    Sjodin, Helena
    Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden..
    Brun, Eva
    Lund Univ, Skane Univ Hosp, Dept Oncol & Radiat Phys, S-22100 Lund, Sweden..
    Ask, Anders
    Lund Univ, Skane Univ Hosp, Dept Oncol & Radiat Phys, S-22100 Lund, Sweden..
    Nilsson, Per
    Lund Univ, Skane Univ Hosp, Dept Oncol & Radiat Phys, S-22100 Lund, Sweden..
    Ekberg, Lars
    Lund Univ, Skane Univ Hosp, Dept Oncol & Radiat Phys, S-22100 Lund, Sweden..
    Bjork-Eriksson, Thomas
    Sahlgrens Univ Hosp, Dept Oncol, Gothenburg, Sweden..
    Nyman, Jan
    Sahlgrens Univ Hosp, Dept Oncol, Gothenburg, Sweden..
    Loden, Britta
    Karlstad Cent Hosp, Dept Clin Oncol, Karlskrona, Sweden..
    Lewin, Freddi
    Ryhov Cty Hosp, Dept Oncol, Jonkoping, Sweden..
    Reizenstein, Johan
    Orebro Univ Hosp, Dept Oncol, Orebro, Sweden..
    Lundin, Erik
    Ryhov Cty Hosp, Dept Oncol, Jonkoping, Sweden..
    Zackrisson, Bjorn
    Umea Univ, Dept Radiat Sci Oncol, S-90187 Umea, Sweden..
    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.

  • 17.
    Pettersson, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Johansson, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Persson, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Berglund, Anders
    Turesson, Ingela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Effects of a dietary intervention on acute gastrointestinal side effects and other aspects of health-related quality of life: A randomized controlled trial in prostate cancer patients undergoing radiotherapy2012In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 103, no 3, p. 333-340Article in journal (Refereed)
    Abstract [en]

    Purpose:

    To study the effect of a dietary intervention on acute gastrointestinal side effects and other aspects of health-related quality of life (HRQOL) in prostate cancer patients referred to radiotherapy.

    Materials and methods:

    A total of 130 patients were randomly assigned to one of two groups: an intervention group (IG, n = 64), instructed to reduce their intake of insoluble dietary fibres and lactose, a standard care group (SC, n = 66), instructed to continue their normal diet. Gastrointestinal side effects and other aspects of HRQOL were evaluated from baseline up to 2 months after completed radiotherapy, using the EORTC QLQ-C30 and QLQ-PR25 and the study-specific Gastrointestinal Side Effects Questionnaire (GISEQ). A scale indicating adherence to dietary instructions was developed from a Food Frequency Questionnaire (FFQ), with lower scores representing better compliance. Descriptive and inferential statistical analyses were conducted.

    Results:

    There was an interaction effect between randomization and time in the FFQ Scores (p < 0.001), indicating that both groups followed their assigned dietary instructions. The dietary intervention had no effect on gastrointestinal side effects or other aspects of HRQOL. During radiotherapy, the percentage of patients with bowel symptoms and bloated abdomen was lower in IG compared to SC, but the between-group differences were not statistically significant. During radiotherapy, the percentage of patients with bowel symptoms, urinary symptoms, pain, fatigue and diminished physical and role functioning increased in both groups.

    Conclusions:

    The dietary intervention had no effect on gastrointestinal side effects or other aspects of HRQOL. The tendency towards lower prevalence of bowel symptoms in IG may indicate some positive effect of the dietary intervention, but methodological refinements, clearer results and longer follow-up are needed before the value of diet change can be established with certainty.

  • 18.
    Pettersson, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Persson, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Berglund, Anders
    Turesson, Ingela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Johansson, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Effects of a dietary intervention on gastrointestinal symptoms after prostate cancer radiotherapy: Long-term results from a randomized controlled trial2014In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 113, no 2, p. 240-247Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE:

    To evaluate the long-term effects of dietary intervention on gastrointestinal symptoms after highly dose-escalated radiotherapy for localized prostate cancer, using boost with protons or high-dose-rate brachytherapy.

    MATERIALS AND METHODS:

    Patients were randomized to an intervention group (n=64) advised to reduce insoluble dietary fiber and lactose intake, or to a standard care group (n=66) advised to continue their usual diet. Gastrointestinal symptoms, other domains of health-related quality of life (HRQOL), and dietary intake were evaluated for ⩽24months post-radiotherapy with the European Organization for Research and Treatment of Cancer quality-of-life questionnaires QLQ-C30 and QLQ-PR25, Gastrointestinal Side Effects Questionnaire, and Food Frequency Questionnaire. The effect of the intervention on gastrointestinal symptoms was evaluated using generalized estimating equations.

    RESULTS:

    Dietary intervention had no obvious effect on long-term gastrointestinal symptoms or HRQOL. The intervention group markedly reduced their dietary fiber and lactose intake during radiotherapy, but adherence tended to decline over time. The vast majority of long-term gastrointestinal symptoms were reported as 'a little', with a noticeable difference from pre-treatment only for unintentional stool leakage, limitations on daily activities, and mucus discharge.

