Urinary Toxicity Research Articles

Stereotactic Pelvic Adjuvant Radiation Therapy in Cancers of the Uterus (SPARTACUS): A Multicenter Prospective Trial Evaluating Acute Toxicities and Patient Reported Outcomes

Adjuvant radiation plays a significant role in reducing locoregional recurrences in uterine cancers. Standard treatment consists of daily radiation for 5 weeks which can be challenging for patients and the healthcare system, especially during the COVID pandemic. Hypofractionated radiotherapy has been evaluated and established in other pelvic malignancies. This study aims to evaluate the acute urinary and bowel toxicities, and patient reported outcomes following stereotactic hypofractionated adjuvant radiation for endometrial cancer.This is a prospective phase I/II trial in which patients with endometrial cancer planned for adjuvant radiation received 30 Gy in 5 fractions, every other day or once weekly. Treatment was delivered at two centers with volumetric arc radiation therapy with a body-vacuum immobilization, bowel enema and 3D image-guidance. Toxicity assessment, outcomes and patient reported quality of life (QOL, EORTC core QLQ-C30 and endometrial EN24) were collected at baseline, fractions (F) 3 and 5, and at regular follow-up intervals. Higher scores represent better global QOL/health status or worse symptoms (scale 0 - 100). Changes in QOL over time were investigated with linear mixed-effects models. A P-value threshold of 0.05 was used for statistical significance. A change in QOL score of ≥ 10 points was considered clinically significant.The median age of the 41 enrolled patients is 66 (range: 51 - 88). Histologies included 29 endometrioid adenocarcinoma, 8 serous/clear cell, 1 carcinosarcoma, and 3 dedifferentiated. Thirty patients had stage 1 disease while 3 had stage 2 and 8 stage 3. Seven patients received sequential chemotherapy and 3 had additional vault brachytherapy. Median follow-up is 9 months, with worst toxicity (GI or GU) of grade 1 and 2 in 63% and 24% respectively. No patients have experienced a grade 3 or higher toxicity. Patient-reported diarrhea and gastrointestinal domain scores were statistically significantly worse than baseline at F5 (mean paired difference = 27.2; 8.7, P < .005) and 6 weeks (mean paired difference = 7.9; 5.1, P < 0.05), and returned to baseline levels at 12 weeks (Table 1). The only clinically significant change (≥ 10) from baseline was in diarrhea at F5. There were no significant changes in urinary domain, overall health and quality of life scores. No locoregional recurrences have been found; 3 patients recurred distantly, of which 2 died of metastatic disease.Stereotactic hypofractionated radiation for uterine cancers is feasible and well-tolerated with short-term follow-up. Longer follow-up and future randomized studies are needed to further evaluate this treatment.

Clinical and Dosimetric Outcomes of MR Guided Prostate SBRT With Daily Online Plan Adaptation

Stereotactic body radiotherapy (SBRT) is increasingly being utilized in the management of localized prostate cancer. MR guided adaptive radiotherapy may be a valuable tool for delivery of prostate SBRT as it allows for MR based soft tissue contouring, real time MR motion management and daily plan adaptation to account for interfraction anatomic variability. The goal of the present study is to identify dosimetric gains that can be achieved with an MR guided adaptive prostate SBRT platform and describe acute clinical outcomes.We reviewed our institutional experience treating patients with prostate cancer with MR guided adaptive SBRT to a dose of 36.25 Gy in 5 fractions. The adaptive workflow involves development of an "original" plan which is re-optimized daily based on anatomical variation for each fraction. "Predicted" plan dosimetry is generated for each fraction by re-calculating the original plan on the re-contoured daily anatomy, estimating what would have been delivered without adaptive capabilities. A "re-optimized" plan is developed based on the anatomy of the day to improve target coverage and organ-at-risk (OAR) metrics. Wilcoxon rank sum testing was used to compare predicted dosimetry to re-optimized dosimetry. Acute urinary and GI toxicity rates were assessed according to CTCAE v5.A cohort of 16 patients treated was analyzed with median follow up time of 3 months. Acute G2+ GU toxicity was observed in 19% and acute G2+ GI toxicity in 6%. No G3+ events were noted. Comparison of dosimetry metrics for PTV coverage, urethra, rectum and bladder are shown in table 1; 100% of fractions required plan adaptation due to either exceeding OAR metrics (68%) or sub-optimal PTV coverage (33%). Adaptive planning increased the proportion of fractions meeting prescription metrics for PTV coverage (V34.44 from 71% to 100%), urethra (V38.78 from 58% to 100%) and rectum (V38.06 from 80% to 100%). Urethral metrics were most frequently violated in predicted plans (42% of fractions) and re-optimized to acceptable dosimetry in 100% of fractions. Re-optimization significantly improved PTV coverage, rectal metrics and urethral metrics.Online adaptive re-optimization significantly improved plan dosimetry and achieved minimal acute toxicity. The clinical benefits of MR guided adaptive prostate SBRT for optimizing target coverage with urethral protection warrant further investigation.

