Late Urinary Toxicity Research Articles

Image-guided brachytherapy for pediatric bladder and/or prostate rhabdomyosarcoma: toward an increased personalization of treatment.: Brachytherapy in uro-pediatric rhabdomyosarcoma

IntroductionRhabdomyosarcoma (RMS) is the most common soft tissue cancer in children. Around 15% of RMS involve the bladder and/or prostate (BP). Overall survival is around 85%. After chemotherapy, patients receive local treatment based on surgery and/or radiotherapy. In recent decades, image guidance and pulsed dose-rate (PDR) brachytherapy have made it possible to personalize treatment, reduce radiation-related toxicity, while maintaining a good tumor control. We report one of the largest series of image-guided brachytherapy for pediatric RMS BP. Material and methodsThe clinical and dosimetric parameters of children treated with brachytherapy for BP RMS between July 2014 and September 2020 were retrospectively reviewed. Patients were treated with a multimodal conservative approach, combining partial conservative surgery (preservation of the bladder neck and urethra), followed by an interstitial brachytherapy procedure. Iridium-192 PDR treatment was administered on the basis of CT and MRI planning. Toxicities were reported according to version 4.0 of the Common Terminology Criteria for Adverse Events. ResultsA total of 75 patients were identified, with a median age of 29 months (range 2–84) at diagnosis. The median brachytherapy dose was 60.06 Gy (143 pulses, 0.42 Gy/pulse). With a median follow-up of 44.1 months (range 0.7–90), the 5-year OS and PFS rates were 97.3% and 92% respectively. Median D50% for the bladder and D1cc for the rectum were 38.6 Gy and 49 Gy respectively. The 5-year probability of survival without severe late urinary toxicity (grade 3 or higher) was estimated at 78.8% (CI95%: 68.1–91.1). A total of 9.3% of children experienced grade 2 or 3 late rectal toxicity. ConclusionsImage-guided PDR brachytherapy offers a personalized treatment for pediatric BP RMS, with a favorable therapeutic index. No prognostic factors for urinary toxicity have been identified. Multicenter studies with larger numbers of patients are needed to clarify these data.

Long-term Results of Hypofractionated Radiotherapy With Intra-prostatic Boosts in Men With Intermediate- and High-risk Prostate Cancer: A Phase II Trial

AimsIn the conventionally fractionated phase III FLAME prostate trial, focal boosts improved local control and biochemical disease-free survival (bDFS). We explored the toxicity and effectiveness of a moderately hypofractionated schedule with focal boosts. Material and methodsBIOPROP20 is a phase II single-arm non-randomised trial for intermediate- to very high-risk localised prostate cancer patients with bulky tumour volumes. Multi-parametric magnetic resonance imaging (MRI) and 18F-choline positron emission tomography-computed tomography (PET-CT) scans were used for staging and boost volume definition. Patients were treated with 60Gy in 20 fractions with a boost dose up to 68Gy. Five patients with positive lymph nodes on the PET-CT scan received radiotherapy to pelvic lymph nodes (45Gy to elective nodes, boosted up to 50Gy to involved nodes). Primary outcomes were acute (≤18 weeks) and late urinary and gastrointestinal toxicity, prospectively recorded up to 5 years with Common Terminology Criteria for Adverse Events v4 (CTCAE). Secondary outcomes were biochemical or clinical progression, metastasis-free survival (MFS), and overall survival (OS). Results61 patients completed radiotherapy with hormone therapy (range: 6–36 months). Cumulative acute and late gastrointestinal toxicity was low at 6.6% and 5.0%, respectively. Cumulative acute and late urinary toxicity was 49.2% and 30.1%, respectively; the prevalence reduced to 5.9% at 5 years. At 5 years: 6 patients had biochemical progression (bDFS: 88.5%; 95% CI: 80.2–97.6%), the MFS was 82.4% (95% CI: 73.0–92.9%), 5 patients died (OS: 91.2%; 95% CI: 84.1–98.9%), one with prostate cancer. The prostate, boost, nodal planning volumes, and the organs at risk (rectum, bowel, urethra, and bladder) met the optimal protocol dose constraints. There was a trend to increased urinary toxicity with increasing urethral (RR: 1.95, 95% CI: 0.73–5.22, p = 0.18), but not bladder dose. ConclusionFocal boosts with a 20 fraction hypofractionated prostate radiotherapy schedule are associated with an acceptable risk of gastrointestinal and urinary toxicity and achieve good cancer control. ClinicalTrials.gov identifierNCT02125175.