    CONCLUSION:

    Long-term gastrointestinal symptoms were predominantly mild, and dietary intervention was not superior to a usual diet in preventing these symptoms.

  • 19.
    Qvarnström, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Simonsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Nyman, Jan
    Gothenburg Univ, Sahlgrenska Univ Hosp, Dept Oncol, Gothenburg, Sweden..
    Hermansson, Ingegerd
    Gothenburg Univ, Sahlgrenska Univ Hosp, Dept Oncol, Gothenburg, Sweden..
    Book, Majlis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Johansson, Karl-Axel
    Gothenburg Univ, Sahlgrenska Univ Hosp, Dept Radiophys, Gothenburg, Sweden..
    Turesson, Ingela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Double strand break induction and kinetics indicate preserved hypersensitivity in keratinocytes to subtherapeutic doses for 7 weeks of radiotherapy2017In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 122, no 1, p. 163-169Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Previously we reported that hyper-radiosensitivity (HRS) was evidenced by quantifying DNA double strand break (DSB) foci in epidermis biopsies collected after delivering radio therapeutic one and five dose fractions. The aim of this study was to determine whether HRS was preserved throughout a 7-week radiotherapy treatment, and also to examine the rate of foci decline and foci persistence between dose fractions.

    Materials and methods: 42 patients with prostate cancer received 7-week fractionated radiotherapy treatment (RT) with daily dose fractions of 0.05-1.10 Gy to the skin. Before RT, and at several times throughout treatment, skin biopsies (n = 452) were collected at 30 min, and 2, 3, 24, and 72 h after dose fractions. DSB-foci markers, gamma H2AX and 53BP1, were labelled in epidermal keratinocytes with immunofluorescence and immunohistochemical staining. Foci were counted both with digital image analysis and manually.

    Results: HRS in keratinocytes was evidenced by the dose-response relationships of DSB foci, observed throughout the treatment course, independent of sampling time and quantification method. Foci observed at 24 h after dose fractions indicated considerable DSB persistence. Accordingly, foci significantly accumulated after 5 consecutive dose fractions. For doses below 0.3 Gy, persistent foci could be observed even at 72 h after damage induction. A comparison of gamma H2AX and 53BP1 quantifications in double-stained biopsies showed similar HRS dose-response relationships.

    Conclusions: These results represented the first evidence of preserved HRS, assessed by gamma H2AX- and 53BP1-labelled DSB foci, throughout a 7-week treatment course with daily repeated subtherapeutic dose fractions.

  • 20.
    Radu, Calin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Berglund, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Short-course preoperative radiotherapy with delayed surgery in rectal cancer: a retrospective study2008In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 87, no 3, p. 343-9Article in journal (Refereed)
    Abstract [en]

    PURPOSE: In the most advanced, non-resectable primary rectal cancers, conventional long-course radiotherapy (RT) (1.8-2Gyx25-28), frequently combined with chemotherapy, has been used since tumour regression is needed in order to allow a radical (R0) resection. In Uppsala, short-course 5x5Gy with planned delayed surgery has been used in patients with contraindications to long-course RT (+/-chemotherapy). The aim is to describe our experience of using this approach in patients not eligible for standard treatment. PATIENTS AND METHODS: During 2002 and 2005, 46 patients with non-resectable rectal cancer (+/-synchronous distant metastases) were treated with 5x5Gy and delayed surgery if possible. The clinical records were retrospectively evaluated. The first group (A) had no metastases (T4NXM0), whereas the other two groups (B+C) had metastases (T4NXM1). In group (B), the patients had predominantly loco-regional disease and were not candidates for combination chemotherapy (high age, co-morbidities), and in group (C) up-front combination chemotherapy was given, with the intention to have surgery of both the primary and the secondaries if sufficient regression at both sites were seen. RESULTS: The patients in the first two groups (A+B) were old (median 79 and 76 years, respectively), and had several co-morbidities. In group (C), median age was 63 years. The 5x5Gy RT was well tolerated by most patients, but grade IV diarrhoea was recorded in three elderly patients. One patient in the group (C) died from neutropenic fever. Many patients were reported to have less local symptoms after the treatment given. Delayed surgery was performed in all but nine patients. Radical surgery (R0+R1) was performed in 22 (92%) (group A), 4 (44%) (group B), and 6 (46%) (group C) patients, respectively. A pCR was seen in four patients (two in group A and two in group C). No postoperative deaths occurred. CONCLUSIONS: Considering the very high age and presence of co-morbidity, the 5x5Gy schedule is well tolerated. Further, considering the very advanced local stage, the schedule has considerable anti-tumour activity and can result in radical surgery in a high proportion of patients.