Targeting the GTV in Medically Inoperable Endometrial Cancer Using Brachytherapy

Standard of care for endometrial cancer is upfront surgery. For women who are not candidates for surgery based on medical comorbidities, definitive brachytherapy (BT) +/- external beam radiation therapy (EBRT) offers an alternative approach. Consensus guidelines define the clinical target volume (CTV) as uterus, cervix, and 1-2 cm of the vagina. Guidelines discuss an optional gross tumor volume (GTV) with a recommended prescription dose of 80 Gy.We used an institutional endometrial cancer database to identify medically inoperable patients who received definitive radiation therapy from 2013-2019. Treatment plans were reviewed to determine doses to GTV, CTV, and organs at risk (OARs). In patients with a definable GTV on MRI and/or PET, BT was prospectively replanned with a goal of GTV D98 EQD2 ≥ 80 Gy, without regard for coverage of the remaining uterus and while respecting OAR dose constraints. The use of EBRT, EBRT dose, and number of BT fractions remained consistent between the original plan and GTV-only replan. Doses to OARs were compared using t-test and Chi-squared test.Fifty-four patients were identified. A definable GTV was present in 44 patients, of which 61.4% had MRI/PET images fused during the original treatment planning process to optimize dose to GTV. In the remainder of patients, diagnostic images were fused to retrospectively determine dose to GTV and target GTV for replanning. On original plans, GTV D90 EQD2 ≥ 80 Gy was achieved in 36 (81.8%) patients, and D98 EQD2 ≥ 80 Gy was achieved in 24 (54.5%) patients with a definable GTV. Local recurrence free survival was 91.1% at 2 years, including 100% in patients with GTV D90 EQD2 ≥ 80 Gy and 66.7% < 80 Gy (P = 0.001), and 100% in patients with GTV D98 EQD2 ≥ 80 Gy and 87.5% < 80 Gy (P = 0.299). Grade 3 toxicity occurred in 6 (10.4%) patients, including 4 cases of proctitis and 2 cases of urinary toxicity. On GTV-only replans, GTV D98 EQD2 ≥ 80 Gy was achieved in 39 (88.6%) patients. Mean D2cc for original plans and GTV-only replans, respectively, were: bladder 73.0 Gy, 47.1 Gy (P < 0.001); rectum 43.2 Gy, 35.3 Gy (P = 0.072); sigmoid 58.0 Gy, 47.0 Gy (P = 0.007); bowel 47.7 Gy, 41.0 Gy (P = 0.078). Bladder D2cc was ≥ 80 Gy in 11 (25.0%) original plans and 4 (9.1%) GTV-only replans (P = 0.043). Sigmoid D2cc was ≥ 65 Gy in 20 (45.4%) original plans and 10 (22.7%) GTV-only replans (P = 0.021).Uterine BT according to current inoperable endometrial cancer guidelines results in OAR doses at or near constraints, with associated toxicity in a patient population with limited functional reserve. BT targeting the GTV results in lower OAR doses compared to standard CTV-directed BT. Adequate dose to the MRI and/or PET-defined GTV is associated with excellent local control. Prospective evaluation of MRI-guided BT to a reduced, GTV-focused volume is warranted.E. Merfeld: None. J.Y. Huang: None. A. Kuczmarska-Haas: None. V. Desai: None. J. Miller: None. M. Lawless: None. C. Wallace: None. B.M. Anderson: Partner; University of Wisconsin. Research Grant; ViewRay. K.A. Bradley: None.

Effect of bladder volume on radiation doses to organs at risk and tumor in cervical cancer during image-guided adaptive brachytherapy and treatment outcome analysis.

