Late Rectal Bleeding Research Articles

Long term rectal function after high-dose prostatecancer radiotherapy: Results from a prospective cohort study

PurposeTo prospectively evaluate long-term late rectal bleeding (lrb) and faecal incontinence (linc) after high-dose radiotherapy (RT) for prostate cancer in the AIROPROS 0102 population, and to assess clinical/dosimetric risk factors. Materials and methodsQuestionnaires of 515 patients with G0 baseline incontinence and bleeding scores (follow-up ⩾6years) were analysed. Correlations between lrb/linc and many clinical and dosimetric parameters were investigated by univariate and multivariate logistic analyses. The correlation between lrb/linc and symptoms during the first 3years after RT was also investigated. ResultsOf 515 patients lrb G1, G2 and G3 was found in 32 (6.1%), 2 (0.4%) and 3 (0.6%) patients while linc G1, G2 and G3 was detected in 50 (9.7%), 3 (0.6%) and 3 (0.6%), respectively. The prevalence of G2–G3 lrb events was significantly reduced compared to the first 3-years (1% vs 2.7%, p=0.016) ⩾G1 lrb was significantly associated with V75Gy (OR=1.07). In multivariate analysis, ⩾G1 linc was associated with V40Gy (OR=1.015), use of antihypertensive medication (OR=0.38), abdominal surgery before RT (OR=4.7), haemorrhoids (OR=2.6), and G2–G3 acute faecal incontinence (OR=4.4), a nomogram to predict the risk of long-term ⩾G1 linc was proposed.Importantly, the prevalence of ⩾G1 linc was significantly correlated with the mean incontinence score during the first 3years after RT (OR=16.3). ConclusionsLong-term (median: 7years) rectal symptoms are prevalently mild and strongly correlated with moderate/severe events occurring in the first 3years after RT. Linc was associated with several risk factors.

Radioprotective effect of calcium channel blockers against late rectal bleeding in prostate cancer

This study was done to assess the impact of clinical factors and in particular the use of drugs for concomitant illnesses on late radiation-induced rectal bleeding in patients with prostate cancer. Patients with histologically proven prostate adenocarcinoma treated with radical radiotherapy and followed up for at least 6months were selected. The correlation between late rectal bleeding and a number of factors was investigated by univariate and multivariate analysis. A total of 278 patients who underwent radiotherapy at our institution between October 2002 and May 2011 were selected. At univariate analysis, delivery of radiation doses higher than 70Gy and use of angiotensin-converting enzyme inhibitors were associated with a higher incidence of rectal bleeding. Conversely, patients who used calcium channel blockers had a lower risk (3-year rectal bleeding-free survival 89.8 versus 66.5%, p=0.043). At multivariate analysis, use of calcium channel blockers was found to have a protective effect with a hazard ratio of 0.3 (95% CI 0.12-0.96). Delivery of higher radiation doses was associated with an increased risk of rectal bleeding (hazard ratio 3.02, 95% CI 1.23-7.38). Use of calcium channel blockers during and after radiotherapy treatment might have a protective effect against late rectal bleeding. If these results are reconfirmed by larger clinical series, calcium channel blockers may be tested as radioprotector agents in clinical trials.

An assessment of PTV margin based on actual accumulated dose for prostate cancer radiotherapy