  • 21.
    Simonsson, Martin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Qvarnström, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Nyman, Jan
    Johansson, Karl-Axel
    Garmo, Hans
    Turesson, Ingela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Low-dose hypersensitive gammaH2AX response and infrequent apoptosis in epidermis from radiotherapy patients2008In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 88, no 3, p. 388-397Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: A low-dose hypersensitivity to radiation can be observed in vitro for many human cell types in terms of increased cell kill per dose unit for doses below 0.5Gy. Quantification of the double-strand break marker gammaH2AX in samples taken in clinical radiotherapy practice has the potential to provide important information about how induction and repair of severe DNA damage and apoptosis are linked to low-dose hypersensitivity. MATERIAL AND METHODS: The effects of exposure to low doses (0.05-1.1Gy) were investigated in skin biopsies taken from prostate cancer patients undergoing the first week of radiotherapy. gammaH2AX foci and apoptotic cells were visualised by immunohistochemistry and quantified by image analysis. RESULTS: The gammaH2AX foci pattern in biopsies taken 30min after a single fraction revealed a low-dose hypersensitivity below 0.3Gy (p=0.0009). The result was consistent for repeated fractions (p=0.00001). No decrease in foci numbers could be detected when comparing biopsies taken 30min and 2h after single fractions of 0.4 and 1.2Gy. The result was consistent for repeated fractions. Only 43 of 168,000 cells in total were identified as apoptotic, yet a dose dependency could be detected after 1week of radiotherapy (p=0.003). CONCLUSIONS: We describe a method based on gammaH2AX to study DNA damage response and apoptosis in a clinical setting. A gammaH2AX hypersensitive response to low doses can be observed in epidermal skin, already 30min following delivered fraction. A very low frequency of apoptosis in normal epithelium suggests that this effect is not an important part of the in vivo response to low doses.

  • 22.
    Stoppel, Gerhild
    et al.
    Med Sch Hannover, Dept Radiotherapy, Hannover, Germany..
    Eich, Hans-Theodor
    Univ Hosp Munster, Dept Radiotherapy, Munster, Germany..
    Matuschek, Christiane
    Heinrich Heine Univ Hosp Dusseldorf, Dept Radiat Oncol, Dusseldorf, Germany..
    Kortmann, Rolf-Dieter
    Univ Leipzig, Dept Radiotherapy, Leipzig, Germany..
    Meyer, Frank
    Dept Radiotherapy Augsburg, Augsburg, Germany..
    Martinsson, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Nilsson, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Kristensen, Ingrid
    Skane Univ Hosp, Dept Clin Sci Oncol & Pathol & Radiat Phys, Lund, Sweden..
    Vordermark, Dirk
    Martin Luther Univ Halle Wittenberg, Dept Radiat Oncol, Wittenberg, Germany..
    Willich, Normann
    Univ Hosp Munster, Dept Radiotherapy, Munster, Germany..
    Christiansen, Hans
    Med Sch Hannover, Dept Radiotherapy, Hannover, Germany..
    Koch, Raphael
    Univ Munster, Inst Biostat & Clin Res, Munster, Germany..
    Steinmann, Diana
    Med Sch Hannover, Dept Radiotherapy, Hannover, Germany..
    Lung toxicity after radiation in childhood: Results of the International Project on Prospective Analysis of Radiotoxicity in Childhood and Adolescence2017In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 125, no 2, p. 286-292Article in journal (Refereed)
    Abstract [en]

    Background and purpose: This study presents the evaluation of acute and late toxicities of the lung in children and adolescents after irradiation in terms of dose-volume effects. Materials and methods: Irradiated children and adolescents in Germany have prospectively been documented since 2001 in the "Registry for the Evaluation of Side-Effects after Radiotherapy in Childhood and Adolescence (RiSK)"; in Sweden since 2008 in the RADTOX registry. Results: Up to April 2012, 1,392 children were recruited from RiSK, and up to June 2013, 485 from the RADTOX-registry. Of these patients, 295 were irradiated to the lung. Information about acute toxicity was available for 228 patients. 179 patients have been documented concerning late toxicity (>= grade 1: n = 28). The acute toxicity rate was noticeably higher in children irradiated with 5-20 Gy (p < 0.05). In the univariate analysis, a shorter time until late toxicity was noticeably associated with irradiation with 5-15 Gy (p < 0.05). Conclusion: Acute and late toxicities appear to be correlated with higher irradiation volumes and low doses. Our data indicate that similar to the situation in adult patients, V5, V10, V15 and V20 should be kept as low as possible (e.g., at least V5 < 50%, V10 and V15 < 35% and V20 < 30%) in children and adolescents to lower the risk of toxicity. (C) 2017 Elsevier B.V. All rights reserved.

  • 23.
    Söderström, Karin
    et al.
    Umea Univ, Umea Univ Hosp, Dept Radiat Sci, Oncol, Umea, Sweden..
    Nilsson, Per
    Lund Univ, Skane Univ Hosp, Dept Oncol & Radiat Phys, S-22100 Lund, Sweden..
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Zackrisson, Björn
    Umea Univ, Umea Univ Hosp, Dept Radiat Sci, Oncol, Umea, Sweden..
    Jaghagen, Eva Levring
    Umea Univ, Dept Odontol Oral & Maxillofacial Radiol, Umea, Sweden..
    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 25 months after the start of RT. Patient-reported choking was analysed at 12 and 60 months 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.

