Severe Genitourinary Toxicity Research Articles

Urinary toxicity after salvage re-irradiation for prostate cancer local failure after definitive radiotherapy: a clinical and dosimetric prognostic factors analysis.

PurposePredictors of long-term toxicity after prostate cancer re-irradiation are scarce. In this study, we retrospectively assessed the impact of clinical/dosimetric data on late genitourinary (GU) toxicity on fourteen radio-recurrent prostate cancer patients treated with salvage radiotherapy (RT).Material and methodsTo identify dose parameters and clinical factors potentially associated to severe long-term GU toxicity, study population was stratified in two groups according to toxicity, including one low-grade group (grade ≤ 2, n = 6) and one high-grade group (grade ≥ 3, n = 8). Dose prescription at primary and salvage-RT in 2 Gy equivalent dose (EQD2Gy) per fraction, treatment techniques, and clinical factors potentially associated to severe GU toxicity were analyzed.ResultsAt salvage-RT, the median EQD2Gy α/β = 3 Gy was significantly higher in the high-toxicity group (85 Gy, range, 71-85 Gy) compared to the low-toxicity group (77 Gy, range, 61-85 Gy) (p = 0.01). All patients treated using salvage-RT with a brachytherapy (BT) boost and with a baseline Framingham risk-score of > 20% (n = 8) developed severe GU toxicity, while none of the remaining patients developed a grade 3 or more GU toxicity (p = 0.0003). V70 > 0 and V75 > 0 of the primary treatment were associated with an increased rate of toxicity.ConclusionsOur analysis shows that the delivery of doses up to 75-80 Gy (EQD2Gy, α/β = 3 Gy) in salvage-RT can be safe in terms of severe GU toxicity avoidance. Furthermore, concomitant cardiovascular comorbidities seem to increase the risk to develop severe GU toxicity.

Urinary Outcomes for Men With High Baseline International Prostate Symptom Scores Treated With Prostate SBRT

PurposeThere are limited data regarding high-dose stereotactic body radiation therapy (SBRT) for prostate cancer in patients with poor baseline urinary function. The purpose of this study was to evaluate genitourinary (GU) toxicity and changes in patient-reported symptom severity scores after prostate SBRT in men with a high pretreatment International Prostate Symptom Score (IPSS). Methods and MaterialsSeven hundred fifty-three patients treated with prostate SBRT at our institution from 2012 to 2019 were identified, of whom 72 consecutive patients with baseline IPSS ≥15 were selected for this study. GU toxicity according to Common Terminology Criteria for Adverse Events (CTCAE) v3.0 and IPSS were prospectively documented at each follow-up visit. Univariable logistic regression was used to evaluate for potential predictors of GU toxicity. ResultsMedian follow-up in survivors was 26.8 months. The rates of acute grade 2 and 3 GU toxicity were 20.8% and 1.4%, respectively. The rates of late grade 2 and 3 GU toxicity were 37.5% and 5.6%, respectively. The majority of grade 2+ toxicities resolved by last follow-up, and when toxicities were regraded per CTCAE v5.0, there were no longer any grade 3 adverse events. Total IPSS and individual symptom subscores improved over time. Compared with baseline, median total IPSS at 24 ± 6 months was significantly lower (18 vs 12; P < .001) and the proportion of patients with severe scores (IPSS ≥20) decreased from 29.2% to 13.9%. Pretreatment urinary urgency was associated with late grade 2+ GU toxicity (odds ratio, 2.10; 95% confidence interval, 1.33-3.31; P = .001). ConclusionsIn men with baseline IPSS ≥15 managed with prostate SBRT, the rate of severe GU toxicity was low and patient-reported symptoms generally improved over time. Thus, high pretreatment IPSS should not deter clinicians from offering prostate SBRT.

Intensity-modulated radiotherapy (IMRT) in the treatment of squamous cell anal canal cancer: acute and early-late toxicity, outcome, and efficacy.

