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To analyze the relationship between mean radiation dose to the bowels and the anal-sphincter and occurrence of 'defecation into clothing without forewarning', a specific and serious fecal incontinence symptom after gynecological radiotherapy. Additional potential risk factors associated with the symptom are explored.Data were collected for 519 eligible gynecological cancer survivors, treated with pelvic radiotherapy, with a median follow-up of 5.8 years, using a study-specific questionnaire and medical records. Correlations between defecation into clothing without forewarning and mean dose to organs at risk; the anal-sphincter region, the rectum, the sigmoid and the small intestines were investigated, also taking other risk factors into account.Twelve percent reported having had the symptom at least once in the preceding six months. Mean doses 50 Gy to the anal-sphincter region, the rectum, the sigmoid and the small intestines were related to the occurrence of the symptom. Significantly associated risk factors were deliveries with high birth weight, heart failure and lactose and/or gluten intolerance. After adjusting for these factors, mean doses 50 Gy to the anal-sphincter region, the sigmoid and the small intestines remained related to the occurrence of the symptom.Mean doses to the bowels and anal-sphincter region are related to the risk of defecation into clothing without forewarning in long-term gynecological cancer survivors treated with pelvic radiotherapy. Further radiobiological modeling may distinguish which organ(s) contribute most to development of the symptom.

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.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.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.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.

Determination of the dose-response relations for oesophageal stricture after radiotherapy of the head and neck.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.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), γ=1.4 (0.8-2.6) and s=0.1 (0.01-0.3).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.

Introduction: Fecal incontinence is a symptom reported by cancer survivors after pelvic radiotherapy and is recognized to be one of the most troubling symptom-induced sources of distress to patients. Objective: To investigate how fecal incontinence, patient-reported as emptying of all stools into clothing without forewarning, impact self-assessed quality of life from a social, psychological, sexual, and functional aspect among gynecological cancer survivors treated with pelvic radiotherapy. Methods: We identified a cohort of 789 eligible women in the Stockholm and Gothenburg areas treated with pelvic radiotherapy alone or as combined treatment of gynecological cancer. From the Swedish Population Registry, we identified 478 control women. Data were collected using a study-specific, validated, postal questionnaire including questions covering symptoms from the pelvic region, demographics, social functioning, psychological, and quality-of-life issues. Results: Participation was 78% for cancer survivors and 72% for control women. The fecal incontinence symptom emptying of all stools into clothing without forewarning was reported by 70 cancer survivors (12%), with lowered quality of life in 74% of the 70 cancer survivors. This symptom kept the survivors from going to parties (relative risk [RR], 11.8; 95% confidence interval [CI], 6.6-21.1), kept the survivors from traveling (RR, 9.3; 95% CI, 5.3-16.5), affected their work ability (RR, 7.9; 95% CI, 3.8-16.4), hindered their sexual life (RR, 9.2; 95% CI, 4.8-17.6), and changed them as persons (RR, 4.9; 95% CI, 2.9-8.1). The prevalence of the symptom emptying of all stools into clothing without forewarning among control women was 3 (1%) of 344. Conclusions: Among gynecological cancer survivors having undergone pelvic radiotherapy alone or as part of a combined treatment, fecal incontinence is associated with social, psychological, sexual, and functional consequences.

Background and purpose To investigate the dose-response relation between the dose to the vagina and the patient-reported symptom ‘absence of vaginal elasticity’ and how time to follow-up influences this relation. Materials and methods The study included 78 long-term gynecological cancer survivors treated between 1991 and 2003 with external beam radiation therapy. Of those, 24 experienced absence of vaginal elasticity. A normal tissue complication model is introduced that takes into account the influence of time to follow-up on the dose-response relation and the patient’s age. The best estimates of the dose-response parameters were calculated using Probit, Probit-Relative Seriality (RS) and Probit-time models. Log likelihood (LL) values and the Akaike Information Criterion (AIC) were used to evaluate the model fit. Results The dose-response parameters for ‘absence of vaginal elasticity’ according to the Probit and Probit-time models with the 68% Confidence Intervals (CI) were: LL=−39.8, D50 = 49.7 (47.2–52.4) Gy, γ 50 = 1.40 (1.12–1.70) and LL = −37.4, D50 = 46.9 (43.5–50.9) Gy, γ 50 = 1.81(1.17–2.51) respectively. Conclusions The proposed model, which describes the influence of time to follow-up on the dose-response relation, fits our data best. Our data indicate that the steepness of the dose-response curve of the dose to the vagina and the symptom ‘absence of vaginal elasticity’ increases with time to follow-up, while D50decreases. • Alevronta E, Avall-Lundqvist E, Al-Abany M, et al. Time-dependent dose-response relation for absence of vaginal elasticity after gynecological radiation therapy. Radiother Oncol 2016. http://dx.doi.org/10.1016/j.radonc.2016.02.013 .

