Frequent Stools Were Related to Reduced Quality of Life and Capacity in Daily Activities: Weekly Observations During and After Pelvic or Abdominal Radiotherapy.

BACKGROUND: Greater knowledge regarding stool frequency and infrequency during pelvic and abdominal irradiation is needed to accurately identify patients at risk of either. OBJECTIVE: To describe occurrence of frequent and infrequent stools during pelvic-abdominal radiotherapy, and to compare quality of life (QoL) and activities of daily living (ADLs) of those patients experiencing frequent stools with those of patients experiencing infrequent stools. METHODS: Longitudinally during radiotherapy, 193 patients (64% had gynecological tumors) documented stool frequency, medications, and QoL using the Functional Assessment of Cancer Therapy-General. RESULTS: Fifty (26%) experienced frequent stools (≥28 stools a week), and 17 (9%) experienced infrequent stools (<3 stools a week). The frequency of stools and the consumption of medication for diarrhea were highest the last week of the radiotherapy period (50% had ≥49 stools a week, and 50% could not even define the number of stools). Thirty-seven of the patients experiencing frequent stools used antidiarrhea medications. Patients with frequent stools experienced lower QoL (P = .035) and capacity in ADLs (P = .023) compared with patients not experiencing frequent stools. CONCLUSIONS: A fourth of patients irradiated over pelvic or abdominal fields experienced frequent stools, defined as moderate to severe diarrhea, and those patients experienced lower QoL and capacity in ADLs compared with patients who did not experience frequent stools. Infrequent stools were rarely experienced. IMPLICATIONS FOR PRACTICE: Cancer nursing professionals should deliver evidence-based strategies to prevent frequent stools and treat frequent stools as an approach to lower the risk of impaired capacity in daily living and worsened QoL.

A prospective analysis of health-related quality of life in intermediate and high-risk prostate cancer patients managed with intensity modulated radiation therapy, with vs. without hormonal therapy.

INTRODUCTION: Combined radiotherapy and hormonal treatment are recommended for intermediate- and high-risk prostate cancer (CaP). This study compared the long-term effects on health-related quality of life (HRQoL) of intermediate- and high-risk CaP patients managed with radiation therapy (RT) with vs. without hormone therapy (HT). METHODS: Patients with intermediate- and high-risk CaP enrolled in the Center for Prostate Disease Research diagnosed from 2007 to 2017 were included. EPIC and SF-36 questionnaires were completed and HRQoL scores were compared for patients receiving RT vs. RT + HT at baseline (pretreatment), 6, 12, 24, 36, 48, and 60 months after CaP diagnosis. Longitudinal patterns of change in HRQoL were modeled using linear regression models, adjusting for baseline HRQoL, age at CaP diagnosis, race, comorbidities, National Comprehensive Cancer Network (NCCN) risk stratum, time to treatment, and follow-up time. RESULTS: Of 164 patients, 93 (56.7%) received RT alone and 71 (43.3%) received RT + HT. Both groups reported comparable baseline HRQoL. Patients receiving RT+HT were more likely to be NCCN high risk as compared to those receiving only RT. The RT + HT patients experienced worse sexual function, hormonal function, and hormonal bother than those who only received RT; however, HRQoL recovered over time for the RT + HT group. No significant differences were observed between groups in urinary and bowel domains or SF-36 mental and physical scores. CONCLUSION: Combined RT + HT treatment was associated with temporary lower scores in sexual and hormonal HRQoL compared with RT only. Intermediate- and high-risk CaP patients should be counseled about the possible declines in HRQoL associated with HT.

Methods of assessing late radiotherapy effects on bowel function.

