Acute Urinary Toxicity Research Articles

Salvage Brachytherapy for Recurrent Prostate Cancer after Definitive Radiation Treatment and Factors That May Impact Outcomes

Salvage low-dose-rate (LDR) brachytherapy is a potential treatment option for patients with locally recurrent prostate cancer following primary radiation therapy. Here we report our single institution outcomes and toxicity when utilizing LDR brachytherapy in the salvage setting. Nineteen patients with biopsy-proven locally recurrent prostate cancer underwent salvage LDR brachytherapy under transrectal ultrasound guidance utilizing 103 Pd to 120 Gy from August 2010 through February 2018. Prostate-specific antigen (PSA) failure was determined utilizing the Phoenix (nadir+2) definition. Toxicity was graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and patient reported questionnaires including the Expanded Prostate Cancer Index Composite (EPIC) and American Urological Association (AUA). Median follow-up was 41 months. The 4- and 5- year PSA relapse-free survival (RFS) following salvage treatment were 78.9% and 68.4%, respectively. Androgen deprivation therapy was utilized in conjunction with salvage treatment in 7 patients (37%). On univariate analysis, 5- year PSA relapse was associated with both patients who experienced early failures after initial definitive treatment (p=.012), or if the patient had received stereotactic body radiation treatment (SBRT) (p=.005) prior to salvage treatment. Of the four patients who were treated following a biopsy-proven recurrence after initial SBRT treatment, two patients (50%) experienced PSA failure at a median of 9 months after their salvage treatment. AUA and EPIC scores showed a significant increase at one-month follow-up after salvage brachytherapy (p = .023) and returned to baseline within six months. Three patients (16%) experienced Grade 3 acute or late urinary toxicity, five patients experienced Grade 2 acute urinary toxicity, and one patient experienced Grade 2 acute rectal toxicity. Post-implant dosimetry did not predict for toxicity. There were no Grade 4 or 5 toxicities. LDR brachytherapy is a viable treatment option in the salvage setting with minimal morbidity. While longer follow-up is needed, early failures from initial radiation treatment and prior SBRT may portend for worse outcomes following salvage LDR brachytherapy.

Exploring the Impact of External Urethral Length on Acute Urinary Toxicity in Patients Undergoing High Dose Rate Brachytherapy for Prostate Cancer

The pre-operative and post-operative length of the external urethra sphincter (EUS) in patients undergoing radical prostatectomy has previously been reported to correlate with urinary incontinence. We aimed to determine if external urethral length impacts rates of urinary incontinence in patients undergoing high dose rate (HDR) brachytherapy. We performed a retrospective cohort study of patients with localized prostate cancer treated with MRI-based HDR brachytherapy monotherapy on a prospectively maintained database of prostate HDR patients treated from 2017-2018. Patients were treated with 13.5 Gy in 2 fractions delivered 1-2 weeks apart. CT images were used for catheter identification, and a T2 weighted MRI was obtained after the implant for target and normal structure delineation. The planning target volume (PTV) consisted of the prostate with an asymmetric expansion of 0-5 mm, with inclusion of the proximal seminal vesicles. Expanded Prostate Cancer Composite - 26 (EPIC-26) was evaluated at baseline, 1 month, 3 months, 6 months, then every 6 months thereafter. Linear mixed effects models were used to estimate mean EPIC-26 scores, International Prostate Symptom Score (IPSS) scores, and CTCAE v.5.0 genitourinary and gastrointestinal toxicity over time based on EUS length which was dichotomized as ≤ (short) or > (long) than the median. During analysis, changes were also classified as minimal clinically important difference (MCID). 46 patients were treated with definitive HDR using MRI-based planning, including 1 NCCN high risk , 32 intermediate risk, and 13 low risk patients. Median follow up was 4.18 months. The median EUS length was 1.7 cm (range 0.5-2.35 cm). There was no difference in baseline mean EPIC-26 scores in any domains. For the Urinary Incontinence domain, baseline mean scores were similar for short and long EUS (87.79 vs. 91.42; p=0.96). Patients with a short EUS had a greater decline in Urinary Incontinence mean scores at 1 month (72.51 vs. 83.59), 3 months (73.16 vs. 92.59), and 6 months (76.47 vs. 93.01), meeting MCID at all time points after treatment, although this was only marginally significantly associated with EPIC-26 urinary incontinence scores (p=0.05). EUS length was not associated with other EPIC-26 scores, changes in IPSS scores, or acute GU or GI toxicity. In concordance with surgical literature, shorter EUS length may be associated with acute urinary incontinence outcomes as assessed by EPIC-26 scores, however our series is limited by short follow-up and small sample size. Further research is required to validate our findings and, if so, may guide discussion with patients in the future regarding risks and benefits of brachytherapy.

