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Dag Rune Olsen

Publications and source records attributed to Dag Rune Olsen.

16 recordsLinked to original sources
PubMed2006

Optimization of tumour control probability in hypoxic tumours by radiation dose redistribution: a modelling study.

Tumour hypoxia is a known cause of clinical resistance to radiation therapy. The purpose of this work was to model the effects on tumour control probability (TCP) of selectively boosting the dose to hypoxic regions in a tumour, while keeping the mean tumour dose constant. A tumour model with a continuous oxygen distribution, incorporating pO(2) histograms published for head and neck patients, was developed. Temporal and spatial variations in the oxygen distribution, non-uniform cell density and cell proliferation during treatment were included in the tumour modelling. Non-uniform dose prescriptions were made based on a segmentation of the tumours into four compartments. The main findings were: (1) Dose redistribution considerably improved TCP for all tumours. (2) The effect on TCP depended on the degree of reoxygenation during treatment, with a maximum relative increase in TCP for tumours with poor or no reoxygenation. (3) Acute hypoxia reduced TCP moderately, while underdosing chronic hypoxic cells gave large reductions in TCP. (4) Restricted dose redistribution still gave a substantial increase in TCP as compared to uniform dose boosts. In conclusion, redistributing dose according to tumour oxygenation status might increase TCP when the tumour response to radiotherapy is limited by chronic hypoxia. This could potentially improve treatment outcome in a subpopulation of patients who respond poorly to conventional radiotherapy.

Cell Hypoxia↗
PubMed2006

EPR dosimetry of radiotherapy photon beams in inhomogeneous media using alanine films.

In the current work, EPR (electron paramagnetic resonance) dosimetry using alanine films (134 microm thick) was utilized for dose measurements in inhomogeneous phantoms irradiated with radiotherapy photon beams. The main phantom material was PMMA, while either Styrofoam or aluminium was introduced as an inhomogeneity. The phantoms were irradiated to a maximum dose of about 30 Gy with 6 or 15 MV photons. The performance of the alanine film dosimeters was investigated and compared to results from ion chamber dosimetry, Monte Carlo simulations and radiotherapy treatment planning calculations. It was found that the alanine film dosimeters had a linear dose response above approximately 5 Gy, while a background signal obscured the response at lower dose levels. For doses between 5 and 60 Gy, the standard deviation of single alanine film dose estimates was about 2%. The alanine film dose estimates yielded results comparable to those from the Monte Carlo simulations and the ion chamber measurements, with absolute differences between estimates in the order of 1-15%. The treatment planning calculations exhibited limited applicability. The current work shows that alanine film dosimetry is a method suitable for estimating radiotherapeutical doses and for dose measurements in inhomogeneous media.

Alanine↗
PubMed2006

Dose optimisation in single plane interstitial brachytherapy.

BACKGROUND AND PURPOSE: Brachytherapy dose distributions can be optimised by modulation of source dwell times. In this study dose optimisation in single planar interstitial implants was evaluated in order to quantify the potential benefit in patients. MATERIAL AND METHODS: In 14 patients, treated for recurrent rectal and cervical cancer, flexible catheters were sutured intra-operatively to the tumour bed in areas with compromised surgical margin. Both non-optimised, geometrically and graphically optimised CT -based dose plans were made. The overdose index (OI), homogeneity index (HI), conformal index (COIN), minimum target dose, and high dose volumes were evaluated. The dependence of OI, HI, and COIN on target volume and implant regularity was evaluated. In addition, 12 theoretical implant configurations were analyzed. RESULTS: Geometrical and graphical optimisation improved the dose plans significantly with graphical optimisation being superior. Graphically optimised dose plans showed a significant decrease of 18%+/-9% in high dose volume (p<0.001). HI, COIN, and OI were significantly improved from 0.50+/-0.05 to 0.60+/-0.05, from 0.65+/-0.04 to 0.71+/-0.04, and from 0.19+/-0.03 to 0.15+/-0.03, respectively (p<0.001 for all). Moreover, minimum target dose increased significantly from 71%+/-5% to 80%+/-5% (p<0.001). The improvement in OI and HI obtained by optimisation depended on the regularity of the implant, such that the benefit of optimisation was larger for irregular implants. OI and HI correlated strongly with target volume limiting the usability of these parameters for comparison of dose plans between patients. CONCLUSIONS: Dwell time optimisation significantly improved the dose distribution regarding homogeneity, conformity, minimum target dose, and size of high dose volumes. Graphical optimisation is fast, reproducible and superior to geometric optimisation.

