| 1. |
- Ahlberg, Alexander, et al.
(författare)
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ESOPHAGEAL STRICTURE AFTER RADIOTHERAPY IN PATIENTS WITH HEAD AND NECK CANCER : EXPERIENCE OF A SINGLE INSTITUTION OVER 2 TREATMENT PERIODS
- 2010
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Ingår i: Head and Neck. - : Wiley. - 1043-3074 .- 1097-0347. ; 32:4, s. 452-461
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Tidskriftsartikel (refereegranskat)abstract
- Background. Risk factors for development of a stricture of the upper esophagus after radiotherapy for head and neck cancer are poorly defined. Methods. This was a retrospective case-control study of patients diagnosed and treated for esophageal stricture after radiotherapy for head and neck cancer. Results. The incidence of esophageal stricture after external beam radiation therapy (EBRT) was 3.3%. Seventy patients with stricture and 66 patients without stricture were identified. A multivariate analysis showed that there was increased risk of stricture in receiving enteral feeding during EBRT or in receiving a mean dose of >45 By to the upper esophagus. Conclusions. Enteral feeding during EBRT is strongly associated with the development of stricture of the esophagus, as is a mean dose of >45 Gy to the upper esophagus. Treatment of the stricture with Savary-Gilliard bougienage or through scope balloon dilatation is safe and successful but often has to be repeated.
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| 2. |
- Alevronta, Eleftheria, et al.
(författare)
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Dose-response relations for stricture in the proximal oesophagus from head and neck radiotherapy
- 2010
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 97:1, s. 54-59
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Determination of the dose-response relations for oesophageal stricture after radiotherapy of the head and neck. Material and methods: In this study 33 patients who developed oesophageal stricture and 39 patients as controls are included. The patients received radiation therapy for head and neck cancer at Karolinska University Hospital, Stockholm, Sweden. For each patient the 3D dose distribution delivered to the upper 5 cm of the oesophagus was analysed. The analysis was conducted for two periods, 1992-2000 and 2001-2005, due to the different irradiation techniques used. The fitting has been done using the relative seriality model. Results: For the treatment period 1992-2005, the mean doses were 49.8 and 33.4 Gy, respectively, for the cases and the controls. For the period 1992-2000, the mean doses for the cases and the controls were 49.9 and 45.9 Gy and for the period 2001-2005 were 49.8 and 21.4 Gy. For the period 2001-2005 the best estimates of the dose-response parameters are D-50 = 61.5 Gy (52.9-84.9 Gy), gamma = 1.4 (0.8-2.6) and s = 0.1 (0.01-0.3). Conclusions: Radiation-induced strictures were found to have a dose response relation and volume dependence (low relative seriality) for the treatment period 2001-2005. However, no dose response relation was found for the complete material.
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| 3. |
- Alevronta, Eleftheria, et al.
(författare)
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Dose-response relationships for an atomized symptom of fecal incontinence after gynecological radiotherapy.
- 2013
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Taylor & Francis. - 1651-226X .- 0284-186X. ; 52:4, s. 719-26
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. The aim of this study was to investigate what bowel organ and delivered dose levels are most relevant for the development of 'emptying of all stools into clothing without forewarning' so that the related dose-responses could be derived as an aid in avoiding this distressing symptom in the future. Material and methods. Of the 77 gynecological cancer survivors treated with radiotherapy (RT) for gynecological cancer, 13 developed the symptom. The survivors were treated between 1991 and 2003. The anal-sphincter region, the rectum, the sigmoid and the small intestines were all delineated and the dose-volume histograms were exported for each patient. The dose-volume parameters were estimated fitting the data to the Relative Seriality (RS), the Lyman and the generalized Equivalent Uniform Dose (gEUD) model. Results. The dose-response parameters for all three models and four organs at risk (OARs) were estimated. The data from the sigmoid fits the studied models best: D50 was 58.8 and 59.5 Gy (RS, Lyman), γ50 was 1.60 and 1.57 (RS, Lyman), s was 0.32, n was 0.13 and a was 7.7 (RS, Lyman, gEUD). The estimated volume parameters indicate that the investigated OARs behave serially for this endpoint. Our results for the three models studied indicate that they have the same predictive power (similar LL values) for the symptom as a function of the dose for all investigated OARs. Conclusions. In our study, the anal-sphincter region and sigmoid fit our data best, but all OARs were found to have steep dose-responses for 'emptying of all stools into clothing without forewarning' and thus, the outcome can be predicted with an NTCP model. In addition, the dose to the four studied OARs may be considered when minimizing the risk of the symptom.