The purpose of this work is to present the results of a margin reduction study involving dosimetric and radiobiologic assessment of cumulative dose distributions, computed using an image guided adaptive radiotherapy based framework. Eight prostate cancer patients, treated with 7–9, 6 MV, intensity modulated radiation therapy (IMRT) fields, were included in this study. The workflow consists of cone beam CT (CBCT) based localization, deformable image registration of the CBCT to simulation CT image datasets (SIM-CT), dose reconstruction and dose accumulation on the SIM-CT, and plan evaluation using radiobiological models. For each patient, three IMRT plans were generated with different margins applied to the CTV. The PTV margin for the original plan was 10 mm and 6 mm at the prostate/anterior rectal wall interface (10/6 mm) and was reduced to: (a) 5/3 mm, and (b) 3 mm uniformly. The average percent reductions in predicted tumor control probability (TCP) in the accumulated (actual) plans in comparison to the original plans over eight patients were 0.4%, 0.7% and 11.0% with 10/6 mm, 5/3 mm and 3 mm uniform margin respectively. The mean increase in predicted normal tissue complication probability (NTCP) for grades 2/3 rectal bleeding for the actual plans in comparison to the static plans with margins of 10/6, 5/3 and 3 mm uniformly was 3.5%, 2.8% and 2.4% respectively. For the actual dose distributions, predicted NTCP for late rectal bleeding was reduced by 3.6% on average when the margin was reduced from 10/6 mm to 5/3 mm, and further reduced by 1.0% on average when the margin was reduced to 3 mm. The average reduction in complication free tumor control probability (P+) in the actual plans in comparison to the original plans with margins of 10/6, 5/3 and 3 mm was 3.7%, 2.4% and 13.6% correspondingly. The significant reduction of TCP and P+ in the actual plan with 3 mm margin came from one outlier, where individualizing patient treatment plans through margin adaptation based on biological models, might yield higher quality treatments.

Use of Anticoagulants Predict Late Rectal Bleeding Following Definitive External Beam Radiation Therapy for Prostate Cancer

To determine the relationship between hematologic modifying drugs and the risk of acute and late radiation proctitis in patients undergoing definitive external beam radiation therapy for prostate cancer.

Impact of MLC Leaf Width on Incidence of the Late Rectal Bleeding After Intensity Modulated Radiation Therapy for Localized Prostate Carcinoma

The aim of this study was to investigate the impact of multileaf collimator (MLC) leaf width on the onset of late rectal bleeding for patients with prostate cancer treated by intensity-modulated radiation therapy (IMRT).

Rectal endoscopy findings following stereotactic body radiation therapy for clinically localized prostate cancer

BackgroundTreating prostate cancer with SBRT could potentially minimize radiation proctitis by reducing high-dose rectal irradiation. In addition, it offers the potential radiobiologic benefits of hypofractionation. This study reports the endoscopic changes and the associated clinical rectal toxicity in these patients.MethodsWe reviewed the records of patients treated from 2008–2011 for localized prostate cancer who had rectal endoscopy following SBRT. SBRT was delivered either as primary treatment in 5 fractions of 7–7.25 Gy, or as an initial boost in 3 fractions of 6.5 Gy followed by conventionally fractionated radiotherapy to 45–50.4 Gy. Endoscopic changes were graded using the Vienna Rectoscopy Score (VRS). Rectal toxicity was graded via CTCAEv.4. Rectal quality of life (QOL) was assessed via the bowel domain of the EPIC-26 questionnaire.ResultsFifty-one patients with a median 23 months follow-up were analyzed. Thirty-five patients completed SBRT monotherapy and 16 patients received SBRT as a boost to conventionally fractionated IMRT. The median interval from SBRT to rectal endoscopy was 13 months. Endoscopy revealed VRS Grade 1–2 telangiectasias for 10 patients and VRS Grade 1–2 mucosal edema for 12 patients. No rectal ulcerations, strictures or necrosis were observed. Grade 1–2 late rectal bleeding occurred in 10 patients. There were no CTCAEv.4 Grade ≥3 toxicities. Mean EPIC bowel scores decreased from a baseline value of 96.9 to 82.3 at 1-month, but subsequently increased to 91.0 at 24 months.ConclusionsIn this cohort that is skewed towards patients with rectal complaints, the rate and severity of endoscopic changes following SBRT is low. Rectal toxicity and QOL were comparable to patients treated with other radiation modalities. Prospective trials examining the endoscopic outcomes following SBRT for prostate cancer are needed for confirmation of the findings of this study.Trial registrationThe Georgetown Institutional Review Board has approved this retrospective study (IRB 2009–510).

