Genitourinary Toxicity In Patients Research Articles

Early findings from the GARUDA trial: The impact of a genetic signature of late radiation toxicity on prostate cancer treatment decision making.

5089 Background: GARUDA (Germline DNA-Based Radiosensitivity Biomarker Influence on Toxicity Following Prostate Radiotherapy) was a single center phase II prospective study evaluating the impact of sharing results from a germline genetic signature (PROSTOX) characterizing patients as having a low or high risk of developing late > 2 genitourinary (GU) toxicity from stereotactic body radiation therapy (SBRT) on decision making and toxicity. The goal of this early analysis was first to see if this information changed treatment choice, and second to see if patients categorized as genetically “low-risk” would have less late GU toxicity than those categorized as genetically “high-risk.” Methods: PROSTOX is a test of germline mutations run in the MiraDx CLIA-certified laboratory. Results were reported to the ordering physician and their patient for joint decision-making before proceeding with treatment selection. To be enrolled on the study patients could choose SBRT or moderately hypofractionated radiation therapy (MHFRT) for treatment of their prostate cancer. 279 men were screened for the GARUDA study between November 2020 and May of 2022. 71 withdrew for a variety of reasons, primarily choosing another location for treatment or form of treatment. 208 patients remained on the protocol and are included in this exploratory analysis. Statistical comparisons of stratified proportions are based on Gaussian approximations to Binomial probabilities. Results: The average age for the cohort was 72.12 with the majority being non-Hispanic and Caucasian. Overall, 85.15% (177) of patients were classified as low-risk and 14.9% of patients (31) were classified as high-risk for late grade > 2 GU toxicity by PROSTOX. There was not a significant difference in predicted toxicity risk by age (72.45 vs 70.2), ethnicity or race. Regarding treatment choice based on toxicity score, in patients determined to be low-risk, 1.2% chose MHFRT, and 98.8% chose MRI- or CT-guided SBRT. In patients who were classified as high-risk, 44.8% chose MHFRT, and 55.2% chose MRI- or CT-guided SBRT. The difference in treatment choice was significant (p < 0.001). In an early analysis of physician scored late > 2 GU toxicity in patients with > 18 months of follow-up (n = 57), 8.8% of patients had toxicity - 4.8% of those predicted to be low-risk, and 27.3% of those predicted to be high-risk (p = 0.015). Conclusions: In this exploratory analysis, predicting toxicity risk with PROSTOX significantly impacted patient and physician radiation treatment choice in localized prostate cancer. Early results also suggest that these changed treatment decisions lowered overall toxicity, which remained significantly different between patients classified as low-risk and high-risk. Analysis is ongoing to include patient reported outcomes and toxicity rates depending on treatment choice for those identified as high-risk. Clinical trial information: NCT04624256 .

Incidence of genitourinary complications following radiation therapy for localised prostate cancer

PurposeStudies of genitourinary toxicity following radiotherapy for prostate cancer are mainly from high volume single institutions and the incidence and burden of treatment remain uncertain. Hence we determine the cumulative incidence of treatment-related genitourinary toxicity in patients with localised prostate cancer treated with primary external beam radiotherapy (EBRT) at a state population level.MethodsWe analysed data from a prospective population-based cohort, including hospital admission and cancer registry data, for men with localised prostate cancer who underwent primary EBRT without nodal irradiation between 1998 and 2019 in South Australia. The 10-year cumulative incidence of genitourinary toxicity requiring hospitalisation or procedures was determined. Clinical predictors of toxicity and the volume of admissions, non-operative, minor operative and major operative procedures were determined.ResultsAll the included patients (n = 3350) had EBRT, with a median (IQR) of 74 Gy (70–78) in 37 fractions (35–39). The 10-year cumulative incidence of was 28.4% (95% CI 26.3–30.6) with a total of 2545 hospital admissions, including 1040 (41%) emergency and 1893 (74%) readmissions. The 10-year cumulative incidence of patients in this cohort requiring a urological operative procedure was 18% (95% CI 16.1–19.9), with a total of 106 (4.2%) non-operative, 1044 (41%) minor operative and 57 (2.2%) major operative urological procedures.ConclusionsGenitourinary toxicity after radiotherapy for prostate cancer is common. Although there continue to be advancements in radiotherapy techniques, patients and physicians should be aware of the risk of late toxicity when considering EBRT.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00345-022-04124-x.