To retrospectively review our experience on 84 patients with squamous cell anal canal cancer (SCAC) within 12months after combined treatment with intensity-modulated RT (IMRT), in terms of acute and early-late toxicity, overall treatment time and interruptions, colostomy-free survival (CFS), and tumor response. Acute gastrointestinal (GI), genitourinary (GU), and cutaneous (CU) toxicities were assessed according to Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03. Early-late toxicity was scored using the Radiation Therapy Oncology Group (RTOG) late radiation morbidity scoring system. Tumor response was evaluated with response evaluation criteria in solid tumors (RECIST) v1.1. Acute toxicity for 84 subjects (100%): severe (≥ G3) GI and skin toxicity was observed in 4 (5%) and 19 patients (23%), respectively. Early-late toxicity for 73 subjects (87%): severe (≥ G3) GI and vulvo-vaginal toxicity was observed in 2 (3%) and 2 (3%) patients, respectively. No acute or early-late severe GU toxicity was reported. A treatment interruption occurred in 65 patients (77%). CFS was 96% (95% CI 89-99) at 6months and 92% (95% CI 83-96) at 12months. At 6months complete response (CR), partial response (PR) and progressive disease (PD) was observed in 70 (83%), 3 (4%), and 7 patients (8%), respectively. At 12months, CR was observed in 60 patients (81%); eleven patients (15%) experienced PD. Our study showed an excellent clinical result and very low acute toxicity rates, confirming the IMRT as standard of care for curative treatment of anal cancer patients. The current trial was registered with the number IEO N87/11.

Urethral and bladder dosimetry of total and focal salvage Iodine-125 prostate brachytherapy: Late toxicity and dose constraints

IntroductionSalvage Iodine-125 brachytherapy (I-125-BT) constitutes a curative treatment approach for patients with organ-confined recurrent prostate cancer after primary radiotherapy. Currently, focal salvage (FS) instead of whole-gland or total salvage (TS) is being investigated, to reduce severe toxicity associated with cumulative radiation dose. Differences in urethral and bladder dosimetry and constraints to reduce late (>90days) genitourinary (GU) toxicity are presented here. Materials and methodsDosimetry on intraoperative ultrasound (US) of 20 FS and 28 TS patients was compared. The prostate, bladder, urethra and bulbomembranous (BM) urethra were delineated. Toxicity was assessed using the CTCAE version 4.0. Dose constraints to reduce toxicity in TS patients were evaluated with receiver operating characteristic (ROC) analysis. ResultsFS I-125 BT significantly reduces bladder and urethral dose compared to TS. Grade 3 GU toxicity occurred once in the FS group. For TS patients late severe (⩾grade 3) GU toxicity was frequent (38% in the total 61 patients and 56% in the 27 analyzed patients). TS patients with ⩾grade 3 GU toxicity showed higher bladder D2cc than TS patients without toxicity (median 43Gy) (p=0.02). The urethral V100 was significantly higher in TS patients with several toxicity profiles: ⩾grade 3 urethral strictures, ⩾grade 2 urinary retention and multiple ⩾grade 2 GU toxicity events. Dose to the BM urethra did not show a relation with stricture formation. ROC-analysis indicated a bladder D2cc <70Gy to prevent ⩾grade 3 GU toxicity (AUC 0.76, 95%CI: 0.56–0.96, p=0.02). A urethral V100 <0.40cc (AUC from 0.73–0.91, p=0.003–0.05) could prevent other late GU toxicity. ConclusionFS I-125 BT reduces urethral and bladder dose significantly compared to TS. With TS, there is an increased risk of cumulative dose and severe GU toxicity. Based on these findings, bladder D2cc should be below 70Gy and urethral V100 below 0.40cc.