Clinical implications in the use of the PBC algorithm versus the AAA by comparison of different NTCP models/parameters

PurposeRetrospective analysis of 3D clinical treatment plans to investigate qualitative, possible, clinical consequences of the use of PBC versus AAA.MethodsThe 3D dose distributions of 80 treatment plans at four different tumour sites, produced using PBC algorithm, were recalculated using AAA and the same number of monitor units provided by PBC and clinically delivered to each patient; the consequences of the difference on the dose-effect relations for normal tissue injury were studied by comparing different NTCP model/parameters extracted from a review of published studies. In this study the AAA dose calculation is considered as benchmark data. The paired Student t-test was used for statistical comparison of all results obtained from the use of the two algorithms.ResultsIn the prostate plans, the AAA predicted lower NTCP value (NTCPAAA) for the risk of late rectal bleeding for each of the seven combinations of NTCP parameters, the maximum mean decrease was 2.2%. In the head-and-neck treatments, each combination of parameters used for the risk of xerostemia from irradiation of the parotid glands involved lower NTCPAAA, that varied from 12.8% (sd=3.0%) to 57.5% (sd=4.0%), while when the PBC algorithm was used the NTCPPBC’s ranging was from 15.2% (sd=2.7%) to 63.8% (sd=3.8%), according the combination of parameters used; the differences were statistically significant. Also NTCPAAA regarding the risk of radiation pneumonitis in the lung treatments was found to be lower than NTCPPBC for each of the eight sets of NTCP parameters; the maximum mean decrease was 4.5%. A mean increase of 4.3% was found when the NTCPAAA was calculated by the parameters evaluated from dose distribution calculated by a convolution-superposition (CS) algorithm. A markedly different pattern was observed for the risk relating to the development of pneumonitis following breast treatments: the AAA predicted higher NTCP value. The mean NTCPAAA varied from 0.2% (sd = 0.1%) to 2.1% (sd = 0.3%), while the mean NTCPPBC varied from 0.1% (sd = 0.0%) to 1.8% (sd = 0.2%) depending on the chosen parameters set.ConclusionsWhen the original PBC treatment plans were recalculated using AAA with the same number of monitor units provided by PBC, the NTCPAAA was lower than the NTCPPBC, except for the breast treatments. The NTCP is strongly affected by the wide-ranging values of radiobiological parameters.

Novel Parameter Predicting Grade 2 Rectal Bleeding After Iodine-125 Prostate Brachytherapy Combined With External Beam Radiation Therapy

To propose a novel parameter predicting rectal bleeding on the basis of generalized equivalent uniform doses (gEUD) after (125)I prostate brachytherapy combined with external beam radiation therapy and to assess the predictive value of this parameter. To account for differences among radiation treatment modalities and fractionation schedules, rectal dose-volume histograms (DVHs) of 369 patients with localized prostate cancer undergoing combined therapy retrieved from corresponding treatment planning systems were converted to equivalent dose-based DVHs. The gEUDs for the rectum were calculated from these converted DVHs. The total gEUD (gEUDsum) was determined by a summation of the brachytherapy and external-beam radiation therapy components. Thirty-eight patients (10.3%) developed grade 2+ rectal bleeding. The grade 2+ rectal bleeding rate increased as the gEUDsum increased: 2.0% (2 of 102 patients) for <70 Gy, 10.3% (15 of 145 patients) for 70-80 Gy, 15.8% (12 of 76 patients) for 80-90 Gy, and 19.6% (9 of 46 patients) for >90 Gy (P=.002). Multivariate analysis identified age (P=.024) and gEUDsum (P=.000) as risk factors for grade 2+ rectal bleeding. Our results demonstrate gEUD to be a potential predictive factor for grade 2+ late rectal bleeding after combined therapy for prostate cancer.