Dosimetric Predictors of Genitourinary Toxicity From a Phase I Trial of Prostate Bed Stereotactic Body Radiation Therapy

PurposeOur purpose was to analyze dose-volume parameters associated with genitourinary (GU) toxicity from a phase I clinical trial of prostate bed stereotactic body radiation therapy. Methods and MaterialsPatients were treated in escalating dose levels of 35, 40, and 45 Gy, over 5 fractions. Data from all 26 patients enrolled in the protocol were analyzed using multiple dose-volume cut points for multiple GU organs at risk. Univariate logistical regression and Fisher exact test were used to assess statistical significance associated with incidence of toxicity. ResultsThe median follow-up was 36 months for all patients. Acute GU toxicity was mild and resolved spontaneously. Eight out of 26 patients (30.7%) developed late GU toxicity of grade 2 or higher. Two patients developed grade 3 ureteral stenosis, 1 in the 35 Gy arm and the other in the 45 Gy arm. Three patients developed grade 2 or higher hematuria/cystitis, and 3 developed grade 2 or higher incontinence. Incidence of grade 3 ureteral stenosis was related to the absolute volume of bladder wall receiving greater than 20, 25, and 30 Gy (P < .01). Grade 2 cystitis and hematuria were related to the volume of bladder wall receiving 20 Gy less than 34% and 35 Gy less than 25% (18.8% vs 60% and 23.8% vs 80%, respectively, P < .05). Incontinence was related to mean urethral dose less than 35 Gy and 25 Gy (4.3% vs 66.7% and 0% vs 37.5%, respectively, P < .05) and volume of urethra receiving 35 Gy less than 24% (8.3% vs 50%, P < .05). ConclusionsThis is the first analysis to report dose-volume thresholds associated with late GU toxicity in patients receiving prostate bed stereotactic body radiation therapy. We recommend limiting the bladder wall receiving 25 Gy to less than 18 cubic centimeters to reduce the risk for late grade 3 ureteral stenosis.

Genitourinary toxicity after permanent iodine-125 seed implantation: The nationwide Japanese prostate cancer outcome study of permanent iodine-125 seed implantation (J-POPS)

PurposeThe purpose of this study was to evaluate acute and late genitourinary (GU) toxicity and to elucidate factors associated with GU toxicity in patients with prostate cancer treated with permanent seed implantation (PI) enrolled in a nationwide prospective cohort study in Japan. Methods and MaterialsOf 2,354 patients enrolled in this study, GU toxicity was evaluated in 2,339 patients at 3, 12, 24, and 36 months after PI. To elucidate independent factors predictive of acute and late Common Terminology Criteria for Adverse Events Grade 2 or higher (Grade ≥2) GU toxicity, multivariate logistic regression analyses were carried out. Regarding acute urinary retention (AUR), the incidence rate and the recovery rate for AUR were estimated using the Kaplan–Meier curve. ResultsApproximately 53% of the patients treated with PI alone and 42% of those treated with combination therapy with PI therapy and external beam radiation therapy showed urinary frequency/urgency at 3 months. The multivariate analysis revealed that age, prostate volume, pretreatment international prostate symptom score, drinking status, and PI were independent predictors of acute GU toxicity Grade ≥2. Of all patients, 53 (2.3%) suffered from AUR, and 49 (92.5%) recovered from AUR with a median time of 4.3 months during the followup period. ConclusionsThe results of GU toxicity in Japanese patients who underwent low-dose-rate brachytherapy were acceptable and comparable to those previously reported in U.S. patients. The patients treated with PI alone showed a significantly higher incidence rate of GU toxicity than did those undergoing combination therapy with PI and external beam radiation therapy in the acute phase.