Oncologic Outcomes of Adjuvant versus Salvage Radiotherapy after Prostatectomy

Introduction: The benefit of adjuvant radiotherapy (AR) or salvage radiotherapy (SR) after prostatectomy is still unclear. We wanted to compare both types of radiotherapy after prostatectomy in terms of oncological and functional results. Methods: We included 173 patients treated at a single center between January 2005 and December 2008. All patients were treated with the same radiotherapy protocol (3D conformal radiotherapy accelerator 6 mV, 66 GY). AR was defined as radiotherapy initiated in a patient with a PSA level <0.2 ng/mL after prostatectomy otherwise it was defined as SR. No patients received neoadjuvant therapy prior to prostatectomy (whether hormone therapy or chemotherapy). Patients in the SR group had a PSA level ≥0.2 ng/mL during the treatment in accordance with the Phoenix criteria. The lymph nodes were irradiated if the patient had no lymph node dissection and if the risk of nodal involvement was >10%. Both groups were compared in terms of biological progression-free, metastasis-free, and overall survival (OS) using log-rank tests. Moreover, acute and late urinary and gastrointestinal toxicity were also compared. Results: One hundred and fifty-seven patients underwent an open retropubic prostatectomy whereas 16 underwent a laparoscopy (6 subperitoneal and 10 transperitoneal). Eighty-six patients had AR with a median time of 6.7 months after surgery and 87 had SR with a median time of 21.4 months after surgery. Median follow-up was 6.7 years. Metastasis-free survival (MFS) was better in the AR than in the SR group (p = 0.01, 6-year MFS 95 and 89%, respectively). OS was also better in the AR than in the SR group (p = 0.02, 6-year OS 100 vs. 95%, respectively). AR was associated with better survival with no biochemical recurrence (85 vs. 63%, p < 0.00001). There was no significant difference between groups for acute or late urinary or gastrointestinal toxicity. Conclusion: Our study suggests that patients treated by AR have better results in terms of OS, disease-specific survival, survival without metastatic recurrence, and survival without biochemical recurrence compared with SR. Toxicity was comparable between both groups.

Forward- and Inverse-Planned Intensity-Modulated Radiotherapy in the CHHiP Trial: A Comparison of Dosimetry and Normal Tissue Toxicity

AimsThe CHHiP (Conventional or Hypofractionated High-dose Intensity Modulated Radiotherapy In Prostate Cancer; CRUK/06/016) trial investigated hypofractionated radiotherapy for localised prostate cancer. Forward- (FP) or inverse-planned (IP) intensity-modulated techniques were permitted. Dose–volume histogram and toxicity data were compared to explore the effects of planning method. Materials and methodsIn total, 337 participants with intermediate-risk disease and prospectively collected toxicity data were included. Patients were matched on prostate and rectum/bladder volumes and on radiotherapy dose for toxicity comparisons. The primary outcome was grade 2 or higher Radiation Therapy Oncology Group (RTOG) bowel or bladder toxicity at 2 years. ResultsIP patients had smaller volumes of rectum irradiated to 50–70 Gy (P < 0.001); FP patients had smaller volumes of bladder irradiated to 74 Gy (P = 0.001). Acute grade 2 + bowel toxicity was worse with FP (27/53 [52%]; 11/53 [21%] IP; P = 0.0002); with no significant differences in acute urinary toxicity. At 2 years, RTOG grade 2 + bowel toxicity rates were FP 0/53 and IP 2/53 and RTOG grade 2 + bladder rates were FP 0/54 and IP 1/57. ConclusionsSignificant differences were found between dose–volume histograms from FP and IP methods. IP may result in small reductions in acute bowel toxicity but both techniques were associated with low rates of late radiotherapy side-effects.