PURPOSE OF REVIEW: Pelvic radiation disease in the form of chronic radiation-induced consequences of treatment is under recognized by healthcare professionals and under reported by patients. Gastrointestinal symptoms are not routinely assessed, and may not be causally associated with previous radiotherapy. These symptoms are therefore often under treated. RECENT FINDINGS: A literature search was conducted in Ovid Medline, which included Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Ovid Embase for articles published between 2016 and April 2018. A total of 11 articles were selected for review. A wide range of patient reported outcome measure instruments are used in research and practice. Clinical symptom grading is restricted to a fewer number of tools but may not always capture issues, such as urgency, that are important to the patient. Clinician and patient concordance in the assessment of outcomes is limited. Initiatives to prompt communication of the relative risks of the late consequences of treatment and comparative effectiveness of treatments decisions are developing, as are new techniques to limit irradiation of healthy tissue. SUMMARY: Nonstandardized outcome measurement reduces the ability to aggregate toxicity and patient outcomes across clinical trials. The development of standardized screening and treatment algorithms for gastrointestinal symptoms can systematically locate and treat gastrointestinal late effects of treatment.

Patient-reported quality of life during definitive and postprostatectomy image-guided radiation therapy for prostate cancer.

PURPOSE: The importance of patient-reported outcomes is well-recognized. Long-term patient-reported symptoms have been described for individuals who completed radiation therapy (RT) for prostate cancer. However, the trajectory of symptom development during the course of treatment has not been well-described in patients receiving modern, image-guided RT. METHODS AND MATERIALS: Quality-of-life data were prospectively collected for 111 prostate cancer patients undergoing RT using the validated Prostate Cancer Symptom Indices, which assessed 5 urinary obstructive/irritative and 6 bowel symptoms. Patients who received definitive RT (N = 73) and postprostatectomy RT (N = 38) were analyzed separately. The frequency and severity of symptoms over multiple time points are reported. RESULTS: An increasing number of patients had clinically meaningful urinary and bowel symptoms over the course of RT. A greater proportion of patients undergoing definitive RT reported clinically meaningful urinary symptoms at the end of RT compared with baseline in terms of flow (33% vs 19%) and frequency (39% vs 18%). Individuals receiving postprostatectomy radiation also reported an increase in symptoms including frequency (29% vs 3%) and nocturia (50% vs 21%). Clinically meaningful bowel symptoms were less commonly reported. Patients receiving definitive RT reported an increase in diarrhea (9% vs 4%) and urgency (12% vs 6%) at the completion of RT compared with baseline. Both bowel and urinary symptoms approached their baseline levels by the time of first follow-up after treatment completion. The majority of patients who had clinically meaningful urinary or bowel symptoms during RT did not have them at 2 years or beyond, and development of new symptoms in the long term was uncommon. CONCLUSIONS: There is a modest increase in urinary and bowel symptoms over the course of treatment for individuals receiving definitive and postprostatectomy image-guided RT. These data can help inform both providers and patients regarding the trajectory of symptoms and allow for reasonable expectations regarding toxicity under treatment.

Plan quality and dosimetric association of patient-reported rectal and urinary toxicities for prostate stereotactic body radiotherapy.

BACKGROUND AND PURPOSE: To study the association between dosimetric parameters with patient-reported quality-of-life (QOL) in urinary irritative/incontinency and bowel functions for prostate stereotactic body radiotherapy (SBRT). MATERIAL AND METHODS: The patient-reported QOL was evaluated using the Expanded Prostate Cancer Index Composite (EPIC-26). According to the progression in QOL score over 12months, patients were assigned to one of three subgroups: score decrement, no change, or increment. The dosimetric parameters were cross-compared among subgroups in urinary and bowel domains using univariate Analysis of Variance (ANOVA). The evaluated dosimetric metrics included target volume, V100 (volume receiving 100% prescription dose); rectal volume/dose-volume endpoints, maximum/mean doses; bladder volume/dose-volume endpoints, and maximum/mean doses. RESULTS: Patients with consistent QOL reduction in urinary irritation function were significantly associated with greater mean bladder dose, greater V85/V90/V95/V100 and D2cc/D10cc. Patients with QOL reduction in urinary incontinence were marginally associated with greater mean bladder dose (p=0.06). None of the evaluated dosimetric parameters showed a significant correlation with QOL score change in bowel function. CONCLUSIONS: Patients with large prostate size were more susceptible to QOL decrements for urinary irritative and incontinency functions. Large bladder V85/V90/V95/V100 was associated with QOL decrements in the urinary irritative domain at 1-year after prostate SBRT.