Genome-wide association study identifies a region on chromosome 11q14.3 associated with late rectal bleeding following radiation therapy for prostate cancer

Background and purposeRectal bleeding can occur following radiotherapy for prostate cancer and negatively impacts quality of life for cancer survivors. Treatment and clinical factors do not fully predict rectal bleeding, and genetic factors may be important. Materials and methodsA genome-wide association study (GWAS) was performed to identify SNPs associated with the development of late rectal bleeding following radiotherapy for prostate cancer. Logistic regression was used to test the association between 614,453 SNPs and rectal bleeding in a discovery cohort (79 cases, 289 controls), and top-ranking SNPs were tested in a replication cohort (108 cases, 673 controls) from four independent sites. Resultsrs7120482 and rs17630638, which tag a single locus on chromosome 11q14.3, reached genome-wide significance for association with rectal bleeding (combined p-values 5.4×10−8 and 6.9×10−7 respectively). Several other SNPs had p-values trending toward genome-wide significance, and a polygenic risk score including these SNPs shows a strong rank-correlation with rectal bleeding (Sommers’ d=5.0×10−12 in the replication cohort). ConclusionsThis GWAS identified novel genetic markers of rectal bleeding following prostate radiotherapy. These findings could lead to the development of a predictive assay to identify patients at risk for this adverse treatment outcome so that dose or treatment modality could be modified.

Dose-distance metric that predicts late rectal bleeding in patients receiving radical prostate external-beam radiotherapy

The relationship between rectal dose distribution and the incidence of late rectal complications following external-beam radiotherapy has been previously studied using dose-volume histograms or dose-surface histograms. However, they do not account for the spatial dose distribution. This study proposes a metric based on both surface dose and distance that can predict the incidence of rectal bleeding in prostate cancer patients treated with radical radiotherapy. One hundred and forty-four patients treated with radical radiotherapy for prostate cancer were prospectively followed to record the incidence of grade ≥2 rectal bleeding. Radiotherapy plans were used to evaluate a dose-distance metric that accounts for the dose and its spatial distribution on the rectal surface, characterized by a logistic weighting function with slope a and inflection point d0. This was compared to the effective dose obtained from dose-surface histograms, characterized by the parameter n which describes sensitivity to hot spots. The log-rank test was used to determine statistically significant (p < 0.05) cut-off values for the dose-distance metric and effective dose that predict for the occurrence of rectal bleeding. For the dose-distance metric, only d0 = 25 and 30 mm combined with a > 5 led to statistical significant cut-offs. For the effective dose metric, only values of n in the range 0.07–0.35 led to statistically significant cut-offs. The proposed dose-distance metric is a predictor of rectal bleeding in prostate cancer patients treated with radiotherapy. Both the dose-distance metric and the effective dose metric indicate that the incidence of grade ≥2 rectal bleeding is sensitive to localized damage to the rectal surface.

Rectal Toxicity 7 Years After High-dose Radiation for Prostate Cancer: Clinical and Dosimetric Predictors

To evaluate long term prevalence of late rectal bleeding (lrb) and late fecal incontinence (linc) after high-dose RT in prostate cancer patients (pts) (AIROPROS 0102 trial, doses: 70-80 Gy, 1.8-2 Gy/fr) and to model the relationship between lrb/linc and clinical/dosimetric factors.

