| 51. |
- Bäck, Sven
(författare)
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Implementation of MRI gel dosimetry in radiation therapy
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Gel dosimetry was used together with magnetic resonance imaging (MRI) to measure three-dimensional absorbed dose distributions in radiation therapy. Two different dosimeters were studied: ferrous- and monomer gel, based on the principles of radiation-induced oxidation and polymerisation, respectively. Single clinical electron and photon beams were evaluated and gel dose distributions were mainly within 2% of conventional detector results. The ferrous-gel was also used for clinical proton beams. A decrease in signal per absorbed dose was found close to the end of the range of the protons (15-20%). This effect was explained as a linear energy transfer dependence, further supported with Monte Carlo simulations. A method for analysing and comparing data from treatment planning system (TPS) and gel measurements was developed. The method enables a new pixel by pixel evaluation, isodose comparison and dose volume histogram verification. Two standard clinical radiation therapy procedures were examined using the developed TPS verification method. The treatment regimes included several beams of different radiation qualities. The TPS calculated data were in very good agreement with the dose distribution measured by the ferrous-gel. However, in a beam abutment region, larger dose difference was found. Beam adjustment errors and a minor TPS underestimation of the lateral scatter contribution outside the primary electron beam may explain the discrepancy. The overall uncertainty in the ferrous-gel dose determination was considerably reduced using an optimised MRI acquisition protocol and a new MRI scanner. The relative dose uncertainty was found to be better than 3.3% for all dose levels (95% confidence level). Using the method developed for comparing measured gel data with calculated treatment plans, the gel dosimetry method was proven to be a useful tool for radiation treatment planning verification.
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| 52. |
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| 53. |
- Johansson, Mikael, et al.
(författare)
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Tumor blood flow and the cytotoxic effects of estramustine and its constituents in a rat glioma model
- 1997
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Ingår i: Neurosurgery. - : Oxford University Press. - 0148-396X .- 1524-4040. ; 41:1, s. 237-244
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Estramustine (EaM) is a conjugate of nor-nitrogen mustard (NNM) and 17 beta-estradiol (E2) that has cytotoxic and radiosensitizing effects on experimental malignant glioma. Its mechanism of action is only partly understood. To further investigate the mechanism in vivo, the effects on tumor blood flow (TBF) and tumor growth were analyzed.METHODS: TBF was measured by radioactive microspheres, and tumor growth was measured by weight. Apoptosis was evaluated by in situ end labeling and gel electrophoresis. The effects of the constituents NNM and E2 were also evaluated.RESULTS: EaM increased TBF to 153.8 ml/100 g/min after 3 days and to 153.9 ml/100 g/min after 10 days of treatment, compared with 94.0 ml/100 g/min in untreated controls. Cerebral blood flow did not change after EaM treatment. NNM increased TBF but also showed a tendency to increase cerebral blood flow. E2 increased TBF, whereas cerebral blood flow was unchanged. EaM resulted in a rapid reduction in tumor weight from 230 mg in untreated animals to 146 mg after 3 days of treatment. EaM induced an early transient fragmentation of deoxyribonucleic acid in glioma but not in the normal brain. Neither NNM nor E2 affected tumor weight.CONCLUSION: EaM increases TBF in the BT4C rat glioma model with a concomitant rapid antitumoral effect. The increase in TBF could partially be induced by an estrogen-like action of EaM, but the rapid cytotoxic effect of the drug is obviously attributed to the intact EaM compound. This cytotoxic effect might be attributable to the induction of programmed cell death.
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| 54. |
- Elfving, Peter
(författare)
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Cytogenetic studies of normal kidney tissue and renal cell carcinoma
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the present thesis normal kidney tissue and renal cell carcinoma (RCC) were studied by cytogenetic and fluorescence in situ hybridization (FISH) methods to investigate chromosomal aberrations. In the first study, 4 samples of nonneoplastic kidney tissue were cultured for cytogenetic analysis and trisomy 7 was found in all cases in 3-15% of the cells. In the second study, cytogenetic analysis of 30 RCC showed that +7 was rarely present together with clonal structural abnormalities, in particular 3p changes, making it highly unlikely that trisomy 7 represents a primary change in RCC. In the third study, nonneoplastic kidney tissue was cultured for 4-46 days and the frequency of trisomy 7 showed no consistent variation during the culturing period studied. In the fourth study, FISH of interphase nuclei was performed in uncultured nonneoplastic kidney tissues and showed that the frequency of +7 varied between 1.0-9.0% of the cells. Combination of FISH with immunostaining with CD3 for T-lymphocytes and cytokeratins for epithelial cells showed that, in all samples, the cells with +7 found in nonneoplastic kidney tissue were epithelial in 20-75% and T-lymphocytes in only 0-5%. Among freshly isolated renal cells, in the fifth study, trisomy 7 was observed mainly in proximal tubular cells positive for brush-border antigen, and, to a lesser extent, in distal tubular cells positive for Tamm-Horsfall glycoprotein. The frequency of trisomy 7 in lymphocytes expressing CD3 or CD22 isolated from nonneoplastic and tumor tissues was substantially lower than in the epithelial cells and was not increased compared with the frequency in control lymphocytes from peripheral blood. These results thus demonstrate that the nonneoplastic kidney cells with trisomy 7 are mainly of epithelial origin, preferentially of the proximal tubule. In the final study, 50 consecutive patients with RCC were followed for a median of 4.2 years. There was a significant association between the degree of cytogenetic complexity and survival, in that patients with five or less aberrations had a better prognosis than those with more than five changes. Patients with del(8p)/-8, +12, and +20 had a significantly worse prognosis compared with those without these aberrations, but +7 had no impact on prognosis.
