Relationships between dose to the gastro-intestinal tract and patient-reported symptom domains after radiotherapy for localized prostate cancer.
BACKGROUND
Gastrointestinal (GI) morbidity after radiotherapy (RT) for prostate cancer is typically addressed by studying specific single symptoms. The aim of this study was to explore the interplay between domains of patient- reported outcomes (PROs) on GI morbidity, and to what extent these are explained by RT dose to the GI tract.


METHODS
The study included men from two Scandinavian studies (N = 211/277) who had undergone primary external beam radiotherapy (EBRT) for localized prostate cancer to 70-78 Gy (2 Gy/fraction). Factor analysis was applied to previously identified PRO-based symptom domains from two study-specific questionnaires. Number of questions: 43; median time to follow-up: 3.6-6.4 years) and dose-response outcome variables were defined from these domains. Dose/volume parameters of the anal sphincter (AS) or the rectum were tested as predictors for each outcome variable using logistic regression with 10-fold cross-validation. Performance was assessed using area under the receiver operating characteristic curve (Az) and model frequency.


RESULTS
Outcome variables from Defecation urgency (number of symptoms: 2-3), Fecal leakage (4-6), Mucous (4), and Pain (3-6) were defined. In both cohorts, intermediate rectal doses predicted Defecation urgency (mean Az: 0.53-0.54; Frequency: 70-75%), and near minimum and low AS doses predicted Fecal leakage (mean Az: 0.63-0.67; Frequency: 83-99%). In one cohort, high AS doses predicted Mucous (mean Az: 0.54; Frequency: 96%), whereas in the other, low AS doses and intermediate rectal doses predicted Pain (mean Az: 0.69; Frequency: 28-82%).


CONCLUSIONS
We have demonstrated that Defecation urgency, Fecal leakage, Mucous, and Pain following primary EBRT for localized prostate cancer primarily are predicted by intermediate rectal doses, low AS doses, high AS doses, or a combination of low AS and intermediate rectal doses, respectively. This suggests that there is a domain-specific dose-response for the GI tract. To reduce risk of GI morbidity, dose distributions of both the AS region and the rectum should, therefore, be considered when prescribing prostate cancer RT.
a Department of Medical Physics , Memorial Sloan Kettering Cancer Center , New York , USA.
Maria
M
Thor
b Division of Clinical Cancer Epidemiology, Department of Oncology , Institute of Clinical Sciences, the Sahlgrenska Academy at the University of Gothenburg , Sweden.
Caroline E
CE
Olsson
a Department of Medical Physics , Memorial Sloan Kettering Cancer Center , New York , USA.
Jung Hun
JH
Oh
c Departments of Medical Physics and Oncology , Aarhus University Hospital , Aarhus , Denmark.
Stine E
SE
Petersen
d Oncology, University of Gothenburg , Gothenburg , Sweden.
David
D
Alsadius
c Departments of Medical Physics and Oncology , Aarhus University Hospital , Aarhus , Denmark.
Lise
L
Bentzen
e Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital , Gothenburg , Sweden.
Niclas
N
Pettersson
c Departments of Medical Physics and Oncology , Aarhus University Hospital , Aarhus , Denmark.
Ludvig P
LP
Muren
b Division of Clinical Cancer Epidemiology, Department of Oncology , Institute of Clinical Sciences, the Sahlgrenska Academy at the University of Gothenburg , Sweden.
Ann-Charlotte
AC
Waldenström
c Departments of Medical Physics and Oncology , Aarhus University Hospital , Aarhus , Denmark.
Morten
M
Høyer
b Division of Clinical Cancer Epidemiology, Department of Oncology , Institute of Clinical Sciences, the Sahlgrenska Academy at the University of Gothenburg , Sweden.
Gunnar
G
Steineck
a Department of Medical Physics , Memorial Sloan Kettering Cancer Center , New York , USA.
Joseph O
JO
Deasy
D000368:Aged; D003672:Defecation / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005242:Fecal Incontinence / Q000209:etiology; D041981:Gastrointestinal Tract / Q000528:radiation effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D058958:Organs at Risk / Q000528:radiation effects; D010146:Pain / Q000209:etiology; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000209:etiology*; D011878:Radiotherapy / Q000009:adverse effects*