| 1. |
- Adra, Jamila, et al.
(författare)
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Distribution of locoregional breast cancer recurrence in relation to postoperative radiation fields and biological subtypes.
- 2019
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Ingår i: International journal of radiation oncology, biology, physics. - : Elsevier BV. - 1879-355X .- 0360-3016. ; 105:2, s. 285-295
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Tidskriftsartikel (refereegranskat)abstract
- and purpose: To investigate incidence and location of locoregional recurrence (LRR) in patients who have received postoperative locoregional radiotherapy (LRRT) for primary breast cancer. LRR-position in relation to applied radiotherapy and the primary tumours biological subtype were analysed with the aim to evaluate current target guidelines and RT techniques in relation to tumour biology.Medical records were reviewed for all patients who received postoperative LRRT for primary BC in southwestern Sweden from 2004-2008 (N=923). Patients with LRR as a first event were identified (N=57, distant failure and death were considered competing risks). CT images identifying LRR were used to compare LRR locations to postoperative LRRT fields. LRR risk and distribution were then related to the primary BC biological subtype and to current target guidelines.Cumulative LRR incidence after 10 years was 7.1% (95%CI 5.5-9.1). Fifty-seven of the 923 patients in the cohort developed LRR (30 local recurrences (LR), 30 regional recurrences (RR), of which 3 cases of simultaneous LR/RR). Most cases of LRR developed fully (56%) or partially (26%) within postoperatively irradiated areas. The most common location for out-of-field RR was cranial to RT fields in the supraclavicular fossa. Patients with an ER- (HR 4.6, p<0.001, 95%CI 2.5-8.4) or HER2+ (HR 2.4, p=0.007, 95%CI 1.3-4.7) primary BC presented higher risks of LRR compared to those with ER+ tumours. ER-/HER2+ tumours more frequently recurred in-field (68%) rather than marginal/out-of-field (32%). In addition, 75% of in-field recurrences derived from an ER-/HER+ tumour, compared to 45% of marginal/out-of-field recurrences. A complete pathological response in the axilla after neoadjuvant treatment was associated with a lower degree of LRR risk (p=0.022).Incidence and locations of LRR seems to be related to the primary BC biological subtype. Individualized LRRT according to tumour biology may be applied to improve outcomes.
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| 2. |
- Alkner, Sara, et al.
(författare)
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Protocol for the T-REX-trial: tailored regional external beam radiotherapy in clinically node-negative breast cancer patients with 1-2 sentinel node macrometastases - an open, multicentre, randomised non-inferiority phase 3 trial.
- 2023
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Ingår i: BMJ open. - 2044-6055. ; 13:9
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Tidskriftsartikel (refereegranskat)abstract
- Modern systemic treatment has reduced incidence of regional recurrences and improved survival in breast cancer (BC). It is thus questionable whether regional radiotherapy (RT) is still beneficial in patients with sentinel lymph node (SLN) macrometastasis. Postoperative regional RT is associated with an increased risk of arm morbidity, pneumonitis, cardiac disease and secondary cancer. Therefore, there is a need to individualise regional RT in relation to the risk of recurrence.In this multicentre, prospective randomised trial, clinically node-negative patients with oestrogen receptor-positive, HER2-negative BC and 1-2 SLN macrometastases are eligible. Participants are randomly assigned to receive regional RT (standard arm) or not (intervention arm). Regional RT includes the axilla level I-III, the supraclavicular fossa and in selected patients the internal mammary nodes. Both groups receive RT to the remaining breast. Chest-wall RT after mastectomy is given in the standard arm, but in the intervention arm only in cases of widespread multifocality according to national guidelines. RT quality assurance is an integral part of the trial.The trial aims to include 1350 patients between March 2023 and December 2028 in Sweden and Norway. Primary outcome is recurrence-free survival (RFS) at 5 years. Non-inferiority will be declared if outcome in the de-escalation arm is not >4.5 percentage units below that with regional RT, corresponding to an HR of 1.41 assuming 88% 5-year RFS with standard treatment. Secondary outcomes include locoregional recurrence, overall survival, patient-reported arm morbidity and health-related quality of life. Gene expression analysis and tumour tissue-based studies to identify prognostic and predictive markers for benefit of regional RT are included.The trial protocol is approved by the Swedish Ethics Authority (Dnr-2022-02178-01, 2022-05093-02, 2023-00826-02, 2023-03035-02). Results will be presented at scientific conferences and in peer-reviewed journals.NCT05634889.
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| 3. |
- Alsadius, David, 1975, et al.
