| 1. |
- Ottosson, Sandra, 1981-, et al.
(författare)
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Weight and body mass index in relation to irradiated volume and to overall survival in patients with oropharyngeal cancer: a retrospective cohort study
- 2014
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Ingår i: Radiation Oncology. - 1748-717X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Weight loss is a common problem in patients with Squamous Cell Carcinoma of the Head and Neck (SCCHN) treated with radiotherapy (RT). The aims of the present study were to determine if treated volume (TV), as a measure of the radiation dose burden, can predict weight loss in patients with oropharyngeal cancer and to analyze weight loss and body mass index (BMI) in the same patient group in relation to 5-year overall survival. Methods: The ARTSCAN trial is a prospective, randomized, multicenter trial in patients with SCCHN. Nutritional data from the ARTSCAN trial were analyzed retrospectively using univariate and multivariate statistical methods based on information on percentage weight loss from the start of RT up to five months after the termination of RT (study cohort 1, n = 232) and information on patients' BMI at the start of RT (study cohort 2, n = 203). TV was defined as the volume of the patient receiving at least 95% of the prescribed dose. TV64.6 (Gy) encompasses macroscopic tumor and TV43.7 (Gy) elective lymph nodes of the neck. Results: TV64.6 Gy and TV43.7 Gy were both significantly correlated with higher weight loss up to five months after the termination of RT in study cohort 1 (p < 0.001 for both). BMI at the start of RT was shown to be a prognostic factor for 5-year overall survival in study cohort 2 but weight loss was not. The hazard ratios and 95% confidence intervals were 3.78 (1.46-9.75) and 2.57 (1.43-4.62) in patients with underweight and normal weight, respectively. Conclusions: TV can predict weight loss during RT in patients with oropharyngeal cancer regardless of clinical stage. A high BMI (>25 kg/m(2)) at the start of RT is positively associated with survival in patients with oropharyngeal cancer.
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| 2. |
- Gaber, Alexander, et al.
(författare)
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Effects of radiation therapy on tissue and serum concentrations of tumour associated trypsin inhibitor and their prognostic significance in rectal cancer patients
- 2011
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Ingår i: Radiation Oncology. - 1748-717X. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Background: We have previously demonstrated that elevated concentrations of tumour-associated trypsin inhibitor (TATI) in both tumour tissue (t-TATI) and in serum (s-TATI) are associated with a poor prognosis in colorectal cancer patients. It was also found that s-TATI concentrations were lower in patients with rectal cancer compared to patients with colon cancer. In this study, we investigated the effects of neoadjuvant radiotherapy (RT) on concentrations of t-TATI and s-TATI in patients with rectal cancer. Methods: TATI was analysed in serum, normal mucosa and tumour tissue collected at various time points in 53 rectal cancer patients enrolled in a case-control study where 12 patients received surgery alone, 20 patients 5 x 5 Gy (short-term) preoperative RT and 21 patients 25 x 2 Gy (long-term) preoperative RT. T-TATI was analysed by immunohistochemistry and s-TATI was determined by an immunofluorometric assay. Mann-Whitney U test and Wilcoxon Z (Z) test were used to assess t-TATI and s-TATI concentrations in relation to RT. Spearman's correlation (R) test was used to explore the associations between t-TATI, s-TATI and clinicopathological parameters. Overall survival (OS) according to high and low t-TATI and s-TATI concentrations was estimated by classification and regression tree analysis, Kaplan-Meier analysis and the log rank test. Results: RT did not affect concentrations of t-TATI or s-TATI. In patients receiving short-term but not long-term RT, s-TATI concentrations were significantly higher 4 weeks post surgery than in serum drawn prior to surgery (Z = -3.366, P < 0.001). T-TATI expression correlated with male gender (R = 0.406, P = 0.008). High t-TATI expression in surgical specimens was associated with a significantly shorter OS (P = 0.045). S-TATI concentrations in serum drawn at all time points were associated with an impaired OS (P = 0.035 before RT, P = 0.001 prior to surgery, P = 0.043 post surgery). At all time points, s-TATI correlated with higher age (P < 0.001-0.021) and with increased s-creatinine concentrations assessed prior to surgery (P = 0.041). Conclusions: The results presented here further validate the utility of t-TATI and s-TATI as prognostic biomarkers in patients with rectal cancer, independent of neoadjuvant RT.