There is no consensus in clinical practice on the optimal bladder volume during brachytherapy. The present study aimed to assess the effect of bladder volume on radiation dose to organs at risk and tumor in cervical cancer during image-guided adaptive brachytherapy and clinical outcome. The retrospective study included patients treated at University of Hong Kong-Shenzhen Hospital between January 2015 and July 2019. Patients with International Federation of Gynecology and Obstetrics (2009) stage IB1-IVB (retroperitoneal lymph nodes metastasis only) cervical cancer treated by external beam radiotherapy with concurrent cisplatin followed by brachytherapy were assessed. A total of 421 brachytherapy insertions were analyzed. Every 83 and 90 cm3 (cc) increase in bladder volume led to an incremental raise of 1 Gy in bladder wall minimum dose received by the most irradiated 1 and 2 cc volumes (D1 and D2cc) of the bladder wall, respectively. An increase in bladder volume was associated with increased D1 and D2cc of bladder (both P<0.001, respectively) and rectal wall (P=0.150 and P=0.084, respectively), and decreased D1cc (P=0.003) and D2cc (P=0.001) of sigmoid wall, the maximum doses to the most minimally exposed 90 (D90) and 95% (D95) of the high risk-clinical target volume (HR-CTV; D90, P=0.010; D95, P=0.006). Patients with cumulative HR-CTV D90≤89.6 Gy had shorter median overall survival (OS) than those with cumulative HR-CTV D90>89.6 Gy (42.1 months vs. not reached, P=0.001). Patients with grade 2 acute urinary toxicity had significantly higher cumulative bladder wall D2cc than those with acute urinary toxicity<grade 2 (86.7±3.7 vs. 78.5±7.9 Gy; P=0.001). As the bladder volume increased, the dose to the bladder and rectal wall increase and dose to the sigmoid colon wall and HR-CTV decrease based on intracavitary brachytherapy. The higher dose of HR-CTV predicted better OS and the higher dose received by the bladder wall was associated with more grade 2 acute urinary toxicity.

Early toxicities of ultrahypofractionated stereotactic body radiotherapy for intermediate risk localized prostate cancer using cone-beam computed tomography and real-time three-dimensional transperineal ultrasound monitoring.

PurposeImage-guided radiotherapy (IGRT) is central to the safe and effective delivery of ultrahypofractionated (UF) stereotactic body radiotherapy (SBRT) for localized prostate cancer. We aim to study the safety of performing UF-SBRT using cone-beam computed tomography (CBCT) and real-time transperineal ultrasound (TPUS) monitoring.Materials and MethodsWe retrospectively review the medical records of 26 patients who had received UF-SBRT for intermediate risk localized prostate cancer in our institution. All patients were treated with SBRT 35–40 Gy to the clinical target volume in 5 fractions over 2–5 weeks. CBCT was used to correct for interfraction displacement while intrafraction displacement of the prostate gland was monitored using TPUS. The primary endpoints were incidence of acute toxicities and patient reported urinary toxicities in terms of the International Prostate Symptom Score: before (IPSS1), at the completion of (IPSS2), and at 3–6 months (IPSS3) after SBRT.ResultsAll men were followed up for at least 3 months after SBRT. Patients experienced transient worsening of their urinary symptoms at the end of SBRT but they usually recovered in 3–6 months afterwards. The median IPSS1, IPSS2, and IPSS3 were 12, 12.5, and 8, respectively. One patient developed grade 3 rectal bleeding which was related to underlying hemorrhoid. No other grade 3–4 acute toxicity was observed.ConclusionIt appears safe to deliver UF-SBRT without fiducial marker for prostate cancer patients using CBCT and non-invasive hybrid imaging modalities for positioning and tracking. Longer follow-up is necessary to monitor the treatment efficacy and long-term toxicities.

Influence of hydrogel spacer placement with prostate brachytherapy on rectal and urinary toxicity.

To determine the influence of rectal hydrogel spacer placement (HSP) on late rectal toxicity outcomes in prostate cancer patients treated with low-dose-rate (LDR) brachytherapy, with or without supplemental external beam radiotherapy (EBRT). A total of 224 patients underwent LDR brachytherapy with HSP, as monotherapy or combined with EBRT, between January 2016 and December 2019. Dosimetric variables reflecting the extent of rectal sparing and late rectal toxicity outcomes were evaluated. This spacer cohort was retrospectively compared to a similar patient group (n = 139) in whom HSP was not used. Hydrogel spacer placement was associated with significantly reduced rectal doses for all dosimetric variables; the median percentage rectal dose to 1 cc of rectum and rectal dose to 2 cc of rectum of the spacer cohort were all significantly lower compared to the non-spacer cohort. The incidence rates of overall (any grade) and grade ≥2 rectal toxicity were lower in patients with HSP compared to patients who did not undergo HSP: 12% and 1.8% vs 31% and 5.8%, respectively. The 3-year cumulative incidence of overall rectal toxicity was significantly lower with HSP than without (15% vs 33%; P < 0.001), corresponding to an overall rectal toxicity reduction on univariable analysis (hazard ratio 0.45, 95% confidence interval 0.28-0.73; P = 0.001). In this patient cohort treated with prostate brachytherapy, none of the urethral dosimetric variables or the presence or absence of HSP was associated with late urinary toxicity. Hydrogel rectal spacer placement is a safe procedure, associated with significantly reduced rectal dose. HSP translates to a decrease in overall late rectal toxicity in patients receiving dose-escalated brachytherapy-based procedures.