Reduction of Postradiation Therapy Urinary Toxicity Via Intrafractional Megavoltage-Kilovoltage Prostate Location Monitoring

We hypothesized that an in-house developed system using megavoltage and kilovoltage image guidance (MKIG) to ensure correct prostate positioning during stereotactic body radiation therapy (SBRT) could potentially avoid unwanted doses to nontarget tissues, leading to reduced toxicities. We built a 3-dimensional MKIG platform that accurately tracks prostate implanted fiducials in real time and clinically translated the system to replace a commercial approach, intrafraction motion review (IMR), which only tracks fiducials in the 2-dimensional kilovoltage views. From 2017 to 2019, 150 patients with prostate cancer were treated with SBRT and monitored using MKIG. The motion trace of the fiducials alerts therapists to interrupt and reposition the prostate when displacement exceeds a 1.5 mm threshold. A comparison cohort of 121 patients was treated with the same dose regimen and treatment technique but managed by IMR. Statistics of intrafractional patient shifts and delivery time were collected to evaluate the workflow efficacy. The incidence of grade ≥2 urinary toxicities was analyzed to assess clinical complications. The median follow-up time was 3.7 years (0.2-8.2 years). MKIG treatments had more treatment shifts (1.09 vs 0.28) and a longer average delivery time per fraction (579 ± 205 seconds vs 357 ± 117 seconds) than IMR treatments. Three-quarters (75%) of shifts resulting from MKIG were ≤3 mm, versus 51% in IMR, indicating that MKIG detected and corrected smaller deviations. The incidence of grade ≥2 urinary toxicity was lower in the MKIG than the IMR cohort: 10.7% versus 19.8% (P = .047). On multivariate analysis of late urinary toxicity, only high (>7) preradiation therapy international prostate symptom score (P < .043) and the use of MKIG were selected (P < .029). Automated and quantitative MKIG introduced minimal workflow impact and was superior to IMR in localizing the prostate during SBRT, which correlated with a clinically significant reduction in late urinary toxicity. Further clinical testing using randomized trials will be required to validate the impact on outcomes.

Late Urinary Toxicity After Extreme or Moderate Hypofractionated Prostate Radiation Therapy in Patients With Prior Transurethral Resection of Prostate

PurposeTo study the late urinary toxicity in patients with prostate cancer with prior transurethral resection of prostate (TURP) and treated with hypofractionated prostate radiotherapy. MethodsPatients diagnosed with prostate cancer, with a prior TURP, and treated with moderate or extreme hypofractionated intensity modulated radiotherapy (MHRT or SBRT), were included in this study. Severity and duration of urinary symptoms observed during serial follow up after at least three months from radiotherapy were graded per CTCAE v5.0 using information from prospectively maintained institutional database. Impact of hypofractionation and other potential contributory factors on cumulative grade 2+ late urinary toxicity was analysed with univariable and multivariable binary logistic regression. ResultsTotal 203 eligible patients were included (MHRT=114, 64-68Gy/25#; SBRT=89, 35-37.5Gy/5#). Median time from TURP to radiotherapy was 10 months (IQR 7-16), similar for MHRT and SBRT. Overall, mean cavity volume was 1.17cc (IQR 0.5-1.35), while in MHRT and SBRT groups was 1.03 cc (IQR 0.4-1.15) and 1.27 cc (IQR 0.5-1.4), respectively. At a median follow up of 37 months, cumulative grade 3 and grade 2 late urinary toxicity was 8.4% (n=17) and 23.2% (n=47) respectively. Grade 3 symptoms were observed at median 29 months (IQR 19-62) after radiotherapy completion, lasting for a median duration of 8 months (IQR 2-14). Hematuria (6.4%) and urinary obstruction (3.4%) were the chief grade 3 symptoms. Multivariable analysis for age, diabetes, pelvic radiotherapy, fraction size, prostate volume, TURP to radiotherapy duration, and TURP cavity volume showed no significant association with late grade 2+ urinary toxicity. Conclusion: In this large cohort of patients with prior TURP and treated with hypofractionated prostate radiotherapy, incidence of severe late urinary adverse effects was <10%, mainly hematuria or urinary obstruction. Most of these were temporary, and no significant contributory factors were identified for late urinary morbidity after TURP and radiotherapy.

