Biomedical subjects

Björn Zackrisson

Publications and source records attributed to Björn Zackrisson.

At least 19 recordsLinked to original sources

PubMed2006

Recombinant erythropoietin beta enhances growth of xenografted human squamous cell carcinoma of the head and neck after surgical trauma.

CONCLUSION: Treatment of anaemia with recombinant human erythropoietin beta (rHuEpo) in patients with squamous cell carcinoma of the head and neck (HNSCC) undergoing curative radiotherapy does not improve cancer control. In fact, incompletely resected patients with HNSCC receiving radiation in combination with rHuEpo showed poorer loco-regional progression-free survival than patients receiving radiation in combination with placebo. It could be hypothesized that the effects of rHuEpo on tumour cell growth might only be manifested in vivo and after cell trauma, and that treating anaemia with rHuEpo might contribute to poor outcome after incomplete surgical resection. OBJECTIVE: The aim of the present study was to examine the effect of rHuEpo alone and in combination with surgical trauma on the growth of human squamous cell carcinoma in vivo, xenografted onto nude mice. MATERIALS AND METHODS: The surgical trauma was inflicted through subcutaneous transection of the tumour with a needle. Immunohistochemical staining verified expression of the EPO receptor in tumour cells. RESULTS: rHuEpo alone had no effect on the growth of xenografted HNSCC. However, a significant increase in tumour growth was observed after surgical trauma in combination with rHuEpo compared with surgery alone (p = 0.0008).

Animals↗

PubMed2006

"Distributed proton radiation therapy"--a new concept for advanced competence support.

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

Ambulatory Care Facilities↗

PubMed2005

The potential of proton beam radiation therapy in head and neck cancer.

A group of Swedish oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy. The estimations have been based on current statistics of tumour incidence, number of patients potentially eligible for radiation treatment, scientific support from clinical trials and model dose planning studies and knowledge of the dose-response relations of different tumours and normal tissues. In head and neck cancer, including thyroid cancer, it is assessed that at least 300 patients annually will gain sufficiently from proton beam therapy, both to improve tumour control and to decrease toxicity to compensate for the increased treatment costs using protons.

Cost-Benefit Analysis↗

PubMed2005

Number of patients potentially eligible for proton therapy.

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

Dose-Response Relationship, Radiation↗

PubMed2004

Intensity modulated radiation therapy with electrons using algorithm based energy/range selection methods.

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

Algorithms↗

PubMed2004

Gelatinases A and B (MMP-2 and MMP-9) in endometrial cancer-MMP-9 correlates to the grade and the stage.

OBJECTIVE: Matrix metalloproteinases (MMPs) have been linked to aggressive behavior in several malignancies. Gelatinases (MMP-2 and MMP-9) in particular are prognostic factors in many adeno- and epithelial cancers. However, no conclusive data exist concerning the role of gelatinases in endometrial cancer. METHODS: Eighty-eight patients with endometrial cancer, treated between 1988 and 1993 in Umeå University Hospital, were included. MMP-2 and MMP-9 proteins were analyzed immunohistochemically from paraffin-embedded tissues by using specific monoclonal antibodies. The staining results were compared to the clinical data. RESULTS: Fifty-two percent of the cases were positive for MMP-9 and 72% for MMP-2. The overexpression of the proteins of either MMP-2 or MMP-9 was associated with poor survival. The predictive value of MMP-2 expression was most distinct in stage I cancers. An association was found between the positivity of MMP-2 and MMP-9. Only 3% of the cases were highly positive for both gelatinases and 18% of the cases were negative for both MMPs. Both gelatinases correlated to the histological grade. MMP-9 also correlated to the clinical stage of the disease, whereas MMP-2 did not. There was no apparent association with either depth of invasion, menopausal status, or the age of the patient. CONCLUSION: MMP-2 and MMP-9 could serve as markers for the clinical behavior of endometrial cancer. They may further be linked to a tendency to cancer relapse. Thus, these gelatinases may turn out to be potentially useful in decision making about the need for an adjuvant treatment.

Endometrial Neoplasms↗

PubMed2004

Can photon IMRT be improved by combination with mixed electron and photon techniques?

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

Combined Modality Therapy↗

PubMed2003

Evolution of free, complexed, and total serum prostate-specific antigen and their ratios during 1 year of follow-up of men with febrile urinary tract infection.

OBJECTIVES: To determine the serum values of free, complexed, and total prostate-specific antigen (PSA) and their ratios in men with febrile urinary tract infection (UTI) during 1 year of follow-up. METHODS: A total of 54 men were prospectively enrolled in the study, and serum samples were obtained at the acute stage of the UTI and after 1, 3, 6, and 12 months. RESULTS: Most men had a rise (median 3.1, 7.2, and 14.1 ng/mL, respectively) in free PSA (fPSA), complexed PSA (cPSA), and total PSA (tPSA) during the acute phase of the UTI. After 1 month, fPSA rapidly decreased to levels that were maintained during the rest of the follow-up period, and cPSA and tPSA declined more slowly. At 1, 3, and 6 months after the infection the fPSA/tPSA and fPSA/cPSA ratios were abnormal in one half to two thirds of the men (median ratio 11%, 15%, and 16% and 17%, 24%, and 24%, respectively), comparable to findings in patients with prostate cancer. CONCLUSIONS: These results confirmed that the prostate is involved in men with febrile UTI. The low fPSA/tPSA and fPSA/cPSA ratios in combination with sustained elevations of cPSA and tPSA for up to 6 months after UTI could be falsely interpreted as a sign of prostate cancer. The prolonged elevation of cPSA indicates a long-lasting inflammation of the nonadenomatous parts of the prostate.