  • 24.
    Tilly, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Olsson, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Hartman, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Coderre, Jeffrey
    Makar, Michael
    Malmquist, Jonas
    Sjöberg, Stefan
    Pettersson, Jean
    Carlsson, Jörgen
    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.
    In vitro determination of toxicity, binding, retention, subcellular distribution and biological efficacy of the boron neutron capture agentDAC-11996In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 38, no 1, p. 41-50Article in journal (Refereed)
    Abstract [en]

    In boron neutron capture therapy (BNCT), 10B is delivered selectively to the tumour cells and the nuclide then forms high-LET radiation (4He2+ and 7Li3+) upon neutron capture. Today much research is focused on development of a variety of boron compounds aimed for BNCT. The compounds must be thoroughly analysed in preclinical tests regarding basic characteristics such as binding and subcellular distribution to enable accurate estimations of dose-modifying factors. DAC-1,2-[2-(3-amino-propyl)-1,2-dicarba-closo-dodecaboran (12)-1-yl-methoxy]- 1,3-propanediol was synthesized at our laboratories and the human colon carcinoma cells LS-174T were used as an in vitro model. The boron compound showed a remarkable intracellular accumulation, 20-100 times higher than the boron content in the culture medium, in cultured cells and was not removed by extensive washes. Approximately half of the boron taken up also remained within the cells for at least 4 days. The DAC-1 compound alone was not toxic at boron concentrations below 2.5 micrograms B/g. The intracellular distribution of the boron compound was investigated by subcellular fractionation experiments and low pH treatments. It is possible that DAC-1 binds to some intracellular molecules or to membranes connected with organelles in the cytoplasm or even to the inside of the outer cell membrane. Another possibility is that the compound, due to the somewhat lipophilic properties, is embedded in the membranes. Thermal neutron irradiations were carried out at the Brookhaven Medical Research Reactor (BMRR). At a survival level of 0.1, DAC-1 + thermal neutrons were about 10.5 times more effective in cell inactivation than the thermal neutrons alone. Monte Carlo calculations gave a mean value of the 10B-dependent specific energy, the dose, of 0.22 Gy. The total physical dose during irradiation of DAC-1-containing cells with a neutron fluence of 0.18 x 10(12) n/cm2 was 0.39 Gy. The dose-modifying factor, at survival level 0.1, when comparing irradiation with thermal neutrons with and without DAC-1 was 3.4, while the dose-modifying factor when comparing neutron irradiations of cells with DAC-1 and irradiation of the cells with 60Co-gamma was 7.3. The results are encouraging and in vivo tests of tissue distributions and tumour uptake should now be carried out.

  • 25.
    Turesson, Ingela
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Nyman, Jan
    Qvarnström, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Simonsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Book, Majlis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Hermansson, Ingegerd
    Sigurdardottir, Sunna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Johansson, Karl-Axel
    A low-dose hypersensitive keratinocyte loss in response to fractionated radiotherapy is associated with growth arrest and apoptosis2010In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 94, no 1, p. 90-101Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: The existence of a hypersensitive radiation response to doses below 0.5Gy is well established for many normal and tumour cell lines. There is also evidence for hypersensitive tissue responses in acute skin damage and kidney function in mice. Recently, we have identified that a hypersensitive gammaH2AX response exists in human epidermis. The aim of this study was to investigate the dose-response of basal clonogenic keratinocytes in normal skin to fractionated radiotherapy with low dose fractions. MATERIALS: Skin punch biopsies were taken before and during radiotherapy from prostate cancer patients undergoing radiotherapy with a curative intent. Areas of epidermis receiving daily fractions of approximately 0.1, 0.2, 0.45 and 1.1Gy were biopsied on the same occasion to determine dose-response for each individual patient. In total, 89 cases were assessed either at 1, 2.5, 3, 4, 5 or 6.5 weeks in the treatment course. Biopsy sampling of another 25 patients was performed from areas receiving 0.45 and 1.1Gy per fraction at regular intervals throughout the 7-week treatment period. The number of basal keratinocytes per mm of the interfollicular epidermis was determined. The DNA damage response of the basal keratinocytes was investigated by immunohistochemical staining for molecular markers of growth arrest, mitosis and cell death, using p21, phospho-H3 and gammaH2AX, respectively. The number of stained keratinocytes in the basal layer was counted manually. The p21 staining was also quantified by digital image analysis. RESULTS: The individual dose-response relationships revealed a low-dose hypersensitivity for reduction of basal keratinocytes throughout 7 weeks of radiotherapy (p<0.01). Growth arrest and cell proliferation assessed at 1 week and 6.5 weeks showed, in both cases, hypersensitive increase of p21 (p<0.01) and hypersensitive depression of mitosis (p<0.01). Manual counting and digital image analysis of p21 showed good agreement. Cell death was infrequent but increased significantly between 1 and 6.5 weeks and displayed a hypersensitive dose-response at the end of the treatment period. CONCLUSIONS: A low-dose hypersensitivity in basal skin keratinocyte reduction is present throughout 7 weeks of radiotherapy. A persistent hypersensitive growth arrest response and cell killing mediate this effect.