Extreme hypofractionated stereotactic radiotherapy for localized prostate Cancer: Efficacy and late urinary toxicity according to transurethral resection of the prostate history

Background and purposeExtreme hypofractionated stereotactic body radiotherapy (SBRT) is a therapeutic alternative for localized low- or intermediate-risk prostate cancer. Despite the availability of several studies, the toxicity profile of SBRT has not been comprehensively described. This real-world evidence study assessed the efficacy and toxicities associated with this regimen, and potential prognosis factors for genitourinary toxicities. Materials and methodsThis retrospective study included 141 consecutive patients with localized prostatic adenocarcinoma treated with CyberKnife™ SBRT, as primary irradiation, at the Oscar Lambret Center between 2010 and 2020. The prescribed dose was 36.25 Gy in 5 fractions. Acute and late toxicities were graded according to the CTCAE (version 5.0). Biochemical recurrence-free survival (bRFS) and overall survival (OS) were estimated using the Kaplan–Meier method. The cumulative incidence of biochemical recurrence (cBR) was estimated using the Kalbfleisch–Prentice method. ResultsAmong the included patients, 13.5 % had a history of transurethral resection of the prostate (TURP). The median follow-up was 48 months. At 5 years, bRFS, cBR, and OS were 72 % (95 %CI: 61–81), 7 % (95 %CI: 3–14), and 82 % (95 %CI: 73–89), respectively. Twenty-nine patients experienced at least one late toxicity of grade ≥ 2; genitourinary (N = 29), including 3 cases of chronic hematuria, and/or gastrointestinal (N = 1). The cumulative incidence of late urinary toxicity of grade ≥ 2 was 20.6 % at 5 years (95 %CI: 13.9–28.1). Multivariate analysis revealed that a history of TURP was significantly associated with late urinary toxicity of grade ≥ 2, after adjusting for clinical target volume (Odds Ratio = 3.06; 95%CI: 1.05–8.86; P = 0.04). ConclusionExtreme hypofractionated SBRT is effective for localized prostate cancer with a low risk of late toxicity. A history of TURP is associated with a higher risk of late urinary toxicity. These findings may contribute to the optimal management of patients treated with this regimen, particularly those with a history of TURP.

High-Grade Late Urinary Toxicity Following Salvage Radiotherapy After Radical Prostatectomy: A Retrospective Cohort Study

Purpose: To find out the incidence and predictors for late high-grade genitourinary (GU) toxicity following salvage radiotherapy (SRT), we investigated the consecutive patients who were treated with SRT after radical prostatectomy.Materials and Methods: Patients who underwent SRT for biochemical recurrence after radical prostatectomy were reviewed. The incidence of GU toxicity was assessed and risk factors for grade ≥2 and ≥3 GU toxicity were evaluated. The STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) guided the reporting of this study.Results: Among the total of 217 patients, 88 patients (40.5%) showed late grade ≥2 GU toxicity. The incidence of late grade ≥3 GU toxicity was 11.5%. The presence of grade ≥2 baseline GU dysfunction (hazard ratio [HR], 6.097; 95% confidence interval [CI], 3.280–11.333; p&lt;0.001) and short interval (&lt;1 year) from surgery to SRT (HR, 1.994; 95% CI, 1.182–3.365; p=0.01) were associated with late grade ≥2 GU toxicity. A short interval from surgery to SRT was an independent predictor of late grade ≥3 GU toxicity (HR, 2.975; 95% CI, 1.135–7.794; p=0.027).Conclusions: The incidence of late high-grade GU toxicity was not uncommon after SRT. Thus, care should be taken when we consider SRT in patients with baseline urinary dysfunction and a short interval from surgery to SRT, to determine an optimal treatment strategy with balancing quality of life and oncologic outcome of patients.