Focal low dose-rate brachytherapy for low to intermediate risk prostate cancer: preliminary experience at an Australian institution.

BackgroundFocal treatment for prostate cancer (PCa) is a hybrid approach combining ablative treatment of the involved prostate gland and continued active surveillance (AS) of the unaffected gland. Low dose-rate (LDR) brachytherapy can be used as a lesion-targeted focal therapy, however, further studies are required to support its use. The aim of this study is to evaluate the dosimetry, toxicity and oncological outcomes of men receiving lesion-targeted focal LDR brachytherapy for low to intermediate risk PCa.MethodsThis is a retrospective cohort study of 26 men with unifocal, low to intermediate grade PCa diagnosed on a combination of multiparametric-magnetic resonance imaging (mp-MRI) and targeted plus template transperineal (TP) biopsy, who received focal LDR brachytherapy at a single institution. Brachytherapy involved a single monotherapy implant using iodine-125 seeds to deliver a prescribed dose of 145 Gy to the index lesion.ResultsThe mean focal planning target volume (F-PTV) as a percentage of the prostate volume was 24.5%. The percentage of the focal gross tumour volume (F-GTV) receiving 100% of the prescription dose was 100% for 12 patients and ≥98% for 18 patients. The median follow-up for toxicity and biochemical control outcomes was 23.1 [interquartile range (IQR) 19.1–31.3] and 24.2 (IQR 17.9–30.0) months, respectively. Grade 2 urinary and erectile toxicities were reported by 29.2% and 45.8% of patients, respectively, with resolution of urinary symptoms to baseline by last follow-up. There were no grade ≥3 urinary or erectile toxicities or grade ≥2 rectal toxicity. All 21 patients who underwent a repeat mp-MRI and TP biopsy at 12–24 months post-treatment were negative for clinically significant disease and 25 (96.2%) patients were free from biochemical failure (FFBF).ConclusionsFocal LDR brachytherapy is associated with a favourable toxicity profile and a high rate of control of significant PCa at 12–18 months post-treatment. We have commenced the LIBERATE prospective registry in focal LDR brachytherapy based on the highly encouraging outcomes of this initial experience.

Clinical predictors of severe late urinary toxicity after curative intensity-modulated radiation therapy for localized prostate cancer.

Intractable late urinary toxicity is a serious complication after radiotherapy for patients with localized prostate cancer (LPC). We assessed clinical factors correlated with severe late urinary toxicity in LPC treated with curative image-guided intensity-modulated radiation therapy (IMRT). A total of 452 patients with LPC treated with IMRT between 2002 and 2016 were retrospectively analyzed. Among them, 432 patients received androgen deprivation therapy (ADT). The median total irradiated doses were 80 (range, 76-80) Gy. Each daily dose was 2 Gy per fraction. The median follow-up was 83 (range, 4-210) months. Late urinary toxicity was scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.03. Grade 3 late urinary toxicity was observed in 27 patients. No cases with grade ≥ 4 late urinary toxicity were observed. The 5-, 10-, and 12.5-year grade 3 late urinary toxicity-free survival rates were 97%, 91.8% and 88.1%, respectively. Age, risk classification, total irradiated dose, ADT duration, antithrombotic therapy (AT), cardiovascular disease, hypertension (HT), diabetes mellitus (DM), dyslipidemia (DL), prior transurethral resection of the prostate (TURP) and prior high-intensity focused ultrasound (HIFU) were investigated for correlations with grade 3 late urinary toxicity. In univariate analysis, AT and prior HIFU and no other studied factors, were correlated with grade 3 late urinary toxicity. AT and prior HIFU appear to be predictive of grade 3 late urinary toxicity. Patients with LPC with these relevant clinical factors should be carefully followed up by sharing detailed information with the urology department.