The Radiumhemmets Scale of Disease-Specific Symptom Assessment-Prostate Cancer has been used in several studies. However, no test-retest reliability study of it has been conducted concerning the assessment of urinary, anal sphincter or large bowel function. The aim of this study was to evaluate the reliability of items assessing these functions.We investigated 89 prostate cancer patients randomly selected from a group of patients diagnosed in Stockholm. The patients answered 24 questions assessing anal sphincter, large bowel and urinary function twice, with a 3-week interval in-between, to assess reliability.Most of the questions assessing bowel and urinary symptoms showed substantial or near-perfect agreement. The kappa value for bowel symptom items wasor = 0.60 for all items, except for defecation urgency (0.40-0.55). The kappa value for urinary symptom items varied between 0.43 and 1.0, except for urinary urgency (0.30-0.39).When comparing the impact of different symptoms of anal sphincter, large bowel or urinary tract dysfunction, it may be important to consider that defecation urgency and urinary urgency have the highest measuring error (low reliability). This error dilutes assessed associations with, for example, decreased quality of life. Nevertheless, the test-retest reliability for anal sphincter, large bowel and urinary symptoms indicates that surveys yield meaningful information.

The aim of this study was to investigate whether external beam radiation treatment with three or four fields affects the risk of long-term distressful symptoms. The study included 145 patients who had been treated in Stockholm from 1993 to 1996 for localized prostate cancer. Bowel, urinary and sexual function as well as symptom-induced distress were assessed by means of a postal questionnaire 29-59 months after therapy. Among patients treated with a multileaf collimator, defecation urgency, diarrhoea and loose stools were more common after four fields than after three fields, but faecal leakage necessitating the use of pads and distress from the gastrointestinal tract were less common (although not statistically significantly so). Among bowel symptoms, the strongest association with gastrointestinal distress was found for faecal leakage. Three fields without a multileaf collimator entailed a higher risk of defecation urgency than three fields with a multileaf collimator. We conclude that the choice of three or four fields may imply a contrasting risk scenario for defecation urgency or diarrhoea in comparison with faecal leakage.

Background and purpose: To investigate whether the type of collimation technique, target dose and treated volume influence the prevalence of intact erectile function after external beam radiation therapy for localized prostate cancer. Patients and methods: A prospective study was conducted to assess erection stiffness before treatment and after follow-ups of 9‐18 months and 4‐5.5 years. Information was collected using the Radiumhemmet Scale of Sexual Function. Results: Thirty-one men were ‘potent’ before the radiation. Fourteen of them were treated with a conventional collimator and 17 were given three-dimensional conformal therapy with the aid of a multileaf collimator. Preserved erectile function at 9‐18 months was found in 17 of the 31 men (55%) and at the 4‐5-year follow-up in five of 22 (23%). Preservation of potency was related to the treatment procedure but not to the treatment volume. Conclusions: Conformal therapy may increase the percentage of men preserving erectile function during radiotherapy for localized prostate cancer; it is possible that the differences to conventional therapy do not depend on treated volume. q 2000 Elsevier Science Ireland Ltd. All rights reserved.

Background: We surveyed the occurrence of physical symptoms among long-term gynaecological cancer survivors after pelvic radiation therapy, and compared with population-based control women. Methods: We identified a cohort of 789 eligible gynaecological cancer survivors treated with pelvic radiation therapy alone or combined with surgery in Stockholm or Gothenburg, Sweden. A control group of 478 women was randomly sampled from the Swedish Population Registry. Data were collected through a study-specific validated postal questionnaire with 351 questions concerning gastrointestinal and urinary tract function, lymph oedema, pelvic bones and sexuality. Clinical characteristics and treatment details were retrieved from medical records. Results: Participation rate was 78% for gynaecological cancer survivors and 72% for control women. Median follow-up time after treatment was 74 months. Cancer survivors reported a higher occurrence of symptoms from all organs studied. The highest age-adjusted relative risk (RR) was found for emptying of all stools into clothing without forewarning (RR 12.7), defaecation urgency (RR 5.7), difficulty feeling the need to empty the bladder (RR 2.8), protracted genital pain (RR 5.0), pubic pain when walking indoors (RR 4.9) and erysipelas on abdomen or legs at least once during the past 6 months (RR 3.6). Survivors treated with radiation therapy alone showed in general higher rates of symptoms. Conclusion: Gynaecological cancer survivors previously treated with pelvic radiation report a higher occurrence of symptoms from the urinary and gastrointestinal tract as well as lymph oedema, sexual dysfunction and pelvic pain compared with non-irradiated control women. Health-care providers need to actively ask patients about specific symptoms in order to provide proper diagnostic investigations and management.