Brachytherapy↗
PubMed2006

Adapting radiotherapy to hypoxic tumours.

In the current work, the concepts of biologically adapted radiotherapy of hypoxic tumours in a framework encompassing functional tumour imaging, tumour control predictions, inverse treatment planning and intensity modulated radiotherapy (IMRT) were presented. Dynamic contrast enhanced magnetic resonance imaging (DCEMRI) of a spontaneous sarcoma in the nasal region of a dog was employed. The tracer concentration in the tumour was assumed related to the oxygen tension and compared to Eppendorf histograph measurements. Based on the pO(2)-related images derived from the MR analysis, the tumour was divided into four compartments by a segmentation procedure. DICOM structure sets for IMRT planning could be derived thereof. In order to display the possible advantages of non-uniform tumour doses, dose redistribution among the four tumour compartments was introduced. The dose redistribution was constrained by keeping the average dose to the tumour equal to a conventional target dose. The compartmental doses yielding optimum tumour control probability (TCP) were used as input in an inverse planning system, where the planning basis was the pO(2)-related tumour images from the MR analysis. Uniform (conventional) and non-uniform IMRT plans were scored both physically and biologically. The consequences of random and systematic errors in the compartmental images were evaluated. The normalized frequency distributions of the tracer concentration and the pO(2) Eppendorf measurements were not significantly different. 28% of the tumour had, according to the MR analysis, pO(2) values of less than 5 mm Hg. The optimum TCP following a non-uniform dose prescription was about four times higher than that following a uniform dose prescription. The non-uniform IMRT dose distribution resulting from the inverse planning gave a three times higher TCP than that of the uniform distribution. The TCP and the dose-based plan quality depended on IMRT parameters defined in the inverse planning procedure (fields and step-and-shoot intensity levels). Simulated random and systematic errors in the pO(2)-related images reduced the TCP for the non-uniform dose prescription. In conclusion, improved tumour control of hypoxic tumours by dose redistribution may be expected following hypoxia imaging, tumour control predictions, inverse treatment planning and IMRT.

Animals↗
PubMed2006

Contralateral breast doses following radiotherapy of the breast and regional lymph nodes: Measurements and treatment planning calculations.

PURPOSE: To measure the dose distribution in the contralateral breast (CB) following radiotherapy of the breast and regional lymph nodes by a 4-field technique, and to examine whether related treatment planning calculations of CB doses reproduce the measurements. MATERIALS AND METHODS: CB doses were measured by thermoluminescence dosimetry on the surface of 8 patients and in an anthropomorphic phantom. Dose calculations at corresponding points of interest were performed by the treatment planning system Helax-TMS 6.1 using the pencil beam or the collapsed cone algorithm. RESULTS: The measured CB doses were typically between 1% and 15% of the prescribed dose. The dose decreased significantly both in the medial-lateral and cranial-caudal direction. The average ratio of the measured to the calculated CB dose was about 0.7 and 0.9 for the pencil beam and the collapsed cone algorithm, respectively. One of the treatment fields aimed at the regional lymph nodes and some of the chest wall gave the highest contribution to the CB dose. CONCLUSIONS: The dose distribution in the CB following locoregional radiotherapy of the breast and regional lymph nodes is quite inhomogeneous. The collapsed cone algorithm may be used for estimating doses to the CB. Some concern is raised regarding the current field arrangement and the consequences for the CB dose.

Algorithms↗
PubMed2006

Initial evaluation of (227)Th-p-benzyl-DOTA-rituximab for low-dose rate alpha-particle radioimmunotherapy.