(författare)
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Mean Absorbed Dose to the Anal-Sphincter Region and Fecal Leakage among Irradiated Prostate Cancer Survivors.
- 2012
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier BV. - 1879-355X .- 0360-3016. ; 84:2
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To supplement previous findings that the absorbed dose of ionizing radiation to the anal sphincter or lower rectum affects the occurrence of fecal leakage among irradiated prostate-cancer survivors. We also wanted to determine whether anatomically defining the anal-sphincter region as the organ at risk could increase the degree of evidence underlying clinical guidelines for restriction doses to eliminate this excess risk. METHODS AND MATERIALS: We identified 985 men irradiated for prostate cancer between 1993 and 2006. In 2008, we assessed long-term gastrointestinal symptoms among these men using a study-specific questionnaire. We restrict the analysis to the 414 men who had been treated with external beam radiation therapy only (no brachytherapy) to a total dose of 70 Gy in 2-Gy daily fractions to the prostate or postoperative prostatic region. On reconstructed original radiation therapy dose plans, we delineated the anal-sphincter region as an organ at risk. RESULTS: We found that the prevalence of long-term fecal leakage at least once per month was strongly correlated with the mean dose to the anal-sphincter region. Examining different dose intervals, we found a large increase at 40 Gy; ≥40 Gy compared with <40 Gy gave a prevalence ratio of 3.8 (95% confidence interval 1.6-8.6). CONCLUSIONS: This long-term study shows that mean absorbed dose to the anal-sphincter region is associated with the occurrence of long-term fecal leakage among irradiated prostate-cancer survivors; delineating the anal-sphincter region separately from the rectum and applying a restriction of a mean dose <40 Gy will, according to our data, reduce the risk considerably.
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| 4. |
- Alsadius, David, 1975, et al.
(författare)
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Tobacco smoking and long-lasting symptoms from the bowel and the anal-sphincter region after radiotherapy for prostate cancer.
- 2011
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Ingår i: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. - : Elsevier BV. - 1879-0887.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Tobacco smoking can cause vascular injury, tissue hypoxia and fibrosis as can ionizing radiation. However, we do not know if tobacco smoking increases the risk of long-term side effects after radiotherapy for prostate cancer. METHODS: We identified 985 men treated with radiotherapy for prostate cancer between 1993 and 2006. In 2008, long-lasting symptoms appearing after radiotherapy for prostate cancer were assessed through a study-specific questionnaire as were smoking habits and demographic factors of all these men. In the questionnaire the prostate-cancer survivors were asked to report symptom occurrence the previous six months. RESULTS: We obtained information on tobacco smoking from 836 of the 985 prostate-cancer survivors with a median time to follow-up of six years (range 2-14years). The prevalence ratio of defecation urgency among current smokers compared to never smokers was 1.6 (95% CI 1.2-2.2). Corresponding prevalence ratio for diarrhea was 2.8 (95% CI 1.2-6.5), the sensation of bowel not completely emptied after defecation 2.1 (95% CI 1.3-3.3) and for sudden emptying of all stools into clothing without forewarning 4.7 (95% CI 2.3-9.7). CONCLUSION: Tobacco smoking among prostate-cancer survivors treated with radiotherapy increases the risk of certain long-lasting symptoms from the bowel and anal-sphincter region.
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| 5. |
- Appelgren, M., et al.
(författare)
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Patient-reported outcomes one year after positive sentinel lymph node biopsy with or without axillary lymph node dissection in the randomized SENOMAC trial
- 2022
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Ingår i: Breast. - : Elsevier BV. - 0960-9776 .- 1532-3080. ; 63, s. 16-23
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: This report evaluates whether health related quality of life (HRQoL) and patient-reported arm morbidity one year after axillary surgery are affected by the omission of axillary lymph node dissection (ALND). Methods: The ongoing international non-inferiority SENOMAC trial randomizes clinically node-negative breast cancer patients (T1-T3) with 1-2 sentinel lymph node (SLN) macrometastases to completion ALND or no further axillary surgery. For this analysis, the first 1181 patients enrolled in Sweden and Denmark between March 2015, and June 2019, were eligible. Data extraction from the trial database was on November 2020. This report covers the secondary outcomes of the SENOMAC trial: HRQoL and patient-reported arm morbidity. The EORTC QLQC30, EORTC QLQ-BR23 and Lymph-ICF questionnaires were completed in the early postoperative phase and at one-year follow-up. Adjusted one-year mean scores and mean differences between the groups are presented corrected for multiple testing.