Normal tissue complication probability (NTCP) models for late rectal bleeding, stool frequency and fecal incontinence after radiotherapy in prostate cancer patients.

BACKGROUND AND PURPOSE: Curative radiotherapy for prostate cancer may lead to anorectal side effects, including rectal bleeding, fecal incontinence, increased stool frequency and rectal pain. The main objective of this study was to develop multivariable NTCP models for these side effects. MATERIAL AND METHODS: The study sample was composed of 262 patients with localized or locally advanced prostate cancer (stage T1-3). Anorectal toxicity was prospectively assessed using a standardized follow-up program. Different anatomical subregions within and around the anorectum were delineated. A LASSO logistic regression analysis was used to analyze dose volume effects on toxicity. RESULTS: In the univariable analysis, rectal bleeding, increase in stool frequency and fecal incontinence were significantly associated with a large number of dosimetric parameters. The collinearity between these predictors was high (VIF>5). In the multivariable model, rectal bleeding was associated with the anorectum (V70) and anticoagulant use, fecal incontinence was associated with the external sphincter (V15) and the iliococcygeal muscle (V55). Finally, increase in stool frequency was associated with the iliococcygeal muscle (V45) and the levator ani (V40). No significant associations were found for rectal pain. CONCLUSIONS: Different anorectal side effects are associated with different anatomical substructures within and around the anorectum. The dosimetric variables associated with these side effects can be used to optimize radiotherapy treatment planning aiming at prevention of specific side effects and to estimate the benefit of new radiation technologies.

Predictors of radiation-induced gastrointestinal morbidity: A prospective, longitudinal study following radiotherapy for carcinoma of the prostate.

Background Chronic gastrointestinal (GI) morbidity occurs in ≥50% of patients after external beam radiotherapy (EBRT) for carcinoma of prostate (CaP). This prospective, longitudinal study examines which baseline measurements of: 1) homocysteine and micronutrients in plasma; 2) chromosome damage/misrepair biomarkers; and 3) anal and rectal dose volume metrics predict GI morbidity after EBRT. Patients and methods In total, 106 patients with CaP had evaluations of GI symptoms (modified LENT-SOMA questionnaires) before EBRT and at one month, one, two and three years after its completion. Other variables measured before EBRT were: 1) plasma concentrations of homocysteine and micronutrients including caroteinoids and selenium; 2) chromosome damage/DNA misrepair (micronuclei/nucleoplasmic bridge) indices; and 3) mean anal and rectal wall doses and volumes of anal and rectal walls receiving ≥40 Gy and ≥60 Gy. Univariate and multivariate analyzes examined the relationships among: 1) plasma levels of homocysteine and micronutrients; 2) indices of chromosome damage/DNA misrepair; and 3) mean anal and rectal wall doses and volumes of anal and rectal walls receiving ≥40 Gy and ≥60 Gy and total GI symptom scores from one month to three years after EBRT. Results Increased frequency and urgency of defecation, rectal mucous discharge and bleeding after EBRT resulted in sustained rises in total GI symptom scores above baseline at three years. On univariate analysis, total GI symptom scores were significantly associated with: 1) plasma selenium and α tocopherol; 2) micronuclei indices of DNA damage; 3) mean anal and rectal wall doses; and 4) volumes of anal and rectal wall receiving ≥40 Gy and ≥60 Gy (p = 0.08-<0.001). On multivariate analysis, only volume of anal wall receiving ≥40 Gy was significant for increased GI symptoms after EBRT (p < 0.001). Conclusion The volume of anal wall receiving ≥40 Gy predicts chronic GI morbidity after EBRT for CaP.

Longitudinal assessment of quality of life after surgery, conformal brachytherapy, and intensity-modulated radiation therapy for prostate cancer.