Moderately Hypofractionated Radiotherapy and Androgen Deprivation Therapy for High-risk Localised Prostate Cancer: Predictors of Long-term Biochemical Control and Toxicity

AimsThere is a paucity of long-term data on outcomes of high-risk prostatic adenocarcinoma after moderately hypofractionated radiotherapy with elective nodal treatment and long-term androgen deprivation therapy (ADT). We report long-term control and toxicity outcomes and analyse the predictors of failure and toxicity. Materials and methodsThe records of 120 consecutive high-risk prostate cancer patients treated in a single institution between February 2012 and December 2016 were retrospectively analysed. A moderately hypofractionted radiotherapy (HypoRT) regimen of 60 Gy in 20 fractions over 4 weeks with simultaneous elective pelvic irradiation to 44 Gy in 20 fractions with intensity-modulated radiotherapy was used, together with long-term ADT with either orchiectomy or medical castration for a total duration of 2–3 years. We analysed biochemical control, metastasis-free survival and late toxicities and their predictive factors using survival analysis. ResultsPatients had locally advanced cancers (cT3 77.5%, median pretreatment prostate-specific antigen 30 ng/ml, Gleason score 8–10 in 45.8%). The median follow-up time was 70 months. The 3- and 5-year probability of freedom from biochemical progression was 93% and 80%, respectively. The 5-year probability of freedom from local relapse/intra-pelvic nodal relapse/distant metastases as the site of first failure was 96%/97%/86%, respectively. Gleason score 8–10 and medical ADT for 2–3 years (as opposed to orchidectomy) were independent risk factors for distant metastases. A total of 18 grade 2 and above late gastrointestinal toxicity events and a total of 23 grade 2 and above late genitourinary toxicity events were documented. Patients who underwent a transurethral resection of prostate prior to radiotherapy had worse urological toxicity. ConclusionsHypoRT with elective nodal treatment results in excellent pelvic control. Distant metastases are the primary mode of failure. Risk of metastases is associated with Gleason score and the duration of ADT. Late urinary toxicities are more common in those with prior transurethral resection of prostate.

Intravesical mitomycin C (MMC) and MMC + cytosine arabinoside for non-muscle-invasive bladder cancer: a randomised clinical trial.

ObjectivesTo compare the urinary pH, recurrence‐free survival (RFS), and safety of adjuvant intravesical therapy in patients with non‐muscle‐invasive bladder cancer (NMIBC) receiving mitomycin C (MMC) therapy and MMC + cytosine arabinoside (Ara‐C) therapy.Patients and MethodsA total of 165 patients with NMIBC from six hospitals were randomly allocated to two groups: weekly instillation of MMC + Ara‐C (30 mg/30 mL + 200 mg/10 mL) for 6 weeks and the same instillation schedule of MMC (30 mg/40 mL). The primary outcome was RFS, and secondary outcomes were urinary pH and toxicity in the two groups.ResultsA total of 81 and 87 patients were randomised into the MMC and MMC + Ara‐C groups, respectively. Overall, the RFS in the MMC + Ara‐C group was significantly longer (P = 0.018) than that in the MMC group. A similar significant difference was detected in patients with intermediate‐risk NMIBC, but not in those with high‐risk NMIBC. The mean (SD) urinary pH was significantly higher in the MMC + Ara‐C group than in the MMC group, at 6.56 (0.61) vs 5.78 (0.64) (P < 0.001), and the frequency of a urinary pH of >7.0 in the MMC and MMC + Ara‐C groups was 6.3% and 26.7%, respectively (P < 0.001). Multivariate analysis models including clinicopathological features and second transurethral resection demonstrated that increased urinary pH was associated with better outcomes (hazard ratio 0.18, 95% confidential interval 0.18–0.038; P < 0.001). In all, there were 14 and 10 adverse events in the MMC and MMC + Ara‐C groups, respectively, without a significant difference (P = 0.113).ConclusionsOur randomised clinical trial suggested that intravesical therapy with MMC and Ara‐C is useful and safe for patients with intermediate‐risk NMIBC. Increase in urinary pH with Ara‐C is speculated as a mechanism for increased anti‐cancer effects.

