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Sökning: WFRF:(Nyman Jan)

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1.
  • Cesta, Carolyn E., et al. (författare)
  • A prospective investigation of perceived stress, infertility-related stress, and cortisol levels in women undergoing in vitro fertilization : influence on embryo quality and clinical pregnancy rate
  • 2018
  • Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : WILEY. - 0001-6349 .- 1600-0412. ; 97:3, s. 258-268
  • Tidskriftsartikel (refereegranskat)abstract
    • IntroductionWomen undergoing fertility treatment experience high levels of stress. However, it remains uncertain if and how stress influences in vitro fertilization (IVF) cycle outcome. This study aimed to investigate whether self-reported perceived and infertility-related stress and cortisol levels were associated with IVF cycle outcomes.Material and methodsA prospective cohort of 485 women receiving fertility treatment was recruited from September 2011 to December 2013 and followed until December 2014. Data were collected by online questionnaire prior to IVF start and from clinical charts. Salivary cortisol levels were measured. Associations between stress and cycle outcomes (clinical pregnancy and indicators of oocyte and embryo quality) were measured by logistic or linear regression, adjusted for age, body mass index, education, smoking, alcohol and caffeine consumption, shiftwork and night work. ResultsUltrasound verified pregnancy rate was 26.6% overall per cycle started and 32.9% per embryo transfer. Stress measures were not associated with clinical pregnancy: when compared with the lowest categories, the adjusted odds ratio (OR) and 95% confidence interval (CI) for the highest categories of the perceived stress score was 1.04 (95% CI 0.58-1.87), infertility-related stress score was OR = 1.18 (95% CI 0.56-2.47), morning and evening cortisol was OR = 1.18 (95% CI 0.60-2.29) and OR = 0.66 (95% CI 0.34-1.30), respectively.ConclusionsPerceived stress, infertility-related stress, and cortisol levels were not associated with IVF cycle outcomes. These findings are potentially reassuring to women undergoing fertility treatment with concerns about the influence of stress on their treatment outcome.
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2.
  • Johansson, Bengt, 1958- (författare)
  • Long-term outcome research on PDR brachytherapy with focus on breast, base of tongue and lip cancer
  • 2010
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Brachytherapy (BT) with continuous low dose rate (LDR) has been used for 100 years and is considered as the radiotherapy method able to deliver a dose in the shortest time with high efficacy and low risk of side effects. The drawbacks are need for patient isolation and radiation exposure of the staff during the treatment. Brenner and Hall published the radiobiology concept for pulsed dose rate (PDR) in 1991.  Short (10-20 minutes), hourly pulses of high dose rate (HDR) given to the same dose, with same overall treatment time will virtually simulate continuous LDR. At the same time new afterloading machine technology became available, where a single millimetre sized radiation 192Iridium source sequentially moves through the applicator in small individually timed steps. The advantages are that the radiation dose can be optimized along the applicator and with no radiation exposure of the staff and no need for patient isolation more than during the pulse. This work deals with four different aspects of PDR BT An experimental comparison of measured absorbed doses outside a left sided breast target on a body equivalent Alderson phantom was made.  Five external beam radiotherapy (EBRT) whole breast treatments to 50 Gy versus five accelerated partial breast irradiations (APBI) by PDR BT to 50 Gy were studied. The absorbed doses were measured in 67 different positions inside the body phantom by thermoluminescence dosimeters. The result shows that dose points distant to the left breast will have 1-1.4 % of the prescribed dose with no difference between EBRT and PDR BT. Organs at risk in short distance (<5 cm) to the target (such as parts of the left lung, heart muscle and the right breast) will have significantly less dose by PDR BT. In conclusion PDR BT has dosimetric advantages close to the target compared to EBRT and cannot do more damage to remote organs. PDR APBI as the adjuvant RT treatment to breast conserving surgery after early breast cancer was studied. Between 1994-2004 we treated 50 women and 51 breasts. The median age of the population was 53 (40-72) years. The cases were radically resected, unifocal T1-2N0-1M0 tumours. PDR BT was given to a dose of 50 Gy for 5 days directed to the operated sector of the breast. The median treated volume was 160 cm3, constituting in median 31 % of the breast volume. The treatment is called accelerated because total treatment time is 5 days compared to 5 weeks for EBRT. After a median follow-up of 130 months (>10 years) we noted 5 (10 %) local recurrences in the treated breast. Four of these recurrences were outside the treated volume. Three women (6 %) developed cancers in the other breast. Early side effects were mild and less than with EBRT. As late side effects we found mild to moderate local fibroses in the treated volume. A cosmetic evaluation was done by both the patient and a nurse and was found to be lower than in other published data (56 % = good to excellent). The 10 years local failure rate is similar to the result from a large Swedish randomized study on whole breast radiotherapy to 50 Gy. The study indicates that PDR BT is highly effective. A combination of EBRT (40.8 Gy) and PDR boost (35 Gy) to T1-4N0-3M0, base of tongue (BOT) cancer, treated during 1994-2007 was analyzed. The study is the first with PDR and second largest with BT worldwide. A number of 83 patients with a median age of 60 (38-82) years were included. BT was given to a mean volume of 58 ccm 2 days after the neck dissection. Median follow-up was 54 months. At 5 years we found 89 % local tumour control, 95 % neck control, 80 % disease free survival and an overall survival of 65 %. Late side effects were 13 % minor transient soft tissue necrosis and 12 % long lasting or permanent soft tissue- or osteoradio-necrosis. The results are among the best published worldwide. An extensive quality of life analysis was done on 45 patients at last follow-up and showed limited, persistent xerostomia and dysphagia. The global quality of life was rated good in 75 % of the patients. The last study presented was PDR mono-brachytherapy (55-60 Gy) to cancer of the lip (T1-3N0M0). The study included 43 patients with a median age of 74 (37-92) years. The treatment time was 5.5-6 days and the mean treated volume was 15 ccm. The median follow-up time was 54 (1-158) months. Five year Kaplan-Meier data showed, local control 94 %, disease free survival 86 % and overall survival 59 %. An early side effect was a strong radiation mucositis and dermatitis, which healed in 1 month. Late side effects were uncommon and the cosmetic appearance and the lip function were found to be normal. Our data in total and per T-stage was compared to a European survey from 1993 on 2794 patients treated by LDR BT. The results are similar and are a strong indication of equal efficacy between PDR and LDR.
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4.
  • Karlsson, Kristin, et al. (författare)
  • Retrospective Cohort Study of Bronchial Doses and Radiation-Induced Atelectasis After Stereotactic Body Radiation Therapy of Lung Tumors Located Close to the Bronchial Tree
  • 2013
  • Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier BV. - 0360-3016 .- 1879-355X. ; 87:3, s. 590-595
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To evaluate the dose-response relationship between radiation-induced atelectasis after stereotactic body radiation therapy (SBRT) and bronchial dose. Methods and Materials: Seventy-four patients treated with SBRT for tumors close to main, lobar, or segmental bronchi were selected. The association between incidence of atelectasis and bronchial dose parameters (maximum point-dose and minimum dose to the high-dose bronchial volume [ranging from 0.1 cm(3) up to 2.0 cm(3)]) was statistically evaluated with survival analysis models. Results: Prescribed doses varied between 4 and 20 Gy per fraction in 2-5 fractions. Eighteen patients (24.3%) developed atelectasis considered to be radiation-induced. Statistical analysis showed a significant correlation between the incidence of radiation-induced atelectasis and minimum dose to the high-dose bronchial volumes, of which 0.1 cm(3) (D-0.1cm3) was used for further analysis. The median value of D-0.1cm3 (alpha/beta = 3 Gy) was EQD(2,LQ) = 147 Gy(3) (range, 20-293 Gy(3)). For patients who developed atelectasis the median value was EQD(2,LQ) = 210 Gy(3), and for patients who did not develop atelectasis, EQD(2,LQ) = 105 Gy(3). Median time from treatment to development of atelectasis was 8.0 months (range, 1.1-30.1 months). Conclusion: In this retrospective study a significant dose-response relationship between the incidence of atelectasis and the dose to the high-dose volume of the bronchi is shown.
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5.