PURPOSE: We evaluated quality-of-life changes (QoL) in 907 patients treated with either radical prostatectomy (open or laparoscopic), real-time planned conformal brachytherapy, or high-dose intensity-modulated radiotherapy (IMRT) on a prospective IRB-approved longitudinal study. METHODS: Validated questionnaires given pretreatment (baseline) and at 3, 6, 9, 12, 15, 18, 24, 36, and 48 months addressed urinary function, urinary bother, bowel function, bowel bother, sexual function, and sexual bother. RESULTS: At 48 months, surgery had significantly higher urinary incontinence than others (both P<.001), but fewer urinary irritation/obstruction symptoms (all P<.001). Very low levels of bowel dysfunction were observed and only small subsets in each group showed rectal bleeding. Brachytherapy and IMRT showed better sexual function than surgery accounting for baseline function and other factors (delta 14.29 of 100, 95% CI, 8.57-20.01; and delta 10.5, 95% CI, 3.78-17.88). Sexual bother was similar. Four-year outcomes showed persistent urinary incontinence for surgery with more obstructive urinary symptoms for radiotherapy. Using modern radiotherapy delivery, bowel function deterioration is less-often observed. Sexual function was strongly affected in all groups yet significantly less for radiotherapy. CONCLUSIONS: Treatment selection should include patient preferences and balance predicted disease-free survival over a projected time vs potential impairment of QoL important for the patient.

Effect of inulin and fructo-oligosaccharide on the prevention of acute radiation enteritis in patients with gynecological cancer and impact on quality-of-life: a randomized, double-blind, placebo-controlled trial.

BACKGROUND/OBJECTIVES: The pathogenesis of enteritis after abdominal radiotherapy (RT) is unknown, although changes in fecal microbiota may be involved. Prebiotics stimulate the proliferation of Lactobacillus spp and Bifidobacterium spp, and this may have positive effects on the intestinal mucosa during abdominal RT. SUBJECTS/METHODS: We performed a randomized, double-blind, placebo-controlled trial involving patients with gynecological cancer who received abdominal RT after surgery. Patients were randomized to receive prebiotics or placebo. The prebiotic group received a mixture of fiber (50 inulin and 50% fructo-oligosaccharide), and the placebo group received 6 g of maltodextrin twice daily from 1 week before to 3 weeks after RT. The number of bowel movements and stool consistency was recorded daily. Diarrhea was evaluated according to the Common Toxicity Criteria of the National Cancer Institute. Stool consistency was assessed using the 7-point Bristol scale. Patients' quality-of-life was evaluated at baseline and at completion of RT using the EORTC-QLQ-C30 (European Organization for Research and Treatment of Cancer quality-of-life Questionnaire C30) test. RESULTS: Thirty-eight women with a mean age of 60.3±11.8 years participated in the study. Both groups (prebiotic (n=20) and placebo (n=18)) were comparable in their baseline characteristics. The number of bowel movements per month increased in both groups during RT. The number of bowel movements per day increased in both groups. The number of days with watery stool (Bristol score 7) was lower in the prebiotic group (3.3±4.4 to 2.2±1.6) than in the placebo group (P=0.08). With respect to quality-of-life, the symptoms with the highest score in the placebo group were insomnia at baseline and diarrhea toward the end of the treatment. In the prebiotic group, insomnia was the symptom with the highest score at both assessments, although the differences were not statistically significant. CONCLUSIONS: Prebiotics can improve the consistency of stools in gynecologic cancer patients on RT. This finding could have important implications in the quality-of-life of these patients during treatment.

Health-related quality-of-life changes due to high-dose-rate brachytherapy, low-dose-rate brachytherapy, or intensity-modulated radiation therapy for prostate cancer.