Gamma-H2AX Foci Decay Ratio as a Stronger Predictive Factor of Late Radiation Toxicity Than Dose-Volume Parameters in a Prospective Cohort of Prostate Cancer Patients

PurposeLate radiation toxicity is a major dose-limiting factor in curative cancer radiation therapy. Previous studies identified several risk factors for late radiation toxicity, including both dose-volume factors and genetic predisposition. Herein, we investigated the contribution of genetic predisposition, particularly compared with dose-volume factors, to the risk of late radiation toxicity in patients treated with highly conformal radiation therapy. Methods and MaterialsWe included 179 patients with prostate cancer who underwent treatment with curative external beam radiation therapy between 2009 and 2013. Toxicity was graded according to the Common Terminology Criteria for Adverse Events version 4.0. Transcriptional responsiveness of homologous recombination repair genes and γ-H2AX foci decay ratios (FDRs) were determined in ex vivo irradiated lymphocytes in a previous analysis. Dose-volume parameters were retrieved by delineating the organs at risk (OARs) on CT planning images. Associations between risk factors and grade ≥2 urinary and bowel late radiation toxicities were assessed using univariable and multivariable logistic regression analyses. The analyses were performed using the highest toxicity grade recorded during the follow-up per patient. ResultsThe median follow-up period was 31 months. One hundred and one patients (56%) developed grade ≥2 late radiation toxicity. Cumulative rates for urinary and bowel grade ≥2 late toxicities were 46% and 17%, respectively. In the multivariable analysis, factors significantly associated with grade ≥2 late toxicity were transurethral resection of the prostate (P = .013), γ-H2AX FDR <3.41 (P = .008), and rectum V70 >11.52% (P = .017). ConclusionsOur results suggest that impaired DNA double-strand break repair in lymphocytes, as quantified by γ-H2AX FDR, is the most critical determining factor of late radiation toxicity. The limited influence of dose-volume parameters could be due to the use of increasingly conformal techniques, leading to improved dose-volume parameters of the organs at risk.

Morbidity following image-guided brachytherapy for cervical cancer: Patient and treatment related factors

PurposeThis retrospective study aims to assess factors associated with the occurrence of toxicity after brachytherapy (BT), as boost after external beam radiotherapy (EBRT) for treatment of invasive cervix carcinoma. METHODS AND MATERIALSAll consecutive patients diagnosed with cervical carcinoma, and treated with concurrent radiochemotherapy from August 2017 to January 2020 were retrospectively included. An isodose conformation index (ICI) was developed to assess the percentage of the prescription isodose contained within the intermediate risk clinical target volume (IR-CTV). ResultsEighty-one patients with invasive cervix carcinoma from stage IB to stage IVa were included. Thirty-two (40%) and 49 (60%) patients were treated with Pulsed Dose Rate (PDR) and High Dose Rate (HDR) BT, respectively. Median follow-up was 19.6 months (5.6–41.2). The main factors associated with development of gastrointestinal toxicity were: the median volume of the prescription isodose (67.9cm[3] [37.6–92.9] vs. 49.1cm[3] [34.5–53.5], p = 0.05), the value of ICI (59% [51%-83%] vs. 86% [65%-96%], p = 0.01), the median equivalent dose delivered to the sigmoid (D2cc= 58.4 GyEQD2 [53.9–61.1] vs. 55.2 GyEQD2 [52.8–57.5], p = 0.06) and the median equivalent dose delivered to the IR-CTV (D90= 63.9 GyEQD2 [60.6–66.4] vs. 61.2 GyEQD2 [59.4–64.5], p = 0.03). The proportion of patients who received EBRT lymph node boost was higher in patients who developed urinary toxicity than in patients who did not (57.1% vs. 28.6%, p = 0.08). Anticoagulant (p = 0.02) and antiaggregant therapy (p = 0.01) were associated with occurrence of both urinary and gastrointestinal toxicity. ConclusionSOur study confirms the predictive value of irradiated volume in the occurrence of gastrointestinal toxicity, as well as the need for a better conformation to the target volume. Precautions should be considered in patients with vascular comorbidities.

Patient assessment of lower urinary tract symptoms using the international prostate symptom score following low-dose-rate prostate brachytherapy