Late Urinary Toxicity and Quality of Life With Pelvic Radiation Therapy for High-Risk Prostate Cancer: Dose-Effect Relations in the POP-RT Randomized Phase 3 Trial

PurposeThe POP-RT phase III randomized trial showed improved biochemical failure-free survival and metastasis-free survival with whole pelvic radiotherapy (WPRT) versus prostate-only radiotherapy (PORT) for high/very high-risk prostate cancer, albeit with worse RTOG late urinary toxicity. We report updated late urinary adverse effects and bladder dose-effect relations within this trial. Materials/MethodsLate urinary toxicity, and cumulative severity of each symptom over the follow-up period was graded using CTCAE v5.0. Bladder dosimetry in 5-Gy increments (V5, V10, V15...V65Gy, V68Gy) in the approved radiotherapy plans was compared for urinary symptoms and overall grade 2+ toxicity. Potential factors influencing urinary toxicity were tested using multivariable logistic regression analysis. Updated urinary quality of life (QOL) scores were compared between the trial arms. ResultsComplete combined data for late urinary symptoms and dosimetry was available for 193/224 patients. At a median follow-up of 75 months, cumulative late urinary CTCAE grade 3 toxicity was low and similar for WPRT and PORT (5.2% vs 4.1%, p=0.49), while grade 2 toxicity was 31.3% vs 22.7% respectively (p=0.12). Cumulative rates of each urinary symptom were similar between both arms. Multivariable analysis with age at diagnosis, known diabetes, tumor stage, trial arm, prior TURP, grade 2+ acute urinary toxicity, low bladder dose (V10Gy) and moderate bladder dose (V40Gy) did not identify any significant association with late urinary toxicity. Urinary QOL scores was similar between both the arms for all the symptoms. ConclusionOver long term follow up, whole pelvic radiotherapy resulted in low (∼5%) and similar grade 3 cumulative urinary toxicity as prostate-only radiotherapy. The long term patient-reported QOL scores were similar. No causative factors affecting the late urinary toxicity were identified.

KDM3B Single-Nucleotide Polymorphisms Impact Radiation Therapy Toxicity Through Circular RNA-Mediated KDM3B Expression and Inflammatory Responses

PurposeGenome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with radiotherapy (RT) toxicities in prostate cancer patients. SNP rs17599026 in intron 21 of KDM3B is significantly associated with the development of late urinary toxicity, specifically in the increase in urinary frequency two years after RT compared with pre-treatment conditions. The present study aimed to provide mechanistic insights for this association. Methods and MaterialsUsing human tissues and cell lines, we examined the protein expression of KDM3B and molecular mechanisms underlying the SNP modulation by variants of KDM3B SNP alleles. In animals with normal and heterozygous expressions of Kdm3b, we examined the relationship between Kdm3b expression and radiation toxicity. ResultsKDM3B rs17599026 lies in a motif important for circular RNA expression which is responsible for sponging miRNAs to regulate KDM3B expression. Using a murine model with heterozygous deletion of Kdm3b gene, we found that lower Kdm3b expression is associated with altered pattern of urination after bladder irradiation, which is related to differential degrees of tissue inflammation as measured by analyses of gene expression, lymphocyte infiltration, and non-invasive ultrasound imaging. ConclusionsKDM3B SNPs can impact its expression through regulating noncoding (nc) RNA expression. Differential KDM3B expression underlies radiation toxicity through tissue inflammation at the molecular and physiological level. Our study outcome offers a foundation for mechanism-based mitigation for radiation toxicity for prostate cancer survivors.

Stereotactic body radiotherapy with CyberKnife® System for low- and intermediate-risk prostate cancer: clinical outcomes and toxicities of CyPro Trial.