PURPOSE: To compare urinary, bowel, and sexual health-related quality-of-life (HRQOL) changes due to high-dose-rate (HDR) brachytherapy, low-dose-rate (LDR) brachytherapy, or intensity-modulated radiation therapy (IMRT) monotherapy for prostate cancer. METHODS AND MATERIALS: Between January 2002 and September 2013, 413 low-risk or favorable intermediate-risk prostate cancer patients were treated with HDR brachytherapy monotherapy to 2700-2800 cGy in two fractions (n = 85), iodine-125 LDR brachytherapy monotherapy to 14,500 cGy in one fraction (n = 249), or IMRT monotherapy to 7400-8100 cGy in 37-45 fractions (n = 79) without pelvic lymph node irradiation. No androgen deprivation therapy was given. Patients used an international prostate symptoms score questionnaire, an expanded prostate cancer index composite-26 bowel questionnaire, and a sexual health inventory for men questionnaire to assess their urinary, bowel, and sexual HRQOL, respectively, pretreatment and at 1, 3, 6, 9, 12, and 18 months posttreatment. RESULTS: Median follow-up was 32 months. HDR brachytherapy and IMRT patients had significantly less deterioration in their urinary HRQOL than LDR brachytherapy patients at 1 and 3 months after irradiation. The only significant decrease in bowel HRQOL between the groups was seen 18 months after treatment, at which point IMRT patients had a slight, but significant, deterioration in their bowel HRQOL compared with HDR and LDR brachytherapy patients. HDR brachytherapy patients had worse sexual HRQOL than both LDR brachytherapy and IMRT patients after treatment. CONCLUSIONS: IMRT and HDR brachytherapy cause less severe acute worsening of urinary HRQOL than LDR brachytherapy. However, IMRT causes a slight, but significant, worsening of bowel HRQOL compared with HDR and LDR brachytherapy.

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. MATERIAL AND 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%). CONCLUSION: 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.

Gastrointestinal dose-histogram effects in the context of dose-volume-constrained prostate radiation therapy: analysis of data from the RADAR prostate radiation therapy trial.

PURPOSE: To use a high-quality multicenter trial dataset to determine dose-volume effects for gastrointestinal (GI) toxicity following radiation therapy for prostate carcinoma. Influential dose-volume histogram regions were to be determined as functions of dose, anatomical location, toxicity, and clinical endpoint. METHODS AND MATERIALS: Planning datasets for 754 participants in the TROG 03.04 RADAR trial were available, with Late Effects of Normal Tissues (LENT) Subjective, Objective, Management, and Analytic (SOMA) toxicity assessment to a median of 72 months. A rank sum method was used to define dose-volume cut-points as near-continuous functions of dose to 3 GI anatomical regions, together with a comprehensive assessment of significance. Univariate and multivariate ordinal regression was used to assess the importance of cut-points at each dose. RESULTS: Dose ranges providing significant cut-points tended to be consistent with those showing significant univariate regression odds-ratios (representing the probability of a unitary increase in toxicity grade per percent relative volume). Ranges of significant cut-points for rectal bleeding validated previously published results. Separation of the lower GI anatomy into complete anorectum, rectum, and anal canal showed the impact of mid-low doses to the anal canal on urgency and tenesmus, completeness of evacuation and stool frequency, and mid-high doses to the anorectum on bleeding and stool frequency. Derived multivariate models emphasized the importance of the high-dose region of the anorectum and rectum for rectal bleeding and mid- to low-dose regions for diarrhea and urgency and tenesmus, and low-to-mid doses to the anal canal for stool frequency, diarrhea, evacuation, and bleeding. CONCLUSIONS: Results confirm anatomical dependence of specific GI toxicities. They provide an atlas summarizing dose-histogram effects and derived constraints as functions of anatomical region, dose, toxicity, and endpoint for informing future radiation therapy planning.

Identification of motor neurons and a mechanosensitive sensory neuron in the defecation circuitry of Drosophila larvae.

Defecation allows the body to eliminate waste, an essential step in food processing for animal survival. In contrast to the extensive studies of feeding, its obligate counterpart, defecation, has received much less attention until recently. In this study, we report our characterizations of the defecation behavior of Drosophila larvae and its neural basis. Drosophila larvae display defecation cycles of stereotypic frequency, involving sequential contraction of hindgut and anal sphincter. The defecation behavior requires two groups of motor neurons that innervate hindgut and anal sphincter, respectively, and can excite gut muscles directly. These two groups of motor neurons fire sequentially with the same periodicity as the defecation behavior, as revealed by in vivo Ca(2+) imaging. Moreover, we identified a single mechanosensitive sensory neuron that innervates the anal slit and senses the opening of the intestine terminus. This anus sensory neuron relies on the TRP channel NOMPC but not on INACTIVE, NANCHUNG, or PIEZO for mechanotransduction.