Temporal patterns of selected late toxicities in patients treated with brachytherapy or brachytherapy plus external beam radiation for prostate adenocarcinoma

What's known on the subject? and What does the study add? While the frequencies and severity of late toxicities following prostate brachytherapy are well known, less has been published with regard to time to first onset. Several series with limited median follow-up have published time to onset. An extensive analysis of timing to late toxicity following brachytherapy for cervical cancer has also been published. This study is the largest of its kind with the longest median follow-up to capture very late events. It can provide a basis for physician and patient education about when late toxicities can reasonably be expected to occur. The study also shows that a significant amount of erectile dysfunction might be more age related than radiation induced. • To assess the timing of first onset of late rectal bleeding, late haematuria and erectile dysfunction (ED) following brachytherapy with or without external beam radiation therapy (EBRT) for prostate adenocarcinoma. • To identify treatment factors and patient characteristics that affect the time to first onset. • In all, 2046 patients were definitively treated for prostate adenocarcinoma with a full (125) I or (103) Pd implant or a partial (103) Pd implant followed by EBRT with 6 years median follow-up (range 2-17 years). • Patients were selected for an event of Radiation Therapy Oncology Group (RTOG) grade 2 or greater rectal bleeding, ≥RTOG grade 2 haematuria, or a drop in the Mount Sinai Erectile Dysfunction Score from potent to impotent (excluding patients who received androgen deprivation therapy). • Life tables were generated to calculate actuarial incidence rates of toxicity. • Wilcoxon rank sum and Cox regression were utilized to identify treatment factors affecting time to onset. • The incidence rate per 1000 patients for 0-2 years, 2-5 years and 5-10 years following radiation for rectal bleeding is 14.3, 15.9 and 6.5, respectively; for haematuria, 14.0, 8.2 and 1.3, respectively; and for ED, 82.4, 48.2 and 42.2, respectively. • Just 5% of rectal bleeding occurs after 5 years from radiation vs 18% of haematuria cases and 22% of ED. • On multivariate analysis, time to first onset of rectal bleeding was affected by the addition of EBRT only whereas the time to onset of haematuria was affected by the biological effective dose of the radiation and the addition of EBRT. • The only factor on multivariate analysis to affect time to onset of ED was the age of the patient at treatment, independent of radiation dose or technique. • Unique temporality to first onset of selected toxicities was observed in patients after radioactive implant for prostate adenocarcinoma with or without EBRT. • Clinicians and patients should be counselled when to expect late toxicities. • The only factor to affect time to onset of ED is the age of the patient, suggesting possible over-reporting of radiation-induced ED in the light of normal age-related events.

The contribution of the cone beam Kv CT (CBKvCT) to the reduction in toxicity of prostate cancer treatment with external 3D radiotherapy

Show that verification through cone beam Kv CT (CBKvCT) in a series of patients treated with 3D external radiotherapy (3DRT) for prostate cancer (PC) is related to a reduction in acute and late toxicity levels. A retrospective, non-randomized study of two homogeneous groups of patients treated between 2005 and 2008, 46 were verified using electronic portal devices (EPIDs) and 48 through CBKvCT. They received 3DRT for localized PC (T1-T3N0M0) and were prescribed the same doses. Treatment was simulated and planned with the same criteria with the same equipment with a median follow-up time of 24 months (12-54 months). Urinary and gastrointestinal toxicity was determined using Common Toxicity Criteria scale, version 4 and RTOG scales. Statistical analysis of data was performed where p < 0.005 being significative. With an overall median follow-up time of 24 months, the levels of proctitis were, respectively, 19.56, 15.21 and 15.2 % in the first group, compared with 4.17, 2.08 and 8.33 % in the second. Statistically, less total and late proctitis, late rectal bleeding, anal fissure, total and acute haematuria, total and acute urinary frequency and total urinary incontinence was observed. No statistically significant evidence of a lowering in toxicity neither in terms of acute and late dysuria nor of a relationship to the TNM, Gleason or PSA or in the grade of stability. Verification through CBKvCT in this series is associated with a statistically significant lowering toxicity. This justifies its use. Greater monitoring would be necessary to assess the impact of verification at the level of biochemical control.