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| 6. |
- Arp, Hans Peter H., et al.
(författare)
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Native Oxy-PAHs, N-PACs, and PAHs in historically contaminated soils from Sweden, Belgium, and France : their soil-porewater partitioning behavior, bioaccumulation in Enchytraeus crypticus, and bioavailability
- 2014
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 48:19, s. 11187-11195
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Tidskriftsartikel (refereegranskat)abstract
- Soil quality standards are based on partitioning and toxicity data for laboratory-spiked reference soils, instead of real world, historically contaminated soils, which would be more representative. Here 21 diverse historically contaminated soils from Sweden, Belgium, and France were obtained, and the soil-porewater partitioning along with the bioaccumulation in exposed worms (Enchytraeus crypticus) of native polycyclic aromatic compounds (PACs) were quantified. The native PACs investigated were polycyclic aromatic hydrocarbons (PAHs) and, for the first time to be included in such a study, oxygenated-PAHs (oxy-PAHs) and nitrogen containing heterocyclic PACs (N-PACs). The passive sampler polyoxymethylene (POM) was used to measure the equilibrium freely dissolved porewater concentration, C-pw, of all PACs. The obtained organic carbon normalized partitioning coefficients, K-TOC, show that sorption of these native PACs is much stronger than observed in laboratory-spiked soils (typically by factors 10 to 100), which has been reported previously for PAHs but here for the first time for oxy-PAHs and N-PACs. A recently developed K-TOC model for historically contaminated sediments predicted the 597 unique, native K-TOC values in this study within a factor 30 for 100% of the data and a factor 3 for 58% of the data, without calibration. This model assumes that TOC in pyrogenic-impacted areas sorbs similarly to coal tar, rather than octanol as typically assumed. Black carbon (BC) inclusive partitioning models exhibited substantially poorer performance. Regarding bioaccumulation, C-pw combined with liposome-water partition coefficients corresponded better with measured worm lipid concentrations, C-lipid (within a factor 10 for 85% of all PACs and soils), than C-pw combined with octanol-water partition coefficients (within a factor 10 for 76% of all PACs and soils). E. crypticus mortality and reproducibility were also quantified. No enhanced mortality was observed in the 21 historically contaminated soils despite expectations from PAH spiked reference soils. Worm reproducibility weakly correlated to C-lipid of PACs, though the contributing influence of metal concentrations and soil texture could not be taken into account. The good agreement of POM-derived C-pw with independent soil and lipid partitioning models further supports that soil risk assessments would improve by accounting for bioavailability. Strategies for including bioavailability in soil risk assessment are presented.
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| 7. |
- de Boniface, J., et al.
(författare)
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The generalisability of randomised clinical trials: an interim external validity analysis of the ongoing SENOMAC trial in sentinel lymph node-positive breast cancer
- 2020
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 180:1, s. 167-176
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Tidskriftsartikel (refereegranskat)abstract
- Purpose None of the key randomised trials on the omission of axillary lymph node dissection (ALND) in sentinel lymph-positive breast cancer have reported external validity, even though results indicate selection bias. Our aim was to assess the external validity of the ongoing randomised SENOMAC trial by comparing characteristics of Swedish SENOMAC trial participants with non-included eligible patients registered in the Swedish National Breast Cancer Register (NKBC). Methods In the ongoing non-inferiority European SENOMAC trial, clinically node-negative cT1-T3 breast cancer patients with up to two sentinel lymph node macrometastases are randomised to undergo completion ALND or not. Both breast-conserving surgery and mastectomy are eligible interventions. Data from NKBC were extracted for the years 2016 and 2017, and patient and tumour characteristics compared with Swedish trial participants from the same years. Results Overall, 306 NKBC cases from non-participating and 847 NKBC cases from participating sites (excluding SENOMAC participants) were compared with 463 SENOMAC trial participants. Patients belonging to the middle age groups (p = 0.015), with smaller tumours (p = 0.013) treated by breast-conserving therapy (50.3 versus 47.1 versus 65.2%, p < 0.001) and less nodal tumour burden (only 1 macrometastasis in 78.8 versus 79.9 versus 87.3%, p = 0.001) were over-represented in the trial population. Time trends indicated, however, that differences may be mitigated over time. Conclusions This interim external validity analysis specifically addresses selection mechanisms during an ongoing trial, potentially increasing generalisability by the time full accrual is reached. Similar validity checks should be an integral part of prospective clinical trials. Trial registration: NCT 02240472, retrospective registration date September 14, 2015 after trial initiation on January 31, 2015
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| 8. |
- Enell, Anja, et al.