Development and validation of a scoring system for late anorectal side-effects in patients treated with radiotherapy for prostate cancer.

PURPOSE: To develop and validate a scoring system for evaluation of long term anorectal dysfunction following radiotherapy for prostate cancer. MATERIALS AND METHODS: Patients treated for prostate cancer with radiotherapy filled in questionnaires on anorectal function and quality of life. Items for the condensed anorectal dysfunction score (RT-ARD) were identified and weighted by binomial regression analysis. The score was tested in a separate patient material by receiver operating characteristic (ROC) analysis and correlations to quality of life domains. RESULTS: A total of 309 patients participated in the study. The items selected were "incontinence for solid stool", "ability to defer defecation", "unproductive call to stool", "clustering of stool", and "mucus in stool." Patients were grouped into three categories according to the RT-ARD score; 0-8 (no RT-ARD), 9-23 (minor RT-ARD), 24-45 (major RT-ARD). ROC analyses revealed high sensitivity (91%) and specificity (85%) for major RT-ARD. The prediction model demonstrated a perfect fit in 60%, moderate fit in 36% and no fit in 4%. There was good correlation between the RT-ARD score and quality of life. CONCLUSIONS: The RT-ARD score is a validated and simple instrument for evaluation of anorectal dysfunction following radiotherapy for prostate cancer, and the RT-ARD score correlates to the patient's quality of life.

Systematic review: anal and rectal changes after radiotherapy for prostate cancer.

PURPOSE: Pelvic radiotherapy may lead to changes of anorectal function resulting in incontinence-related complaints. The aim of this study was to systematically review objective findings of late anorectal physiology and mucosal appearance after irradiation for prostate cancer. METHODS: MEDLINE, EMBASE, and the Cochrane library were searched. Original articles in which anal function, rectal function, or rectal mucosa were examined ≥3 months after EBRT for prostate cancer were included. RESULTS: Twenty-one studies were included with low to moderate quality. Anal resting pressures significantly decreased in 6 of the 9 studies including 277 patients. Changes of squeeze pressure and rectoanal inhibitory reflex were less uniform. Rectal distensibility was significantly impaired after EBRT in 7 of 9 studies (277 patients). In 4 of 9 studies on anal and in 5 of 9 on rectal function, disturbances were associated with urgency, frequent bowel movements or fecal incontinence. Mucosal changes as assessed by the Vienna Rectoscopy Score revealed telangiectasias in 73 %, congestion in 33 %, and ulceration in 4 % of patients in 8 studies including 346 patients, but no strictures or necrosis. Three studies reported mucosal improvement during follow-up. Telangiectasias, particularly multiple, were associated with rectal bleeding. Not all bowel complaints (30 %) were related to radiotherapy. CONCLUSIONS: Low to moderate quality evidence indicates that EBRT reduces anal resting pressure, decreases rectal distensibility, and frequently induces telangiectasias of rectal mucosa. Objective changes may be associated with fecal incontinence, urgency, frequent bowel movements, and rectal bleeding, but these symptoms are not always related to radiation damage.

Assessment of late urinary, bowel and sexual function after dose escalation from 70 to 76 Gy using image-guided radiotherapy in curative treatment of prostate cancer.

OBJECTIVE: The aim of this study was to evaluate the late urinary, bowel and sexual function among men with localized or locally advanced prostate cancer treated with curative radiotherapy after the introduction of image-guided radiotherapy to 76 Gy using the Swedish BeamCath® technique. MATERIAL AND METHODS: All patients treated with curative radiotherapy during 2003-2006 were invited to participate in this retrospective study. In total, 87% (158/181) participated in the study. The median observation time was 35 months. Comparisons were made between the standard 70 Gy (n = 73) and the 76 Gy (n = 85) treatment groups. Assessments of late urinary, bowel and sexual function were questionnaire based, and included function items in the Expanded Prostate Cancer Index Composite. RESULTS: Most late urinary and bowel symptoms were reported to occur seldom or never in the majority of men, while late sexual toxicity was reported in a large proportion (66%) of men. Seven men (4%) used diapers. Only 25% (n = 40) reported having an erection firm enough for intercourse. None of the reported urinary or sexual function symptoms differed between the treatment groups. Rectal urgency at least once daily was a more frequent symptom in the 70 Gy group than the 76 Gy group (28% vs 9%, p = 0.006). Painful bowel movements were a more common symptom in the 70 Gy group (11% vs 1%, p = 0.01). CONCLUSION: Dose escalation up to 76 Gy using the BeamCath technique was not associated with more late toxicities than the standard 70 Gy dose.