Dose to the bladder neck in MRI-guided high-dose-rate prostate brachytherapy: Impact on acute urinary toxicity and health-related quality of life

PurposeTo assess the impact of the dose to the bladder neck (BN) on acute urinary toxicity (AUT) and health-related quality of life (uHRQoL) in patients with prostate cancer treated with MRI-guided high-dose-rate brachytherapy combined to external beam radiotherapy. Methods and MaterialsSixty-one patients were treated with a single 15-Gy MRI-guided high-dose-rate brachytherapy followed by external beam radiotherapy as part of a prospective Phase II trial. The BN was delineated in retrospect on T2-weighted images. AUT and uHRQoL data were collected prospectively using Common Terminology Criteria for Adverse Events version 4.0 and the expanded prostate index composite. A minimally important difference (MID) was defined as a deterioration of uHRQoL scores at 3 months ≥ 0.5 standard deviation of baseline score. Linear and logistic regression models were used. ResultsThe median BN volume was 0.6 cc. The median BN and urethral maximum dose (BNDmax and UDmax) were 22 Gy and 20 Gy, respectively. BNDmax was significantly associated with UDmax (p = 0.03). AUT Grade 2 + was observed in 32% of patients. Among those, 4 patients had an acute urinary retention (AUR). No Grade 4 + toxicity was reported. At 3 months, 47% of patients reported an MID in urinary uHRQoL. None of the dosimetric parameters including BNDmax was associated with acute Grade 2 + urinary toxicity or MID. However, 3 of 4 patients with AUR had a BNDmax in the highest quartile; >175% of prescription dose. ConclusionsAlthough a high BN dose was observed in patients who had an AUR, the predictive value of this parameter is yet to be determined in a larger cohort.

Disease Control With Delayed Salvage Radiotherapy for Macroscopic Local Recurrence Following Radical Prostatectomy.

Purpose: To retrospectively assess clinical outcomes and toxicity profile of prostate cancer patients treated with delayed dose-escalated image-guided salvage radiotherapy (SRT) for macroscopic local recurrence after radical prostatectomy (RP).Material and Methods: We report on a cohort of 69 consecutive patients with local recurrence after RP and no evidence of regional or distant metastasis who were referred for salvage radiotherapy between 2007 and 2016. SRT consisted of 64–66 Gy (2 Gy/fraction) to the prostatic bed followed by dose escalation to 72–74 Gy (2Gy/fraction) to the macroscopic disease. All patients received concurrent short-term androgen deprivation therapy (ADT). Biochemical recurrence-free survival (bRFS) and clinical progression-free-survival (cPFS) were depicted using Kaplan-Meier method. Multivariable Cox proportional hazards regression assessed predictors of survival outcomes. Baseline, acute, and late urinary and gastrointestinal (GI) toxicity rates were reported using CTCAE v4.03.Results: Median time from RP to SRT was 66 months (IQR: 32–124). Median pre-SRT prostate-specific antigen (PSA) was 2.7 ng/ml (IQR: 0.9–6.5). Median follow-up after SRT was 38 months (IQR: 24–66). The 3- and 5-year bRFS were 58 and 44%, respectively. The 3- and 5-year cPFS were 91 and 76%, respectively. Median time from SRT to clinical disease progression was 102 months (IQR 77.5–165). At baseline, 3 patients (4%) had grade 3 urinary symptoms. Six patients (9%) developed acute and six patients (9%) developed late grade 3 urinary toxicity. Five patients (7%) had acute grade 2 GI toxicity. No acute grade 3 GI toxicity was reported. Late grade 3 GI toxicity was reported in one patient (1.5%).Conclusions: Delayed dose-escalated SRT combined with short-course ADT for macroscopic LR after RP was associated with 44% bRFS and 76% cPFS at 5 years. Albeit improved patient stratification is warranted, these data suggest that delayed SRT provides inferior tumor control compared to early intervention.

Voxel-Based Analysis for Identification of Urethrovesical Subregions Predicting Urinary Toxicity After Prostate Cancer Radiation Therapy