Stereotactic body radiotherapy (SBRT) of 35-36.25 Gy in five fractions with the CyberKnife System yields excellent control with low toxicity in low-intermediate-risk prostate cancer patients. We found no differences in biochemical control and overall survival in relation to dose. There were no significant differences in toxicity or quality of life between the two groups. Stereotactic body radiotherapy (SBRT) is an emerging therapeutic approach for low- and intermediate-risk prostate cancer. We present retrospective data on biochemical control, toxicity, and quality of life of CyPro Trial. A total of 122 patients with low- and intermediate-risk prostate cancer were treated with the CyberKnife System at a dose of 35 Gy or 36.25 Gy in five fractions. Biochemical failure (BF)/biochemical disease-free survival (bDFS) was defined using the Phoenix method (nadir + 2 ng/ml). Acute/late rectal and urinary toxicities were assessed by the Radiation Therapy Oncology Group (RTOG) toxicity scale. Quality of life (QoL) was assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C30 and PR25. International Erectile Function Index-5 (IIEF5) and International Prostate Symptom Score (IPSS) questionnaires were administered at baseline, every 3 months after treatment during the first years, and then at 24 months and 36 months. The 1-, 2-, and 5-year DFS rates were 92.9%, 92.9%, and 92.3%, respectively, while the 1-, 2-, and 5-year bDFS rates were 100%, 100%, and 95.7%, respectively. With regard to risk groups or doses, no statistically significant differences were found in terms of DFS or bDFS. Grade 2 urinary toxicity was acute in 10% and delayed in 2% of patients. No Grade 3 acute and late urinary toxicity was observed. Grade 2 rectal toxicity was acute in 8% and late in 1% of patients. No Grade 3-4 acute and late rectal toxicity was observed. Grade 2 acute toxicity appeared higher in the high-dose group (20% in the 36.25-Gy group versus 3% in the 35-Gy group) but was not statistically significant. Our study confirms that SBRT of 35-36.25 Gy in five fractions with the CyberKnife System produces excellent control with low toxicity in patients with low-intermediate-risk prostate cancer. We found no dose-related differences in biochemical control and overall survival. Further confirmation of these results is awaited through the prospective phase of this study, which is still ongoing.

Late Urinary Toxicity and QoL with Curative Radiotherapy for High-Risk Prostate Cancer: Dose-Effect Relations in the POP-RT Randomized Phase III Trial

Whole pelvic radiotherapy (WPRT) showed better biochemical failure-free survival and metastasis-free survival than prostate-only radiotherapy (PORT) in the phase III randomized POP-RT trial for high and very high-risk prostate cancer, albeit with higher RTOG grade 2 late urinary toxicity. We report updated long term, symptom-wise comparison and dose-effect relations from this trial. Late urinary toxicity, and cumulative severity of each symptom over the follow-up period was graded using CTCAE v5.0. Grade 2+ toxicities were compared between the trial arms by chi square test. Bladder dosimetry in 5-Gy increments (V5, V10, V15...V65 Gy, V68 Gy) from the trial database of approved radiotherapy plans, was compared for each urinary symptom and overall late gr2+ toxicity by student t-test. Observed differences in dosimetric parameters were tested using multivariable logistic regression analysis, including age at diagnosis, known diabetes, tumor stage, trial arm, and prior transurethral resection of prostate (TURP). Urinary QOL scores were compared between arms using generalised linear mixed model. Combined late symptom-wise toxicity and dose-volume data were available for analysis for 193/224 patients. At a median follow-up of 75 months, cumulative CTCAE gr2+ late urinary toxicity remained higher with WPRT than PORT, though not statistically significant (36.5% vs 26.8%, p = 0.15). Grade 3 toxicity was low and similar in both arms. Symptom-wise cumulative rates showed no significant difference between arms (Table 1). Dosimetric comparison showed significantly higher bladder V5-V15 in patients with gr2+ toxicity over those with <gr2 urinary toxicity. On symptom-wise analysis, V5-V40 range was significantly higher for presence of dysuria, hematuria, and urgency. No significant differences were observed over higher dose range for any urinary symptom. On multivariable analysis, no significant association was identifiable between bladder dosimetry and urinary symptoms. Urinary QOL scores was similar between both the arms for all the symptoms. Compared to prostate-only radiotherapy, whole pelvic radiotherapy resulted similar Grade 3 urinary toxicity of about 5% with about 10% higher cumulative grade 2+ urinary toxicity over long term follow up. This difference was not reflected in patient-reported QOL. WPRT particularly increased urgency and hematuria. Larger bladder volume being irradiated with 5Gy to 15Gy dose range could contribute to increase in urinary symptoms.