Increased rectal wall stiffness after prostate radiotherapy: relation with fecal urgency.

BACKGROUND: Late anorectal toxicity is a frequent adverse event of external beam radiotherapy (EBRT) for prostate cancer. The pathophysiology of anorectal toxicity remains unknown, but we speculate that rectal distensibility is impaired due to fibrosis. Our goal was to determine whether EBRT induces changes of rectal distensibility as measured by an electronic barostat and to explore whether anorectal complaints are related to specific changes of anorectal function. METHODS: Thirty-two men, irradiated for localized prostate carcinoma, underwent barostat measurements, anorectal manometry, and completed a questionnaire prior to and 1 year after radiotherapy. The primary outcome measure was rectal distensibility in response to stepwise isobaric distensions. In addition, we assessed sensory thresholds, anal pressures, and anorectal complaints. KEY RESULTS: External beam radiotherapy reduced maximal rectal capacity (227 ± 14 mL vs 277 ± 15 mL; P < 0.001), area under the pressure-volume curve (3212 ± 352 mL mmHg vs 3969 ± 413 mL mmHg; P < 0.005), and rectal compliance (15.7 ± 1.2 mL mmHg(-1) vs 17.6 ± 0.9 mL mmHg(-1) ; P = 0.12). Sensory pressure thresholds did not significantly change. Sixteen of the 32 patients (50%) had one or more anorectal complaints. Patients with urgency (n = 10) had a more reduced anal squeeze and maximum pressure (decrease 29 ± 11 mmHg vs 1 ± 7 mmHg; P < 0.05 and 31 ± 12 mmHg vs 2 ± 8 mmHg; P < 0.05 respectively) compared with patients without complaints, indicating a deteriorated external anal sphincter function. CONCLUSIONS & INFERENCES: Irradiation for prostate cancer leads to reduced rectal distensibility. In patients with urgency symptoms, anal sphincter function was also impaired.

Differences in radiation dosimetry and anorectal function testing imply that anorectal symptoms may arise from different anatomic substrates.

PURPOSE: To explore the influence of functional changes and dosimetric parameters on specific incontinence-related anorectal complaints after prostate external beam radiotherapy and to estimate dose-effect relations for the anal wall and rectal wall. METHODS AND MATERIALS: Sixty patients, irradiated for localized prostate cancer, underwent anorectal manometry and barostat measurements to evaluate anal pressures, rectal capacity, and rectal sensory functions. In addition, 30 untreated men were analyzed as a control group. In 36 irradiated patients, the anal wall and rectal wall were retrospectively delineated on planning computed tomography scans, and dosimetric parameters were retrieved from the treatment plans. Functional and dosimetric parameters were compared between patients with and without complaints, focusing on urgency, incontinence, and frequency. RESULTS: After external beam radiotherapy, reduced anal pressures and tolerated rectal volumes were observed, irrespective of complaints. Patients with urgency and/or incontinence showed significantly lower anal resting pressures (mean 38 and 39 vs. 49 and 50 mm Hg) and lower tolerated rectal pressures (mean 28 and 28 vs. 33 and 34 mm Hg), compared to patients without these complaints. In patients with frequency, almost all rectal parameters were reduced. Several dosimetric parameters to the anal wall and rectal wall were predictive for urgency (e.g., anal D(mean)>38 Gy), whereas some anal wall parameters correlated to incontinence and no dose-effect relation for frequency was found. CONCLUSIONS: Anorectal function deteriorates after external beam radiotherapy. Different incontinence-related complaints show specific anorectal dysfunctions, suggesting different anatomic and pathophysiologic substrates: urgency and incontinence seem to originate from both anal wall and rectal wall, whereas frequency seems associated with rectal wall dysfunction. Also, dose-effect relations differed between these complaints. This implies that anal wall and rectal wall should be considered separate organs in radiotherapy planning.

