Incidence Of Late Rectal Toxicity Research Articles

Locally advanced cervical cancer: how the improvement in techniques in external beam radiotherapy and brachytherapy impacts on survival outcomes and long-term toxicities.

Platinum-based chemoradiotherapy and brachytherapy are the standard treatment for locally advanced cervical cancer. Reported long-term outcomes for treated with both IMRT and 3D-Image-guided-adaptive brachytherapy are lacking. This retrospective study included 165 patients with FIGO Stage IB-IVB cervical cancer, treated with chemoradiotherapy in combination with brachytherapy. External beam radiotherapy was delivered as IMRT/VMAT/TOMO helical or 3DCRT. The intracavitary brachytherapy treatment (ICBT) was performed using two different planning system (with or without optimization). Among the patient subgroups, comprising those who received IMRT/VMAT/Tomo helical and 3DCRT, as well as those who underwent ICBT planning optimization and those who did not, homogeneity was observed in terms of age, performance status, T stage, N status, TNM stage, and histology. With a median follow-up time of 60.5months, the 5-year overall survival (OS) in the 3DCRT and IMRT groups was 74.9% and 92.8%, respectively (p = 0.033). The 5-year OS in the ICBT planning optimization group was 93.7%, compared to 75% in the non-optimization group (p = 0.014). Regarding late radiation toxicities, patients in the IMRT group had a lower incidence of chronic rectal toxicity compared to those in the 3DCRT group (6.5% vs. 34.1%, p = 0.001). The group with ICBT planning optimization had a lower incidence of late urinary toxicities (10.4%) compared to the non-optimized ICBT planning group (18.2%, p = 0.012). Similarly, the ICBT planning optimization group had a lower incidence of late rectal toxicity (6.5% with 80% grade 1 and 20% grade 2) compared to the non-optimized ICBT planning group (34.1%, p = 0.001). In this series, the group of patients receiving optimized ICBT had an advantage in terms of OS and CSS suggesting that the use of new Treatment Planning Systems associated with 3D imaging, improves the long-term survival. Additionally, a significant reduction in late rectal and urinary toxicity has been observed.

Avoidance of late rectal toxicity after high-dose-rate brachytherapy boost treatment for prostate cancer

PURPOSETo elucidate potential risk factors important for the appearance of late rectal toxicity (LRT) after high-dose-rate boost treatment (HDRBT) of prostate cancer and to validate the predictive value of the minimal dose to the most exposed 2 cc of rectum received with HDRBT (D2ccrect). METHODS AND MATERIALSThe study of LRT, defined as relative deterioration of defecation problems (RDDP) (stool frequency, pain, rectal bleeding, fecal urgency, and incontinence) during follow-up period, was carried out on 88 patients, consecutively treated from October 2006 through April 2011 with HDRBT of 3 × 6–7 Gy to 50–50.4 Gy of EBRT. The impact of patients and treatment characteristics on third year prevalence of RDDP was analyzed by using binary logistic regression method. ResultsAt third year of follow-up, RDDP was evidenced in 30 of 77 (39.0%) patients. More important as D2ccrect (OR, 1.15; 95% CI, 0.99–1.34; p = .059) was minimal dose to the most exposed 1 cc of the rectum (D1ccrect; OR, 1.15; 95% CI, 1.01–1.31; p = .032), whereas the sum of D1ccrect and EBRT mean rectal dose (EDmeanrect) was the only significant parameter in multivariate analysis (OR, 1.12; 95% CI, 1.04–1.22; p = .004). Based on a multivariate model, the safe compound 2 Gy equivalent dose was estimated at 44.4 Gy with the average ratio of D1ccrect:EDmeanrect = 1:3.1 (95% CI ± 1.8) and negative predictive value of 0.828. ConclusionsThe study confirms the value of composite dose parameter and the importance of rectal high-dose and low-dose regions for LRT. Taking account of suggested dose constraints and CT/MRI-based HDRBT, the incidence of LRT can be reduced by a half.