Radioimmunotherapy has proven clinically effective in patients with non-Hodgkin's lymphoma. Radioimmunotherapy trials have so far been performed with beta-emitting isotopes. In contrast to beta-emitters, the shorter range and high linear energy transfer (LET) of alpha particles allow for more efficient and selective killing of individually targeted tumor cells. However, there are several obstacles to the use of alpha-particle immunotherapy, including problems with chelation chemistry and nontarget tissue toxicity. The alpha-emitting radioimmunoconjugate (227)Th-DOTA-p-benzyl-rituximab is a new potential anti-lymphoma agent that might overcome some of these difficulties. The present study explores the immunoreactivity, in vivo stability and biodistribution, as well as the effect on in vitro cell growth, of this novel radioimmunoconjugate. To evaluate in vivo stability, uptake in balb/c mice of the alpha-particle-emitting nuclide (227)Th alone, the chelated form, (227)Th-p-nitrobenzyl-DOTA and the radioimmunoconjugate (227)Th-DOTA-p-benzyl-rituximab was compared in a range of organs at increasing time points after injection. The immunoreactive fraction of (227)Th-DOTA-p-benzyl-rituximab was 56-65%. During the 28 days after injection of radioimmunoconjugate only, very modest amounts of the (227)Th had detached from DOTA-p-benzyl-rituximab, indicating a relevant stability in vivo. The half-life of (227)Th-DOTA-p-benzyl-rituximab in blood was 7.4 days. Incubation of lymphoma cells with (227)Th-DOTA-p-benzyl-rituximab resulted in a significant antigen-dependent inhibition of cell growth. The data presented here warrant further studies of (227)Th-DOTA-p-benzyl-rituximab.

Alpha Particles↗
PubMed2005

Respiratory motion prediction by using the adaptive neuro fuzzy inference system (ANFIS).

The quality of radiation therapy delivered for treating cancer patients is related to set-up errors and organ motion. Due to the margins needed to ensure adequate target coverage, many breast cancer patients have been shown to develop late side effects such as pneumonitis and cardiac damage. Breathing-adapted radiation therapy offers the potential for precise radiation dose delivery to a moving target and thereby reduces the side effects substantially. However, the basic requirement for breathing-adapted radiation therapy is to track and predict the target as precisely as possible. Recent studies have addressed the problem of organ motion prediction by using different methods including artificial neural network and model based approaches. In this study, we propose to use a hybrid intelligent system called ANFIS (the adaptive neuro fuzzy inference system) for predicting respiratory motion in breast cancer patients. In ANFIS, we combine both the learning capabilities of a neural network and reasoning capabilities of fuzzy logic in order to give enhanced prediction capabilities, as compared to using a single methodology alone. After training ANFIS and checking for prediction accuracy on 11 breast cancer patients, it was found that the RMSE (root-mean-square error) can be reduced to sub-millimetre accuracy over a period of 20 s provided the patient is assisted with coaching. The average RMSE for the un-coached patients was 35% of the respiratory amplitude and for the coached patients 6% of the respiratory amplitude.

Algorithms↗
PubMed2004

Electron paramagnetic resonance (EPR) dosimetry using lithium formate in radiotherapy: comparison with thermoluminescence (TL) dosimetry using lithium fluoride rods.

Solid-state radiation dosimetry by electron paramagnetic resonance (EPR) spectroscopy and thermoluminescence (TL) was utilized for the determination of absorbed doses in the range of 0.5-2.5 Gy. The dosimeter materials used were lithium formate and lithium fluoride (TLD-100 rods) for EPR dosimetry and TL dosimetry, respectively. 60Co gamma-rays and 4, 6, 10 and 15 MV x-rays were employed. The main objectives were to compare the variation in dosimeter reading of the respective dosimetry systems and to determine the photon energy dependence of the two dosimeter materials. The EPR dosimeter sensitivity was constant over the dose range in question, while the TL sensitivity increased by more than 5% from 0.5 to 2.5 Gy, thus displaying a supralinear dose response. The average relative standard deviation in the dosimeter reading per dose was 3.0% and 1.2% for the EPR and TL procedures, respectively. For EPR dosimeters, the relative standard deviation declined significantly from 4.3% to 1.1% over the dose range in question. The dose-to-water energy response for the megavoltage x-ray beams relative to 60Co gamma-rays was in the range of 0.990-0.979 and 0.984-0.962 for lithium formate and lithium fluoride, respectively. The results show that EPR dosimetry with lithium formate provides dose estimates with a precision comparable to that of TL dosimetry (using lithium fluoride) for doses above 2 Gy, and that lithium formate is slightly less dependent on megavoltage photon beam energy than lithium fluoride.