Analysis of late toxicity associated with external beam radiation therapy for prostate cancer with uniform setting of classical 4-field 70 Gy in 35 fractions: a survey study by the Osaka Urological Tumor Radiotherapy Study Group

We aimed to analyse late toxicity associated with external beam radiation therapy (EBRT) for prostate cancer using uniform dose-fractionation and beam arrangement, with the focus on the effect of 3D (CT) simulation and portal field size. We collected data concerning patients with localized prostate adenocarcinoma who had been treated with EBRT at five institutions in Osaka, Japan, between 1998 and 2006. All had been treated with 70 Gy in 35 fractions, using the classical 4-field technique with gantry angles of 0°, 90°, 180° and 270°. Late toxicity was evaluated strictly in terms of the Common Terminology Criteria for Adverse Events Version 4.0. In total, 362 patients were analysed, with a median follow-up of 4.5 years (range 1.0–11.6). The 5-year overall and cause-specific survival rates were 93% and 96%, respectively. The mean ± SD portal field size in the right–left, superior–inferior, and anterior–posterior directions was, respectively, 10.8 ± 1.1, 10.2 ± 1.0 and 8.8 ± 0.9 cm for 2D simulation, and 8.4 ± 1.2, 8.2 ± 1.0 and 7.7 ± 1.0 cm for 3D simulation (P < 0.001). No Grade 4 or 5 late toxicity was observed. The actuarial 5-year Grade 2–3 genitourinary and gastrointestinal (GI) late toxicity rates were 6% and 14%, respectively, while the corresponding late rectal bleeding rate was 23% for 2D simulation and 7% for 3D simulation (P < 0.001). With a uniform setting of classical 4-field 70 Gy/35 fractions, the use of CT simulation and the resultant reduction in portal field size were significantly associated with reduced late GI toxicity, especially with less rectal bleeding.

Treatment and prognosis of patients with late rectal bleeding after intensity-modulated radiation therapy for prostate cancer

BackgroundRadiation proctitis after intensity-modulated radiation therapy (IMRT) differs from that seen after pelvic irradiation in that this adverse event is a result of high-dose radiation to a very small area in the rectum. We evaluated the results of treatment for hemorrhagic proctitis after IMRT for prostate cancer.MethodsBetween November 2004 and February 2010, 403 patients with prostate cancer were treated with IMRT at 2 institutions. Among these patients, 64 patients who developed late rectal bleeding were evaluated. Forty patients had received IMRT using a linear accelerator and 24 by tomotherapy. Their median age was 72 years. Each patient was assessed clinically and/or endoscopically. Depending on the severity, steroid suppositories or enemas were administered up to twice daily and Argon plasma coagulation (APC) was performed up to 3 times. Response to treatment was evaluated using the Rectal Bleeding Score (RBS), which is the sum of Frequency Score (graded from 1 to 3 by frequency of bleeding) and Amount Score (graded from 1 to 3 by amount of bleeding). Stoppage of bleeding over 3 months was scored as RBS 1.ResultsThe median follow-up period for treatment of rectal bleeding was 35 months (range, 12–69 months). Grade of bleeding was 1 in 31 patients, 2 in 26, and 3 in 7. Nineteen of 45 patients (42%) observed without treatment showed improvement and bleeding stopped in 17 (38%), although mean RBS did not change significantly. Eighteen of 29 patients (62%) treated with steroid suppositories or enemas showed improvement (mean RBS, from 4.1 ± 1.0 to 3.0 ± 1.8, p = 0.003) and bleeding stopped in 9 (31%). One patient treated with steroid enema 0.5-2 times a day for 12 months developed septic shock and died of multiple organ failure. All 12 patients treated with APC showed improvement (mean RBS, 4.7 ± 1.2 to 2.3 ± 1.4, p < 0.001) and bleeding stopped in 5 (42%).ConclusionsAfter adequate periods of observation, steroid suppositories/enemas are expected to be effective. However, short duration of administration with appropriate dosage should be appropriate. Even when patients have no response to pharmacotherapy, APC is effective.