Implantation of Row One Needles 1-2 mm Anterior to the Posterior Margin of the Prostate Gland Results in Excellent PSA Control and Minimal Rectal Toxicity After I-125 Brachytherapy

Positioning of the posterior-most row of seeds (row 1) during prostate brachytherapy (PB) determines dose coverage to both the cancer-prone posterior peripheral zone and the anterior rectal wall and therefore impacts cure rates as well as the incidence of late rectal toxicity. Studies correlating row 1 position of needles and seeds and clinical outcomes after PB are lacking. Thus we undertook this analysis to demonstrate the safety and efficacy of our practice of positioning row 1 in patients during PB. We randomly selected 50 patients for this study who had a minimum 4 year follow-up from the 350 patients who have undergone I-125 PB at our institution. PB was performed with loose I-125 seeds to deliver a minimum peripheral dose of 144 Gy using a modified uniform loading technique. In all patients, row 1 on the template was positioned at a distance of 1-2 mm anterior to the posterior margin of the prostate gland from base to apex by angulating the rectal probe posteriorly to match the curvature of the prostate gland. Median patient age was 67 years, eight (16%) had diabetes, 12 (24%) were on blood thinners, one patient had ulcerative colitis. Patient records were evaluated for biochemical relapse free survival (RFS) and late rectal toxicity according to the RTOG criteria. Each patient's day 1 post-implant CT scan was reviewed for prostate quadrant dosimetry and various measures of rectal dosimetry including V100%, V100 Gy, rectal wall surface area dosimetry and seed number/distance from the rectal wall. After median follow-up of 63.5 months (range, 48-96 months) biochemical RFS was 100%. The median V100% of the anterior and posterior quadrants of the prostate was 91.8% and 90.9%, respectively. Median number of seeds < 5 mm, < 3 mm and < 1 mm from the rectal wall was 8 (0-26), 2 (0-17), and 0 (0-4), respectively. Median rectal V100% was 0.94 cc and rectal V100 Gy was 3.67 cc. Median rectal surface area receiving at least 100 Gy, 200 Gy and 100% of the prescription dose was 10.22 cm2, 0.80 cm2 and 4.88 cm2, respectively. The rate of RTOG grade 1 late rectal toxicity was 9/50 (18%). No patients had grade 2 or higher late toxicity. On multivariate analysis late grade 1 rectal toxicity was significantly associated with the presence of any seeds located < 5 mm from the anterior rectal wall (OR 1.19, p = 0.046) and the rectal surface area receiving at least 100 Gy (OR 1.32, p = 0.049). These results confirm the long-term safety and efficacy of implanting row 1 needles at a distance of 1-2 mm anterior to the posterior margin of the prostate gland during PB. This practice can provide good dosimetric coverage of the posterior peripheral zone with excellent biochemical RFS and minimal rectal toxicity in spite of the localized delivery of high radiation doses to the anterior rectal wall.

Comparison of low and intermediate source strengths for 125I prostate brachytherapy implants

To compare the implant quality and clinical outcomes for patients treated with low and intermediate strength (125)I seeds in prostate brachytherapy implants. This retrospective review included 390 consecutive patients treated with prostate brachytherapy from 1999 to 2006. The first 142 patients were implanted with source strengths lower than 0.415U (0.327mCi), with the subsequent 248 patients implanted with source strengths higher than 0.493U (0.388mCi). Clinical, dosimetric, toxicity, and outcome data were compared between these two cohorts of patients. Despite having similar prostate volumes, fewer sources (median, 95 vs. 113; p<0.0001) and fewer needles (median, 23 vs. 29; p<0.0001) were implanted in the intermediate strength cohort. The postimplant dosimetry demonstrated better quality implants in patients treated with intermediate strength sources (median D90, 160.0Gy vs. 139.6Gy; p<0.0001), with greater dose inhomogeneity identified in the intermediate strength cohort of patients. A higher incidence of late rectal toxicity was identified in patients treated with intermediate strength sources despite lower rectal doses in this cohort. The biochemical relapse-free survival, prostate cancer survival, and overall survival were not significantly different between the two cohorts. The transition from low to intermediate strength sources has led to fewer resources being used and improved postoperative dosimetry. Although there were more rectal complications identified in the intermediate strength cohort of patients in this analysis, there were no other significantly worse clinical or biochemical outcomes for patients implanted with intermediate strength sources.