  • Lunde, Ngoc Nguyen, et al. (författare)
  • Legumain is upregulated in acute cardiovascular events and associated with improved outcome - potentially related to anti-inflammatory effects on macrophages
  • 2020
  • Ingår i: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 296, s. 74-82
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aims: We have previously found increased levels of the cysteine protease legumain in plasma and plaques from patients with carotid atherosclerosis. This study further investigated legumain during acute cardiovascular events.Methods: Circulating levels of legumain from patients and legumain released from platelets were assessed by enzyme-linked-immunosorbent assay. Quantitative PCR and immunoblotting were used to study expression, while localization was visualized by immunohistochemistry.Results: In the SUMMIT Malmo cohort (n = 339 with or without type 2 diabetes and/or cardiovascular disease [CVD], and 64 healthy controls), the levels of circulating legumain were associated with the presence of CVD in non-diabetics, with no relation to outcome. In symptomatic carotid plaques and in samples from both coronary and intracerebral thrombi obtained during acute cardiovascular events, legumain was co-localized with macrophages in the same regions as platelets. In vitro, legumain was shown to be present in and released from platelets upon activation. In addition, THP-1 macrophages exposed to releasate from activated platelets showed increased legumain expression. Interestingly, primary peripheral blood mononuclear cells stimulated with recombinant legumain promoted anti-inflammatory responses. Finally, in a STEMI population (POSTEMI; n = 272), patients had significantly higher circulating legumain before and immediately after percutaneous coronary intervention compared with healthy controls (n = 67), and high levels were associated with improved outcome.Conclusions: Our data demonstrate for the first time that legumain is upregulated during acute cardiovascular events and is associated with improved outcome.
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6.
  • Zackrisson, Björn, et al. (författare)
  • Two-year results from a Swedish study on conventional versus accelerated radiotherapy in head and neck squamous cell carcinoma - The ARTSCAN study
  • 2011
  • Ingår i: Radiotherapy and Oncology. - : Elsevier. - 0167-8140 .- 1879-0887. ; 100:1, s. 41-48
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose: Studies on accelerated fractionation (AF) in head and neck cancer have shown increased local control and survival compared with conventional fractionation (CF), while others have been non-conclusive. In 1998 a national Swedish group decided to perform a randomised controlled clinical study of AF. Materials and methods: Patients with verified squamous cell carcinoma of the oral cavity, oropharynx, larynx (except glottic T1-T2, N0) and hypopharynx were included. Patients with prior chemotherapy or surgery were excluded. Patients were randomised to either CF (2Gy/day, 5days/week for 7 weeks, total dose 68Gy) or to AF (1.1Gy+2.0Gy/day, 5days/week for 4.5weeks, total dose 68Gy). An extensive quality assurance protocol was followed throughout the study. The primary end point was loco-regional tumour control (LRC) at two years after treatment. RESULTS: The study was closed in 2006 when 750 patients had been randomised. Eighty-three percent of the patients had stages III-IV disease. Forty eight percent had oropharyngeal, 21% laryngeal, 17% hypopharyngeal and 14% oral cancers. There were no significant differences regarding overall survival (OS) or LRC between the two regimens. The OS at two years was 68% for AF and 67% for CF. The corresponding figures for LRC were 71% and 67%, respectively. There was a trend towards improved LRC for oral cancers treated (p=0.07) and for large tumours (T3-T4) (p=0.07) treated with AF. The AF group had significantly worse acute reactions, while there was no significant increase in late effects. Conclusion: Overall the AF regimen did not prove to be more efficacious than CF. However, the trend towards improved results in AF for oral cancers needs to be further investigated.  
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7.
  • Abel, Edvard, 1970, et al. (författare)
  • Fatigue in Patients With Head and Neck Cancer Treated With Radiation Therapy: A Prospective Study of Patient-Reported Outcomes and Their Association With Radiation Dose to the Cerebellum
  • 2022
  • Ingår i: Advances in Radiation Oncology. - : Elsevier BV. - 2452-1094. ; 7:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Although fatigue is a known side effect in patients with head and neck cancer (HNC) receiving radiation therapy, knowledge regarding long-term fatigue and dose-response relationships to organs at risk is scarce. The aim of this prospective study was to analyze patient-reported fatigue in patients with HNC receiving radiation therapy and to explore any possible association with organ-at-risk doses. Methods and Materials: Patients with HNC referred for curative radiation therapy were eligible for inclusion in the study. To assess patient-reported fatigue, quality of life questionnaires (European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-FA12) were distributed before treatment and 1, 3, 6, 12, 24, and 60 months after the start of treatment. Mean dose (Dmean) and near maximum dose (D2%) of the cerebellum and brain stem were evaluated in relation to baseline-adjusted fatigue scores at 3 months. Results: One hundred twenty-six patients treated with intensity modulated radiation therapy between 2008 and 2010 were available for final analysis. Female sex and age <60 years were associated with higher fatigue at baseline, whereas patients also treated with chemotherapy had reduced physical and emotional fatigue at 6 months. Physical fatigue (QLQ-FA12 scale) increased from baseline up to 3 months (29 vs 59; P < .0001) but showed no difference compared with baseline from 1 to 5 years. Emotional fatigue was significantly lower at 5 years compared with baseline (14 vs 28; P < .0001). Patients with cerebellum Dmean > 3.5 Gy had higher mean physical fatigue scores at 3 months (38 vs 27; P = .036). Conclusions: Although there is a significant increase in fatigue scores for patients with HNC up to 1 year after radiation therapy, this study showed a return to baseline levels at 5 years. A possible association was found between physical fatigue and a higher mean dose to the cerebellum.
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8.
  • Abel, Edvard, 1970, et al. (författare)
  • Impact on quality of life of IMRT versus 3-D conformal radiation therapy in head and neck cancer patients: A case control study
  • 2017
  • Ingår i: Advances in Radiation Oncology. - : Elsevier BV. - 2452-1094. ; 2:3, s. 346-353
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective The purpose of this study was to prospectively and longitudinally compare the health-related quality of life (HRQOL) outcomes between head and neck (HN) cancer patients treated with parotid-sparing intensity modulated radiation therapy (IMRT) and patients treated with 3-dimensional conventional radiation therapy (3D-CRT). Methods and materials Before and up to 12 months after treatment, HRQOL was recorded in patients with HN cancer who were referred to the Department of Oncology at Sahlgrenska University Hospital for curative IMRT. The study group's HRQOL was compared with a matched group of patients from previous descriptive HRQOL studies treated with 3D-CRT. Both groups' HRQOL was measured by the European Organization for Research and Treatment for Cancer QLQ-C30 and European Organization for Research and Treatment for Cancer QLQ-HN35 at 6 time points in the first year after diagnosis. Results Two hundred and seven patients were included, 111 treated with IMRT and 96 matched controls treated with 3D-CRT. Both groups' HRQOL deteriorated during and after treatment. Just after treatment, worse HRQOL scores were observed in the IMRT group regarding insomnia (38 vs 27; P = .032), appetite loss (64 vs 50; P = .019), senses (54 vs 41; P = .017), and coughing (39 vs 26, P = .009). At 12 months, however, significantly better HRQOL scores were observed in the IMRT group regarding problems with dry mouth (72 vs 62; P = .018), pain (28 vs 20; P = .018), sexuality (37 vs 23; P = .016), social contacts (10 vs 6; P = .026), cognitive functioning (79 vs 87; P = .0057), and financial difficulties (12 vs 20; P = .0019). Conclusions This study further supports the hypothesis that the introduction of IMRT has improved the long-term quality of life of HN cancer patients who have been treated with radiation therapy, but might cause more acute side effects. Longer follow-up is needed to study late complications.
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9.
  • Abel, Edvard, 1970, et al. (författare)
  • Long-Term Aspects of Quality of Life in Head and Neck Cancer Patients Treated With Intensity Modulated Radiation Therapy: A 5-Year Longitudinal Follow-up and Comparison with a Normal Population Cohort
  • 2020
  • Ingår i: Advances in Radiation Oncology. - : Elsevier BV. - 2452-1094. ; 5:1, s. 101-110
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2019 The Author(s) Purpose: Knowledge of long-term health-related quality of life (HRQOL) in patients with advanced head and neck cancer treated with intensity modulated radiation therapy is scarce. Methods and Materials: HRQOL in 126 patients with advanced head and neck cancer treated with intensity modulated radiation therapy was followed longitudinally from diagnosis to 5 years after treatment with the European Organization for Research and Treatment of Cancer's QLQ-C30, the European Organization for Research and Treatment of Cancer's Head and Neck Cancer Module, and the M.D. Anderson Dysphagia Inventory. The survivors' HRQOL was compared with an age- and sex-matched normal population cohort. Results: At 5 years, 73 of the 95 surviving patients had completed the study. Significant reductions in general pain (29 vs 12), head and neck (HN) pain (22 vs 14), and feeling ill (20 vs 10) were found, and emotional functioning (70 vs 83) and global quality of life (67 vs 74) improved, compared with baseline values. Conversely, dry mouth (19 vs 56), senses (8 vs 27), teeth problems (10 vs 22), opening mouth (19 vs 56), and sticky saliva (15 vs 40) were markedly worse, although significant improvements had occurred over time after treatment. Anderson Dysphagia Inventory scores >80 at 5 years indicated good swallowing function. In a subgroup analysis, dry mouth and senses were significantly better in patients treated with chemoradiotherapy. Comparison to a normal population cohort's HRQOL shows that the study group experienced a wide array of symptoms affecting their quality of life. Conclusions: The results of this large, long-term follow-up study show that a majority of patients report a reasonable quality of life 5 years after treatment and that there seems to be continuous improvement over time. Comparison with a normal population cohort, however, underlines the fact that classical side effects remain, even with improved radiation techniques. Additional emphasis on normal-tissue-sparing radiation therapy is warranted, with close attention devoted to HRQOL outcomes.