Intensity Modulated Radiation Therapy and Image-Guided Adapted Brachytherapy for Cervix Cancer

This study reported long-term outcomes of patients with cervical cancer who were treated with intensity modulated radiation therapy and 3-dimensional (3D) image-guided adapted brachytherapy (IMRT/3D-IGABT) compared with those treated with 2-dimensional (2D) external irradiation and 2D brachytherapy (2D EBRT/BT). This study included patients with newly diagnosed cervical cancer and pretreatment fluorodeoxyglucose positron emission tomography scans who were treated with curative-intent irradiation from 1997 to 2013. The treatment policy changed from using 2D EBRT/BT to IMRT/3D-IGABT in 2005. Patterns of recurrence, cancer-specific survival (CSS), and overall survival (OS) were evaluated. Late gastrointestinal and genitourinary toxicity were scored with National Cancer Institute Common Terminology Criteria for Adverse Events. The median follow-up for patients alive at the time of last follow-up in the 2D EBRT/BT group (n=300) was 15.3years (range, 10.8-20.5years). In the IMRT/3D-IGABT group (n=300), it was 7years (range, 5-12.4years). According to the International Federation of Gynecology and Obstetrics, 33% of tumors were stage IB1 to IB2, 41% were stage IIA to IIB, and 26% were stage IIIA to IVA. The results after 5years for patients treated with 2D EBRT/BT showed that freedom from relapse (FFR) was 57%, CSS was 62%, and OS was 57%. For the IMRT/3D-IGABT group, the 5-year results showed that FFR was 65% (P=.04), CSS was 69% (P=.01), and OS was 61% (P=.04). When stratified by lymph node status according to positron emission tomography scan results, disease control was most improved with IMRT/3D-IGABT versus 2D EBRT/BT in patients with positive pelvic lymph nodes only (P=.02). Cumulatively, 88 of 600 patients (15%) had grade ≥3 late bowel/bladder toxicity. The 2D EBRT/BT group had 55 patients (18%), and the IMRT/3D-IGABT group had 33 patients (11%; P=.02). IMRT/3D-IGABT was associated with improved survival and decreased gastrointestinal and genitourinary toxicity in patients with cervical cancer compared with those who received 2D EBRT/BT.

Intensity-modulated radiation therapy for definitive treatment of cervical cancer: a meta-analysis

BackgroundTo compare the efficacies and toxicities of intensity-modulated radiotherapy (IMRT) with three-dimensional conformal radiotherapy (3D-CRT) or conventional two-dimensional radiotherapy (2D-RT) for definitive treatment of cervical cancer.MethodsA meta-analysis was performed using search engines, including PubMed, Cochrane Library, Web of Science, and Elsevier. In the meta-analysis, odds ratios (ORs) were compared for overall survival (OS), disease-free survival (DFS), and acute and chronic toxicities.ResultsIncluded data were analysed using RevMan 5.2 software. Six studies encompassing a total of 1008 patients who received definitive treatment (IMRT = 350, 3-DCRT/2D-RT = 658) were included in the analysis. A comparison of 3-year OS and 3-year DFS revealed no significant differences between IMRT and 3D-CRT or 2D-RT (3-year OS: OR = 2.41, 95% confidence interval [CI]: 0.62–9.39, p = 0.21; 3-year DFS: OR = 1.44, 95% CI: 0.69–3.01, p = 0.33). The incidence of acute gastrointestinal (GI) toxicity and genitourinary (GU) toxicity in patients who received IMRT was significantly lower than that in the control group (GI: Grade 2: OR = 0.5, 95% CI: 0.28–0.89, p = 0.02; Grade 3 or higher: OR = 0.55, 95% CI: 0.32–0.95, p = 0.03; GU: Grade 2: OR = 0.41, 95% CI: 0.2–0.84; p = 0.01; Grade 3 or higher: OR = 0.31, 95% CI: 0.14–0.67, p = 0.003). Moreover, the IMRT patients experienced fewer incidences of chronic GU toxicity than did the control group (Grade 3: OR = 0.09, 95% CI: 0.01–0.67, p = 0.02).ConclusionIMRT and conventional radiotherapy demonstrated equivalent efficacy in terms of 3-year OS and DFS. Additionally, IMRT significantly reduced acute GI and GU toxicities as well as chronic GU toxicity in patients with cervical cancer.