  • 26. Valentini, Vincenzo
    et al.
    Aristei, Cynthia
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Minsky, Bruce D
    Beets-Tan, Regina
    Borras, Jose M
    Haustermans, Karin
    Maingon, Philippe
    Overgaard, Jens
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Quirke, Phil
    Schmoll, Hans-Joachim
    Sebag-Montefiore, David
    Taylor, Irving
    Van Cutsem, Eric
    Van de Velde, Cornelius
    Cellini, Numa
    Latini, Paolo
    Multidisciplinary Rectal Cancer Management: 2nd European Rectal Cancer Consensus Conference (EURECA-CC2)2009In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 92, no 2, p. 148-163Article, review/survey (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: During the first decade of the 21st century a number of important European randomized studies were published. In order to help shape clinical practice based on best scientific evidence from the literature, the International Conference on 'Multidisciplinary Rectal Cancer Treatment: Looking for an European Consensus' (EURECA-CC2) was organized in Italy under the endorsement of European Society of Medical Oncology (ESMO), European Society of Surgical Oncology (ESSO), and European Society of Therapeutic Radiation Oncology (ESTRO). METHODS: Consensus was achieved using the Delphi method. The document was available to all Committee members as a web-based document customized for the consensus process. Eight chapters were identified: epidemiology, diagnostics, pathology, surgery, radiotherapy and chemotherapy, treatment toxicity and quality of life, follow-up, and research questions. Each chapter was subdivided by a topic, and a series of statements were developed. Each member commented and voted, sentence by sentence thrice. Sentences upon which an agreement was not reached after voting round # 2 were openly debated during a Consensus Conference in Perugia (Italy) from 11 December to 13 December 2008. A hand-held televoting system collected the opinions of both the Committee members and the audience after each debate. The Executive Committee scored percentage consensus based on three categories: "large consensus", "moderate consensus", and "minimum consensus". RESULTS: The total number of the voted sentences was 207. Of the 207, 86% achieved large consensus, 13% achieved moderate consensus, and only 3 (1%) resulted in minimum consensus. No statement was disagreed by more than 50% of the members. All chapters were voted on by at least 75% of the members, and the majority was voted on by >85%. CONCLUSIONS: This Consensus Conference represents an expertise opinion process that may help shape future programs, investigational protocols, and guidelines for staging and treatment of rectal cancer throughout Europe.

  • 27. Valentini, Vincenzo
    et al.
    Beets-Tan, Regina
    Borras, Josep M.
    Krivokapić, Zoran
    Leer, Jan Willem
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Rödel, Claus
    Schmoll, Hans Joachim
    Scott, Nigel
    Van de Velde, Cornelius
    Verfaillie, Christine
    Evidence and research in rectal cancer2008In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 87, no 3, p. 449-474Article, review/survey (Refereed)
    Abstract [en]

    The main evidences of epidemiology, diagnostic imaging, pathology, surgery, radiotherapy, chemotherapy and follow-up are reviewed to optimize the routine treatment of rectal cancer according to a multidisciplinary approach. This paper reports on the knowledge shared between different specialists involved in the design and management of the multidisciplinary ESTRO Teaching Course on Rectal Cancer. The scenario of ongoing research is also addressed. In this time of changing treatments, it clearly appears that a common standard for large heterogeneous patient groups have to be substituted by more individualised therapies based on clinical-pathological features and very soon on molecular and genetic markers. Only trained multidisciplinary teams can face this new challenge and tailor the treatments according to the best scientific evidence for each patient.

  • 28. Vatnitsky, S
    et al.
    Moyers, M
    Miller, D
    Abell, G
    Slater, JM
    Pedroni, E
    Coray, A
    Mazal, A
    Newhauser, W
    Jaekel, O
    Heese, J
    Fukumura, A
    Futami, Y
    Verhey, L
    Daftari, I
    Grusell, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, The Svedberg Laboratory.
    Molokanov, A
    Bloch, C
    Proton dosimetry intercomparison based on the ICRU report 59 protocol1999In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 51, no 3, p. 273-279Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE:

    A new protocol for calibration of proton beams was established by the ICRU in report 59 on proton dosimetry. In this paper we report the results of an international proton dosimetry intercomparison, which was held at Loma Linda University Medical Center. The goals of the intercomparison were, first, to estimate the level of consistency in absorbed dose delivered to patients if proton beams at various clinics were calibrated with the new ICRU protocol, and second, to evaluate the differences in absorbed dose determination due to differences in 60Co-based ionization chamber calibration factors.