Electron Spin Resonance Spectroscopy↗
PubMed2003

Definitive radiotherapy of prostate cancer: the possible role of staging lymphadenectomy.

PURPOSE: To evaluate the postradiotherapy 5-year cancer-specific (CSS), clinical progression-free (cPFS), and overall (OS) survival rates in patients with pN0 M0 prostate cancer (PC). METHODS: Between 1989 and 1996, 203 consecutive pN0 M0 PC patients (T1-2, 66; T3-4, 137) received conformal prostatic four-field radiotherapy (median target dose 66 Gy). Any hormone manipulation was delayed until clinical progression (growth of the primary tumor or development of distant metastases). RESULTS: After a median observation time of 87 months (range 11-156), 99 patients had relapsed clinically and 70 patients were dead, 37 of them as a result of prostate cancer. Five-year CSS, cPFS, and OS rates were, respectively, 90% (95% CI 86-94%), 64% (95% CI 57-71%), and 82% (95% CI 77-87%), with no difference of OS compared with age-matched males from the general population. Gleason score (< or =7A vs. > or =7B) and the T category predicted cPFS, whereas CSS was associated with Gleason score only. Preradiotherapy PSA failed to predict survival. Patients with T1-2 Gleason score < or =7A had a 97% 5-year CCS, as compared with 89% for all other patients. A median of eight lymph nodes (range 0-29) were described in the specimens from pelvic lymphadenectomy (LA). CONCLUSION: Despite still preliminary observations, our 5-year results challenge the use of combined hormone radiotherapy in patients who are proven to be pN0 by preradiotherapy LA; in particular, in patients with T1-2/Gleason score < or =7A, whereas the survival in all other patients with pN0 M0 prostate cancer may be improved by adjuvant androgen deprivation.

Aged↗
PubMed2003

Radiation therapy induced changes in male sex hormone levels in rectal cancer patients.

BACKGROUND AND PURPOSE: To determine the effect of curative radiation therapy (46-50 Gy) on the sex hormone levels in male rectal cancer patients. MATERIALS AND METHODS: Twenty-five male rectal cancer patients (mean age 65 years), receiving pelvic radiation therapy (2 Gyx23-25 fractions in 5 weeks) were included. Serum testosterone, FSH and LH were determined before start of treatment, at the 10th and 25th fractions, and 4-6 weeks after completed radiotherapy. The testicular dose was determined by thermoluminescent dosimetry. RESULTS: Five weeks of radiation therapy (46-50 Gy) resulted in a 100% increase in serum FSH, a 70% increase in LH, and a 25% reduction in testosterone levels. After treatment, 35% of the patients had serum testosterone levels below lower limit of reference. The mean radiation dose to the testicles was 8.4 Gy. A reduction in testosterone values was observed already after a mean dose of 3.3 Gy (10th fraction). CONCLUSION: Radiation therapy (46-50 Gy) for rectal cancer resulted in a significant increase in serum FSH and LH and a significant decrease in testosterone levels, indicating that sex hormone production is sensitive to radiation exposure in patients with a mean age of 65 years.

Aged↗
PubMed2003

Brachytherapy for prostate cancer: a systematic review of clinical and cost effectiveness.

OBJECTIVES: Brachytherapy is emerging as a new treatment option for prostate cancer, and is increasingly being used in Europe and North America. METHODS: A systematic review of studies that compared clinical or cost effectiveness of prostate brachytherapy with radical prostatectomy or external beam radiation for patients with localised prostate cancer. RESULTS: No randomised controlled trials were identified, but five observational studies with comparable patient groups were included in the review. There were no valid data on overall or disease-free survival. There was no difference in disease-free survival based on PSA as a surrogate measure, or in rates of complications. No cost effectiveness studies were found. Based on Norwegian data, the one-year cost of the three treatment options seem fairly similar, while long term cost data are lacking due to lack of data on long term clinical outcome. CONCLUSION: The evidence on the clinical effectiveness of therapies for localised prostate cancer is scarce, but the outcome appears to be comparable for radical prostatectomy, external beam radiotherapy and brachytherapy.

Aged↗
PubMed2003

Information technology in action: the example of Norway.