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| 4. |
- Alevronta, Eleftheria, et al.
(författare)
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Dose-response relationships of intestinal organs and excessive mucus discharge after gynaecological radiotherapy
- 2021
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 16:4 April
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Tidskriftsartikel (refereegranskat)abstract
- Background The study aims to determine possible dose-volume response relationships between the rectum, sigmoid colon and small intestine and the ‘excessive mucus discharge’ syndrome after pelvic radiotherapy for gynaecological cancer. Methods and materials From a larger cohort, 98 gynaecological cancer survivors were included in this study. These survivors, who were followed for 2 to 14 years, received external beam radiation therapy but not brachytherapy and not did not have stoma. Thirteen of the 98 developed excessive mucus discharge syndrome. Three self-assessed symptoms were weighted together to produce a score interpreted as ‘excessive mucus discharge’ syndrome based on the factor loadings from factor analysis. The dose-volume histograms (DVHs) for rectum, sigmoid colon, small intestine for each survivor were exported from the treatment planning systems. The dose-volume response relationships for excessive mucus discharge and each organ at risk were estimated by fitting the data to the Probit, RS, LKB and gEUD models. Results The small intestine was found to have steep dose-response curves, having estimated dose-response parameters: γ : 1.28, 1.23, 1.32, D : 61.6, 63.1, 60.2 for Probit, RS and LKB respectively. The sigmoid colon (AUC: 0.68) and the small intestine (AUC: 0.65) had the highest AUC values. For the small intestine, the DVHs for survivors with and without excessive mucus discharge were well separated for low to intermediate doses; this was not true for the sigmoid colon. Based on all results, we interpret the results for the small intestine to reflect a relevant link. Conclusion An association was found between the mean dose to the small intestine and the occurrence of ‘excessive mucus discharge’. When trying to reduce and even eliminate the incidence of ‘excessive mucus discharge’, it would be useful and important to separately delineate the small intestine and implement the dose-response estimations reported in the study.
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| 5. |
- Alevronta, Eleftheria, et al.
(författare)
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Dose-response relationships of the sigmoid for urgency syndrome after gynecological radiotherapy.
- 2018
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Ingår i: Acta oncologica (Stockholm, Sweden). - 1651-226X .- 0284-186X. ; 57:10, s. 1352-1358
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Tidskriftsartikel (refereegranskat)abstract
- To find out what organs and doses are most relevant for 'radiation-induced urgency syndrome' in order to derive the corresponding dose-response relationships as an aid for avoiding the syndrome in the future.From a larger group of gynecological cancer survivors followed-up 2-14years, we identified 98 whom had undergone external beam radiation therapy but not brachytherapy and not having a stoma. Of those survivors, 24 developed urgency syndrome. Based on the loading factor from a factor analysis, and symptom frequency, 15 symptoms were weighted together to a score interpreted as the intensity of radiation-induced urgency symptom. On reactivated dose plans, we contoured the small intestine, sigmoid colon and the rectum (separate from the anal-sphincter region) and we exported the dose-volume histograms for each survivor. Dose-response relationships from respective risk organ and urgency syndrome were estimated by fitting the data to the Probit, RS, LKB and gEUD models.The rectum and sigmoid colon have steep dose-response relationships for urgency syndrome for Probit, RS and LKB. The dose-response parameters for the rectum were D50: 51.3, 51.4, and 51.3Gy, γ50=1.19 for all models, s was 7.0e-09 for RS and n was 9.9×107 for LKB. For Sigmoid colon, D50 were 51.6, 51.6, and 51.5Gy, γ50 were 1.20, 1.25, and 1.27, s was 2.8 for RS and n was 0.079 for LKB.Primarily the dose to sigmoid colon as well as the rectum is related to urgency syndrome among gynecological cancer survivors. Separate delineation of the rectum and sigmoid colon in order to incorporate the dose-response results may aid in reduction of the incidence of the urgency syndrome.