Evaluation of the Celecoxib Effect against Radiotherapy Induced Acute Toxicities in the Patients with Prostate Cancer Compared with Placebo Group

Background: Acute toxicities in patients with prostate cancer who accede to radiation therapy usually affect the patients’ quality of life and these toxicities are sometimes dose limiting. Objectives: This study was performed to determine the efficacy and safety of celecoxib together with radiation therapy. Methods: Forty prostate cancer patients undergoing external beam radiotherapy (EBRT) were enrolled to receive either placebo or celecoxib. The patients received external-beam radiotherapy up to 70 Gy daily fractions of 1.8 - 2 Gy. The patients received oral celecoxib or placebo 200 mg twice daily. The first celecoxib or placebo was administered 3 hours before each radiotherapy fraction and the second, 12 hours after the first consumption. RTOG based gastrointestinal (GI) and genitourinary (GU) acute toxicity scoring were performed pre-treatment, at least once weekly during radiotherapy and once 1 month after the end of the treatment. Results: Celecoxib was well tolerated. Thirty-nine patients (39/40) fully completed treatment according to protocol. No grade 4 toxicity was seen in two groups. A significant reduction in GU ≥ 2 toxicity was observed in the celecoxib group (P = 0. 006). No significant difference was found between the two groups with respect to GI ≥ 2 toxicity (P = 0. 621). Conclusions: We demonstrated that the combination of celecoxib with radiotherapy is well tolerated and decreased acute toxicities especially GU toxicity in patients with prostate cancer.

Dosimetric and Clinical Predictors of Long-Term Toxicity in Patients Undergoing Hypofractionated Prostate Radiation Therapy: Results From a Randomized Phase 3 Trial

To identify the rates of long term gastrointestinal (GI) or genitourinary (GU) toxicity in patients receiving hypofractionated (HIMRT) or conventionally fractionated intensity modulated radiation therapy (CIMRT) and to identify predictors of long term toxicity in patients receiving HIMRT. Men with clinically localized prostate cancer treated on a phase III randomized prospective trial were randomized to 76 Gy in 38 fractions (CIMRT) or 70.2 Gy in 26 fractions (HIMRT). Dosimetric constraints for the HIMRT patients were a rectal V50 Gy and V31 Gy of ≤17% and ≤35%, respectively. The bladder V50 Gy and V31 Gy were ≤25% and ≤50%, respectively. The derivation of HIMRT constraints was based on conservative extrapolations used for CIMRT patients (rectal V65 <17% and V40 <35%; bladder V65 <25% and V40 <50%). Late toxicity was compared between treatment groups utilizing the Kaplan-Meier method. CART analysis was used to identify dosimetric thresholds associated with an increased risk of grade 2+ (G2+) GI or GU toxicity. A total of 296 patients (148 CIMRT; 148 HIMRT) had evaluable dosimetric data. The median follow-up was 103 months (range = 13-157). There was no difference in late GU or GI toxicity in patients receiving HIMRT or CIMRT. The 8-year actuarial G2+ GI toxicity in patients receiving HIMRT and CIMRT was 10.5% and 16.2%, respectively (P = 0.96). The 8-year actuarial G2+ GU toxicity in patients receiving HIMRT and CIMRT was 40.5% and 25.1% respectively (P = 0.24). When examining the HIMRT cohort, there were no dosimetric variables associated with an increased risk of GU toxicity. Patients with a maximum rectal dose >34.67 Gy had an increased rate of G2+ GI toxicity (P = 0.04). There were no other dosimetric variables associated with an increased risk of GI toxicity. On univariate analysis, age >70 (P = 0.023) was the only factor associated with an increased risk of G2+ GU toxicity, there was a trend towards increased G2+ GU toxicity in patients with a baseline IPSS score >20 (P = 0.052), androgen deprivation therapy use (P = 0.065), and receipt of nodal radiation (P = 0.086). There were no variables associated with GU toxicity on multivariate analysis. There was a trend towards increased G2+ GI toxicity in patients >70 years old (P = 0.060). There were no factors associated with GI toxicity on multivariate analysis. In this randomized phase III study, there was no difference in long term toxicity between patients undergoing CIMRT or HIMRT. Due to the conservative dosimetric constraints utilized in patients receiving HIMRT, rates of late GI and GU toxicity were low. The dosimetric constraints used in this study for the HIMRT patients may serve as normal tissue constraints for practical clinical use.