Increasing the risk of late rectal bleeding after high-dose radiotherapy for prostate cancer: The case of previous abdominal surgery. Results from a prospective trial

PurposeTo evaluate and discuss the role of specific types of abdominal surgery (SURG) before radical radiation therapy as a risk factor for late rectal toxicity in prostate cancer patients. MethodsResults concerning questionnaire-based scored late bleeding and faecal incontinence in 718 patients with a complete follow-up of 36months were analysed, focusing on the impact of specific pre-radiotherapy abdominal/pelvic surgery procedures. Patients were accrued in the prospective study AIROPROS 0102. Different types of surgery (rectum-sigma resection, kidney resection, cholecystectomy or appendectomy) were considered as covariates together with a number of different parameters previously found to be predictive of late toxicity and including clinical as well as dosimetric parameters. Univariate (UVA) and multivariate (MVA) logistic analyses were carried out. ResultsIn total 69/718 patients were previously submitted to one or more surgical procedures, mostly cholecystectomy (n=21) and appendectomy (n=27). Actuarial incidences of G2–G3 and G3 bleeding were 52 (7.2%) and 24 (3.3%) respectively; 19 (2.6%) chronic incontinence events were registered.Cholecystectomy was found to be highly correlated with late rectal bleeding at UVA: OR=4.3 and p=0.006 for G2–G3 and OR=5.4 and p=0.01 for G3. Considering MVA (including dosimetric and clinical factors), G2–G3 bleeding was significantly correlated to cholecystectomy (OR=6.5, p=0.002), V75Gy (OR=1.074, p=0.003) and secondarily with appendectomy (OR=2.7, p=0.10), presence of acute radioinduced rectal bleeding (OR=1.70, p=0.21) and androgen deprivation (OR=0.67, p=0.25).Appendectomy (OR=5.9, p=0.004) and cholecystectomy (OR=5.5, p=0.016) were very strong predictors of G3 bleeding with V75Gy playing a less significant role (OR=1.037, p=0.26). Conversely, no specific surgery was correlated with actuarial or chronic incontinence. ConclusionsThis analysis highlights previous SURG as the best predictor of late rectal bleeding. Among the different types of abdominal surgery, cholecystectomy and appendectomy play the major role, especially for severe late bleeding.

Early Proctoscopy is a Surrogate Endpoint of Late Rectal Toxicity in Prostate Cancer Treated With Radiotherapy

To predict the grade and incidence of late clinical rectal toxicity through short-term (1 year) mucosal alterations. Patients with prostate adenocarcinoma treated with curative or adjuvant radiotherapy underwent proctoscopy a year after the course of radiotherapy. Mucosal changes were classified by the Vienna Rectoscopy Score (VRS). Late toxicity data were analyzed according to the Kaplan-Meier method. Comparison between prognosis groups was performed by log-rank analysis. After a median follow-up time of 45 months (range, 18-99), the 3-year incidence of grade ≥ 2 rectal late toxicity according to the criteria of the European Organization for Research and Treatment of Cancer and the Radiation Therapy Oncology Group was 24%, with all patients (24/24; 100%) experiencing rectal bleeding. The occurrence of grade ≥ 2 clinical rectal late toxicity was higher in patients with grade ≥ 2 (32% vs. 15 %, p = 0.02) or grade ≥ 3 VRS telangiectasia (47% vs. 17%, p ≤ 0.01) and an overall VRS score of ≥ 2 (31% vs. 16 %, p = 0.04) or ≥ 3 (48% vs. 17%, p = 0.01) at the 1-year proctoscopy. Early proctoscopy (1 year) predicts late rectal bleeding and therefore can be used as a surrogate endpoint for late rectal toxicity in studies aimed at reducing this frequent complication.