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| 6. |
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| 7. |
- Alevronta, Eleftheria
(författare)
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Towards better quality of life after radiation therapy by improved response modeling
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: To improve the quality of life of radiotherapy cancer survivors we need to improve our knowledge of the dose, volume and time-response relations of radiotherapy induced late effects. Aims: The aim of the thesis was to investigate predictors for normal-tissue complications of head and neck, and gynecological radiotherapy using response modeling. We aimed to study this effect by using existing and new normal-tissue complication models. Methods: In this thesis, we included 72 patients, who had received external beam radiation therapy (EBRT) for head and neck cancer in Stockholm. Of those, 33 developed esophageal stricture to the proximal esophagus. Gynecological-cancer survivors were treated with pelvic-radiation therapy only or in combination with other treatments in the Stockholm and Gothenburg regions during 1991 to 2003 were also investigated. Dose-volume histograms (DVHs) of 519 gynecological cancer survivors and 73 head and neck cancer survivors were extracted from the treatment planning systems. The dose-effect relations between the symptom ‘emptying of all stools into clothing without forewarning’ and bowel organs and the anal-sphincter were investigated, considering additional possible risk factors. The dose-volume response relations for these organs at risk (OAR) were also investigated for 77 gynecological cancer survivors, who were treated with EBRT only. Moreover, the dose, volume and time-effect of the dose to the vagina and ‘absence of vaginal elasticity’ were investigated for 78 survivors treated with EBRT only. A novel model is proposed, describing the influence of follow-up time on the dose-response relations. To explore the dose-volume effect of the late complications the Relative Seriality, the Lyman and the gEUD models were fitted to the dose volume data. To investigate the dose-effects and the dose-time effects the Probit and the proposed Probit-time models were also used. Results: The best estimates of the dose–response parameters indicated a steep dose-response relation for the radiation induced esophageal strictures for the period of 2001–2005. Mean doses higher than 50 Gy to the anal-sphincter and bowel organs were related with the occurrence of ‘emptying all stools into clothing without fore-warning’. Dose to the anal-sphincter region and sigmoid seemed to be most relevant, but all OARs were found to have steep dose-responses for this symptom. According to the estimated volume parameters the investigated OARs do not show any volume effect for this endpoint. All the studied models had the same predictive power for the symptom as a function of the dose for all investigated OARs. The Probit-time model fit our data better than the pure Probit for ‘absence of vaginal elasticity’. According to the volume parameter from the relative seriality, the vagina has shown a pronounced volume effect for this endpoint. Findings: Dose-response relations and volume dependence were found for the radiation induced esophageal strictures. The EBRT dose to the bowel organs and the anal-sphincter were related to the occurrence of ‘empty-ing of all stools into clothing without forewarning’. The mean dose to the vagina was related to the occurrence of ‘absence of vaginal elasticity’. The steepness of the dose-response relation for the mean dose to the vagina and the symptom increased with time. Implications: The risk of ‘emptying of all stools into clothing without forewarning’ might be lowered by delineating the anal-sphincter region and the sigmoid as well as the rectum and the small intestines during the treatment planning process. This thesis suggests radiobiological parameters for the proximal esophagus, the analsphincter region, the bowel organs and the vagina. Those parameters could be used in terms of avoiding the studied normal-tissue complications in the future. Finally, our findings suggest that the effect of time be considered at the time of treatment and communication with the patient.
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| 8. |
- Bull, Cecilia, 1977, et al.