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10.
  • Alm, Jan, 1947- (författare)
  • Dyslexia: Relevance of Concepts, Validity of Measurements, and Cognitive Functions
  • 2004
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The thesis opens with an exposition of different uses of the term dyslexia. In that context its conceptual relevance is discussed. The empirical studies investigate a) different aspects of validity of cognitive and achievement instruments often used in diagnostic assessment of dyslexia, b) different cognitive profiles for adults with dyslexia, and c) the relationship between cognitive and achievement measures.Study I demonstrated the factor structure of the Swedish WAIS-R to be in close agreement with results of comparable analyses on normal and clinical groups in many countries world-wide, giving strong support for the construct validity of the Swedish WAIS-R for a group of adults diagnosed with dyslexia. The results from the three-factor solution were interpreted in terms of theoretical constructs, notably those posited by Carroll (1993) and Horn (1989).The cognitive profiles of a sample of Swedish adults diagnosed with dyslexia—when using the three factors, the ACID profile, and the four-category Bannatyne profile—all resemble closely the profiles observed for a wide array of U.S. samples of children and adults diagnosed with dyslexia or learning disabilities. Gender differences on Digit Symbol, favoring females, were substantial in magnitude for the present sample, consistent with a bulk of research on gender differences for samples of normal individuals and of those identified with learning problems.In Study II, factor analysis of nine Swedish achievement tests often used for dyslexia assessment yielded five meaningful factors in a group of adults diagnosed with dyslexia. Factors appeared to measure decoding, visual speed, reading comprehension, reading fluency, and phonological ability. The relationship between the five achievement factors and WAIS-R variables was subsequently examined. The Visual Speed and Reading Comprehension factors each correlated significantly with four of six global WAIS-R scores (two of three IQs and two of three factor scores). Visual Speed tended to correlate significantly with nonverbal scores and Reading Comprehension with verbal scores. Although the Phonological Ability factor did not correlate significantly with any verbal or nonverbal global score, it did correlate significantly with the Freedom from Distractibility factor and with all its component subtests—Digit Span, Arithmetic, and Digit Symbol. Decoding (technical reading skill) showed no significant relationship to any WAIS-R variable studied. More surprisingly, the Reading Fluency factor failed to show significant relationships to the WAIS-R.Study III examined the validity of The Word Chain Test, a frequently used instrument in Swedish screening and diagnostic assessments of dyslexia. Different sources of validity evidence were evaluated. In summary, the results failed to support validity both for the WRI-index and the Wordchain subtest, suggesting that the instrument seems to be of questionable value in screening or diagnostic assessment of dyslexia.
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11.
  • Axelsson, Lars, et al. (författare)
  • Effect of prophylactic percutaneous endoscopic gastrostomy tube on swallowing in advanced head and neck cancer: A randomized controlled study.
  • 2017
  • Ingår i: Head & neck. - : Wiley. - 1097-0347 .- 1043-3074. ; 39:5, s. 908-915
  • Tidskriftsartikel (refereegranskat)abstract
    • Dysphagia is common in head and neck cancer. A percutaneous endoscopic gastrostomy (PEG) tube is used to facilitate nutrition; however, some retrospective studies have indicated that the PEG tube causes dysphagia.A randomized study of patients with head and neck cancer was conducted with up to 10 years of follow-up. Patients were randomized to either the prophylactic PEG tube group (study group) or the common clinical nutritional support group (control group). At each follow-up, a dietician assessed the oral intake, noted the patients' weight, and if the patients used a PEG tube. Dysphagia was also assessed by the quality of life questionnaire, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Head and Neck 35-questions (EORTC-QLQ-H&N35).One hundred thirty-four patients were included in this study. There was no significant difference in swallowing function between the groups after 12 months, 24 months, and 8 years based on the EORTC-QLQ-H&N35, the oral intake scale, tube dependence, esophageal intervention, weight, body mass index (BMI), and overall survival.A prophylactic PEG tube can be used without an increased risk of long-term dysphagia in patients with head and neck cancer. © 2017 Wiley Periodicals, Inc. Head Neck, 2017.
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12.
  • Axelsson, Lars, et al. (författare)
  • Prognostic factors for head and neck cancer of unknown primary including the impact of human papilloma virus infection
  • 2017
  • Ingår i: Journal of Otolaryngology-Head & Neck Surgery. - : Springer Science and Business Media LLC. - 1916-0216. ; 46
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Head and neck cancer of unknown primary (HNCUP) is rare and prospective studies are lacking. The impact of different prognostic factors such as age and N stage is not completely known, the optimal treatment is not yet established, and the reported survival rates vary. In the last decade, human papilloma virus (HPV) has been identified as a common cause of and important prognostic factor in oropharyngeal cancer, and there is now growing interest in the importance of HPV for HNCUP. The aim of the present study on curatively treated HNCUP was to investigate the prognostic importance of different factors, including HPV status, treatment, and overall survival. Methods: A search for HNCUP was performed in the Swedish Cancer Registry, Western health district, between the years 1992-2009. The medical records were reviewed, and only patients with squamous cell carcinoma or undifferentiated carcinoma treated with curative intent were included. The tumor specimens were retrospectively analyzed for HPV with p16 immunostaining. Results: Sixty- eight patients were included. The mean age was 59 years. The majority were males, and had N2 tumors. Sixty-nine percent of the tumors were HPV positive using p16 staining. Patients who were older than 70 years, patients with N3-stage tumors, and patients with tumors that were p16 negative had a significantly worse prognosis. The overall 5-year survival rate for patients with p16-positive tumors was 88% vs 61% for p16- negative tumors. Treatment with neck dissection and postoperative radiation or (chemo) radiation had 81 and 88% 5- year survival rates, respectively. The overall and disease- free 5-year survival rates for all patients in the study were 82 and 74%. Conclusions: Curatively treated HNCUP had good survival. HPV infection was common. Independent prognostic factors for survival were age over 70 years, HPV status and N3 stage. We recommend that HPV analysis should be performed routinely for HNCUP. Treatment with neck dissection and postoperative radiation or (chemo) radiation showed similar survival rates.
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13.
  • Axelsson, Lars, et al. (författare)
  • Swedish National Multicenter Study on Head and Neck Cancer of Unknown Primary: Prognostic Factors and Impact of Treatment on Survival
  • 2021
  • Ingår i: International Archives of Otorhinolaryngology. - : Georg Thieme Verlag KG. - 1809-9777 .- 1809-4864. ; 25:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction Head and neck cancer of unknown primary (HNCUP) is a rare condition whose prognostic factors that are significant for survival vary between studies. No randomized treatment study has been performed thus far, and the optimal treatment is not established. Objective The present study aimed to explore various prognostic factors and compare the two main treatments for HNCUP: neck dissection and (chemo) radiation vs primary (chemo) radiation. Methods A national multicenter study was performed with data from the Swedish Head and Neck Cancer Register (SweHNCR) and from the patients' medical records from 2008 to 2012. Results Two-hundred and sixty HNCUP patients were included. The tumors were HPVpositive in 80%. The overall 5-year survival rate of patients treated with curative intent was 71%. Age (p < 0.001), performance status (p = 0.036), and N stage (p = 0.046) were significant factors for overall survival according to the multivariable analysis. Treatment with neck dissection and (chemo) radiation (122 patients) gave an overall 5-year survival of 73%, and treatment with primary (chemo) radiation (87 patients) gave an overall 5-year survival of 71%, with no significant difference in overall or disease-free survival between the 2 groups. Conclusions Age, performance status, and N stage were significant prognostic factors. Treatment with neck dissection and ( chemo) radiation and primary (chemo)
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14.
  • Aziz, Luaay, 1963, et al. (författare)
  • T but not N stage predicts survival for patients with tonsillar carcinoma treated with external radiotherapy and brachytherapy
  • 2010
  • Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 49:6, s. 821-825
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Our aim was to determine the efficacy of a therapeutic schedule including external radiation and brachytherapy in a consecutive and retrospective series of tonsillar carcinoma patients. Patients and methods. Ninety-six patients with tonsillar carcinoma were treated between 1988 and 2000 and were followed up for at least for three years. All patients were treated with accelerated hyperfractionated external radiotherapy, 68 patients had additional brachytherapy and 69 patients with advanced stages also received chemotherapy. There was no planned surgery even though 73% had N+ disease. Eleven patients with persistent neck nodes underwent ultimate salvage surgery. Results. The overall three-year survival (OS) was 70%. OS for the T stage was T1 90%, T2 89%, T3 54% and T4 60%. The corresponding numbers for the N stage were N0 61.5%, N1 73%, N2 78% and N3 66%. Accordingly OS was influenced by the T stage (p>0.001) rather than by N stage. Only four patients with salvage surgery had viable tumour cells in the specimen, their survival was not inferior. Discussion. The primary tumour stage is an essential determinant for survival in patients with irradiated tonsillar carcinoma. Neck dissection should be confined only as a salvage procedure.