To correlate changes in urinary patient-reported outcomes including the International Prostate Symptom Score (IPSS), acute urinary retention and urethral stricture with urethral dose in those treated with low dose rate (LDR) prostate brachytherapy. Patients treated with prostate LDR between 2012 and 2019 (n=117) completed IPSS urinary symptom assessments prior to treatment and at each follow-up. CT simulation was obtained with urinary catheter 1-month post-implant for dosimetric analysis. 113 patients with pre- and ≥1 post-LDR IPSS score available were analyzed. Urethral dosimetric parameters including U75, U100, U125, U150 and U200 were abstracted from post-implant dosimetry and assessed for association with urinary toxicity using bivariate logistic regression and Spearman correlation. Outcomes included clinically significant change (CSC, defined as 4 or more points or 25% rise above baseline) in IPSS score at 6 and 12 months, acute urinary retention (AUR), and urethral stricture (US). 89 (79%) patients were treated with LDR monotherapy (145 Gy) and 24 (21%) with LDR boost (110 Gy)with external beam radiation therapy. Twenty(18%) had baseline IPSS ≥15. Median IPSS scores were: baseline 6 (3-12; n=113), 1-month 17 (10-25; n=110), 6 months 12 (7-18; n=77), 1 year 8 (5-14; n=52). CSC-6 was observed in 59 (77%), CSC-12 in 26 (50%), AUR in 12 (11%), and US in 4 (4%). No association was identified between urethral dose parameters and CSC-6, CSC-12, AUR, or US. No correlation between urethral dose and IPSS at 6- and 12-months was identified. The IPSS ≥15 group exhibited lower rates of CSC-12 (13% v. 57%, p=0.05) but not CSC-6 (55% v. 80%, p=0.12). We did not find a relationship between urethral dose and IPSS elevation, AUR or US. We did identify a significantly lower change in IPSS at 12 months for those with baseline IPSS ≥15 compared to those with low baseline scores.

PO-1363 Prediction of urinary toxicity after prostate cancer RT: long term evaluation

PO-1363 Prediction of urinary toxicity after prostate cancer RT: long term evaluation

Dosimetric feasibility of stereotactic irradiation of primary prostate cancer at 5x9 Gy with a method of urethral sparing.

The most commonly used dose for prostate cancer stereotactic body radiotherapy (SBRT) is 5 × 7.25 Gy. The aim of this study was to evaluate the dosimetric feasibility of a 5 × 9 Gy SBRT regimen while still limiting the dose to the urethra to 5 × 7.25 Gy. This dosimetric study is part of the groundwork for a future Phase III randomized trial. The prostate, the urethra and the tumors were delineated on 20 dosimetric CT-scans with MRI-registration. The planning target volume (PTVp) was defined as a 5 mm expansion (3 mm posteriorly) of the prostate. The planning at risk volume (PRVu) was defined as a 2 mm expansion of the urethra. The tumors were delineated on the MRI (GTVt) and a 3 mm-margin was added to create a tumoral planning target volume (PTVt). IMRT plans were optimized to deliver 5 × 9 Gy to the PTVp, limiting the dose to the PRVu to 5 × 7.25 Gy. Results are presented using average (range) values. PTVp doses were D98% = 36.2 Gy (35.6-36.8), D2% = 46.9 Gy (46.5-47.5) and mean dose = 44.1 Gy (43.8-44.5). The dose to the PRVu was within tolerance limits for all 20 patients: V34.4Gy = 99.8% (99.2-100) and D5% = 38.7 Gy (38.6-38.8). Dose coverage of PTV-PRVu was D95% = 40.6 Gy (40.5-40.9), D5% = 46.6 Gy (46.2-47.2) and mean dose = 44.6 Gy (44.3-44.9). Dose to the PTVt reached 44.6 Gy (41.2-45.9). Doses to the OAR were respected, except V36Gy ≤1 cc for the rectum. A SBRT dose-escalation to 5 × 9 Gy on the prostate while sparing the urethra + 2 mm at 36.25 Gy is feasible without compromising dose coverage to the tumor. This radiation regimen will be used for a Phase-III trial. In prostate SBRT, dose optimization on the urethra is feasible and could decrease urinary toxicities.

Relationship of Urethral Dose and Genitourinary Toxicity Among Patients Receiving Vaginal High Dose Rate Interstitial Brachytherapy

