Massoud al-Abany

Dose-Response Relations for Anal Sphincter Regarding Fecal Leakage and Blood or Phlegm in Stools after Radiotherapy for Prostate Cancer

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 D50 = 70.2 Gy, γ = 1.22, s = 0.35 for fecal leakage and D50 = 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.Hintergrund:Um die Strahlenbehandlung des Prostatakarzinoms optimieren zu können, ist ein Modell der Dosis-Wirkungs-Beziehung für die Analsphinkterfunktion notwendig, dessen Parameter verlässlich geschätzt werden können. Es sollte die klinischen Endpunkte Stuhlinkontinenz und Blut oder Schleim im Stuhl beschreiben. Zusätzlich sollte die Gültigkeit des Relative-Seriality-Modells überprüft werden, indem die Befunde des klinischen Follow-up mit den prognostizierten Komplikationsraten verglichen werden.Patienten und Methodik:Diese Studie umfasst 65 Patienten, die wegen eines klinisch manifesten lokalisierten Adenokarzinoms der Prostata eine Strahlenbehandlung erhalten hatten. Das klinische Ergebnis und die Dosisverteilung im Analsphinkter waren für jeden Patienten verfügbar. Klinische Symptome des Darms und der Harnwege wurden mittels eines Fragebogens erfasst. Die Parameter des Relative-Seriality-Modells wurden mit Hilfe der Maximum-Likelihood-Methode bestimmt. Bei einer Untergruppe der Patienten wurden die besten Schätzwerte der Parameter angewendet. Der klinische Nutzen für die Prognose von Komplikationen des Analsphinkters konnte dargestellt werden.Ergebnisse:Die Schätzwerte der Parameter der zwei klinischen Endpunkte sind D50 = 70,2 Gy, γ = 1,22, s = 0,35 für Stuhlinkontinenz und D50 = 74,0 Gy, γ = 0,75, s ≈ 0 für Blut oder Schleim im Stuhl. Die Standardabweichungen der Parameter wurden ebenso berechnet wie die Konfidenzintervalle. Die Analyse (untersucht wurden: Probability of Finding worse Fit = 60,2%, die Fläche unter ROC-Kurven 0,72 bzw. 0,69 und χ2 = 0,97 und 0,86) beweist, dass das Behandlungsergebnis bei den untersuchten Patienten mit Hilfe des Relative-Seriality-Modells gut wiedergegeben wird.Schlussfolgerungen:Die Stuhlinkontinenz zeigt eine mittlere Relative Seriality, während für Blut oder Schleim im Stuhl eine starke Volumenabhängigkeit gefunden wurde (geringe Relative Seriality). Eine Reduktion der biologisch effektiven, uniformen Dosis des Analsphinkters unter 40-45 Gy könnte die Risiken der Stuhlinkontinenz und von Blut oder Schleim im Stuhl für Prostatakarzinom-Patienten signifikant senken.

Dose-Response Relations for Anal Sphincter Regarding Fecal Leakage and Blood or Phlegm in Stools after Radiotherapy for Prostate Cancer Radiobiological Study of 65 Consecutive Patients

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 D50 = 70.2 Gy, γ = 1.22, s = 0.35 for fecal leakage and D50 = 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.Hintergrund:Um die Strahlenbehandlung des Prostatakarzinoms optimieren zu können, ist ein Modell der Dosis-Wirkungs-Beziehung für die Analsphinkterfunktion notwendig, dessen Parameter verlässlich geschätzt werden können. Es sollte die klinischen Endpunkte Stuhlinkontinenz und Blut oder Schleim im Stuhl beschreiben. Zusätzlich sollte die Gültigkeit des Relative-Seriality-Modells überprüft werden, indem die Befunde des klinischen Follow-up mit den prognostizierten Komplikationsraten verglichen werden.Patienten und Methodik:Diese Studie umfasst 65 Patienten, die wegen eines klinisch manifesten lokalisierten Adenokarzinoms der Prostata eine Strahlenbehandlung erhalten hatten. Das klinische Ergebnis und die Dosisverteilung im Analsphinkter waren für jeden Patienten verfügbar. Klinische Symptome des Darms und der Harnwege wurden mittels eines Fragebogens erfasst. Die Parameter des Relative-Seriality-Modells wurden mit Hilfe der Maximum-Likelihood-Methode bestimmt. Bei einer Untergruppe der Patienten wurden die besten Schätzwerte der Parameter angewendet. Der klinische Nutzen für die Prognose von Komplikationen des Analsphinkters konnte dargestellt werden.Ergebnisse:Die Schätzwerte der Parameter der zwei klinischen Endpunkte sind D50 = 70,2 Gy, γ = 1,22, s = 0,35 für Stuhlinkontinenz und D50 = 74,0 Gy, γ = 0,75, s ≈ 0 für Blut oder Schleim im Stuhl. Die Standardabweichungen der Parameter wurden ebenso berechnet wie die Konfidenzintervalle. Die Analyse (untersucht wurden: Probability of Finding worse Fit = 60,2%, die Fläche unter ROC-Kurven 0,72 bzw. 0,69 und χ2 = 0,97 und 0,86) beweist, dass das Behandlungsergebnis bei den untersuchten Patienten mit Hilfe des Relative-Seriality-Modells gut wiedergegeben wird.Schlussfolgerungen:Die Stuhlinkontinenz zeigt eine mittlere Relative Seriality, während für Blut oder Schleim im Stuhl eine starke Volumenabhängigkeit gefunden wurde (geringe Relative Seriality). Eine Reduktion der biologisch effektiven, uniformen Dosis des Analsphinkters unter 40-45 Gy könnte die Risiken der Stuhlinkontinenz und von Blut oder Schleim im Stuhl für Prostatakarzinom-Patienten signifikant senken.

Long-term Symptoms after External Beam Radiation Therapy for Prostate Cancer with Three or Four Fields

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.

Self-reported symptoms of faecal incontinence among long-term gynaecological cancer survivors and population-based controls.

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.

Fecal incontinence affecting quality of life and social functioning among long-term gynecological cancer survivors.

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.

Esophageal stricture after radiotherapy in patients with head and neck cancer: Experience of a single institution over 2 treatment periods

Risk factors for development of a stricture of the upper esophagus after radiotherapy for head and neck cancer are poorly defined.

Dose to the anal sphincter region and risk of fecal leakage

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:

Pain and Mean Absorbed Dose to the Pubic Bone After Radiotherapy Among Gynecological Cancer Survivors

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 <52.5 Gy to the pubic bone and 5/12 (42%) to mean absorbed external beam doses ≥ 52.5 Gy. Thirty-three survivors reported pain affecting sleep, a 13-fold increased prevalence compared with control women. Forty-nine survivors reported functional impairment measured as pain walking indoors, a 10-fold increased prevalence. CONCLUSIONS Mean absorbed external beam dose above 52.5 Gy to the pubic bone increases the occurrence of pain in the pubic bone and may affect daily life of long-term survivors treated with radiotherapy for gynecological cancer.

Dose-response relations for stricture in the proximal oesophagus from head and neck radiotherapy

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), γ=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.

Relative Importance of Hip and Sacral Pain Among Long-Term Gynecological Cancer Survivors Treated With Pelvic Radiotherapy and Their Relationships to Mean Absorbed Doses

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.