To apply a voxel-based analysis to identify urethrovesical symptom-related subregions (SRSs) associated with acute and late urinary toxicity in prostate cancer radiation therapy. Two hundred seventy-two patients with prostate cancer treated with intensity-modulated radiation therapy/image-guided radiation therapy were analyzed prospectively. Each patient's computed tomography imaging was spatially normalized to a common coordinate system via nonrigid registration. The obtained deformation fields were used to map the dose of each patient to the common coordinate system. A voxel-based statistical analysis was applied to generate 3-dimensional dose-volume maps for different urinary symptoms, allowing the identification of corresponding SRSs with statistically significant dose differences between patients with or without toxicity. Each SRS was propagated back to each individual's native space, and dose-volume histograms (DVHs) for the SRSs and the whole bladder were computed. Logistic and Cox regression were used to estimate the SRS's prediction capability compared with the whole bladder. A local dose-effect relationship was found in the bladder and the urethra. SRSs were identified for 5 symptoms: acute incontinence in the urethra, acute retention in the bladder trigone, late retention and dysuria in the posterior part of the bladder, and late hematuria in the superior part of the bladder, with significant dose differences between patients with and without toxicity, ranging from 1.2 to 9.3Gy. The doses to the SRSs were significantly predictive of toxicity, with maximum areas under the receiver operating characteristic curve of 0.73 for acute incontinence, 0.62 for acute retention, 0.70 for late retention, 0.81 for late dysuria, and 0.67 for late hematuria. The bladder DVH was predictive only for late retention, dysuria, and hematuria (area under the curve, 0.65-0.72). The dose delivered to the urethra and the posterior and superior parts of the bladder was predictive of acute incontinence and retention and of late retention, dysuria, and hematuria. The dose to the whole bladder was moderately predictive.

Five-Year Outcomes of a Phase 1 Dose-Escalation Study Using Stereotactic Body Radiosurgery for Patients With Low-Risk and Intermediate-Risk Prostate Cancer

To report toxicity outcomes, prostate-specific antigen (PSA) relapse, and cumulative incidence posttreatment biopsy results among patients treated on a prospective dose escalation study using ultra-hypofractionated stereotactic body radiation therapy (SBRT) for patients with low- and intermediate-risk prostate cancer. A total of 136 patients were enrolled in a phase 1 dose-escalation study to determine the tolerance of escalating radiation dose levels of SBRT for the treatment of localized prostate cancer. The initial dose level was 32.5Gy in 5 fractions, and doses were then sequentially escalated to 35Gy, 37.5Gy, and 40Gy. Eligibility criteria included only patients with low and intermediate risk, and the maximum prostate volume was 60cm3. Patients treated with neoadjuvant androgen deprivation were excluded. The median follow-up in survivors for the 4 dose levels was 5.9, 5.4, 4.1, and 3.5years, respectively. The incidence of acute grade 2 rectal toxicities for dose levels 1 to 4 were 0%, 2.9%, 2.8%, and 11.4% respectively. No grade 3 or 4 acute rectal toxicities were observed. The incidence of acute grade 2 urinary toxicities for dose levels 1 to 4 were16.7%, 22.9%, 8.3%, and 17.1%, respectively. No grade 3 or 4 acute urinary toxicities were observed. No grade 2 or higher rectal toxicities were observed. The incidence of late grade 2 urinary toxicities for dose levels 1 to 4 was 23.3%, 25.7%, 27.8%, and 31.4%, respectively. Only 1 late grade 3 urinary toxicity (urethral stricture) developed in the 40-Gy dose arm; the stricture was corrected with transurethral resection. No grade 4 late urinary toxicity was observed. The 5-year cumulative incidence of prostate-specific antigen failure for dose levels 1 to 4 was 15%, 6%, 0%, and 0%. The incidence of a 2-year positive posttreatment biopsy was 47.6%, 19.2%, 16.7%, and 7.7%, respectively for the 4 dose arms (P=.013). SBRT doses ranging from 32.5 to 40Gy in 5 fractions were well tolerated without severe urinary or rectal toxicities. Biopsy outcomes suggest improved rates of tumor clearance observed with higher doses.

Early Toxicity of a Phase 2 Trial of Combined Salvage Radiation Therapy and Hormone Therapy in Oligometastatic Pelvic Node Relapses of Prostate Cancer (OLIGOPELVIS GETUG P07)

