Acute Genitourinary Research Articles

High-dose-rate brachytherapy boost for prostate cancer treatment: Different combinations of hypofractionated regimens and clinical outcomes

PurposeTo report the outcomes of our high-dose-rate brachytherapy (HDR-BT) boost experience in localized prostate cancer treated with different combinations of radiation doses and fractionation. Material and methodsBetween 1999 and 2011, 832 patients were treated with different regimens of external beam radiotherapy (EBRT) and HDR-BT. These regimens were converted into three biologically effective dose (BED) groups. The biochemical failure-free survival (BFFS), reported with the phoenix definition and prostate-specific antigen (PSA) >0.2ng/ml at 5-year, genitourinary (GU) and gastrointestinal (GI) toxicities were compared between the groups. ResultsThe 5-, 10-year BFFS for the entire cohort were 94.6% and 92.5%, for overall survival (OS) 96.1% and 80.3% and for prostate cancer-specific survival (PCSS) 99.5% and 97.8%. The percentage of patients with a 5-year PSA level <0.2ng/ml was 68.6%, 78.7% and 86.7% in the BED group of <250, 250–260 and >260Gy (p=0.005) while the 5-year BFFS rates according to phoenix definition were 97.3%, 94.3% and 94.9% for BED group <250, 250–260 and >260Gy (p=0.453). On multivariate logistic regression, patients in the BED>260Gy group were significantly more likely to remain free from 5-year PSA values ≥0.2ng/mL compared with those in the BED<250Gy group (OR: 0.350, p=0.011). Grade≥3 acute GU toxicity was reported in 2 patients (4.7%) for BED>260Gy while grade≥3 late GU toxicity was reported in 6 (1.7%) and 9 (4.9%) patients for 250–260Gy and >260Gy BED groups. ConclusionsThe increase in BED with the hypofractionated regimens correlates with an improvement in biochemical control with of urinary toxicity. This increase in urinary toxicity is small and clinically acceptable.

Correlating Acute and Chronic Genitourinary Toxicity and Dose-Volume Parameters in Ultrasound-Based Planning for High-Dose Rate Prostate Brachytherapy

Correlating Acute and Chronic Genitourinary Toxicity and Dose-Volume Parameters in Ultrasound-Based Planning for High-Dose Rate Prostate Brachytherapy

PD72-10 ASSESSING THE RISK OF EARLY AND LATE TOXICITY OF POST-PROSTATECTOMY RADIATION THERAPY: A LONG-TERM MULTI-INSTITUTIONAL ANALYSIS

PD72-10 ASSESSING THE RISK OF EARLY AND LATE TOXICITY OF POST-PROSTATECTOMY RADIATION THERAPY: A LONG-TERM MULTI-INSTITUTIONAL ANALYSIS

Moderate Hypofractionated Postprostatectomy Volumetric Modulated Arc Therapy With Daily Image Guidance (VMAT-IGRT): AMono-institutional Report on Feasibility and Acute Toxicity.

The aim of this study was to evaluate the acute toxicity profiles of a moderate hypofractionated regimen with volumetric modulated arc therapy (VMAT) in patients with prostate cancer (PC) who underwent radical prostatectomy. From December 2012 to February 2016, 125 patients, previously having undergone radical prostatectomy, received adjuvant (64 patients) or salvage (61 patients) radiotherapy (RT) inside an institutional protocol of moderate hypofractionation schedule using the VMAT technique (Varian RapidArc, Palo Alto, CA). Eligible patients were< 85 years old, with an Eastern Cooperative Oncology Group performance status of 0 to 2, histologically proven adenocarcinoma of the prostate without distant metastases, and pathologic stage pT2-4 N0-1, with at least 1 of the following risk factors: capsular perforation, positive surgical margins, seminal vesicle invasion, and/or postoperative prostate-specific antigen > 0.2 ng/mL. Patients were stratified into low (1%), intermediate (9%), and high-risk (90%) groups. The median age was 68 years. The median doses were 66 Gy (range, 65.5-71.4 Gy) to the prostatic bed and 52.5 Gy (range, 50.4-54 Gy) to the pelvic lymph nodes, in 28 or 30 fractions. The acute genitourinary (GU) and gastrointestinal (GI) toxicities were scored according to the Common Terminology Criteria for Adverse Events, v4. All 125 patients completed the planned treatment, with good tolerance. After RT, the median follow-up was 18 months. Acute toxicities were recorded for the GU (G0, 45/125 [36%]; G1, 63/125 [50.4%]; G2, 16/125 [12.8%]; G3, 1/125 [0.8%]) and the GI (G0, 42/125 [33.6%]; G1, 72/125 [57.6%]; G2, 11/125 [8.8%]; no G3). Analyzing data according to RT intent, a higher rate of GU toxicity≥ 2 was found in the adjuvant setting (17.1%) with respect to the salvage group (9.8%); P= .01 with the Fisher exact text. Furthermore, at statistical analysis, no difference was found between the type of surgery (robotic, laparoscopic, or open) and incidence of urinary incontinence (P= .8). The actuarial Kaplan-Meier rates for biochemical disease-free survival were 94% and 77% for adjuvant and salvage RT, at 36 months. Moderate hypofractionated postoperative RT with VMAT was feasible and safe with acceptable acute GU and GI toxicities. Longer follow-up is needed to assess late toxicity and clinical outcomes.