Clinical outcomes with high-dose image guided radiotherapy (IGRT) compared with non-IGRT for the treatment of clinically localized prostate cancer.

12 Background: To compare toxicity profiles and biochemical tumor control outcomes between patients treated with high-dose image-guided radiotherapy (IGRT) and high-dose intensity-modulated radiotherapy (IMRT) for clinically localized prostate cancer. Methods: 186 patients with prostate cancer were treated with IGRT to a dose of 86.4 Gy with daily correction of the target position based upon kilovoltage imaging of implanted prostatic fiducial markers. This group of patients was retrospectively compared with a similar cohort of 190 patients who were treated with IMRT to the same prescription dose without, implanted fiducial markers in place (non-IGRT). In both groups the margins used for the prostate were the same. The median follow-up time was 2.8 years (range, 2-4 years). Results: A significant reduction in late urinary toxicity was observed for IGRT patients compared with the non-IGRT patients. The 3-year likelihood of urinary toxicity for the IGRT and non-IGRT cohorts were 10.4% and 20.0%, respectively (p=0.02).Multivariate analysis identifying predictors for late urinary toxicity demonstrated that, in addition to the baseline IPSS, IGRT was associated with significantly less late urinary toxicity compared with non-IGRT. The incidence of late rectal toxicity was low for both treatment groups (1.0% and 1.6%, respectively; p = 0.81). No differences in prostate-specific antigen relapse–free survival outcomes were observed for low- and intermediate-risk patients when treated with IGRT and non-IGRT. For high-risk patients a significant improvement was observed at 3-years for patients treated with IGRT compared with non-IGRT. Conclusions: IGRT is associated with a reduction in late urinary toxicity and improvement in biochemical tumor control after definitive high-dose external beam radiotherapy compared with high-dose IMRT. These data suggest that, for definitive radiotherapy, the placement of fiducial markers and daily tracking of target positioning should be the preferred mode of external beam radiotherapy delivery for the treatment of prostate cancer.

Searching for Optimal Dose–Volume Constraints to Reduce Rectal Toxicity after Hypofractionated Radiotherapy for Prostate Cancer

Aims Late rectal toxicity is a major concern for prostate cancer patients treated with radiotherapy. Rectal dose–volume constraints, set as guidelines to reduce its incidence, vary among institutions. From a group of patients uniformly treated with hypofractionated radiotherapy, we correlated the incidence of late rectal toxicity with rectal dose–volume rectal constraints as described in three randomised trials for prostate cancer. Materials and methods Favourable-risk prostate cancer patients received a dose of 66 Gy in 22 fractions without hormonal therapy. Toxicity was prospectively assessed using Common Toxicity Criteria v3. The whole or part of the rectum and rectal wall were contoured as an organ at risk for all patients. The rectal constraints of the RTOG 0126, RTOG 0415 and the PROFIT trials were used to correlate with late rectal toxicity. Results The median follow-up time was 58 months. Late rectal toxicity was 62, 20 and 18% for grades 0, 1 and 2/3, respectively. No statistically significant correlation was found between late rectal toxicity and the rectal constraints used in the three trials. The number of patients violating the recommended constraints was similar for the group with grade 2/3 toxicity and the group without any toxicity. Analysis derived from the actual dose–volume histogram dose parameters of this group of patients did not show a relationship between dose to volume of the rectum and late rectal toxicity that could generate a guideline of dose constraints. Conclusion For this group of patients, despite the use of recognised dose–volume constraint guidelines of three trials, we were unable to establish a relationship between these constraints and the late rectal toxicity registered. Further studies on the correlation of dosimetric parameters with rectal toxicity, particularly for hypofractionated regimens, are required. Non-dosimetric factors may also be involved in the risk of late rectal toxicity.