Adolescent↗

PubMed2003

The effect of fraction time in intensity modulated radiotherapy: theoretical and experimental evaluation of an optimisation problem.

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

Animals↗

PubMed2003

Follow-up of men with elevated prostate-specific antigen and one set of benign biopsies at prostate cancer screening.

OBJECTIVE: To study the follow-up of men with elevated prostate-specific antigen (PSA) (>3 ng/ml) after one benign set of sextant biopsies. From the Göteborg branch of the European Randomised Study of Screening for Prostate Cancer (ERSPC). METHOD: 456 men with one set of benign sextant biopsies were followed every second year for 4 years with PSA determinations. In cases of elevated PSA, transrectal ultrasound (TRUS) guided sextant biopsies were suggested. Digital rectal examination (DRE), prostate volume, PSA, PSA density (PSAD) and the ratio between free and total PSA (PSA F/T) were recorded. RESULTS: Complete data were available for 322 men. 3 groups were identified. In 84/322 (26%) men cancer was found ("cancer" group). 182/322 (56%) had benign biopsies ("benign" group) and 56/322 (17%) had normalised PSA ("normalised PSA" group). Median prostate volumes were 36, 46, and 33 cc respectively in the three groups. DRE and/or TRUS were abnormal in only 30% of the men in all groups. Cancer was not found in any prostate >70 cc volume. In prostates of <20 cc either cancer was found or PSA was normalised. The "normalised PSA" group had initial PSA, PSAD and PSA F/T similar to cancer, normalising during follow-up. CONCLUSIONS: Patients with one negative sextant biopsy still have a high likelihood of cancer, especially men with persistently elevated PSA and small prostates (<20 cc) while the majority of men with large prostates (>70 cc) have PSA elevation due to benign prostate hyperplasia (BPH) and not to cancer.

Aged↗

PubMed2003

Radiation therapy dose delivery.

In an investigation by the Swedish Cancer Society, the present status critical issues and future aspects and potentials in each of nine major areas of radiation therapy research were described by an expert group. The report presented here deals with radiation therapy dose delivery. dose distributions, beam shaping and intensity modulation.

Humans↗

PubMed2003

Biological response to radiation therapy.

In an investigation by the Swedish Cancer Society, the present status, critical issues and future aspects and potentials were described by an expert group for each of nine major areas of radiation therapy research. This article deals with biological response to radiation. Separate sections deal with molecular responses to radiation, the stem cell and clonogenic cell concepts and the importance of cell proliferation, cell and tissue responses to doses above and below 1 Gy, respectively, the potential role of intercellular signalling pathways, the so-called bystander effect and radiation biology-based therapy planning and treatment optimization.

Bystander Effect↗

PubMed2003

Research and development of radiation therapy in clinical routines.

In an investigation conducted by the Swedish Cancer Society, the present status, critical issues and future aspects and potentials were described by an expert group for each of nine major areas of radiation therapy research. In this report, research and development in radiation therapy clinical routines is described. The terms research, development, quality assurance, quality control and clinical routines in radiation therapy are also defined.

Clinical Competence↗

PubMed2003

A systematic overview of radiation therapy effects in head and neck cancer.