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| 3. |
- Gunnlaugsson, Adalsteinn, et al.
(författare)
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Change in prostate volume during extreme hypo-fractionation analysed with MRI
- 2014
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Ingår i: Radiation Oncology. - 1748-717X .- 1748-717X. ; 9, s. 22-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hypo-fractionated external beam radiotherapy with narrow CTV-PTV margins is increasingly applied for prostate cancer. This demands a precise target definition and knowledge on target location and extension during treatment. It is unclear how increase in fraction size affects changes in prostate volume during treatment. Our aim was to study prostate volume changes during extreme hypo-fractionation (7 x 6.1 Gy) by using sequential MRIs. Methods: Twenty patients treated with extreme hypo-fractionation were recruited from an on-going prospective randomized phase III trial. An MRI scan was done before start of treatment, at mid treatment and at the end of radiotherapy. The prostate was delineated at each MRI and the volume and maximum extension in left-right, anterior-posterior and cranial-caudal directions were measured. Results: There was a significant increase in mean prostate volume (14%) at mid treatment as compared to baseline. The prostate volume remained enlarged (9%) at the end of radiotherapy. Prostate swelling was most pronounced in the anterior-posterior and cranial-caudal directions. Conclusions: Extreme hypo-fractionation induced a significant prostate swelling during treatment that was still present at the time of last treatment fraction. Our results indicate that prostate swelling is an important factor to take into account when applying treatment margins during short extreme hypo-fractionation, and that tight margins should be applied with caution.
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| 4. |
- Gunnlaugsson, Adalsteinn, et al.
(författare)
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The effect on the small bowel of 5-FU and oxaliplatin in combination with radiation using a microcolony survival assay
- 2009
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Ingår i: Radiation Oncology. - London : BioMed Central. - 1748-717X .- 1748-717X. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Background: In locally advanced rectal cancer, 5-Fluorouracil (5-FU)-based chemoradiation is the standard treatment. The main acute toxicity of this treatment is enteritis. Due to its potential radiosensitizing properties, oxaliplatin has recently been incorporated in many clinical chemoradiation protocols. The aim of this study was to investigate to what extent 5-FU and oxaliplatin influence the radiation (RT) induced small bowel mucosal damage when given in conjunction with single or split dose RT.Methods: Immune competent balb-c mice were treated with varying doses of 5-FU, oxaliplatin (given intraperitoneally) and total body RT, alone or in different combinations in a series of experiments. The small bowel damage was studied by a microcolony survival assay. The treatment effect was evaluated using the inverse of the slope (D(0)) of the exponential part of the dose-response curve.Results: In two separate experiments the dose-response relations were determined for single doses of RT alone, yielding D(0) values of 2.79 Gy (95% CI: 2.65 - 2.95) and 2.98 Gy (2.66 - 3.39), for doses in the intervals of 5-17 Gy and 5-10 Gy, respectively. Equitoxic low doses (IC5) of the two drugs in combination with RT caused a decrease in jejunal crypt count with significantly lower D(0): 2.30 Gy (2.10 - 2.56) for RT+5-FU and 2.27 Gy (2.08 - 2.49) for RT+oxaliplatin. Adding both drugs to RT did not further decrease D(0):2.28 Gy (1.97 - 2.71) for RT+5-FU+oxaliplatin. A clearly higher crypt survival was noted for split course radiation (3 x 2.5 Gy) compared to a single fraction of 7.5 Gy. The same difference was seen when 5-FU and/or oxaliplatin were added.Conclusion: Combining 5-FU or oxaliplatin with RT lead to an increase in mucosal damage as compared to RT alone in our experimental setting. No additional reduction of jejunal crypt counts was noted when both drugs were combined with single dose RT. The higher crypt survival with split dose radiation indicates a substantial recovery between radiation fractions. This mucosalsparing effect achieved by fractionation was maintained also when chemotherapy was added.