(författare)
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Combining Leaching and Passive Sampling To Measure the Mobility and Distribution between Porewater, DOC, and Colloids of Native Oxy-PAHs, N-PACs, and PAHs in Historically Contaminated Soil
- 2016
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 50:21, s. 11797-11805
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Tidskriftsartikel (refereegranskat)abstract
- Different methods to quantify soil porewater concentrations of contaminants will provide different types of information. Passive sampling measurements give freely dissolved porewater concentrations (C-pw,C-free), while leaching tests provide information on the mobile concentration (C-pw,C-leach), including contaminants associated with dissolved organic carbon (DOC) and particles/colloids in the porewater. This study presents a novel combination of these two measurements, to study the sorption and mobility of polycyclic aromatic compounds (PACs) to DOC and particulate organic carbon (POC) in 10 historically contaminated soils. The PACs investigated were polycyclic aromatic hydrocarbons (PAHs), oxygenated-PAHs, and nitrogen containing heterocyclic PACs. Observed C-pw,C-leach was up to 5 orders of magnitude higher than C-pw,C-free; implying large biases when C-pw,C-leach is used to assess bioavailability or soil partitioning. Sorption of PACs to DOC and POC was important for the mobility of compounds with log K-OW > 4. Average DOC/water-partitioning coefficients (K-DOC) correlated well with KOW (log K-DOC = 0.89 x log K-OW +1.03 (r(2) = 0.89)). This relationship is likely more accurate for historically contaminated soils than previously published data, which suffer from artifacts caused by problems in measuring C-pw,C-free correctly or not using historically contaminated soils. POC/water-partitioning coefficients (K-POC) were orders of magnitude larger than corresponding K-DOC, suggesting sorption to mobile particles/colloids is the dominant mechanism for PAC mobility.
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| 9. |
- Josefsson, Sarah, et al.
(författare)
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Determination of polyoxymethylene (POM) - water partition coefficients for oxy-PAHs and PAHs
- 2015
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 119, s. 1268-1274
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Tidskriftsartikel (refereegranskat)abstract
- Oxygenated polycyclic aromatic hydrocarbons (oxy-PAHs) are a class of ubiquitously occurring pollutants of which little is known. They can be co-emitted with PAHs or formed from PAHs in the environment. The environmental fate and risk of oxy-PAHs are difficult to assess due to a lack of methods to quantify their pore water concentrations. One sampler that can be used to determine freely dissolved concentrations of organic contaminants is polyoxymethylene (POM). In this study, POM - water partition coefficients (K-POM) were determined for 11 oxy-PAHs. K-POM values of 8 PAHs with similar hydrophobicities as the oxy-PAHs were determined for comparison. Results showed that log K-POM values ranged from 2.64 to 4.82 for the PAHs (2-4 rings), similar to previously determined values. LogK(pom) values for investigated oxy-PAHs ranged from 0.96 to 5.36. The addition of carbonylic oxygen on a parent PAH generally lowered K-POM by 0.5 to 1.0 log units, which is attributable to the presence of carbonylic oxygens increasing water solubility. The K-POM values presented here will facilitate simultaneous assessments of freely dissolved water concentrations of oxy-PAHs and PAHs in environmental media.
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| 10. |
- Karlsson, Per, 1963, et al.
(författare)
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Radiotherapy for metastatic lesions
- 2017
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Ingår i: Breast Cancer. Veronesi U., Goldhirsch A., Veronesi P., Gentilini O., Leonardi M. (eds).. - Cham : Springer. - 9783319488486 ; , s. 685-693
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Modern imaging and the development of new precise techniques in radiotherapy has changed the possibilities to detect and treat metastatic lesions. Metastatic breast cancer includes a wide range of clinical scenarios, and the use of radiotherapy must be adjusted to the patient need, all the way from symptom control with a single fraction late in life to potentially curative extensive radiotherapy in oligometastatic disease. The role of palliative radiotherapy in various metastatic sites and the evidence behind different fractionation schedules are reviewed. Treatments of metastatic spinal cord compression and radiotherapy in locally recurrent disease are discussed. The possibilities of stereotactic radiotherapy for brain metastases as well as stereotactic body radiotherapy for oligometastatic disease are presented and summarized. The integration of the systemic treatment with the radiotherapy and the importance of listening to the patient need and to put the radiotherapy decision within the context of a multidisciplinary team are emphasized. © Springer International Publishing AG 2017.
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