Acute and Late Genitourinary Toxicity after 72 Gy of Conventionally Fractionated Conformal Radiotherapy for Localised Prostate Cancer: Impact of Individual and Clinical Parameters

AimOur aim was to estimate the incidence of acute and late genitourinary toxicity in patients treated with three-dimensional conformal radiotherapy (3DCRT) for localised prostate cancer and to estimate the possible influence of individual and clinical characteristics. Materials and methodsBetween September 2009 and September 2013, 225 patients with localised prostate cancer were treated with 3DCRT. Ninety-four patients with an estimated risk of lymph node involvement ≤15%, according to the Roach formula, were evaluated in this study. All patients received a total dose of 72 Gy in 36 fractions. Acute and late genitourinary toxicity were graded according to the European Organization for Research and Treatment of Cancer radiation morbidity scoring scale. Characteristics such as age, smoking status, previous abdominal or pelvic surgery (PAPS), diabetes mellitus and the use of diuretics were analysed as possible predictive factors of toxicity. The median follow-up was 27 months. ResultsGrade ≥2 acute toxicity during 3DCRT developed in 25 of 94 patients (26.5%). Predictive factors of acute genitourinary toxicity grade ≥2 in the multivariate logistic regression analysis (MVA) were current smoking status (P = 0.003), PAPS (P = 0.012) and the use of diuretics (P = 0.017). The 2 and 3 year cumulative risk of late genitourinary toxicity grade ≥1 was 25.3% and 30.2%, respectively. In the MVA, acute genitourinary toxicity was significantly associated with late genitourinary toxicity (P = 0.024). ConclusionCurrent smoking status, PAPS and the use of diuretics have a significant effect on the occurrence of acute genitourinary toxicity grade ≥2. The occurrence of any grade of acute genitourinary toxicity has a significant influence on the development of any grade of late genitourinary toxicity.

Low-dose aspirin mitigates acute radiation-induced genitourinary toxicity in patients with prostate adenocarcinoma

Objective Patients undergoing radiotherapy for prostate adenocarcinoma (PCA) primarily experience genitourinary (GU) and gastrointestinal (GI) toxicity. Recent publications indicate associations between aspirin and PCA outcomes. The effect of daily low-dose aspirin on radiotherapy toxicity was assessed in a large patient population.

Low-Dose Aspirin Mitigates Acute Radiation-Induced Genitourinary Toxicity in Patients With Prostate Adenocarcinoma

Low-Dose Aspirin Mitigates Acute Radiation-Induced Genitourinary Toxicity in Patients With Prostate Adenocarcinoma