Limited pelvic nodal relapse of prostatic cancer is a paramount challenge for locoregional salvage treatments. Salvage whole pelvis radiation therapy as considered in the BLINDED trial is an attractive option, but there are concerns about its toxicity. This article describes early toxicity with the technique. BLINDED was a prospective multicenter phase 2 trial investigating high-dose salvage pelvic irradiation with an additional dose to the fluorocholine-based positron emission tomography-positive pelvic lymph nodes, combined with 6-month androgen blockade. The prescribed dose was 54Gy in 1.8Gy fractions with up to 66Gy in 2.2Gy fractions to the pathologic pelvic lymph nodes. Early toxicity was defined as toxicity until 1year after radiation therapy. Patients quality of life was assessed using the European Organisation for Research and Treatment of Cancer questionnaires (QLQ-C30 and QLQ-PR25). Seventy-four patients were recruited in 15 French radiation oncology departments between August 2014 and July 2016. Seven were excluded before treatment because of violation of the inclusion criteria. The intention-to-treat analysis therefore included 67 patients. Half had received prior prostatic irradiation. Median age was 67.7±6.5years. Grade 2 acute urinary toxicity was observed in 9 of 67 patients (13.4%), and grade 2 1-year toxicity occurred in 4 of 67 patients (6%). Three patients (4.4%) had grade 3 urinary toxicity. Grade 2 acute digestive toxicity was observed in 10 of 67 patients (14.9%), and grade 2 1-year toxicity occurred in 4 of 67 patients (6%). Patients with prior prostate bed irradiation did not exhibit increased urinary or digestive toxicity. The European Organisation for Research and Treatment of Cancer questionnaire scores at 1year did not worsen significantly. The acute and 1-year toxicity of the BLINDED protocol was satisfactory, even in patients with a history of prostatic irradiation.

Short-term Toxicity of High Dose Rate Brachytherapy in Prostate Cancer Patients with Inflammatory Bowel Disease

AimsInflammatory bowel disease (IBD) has historically been considered a risk factor for increased bowel toxicity in patients receiving pelvic external beam radiotherapy. The risk is reduced in intensity-modulated radiotherapy compared with three-dimensional conformal radiotherapy. The effect of brachytherapy has been less extensively researched. Despite the increased dose to the gross tumour volume and decreased dose to organs at risk, previous studies have recommended avoidance of low dose rate (LDR) brachytherapy in patients with IBD, due to increased bowel toxicity. We investigated the effect of high dose rate (HDR) brachytherapy in IBD. Materials and methodsEleven IBD patients across four different sites (in the UK and Spain) who received HDR brachytherapy, between 2012 and 2015, were followed for up to 12 months. Acute bowel and urinary toxicity data were collected and recorded. ResultsThe median length of follow-up was 6 months (range between 6 weeks and 12 months). Five patients had Crohn's disease and six patients had ulcerative colitis. Only one patient (with Crohn's disease) had active disease at the time of treatment. This patient reported no bowel toxicity. Of the remaining patients, two suffered grade 1 diarrhoea (at 6 weeks and 6 months); three suffered grade 1 proctitis (at 6 weeks and 6 months). There was no grade ≥2 bowel toxicity. The most severe toxicity was grade 2 urinary frequency in one patient (at 6 weeks). DiscussionThis small, prospective case series suggests that, in the short term, HDR brachytherapy is safe and well tolerated in IBD patients. Therefore, IBD should not automatically disqualify patients from, at least, HDR brachytherapy. The reason why these results differ from previous LDR studies possibly reflects the benefit of inverse planning, which more readily achieves rectal dose constraints in HDR brachytherapy.

An Early Analysis of Toxicity Using 2 Different HDR Brachytherapy Regimens in the Treatment of Prostate Cancer

Prostate cancer is the most common cancer among men, therefore optimizing a curative, minimally toxic, and cost-effective treatment option is ideal. High-dose rate brachytherapy (HDR-BT) is one option that continues to become more cost-effective, with larger fraction sizes and fewer total treatments. This study is an assessment of acute and early late urinary and gastrointestinal (GI) toxicities with two different HDR-BT regimens in the treatment of prostate cancer.

Some Decline Of Urinary Toxicity In Patients Treated With I-125 Prostate Brachytherapy Boost During A 10-Year Period

To determine whether overall, acute and late urinary toxicity rates improved with a prostate brachytherapy boost program at a single institution over 10 years.