In Europe, Norway has played since the 1990 a pioneering role in applying telemedicine in healthcare services. 4.5 millions occupy a country nearly as large as the former West Germany with a coast line as long as the equator and stretching 2500 km from the south to the north. The most northern counties are very sparsely populated. Therefore the government decided to build a national research centre for telemedicine at the regional hospital of Tromsø north of the polar circle with the aim of exploring the new telemedicine techniques in the different branches of medicine. Later political support was based on the wish to increase quality and safety of diagnostic and therapeutic procedures and of saving costs.

Medical Informatics Applications↗
PubMed2002

[Brachytherapy in prostatic cancer].

BACKGROUND: Brachytherapy is increasingly used in the treatment of early prostate cancer, but has not been implemented as a treatment option in Norway. Recent advances in imaging techniques and the radiation technology itself has facilitated improvements in and better standardisation of brachytherapy. MATERIAL AND METHODS: An group of expert assisted the Norwegian Centre for Health Technology Assessment (SMM) in a systematic review of the evidence on the clinical effectiveness of prostate brachytherapy. The literature was identified by a defined search strategy, and assessed for relevance and validity. Only controlled or comparative studies were included in the review. RESULTS: There were no randomized controlled trials or large prospective studies. Many of the relevant studies were of poor validity. None of the included studies had sufficient follow-up for overall or disease free survival. There were no differences between brachytherapy, external beam therapy or radical prostatectomy in disease free survival (PSA measures) or in rates of complications. INTERPRETATION: There is a lack of valid data from large prospective studies on the clinical effectiveness of brachytherapy. On the other hand, the clinical effectiveness of radical prostatectomy and external beam radiotherapy is also poorly documented. Results from one large randomized controlled trial comparing radical prostatectomy with brachytherapy in the USA will not be available within the next ten years.

Brachytherapy↗
PubMed2002

Preoperative irradiation and surgery for recurrent rectal cancer. Will intraoperative radiotherapy (IORT) be of additional benefit? A prospective study.

BACKGROUND: The therapeutic gain of surgery for recurrent rectal cancer is not clear, particularly with regard to the addition of intraoperative radiotherapy (IORT). METHODS: Patients (107) with isolated pelvic recurrence of rectal cancer received preoperative external radiotherapy of 46-50 in 2 Gy fractions. At surgery 59 patients had IORT 12-18 Gy. Survival and local recurrence was analysed with regard to surgical resection stages and IORT. RESULTS: Patients (44) had R0- and 39 R1-resections, 24 R2-resections or exploratory laparotomy. IORT was given most often after R1-resections, least in R0-patients. Estimated 5-year survival was overall around 30%, around 60% in the R0-, around 25% for R1- and 0% in R2-patients. Local recurrence was around 30% in the R0- and around 65% in R1-stage patients. R0-/R1-stage patients survived statistically significantly longer than the R2-group otherwise there was no statistical significant difference between IORT and non-IORT groups in any R-stages regarding overall survival or local recurrence. CONCLUSIONS: Macroscopic removal of the recurrence improves survival. Whether R0- is better than R1-resections is not clear. The effect of IORT is not a major one. IORT need be evaluated in randomised controlled trials.

Humans↗
PubMed2002

Cell cycle inhibitors and outcome after radiotherapy in bladder cancer patients.

The aim of this study was to correlate the expression of cell cycle inhibitors with outcome of patients with muscle-invasive bladder cancer treated with preoperative radiotherapy (46 Gy/4-5 weeks or 20 Gy/1 week) and cystectomy. Patients with pT3b (n = 42) or pT0 (n = 17) were included in the study. Expression of p16INK4a and p27KIP1 was assessed immunohistochemically in pre-radiotherapy biopsies and cystectomy specimens. Previously reported results of p21CP1 expression were also included. No difference in pretreatment protein expression was found between patients with pT0 and pT3b. Expression of p21CIP1 and p27KIP1 was lower in cystectomy specimens than in pretreatment biopsies. None of the proteins showed significant impact on survival when analysed separately. However, patients with tumours showing > 50% expression of p16INK4a, p21CIP1, or p27KIP1 displayed poorer cancer-specific survival rates compared with the remaining patients (p = 0.025). This effect was more pronounced in patients receiving 46 Gy than in those receiving 20 Gy. In conclusion, low expression of cell cycle inhibitors is related to favourable survival after pre-cystectomy radiotherapy.

Carcinoma, Transitional Cell↗