Late rectal bleeding after 3D-CRT for prostate cancer: development of a neural-network-based predictive model

The aim of this study was to develop a model exploiting artificial neural networks (ANNs) to correlate dosimetric and clinical variables with late rectal bleeding in prostate cancer patients undergoing radical radiotherapy and to compare the ANN results with those of a standard logistic regression (LR) analysis. 718 men included in the AIROPROS 0102 trial were analyzed. This multicenter protocol was characterized by the prospective evaluation of rectal toxicity, with a minimum follow-up of 36 months. Radiotherapy doses were between 70 and 80 Gy. Information was recorded for comorbidity, previous abdominal surgery, use of drugs and hormonal therapy. For each patient, a rectal dose–volume histogram (DVH) of the whole treatment was recorded and the equivalent uniform dose (EUD) evaluated as an effective descriptor of the whole DVH. Late rectal bleeding of grade ≥ 2 was considered to define positive events in this study (52 of 718 patients). The overall population was split into training and verification sets, both of which were involved in model instruction, and a test set, used to evaluate the predictive power of the model with independent data. Fourfold cross-validation was also used to provide realistic results for the full dataset. The LR was performed on the same data. Five variables were selected to predict late rectal bleeding: EUD, abdominal surgery, presence of hemorrhoids, use of anticoagulants and androgen deprivation. Following a receiver operating characteristic analysis of the independent test set, the areas under the curves (AUCs) were 0.704 and 0.655 for ANN and LR, respectively. When evaluated with cross-validation, the AUC was 0.714 for ANN and 0.636 for LR, which differed at a significance level of p = 0.03. When a practical discrimination threshold was selected, ANN could classify data with sensitivity and specificity both equal to 68.0%, whereas these values were 61.5% for LR. These data provide reasonable evidence that results obtained with ANNs are superior to those achieved with LR when predicting late radiotherapy-related rectal bleeding. The future introduction of patient-related personal characteristics, such as gene expression profiles, might improve the predictive power of statistical classifiers. More refined morphological aspects of the dose distribution, such as dose surface mapping, might also enhance the overall performance of ANN-based predictive models.

Parameters for the Lyman Kutcher Burman (LKB) model of Normal Tissue Complication Probability (NTCP) for specific rectal complications observed in clinical practise

Background and purposeThe Normal Tissue Complication Probability (NTCP) for rectum is usually defined for late rectal bleeding. This study calculates NTCP parameter values for additional rectal toxicity endpoints observed in clinical practise. Materials and methods388 patients from the multicentre MRC-RT01 prostate conformal radiotherapy trial (ISRCTN 47772397) were used to derive independent Lyman Kutcher Burman model (LKB) parameters for five late rectal toxicity endpoints: rectal bleeding, proctitis, stool frequency, loose stools and rectal urgency. The parameters were derived using maximum likelihood estimation. Bootstrap and leave-one-out methods were employed to test the generalisability of the results for use in a general population. ResultsA consistent pattern of increasing value of TD50(1) for Grade 2 toxicity only compared to Grades 1 and 2 toxicity was observed for all endpoints. Parameter values varied between endpoints (particularly for the volume parameter n). TD50(1), m and n were 68.5Gy (95% CI)(66.8–70.8), 0.15 (0.13–0.17) and 0.13 (0.10–0.17), respectively, for G2 rectal bleeding. Bootstrap and leave-one-out results showed that the rectal bleeding and proctitis parameter fits were extremely robust. ConclusionsThe variation between the values derived for different endpoints may indicate different patho-physiological responses of the rectum to radiation. Therefore different parameter sets would be required to predict specific rectal toxicity endpoints.

Helical Tomotherapy with a 2.2-Gy Daily Fraction and Dose Reduction for the Rectum for Localized Prostate Cancer

In standard intensity-modulated radiation therapy (IMRT) for localized prostate cancer, a long treatment period of 8 weeks or longer is a problem for actively working patients and late rectal bleeding bothers a proportion of patients (up to 15%). To ameliorate these disadvantages, we have used helical tomotherapy with a 2.2-Gy daily fraction and dose reduction for the rectum. After experiences of nearly 5 years, we evaluated toxicity and efficacy of this treatment.