Purpose To investigate the relative importance of patient-reported hip and sacral pain after pelvic radiotherapy (RT) for gynecological cancer and its relationship to the absorbed doses in these organs. Methods and Materials We used data from a population-based study that included 650 long-term gynecological cancer survivors treated with pelvic RT in the Gothenburg and Stockholm areas in Sweden with a median follow-up of 6 years (range, 2–15) and 344 population controls. Symptoms were assessed through a study-specific postal questionnaire. We also analyzed the hip and sacral dose-volume histogram data for 358 of the survivors. Results Of the survivors, one in three reported having or having had hip pain after completing RT. Daily pain when walking was four times as common among the survivors compared to controls. Symptoms increased in frequency with a mean absorbed dose >37.5 Gy. Also, two in five survivors reported pain in the sacrum. Sacral pain also affected their walking ability and tended to increase with a mean absorbed dose >42.5 Gy. Conclusions Long-term survivors of gynecological cancer treated with pelvic RT experience hip and sacral pain when walking. The mean absorbed dose was significantly related to hip pain and was borderline significantly related to sacral pain. Keeping the total mean absorbed hip dose below 37.5 Gy during treatment might lower the occurrence of long-lasting pain. In relation to the controls, the survivors had a lower occurrence of pain and pain-related symptoms from the hips and sacrum compared with what has previously been reported for the pubic bone.

PURPOSE: To analyze the relationship between mean absorbed dose to the pubic bone after pelvic radiotherapy for gynecological cancer and occurrence of pubic bone pain among long-term survivors.METHODS AND MATERIALS: In an unselected, population-based study, we identified 823 long-term gynecological cancer survivors treated with pelvic radiotherapy during 1991-2003. For comparison, we used a non-radiation-treated control population of 478 matched women from the Swedish Population Register. Pain, intensity of pain, and functional impairment due to pain in the pubic bone were assessed with a study-specific postal questionnaire.RESULTS: We analyzed data from 650 survivors (participation rate 79%) with median follow-up of 6.3 years (range, 2.3-15.0 years) along with 344 control women (participation rate, 72 %). Ten percent of the survivors were treated with radiotherapy; ninety percent with surgery plus radiotherapy. Brachytherapy was added in 81%. Complete treatment records were recovered for 538/650 survivors, with dose distribution data including dose-volume histograms over the pubic bone. Pubic bone pain was reported by 73 survivors (11%); 59/517 (11%) had been exposed to mean absorbed external beam doses

Aim of the study To make a comprehensive, detailed inventory of gastrointestinal symptoms reported by gynaecological cancer survivors and control women from the general population. Method We identified a cohort of 789 eligible women in the Stockholm and Gothenburg areas, treated with pelvic radiotherapy during the period 1991–2003, alone or as combined treatment, for gynaecological cancer. As controls, we randomly recruited 478 women, frequency matched by age and residence from the Swedish Population Registry. We collected data in 2006 by means of a study-specific, validated, postal questionnaire including 351 questions covering symptoms from the pelvic region. We asked about demographics, psychological and quality-of-life issues as well as social functioning. Results Participation was 78% for cancer survivors and 72% for controls. Mean follow-up was 7.2 years. In this large, population-based study, the greatest age-adjusted absolute risk difference between cancer survivors and control women was observed for the symptom defaecation urgency with faecal leakage and the highest age-adjusted relative risk for emptying of all stools into clothing without forewarning. Conclusions Cancer survivors having undergone pelvic radiotherapy alone or as part of combined treatment between the period 1991–2003 for a gynaecological malignancy had a higher occurrence of long-lasting gastrointestinal symptoms as compared to population controls.

Risk factors for development of a stricture of the upper esophagus after radiotherapy for head and neck cancer are poorly defined.This was a retrospective case-control study of patients diagnosed and treated for esophageal stricture after radiotherapy for head and neck cancer.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 of45 Gy to the upper esophagus.Enteral feeding during EBRT is strongly associated with the development of stricture of the esophagus, as is a mean dose of45 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.