(författare)
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A novel mouse model of radiation-induced cancer survivorship diseases of the gut
- 2017
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Ingår i: American journal of physiology. Gastrointestinal and liver physiology. - : American Physiological Society. - 1522-1547 .- 0193-1857. ; 313:5, s. G456-G466
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Tidskriftsartikel (refereegranskat)abstract
- A deeper understanding of the radiation-induced pathophysiological processes that develop in the gut is imperative to prevent, alleviate, or eliminate cancer survivorship diseases after radiotherapy to the pelvic area. Most rodent models of high-dose gastrointestinal radiation injury are limited by high mortality. We therefore established a model that allows for the delivering of radiation in fractions at high doses while maintaining long-term survival. Adult male C57/BL6 mice were exposed to small-field irradiation, restricted to 1.5 cm of the colorectum using a linear accelerator. Each mouse received 6 or 8 Gy, two times daily in 12-h intervals in two, three, or four fractions. Acute cell death was examined at 4.5 h postirradiation and histological changes at 6 wk postirradiation. Another group was given four fractions of 8 Gy and followed over time for development of visible symptoms. Irradiation caused immediate cell death, mainly limited to the colorectum. At 6 wk postirradiation, several crypts displayed signs of radiation-induced degeneration. The degenerating crypts were seen alongside crypts that appeared perfectly healthy. Crypt survival was reduced after the fourth fraction regardless of dose, whereas the number of macrophages increased. Angiogenesis was induced, likely as a compensatory mechanism for hypoxia. Four months postirradiation, mice began to show radiation-induced symptoms, and histological examination revealed an extensive crypt loss and fibrosis. Our model is uniquely suitable for studying the long-term trajectory and underlying mechanisms of radiation-induced gastrointestinal injury. NEW & NOTEWORTHY A novel mouse model for studying the long-term trajectory of radiation-induced gut injury. The method allows for the use of high doses and multiple fractions, with minor impact on animal health for at least 3 mo. Crypt loss and a slow progression of fibrosis is observed. Crypt degeneration is a process restricted to isolated crypts. Crypt degeneration is presented as a convenient proxy endpoint for long-term radiation-induced gut injury.
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| 9. |
- Bull, Cecilia, 1977, et al.
(författare)
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Intra-abdominal Surgery and Intestinal Syndromes After Pelvic Radiation Therapy
- 2024
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Ingår i: ADVANCES IN RADIATION ONCOLOGY. - 2452-1094. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To determine the effects of intra-abdominal surgery on the intensities of 5 radiation -induced intestinal syndromes in survivors of pelvic cancer. Methods and Materials: The analysis included 623 women born in 1927 or later who had survived cancer. They all had received external radiation therapy toward the pelvic area to treat gynecologic cancers. Information from 344 women who did not undergo irradiation, matched for age and residency, was also included. Main outcome measures after the surgical procedures were the intensity scores for 5 radiation -induced intestinal syndromes: urgency-tenesmus syndrome, fecal -leakage syndrome, excessive mucus discharge, excessive gas discharge, and blood discharge. The scores were based on symptom frequencies obtained from patient -reported outcomes and on factor loadings obtained from a previously reported factor analysis. Follow-up was 2 to 15 years after radiation therapy. Results: Among survivors of cancer, intra-abdominal surgery increased the intensity of the urgency-tenesmus syndrome, the fecalleakage syndrome, excessive gas discharge, and blood discharge but had a negligible effect on mucus discharge. Intra-abdominal surgery had an especially negative effect on the urgency-tenesmus syndrome. Although the combination of appendectomy with 1 or more other intra-abdominal surgeries resulted in the highest score for all syndromes, appendectomy alone had weak to no effect. In women who did not undergo irradiation, a similar pattern was seen, albeit with much lower scores. Conclusions: We found intra-abdominal surgery to be a risk factor among survivors of gynecologic cancer, increasing the intensity score of 4 out of 5 radiation -induced intestinal syndromes. During radiation therapy, it may be worthwhile to pay extra attention to the dose of unwanted ionizing radiation to the intestines if the patient previously has undergone intra-abdominal surgery.
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| 10. |
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