Comparison of Acute Urinary Toxicity Following Single Fraction HDR Brachytherapy Boost versus LDR Brachytherapy Monotherapy in the Treatment of Prostate Cancer

Comparison of Acute Urinary Toxicity Following Single Fraction HDR Brachytherapy Boost versus LDR Brachytherapy Monotherapy in the Treatment of Prostate Cancer

An Investigation of Dosimetric Correlates of Acute Toxicity in Prostate Stereotactic Body Radiotherapy: Dose to Urinary Trigone is Associated with Acute Urinary Toxicity

AimsThere are limited data on dosimetric correlates of toxicity in stereotactic body radiotherapy (SBRT) for prostate cancer. We aimed to identify potential relationships between dose and toxicity using conventional dose–volume histograms (DVHs) and dose–surface maps (DSMs). Materials and methodsUrinary bladder trigone and rectum DSMs were produced for a single-institution service evaluation cohort of 50 patients receiving SBRT for localised prostate cancer, together with conventional DVHs for bladder and rectum. Patients had been prospectively recruited to this cohort and treated according to a pre-defined protocol to a dose of 36.25 Gy in five fractions. Radiation Therapy Oncology Group (RTOG) and International Prostate Symptom Score (IPSS) toxicity data were recorded prospectively. Logistic regression was used to identify dosimetric predictors of acute IPSS+10 (rise of 10 points or more above baseline) and grade 2+ RTOG toxicity. ResultsOn univariate analysis, trigone area receiving 40 Gy and trigone Dmax were associated with IPSS+10 (odds ratio 1.06 [1.02–1.11], P = 0.007 and odds ratio 1.54 [1.06–2.25], P = 0.024, respectively). These two variables were highly correlated. In a multivariate model, including all baseline variables, trigone Dmax remained associated with IPSS+10 (odds ratio 1.91 [1.13–3.22], P = 0.016). These findings were not significant with Holm–Bonferroni correction for multiple testing (corrected P value threshold 0.006). No associations were seen between rectal toxicity and DVH or DSM parameters. ConclusionsOur study suggests a potential relationship between high doses to the urinary bladder trigone and patient-reported urinary toxicity in prostate SBRT, and is consistent with previous studies in conventionally fractionated radiotherapy, justifying further evaluation in larger cohorts.

3D-conformal hypofractionated radiotherapy for prostate cancer with daily transabdominal ultrasonography prostate localization: toxicity and outcome of a pilot study.

To evaluate the feasibility, toxicity and patient outcome of hypofractionated 3-dimensional conformal radiotherapy for low- and intermediate-risk prostate cancer, using daily an ultrasound targeting system (BAT). Between May 2005 and October 2006, 25 patients (cT1-T2, GS < or = 7, mean initial PSA = 7.06 ng/ml) received a dose of 72 Gy in 30 fractions. Only the prostate was included in the clinical target volume. Immediately before each radiotherapy session, BATTM ultrasound alignment was performed. Acute and late toxicity was evaluated according to the Radiation Therapy Oncology Group criteria; the Phoenix definition (PSA = nadir + 2 ng/ml) was applied to define biochemical failure. BAT localization data were provided for 300 out of 750 procedures. No interruptions in 3-dimensional conformal radiotherapy due to toxicity were registered. There was no acute rectal toxicity in 52% of patients; 28% had G1, 16% had G2, and 1 patient had a G3 event. No acute urinary toxicity was observed in 28% of the patients. G1 toxicity occurred in 40%, G2 in 28%, and G3 in 1 patient; no G4 event was observed. With an average follow-up of 45 months, one biochemical relapse was observed; late toxicity showed an excellent profile: 78% of the patients had no rectal toxicity, 16% had G1, and 1 patient had G2 toxicity. Most of the patients (68%) had no late urinary complications, whereas 32% had G1 toxicity. Localization data showed systematic and random errors in relation to some procedure biases. Promising tumor control and toxicity profile were observed with this mildly hypofractionated BAT-based 3-dimensional conformal radiotherapy.

Conformal radiotherapy of clinically localized prostate cancer: analysis of rectal and urinary toxicity and correlation with dose-volume parameters.