Comparison of clinical outcomes and toxicity in endometrial cancer patients treated with adjuvant intensity-modulated radiation therapy or conventional radiotherapy

To evaluate the treatment outcomes and toxicity in endometrial cancer patients treated with hysterectomy and adjuvant intensity-modulated radiation therapy (IMRT) or conventional radiotherapy (CRT). There were 101 patients with stage IA-IIIC2 endometrial carcinoma treated with hysterectomy and adjuvant radiotherapy. In total, 36 patients received adjuvant CRT and 65 were treated with adjuvant IMRT. The endpoints were overall survival, local failure-free survival, and disease-free survival. Patients were assessed for acute toxicity weekly according to the Common Terminology Criteria for Adverse Events version 3.0. Late toxicity was evaluated according to the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Schema. The 5-year overall survival, local failure-free survival, and disease-free survival for the CRT group and the IMRT group were 82.9% versus 93.5% (p = 0.26), 93.7% versus 89.3% (p = 0.68), and 88.0% versus 82.8% (p = 0.83), respectively. Four (11.1%) patients had Grade 3 or greater acute gastrointestinal (GI) toxicity and three (8.3%) patients had Grade 3 or greater acute genitourinary (GU) toxicity in the CRT group, whereas four (6.2%) patients had Grade 3 or greater acute GI toxicity in the IMRT group and no patient had severe GU toxicity. There was one (2.8%) patient who had Grade 3 or greater late GI toxicity and one (2.8%) patient had Grade 3 or greater late GU toxicity in the CRT group, whereas no patient had severe GI or GU toxicity in the IMRT group. Adjuvant IMRT for endometrial cancer patients had comparable clinical outcomes with CRT and had less acute and late toxicity.

A 2-Stage Genome-Wide Association Study to Identify Single Nucleotide Polymorphisms Associated with Development of Urinary Symptoms After Radiotherapy for Prostate Cancer

We identified single nucleotide polymorphisms associated with change in the AUA Symptom Score after radiotherapy for prostate cancer. A total of 723 patients treated with brachytherapy with or without external beam radiation therapy were assessed at baseline and annually after radiotherapy using the AUA Symptom Score. A 2-stage genome-wide association study was performed with the primary end point of change in AUA Symptom Score from baseline at each of 4 followup periods. Single nucleotide polymorphism associations were assessed using multivariable linear regression adjusting for pre-radiotherapy AUA Symptom Score severity category and clinical variables. Fisher's trend method was used to calculate combined p values from the discovery and replication cohorts. A region on chromosome 9p21.2 containing 8 single nucleotide polymorphisms showed the strongest association with change in AUA Symptom Score (combined p values 8.8×10(-6) to 6.5×10(-7) at 2 to 3 years after radiotherapy). These single nucleotide polymorphisms form a haplotype block that encompasses the inflammation signaling gene IFNK. These single nucleotide polymorphisms were independently associated with change in AUA Symptom Score after adjusting for clinical predictors including smoking history, hypertension, α-blocker use and pre-radiotherapy AUA Symptom Score. An additional 24 single nucleotide polymorphisms showed moderate significance for association with change in AUA Symptom Score. Several of these single nucleotide polymorphisms were more strongly associated with change in specific AUA Symptom Score items, including rs13035033 in the MYO3B gene, which was associated with straining (beta coefficient 0.9, 95% CI 0.6-1.2, p = 5.0×10(-9)). If validated, these single nucleotide polymorphisms could provide insight into the biology underlying urinary symptoms following radiotherapy and could lead to development of an assay to identify patients at risk for experiencing these effects.

Severe Genitourinary Toxicity Following Radiation Therapy for Prostate Cancer—How Long Does it Last?

Radiation therapy is a common treatment for localized prostate cancer but long-term data are sparse on treatment related toxicity compared to observation. We evaluated the time course of grade 2-4 genitourinary toxicities in men treated with primary radiation or observation for T1-T2 prostate cancer. We performed a population based cohort study using Medicare claims data linked to SEER (Surveillance, Epidemiology and End Results) data. Cumulative incidence functions for time to first genitourinary event were calculated based on the competing risks model with death before any genitourinary event as a competing event. The generalized estimating equation method was used to evaluate the risk ratios of recurrent events. Of the study patients 60,134 received radiation therapy and 25,904 underwent observation. The adjusted risk ratio for genitourinary toxicity was 2.49 (95% CI 2.00-3.11) for 10 years and thereafter. Patients who had required prior procedures for obstruction/stricture, including transurethral prostate resection, before radiation therapy were at significantly increased risk for genitourinary toxicity (risk ratio 2.78, 95% CI 2.56-2.94). This study demonstrates that the increased risk of grade 2-4 genitourinary toxicities attributable to radiation therapy persists 10 years after treatment and thereafter. Patients who required prior procedures for obstruction/stricture were at higher risk for genitourinary toxicity than those without these preexisting conditions.