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15.
  • Baumann, Pia, et al. (författare)
  • Factors important for efficacy of stereotactic body radiotherapy of medically inoperable stage I lung cancer. A retrospective analysis of patients treated in the Nordic countries.
  • 2006
  • Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 45:7, s. 787-95
  • Tidskriftsartikel (refereegranskat)abstract
    • We reviewed results of SBRT treatment of 138 patients with medically inoperable stage I NSCLC treated during 1996-2003 at five different centres in Sweden and Denmark. Mean age was 74 years (range 56-90) with 69 men and 72 women. SBRT was delivered using a 3D conformal multifield technique and a stereotactic body frame. Doses delivered were 30-48 Gy (65% isodose at the periphery of planning target volume, PTV) in 2-4 fractions. Equivalent dose in 2 Gy fractions (EQD2) was in the range of 50-100 Gy. Mean gross tumour volume (GTV) was 39 cm3 (2-436), and planning target volume was 101 cm3 (11-719). Overall response rate (CR, PR) was 61% (84/138). SD was noted in 36% (50/138). During a median follow-up period of 33 months (1-107), 16 (12%) local failures occurred, ten of which also included distant metastases. Local failure was associated with tumour size, target definition and central or pleura proximity. Distant metastases occurred in 25% (35/138) of the patients. Ninety-one (65%) patients died during follow-up of which 55 patients (60%) died of other causes than lung cancer. Three- and 5-year overall survival was 52 and 26% respectively. Lung cancer specific 3- and 5-year overall survival was 66 and 40% respectively. Fifty nine percent (83/138) of the patients had no side effects. Fourteen patients experienced grade 3-4 toxicity according to radiation therapy oncology group (RTOG). EQD2 (> v.s.<55.6 Gy) showed a statistically significant benefit survival for the higher doses. SBRT for stage I NSCLC results in favourable local control not inferior to fractionated RT and with acceptable toxicity.
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16.
  • Baumann, Pia, et al. (författare)
  • Outcome in a prospective phase II trial of medically inoperable stage I non-small-cell lung cancer patients treated with stereotactic body radiotherapy.
  • 2009
  • Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755 .- 0732-183X. ; 27:20, s. 3290-6
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: The impact of stereotactic body radiotherapy (SBRT) on 3-year progression-free survival of medically inoperable patients with stage I non-small-cell lung cancer (NSCLC) was analyzed in a prospective phase II study. PATIENTS AND METHODS: Fifty-seven patients with T1NOMO (70%) and T2N0M0 (30%) were included between August 2003 and September 2005 at seven different centers in Sweden, Norway, and Denmark and observed up to 36 months. SBRT was delivered with 15 Gy times three at the 67% isodose of the planning target volume. RESULTS: Progression-free survival at 3 years was 52%. Overall- and cancer-specific survival at 1, 2, and 3 years was 86%, 65%, 60%, and 93%, 88%, 88%, respectively. There was no statistically significant difference in survival between patients with T1 or T2 tumors. At a median follow-up of 35 months (range, 4 to 47 months), 27 patients (47%) were deceased, seven as a result of lung cancer and 20 as a result of concurrent disease. Kaplan-Meier estimated local control at 3 years was 92%. Local relapse was observed in four patients (7%). Regional relapse was observed in three patients (5%). Nine patients (16%) developed distant metastases. The estimated risk of all failure (local, regional, or distant metastases) was increased in patients with T2 (41%) compared with those with T1 (18%) tumors (P = .027). CONCLUSION: With a 3-year local tumor control rate higher than 90% with limited toxicity, SBRT emerges as state-of-the-art treatment for medically inoperable stage I NSCLC and may even challenge surgery in operable instances.
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17.
  • Baumann, Pia, et al. (författare)
  • Stereotactic body radiotherapy for medically inoperable patients with stage I non-small cell lung cancer - a first report of toxicity related to COPD/CVD in a non-randomized prospective phase II study.
  • 2008
  • Ingår i: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 88:3, s. 359-67
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND AIMS: In a retrospective study using stereotactic body radiotherapy (SBRT) in medically inoperable patients with stage I NSCLC we previously reported a local control rate of 88% utilizing a median dose of 15Gyx3. This report records the toxicity encountered in a prospective phase II trial, and its relation to coexisting chronic obstructive pulmonary disease (COPD) and cardio vascular disease (CVD). MATERIAL AND METHODS: Sixty patients were entered in the study between August 2003 and September 2005. Fifty-seven patients (T1 65%, T2 35%) with a median age of 75 years (59-87 years) were evaluable. The baseline mean FEV1% was 64% and median Karnofsky index was 80. A total dose of 45Gy was delivered in three fractions at the 67% isodose of the PTV. Clinical, pulmonary and radiological evaluations were made at 6 weeks, 3, 6, 9, 12, 18, and 36 months post-SBRT. Toxicity was graded according to CTC v2.0 and performance status was graded according to the Karnofsky scale. RESULTS: At a median follow-up of 23 months, 2 patients had relapsed locally. No grade 4 or 5 toxicity was reported. Grade 3 toxicity was seen in 12 patients (21%). There was no significant decline of FEV1% during follow-up. Low grade pneumonitis developed to the same extent in the CVD 3/17 (18%) and COPD 7/40 (18%) groups. The incidence of fibrosis was 9/17 (53%) and pleural effusions was 8/17 (47%) in the CVD group compared with 13/40 (33%) and 5/40 (13%) in the COPD group. CONCLUSION: SBRT for stage I NSCLC patients who are medically inoperable because of COPD and CVD results in a favourable local control rate with a low incidence of grade 3 and no grade 4 or 5 toxicity.
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18.
  • Berg, Malin, 1976, et al. (författare)
  • A randomized study comparing the nutritional effects of radiotherapy with cetuximab versus cisplatin in patients with advanced head and neck cancer
  • 2024
  • Ingår i: HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK. - 1043-3074 .- 1097-0347. ; 46:4, s. 760-771
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundHead and neck cancer (HNC) patients have a high risk of developing malnutrition. This randomized study aimed to compare the effect of weekly cisplatin or cetuximab combined with radiotherapy on weight loss at 3 months after treatment was started. Secondary outcomes were the prevalence of malnutrition using the Global Leadership Initiative on Malnutrition (GLIM) criteria, feeding tube dependence and health related quality of life from a nutritional perspective.MethodsPatients from the ARTSCAN III study with advanced HNC were assessed for weight, body composition, enteral tube dependence and selected quality-of-life scores (EORTC QLQ-C30 and QLQ-H&N35) at diagnosis and 6 weeks 3, 6 and 12 months after treatment initiation.ResultsOf the 80 patients, 38 and 42 were randomized to receive cetuximab and cisplatin treatment, respectively. There was no significant difference in weight loss at 3 months between the two study groups. However, the cetuximab group had significantly less weight loss, fewer enteral feeding tubes and better physical functioning at the end of treatment but more pain-related problems 3 months after treatment initiation. No differences between the groups were found at 6 and 12 months. The prevalence of malnutrition was not significantly different at any time point.ConclusionThe hypothesized benefit of concomitant treatment with cetuximab over cisplatin regarding the prevalence of malnutrition was not supported by this study.
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19.
  • Berg, Malin, 1976, et al. (författare)
  • Fatigue in Long-Term Head and Neck Cancer Survivors From Diagnosis Until Five Years After Treatment
  • 2023
  • Ingår i: Laryngoscope. - : Wiley. - 0023-852X.
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Fatigue due to cancer is a challenging symptom that might be long-lasting after cancer treatment. The aim of this study was to follow the development of fatigue among head and neck cancer (HNC) patients prospectively and longitudinally and to analyze predictors for acute and chronic fatigue. Methods: HNC patients treated with curative intent were included at diagnosis and completed the following questionnaires multiple times, up to 5 years after treatment: the EORTC QLQ-FA12 for fatigue, EORTC QLQ-C30, and HNC-specific EORTC QLQ-H&N35 together with an anxiety and depression questionnaire. Predictors of fatigue were evaluated at 3 months and 5 years after treatment. Results: Of the 311 study participants, 74% responded at the 5-year follow-up. Physical fatigue was significantly worse 3 months after treatment, while emotional and cognitive fatigue were the worst at diagnosis and at 3 months. All fatigue domains were significantly better after 1 year, and the fatigue scores remained stable from 1 until 5 years after treatment. Three months after chemoradiotherapy, physical fatigue was more significant, but no long-term differences due to treatment modalities were found. Depression and anxiety were predictors for chronic emotional fatigue, and local HN pain and swallowing problems were predictors for chronic physical fatigue. Better global quality of life at diagnosis was associated with less physical and emotional fatigue. Conclusion: Fatigue was worst in the short term for HNC patients and improved after 1 year, and long-term fatigue remained stable up to 5 years after treatment. A few predictors for chronic fatigue were found. Level of Evidence: 3 Laryngoscope, 2023. © 2023 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.