Background: The estimation of the parameters that describe the dose-response relations of anal sphincter regarding the clinical endpoints of fecal leakage and blood or phlegm in stools is important in the optimization of prostate cancer radiotherapy. Also, the validity of the relative seriality model for this clinical case needs to be examined by associating the clinical follow-up results with the predicted complication rates. Patients and Methods: In this study, 65 patients who received radiation therapy for clinically localized prostate adenocarcinoma are analyzed. The clinical treatment outcome and the three-dimensional dose distribution delivered to anal sphincter were available for each patient. A questionnaire was used for assessing the clinical bowel and urinary symptoms. A maximum likelihood fitting was performed to calculate the best estimates of the parameters used by the relative seriality model. The clinical utilization of the calculated parameters in predicting anal sphincter complication probabilities was illustrated by applying the best estimate of the parameters to a subset of the patient population. Results: The estimated values of the parameters for the two clinical endpoints are D 50 = 70.2 Gy, γ = 1.22, s = 0.35 for fecal leakage and D 50 = 74.0 Gy, γ = 0.75, s ≈ 0 for blood or phlegm in stools. The standard deviations of the parameters were also calculated together with the confidence intervals of the dose-response curves. The analysis proved that the treatment outcome pattern of the patient material can suitably be reproduced by the relative seriality model (probability of finding a worse fit = 60.2%, the area under the receiver operating characteristic curve = 0.72 and 0.69 and χ2-test = 0.97 and 0.86, respectively). Conclusion: Fecal leakage is characterized by a medium relative seriality whereas blood or phlegm in stools was found to have strong volume dependence (low relative seriality). Diminishing the biologically effective uniform dose to anal sphincter < 40–45 Gy may significantly reduce the risk of fecal leakage or blood or phlegm in stools for patients irradiated for prostate cancer.

To investigate dysfunction caused by unwanted radiation to the anal-sphincter region and the rectum.A questionnaire assessing bowel symptoms, sexual function, and urinary symptoms was sent to 72 patients with clinically localized prostatic adenocarcinoma treated by external beam radiation therapy at the Radiumhemmet, Karolinska Hospital, in Stockholm, Sweden, 2-4 years after treatment. The mean percentage dose-volume histograms for patients with and without the specific symptom were calculated.Of the 65 patients providing information, 9 reported fecal leakage, 10 blood and mucus in stools, 10 defecation urgency, and 7 diarrhea or loose stools. None of the 19 and 13 patients who received, respectively, a dose ofor =35 Gy toor =60% oror =40 Gy toor =40% of the anal-sphincter region volume reported fecal leakage (p0.05). In dose-volume histograms, a statistically significant correlation was found between radiation to the anal-sphincter region and the risk of fecal leakage in the interval 45-55 Gy. There was also a statistically significant correlation between radiation to the rectum and the risk of defecation urgency and diarrhea or loose stools in the interval 25-42 Gy. No relationship was found between anatomic rectal wall volume and the investigated late effects.Although the limited data in this study prevent the definition of a conclusive threshold regarding volume and dose to the anal-sphincter region and untoward morbidity, it seems that careful monitoring of unnecessary irradiation to this area should be done because it can potentially help reduce the risk of adverse effects, such as fecal leakage. Future studies should pay more attention to the anal-sphincter region and help to more rigorously define its radiotherapeutic tolerance.

From the Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institutet, (M. al-Abany, A´ .R. Helgason, G. Steineck), the Stockholm Center for Public Health (A´ .R. Helgason), Department ofMedical Hospital Radiation Physics, So¨der Hospital (A.-K. A˚ gren Cronqvist), Department of Medical RadiationPhysics, Karolinska Institutet (B. Lind, P. Mavroidis), Uro-oncology, Radiumhemmet, Karolinska Hospital (P.Wersa¨ll), Department of Oncology, Radiumhemmet, Karolinska Hospital (H. Lind) and the Department ofRadiology, Karolinska Hospital (E. Qvanta), Stockholm, SwedenCorrespondence to: Professor Gunnar Steineck, Clinical Cancer Epidemiology, Karolinska Hospital Z6:01, SE-17176 Stockholm, Sweden. Tel

In order to suggest therapy modifications with the aim of diminishing the risk of therapy-induced long-term distressful symptoms in cancer survivors, data are needed relating details of therapy to the long-term symptom situation. In this article, the concepts and means used to assess the latter while developing the Radiumhemmet scale for symptom assessment are described. The focus is on the subjective long-term situation, and symptoms as a perceived abnormality are defined. For conceptual clarity, one symptom at a time is considered, excluding scales in which items are summarized. Moreover, measures of disease occurrence in the population are translated (epidemiologically) into measures of symptom occurrence in an individual. Nature distinguishes one long-term symptom from another. Occurrence of a symptom in an individual is measured by an incidence (e.g. number of defecations per week) or prevalence rate (e.g. urinations with involuntary cessation divided by the total number of urinations). Any scale expressing symptom intensity is arbitrary, be it 'verbal' (no/little/moderate/much pain) or visual (analogue or with integers). A time period describes symptom duration. The relevance of a symptom to emotions and social activities, sometimes cited as the associated symptom-induced distress, is a separate issue from symptom occurrence, intensity, and duration.