AimsInterstitial brachytherapy (ISBT) plays an important role in the management of locally advanced gynaecological malignancies. However, the relationship between urinary toxicity and dose to the urethra is not well understood. We sought to evaluate the correlation between urethral dose and the incidence of genitourinary complications among patients undergoing vaginal high dose rate ISBT. Materials and methodsEighty-three patients treated with ISBT between August 2014 and April 2018 were retrospectively reviewed. CTCAE version 5.0 was used to grade toxicity. Individual treatment plans were evaluated to collect dose parameters. Urethral contours were added to the structure sets using a uniform 1 cm diameter brush and minimum doses to the hottest 0.1, 0.2 and 0.5 cm3 (D0.1cm3, D0.2cm3 and D0.5cm3) of the urethra were obtained. Total (ISBT ± external beam radiotherapy) equivalent doses in 2 Gy fractions (EQD2) received by the targets and organs at risk were calculated. Numerical counts (%) and medians (interquartile range) were used to characterise the data. Fisher's exact and the Mann–Whitney–Wilcox tests were used as appropriate. Receiver operator curve analysis was used to define the urethral threshold dose that correlated to genitourinary toxicity. ResultsThe median age and follow-up times were 67 years (59–75) and 25 months (16–37), respectively. Patients had predominantly primary endometrial (49%) and vaginal (37%) cancer, with four (5%) patients with metastatic rectal cancer to the vagina. Twenty-four of 79 (30%) patients experienced acute genitourinary toxicity and 34 of 71 (48%) experienced late genitourinary toxicity. In both analyses, the median urethral dose was significantly higher among those with toxicity. Receiver operator curve analysis indicated that D0.1cm3, D0.2cm3 and D0.5cm3 of the urethra were associated with the development of toxicity at doses >78, >71 and >62 Gy, respectively. ConclusionUrethral dose seems to predict genitourinary toxicity in ISBT of vaginal tumours. Further study with an expanded cohort and longer follow-up is warranted.

Conventional 3D conformal radiotherapy and volumetric modulated arc therapy for cervical cancer: Comparison of clinical results with special consideration of the influence of patient- and treatment-related parameters

PurposeIntensity-modulated radiotherapy (IMRT) for cervical cancer yields favorable results in terms of oncological outcomes, acute toxicity, and late toxicity. Limited data are available on clinical results with volumetric modulated arc therapy (VMAT). This study’s purpose is to compare outcome and toxicity with VMAT to conventional 3D conformal radiotherapy (3DCRT), giving special consideration to the influence of patient- and treatment-related parameters on side effects.Materials and methodsPatients with cervical cancer stage I–IVA underwent radiotherapy alone or chemoradiotherapy using 3DCRT (n = 75) or VMAT (n = 30). Survival endpoints were overall survival, progression-free survival, and locoregional control. The National Cancer Institute Common Terminology Criteria for Adverse Events and the Late Effects of Normal Tissues criteria were used for toxicity assessment. Toxicity and patient- and treatment-related parameters were included in a multivariable model.ResultsThere were no differences in survival rates between treatment groups. VMAT significantly reduced late small bowel toxicity (OR = 0.10, p = 0.03). Additionally, VMAT was associated with an increased risk of acute urinary toxicity (OR = 2.94, p = 0.01). A low body mass index (BMI; OR = 2.46, p = 0.03) and overall acute toxicity ≥grade 2 (OR = 4.17, p < 0.01) were associated with increased overall late toxicity.ConclusionWe demonstrated significant reduction of late small bowel toxicity with VMAT treatment, an improvement in long-term morbidity is conceivable. VMAT-treated patients experienced acute urinary toxicity more frequently. Further analysis of patient- and treatment-related parameters indicates that the close monitoring of patients with low BMI and of patients who experienced relevant acute toxicity during follow-up care could improve late toxicity profiles.

PO35: Is There Any Dosimetric Predictor of Urinary and Bowel Toxicity for Exclusive Adjuvant Vaginal Cuff Brachytherapy in Early Stage Endometrial Cancer?

Purpose: Adjuvant vaginal cuff brachytherapy (VBT) provides excellent local control in patients with early stage endometrial cancer (EC). VBT delivers a conformal dose to the vagina with less dose to surrounding normal tissues compared to external beam radiotherapy. Due to the low toxicity reported in EC patients treated with VBT alone, to our knowledge, there are no dose constraints to the organs at risk described in the literature. We purpose to evaluate toxicity of exclusive VBT in EC patients and to assess its relation with dosimetric parameters.

PRSOR10 Presentation Time: 12:45 PM: Effect of Short-Term Corticosteroid Usage on Acute Urinary Toxicity Following Cs-131 Prostate Brachytherapy

PRSOR10 Presentation Time: 12:45 PM: Effect of Short-Term Corticosteroid Usage on Acute Urinary Toxicity Following Cs-131 Prostate Brachytherapy

PRSOR10 Presentation Time: 12:45 PM: Effect of Short-Term Corticosteroid Usage on Acute Urinary Toxicity Following Cs-131 Prostate Brachytherapy

Purpose: To evaluate short-term patient reported urinary quality of life (QoL) scores in patients with prostate cancer treated at our institution with and without prednisone following Cesium-131 (131Cs) prostate LDR brachytherapy.