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| 55. |
- Blom, René
(författare)
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Sarcoma of the female genital tract : Histopathology, DNA cytometry, p53 and mdm-2 analysis related to prognosis
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Sarcomas of the female genital tract are rare tumors and account for less than 5% of gynecologic malignancies. Traditionally, gynecologic sarcomas have been divided into different tumor types according to their histopathological features. The most common are leiomyosarcoma (LMS), malignant mixed Müllerian tumors (MMMT), endometrial stromal sarcoma (ESS) and (Müllerian) adenosarcoma. The different tumor types are highly aggressive with early lymphatic and/or hematogenous spread. Treatment is difficult and it is believed that sarcomas have a low radio-and chemosensitivity, and the mainstay in treatment is surgical removal of the tumor. The most important prognostic feature has been tumor stage. Nevertheless, there are some early-stage tumors that run a biological course different from that expected and additional prognostic factors indicating high-risk tumors are desirable.The study cohort consists of 49 uterine LMS, 44 uterine MMMTs, 17 uterine ESS, 11 uterine adenosarcomas and 26 ovarian MMMTs. The tumors were analyzed in a retrospective manner for DNA ploidy, S-phase fraction (SPF), p53 and mdm-2 expression, as well as traditional clinical and pathological prognostic factors, such as tumor stage. grade, atypia and mitotic index.Of the 49 LMS, 36 (86%) were non-diploid and 13 (27%) were p53-positive. Among the 44 uterine MMMTs, 30 (68%) were non-diploid and 27 (61%) had an SPF>10%. Twenty-seven (61%) overexpressed p53 and 11 (25%) were mdm-2 positive. Furthermore, 40 (91%) of the uterine MMMTs had a high mitotic count and 42 (95%) had high grade cytologic atypia. All low-grade ESS were DNA diploid and had a low SPF. Among the four high-grade ESS, three (75%) were DNA aneuploid and three (75%) were p53-positive. Among 1 1 adenosarcomas, eight (73%) were non-diploid. All ovarian MMMTs were non-diploid and all but two had an SPF>10%. 19 (73%) ovarian MMMTs were p53positive.The 5-year survival rate was 33% for LMS, 38% for uterine MMMT, 57% for ESS, 69% for adenosarcoma and 30% for ovarian MMMT.Thirty-five (71%) patients with LMS died of disease and two of intercurrent disease. Stage was found to be the most important factor for survival (p=0.007); in addition DNA ploidy (p=0.045) and SPF (p=0.041) had prognostic significance.Twenty-seven (61%) patients with uterine MMMT died of disease and six (14%) died of intercurrent disease. Stage was the only prognostic factor for survival.Nine (53%) patients with ESS died of disease. There was a significant correlation of survival to tumor grade (p=0.007), DNA ploidy (p=0.026), SPF (p=0.048) and stage (p=0.026).Of the 11 patients with adenosarcoma, four (36%) patients died of disease and three (27%) patients died of intercurrent disease. There were no variables that correlated with survival.Eighteen (69%) patients with ovarian MMMT died of disease and two (8%) patients died of intercurrent disease. In a multivariate analysis, only stage reached independent prognostic significance for survival (p=0.023).In summary, stage represents the most important prognostic factor for survival for uterine and ovarian sarcomas. DNA flow cytometry is useful in gaining additional prognostic information for LMS and ESS. P53-and mdm-2 overexpression had no prognostic value for survival rate. Most of the MMMT overexpressed p53 and were non-diploid. Treatment of sarcomatous neoplasms is difficult and the mainstay remains surgical removal of the tumor. For patients with early stage sarcoma there was a high recurrence rate, which suggests that a large proportion of patients may have systemic micrometastasic disease at the time of diagnosis. Recurrent and metastatic uterine sarcoma remains an incurable disease, and treatment must be considered palliative.
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| 56. |
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| 57. |
- Eriksson, Mikael, et al.