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20.
  • Berg, Malin, 1976, et al. (författare)
  • The effect of age on health-related quality of life for head and neck cancer patients up to 1 year after curative treatment
  • 2022
  • Ingår i: Journal of Geriatric Oncology. - : Elsevier BV. - 1879-4068. ; 13:1, s. 60-66
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The aim was to evaluate the effect of age on health-related quality of life (HRQOL) for patients with head and neck cancer (HNC), treated with curative intent, in the Western healthcare region of Sweden. Materials and Methods: In this prospective observational study, 311 HNC patients completed quality of life questionnaires for cancer (EORTC QLQ-C30 and EORTC QLQ-H&N35) and for older patients with cancer (EORT QLQELD14) at diagnosis and 3, 6, and 12 months after start of treatment. Mean scores for patients >_70 years old were compared to younger patients (50 to 69 years old) to assess differences in HRQOL. Results: Of the 311 study participants, 105 patients were >_70 years old (median age 76.7), of which 32 were >_80 years of age. Most HRQOL scores were equal or better for older adult patients at 3 months after treatment, but physical function was better for younger adult patients up to 12 months after treatment. At 6 months the HRQOL was similar (older patients had less appetite loss and financial difficulties), while the oldest patients (>_80 years) had worse fatigue, role function, and feeling ill at 12 months. For the EORTC-ELD-14 questionnaire, older patients scored better for worries at diagnosis and reported more difficulties in maintaining purpose at 12 months after treatment. Conclusion: When curative treatment is administered, older adult patients with HNC have similar or even better HRQOL compared to younger adult patients, except for physical function, during the first year. (c) 2021 Elsevier Ltd. All rights reserved.
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21.
  • Bergman, Bengt, 1953, et al. (författare)
  • Lungcancer
  • 2009
  • Ingår i: Lungmedicin Kap. 9. Sandström T & Eklund A red.. - 9789144008479 ; , s. 135-153
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
  •  
22.
  • Bergquist, Henrik, 1969, et al. (författare)
  • Combined stent insertion and single high-dose brachytherapy in patients with advanced esophageal cancer - results of a prospective safety study.
  • 2011
  • Ingår i: Diseases of the esophagus. - : Oxford University Press (OUP). - 1442-2050 .- 1120-8694. ; Early View
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous randomized studies comparing the two commonly used palliative treatments for incurable esophageal cancer, i.e. stent insertion and intraluminal brachytherapy, have revealed the pros and cons of each therapy. While stent treatment offers a more prompt effect, brachytherapy results in more long-lasting relief of dysphagia and a better health-related quality of life (HRQL) in those living longer. This prospective pilot study aimed to explore the feasibility and safety of combining these two regimes and incorporating a single high dose of internal radiation. Patients with newly diagnosed, incurable cancer of the esophagus and dysphagia were eligible for inclusion, and stent insertion followed by a single dose (12Gy) of brachytherapy was performed as a two-stage procedure. Clinical parameters including HRQL and adverse events were registered at inclusion, and 1, 2, 3, 6, and 12 months later. Twelve patients (nine males) with a median age of 73 years (range 54-85) were included. Stent insertion followed by a single dose of brachytherapy was successfully performed in all but one patient who was treated with stent only. Relief of dysphagia was achieved in the majority of cases (10/11, P < 0.05), but HRQL did not improve except for dysphagia-related items. Only minor adverse events, including chest pain, reflux, and restenosis, were reported. The median survival time after inclusion was 6.6 months. Our conclusion is that the combination of stent insertion and single high-dose brachytherapy seems to be a feasible and safe palliative regime in patients with advanced esophageal cancer. Randomized trials comparing the efficacy of this strategy to stent insertion or brachytherapy alone are warranted.
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23.
  •  
24.
  • Bergqvist, David, et al. (författare)
  • Svårkontrollerad blödning vid kirurgi - praktiska åtgärder
  • 2007
  • Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 104:6, s. 407-411
  • Tidskriftsartikel (refereegranskat)abstract
    • Difficult-to-control intraoperative bleeding--practical measures Bleeding with difficulties obtaining haemostasis can be a catastrophe. This paper summarizes a symposium with the above title. A short introduction gives the background of normal haemostasis as well as iatrogenic vascular injuries as reflected in the Swedish vascular registry (Swedvasc). Practical guidelines are given on how to manage situations of severe haemorrhage with the help of pharmacological substances, local haemostatics, endovascular methodology and open surgery.
  •  
25.
  • Björkblom, Benny, et al. (författare)
  • Constitutively Active Cytoplasmic c-Jun N-Terminal Kinase 1 Is a Dominant Regulator of Dendritic Architecture: Role of Microtubule-Associated Protein 2 as an Effector
  • 2005
  • Ingår i: Journal of Neuroscience. - : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 25:27, s. 6350-6361
  • Tidskriftsartikel (refereegranskat)abstract
    • Normal functioning of the nervous system requires precise regulation of dendritic shape and synaptic connectivity. Here, we report a severe impairment of dendritic structures in the cerebellum and motor cortex of c-Jun N-terminal kinase 1 (JNK1)-deficient mice. Using an unbiased screen for candidate mediators, we identify the dendrite-specific high-molecular-weight microtubule-associated protein 2 (MAP2) as a JNK substrate in the brain. We subsequently show that MAP2 is phosphorylated by JNK in intact cells and that MAP2 proline-rich domain phosphorylation is decreased in JNK1-/- brain. We developed compartment-targeted JNK inhibitors to define whether a functional relationship exists between the physiologically active, cytosolic pool of JNK and dendritic architecture. Using these, we demonstrate that cytosolic, but not nuclear, JNK determines dendritic length and arbor complexity in cultured neurons. Moreover, we confirm that MAP2-dependent process elongation is enhanced after activation of JNK. Using JNK1-/- neurons, we reveal a dominant role for JNK1 over ERK in regulating dendritic arborization, whereas ERK only regulates dendrite shape under conditions in which JNK activity is low (JNK1-/- neurons). These results reveal a novel antagonism between JNK and ERK, potentially providing a mechanism for fine-tuning the dendritic arbor. Together, these data suggest that JNK phosphorylation of MAP2 plays an important role in defining dendritic architecture in the brain.
  •  
26.
  • Björnberg, Olof, et al. (författare)
  • A Bifunctional dCTP Deaminase-dUTP Nucleotidohydrolase from the Hyperthermophilic Archaeon Methanocaldococcus jannaschii
  • 2003
  • Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 278:23, s. 20667-20672
  • Tidskriftsartikel (refereegranskat)abstract
    • By the sequential action of dCTP deaminase and dUTPase, dCTP is converted to dUMP, the precursor of thymidine nucleotides. In addition, dUTPase has an essential role as a safeguard against uracil incorporation in DNA. The putative dCTP deaminase (MJ0430) and dUTPase (MJ1102) from the hyperthermophilic archaeon Methanocaldococcus jannaschii were overproduced in Escherichia coli. Unexpectedly, we found the MJ0430 protein capable of both reactions, i.e. hydrolytic deamination of the cytosine ring and hydrolytic cleavage of the phosphoanhydride bond between the - and -phosphates. When the reaction was followed by thin layer chromatography using [3H]dCTP as substrate, dUMP and not dUTP was identified as a reaction product. In the presence of unlabeled dUTP, which acted as an inhibitor, no label was transferred from [3H]dCTP to the pool of dUTP. This finding strongly suggests that the two consecutive steps of the reaction are tightly coupled within the enzyme. The hitherto unknown bifunctionality of the MJ0430 protein appears beneficial for the cells because the toxic intermediate dUTP is never released. The MJ0430 protein also catalyzed the hydrolysis of dUTP to dUMP but with a low affinity for the substrate (Km >100 µM). According to limited proteolysis, the C-terminal residues constitute a flexible region. The other protein investigated, MJ1102, is a specific dUTPase with a Km for dUTP (0.4 µM) comparable in magnitude with that found for previously characterized dUTPases. Its physiological function is probably to degrade dUTP derived from other reactions in nucleotide metabolism.
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27.
  • Bratulic, Sinisa, 1981, et al. (författare)
  • Noninvasive detection of any-stage cancer using free glycosaminoglycans.