Improved Overall Survival in Prostate Cancer With Increasing Dose

Purpose/Objective(s): Patients treated with radiation therapy for prostate adenocarcinoma (PCA) experience both acute and late genitourinary (GU) and gastrointestinal (GI) toxicity. Recent publications indicate a possible association between aspirin use and GI toxicity during radiation therapy for PCA. We sought to assess the effect of daily low-dose aspirin on acute and late GI and GU toxicity associated with radiation therapy for PCA in a large patient population. Materials/Methods: We queried an IRB-monitored, prospectively-acquired database of patients treated for PCA at our affiliated hospitals. For patients treated with definitive radiation therapy for PCA, we measured the association between aspirin use and Common Terminology Criteria for Adverse Events (CTCAE) GI/GU toxicity scores. Patient and treatmentrelated factors, such as age, race, total dose, T stage, hormonal therapy, use of pelvic nodal irradiation, length of time with acute toxicity records, and follow-up time were used as covariates. Univariate and multivariate analyses were performed using ordinal logistic regression models. Results: Between 1991 and 2013, 972 patients were eligible for analysis. 210 patients were on daily low-dose aspirin during treatment. On multivariate analysis, aspirin use was significantly associated with reduced acute GU toxicity (OR 0.73, 95% CI Z 0.55-0.99, p Z 0.040). There was no statistically significant worsening of acute GI (OR 0.77, 95% CI Z 0.581.03, p Z 0.079) or late GU toxicity (OR 0.93, 95% CI Z 0.69-1.25, p Z 0.632) associated with aspirin use. There was a trend for reduced late GI toxicity in patients taking daily aspirin (OR 0.69, 95% CI Z 0.48-1.01, p Z 0.056). Conclusions: Aspirin use was independently associated with reduced acute GU toxicity in patients undergoing radiation therapy for PCA. Late GU and GI toxicity were not worsened by aspirin use during radiation, and late GI toxicity trended towards improvement with aspirin use. While these results require validation in a prospective study, aspirin use during radiation therapy for PCA should be considered, as low-dose aspirin is a safe, inexpensive medication already separately recommended for many patients planned for radiation therapy. Author Disclosure: J.L. Mikell: None.W.A. Hall: None. D.C. Nickleach: None. N.K. Jegadeesh: None. P.J. Rossi: None. A.B. Jani: None.

Is There an Increase in Genitourinary Toxicity in Patients Treated With Transurethral Resection of the Prostate and Radiotherapy?

Transurethral resection of the prostate (TURP) is considered by some as a risk factor for genitourinary (GU) toxicity after radiotherapy (RT). However, there are conflicting results regarding the interaction between RT and TURP with respect to GU toxicity. The purpose of this report is to review the published data concerning TURP before or after RT and its effect on urinary complication. A systematic literature review based on database searches in MEDLINE, EMBASE, Pubmed, Ovid, and Chochrane Library. The eligibility criteria of final review were (1) definitive RT for prostate cancer is reported; (2) comparison of GU toxicities between patients with and without TURP is reported; (3) minimum 5 patients after TURP are included. Twelve articles regarding overall GU toxicity, 15 articles regarding urinary incontinence, and 13 articles regarding urinary or bladder neck stricture met eligibility criteria, and they were included in the final review. A quantitative synthesis from the data of selected articles was impossible because of variable grading systems and variable definitions in their comparisons between patients with and without TURP. However, most published articles demonstrated the increased risk of GU toxicity with TURP in patients treated with RT. Our systematic review strongly suggests that TURP is one of the risk factors of GU toxicity after RT. This needs to be taken seriously when prostate cancer patients with TURP are considered for RT either external beam or brachytherapy.

Body mass index can affect gastrointestinal and genitourinary toxicity in patients with prostate cancer treated with external beam radiation therapy

The aim of the present study was to determine the impact of obesity on radiation-induced gastrointestinal (GI) and genitourinary (GU) toxicity. The cases of 54 patients with prostate cancer, treated with three-dimensional conformal radiation therapy (RT), were reviewed. For each patient, the body mass index (BMI), distance between the prostate and rectum (D) on a computerised tomography scan and the dosimetric parameters of the rectum and bladder in the planning data of RT, were analyzed. GI and GU toxicity was assessed during and following RT. The results of the patients with a BMI of <25 (lower BMI) were compared with those of the patients with a BMI of ≥25 (higher BMI). The higher BMI group exhibited significantly lower doses of V60 and V65 in the rectum than the lower BMI group. No significant differences were found in D and bladder doses between the two groups. The incidence of acute GI and GU toxicity and late GI and GU toxicity were 41.7, 19.4, 35.3 and 5.7% in the lower BMI group, respectively, and 27.8, 27.8, 5.9 and 35.3% in the higher BMI group, respectively. In addition, a significant difference was found in the incidence of late GU toxicity between the two groups. Among patients who underwent RT for prostate cancer, those with higher BMIs had a tendency to show lower incidences of GI toxicity and higher incidences of GU toxicity than patients with lower BMIs. To conclude, an increased effort must be made to reduce rectal doses in patients with lower BMIs. Conversely, increased care for GU toxicity must be provided for overweight patients.