UNLABELLED: A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for head and neck cancer is based on data from 39 randomized trials and 1 meta-analysis. In total, 40 scientific articles are included, involving 20893 patients. The results were compared with those of a similar overview from 1996 including 79 174 patients. The conclusions reached can be summarized as follows: General, non-nasopharynx. Substantial evidence indicates that the tumour effect of radiotherapy can be increased by the concomitant administration of chemotherapeutic agents, particularly cisplatin and 5-fluorouracil. There is moderate evidence of a survival benefit of radiation combined with concomitant chemotherapy compared to radiation alone. However, the results are equivocal. There is substantial evidence in published studies for an increased frequency of severe acute side effects as a result of concomitant chemotherapy and radiotherapy. There are very few studies that allow any estimates of the risk for serious late side effects. There is a weak indication of an increased risk for serious fibrosis. COMMENT: The general quality of studies and the lack of information on serious side effects indicate a need for large, well-designed clinical studies with a reasonable follow-up. Larynx preservation studies. There is strong evidence that larynx preservation is possible in 50% of the patients surviving for 5 years with hypopharyngeal cancers when treated with neoadjuvant chemotherapy and radical radiotherapy There is a non-significant trend for the overall survival being lower in non-surgically treated patients than in those treated with primary surgery and postoperative radiotherapy Nasopharynx. There is moderate evidence that patients with nasopharyngeal carcinomas of the endemic type benefit from therapy with a combination of chemotherapy and radical radiotherapy. However, the results from the reported studies are equivocal. There is some indication that the acute side effects of radiation are more severe in the concomitant setting than in the neoadjuvant. COMMENT: There are no data on serious late toxicity. Dose, fractionation schedules. There is some evidence that certain schedules of altered fractionation improve tumour control without increasing severe late side effects. There is some evidence that nervous tissues are more susceptible to damage by altered fractionation. Solid data shows that altered fractionation increases acute side effects. There is moderate evidence that accelerated hyperfractionation may reduce the frequency of serious late side effects while retaining a similar tumour effect as conventional radiotherapy Hypoxic cell sensitizers. Most reported trials reject the usefulness of nitroimidazole derivatives for sensitization of hypoxic tumour cells. There is some evidence that patients with tumours in the pharynx and larynx may benefit from sensitization by nimorazole. Prophylactic treatment of side effects. There is weak evidence that local antibiotics have a clinically significant effect in preventing acute radiotherapy side effects. There is insufficient evidence that radioprotective agents offer clinically significant protection of parotid glands (one study in two publications). There is insufficient evidence that radioprotective agents do not spare tumour tissue. Since the previous report no randomized studies comparing the effectiveness of external beam radiotherapy and brachytherapy have been performed. Both methods are well established and have independently proved to be effective in the treatment of certain head and neck cancers. No conclusion can be drawn regarding their relative effectiveness. Since the previous report no data to guide the use of intraoperative radiotherapy have been identified.

Adult↗

PubMed2002

Multileaf collimation of electrons--clinical effects on electron energy modulation and mixed beam therapy depending on treatment head design.

The aim of this study was to explore the possibilities of using multileaf-collimated electron beams for advanced radiation therapy with conventional scattering foil flattened beams. Monte Carlo simulations were performed with the aim to improve electron beam characteristics and enable isocentric multileaf collimation. The scattering foil positions, monitor chamber thickness, the MLC location and the amount of He in the treatment head were optimized for three common commercial accelerators. The performance of the three optimized treatment head designs was compared for different SSDs in air, at treatment depth in water and for some clinical cases. The effects of electron/photon beam matching including generalized random and static errors using Gaussian one-dimensional (1 D) error distributions, and also electron energy modulation, were studied at treatment depth in water. The modification of the treatment heads improved the electron beam characteristics and enabled the use of multileaf collimation in isocentric delivery of both electron and photon beams in a mixed beam IMRT procedure.

Air↗

PubMed2002

Comparison between a conventional treatment energy and 50 MV photons for the treatment of lung tumours.

Radiation therapy in the thoracic region is difficult due to the presence of many dose-limiting structures and the large density differences that affect the dose distribution. Conventional irradiation techniques use low-energy photon beams to avoid build-up effects superficially in the tumour and increased lateral scattering of the beams. For deep-seated tumours higher beam energies could have lung-sparing properties that would enable dose escalation. A comparison was made for a conventional low photon energy (6 MV) and 50 MV photons for the treatment of a lung tumour. A representative patient geometry was selected, consisting of a small tumour semi-enclosed in lung tissue. Treatment plans were designed using a commercial 3D-pencil beam treatment planning system. The treatment beams designed in the TPS were simulated with the Monte Carlo code EGS4/BEAM and the dose distribution in the phantom created from the patients CT-data was calculated using MCDOSE with identical beam geometry for both energies. The intrinsic difference between the two photon energies implies a sparing effect of lung that can be utilized for dose escalation. For a treatment with two beams the mean total dose to the tumour could be increased by 5.3% for 50 MV, corresponding to 3.2 Gy for a prescription dose of 60 Gy, with the same complication probability for the treated lung as for 6 MV. In conclusion, high-energy beams have qualities that can be taken advantage of for irradiation of lung tumours. Optimum solutions would probably require the use of both high- and low-energy beams.

Humans↗

PubMed2002

Sensitizing and protective substances in radiation therapy and predictive assays.

In an investigation by the Swedish Cancer Society, an expert group described the present status, critical issues and future aspects and potentials for each of nine major areas of radiation therapy research. The present report deals with the use of sensitizing and protective substances in radiation therapy and predictive assays on normal tissues and tumour response.

Cell Hypoxia↗

PubMed2002

Swedish Cancer Society radiation therapy research investigation.

In an investigation by the Swedish Cancer Society, the present status, critical issues and future aspects and prospects were described by an expert group for each of nine major areas of radiation research. A summary of the investigation is presented in this report. A more extensive summary (in Swedish) can be found at www.Cancerfonden.se. It is concluded that radiation therapy plays an increasingly important role in curative and palliative tumour treatment and presents a considerable challenge to research. Several suggestions are made that could improve the possibilities for high-quality radiation therapy research in Sweden.

Humans↗