Reduction of Late Urinary Toxicity from Prostate Cancer Radiotherapy via Intrafractional MV-kV Image Guidance

Prostate cancer localization during radiotherapy is difficult and introduces positional variability during treatment. Here we evaluate the impact on treatment toxicities of an in-house system that uses MV and kV imaging guidance (MKIG) to track implanted fiducials during stereotactic body radiotherapy (SBRT) for localized prostate cancer. A 3D MKIG platform that tracks prostate implanted fiducials in real-time was built and clinically translated to replace a prior commercial approach called intrafraction motion review (IMR), which tracks thefiducials in 2D kV view only. MKIG has been shown to correct both superior-inferior and anterior-posterior (AP) motions that are harmful to critical organs and is superior to IMR for intrafractional motion management, which is less sensitive to AP motions. From 2017 to 2019, 150 patients with localized prostate cancer were treated with SBRT to 40 Gy in 5 fractions. During the delivery of volumetric modulated arc therapy, orthogonal MV-kV pairs were simultaneously acquired at every 20° gantry rotation and rigidly registered to the reference image templates created from the planning CT. Calculated 3D translations of implanted fiducials were used to localize the prostate and alert the therapist to interrupt and reposition the prostate when exceeding a 1.5-2 mm threshold. A comparison cohort of 121 prostate patients was treated from 2015 to 2016 with the same prescription dose and treatment technique but instead managed by IMR, where the therapist interrupted treatment based on a 2mm expansion of the fiducial contours superimposed on the kV images. Statistics of intrafractional interruptions, patient shifts, and overall delivery time were collected to evaluate the efficacy of the clinical workflow. The incidence of late grade ≥2 toxicities was analyzed to assess clinical complications. The median follow-up time was 5.5 years (range of 3.6 to 8.0 years). The MKIG cohort had more interruptions per fraction (1.09 vs. 0.28) and longer average delivery time per fraction (579±205s vs. 357±117s) than IMR. 75% of shifts resulting from MKIG were less than 3mm, compared to 51% in IMR, indicating that MKIG tended to detect and correct smaller deviations (p<0.001). The baseline International Prostate Symptom Score was 7.9 in the MKIG cohort vs. 8.4 in IMR (p = 0.41). The incidence of late grade ≥2 urinary toxicity was lower in the MKIG than IMR cohort: 10.7% vs. 19.8% (p = 0.05). One grade ≥2 rectal toxicity was observed in the IMR cohort but none in MKIG. Wehave demonstrated that MKIG is a clinically practical and effective method for monitoring and correcting prostate positional deviations during SBRT of prostate cancer. MKIG is better suited than 2D IMR to localize the prostate and trigger patient repositioning during treatment. A statistically and clinically significant reduction in urinary toxicity was observed. The potential expansion of MKIG to other clinical sites and translation to other centers should be considered.

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

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

Locoregional Treatment in Patients With Metastatic Cervical Cancer: Benefit of Dose Escalation Strategies

The objective of this work was to examine the benefit of an intensive locoregional treatment including an image guided adaptive brachytherapy (IGABT) among patients with cervical cancer and extrapelvic extension. Medical records of consecutive patients with a metastatic cervical cancer and receiving external beam radiation therapy and IGABT boost in Gustave Roussy Institute as part of their first line of treatment were examined. Depending on tumor sites, patients received pelvic ± para-aortic external beam radiation therapy. For those with visceral or supradiaphragmatic lymph node metastases, chemoradiation was delivered after usually 3 cycles of chemotherapy. All patients received a brachytherapy boost, guided by magnetic resonance imaging and aimed at increasing the dose to the high-risk clinical target volume (CTVHR). Local control (LC), patient overall survival (OS), progression-free survival, and radiation therapy-related side effects were examined, and prognostic factors were searched. One hundred sixty-four patients were included; 76.2% had para-aortic lymph node extension without distant metastasis (N2) and 23.8% had distant metastatic sites (M1). There was not a statistically significant difference in survival between both groups. With a median follow-up of 36 months, OS, progression-free survival, and LC at 3 years were 55.5% (95% CI, 48%-64%), 40.6% (95% CI, 38%-54%), and 90% (95% CI, 85%-96%), respectively. In multivariate analysis, a D90CTVHR dose ≥80 Gy was significant for better OS (hazard ratio, 0.96; 95% CI, 0.94-0.98; P < .001). Most toxicities were mild to moderate, with 2% grade 3 late urinary toxicity, 7% late grade 2 vaginal sequelae, and 1 grade 3 proctitis. During follow-up, rectovaginal fistula occurred in 2 patients without local relapse. IGABT permits dose escalation and high LC rates for patients with cervical cancer and extrapelvic extension. Dose/effect relationships for survival were shown. Because of high frequency of distant events, systemic intensification should be tested more specifically among these patients.