    MATERIALS AND METHODS:

    Eleven institutions participated in the intercomparison. Measurements were performed in a polystyrene phantom at a depth of 10.27 cm water equivalent thickness in a 6-cm modulated proton beam with an accelerator energy of 155 MeV and an incident energy of approximately 135 MeV. Most participants used ionization chambers calibrated in terms of exposure or air kerma. Four ionization chambers had 60Co-based calibration in terms of absorbed dose-to-water. Two chambers were calibrated in a 60Co beam at the NIST both in terms of air kerma and absorbed dose-to-water to provide a comparison of ionization chambers with different calibrations.

    RESULTS:

    The intercomparison showed that use of the ICRU report 59 protocol would result in absorbed doses being delivered to patients at their participating institutions to within +/-0.9% (one standard deviation). The maximum difference between doses determined by the participants was found to be 2.9%. Differences between proton doses derived from the measurements with ionization chambers with N(K)-, or N(W) - calibration type depended on chamber type.

    CONCLUSIONS:

    Using ionization chambers with 60Co calibration factors traceable to standard laboratories and the ICRU report 59 protocol, a distribution of stated proton absorbed dose is achieved with a difference less than 3%. The ICRU protocol should be adopted for clinical proton beam calibration. A comparison of proton doses derived from measurements with different chambers indicates that the difference in results cannot be explained only by differences in 60Co calibration factors.

  • 29. 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.

  • 30. Waligórski, Michael P R
    et al.
    Hollmark, Malin
    Gudowska, Irena
    Lesia, Jan
    Cellular parameters and RBE-LET dependences for modelling heavy-ion radiotherapy.2004In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 73 Suppl 2, p. S173-5Article in journal (Refereed)
    Abstract [en]

    Sets of four parameters (m, E0, sigma0 and kappa) of the cellular track structure model of Katz have been fitted to recently published data concerning human melanoma (AA) and mammalian (V79) cells exposed to a variety of lighter ions and to mixed ion-Co60 and ion-ion irradiation. Using these parameters, model predictions of V79 survival were verified against experimental data. RBE-LET dependences were calculated and compared with experimental data obtained for V79 cells after exposure to 3He, 12C and 20Ne ion beams. The presented track-segment approach used in track structure calculations, while satisfactory for heavier ions, may be of limited value for predicting the RBE-LET dependence of proton and helium radiotherapy beams in regions close to the distal range of these particles. We discuss the predictive capability of this model and propose standards in reporting cellular radiobiology data for application in modelling heavy ion beam radiotherapy.

  • 31.
    Weber, Damien C.
    et al.
    ETH Domain, Paul Scherrer Inst, Ctr Proton Therapy, CH-5232 Villigen, Switzerland.;EORTC, RTQA Strateg Comm, Brussels, Belgium..
    Abrunhosa-Branquinho, Andre
    EORTC HQ, Brussels, Belgium..
    Bolsi, Alessandra
    ETH Domain, Paul Scherrer Inst, Ctr Proton Therapy, CH-5232 Villigen, Switzerland..
    Kacperek, Andrzej
    Clatterbridge Canc Ctr, Eye Proton therapy Ctr, Bebington, England..
    Dendale, Remi
    Inst Curie, Protontherapy Ctr ICPO, Paris, France..
    Geismar, Dirk
    Univ Hosp Essen, West German Proton Therapy Ctr Essen, Clin Particle Therapy, Munich, Germany..
    Bachtiary, Barbara
    Rinecker Proton Therapy Ctr, Munich, Germany..
    Hall, Annika
    Skandionklinick, Uppsala, Sweden..
    Heufelder, Jens
    Herfarth, Klaus
    Heidelberg Univ, Heidelberg, Germany.;Univ Heidelberg Hosp, Heidelberg, Germany..
    Debus, Juergen
    Heidelberg Univ, Heidelberg, Germany.;Univ Heidelberg Hosp, Heidelberg, Germany..
    Amichetti, Maurizio
    Charite Univ Med Berlin, BerlinProtonen HZB, Berlin, Germany.;Azienda Prov Serv Sanitari, Proton Therapy Ctr, Trento, Italy..
    Krause, Mechthild
    Tech Univ Dresden, Fac Med, Dept Radiat Oncol, Dresden, Germany.;Tech Univ Dresden, OncoRay Natl Ctr Radiat Res Oncol, Fac Med, Dresden, Germany.;Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dresden, Germany.;Helmholtz Zentrum Dresden, Dresden, Germany..
    Orecchia, Roberto
    Ctr Nazl Adroterapia Oncolog, European Inst Oncol, Sci Directorate, Milan, Italy.;Ctr Nazl Adroterapia Oncolog, European Inst Oncol, Sci Directorate, Pavia, Italy..
    Vondracek, Vladimir
    Proton Therapy Ctr, Prague, Czech Republic..
    Thariat, Juliette
    Univ Sophia Antipolis, Ctr Antoine Lacassagne, Nice, France..
    Kajdrowicz, Tomasz
    Phys Polish Acad Sci, Inst Nucl, Krakow, Poland..
    Nilsson, Kristina
    Uppsala University, The Svedberg Laboratory.
    Grau, Cai
    Aarhus Univ Hosp, Dept Oncol, Aarhus, Denmark..
    Profile of European proton and carbon ion therapy centers assessed by the EORTC facility questionnaire2017In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 124, no 2, p. 185-189Article in journal (Refereed)
    Abstract [en]

    Background: We performed a survey using the modified EORTC Facility questionnaire (pFQ) to evaluate the human, technical and organizational resources of particle centers in Europe.