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| 5. |
- Rasmusson, Elisabeth, et al.
(författare)
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Low rate of lymphedema after extended pelvic lymphadenectomy followed by pelvic irradiation of node-positive prostate cancer
- 2013
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Ingår i: Radiation Oncology. - 1748-717X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of the present study was to evaluate the prevalence and severity of lower limb lymphedema after pelvic lymphadenectomy and radiotherapy to the pelvic lymph nodes in patients with prostate cancer. Methods: Twenty-six patients underwent combined treatment for high-risk node-positive prostate cancer at Skane University Hospital between April 2008 and March 2011. The treatment consisted of extended pelvic lymphadenectomy followed by androgen deprivation therapy and radiotherapy. The pelvic lymphnodes, prostate and seminal vesicles were treated with external beam radiotherapy (EBRT) to an absorbed dose of 50 Gy followed by a brachytherapy (BT) boost of 2x10 Gy to the prostate only. Twenty-two patients accepted an invitation to a clinical examination with focus on lower limb swelling. The median time between the end of radiotherapy and examination was 2.2 years (range 1.2-4.1). Results: Six patients (27%) experienced grade 1 lymphedema and two patients (9%) grade 2 while none had grade 3 or 4 according to the CTC Common Toxicity Criteria scale 4.0. Three patients required treatment with compression stockings. Conclusion: Brachytherapy and pelvic EBRT have a low incidence of lymphedema (at median 2.2 y after treatment) in patients with high-risk node-positive prostate cancer that have undergone pelvic lymph node dissection.
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| 6. |
- Lindblom, Emely, et al.
(författare)
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Treatment fractionation for stereotactic radiotherapy of lung tumours: a modelling study of the influence of chronic and acute hypoxia on tumour control probability
- 2014
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Ingår i: Radiation Oncology. - 1748-717X .- 1748-717X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Stereotactic body radiotherapy (SBRT) for non-small-cell lung cancer (NSCLC) has led to promising local control and overall survival for fractionation schemes with increasingly high fractional doses. A point has however been reached where the number of fractions used might be too low to allow efficient local inter-fraction reoxygenation of the hypoxic cells residing in the tumour. It was therefore the purpose of this study to investigate the impact of hypoxia and extreme hypofractionation on the tumour control probability (TCP) from SBRT.Methods: A three-dimensional model of tumour oxygenation able to simulate oxygenation changes on the microscale was used. The TCP was determined for clinically relevant SBRT fractionation schedules of 1, 3 and 5 fractions assuming either static tumour oxygenation or that the oxygenation changes locally between fractions due to fast reoxygenation of acute hypoxia without an overall reduction in chronic hypoxia.Results: For the schedules applying three or five fractions the doses required to achieve satisfying levels of TCP were considerably lower when local oxygenation changes were assumed compared to the case of static oxygenation; a decrease in D50 of 17.7 Gy was observed for a five-fractions schedule applied to a 20% hypoxic tumour when fast reoxygenation was modelled. Assuming local oxygenation changes, the total doses required for a tumor control probability of 50% were of similar size for one, three and five fractions.Conclusions: Although attractive from a practical point of view, extreme hypofractionation using just one single fraction may result in impaired local control of hypoxic tumours, as it eliminates the possibility for any kind of reoxygenation.
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| 7. |
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| 8. |
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| 9. |
- Ding, Zhen-Yu, et al.