  • 2022
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:50
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer mortality is exacerbated by late-stage diagnosis. Liquid biopsies based on genomic biomarkers can noninvasively diagnose cancers. However, validation studies have reported ~10% sensitivity to detect stage I cancer in a screening population and specific types, such as brain or genitourinary tumors, remain undetectable. We investigated urine and plasma free glycosaminoglycan profiles (GAGomes) as tumor metabolism biomarkers for multi-cancer early detection (MCED) of 14 cancer types using 2,064 samples from 1,260 cancer or healthy subjects. We observed widespread cancer-specific changes in biofluidic GAGomes recapitulated in an in vivo cancer progression model. We developed three machine learning models based on urine (Nurine = 220 cancer vs. 360 healthy) and plasma (Nplasma = 517 vs. 425) GAGomes that can detect any cancer with an area under the receiver operating characteristic curve of 0.83-0.93 with up to 62% sensitivity to stage I disease at 95% specificity. Undetected patients had a 39 to 50% lower risk of death. GAGomes predicted the putative cancer location with 89% accuracy. In a validation study on a screening-like population requiring ≥ 99% specificity, combined GAGomes predicted any cancer type with poor prognosis within 18 months with 43% sensitivity (21% in stage I; N = 121 and 49 cases). Overall, GAGomes appeared to be powerful MCED metabolic biomarkers, potentially doubling the number of stage I cancers detectable using genomic biomarkers.
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28.
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29.
  • Brämerson, Annika, 1960, et al. (författare)
  • Olfactory loss after head and neck cancer radiation therapy
  • 2013
  • Ingår i: Rhinology. - 0300-0729 .- 1996-8604. ; 51:3, s. 206-209
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: A reduced sense of smell may be one explanation for why patients with cancer in the ear, nose and throat (ENT) region who are treated with radiation therapy lose weight. The purpose of this study was to investigate whether radiation therapy has a negative effect on olfactory function and, if so, whether this effect is dose-related.METHODOLOGY: Seventy-one patients were tested using odour-detection sensitivity and olfactory identification tests before radiation therapy and 20 months after it.RESULTS: Patients who received radiation close to the olfactory organ showed a reduced sense of smell, in both tests. A multiple regression analysis showed that the radiation dose was related to decline in the olfactory function, while age, sex, chemotherapy and interactions between these variables were not.CONCLUSION: Radiation therapy can damage olfactory cells.
  •  
30.
  • Bröchner, Jan, 1948, et al. (författare)
  • Outsourcing facilities services: needs and practices of Swedish owners of commercial property
  • 2004
  • Ingår i: Proceedings CIB W70 Facilities Management and Maintenance International Symposium, Hong Kong, 7-8 December 2004. ; , s. 395-400
  • Konferensbidrag (refereegranskat)abstract
    • Why and how facilities services are outsourced is a question that continues to attract interest. The purpose of this study has been to investigate links between categories of property owners and their demand for packaged facilities services. The empirical part is based on questionnaire responses from 20 large owners of commercial property in Sweden, and on interviews with 11 of these owners. Owners are characterized by portfolio value, geographical spread of properties, investment horizon, core business, and average tenant size. Three owner segments are identified and tentatively labelled Building Managers, Active Asset Managers, and Passive Asset Managers. Their outsourcing policies and practices differ clearly.
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31.
  •  
32.
  • Burnet, N G, et al. (författare)
  • Describing patients' normal tissue reactions: concerning the possibility of individualising radiotherapy dose prescriptions based on potential predictive assays of normal tissue radiosensitivity. Steering Committee of the BioMed2 European Union Concerted Action Programme on the Development of Predictive Tests of Normal Tissue Response to Radiation Therapy.
  • 1998
  • Ingår i: International journal of cancer. Journal international du cancer. - 0020-7136. ; 79:6, s. 606-13
  • Tidskriftsartikel (refereegranskat)abstract
    • Clinical radiotherapeutic doses are limited by the tolerance of normal tissues. Patients given a standard treatment exhibit a range of normal tissue reactions, and a better understanding of this individual variation might allow for individualisation of radiotherapeutic prescriptions, with consequent improvement in the therapeutic ratio. At present, there is no simple way to describe normal tissue reactions, which hampers communication between clinic and laboratory and between groups from different centres. There is also no method for comparing the severity of reactions in different normal tissues. This arises largely because there is no definition of a "normal" reaction, an "extreme" reaction or the particular term "over-reactor" (OR). This report proposes definitions for these terms, as well as a simple terminology for describing normal tissue reactions in patients having radiotherapy. The "normal" range represents the individual variation in normal tissue reactions amongst large numbers of patients treated in the same way which is within clinically acceptable limits. The term "OR" is applied to an individual whose reaction is more severe than the normal range but also implies that this forced a major change in the radiotherapeutic prescription or that the reactions were very severe or fatal. A "severe OR" would develop serious problems with a typical radical dose, while an "extreme OR" would have such difficulties at a much lower dose. To describe the normal range, a numerical scale is suggested, from 1 to 5, resistant to sensitive. The term "highly radiosensitive" (HR) is suggested for category 5. An "informal" relative scale, as suggested here, is quick and simple. It should allow comparison between different hospitals, compensate for differences in radiotherapeutic dose and technique and allow comparison of reactions between different anatomical sites. It should be adequate for discriminating patients at the extremes of the normal range from those at the centre. It is hoped that the definitions and terminology proposed here will aid communication in the field of predictive testing of normal tissue radiosensitivity.
  •  
33.
  • Burnet, N G, et al. (författare)
  • Normal tissue radiosensitivity--how important is it?
  • 1996
  • Ingår i: Clinical oncology (Royal College of Radiologists (Great Britain)). - 0936-6555. ; 8:1, s. 25-34
  • Tidskriftsartikel (refereegranskat)abstract
    • The success of radiotherapy in eradicating tumours depends on the total radiation dose, but what limits this dose is the tolerance of the normal tissues within the treatment volume. Selection of the appropriate dose for all patients is based on a balance between minimising the incidence of severe normal tissue complications and maximizing the probability of local control. In patients treated to the same radical dose, a wide range of reactions is seen; in many clinical situations, radical doses are limited by the minority of patients whose normal tissues are particularly sensitive. Clinical studies of radiotherapy reactions have demonstrated that a large part of the spectrum of normal tissue reactions, perhaps as much as 80%, is due to differences in individual normal tissue sensitivity. This suggests that it might be possible to measure this sensitivity and to change treatment accordingly. The main objective of normal tissue sensitivity testing is to permit dose escalation without increased normal tissue complication rates in patients with more resistant normal tissues. Calculations suggest that the most "resistant' 40% of patients could be dose escalated by 17%-18%, which is likely to be associated with significant gains in local control, perhaps by as much as 34%-36%; this should translate into an increase in overall survival. It should also be possible to identify those relatively few patients who suffer serious normal tissue morbidity with conventional doses. Thus, if successful, predictive testing of normal tissue response should improve the therapeutic ratio of radiotherapy.
  •  
34.
  • Burnet, N G, et al. (författare)
  • Prediction of normal-tissue tolerance to radiotherapy from in-vitro cellular radiation sensitivity.
  • 1992
  • Ingår i: Lancet. - 0140-6736. ; 339:8809, s. 1570-1
  • Tidskriftsartikel (refereegranskat)abstract
    • The success of radiotherapy depends on the total radiation dose, which is limited by the tolerance of surrounding normal tissues. Since there is substantial variation among patients in normal-tissue radiosensitivity, we have tested the hypothesis that in-vitro cellular radiosensitivity is correlated with in-vitro normal-tissue responses. We exposed skin fibroblast cell lines from six radiation-treated patients to various doses of radiation and measured the proportions surviving. There was a strong relation between fibroblast sensitivity in vitro and normal-tissue reactions, especially acute effects. Assessment of radiosensitivity could lead to improved tumour cure rates by enabling radiation doses to be tailored to the individual.
  •  
35.
  • Burnet, N G, et al. (författare)
  • The relationship between cellular radiation sensitivity and tissue response may provide the basis for individualising radiotherapy schedules.
  • 1994
  • Ingår i: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. - 0167-8140. ; 33:3, s. 228-38
  • Tidskriftsartikel (refereegranskat)abstract
    • There is a wide variation in normal tissue reactions to radiotherapy and in many situations the severity of these reactions limits radiotherapy dose. Clinical fractionation studies carried out in Gothenburg have demonstrated that a large part of the spectrum of normal tissue reactions is due to differences in individual normal tissue sensitivity. If this variation in normal tissue reactions is due to differences in intrinsic cellular radiosensitivity, it should be possible to predict tissue response based on measurement of cellular sensitivity. Here we report the initial results of a study aimed at establishing whether a direct relationship exists between cellular radiosensitivity and tissue response. Ten fibroblasts strains, including four duplicates, were established from a group of patients in the Gothenburg fractionation trials who had received radiotherapy following mastectomy. Skin doses were measured and both acute and late skin changes were observed following radiotherapy. Right and left parasternal areas were treated with different dose fractionation schedules. Clonogenic assays were used to assess intrinsic cellular radiosensitivity, and all experiments were carried out without prior knowledge of the clinical response, or which strains were duplicates. Irradiation was carried out using 60Co gamma-rays at high dose-rate (HDR) of 1-2 Gy/min and low dose-rate (LDR) of 1 cGy/min. A spectrum of sensitivity was seen, with SF2 values of 0.17-0.28 at HDR and 0.25-0.34 at LDR, and values of D0.01 of 5.07-6.38 Gy at HDR and 6.43-8.12 Gy at LDR. Comparison of the in vitro results with the clinical normal tissue effects shows a correlation between cellular sensitivity and late tissue reactions, which is highly significant with p = 0.02. A correlation between cellular sensitivity and acute effects was noted in the left-sided parasternal fields, but not the right. This is thought to be coincidental, and without biological significance. Our results suggest that cellular sensitivity might form the basis for the development of an assay system capable of predicting late normal tissue effects to curative radiotherapy, which might allow dose escalation in some patients. Increased local control and cure, with unchanged or improved normal tissue complications, could result from such individualised radiotherapy prescriptions.