Cross validation of the prostate cancer radiotherapy late toxicity (PCRT) questionnaire with the expanded prostate cancer index composite (EPIC) instrument.

INTRODUCTION: A 29-item prostate cancer radiotherapy (PCRT) questionnaire with genitourinary (GU), gastrointestinal (GI), and sexual (S) domains has been previously validated for the assessment of late toxicity health-related quality of life (HRQoL) effects. The study objective was to cross-validate the PCRT domains versus the expanded prostate cancer index composite (EPIC) questionnaire urinary (U), bowel (B), hormonal (H), and S subscales. METHODS AND MATERIALS: A single-institution cross-sectional PCRT patient cohort was surveyed. Descriptive and intra- and inter-class correlation coefficient statistics for the various EPIC and PCRT HRQoL domain scores were generated. Univariable and multivariable Cox and logistic regressions were performed depending on the HRQoL endpoint being assessed. RESULTS: A total of 189/276 patients (68%) completed questionnaires with EPIC and PCRT missing data rates of 9% and 4%, respectively. Mean age was 75.8 years (SD 5.5) and the mean time of questionnaire completion after radiotherapy was 852 days (range 212-1454 days). Mean EPIC urinary (85.1 SD 12.9), bowel (84.1 SD 15.8), sexual (21.8 SD 20.7), and hormonal (85.3 SD 13.7) as well as PCRT genitourinary (66.1 SD 15.3), gastrointestinal (83.6 SD 14.3), and sexual (39.4 SD 21.6) domain scores were calculated. Intraclass correlation coefficients comparing corresponding EPIC/PCRT domains ranged from 0.50-0.88. Interclass correlation coefficients for non-corresponding EPIC/PCRT domains ranged from 0.16-0.43 and 0.23-0.30, respectively. EPIC B/U, PCRT GI/GU and PCRT S required arcsin square root transformation and EPIC S/H domains required dichotomous transformations prior to univariable/multivariable analyses. Multivariable analysis demonstrated novel associations between predictive variables and HRQoL domains including between the PTV-bladder overlap volume and PCRT GU score. CONCLUSIONS: The PCRT is a compact, valid, and HRQoL instrument with very high questionnaire compliance rates and similar statistical properties to the EPIC instrument. However, dichotomization of the PRCT S data was not required which suggests some potential statistical advantage to the PCRT.

Impact of preoperative radiotherapy on general and disease-specific health status of rectal cancer survivors: a population-based study.

PURPOSE: To date, few studies have evaluated the impact of preoperative radiotherapy (pRT) on long-term health status of rectal cancer survivors. Using a population-based sample, we assessed the impact of pRT on general and disease-specific health status of rectal cancer survivors up to 10 years post diagnosis. The health status of older (≥75 years old at diagnosis) pRT survivors was also compared with that of younger survivors. METHODS AND MATERIALS: Survivors identified from the Eindhoven Cancer Registry treated with surgery only (SU) or with pRT between 1998 and 2007 were included. Survivors completed the Short Form-36 (SF-36) health survey questionnaire and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal 38 (EORTC QLQ-CR38) questionnaire. The SF-36 and EORTC QLQ-CR38 (sexuality subscale) scores of the survivors were compared to an age- and sex-matched Dutch normal population. RESULTS: A total of 340 survivors (response, 85%; pRT survivors, 71%) were analyzed. Overall, survivors had similar general health status. Both short-term (<5 years) and long-term (≥5 years) pRT survivors had significantly poorer body image and more problems with gastrointestinal function, male sexual dysfunction, and defecation than SU survivors. Survivors had comparable general health status but greater sexual dysfunction than the normal population. Older pRT survivors had general and disease-specific health status comparable to that of younger pRT survivors. CONCLUSIONS: For better survivorship care, rectal cancer survivors could benefit from increased clinical and psychological focus on the possible long-term morbidity of treatment and its effects on health status.