Late Rectal Toxicity on RTOG 94-06: Analysis Using a Mixture Lyman Model

To estimate the parameters of the Lyman normal-tissue complication probability model using censored time-to-event data for Grade ≥2 late rectal toxicity among patients treated on Radiation Therapy Oncology Group 94-06, a dose-escalation trial designed to determine the maximum tolerated dose for three-dimensional conformal radiotherapy of prostate cancer. The Lyman normal-tissue complication probability model was fitted to data from 1,010 of the 1,084 patients accrued on Radiation Therapy Oncology Group 94-06 using an approach that accounts for censored observations. Separate fits were obtained using dose-volume histograms for whole rectum and dose-wall histograms for rectal wall. With a median follow-up of 7.2 years, the crude incidence of Grade ≥2 late rectal toxicity was 15% (n = 148). The parameters of the Lyman model fitted to dose-volume histograms data, with 95% profile-likelihood confidence intervals, were TD(50) = 79.1 Gy (75.3 Gy, 84.3 Gy), m = 0.146 (0.107, 0.225), and n = 0.077 (0.041, 0.156). The fit based on dose-wall histogram data was not significantly different. Patients with cardiovascular disease had a significantly higher incidence of late rectal toxicity (p = 0.015), corresponding to a dose-modifying factor of 5.3%. No significant association with late rectal toxicity was found for diabetes, hypertension, rectal volume, rectal length, neoadjuvant hormone therapy, or prescribed dose per fraction (1.8 Gy vs. 2 Gy). These results, based on a large cohort of patients from a multi-institutional trial, are expected to be widely representative of the ability of the Lyman model to describe the long-term risk of Grade ≥2 late rectal toxicity after three-dimensional conformal radiotherapy of prostate cancer.

Dose–Volume Constraints to Reduce Rectal Side Effects From Prostate Radiotherapy: Evidence From MRC RT01 Trial ISRCTN 47772397

Radical radiotherapy for prostate cancer is effective but dose limited because of the proximity of normal tissues. Comprehensive dose-volume analysis of the incidence of clinically relevant late rectal toxicities could indicate how the dose to the rectum should be constrained. Previous emphasis has been on constraining the mid-to-high dose range (>/=50 Gy). Evidence is emerging that lower doses could also be important. Data from a large multicenter randomized trial were used to investigate the correlation between seven clinically relevant rectal toxicity endpoints (including patient- and clinician-reported outcomes) and an absolute 5% increase in the volume of rectum receiving the specified doses. The results were quantified using odds ratios. Rectal dose-volume constraints were applied retrospectively to investigate the association of constraints with the incidence of late rectal toxicity. A statistically significant dose-volume response was observed for six of the seven endpoints for at least one of the dose levels tested in the range of 30-70 Gy. Statistically significant reductions in the incidence of these late rectal toxicities were observed for the group of patients whose treatment plans met specific proposed dose-volume constraints. The incidence of moderate/severe toxicity (any endpoint) decreased incrementally for patients whose treatment plans met increasing numbers of dose-volume constraints from the set of V30<or=80%, V40<or=65%, V50<or=55%, V60<or=40%, V65<or=30%, V70<or=15%, and V75<or=3%. Considering the entire dose distribution to the rectum by applying dose-volume constraints such as those tested here in the present will reduce the incidence of late rectal toxicity.

Patient-Assessed Late Toxicity Following High-Dose Image-Guided Radiation Therapy for Prostate Cancer and Correlation with Dose-Volume Histograms

Purpose/Objective: While dose escalation has been shown to improve disease-free survival in prostate cancer, it is also associated with a greater incidence of late rectal toxicity. Numerous studies of dose-volume histograms (DVHs) have shown that rectal toxicity is positively correlated with the percentage of rectal wall exposed to high radiation doses.