Rectal and urinary toxicities are the principal limiting factors in delivering a high target dose to patients affected by prostate cancer. The verification of such toxicity is an important step before starting a dose-escalation program. The present observational study reports on the acute and late rectal and urinary toxicity in relation with dose-volume parameters in 104 patients with localized prostate cancer treated with 3-dimensional conformal radiation therapy. One hundred and four patients with stage T1b-T3b prostate cancer were treated with three-dimensional conformal radiation therapy to a total dose of 74 Gy, 2 Gy per fraction. Rigid dose constraints were applied for rectum and bladder. Acute and late rectal and urinary toxicities were analyzed also in relation to dose-volume histograms. Biochemical relapse-free survival was defined according to the American Society of Therapeutic Radiation Oncology (ASTRO) criteria and to the RTOG-ASTRO Phoenix Consensus Conference Recommendations using the Kaplan-Meier method. No grade 3 toxicity was observed. Acute and late grade 2 toxicity rates were 5.8% and 9.0% for rectum and 12.5% and 2.0% for bladder, respectively. Rectal V70 influenced the occurrence of late grade 2 toxicity. A relationship between acute and late urinary toxicity was also found. After a median follow-up of 30 months (range, 20-50), the actuarial overall and biochemical relapse-free survival rates were 84% and 77%, respectively, with a significant difference between low-intermediate and high-risk patients. Conformal radiotherapy to the dose of 74 Gy was administered with good compliance. The incidence of acute and late toxicity was relatively low in accord with our dose constraints. Rectal V70 proved to be a reliable prognosticator of late toxicity. Overall survival and biochemical relapse-free survival rates were more favorable for low and intermediate-risk and significantly less favorable for high-risk patients.

125I brachytherapy for localized prostate cancer: a single institution experience.

To evaluate the clinical outcome of a cohort of localized prostate cancer patients treated with 125I permanent brachytherapy at the University of Turin. A retrospective analysis was carried out on 167 consecutive patients with early stage prostate adenocarcinoma who underwent 125I brachytherapy between January 2003 and December 2010. A minimum follow-up of ≥ 12 months was mandatory for inclusion. Biochemical disease-free survival (defined on the basis of the ASTRO definition and the ASTRO-Phoenix definition) was chosen as the primary end point. Secondary end points were gastrointestinal and genitourinary toxicity (acute and late, defined according to the RTOG scale). With a median follow-up of 42 months (range, 13.5-90.7), biochemical disease-free survival at 3 and 5 years was respectively 91.1% and 85.7%, according to the ASTRO definition and 94.5% and 85.1% according to ASTRO-Phoenix definition (for statistical purposes, only the ASTRO definition was used). Hormone treatment and nadir PSA (cutoff of 0.35 ng/ml) were the only factors affecting biochemical disease-free survival both on univariate (P = 0.02 and P = 0.001, respectively) and multivariate analysis (HR 0.024; P = 0.021 and HR 21.6; P = 0.006, respectively). Only 3.6% of patients experienced ≥ grade 3 acute urinary toxicity and 5% ≥ grade 3 late urinary toxicity. Prior transurethral prostate resection was the only independent predictor of grade 3 late urinary toxicity on multivariate analysis (HR 0.13; P = 0.009). This mono-institutional series confirmed that brachytherapy is an effective and safe treatment modality for localized prostate cancer, with acceptable short- and long-term morbidity rates.

Efficacy and tolerance of high-dose-rate brachytherapy boost after external radiotherapy in the treatment of squamous cell carcinoma of the anal canal.

PurposeThe aim of this study was to evaluate the efficacy and toxicity of high-dose-rate brachytherapy (HDR-BT) boost in anal squamous cell carcinoma (ASCC).Material and methodsThis was a monocentric retrospective study involving patients treated by external irradiation (± chemotherapy), with HDR-BT boost, for a localized ASCC. Clinical evaluation was performed every six months. Oncological results were analyzed with: local relapse-free survival (LRFS), colostomy-free survival (CFS), metastatic-free survival (MFS), disease-free survival (DFS), and overall survival (OS). Acute and late toxicities were collected (CTCV4.0) and LENT/SOMA score was performed.ResultsFrom May 2005 to January 2018, 46 patients (pts) were analyzed. The median follow-up was 61 months (10-145 months), the median age was 65 years (34-84 years), with a sex ratio M/F = 0.24. The TNM classification was as follows: T1 – 13 pts (21.7%), T2 – 34 pts (73.9%), T3 – 2 pts (4.3%), N+ – 6 pts (13.1%). External beam radiotherapy (EBRT) delivered a median dose of 45 Gy (36-50.4 Gy) in 25 fractions, and HDR-BT 12 Gy (10-18 Gy) in 3 fractions. The median overall treatment time (OTT) was 58 days (41-101 days), with a median EBRT/brachytherapy interval of 17 days (4-60 days). Oncological findings showed 5-year rates of LRFS 81.2%, MFS 88.7%, DFS 70%, and OS 90%. All abdominoperineal amputations were performed in case of local relapse (4 pts, 8.7%), leading to a 5-year CFS of 79.5%. Acute urinary toxicities were frequent (G1 41.3%, G2 4.3%). The acute digestive toxicities were: G1 71.7%, G2 6.5%, and G3 2.2%. The late urinary toxicities were: G1 4.3%, G2 2.2%, and G3 2.2%. Late digestive toxicities were: G1 56.5%, G2 8.7%, G3 2.2%, and G4 2.2%.ConclusionsIn ASCC management, HDR-BT boost appears to be a treatment with a long-term acceptable toxicity profile, shorter than EBRT boost, with a reduction of side effects.