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36.
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37.
  • Carlomagno, F, et al. (författare)
  • Comparison of DNA repair protein expression and activities between human fibroblast cell lines with different radiosensitivities.
  • 2000
  • Ingår i: International journal of cancer. Journal international du cancer. - 0020-7136. ; 85:6, s. 845-9
  • Tidskriftsartikel (refereegranskat)abstract
    • In order to investigate the molecular basis of variation in response to ionising radiation (IR) in radiotherapy patients, we have studied the expression of several genes involved in DNA double-strand break repair pathways in fibroblast cell lines. Ten lines were established from skin biopsies of cancer patients with different normal-tissue reactions to IR, and 3 from a control individual. For all 10 test cell lines, the cellular radiosensitivity was also known. Using Western blots we measured, in non-irradiated cells, the basal expression levels of ATM, Rad1 and Hus1, involved in the control of cellular DNA damage checkpoints, together with DNA-PKcs, Ku70, Ku80; XRCC4, ligaseIV and Rad51, involved in radiation- induced DSB repair. We also analysed the in vitro enzymatic activities, under non-irradiated conditions, of the DNA-PK and XRCC4/ligaseIV complexes. The levels of expression of the different proteins were similar in all the cell lines, but the activities of the DNA-PK and XRCC4/ligaseIV complexes showed some differences. These differences did not correlate with either the normal tissue response of the patient in vivo or with cellular radiation sensitivity in vitro. The activity differences of these enzyme complexes, therefore, do not account for the variation of responses seen between patients.
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38.
  • Carlström, Eric, 1957, et al. (författare)
  • The unannounced patient in the corridor - trust, friction and person centered care.
  • 2017
  • Ingår i: International Journal of Health Planning and Management. - : Wiley. - 0749-6753 .- 1099-1751. ; 32:1
  • Tidskriftsartikel (refereegranskat)abstract
    • In this study, a Swedish cancer clinic was studied where three to four unscheduled patients sought support from the hospital on a daily basis for pain and nutrition problems. The clinic was neither staffed nor had a budget to handle such return visits. In order to offer the patients a better service and decrease the workload of the staff in addition to their everyday activities, a multidisciplinary team was established to address the unscheduled return visits. The team was supposed to involve the patient, build trust, decrease the friction, and contribute to a successful rehabilitation process. Data were collected from the patients and the staff. Patients who encountered the team (intervention) and patients who encountered the regular ad hoc type of organization (control) answered a questionnaire measuring trust and friction. Nurses in the control group spent 35% of their full‐time employment, and the intervention group staffed with nurses spent 30% of their full‐time employment in addressing the needs of these return patients. The patients perceived that trust between them and the staff was high. In summary, it was measured as being 4.48 [standard deviation (SD) = 0.82] in the intervention group and 4.41 (SD = 0.79) in the control group using the 5‐point Likert scale. The data indicate that using a multidisciplinary team is a promising way to handle the problems of unannounced visits from patients. Having a team made it cost effective for the clinic and provided a better service than the traditional ad hoc organization.
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39.
  • Cederholm, Tommy, et al. (författare)
  • Forskaren, samhället och jäv
  • 2008
  • Ingår i: Läkartidningen. - 0023-7205. ; 105:16, s. 7-1206
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
  •  
40.
  •  
41.
  • Davidsson, Jan, et al. (författare)
  • Structural determination of a transient isomer of CH2I2 by picosecond x-ray diffraction
  • 2005
  • Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 94:24
  • Tidskriftsartikel (refereegranskat)abstract
    • Ultrafast time-resolved spectroscopic studies of complex chemical reactions in solution are frequently hindered by difficulties in recovering accurate structural models for transient photochemical species. Time-resolved x-ray and electron diffraction have recently emerged as techniques for probing the structural dynamics of short lived photointermediates. Here we determine the structure of a transient isomer of photoexcited CH2I2 in solution and observe the downstream reactions of the initial photoproducts. Our results illustrate how geminate recombination proceeds via the formation of a transient covalent bond onto the iodine atom remaining with the parent molecule. Further intramolecular rearrangements are thus required for the CH2I-I isomer to return to CH2I2. The generation of I-3(-) from those iodine radicals escaping the solvent cage is also followed with time.
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42.
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43.
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44.
  • Djärv, Emma, et al. (författare)
  • Dummy run for a phase II study of stereotactic body radiotherapy of T1-T2 N0M0 medical inoperable non-small cell lung cancer.
  • 2006
  • Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 45:7, s. 973-7
  • Tidskriftsartikel (refereegranskat)abstract
    • In forthcoming multicentre studies on stereotactic body radiotherapy (SBRT) compliance with volume and dose prescriptions will be mandatory to avoid unnecessary heterogeneity bias. To evaluate compliance in a multicentre setting we used two cases from an ongoing phase II study of SBRT of T1-T2N0M0 inoperable NSCLC in a dummy run oriented on volumes and doses. Six Scandinavian centres participated. Each centre received CT-scans covering the whole lung volumes of two patients with instructions to follow the study protocol when outlining tumour and target volumes, prescribing doses and creating dose plans. Volumes and doses of the 12 dose plans were evaluated according to the study protocol. For the two patients the GTV volume range was 24 to 39 cm3 and 26 to 41 cm3, respectively. The PTV volume range was 90 to 116 cm3, and 112 to 155 cm3, respectively. For all plans the margin between CTV and PTV in all directions followed in detail the protocol. The prescribed dose was for all centres 45 Gy/3 fractions (isocentre dose about 66 Gy). The mean GTV doses ranged from 63 to 67 Gy and from 63 to 68 Gy, respectively. The minimum doses for GTV were between 50-64 Gy and between 55-65 Gy, respectively. The dose distribution was conformed to PTV for 10 of 12 plans and 2 of 12 plans from one centre had sub-optimal dose distribution. Most of the volume and dose parameters for the participating centres showed fully acceptable compliance with the study protocol.
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45.
  • Ek, Anna, et al. (författare)
  • A Parent Treatment Program for Preschoolers With Obesity : A Randomized Controlled Trial
  • 2019
  • Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 0031-4005 .- 1098-4275. ; 144:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background And Objectives: Early obesity treatment seems to be the most effective, but few treatments exist. In this study, we examine the effectiveness of a parent-only treatment program with and without booster sessions (Booster or No Booster) focusing on parenting practices and standard treatment (ST).Methods: Families of children 4 to 6 years of age with obesity were recruited from 68 child care centers in Stockholm County and randomly assigned to a parent-only program (10 weeks) with or without boosters (9 months) or to ST. Treatment effects on primary outcomes (BMI z score) and secondary outcomes (BMI and waist circumference) during a 12-month period were examined with linear mixed models. The influence of sociodemographic factors was examined by 3-way interactions. The clinically significant change in BMI z score (−0.5) was assessed with risk ratios.Results: A total of 174 children (mean age: 5.3 years [SD = 0.8]; BMI z score: 3.0 [SD = 0.6], 56% girls) and their parents (60% foreign background; 39% university degree) were included in the analysis (Booster, n = 44; No Booster, n = 43; ST, n = 87). After 12 months, children in the parent-only treatment had a greater reduction in their BMI z score (0.30; 95% confidence interval [CI]: −0.45 to −0.15) compared with ST (0.07; 95% CI: −0.19 to 0.05). Comparing all 3 groups, improvements in weight status were only seen for the Booster group (−0.54; 95% CI: −0.77 to −0.30). The Booster group was 4.8 times (95% CI: 2.4 to 9.6) more likely to reach a clinically significant reduction of ≥0.5 of the BMI z score compared with ST.Conclusion: A parent-only treatment with boosters outperformed standard care for obesity in preschoolers.
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46.
  • Eklund, Ella A, et al. (författare)
  • KRAS mutations impact clinical outcome in metastatic non-small cell lung cancer.