Carbon Ion Radiotherapy in Advanced Hypofractionated Regimens for Prostate Cancer: From 20 to 16 Fractions

To assess the effects of differences in dose fractionation on late radiation toxicity and biochemical control in patients with prostate cancer treated with carbon ion radiotherapy (C-ion RT). A total of 740 prostate cancer patients who received C-ion RT between April 2000 and February 2009 were analyzed. Of those, 664 patients followed for at least 1 year were analyzed with regard to late radiation toxicity. Biochemical relapse-free (BRF) and overall survival (OS) rates in patient subgroups with each dose-fractionation were analyzed. Only 1 case of grade 3 genitourinary (GU) morbidity was observed in 20 fractions, and none of the patients developed higher grade morbidities. The incidence of late GU toxicity in patients treated with 16 fractions was lower than that of patients treated with 20 fractions. The OS rate and BRF rate of the entire group at 5 years were 95.2% and 89.7%, respectively. The 5-year BRF rate of the patients treated with 16 fractions of C-ion RT (88.5%) was comparable to that of the patients treated with 20 fractions (90.2%). C-ion RT of 57.6 GyE (the physical C-ion dose [Gy]×RBE) in 16 fractions could offer an even lower incidence of genitourinary toxicity and comparable BRF rate than that in 20 fractions. Advancement in hypofractionation could be safely achieved with C-ion RT for prostate cancer.

Urethra low-dose tunnels: Validation of and class solution for generating urethra-sparing dose plans using inverse planning simulated annealing for prostate high-dose-rate brachytherapy

PurposeUrethral dose is related to severity of genitourinary toxicity in patients treated with brachytherapy for prostate cancer. This work describes a dose planning method that uses inverse planning to create a low-dose tunnel around the urethra and presents a class solution to achieve this additional dose sparing of the urethra. MethodsFifteen patients on the Radiation Therapy Oncology Group (RTOG) 0321 protocol were treated for prostate cancer with a high-dose-rate brachytherapy dose boost to an external beam radiation treatment regimen. All were treated with 9.5Gy for each of the two fractions after 45Gy of the external beam radiation. The inverse-planning algorithm, inverse planning simulated annealing (IPSA), was used to create both the standard RTOG protocol (SRP) plan for treatment and the a posteriori urethra dose sparing (UDS) plan consisting of a dose tunnel along the urethra. Both plans maintained the protocol parameters: prostate V100 (volume receiving 100% of prescribed dose)>90% and bladder and rectum V75<1 cm3. In the SRP plans, the urethra surface was optimized to receive <125% of the prescription dose and in the UDS plans <100%. Dose-volume histograms for the clinical treatment volume, bladder, rectum, penile bulb, and urethra for both plans are compared using a paired sample t test with significance claimed for probability values<0.05. ResultsUDS planning reduced the urethra V100 from 88% to 58% on average (p<0.01) and the V125 from 3.3% to 0.2% (p < 0.01). Bladder and rectum V75 were maintained at <1 cm3 and not significantly different between plans. Prostate coverage was maintained per protocol at V100>90%, with mean for the SRP V100=93% versus UDS plan V100=90%. Prostate D90 for SRP was 104% versus UDS plan D90=101%. For all patients, the UDS achieved a dose tunnel surrounding the length of the intraprostatic urethra. The class solution for generating UDS is presented. ConclusionsA urethral sparing–focused planning solution using IPSA reduces mean urethral dose by 34%, as compared with IPSA-generated plans based on the RTOG 0321 protocol. This is done while maintaining prostate coverage and critical structure dose. This technique can be applied to all patients in whom urethra toxicity is of particular concern.