Brachytherapy for localized prostate cancer in the modern era: a comparison of patient-reported quality of life outcomes among different techniques.

PurposeTo report our institutional quality of life (QOL) data for low-dose-rate (LDR) monotherapy (LDR mono), high-dose-rate (HDR) monotherapy (HDR mono), and EBRT with an HDR brachytherapy boost (HDR boost).Material and methodsThe charts of 165 patients with localized adenocarcinoma of the prostate treated with LDR monotherapy (LDR mono), HDR monotherapy (HDR mono), and EBRT with an HDR brachytherapy boost (HDR boost) at a single institution between 2012 and 2015 were reviewed. All patients completed the American Urological Association symptom score (AUASS) and Expanded Prostate Index for Prostate Cancer – Clinical Practice (EPIC-CP) quality of life assessments prior to treatment and at least one follow-up survey. Time points included baseline, ≤ 2 months, 2-≤ 6 months, 6-≤ 12 months, 12-≤ 18 months, 18-≤ 24 months, 24-≤ 30 months, and > 30 months. Linear mixed models were performed to test for significant changes and differences in each outcome over time.ResultsMean follow-up was 19.5 months. All major functional QOL domains were affected after treatment with brachytherapy for localized prostate cancer. All domains improved over time, with the exception of sexual function scores for all groups and urinary incontinence scores for the HDR mono group. Patients treated with LDR did have higher AUA, irritability/obstructive symptoms, incontinence, bowel, and QOL scores acutely compared to the HDR and HDR + boost groups. Vitality scores were significantly worse in the HDR boost group both acutely and at the > 30-month time point.ConclusionsPatients receiving HDR brachytherapy had lower acute urinary and rectal toxicity compared to the patients receiving LDR, even when combined with EBRT. However, long-term toxicity was similar.

Predictors of urinary and rectal toxicity after external conformed radiation therapy in prostate cancer: Correlation between clinical, tumor and dosimetric parameters and radical and postoperative radiation therapy

ObjectiveTo determine rectal and urinary toxicity after external beam radiation therapy (EBRT), assessing the results of patients who undergo radical or postoperative therapy for prostate cancer (pancreatic cancer) and their correlation with potential risk factors. MethodA total of 333 patients were treated with EBRT. Of these, 285 underwent radical therapy and 48 underwent postoperative therapy (39 cases of rescue and 9 of adjuvant therapy). We collected clinical, tumor and dosimetric variable to correlate with toxicity parameters. We developed decision trees based on the degree of statistical significance. ResultsThe rate of severe acute toxicity, both urinary and rectal, was 5.4% and 1.5%, respectively. The rate of chronic toxicity was 4.5% and 2.7%, respectively. Twenty-seven patients presented haematuria, and 9 presented hemorrhagic rectitis. Twenty-five patients (7.5%) presented permanent limiting sequela. The patients with lower urinary tract symptoms prior to the radiation therapy presented poorer tolerance, with greater acute bladder toxicity (p=0.041). In terms of acute rectal toxicity, 63% of the patients with mean rectal doses >45Gy and anticoagulant/antiplatelet therapy developed mild toxicity compared with 37% of the patients with mean rectal doses <45Gy and without anticoagulant therapy. We were unable to establish predictors of chronic toxicity in the multivariate analysis. The long-term sequelae were greater in the patients who underwent urological operations prior to the radiation therapy and who were undergoing anticoagulant therapy. ConclusionsThe tolerance to EBRT was good, and severe toxicity was uncommon. Baseline urinary symptoms constitute the predictor that most influenced the acute urinary toxicity. Rectal toxicity is related to the mean rectal dose and with anticoagulant/antiplatelet therapy. There were no significant differences in severe toxicity between radical versus postoperative radiation therapy.