  • 2022
  • Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:9
  • Tidskriftsartikel (refereegranskat)abstract
    • There is an urgent need to identify new predictive biomarkers for treatment response to both platinum doublet chemotherapy (PT) and immune checkpoint blockade (ICB). Here, we evaluated whether treatment outcome could be affected by KRAS mutational status in patients with metastatic (Stage IV) non-small cell lung cancer (NSCLC). All consecutive patients molecularly assessed and diagnosed between 2016-2018 with Stage IV NSCLC in the region of West Sweden were included in this multi-center retrospective study. The primary study outcome was overall survival (OS). Out of 580 Stage IV NSCLC patients, 35.5% harbored an activating mutation in the KRAS gene (KRASMUT). Compared to KRAS wild-type (KRASWT), KRASMUT was a negative factor for OS (p = 0.014). On multivariate analysis, KRASMUT persisted as a negative factor for OS (HR 1.478, 95% CI 1.207-1.709, p < 0.001). When treated with first-line platinum doublet (n = 195), KRASMUT was a negative factor for survival (p = 0.018), with median OS of 9 months vs. KRASWT at 11 months. On multivariate analysis, KRASMUT persisted as a negative factor for OS (HR 1.564, 95% CI 1.124-2.177, p = 0.008). KRASMUT patients with high PD-L1 expression (PD-L1high) had better OS than PD-L1highKRASWT patients (p = 0.036). In response to first-line ICB, KRASMUT patients had a significantly (p = 0.006) better outcome than KRASWT patients, with a median OS of 23 vs. 6 months. On multivariable Cox analysis, KRASMUT status was an independent prognostic factor for better OS (HR 0.349, 95% CI 0.148-0.822, p = 0.016). kRAS mutations are associated with better response to treatment with immune checkpoint blockade and worse response to platinum doublet chemotherapy as well as shorter general OS in Stage IV NSCLC.
  •  
47.
  • Ertzgaard, Per, 1958-, et al. (författare)
  • Oculomotor screening and neuro-visual rehabilitation following pediatric brain tumor resection
  • 2023
  • Ingår i: Journal of Pediatric Rehabilitation Medicine. - : Ios press. - 1874-5393 .- 1875-8894. ; , s. 1-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Visual difficulties are common after brain tumors, despite a lack of visual complaints at diagnosis. These include difficulties with eye movements, visual coordination, vergence, accommodation, and photophobia, in addition to more obvious problems such as visual field defects.This case report presents the results of a thorough neuro-visual evaluation in a boy with sequelae after a brain tumor including intermittent double vision that was not explained by routine visual examination. Subjective complaints included poor reading perseverance, intermittent blurred and double vision, headache around the eyes when performing near activities, less efficient eye movement behavior in reading tasks, and increased sensitivity to visual motion. The patient participated in a multidisciplinary visual rehabilitation program that included reading glasses with prism compensation and tinted glasses, as well as training with the aim of improving eye teaming, near vision functions, and perseverance in eye movements.The patient responded quickly to the vision therapy program, with positive changes after just four weeks. Repeated neuro-visual evaluations over eight months showed remarkable improvements that were stable over time. This encouraging case report supports the notion that neuro-visual evaluation and rehabilitation should be included in the follow-up of patients after brain tumors.
  •  
48.
  • Fernström, Erik, et al. (författare)
  • Cerebrospinal fluid markers of extracellular matrix remodelling, synaptic plasticity and neuroinflammation before and after cranial radiotherapy
  • 2018
  • Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820. ; 284:2, s. 211-225
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Advances in the treatment of brain tumours have increased the number of long-term survivors, but at the cost of side effects following cranial radiotherapy ranging from neurocognitive deficits to outright tissue necrosis. At present, there are no tools reflecting the molecular mechanisms underlying such side effects, and thus no means to evaluate interventional effects after cranial radiotherapy. Therefore, fluid biomarkers are of great clinical interest. Objective Cerebrospinal fluid (CSF) levels of proteins involved in inflammatory signalling, synaptic plasticity and extracellular matrix (ECM) integrity were investigated following radiotherapy to the brain. Methods Patients with small-cell lung cancer (SCLC) eligible for prophylactic cranial irradiation (PCI) were asked to participate in the study. PCI was prescribed either as 2 Gy/fraction to a total dose of 30 Gy (limited disease) or 4 Gy/fraction to 20 Gy (extensive disease). CSF was collected by lumbar puncture at baseline, 3 months and 1 year following PCI. Protein concentrations were measured using immunobased assays or mass spectrometry. Results The inflammatory markers IL-15, IL-16 and MCP-1/CCL2 were elevated in CSF 3 months following PCI compared to baseline. The plasticity marker GAP-43 was elevated 3 months following PCI, and the same trend was seen for SNAP-25, but not for SYT1. The investigated ECM proteins, brevican and neurocan, showed a decline following PCI. There was a strong correlation between the progressive decline of soluble APP and brevican levels. Conclusion To our knowledge, this is the first time ECM-related proteins have been shown to be affected by cranial radiotherapy in patients with cancer. These findings may help us to get a better understanding of the mechanisms behind side effects following radiotherapy.
  •  
49.
  • Fernström, Erik, et al. (författare)
  • Results of preoperative chemoradiotherapy for patients with advanced cancer of the nasal cavity and paranasal sinuses.
  • 2017
  • Ingår i: Acta oto-laryngologica. - : Informa UK Limited. - 1651-2251 .- 0001-6489. ; 137:12, s. 1292-1300
  • Tidskriftsartikel (refereegranskat)abstract
    • Curative treatment of nasal cavity and paranasal sinus cancer is challenging due to the proximity to critical anatomical structures. The purpose of this study was to analyze the impact of trimodality therapy with preoperative chemotherapy and reduced-dose radiotherapy followed by organ-preserving surgery for treating patients with nasal cavity and paranasal sinus cancer.This retrospective study included all 156 patients diagnosed with sinonasal cancer in western Sweden between 1986 and 2009. We determined the treatment selection pattern and treatment outcomes for 79 patients treated with preoperative chemoradiotherapy.Squamous cell carcinoma was the most common histology. The five-year overall survival was 54%, and 85% of these patients had T3 or T4 tumors. The five-year cumulative incidence rate of local recurrence was 32%. The five-year overall survival in patients with squamous cell carcinoma and adenocarcinoma was 45% and 76%, respectively. The median preoperative radiation dose was 48Gy. Orbital exenteration was performed in 7% of patients.Preoperative chemoradiotherapy may be beneficial for patients with advanced sinonasal cancer when primary radical surgery is challenging. Survival outcomes were comparable to outcomes reported in the literature despite conservative surgery and relatively low radiation doses in patients with locally advanced tumors.
  •  
50.
  • Fessé, Per, 1973- (författare)
  • Epidermal Melanocyte Response to Radiotherapy
  • 2021
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Cutaneous interfollicular melanocytes protect the skin from UV-radiation (UVR), and their response to UVR is well established. To date, the response activated in melanocytes by repeated genotoxic insults from radiotherapy (RT) has not been explored. Assuming that the molecular pathways involved in the melanocyte response to UVR are similar upon ionizing radiation, the aim of this work was to examine the effects of RT concerning UVR-response proteins and resistance to DNA damage to reveal mechanisms behind hyperpigmentation and depigmentation caused by RT. The results are based on immunostained tissue sections of 530 not sun-exposed skin punch biopsies. These are collected before, during, and after the end of adjuvant RT from the thoracic wall of breast cancer patients and the hip region of prostate cancer patients receiving curative RT. Fractionated RT with daily doses between 0.05 and 2.0 Gy, as well as hypofractionation and accelerated fractionation were investigated. Based on this clinical assay sterilizing the hair follicles, excluding migration of immature melanocytes from the bulge, it was ensured that interfollicular melanocytes are an autonomous self-renewing cell population with cells presenting different degrees of differentiation of which one fourth is immature; the melanocytes divide rarely and are absolute radioresistant to any dose schedule of RT applied, keeping the number of melanocytes intact. Hyperradiosensitivity to dose fractions of 0.05 to 0.3 Gy is observed for DNA double strand breaks (DSBs), differentiation and anti-apoptotic signaling. Proliferation is not stimulated and apoptosis is negligible upon exposure to RT, and also post-treatment. Melanocyte differentiation is maintained during RT, but dedifferentiation occurs after RT ends. The expected activation of the p53/p21 signaling upon RT appears in keratinocytes but is attenuated in melanocytes. A new observation is that melanocytes constitutively express BMI1, further upregulated upon irradiation, indicating that melanocytes have stem cell properties, which suggest that BMI1 prevents apoptosis, terminal differentiation and premature senescence and likely allows dedifferentiation by suppressing the p53/p21-mediated response to genotoxic damage, in addition to the repression of p16 and ARF. Melanocytes exhibit and accumulate a higher amount of DSBs during the RT period compared to keratinocytes, indicating reduced repair capacity of DSBs in melanocytes. Thus, only efficient pro-survival mechanisms can explain the melanocyte radioresistance regarding cell death. The findings in this thesis suggest that melanocytes are protected by activation of the BMI1-NF-kappa/β-CXCL8/CXCR2 pathway, in addition to upregulation of Bcl-2 by melanocyte-specific MITF (microphthalmia-associated transcription factor).
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