    Material and methods: The modified pFQ consisted of 235 questions distributed in 11 sections accessible on line on an EORTC server. Fifteen centers from 8 countries completed the pFQ between May 2015 and December 2015.

    Results: The average number of patients treated per year and per particle center was 221 (range, 40-557). The majority (66.7%) of centers had pencil beam or raster scanning capability. Four (27%) centers were dedicated to eye treatment only. An increase in the patients-health professional FTE ratio was observed for eye tumor only centers when compared to other centers. All centers treated routinely chordomas/-chondrosarcomas, brain tumors and sarcomas but rarely breast cancer. The majority of centers treated pediatric cases with particles. Only a minority of the queried institutions treated non-static targets.

    Conclusions: As the number of particle centers coming online will increase, the experience with this treatment modality will rise in Europe. Children can currently be treated in these facilities in a majority of cases. The majority of these centers provide state of the art particle beam therapy.

  • 32.
    Wennstig, Anna-Karin
    et al.
    Umea Univ, Dept Surg & Perioperat Sci, Surg, S-90187 Umea, Sweden.;Sundsvall Hosp, Dept Oncol, SE-85186 Sundsvall, Sweden..
    Garmo, Hans
    Kings Coll London, Fac Life Sci & Med, London WC2R 2LS, England.;Reg Canc Ctr, Uppsala, Sweden..
    Hållström, Per
    Gavle Cent Hosp, Dept Oncol, Gavle, Sweden..
    Nyström, Petra Witt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Edlund, Per
    Gavle Cent Hosp, Dept Oncol, Gavle, Sweden..
    Blomqvist, Carl
    Univ Orebro, Dept Oncol, Orebro, Sweden..
    Sund, Malin
    Umea Univ, Dept Surg & Perioperat Sci, Surg, S-90187 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, Gavle, Sweden.;Visby Hosp, Dept Oncol, Visby, Sweden..
    Inter-observer variation in delineating the coronary arteries as organs at risk2017In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 122, no 1, p. 72-78Article in journal (Refereed)
    Abstract [en]

    Purpose: To determine the inter-observer variation in delineating the coronary arteries as organs at risk (OAR) in breast cancer (BC) radiotherapy (RT) and how this variation affects the estimated coronary artery radiation dose.

    Method: Delineation of the left main and the left anterior descending coronary artery (LMCA and LAD), and the right coronary artery (RCA), by using the heart atlas by Feng et al., was performed by three radiation oncologists in 32 women who had received adjuvant RT for BC. Centres of the arteries were calculated and distances between artery centres were measured and the artery radiation doses were estimated. The intraclass correlation coefficient (ICC) was used to quantify the variability in doses.

    Results: Along the extent of RCA, the median distance between centres of arteries varied from 2 to 9 mm with similar patterns over pairs of oncologists. For the LMCA-LAD the median distance varied from 1 to 4 mm. The estimated maximum radiation doses showed an ICC variation from 0.82 to 0.97.

    Conclusion: The coronary arteries can be reliably identified and delineated as OARs in BC RT. The spatial variance is limited and the total variation in radiation dose is almost completely determined by the between patient variation.

  • 33. Zegers, Catharina M L
    et al.
    van Elmpt, Wouter
    Wierts, Roel
    Reymen, Bart
    Sharifi, Hoda
    Ollers, Michel C
    Hoebers, Frank
    Troost, Esther G C
    Wanders, Rinus
    van Baardwijk, Angela
    Brans, Boudewijn
    Eriksson, Jonas
    VU University Medical Center Amsterdam.
    Windhorst, Bert
    Mottaghy, Felix M
    De Ruysscher, Dirk
    Lambin, Philippe
    Hypoxia imaging with [(18)F]HX4 PET in NSCLC patients: Defining optimal imaging parameters.2013In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 109, no 1, p. 58-64Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: [(18)F]HX4 is a promising hypoxia PET-tracer. Uptake, spatio-temporal stability and optimal acquisition parameters for [(18)F]HX4 PET imaging were evaluated in non-small cell lung cancer (NSCLC) patients.

    MATERIALS AND METHODS: [(18)F]HX4 PET/CT images of 15 NSCLC patients were acquired 2h and 4h after injection (p.i.). Maximum standardized-uptake-value (SUVmax), tumor-to-blood-ratio (TBRmax), hypoxic fraction (HF) and contrast-to-noise-ratio (CNR) were determined for all lesions. To evaluate spatio-temporal stability, DICE-similarity and Pearson correlation coefficients were calculated. Optimal acquisition-duration was assessed by comparing 30, 20, 10 and 5min acquisitions.