(författare)
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Livin expression is an independent factor in rectal cancer patients with or without preoperative radiotherapy
- 2013
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Ingår i: Radiation Oncology. - London, United Kingdom : BioMed Central. - 1748-717X .- 1748-717X. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study was aimed to investigate the expression significance of Livin in relation to radiotherapy (RT), clinicopathological and biological factors of rectal cancer patients.Methods: This study included 144 primary rectal cancer patients who participated in a Swedish clinical trial of preoperative radiotherapy. Tissue microarray samples from the excised primary rectal cancers, normal mucosa and lymph node metastases were immunostained with Livin antibody. The proliferation of colon cancer cell lines SW620 and RKO was assayed after Livin knock-down.Results: The expression of Livin was significantly increased from adjacent (P = 0.051) or distant (P = 0.028) normal mucosa to primary tumors. 15.4% (2/13) and 39.7% (52/131) patients with Livin-negative and positive tumors died at 180 months after surgery, and the difference tended to be statistically significant (P = 0.091). In multivariate analyses, the difference achieved statistical significance, independent of TNM stage, local and distant recurrence, grade of differentiation, gender, and age (odds ratio = 5.09, 95% CI: 1.01-25.64, P = 0.048). The in vitro study indicated colon cancer cells with Livin knock-down exhibited decreased proliferation compared with controls after RT.Conclusions: The expression of Livin was was independently related to survival in rectal cancer patients, suggesting Livin as a useful prognostic factor for rectal cancer patients.
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| 10. |
- Ferreira, Brigida C., et al.
(författare)
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Radiobiological evaluation of forward and inverse IMRT using different fractionations for head and neck tumours
- 2010
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Ingår i: Radiation Oncology. - 1748-717X. ; 5, s. 57-
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To quantify the radiobiological advantages obtained by an Improved Forward Planning technique (IFP) and two IMRT techniques using different fractionation schemes for the irradiation of head and neck tumours. The conventional radiation therapy technique (CONVT) was used here as a benchmark. Methods: Seven patients with head and neck tumours were selected for this retrospective planning study. The PTV1 included the primary tumour, PTV2 the high risk lymph nodes and PTV3 the low risk lymph nodes. Except for the conventional technique where a maximum dose of 64.8 Gy was prescribed to the PTV1, 70.2 Gy, 59.4 Gy and 50.4 Gy were prescribed respectively to PTV1, PTV2 and PTV3. Except for IMRT2, all techniques were delivered by three sequential phases. The IFP technique used five to seven directions with a total of 15 to 21 beams. The IMRT techniques used five to nine directions and around 80 segments. The first, IMRT1, was prescribed with the conventional fractionation scheme of 1.8 Gy per fraction delivered in 39 fractions by three treatment phases. The second, IMRT2, simultaneously irradiated the PTV2 and PTV3 with 59.4 Gy and 50.4 Gy in 28 fractions, respectively, while the PTV1 was boosted with six subsequent fractions of 1.8 Gy. Tissue response was calculated using the relative seriality model and the Poisson Linear-Quadratic-Time model to simulate repopulation in the primary tumour. Results: The average probability of total tumour control increased from 38% with CONVT to 80% with IFP, to 85% with IMRT1 and 89% with IMRT2. The shorter treatment time and larger dose per fraction obtained with IMRT2 resulted in an 11% increase in the probability of control in the PTV1 with respect to IFP and 7% relatively to IMRT1 (p < 0.05). The average probability of total patient complications was reduced from 80% with CONVT to 61% with IFP and 31% with IMRT. The corresponding probability of complications in the ipsilateral parotid was 63%, 42% and 20%; in the contralateral parotid it was 50%, 20% and 9%; in the oral cavity it was 2%, 15% and 4% and in the mandible it was 1%, 5% and 3%, respectively. Conclusions: A significant improvement in treatment outcome was obtained with IMRT compared to conventional radiation therapy. The practical and biological advantages of IMRT2, employing a shorter treatment time, may outweigh the small differences obtained in the organs at risk between the two IMRT techniques. This technique is therefore presently being used in the clinic for selected patients with head and neck tumours. A significant improvement in the quality of the dose distribution was obtained with IFP compared to CONVT. Thus, this beam arrangement is used in the clinical routine as an alternative to IMRT.
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