The Impact of Pretreatment Prostate Volume on Severe Acute Genitourinary Toxicity in Prostate Cancer Patients Treated With Intensity-Modulated Radiation Therapy

To assess the impact of pretreatment prostate volume on the development of severe acute genitourinary toxicity in patients undergoing intensity-modulated radiation therapy (IMRT) for prostate cancer. Between 2004 and 2007, a consecutive sample of 214 patients who underwent IMRT (75.6 Gy) for prostate cancer at two referral centers was analyzed. Prostate volumes were obtained from computed tomography scans taken during treatment simulation. Genitourinary toxicity was defined using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 guidelines. Acute toxicity was defined as any toxicity originating within 90 days of the completion of radiation therapy. Patients were characterized as having a small or large prostate depending on whether their prostate volume was less than or greater than 50 cm(3), respectively. Genitourinary toxicity was compared in these groups using the chi-square or Fisher's exact test, as appropriate. Bivariate and multivariate logistic regression analysis was performed to further assess the impact of prostate volume on severe (Grade 3) acute genitourinary toxicity. Patients with large prostates (>50 cm(3)) had a higher rate of acute Grade 3 genitourinary toxicity (p = .02). Prostate volume was predictive of the likelihood of developing acute Grade 3 genitourinary toxicity on bivariate (p = .004) and multivariate (p = .006) logistic regression. Every 27.0 cm(3) increase in prostate volume doubled the likelihood of acute Grade 3 genitourinary toxicity. Patients with larger prostates are at higher risk for the development of severe acute genitourinary toxicity when treated with IMRT for prostate cancer.

Late gastrointestinal (GI) and genitourinary (GU) toxicity following intensity modulated radiation therapy (IMRT) for prostate cancer

Purpose: IMRT using a rectal catheter/balloon for prostate immobilization has been shown to decrease acute GI and GU toxicity. (Int J Radiat Oncol Biol Phys 49(3):705-712;2001) To report the late GI and GU toxicity in patients with localized prostate cancer treated with IMRT to a moderate dose escalation

Conformal Radiotherapy for Prostate Cancer&Longer Duration of Acute Genitourinary Toxicity in Patients with Prior History of Invasive Urological Procedure

The incidence and predictors of acute toxicity were evaluated in patients treated with three-dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer. Between December 1997 and November 1999, 116 patients with T1-T3 prostatic carcinoma were enrolled in the study. Ninety patients were treated with 70 Gy and 26 patients with T3 tumors received 74 Gy. Of the 116 patients 42 (36.2%) had a prior history of invasive urological procedure (IUP) (transurethral resection of the prostate or transvesical prostatectomy for benign prostatic hyperplasia). Acute gastrointestinal (GI) and genitourinary (GU) symptoms were graded according to the EORTC/RTOG scoring system. Toxicity duration after the completion of 3D-CRT was recorded. The majority of patients experienced only mild or no (Grade 1) acute toxicities. Medications for GI and GU symptoms (Grade 2) were required by 28.4% and 12.9% of patients, respectively. Only one case of Grade 3 GI toxicity (0.9%) was observed. Seven patients (6.1%) experienced severe GU toxicity (Grade 3 or 4). No correlation was found between acute toxicity and age, stage, dose (70 Gy vs. 74 Gy), IUP and pelvic lymphadenectomy. A significant relationship was observed between the duration of acute GU toxicity and prior IUP. Symptoms persisted for more than 4 weeks in 51.9% and 26.0% of patients with and without a prior history of IUP, respectively (p = 0.02). The incidence of acute complications, associated with 3D-CRT for prostate cancer, was acceptable in our cohort of patients. A prior history of IUP resulted in a significantly longer duration of acute GU toxicity.