External Beam Radiation Therapy After Transurethral Resection of the Prostate: A Report on Acute and Late Genitourinary Toxicity

To describe genitourinary (GU) toxicity in men with a history of transurethral resection of the prostate (TURP) treated with external beam radiation therapy (EBRT) for prostate cancer. Seventy-one men with a history of TURP were treated with EBRT for prostate cancer. The median time from TURP to EBRT was 15 months. The median EBRT dose was 70 Gy, and 21 men (30%) received androgen deprivation therapy (ADT). Acute GU toxicity and late GU toxicity were scored by Radiation Therapy Oncology Group criteria and compared with a cohort of 538 men without prior TURP. The median follow-up for men with TURP and men without TURP was 40 months and 50 months, respectively (p = 0.7605). The rate of acute Grade 2 GU toxicity or higher was 41%, and was increased with a history of more than 1 TURP (73% vs. 31%, p = 0.0036). The 4-year rate of freedom from late Grade 3 GU toxicity or higher was 84%, and was decreased with ADT (45% vs. 95% without ADT, p = 0.0024). By last follow-up, maximal GU toxicity tended to resolve (p < 0.0001) and there was no worsening of urinary symptom scores (p = 0.6911). Compared to men without a prior TURP, TURP patients had a lower rate of freedom from late Grade 3 toxicity or higher (84% vs. 96%, p = 0.0483). Multivariate analysis suggested a higher rate of late Grade 3 toxicity or higher with TURP (risk ratio, 2.87; p = 0.0612) and EBRT dose of 74 Gy or greater (risk ratio, 2.26; p = 0.0521). Men treated for prostate cancer with EBRT after TURP have a higher risk of severe GU toxicity; however, the overall incidence is low, and toxicity tends not to persist.

A Preliminary Results of a Randomized Trial Comparing Monthly 5-flourouracil and Cisplatin to W eekly Cisplatin A lone Combined with Concurrent Radiotherapy for Locally Advanced Cervical Cancer

To determine the superior chemotherapeutic regimen between monthly 5-FU plus cisplatin (FP) and weekly cisplatin alone in concurrent chemoradiotherapy for locally advanced cervical cancer, the compliance of treatment, response, survival and toxicities were analyzed between the two arms. Between March 1998 and December 2001, 61 patients with locally advanced cervical cancer (stage IIB through IVA) and negative para-aortic lymph nodes were randomly assigned to either 'monthly FP' (arm I, n=34) or 'weekly cisplatin' (arm II, n=27) with concurrent radiotherapy. The patients of arm I received FP (5-FU 1,000 mg/m(2)/day + cisplatin 20 mg/m(2)/day, for 5 days, for 3 cycles at 4 week intervals) and those of arm II received cisplatin (30 mg/m(2)/day, for 6 cycles at 1 week intervals) with concurrent radiotherapy. The radiotherapy consisted of 41.4 approximately 50.4 Gy external beam irradiation in 23 approximately 28 fractions to the whole pelvis, with high dose rate brachytherapy delivering a dose of 30 approximately 35 Gy in 6 approximately 7 fractions to point A. During the brachytherapy, a parametrial boost was delivered. The median follow-up period for survivors was 44 months. The compliance of treatment in monthly FP weekly cisplatin arms were 62 and 81%, respectively. The complete response rates at 3 months were 96 and 88% in arms I and II, respectively. The 4-year overall survival and disease free survival rates were 64 and 54% in the arm I and 77 and 66% in the arm II, respectively. The incidence of hematologic toxicity more than grade 2 was 29% in the arm I and 15% in the arm II. Only one patient in arm I experienced grade 3 gastrointestinal toxicity. No severe genitourinary toxicity was observed. No significant difference was observed in the compliance, responses, survival rates and acute toxicities between the two treatment arms. More patients and further follow up will be required.

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

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