(författare)
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Increased cancer incidence in physicians, dentists, and health care workers
- 1998
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Ingår i: Oncology Reports. - 1021-335X. ; 5:6, s. 1413-1418
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Tidskriftsartikel (refereegranskat)abstract
- Some earlier reports have indicated increased incidence or mortality of specific tumor types in various health care professions. In this study we have evaluated cancer incidence in physicians, dentists, and other health care workers using the Swedish Cancer Environment Register (CER), which was formed by record-linkage between the 1970 census on current occupation and Cancer Register incidence data in 1971-84. In all three profession categories studied an increased risk was found, as well for all malignant tumors combined, as for specific tumor types regarding the different occupations. Possible etiological factors responsible for these risks are discussed.
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| 58. |
- Finizia, Caterina, 1961, et al.
(författare)
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Advanced laryngeal cancer T3-T4 in Sweden: a retrospective study 1986-1990. Survival and locoregional control related to treatment.
- 1996
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Ingår i: Acta oto-laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 116:6, s. 906-12
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Tidskriftsartikel (refereegranskat)abstract
- Different treatment modalities for advanced laryngeal cancer are much discussed in the literature. One-hundred-and-sixty patients with T3-4, N0-3, M0-1 laryngeal cancer diagnosed in Sweden between 1986 and 1990 were retrospectively analysed. One hundred (65 T3: 35 T4) received radical radiotherapy with salvage surgery (RRSS) in case of residual or recurrent disease. Thirty-eight (11T3: 27 T4) patients received surgery with or without radiotherapy (S +/- RT). Twenty-two patients received no treatment. After a median follow up of 4.4 years, the estimated 5-year actuarial corrected survival and 3-year locoregional control were 59% and 44% for T3 RRSS and 47% and 54% for T3 S +/- RT. No significant difference between the different treatment modalities was found. The 5-year corrected survival rate and the locoregional control at 3 years between T4-RRSS (32%; 26%) and T4-S + RT (58%; 68%) groups were significantly different (p < 0.05 and p < 0.01). This might suggest that surgery with or without radiotherapy still has its place as a treatment modality for patients with advanced T4 laryngeal carcinoma.
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| 59. |
- Hafström, Lars-Olof, 1936, et al.
(författare)
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Isolated hepatic perfusion with extracorporeal oxygenation using hyperthermia TNF alpha and melphalan: Swedish experience.
- 1998
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Ingår i: Recent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer. - 0080-0015. ; 147, s. 120-6
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Tidskriftsartikel (refereegranskat)abstract
- A phase I trial was performed to determine the toxicity and efficacy of isolated hepatic perfusion with tumour necrosis factor alpha (TNF) and melphalan (Alkeran) under mild hyperthermic conditions. Eleven patients with unresectable metastatic malignancies in the liver (malignant melanoma, leiomyosarcoma, colorectal cancer) underwent the procedure. Compared to our earlier experience with melphalan and cis-platinum under hyperthermic conditions (41.7 degrees C), this phase I study with TNF 30-200 micrograms and melphalan ).5 mg/kg body weight under 39 degrees C hyperthermia neither improved the response rate nor decreased the serious adverse effects. Two patients died within the first postoperative month owing to coagulopathy or multiple organ failure. Five patients were reoperated owing to postoperative bleeding. Three of six patients with liver metastases from malignant melanoma or leiomyosarcoma and none of five patients with liver metastases from colorectal cancer showed a partial response.
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| 60. |
- Hartman, Torbjörn
(författare)
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Tumour targeting with stable and radioactive nuclides : Dosimetric aspects at the cellular level
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Targeting with radioactive nuclides or nuclides that can be activated by neutrons may be a powerful tool for treatment of invasive tumours and disseminated tumour cells. The targeting agents are designed to find tumour cells and deliver the nuclides. The aim of the thesis was to investigate the dosimetry at the cellular level for three forms of radiation of interest for targeted radiotherapy: neutron activated emission of 4He- and 7Li- ions from 10B; high energy β-particles from 131I and α- particles from 211At. Computer models of cells and groups of cellswere developed for Monte Carlo simulations and point dose kernel calculations of the energy depositions in the cell nuclei.Simulations of boron neutron capture therapy (BNCT), mostly with a thermal neutron fluence of 5x1012 cm-2, showed that 108 atoms of 10B per cell always gave too low doses. Located in the nucleus, 109 atoms of 10B gave therapeutically interesting doses while location elsewhere in the cell gave insufficient dose to the nucleus. Boron dependent enhancement of tumour doses in fast neutron therapy demand at least 100 ppm of 10B in the tumour cells, a concentration at which BNCT, compared to fast neutron therapy, showed to give higher tumour doses and lower doses to normal tissue.With 105 atoms of 131I per cell and an effective half-life of 24 h the 131I had to be located in the nucleus to give therapeutically interesting doses in single cells. However, in tumour cell clusters with a diameter larger than 40 µm therapeutic doses were reached due to crossfire irradiation.211At is a most promising radionuclide for targeting of single cells or microscopic metastases. Between 30 and 1000 atoms of 211At per cell, depending on cell size and position of 211At, suffice to deliver, on the average, 10 Gy in the nucleus of a single cell, a dose relevant for therapy.
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