Effect of oral sucralfate on late rectal injury associated with radiotherapy for prostate cancer: A double-blind, randomized trial

To assess whether oral sucralfate is effective in preventing late rectal injury in prostate cancer patients treated with radiotherapy. A double-blind, placebo-controlled, randomized trial was conducted across four institutions in Australia. Patients receiving definitive radiotherapy for prostate cancer were randomized to receive either 3 g of oral sucralfate suspension or placebo twice daily. Data on patients' symptoms were collected for 2 years, and flexible sigmoidoscopy was scheduled at 12 months after treatment. A total of 338 patients were randomized, of whom 298 had adequate follow-up data available for an analysis of late symptoms. Of the 298 patients, 143 were randomized to receive sucralfate and 155 placebo. The cumulative incidence of Radiation Therapy Oncology Group Grade 2 or worse late rectal toxicity at 2 years was 28% for placebo and 22% for the sucralfate arm (p = 0.23; 95% confidence interval for the difference -3% to 16%). Seventeen percent of patients in the sucralfate group had significant bleeding (Grade 2 or worse) compared with 23% in the placebo group (p = 0.18, 95% confidence interval -15% to 3%). No statistically significant difference was found between the two groups with respect to bowel frequency (p = 0.99), mucus discharge (p = 0.64), or fecal incontinence (p = 0.90). Sigmoidoscopy findings showed a nonstatistically significant reduction in Grade 2 or worse rectal changes from 32% with placebo to 27% in the sucralfate group (p = 0.25). This trial demonstrated no statistically significant reduction in the incidence of late rectal toxicity in patients randomized to receive sucralfate. However, this result was considered inconclusive, because the trial was unable to exclude clinically important differences in the late toxicity rates.

Hypofractionated boost in prostate cancer radiotherapy as part of two different dose escalation strategies, HDR brachytherapy or IMRT: A late rectal toxicity assessment

Hypofractionated boost in prostate cancer radiotherapy as part of two different dose escalation strategies, HDR brachytherapy or IMRT: A late rectal toxicity assessment

Hypofractionated boost in prostate cancer radiotherapy as part of two different dose escalation strategies, HDR brachytherapy or IMRT: A late rectal toxicity assessment

To assess the incidence of late rectal toxicity with two different radiotherapy hypofractionated boost techniques aiming to escalate the dose for prostate cancer treatment: high dose rate (HDR) brachytherapy (BT) versus intensity modulation under stereotactic conditions (IMRT).

Late rectal bleeding following combined x-ray and proton high dose irradiation for patients with stages T3–T4 prostate carcinoma

Purpose : Dose escalation for prostate cancer by external beam irradiation is feasible by a 160 MeV perineal proton beam that reduces the volume of rectum irradiated. We correlated the total doses received to portions of the anterior rectum to study the possible relationship of the volume irradiated to the incidence of late rectal toxicity. Methods : We have randomized 191 patients with stages T3 and T4 prostatic carcinoma to one of two treatment dose arms. These were: 1) 75.6 Cobalt-Gy-equivalent (CGE), 50.4 Gy delivered by 107−25 MV photons followed by 25.2 CGE delivered perineally by protons (Arm 1) or 2) 67.2 CGE delivered by 10−25 MV photons (Arm 2). Results : With a median follow-up of 3.7 years, post-irradiation rectal bleeding (grades 1 and 2 only, none requiring surgery or hospitalization) from telangietatic rectal mucosal vessels has occurred in 34% of 99 Arm-1 patients and 16% of 92 Arm-2 patients ( p = 0.013). Dose-volume histograms (DVHs) for the anterior rectal wall, the posterior rectal wall and the total rectum in 41 patients treated on Arm 1 were calculated from the three dimensional dose distributions. Rectal bleeding has occurred in 14 or 34% of the 41 DVH-analyzed subset of Arm-1 patients. Both the fractional volume of the anterior rectum and the total dose received by fractional volumes of the anterior rectum significantly correlate with the actuarial probability of bleeding. Conclusions : Clinicians planning dose escalation to men with localized prostate cancer should approve with caution treatment plans raising more than 40% of the anterior rectum to more than 75 CGE without additional effort to protect the rectal mucosa because this late sequela data indicate that more than half of these men will otherwise have rectal bleeding.