    RESULTS: Considerable uptake (TBR >1.4) was observed in 18/25 target lesions. TBRmax increased significantly from 2h (1.6±0.3) to 4h p.i. (2.0±0.6). Uptake patterns at 2h and 4h p.i. showed a strong correlation (R=0.77±0.10) with a DICE similarity coefficient of 0.69±0.08 for the 30% highest uptake volume. Reducing acquisition-time resulted in significant changes in SUVmax and CNR. TBRmax and HF were only affected for scan-times of 5min.

    CONCLUSIONS: The majority of NSCLC lesions showed considerable [(18)F]HX4 uptake. The heterogeneous uptake pattern was stable between 2h and 4h p.i. [(18)F]HX4 PET imaging at 4h p.i. is superior to 2h p.i. to reach highest contrast. Acquisition time may be reduced to 10min without significant effects on TBRmax and HF.

  • 34.
    Åström, Lennart
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Grusell, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science. Uppsala University, The Svedberg Laboratory.
    Sandin, Fredrik
    Regional Cancer Center Uppsala-Örebro, Sweden.
    Turesson, Ingela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. King's College, London, UK.
    Two decades of high dose rate brachytherapy with external beam radiotherapy for prostate cancer2018In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, article id S0167-8140(17)32780-9Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: High-dose-rate brachytherapy (HDR-BT) has optimal prerequisites in radiotherapy of prostate cancer (PC) with a conformal dose distribution and high doses per fraction giving a biological dose escalation. We report the outcome after HDR-BT and external beam radiotherapy (EBRT) after 20 years of experience.

    MATERIAL AND METHODS: The study includes 623 patients, median age of 66 years, treated from 1995 to 2008 and a median follow up of 11 years (range 2-266 months). Androgen deprivation therapy was given to 429 patients (69%). The HDR-BT was given with two 10 Gy fractions and the EBRT with 2 Gy fractions to 50 Gy.

    RESULTS: The 10-year PC-specific survival was 100%, 92%, 91%, and 75% for low-, intermediate-, high- and very high-risk patients respectively, and the 10-year probability of PSA relapse was 0%, 21%, 33%, and 65% respectively. The 10-year actuarial prevalence for ≥grade 2 GU- and GI-toxicities were 28% and 12% respectively and for ≥grade 3, 4% and 1% respectively. Urethral stricture was the most frequent GU complication with a 10-year actuarial incidence of 10%. Treatment without dose constraints for the urethra conferred a higher incidence 18%, compared to 5% after 2003 (p < 0.001). Sixteen patients experienced grade 4 GU toxicity, of which 13 were treated before 2003. No grade 4 rectal toxicity was seen.

    CONCLUSION: The combination of EBRT and HDR-BT with adequate dose constraints to risk organs provides satisfactory long-term tumour control even in high-risk patients. GI toxicity stabilised but GU toxicity progressed during the 10-year follow up.

  • 35.
    Åström, Lennart
    et al.
    Department of Oncology, University of Gothenburg, Gothenburg, Sweden.
    Pedersen, Dorte
    Mercke, Claes
    Holmäng, Sten
    Johansson, Karl Axel
    Long-term outcome of high dose rate brachytherapy in radiotherapy of localised prostate cancer2005In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 74, no 2, p. 157-61Article in journal (Refereed)
    Abstract [en]

    Background and purpose: High dose rate brachytherapy (HDR-BT) in prostate cancer (PC) is receiving increasing interest. The steep dose gradient gives a possibility to escalate the dose to the prostate. If the a/b ratio is low for PC, hypofractionation will be of advantage. A retrospective analysis of outcome in patients (pts) consecutively treated with combined HDR-BT and conformal external beam radiotherapy (ERT) was performed. Material and methods: Data from 214 pts treated consecutively from 1988 to 2000 were analysed. The median age was 64 years (50–77). Median follow up was 4 years (12–165 months). Pre-irradiatory endocrine therapy was given to 150 pts (70%). The pts were divided into low-, intermediate- and high (80/87/47 pts) risk groups according to the occurrence of none, one, or more risk factors defined by T-classification, PSA and histopathology. ERT was given with 2 Gy fractions to 50 Gy. HDR-BT consisted of two 10 Gy fractions. Results: Overall 5-year biochemical no evidence of disease (bNED) was 82%, and for the low-, intermediate-, and high-risk group bNED was 92, 88 and 61%, respectively. PSA-relapse was found in 17, local recurrence in 3 and distant metastases in 13 pts. Five pts died of PC. No recurrences were observed after 5 years. Severe late complications were few. Urethral stricture (13 pts) was the most frequent. No severe rectal complications were seen. Conclusion: Dose escalation with HDR-BT is safe and effective in radiotherapy of localised PC.

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