Associations of Clinical and Dosimetric Parameters with Urinary Toxicities after Prostate Brachytherapy: A Long-Term Single-Institution Experience.

To examine the association of clinical, treatment, and dose parameters with late urinary toxicity after low-dose-rate brachytherapy (LDR-BT) for prostate cancer, we retrospectively studied patients with prostate cancer who underwent LDR-BT from January 2007 through December 2016. Urinary toxicity was assessed using the International Prostate Symptom Score (IPSS) and Overactive Bladder (OAB) Symptom Score (OABSS). Severe and moderate lower urinary tract symptoms (LUTS) were defined as IPSS ≥ 20 and ≥ 8, respectively; OAB was defined as a nocturnal frequency of ≥ 2 and a total OABSS of ≥ 3. In total, 203 patients (median age: 66 years) were included, with a mean follow-up of 8.4 years after treatment. The IPSS and OABSS worsened after 3 months of treatment; these scores improved to pretreatment levels after 18-36 months in most patients. Patients with a higher baseline IPSS and OABSS had a higher frequency of moderate and severe LUTS and OAB at 24 and 60 months, respectively. LUTS and OAB at 24 and 60 months were not correlated with the dosimetric factors of LDR-BT. Although the rate of long-term urinary toxicities assessed using IPSS and OABSS was low, the baseline scores were related to long-term function. Refining patient selection may further reduce long-term urinary toxicity.

PO-1537 What factors may influence late urinary toxicities after radiation therapy of prostate cancers?

PO-1537 What factors may influence late urinary toxicities after radiation therapy of prostate cancers?

PD-0572 Late urinary toxicity with extreme and moderate hypofractionated prostate RT with prior TURP

PD-0572 Late urinary toxicity with extreme and moderate hypofractionated prostate RT with prior TURP

The Association between Acute and Late Genitourinary and Gastrointestinal Toxicities: An Analysis of the PACE B Study

Several studies have demonstrated the association between acute and late radiotherapy toxicity in prostate cancer using older radiotherapy techniques. However, whether this association is present with newer techniques such as stereotactic body radiotherapy (SBRT), remains unclear. We use univariable and multivariable logistic regression to analyse the association between grade 2 or worse acute gastrointestinal (GI) and genitourinary (GU) toxicities with equivalent late toxicities in patients treated with SBRT and conventional or moderately fractionated radiotherapy (CRT) within the PACE-B study. 842 patients were included in this analysis. Common Terminology Criteria for Adverse Events (CTCAE) was the primary clinician reported outcome measure used in this analysis. In univariable analysis, experiencing a grade 2+ acute GU toxicity was significantly associated with developing a grade 2+ late GU toxicity after SBRT (OR 4.63, 95% CI (2.96-7.25), p < 0.0001) and CRT (OR 2.83, 95% CI (1.69-4.71), p < 0.0001). This association remained significant in multivariable analysis. In univariable analysis, experiencing a grade 2+ acute GI toxicity was also associated with developing a grade 2+ late GI toxicity after SBRT (OR 3.67, 95% CI (1.91-7.03), p < 0.0001) and CRT (OR 4.4, 95% CI (2.04-9.47), p < 0.0001). This association also remained significant in multivariable analysis. Grade 2+ baseline GU symptoms were also associated with grade 2+ late urinary toxicity in both univariable and multivariable analysis. Overall, acute toxicity is an important predictor variable for late GU/GI toxicity after localised prostate radiotherapy using SBRT and CRT. Future work should test whether optimising symptoms pre-treatment and early intervention in those with significant acute toxicities could mitigate the development late of toxicity.

Validation of the bladder neck as an important organ at risk in prostate seed brachytherapy based on D2cc: A single-institution, retrospective review.

International guidelines recommend urethral dose volume constraints to minimize the risk of urinary toxicity after prostate brachytherapy. An association between dose to the bladder neck (BN) and toxicity has previously been reported, and we sought to evaluate the impact of this organ at risk on urinary toxicity, based on intra-operative contouring. Rates of acute and late urinary toxicity (AUT and LUT, respectively) were graded according to CTCAE version 5.0 for 209 consecutive patients who underwent low-dose-rate (LDR) brachytherapy monotherapy, with approximately equal numbers treated before and after we began routinely contouring the BN. AUT and LUT were compared in patients treated before and after we began contouring the OAR, and also for those treated after we began contouring who had a D2cc of greater than or less than 50% prescription dose. AUT and LUT fell after intra-operative BN contouring was instituted. Rates of grade ≥ 2 AUT fell from 15/101 (15%) to 9/104 (8.6%), p = 0.245. Grade ≥ 2 LUT decreased from 32/100 (32%) to 18/100 (18%), p = 0.034. Grade ≥ 2 AUT was observed in 4/63 (6.3%) and 5/34 (15%) of those with a BN D2cc >/≤ 50%, respectively, of prescription dose. Corresponding rates for LUT were 11/62 (18%) and 5/32 (16%). There were lower urinary toxicity rates for patients treated after we commenced routine intra-operative contouring of the BN. No clear relationship was observed between dosimetry and toxicity in our population.

Mechanisms, mitigation, and management of urinary toxicity from prostate radiotherapy.

Urinary toxicity is common following pelvic radiotherapy and can have a substantial negative effect on survivorship. Due to its prevalence and the increasing number of related clinical trials, localised prostate cancer radiotherapy is a useful illustrative tool to explore urinary toxicity. A good understanding of the interplay between anatomy, radiation-sensitive cell populations, and treatment sequencing is necessary for optimal outcomes. Emerging evidence suggests that the prostatic urethra is a radiation-sensitive structure, not only for stricture development, but also chronic irritative symptoms. Tools now exist not only to identify the urethra, but also to direct radiation dose away from the urethra, with early data suggesting that this reduces moderate-to-severe late urinary toxicity. Coupled with new evidence supporting dominant nodule microboosting and ultrahypofractionation as emerging standards of care, urethral sparing radiotherapy is a powerful tool against radiation induced urinary toxicity while also maximising disease control.

Acute and Late Toxicity of Prostate-Only or Pelvic SBRT in Prostate Cancer: A Comparative Study

<h3>Purpose/Objective(s)</h3> To compare the urinary and gastrointestinal toxicity with or without the inclusion of pelvic nodal regions in patients treated with extreme hypofractionated stereotactic radiotherapy (SBRT) for prostate cancer. <h3>Materials/Methods</h3> Patients treated with definitive SBRT for non-metastatic adenocarcinoma prostate were identified from a prospectively maintained institutional database and details of radiotherapy volume, dose, acute and late adverse effects were analyzed. Symptoms of acute (within 90 days of completing SBRT) and late gastrointestinal and urinary toxicities were graded using CTCAE version 5.0. Each symptom was scored according to the worst reported grading during treatment and follow-up period. ‘Non-infective cystitis' was considered as ‘urinary toxicity' because it encompasses all other urinary symptoms. Cumulative toxicity rates between prostate-only SBRT (PO-SBRT) and whole pelvic SBRT (WP-SBRT) were compared using chi-square test. <h3>Results</h3> Total 220 patients were analyzed (PO-SBRT=118, WP-SBRT=102), with most having locally advanced disease (PO-SBRT 60% high risk, 40% intermediate risk; WP-SBRT 79% node positive, 21% high risk). Median SBRT dose was 36.25Gy (IQR 35-36.25) to the prostate (EQD2=90.6Gy, a/b=1.5Gy) and simultaneous integrated 25Gy to the pelvis (EQD2=46.3Gy) in five fractions on alternate days. No grade 3-4 acute toxicities were observed except one grade 3 urinary obstruction (PO-SBRT). WP-SBRT was associated with significantly higher grade 2 acute GI toxicity (29.4% vs 14.7%, p=0.008), acute proctitis (23.5% vs 11.2%, p=0.016) and acute diarrhea (13.7% vs 1.7%, p=0.001). At a median follow-up of 28 months, grade 2 late urinary toxicity was significantly higher with WP-SBRT (45.6% vs 25.0%, p=0.003), while gastrointestinal toxicity was similar in both the groups (18.9% vs 13.4% p=0.1). Grade 3 late toxicities were low in both the groups (urinary 2.5%, gastrointestinal 1%). <h3>Conclusion</h3> WP-SBRT is associated with significant increase in acute GI and late urinary toxicities compared to PO-SBRT. Prospective validation of these findings is ongoing.