ASCENDE-RT: An Analysis of Treatment-Related Morbidity for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost with a Dose-Escalated External Beam Boost for High- and Intermediate-Risk Prostate Cancer

Toreport the genitourinary (GU) and gastrointestinal (GI) morbidity and erectile dysfunction in a randomized trial comparing 2 methods of dose escalation for high- and intermediate-risk prostate cancer. ASCENDE-RT (Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy) enrolled 398 men, median age 68years, who were then randomized to either a standard arm that included 12months of androgen deprivation therapy and pelvic irradiation to 46Gy followed by a dose-escalated external beam radiation therapy (DE-EBRT) boost to 78Gy, or an experimental arm that substituted a low-dose-rate prostate brachytherapy (LDR-PB) boost. At clinic visits, investigators recorded GU and GI morbidity and information on urinary continence, catheter use, and erectile function. Exclusion of 15 who received nonprotocol treatment and correction of 14 crossover events left 195 men who actually received a DE-EBRT boost and 188, an LDR-PB boost. Median follow-up was 6.5years. The LDR-PB boost increased the risk of needing temporary catheterization and/or requiring incontinence pads. At 5years the cumulative incidence of grade 3 GU events was 18.4% for LDR-PB, versus 5.2% for DE-EBRT (P<.001). Compared with the cumulative incidence, the 5-year prevalence of grade 3 GU morbidity was substantially lower for both arms (8.6% vs 2.2%, P=.058). The 5-year cumulative incidence of grade 3 GI events was 8.1% for LDR-PB, versus 3.2% for DE-EBRT (P=.124). The 5-year prevalence of grade 3 GI toxicity was lower than the cumulative incidence for both arms (1.0% vs 2.2%, respectively). Among men reporting adequate baseline erections, 45% of LDR-PB patients reported similar erectile function at 5years, versus 37% after DE-EBRT (P=.30). The incidence of acute and late GU morbidity was higher after LDR-PB boost, and there was a nonsignificant trend for worse GI morbidity. No differences in the frequency of erectile dysfunction were observed.

Impact of vaginal cylinder diameter on outcomes following brachytherapy for early stage endometrial cancer.

ObjectiveTo examine the outcomes (tolerability, toxicity, and recurrence) of vaginal brachytherapy (VBT) among endometrial cancer (EC) patients treated with small cylinder size.MethodsPatients with EC who received adjuvant VBT between September 2011 and December 2015 were reviewed. Patients were fitted with the largest vaginal cylinder they could comfortably accommodate, from 2.0–3.0 cm diameter. Small cylinders were defined as size 2.3 cm or less. Patient, tumor, or treatment characteristics were correlated with need for small cylinders. Treatment tolerability, measures of gastrointestinal (GI), genitourinary (GU), and vaginal toxicity, and rates of recurrence were analyzed.ResultsThree hundred four patients were included. Small cylinders were used in 51 patients (17%). Normal body mass index (BMI; p<0.001), nulligravidity (p<0.001), and shorter vaginal length (p<0.001) were associated with small cylinder size. There was no acute or late grade 3 toxicity. Rates of acute (grade 1–2) GI, GU, or vaginal symptoms were low (10%, 11%, and 19%, respectively). Small cylinder size was associated with increased likelihood of reporting acute GI (p<0.05) but not GU or vaginal symptoms. Small cylinder size was associated with higher risk of grade 1–2 vaginal stenosis (odds ratio [OR]=4.7; 95% confidence interval [CI]=1.5–14.7; p=0.007). There was no association between cylinder size and recurrence rate (p=0.55).ConclusionVBT is generally very well tolerated, however, patients fitted with smaller cylinders (commonly nulligravid and low BMI) may have increased side effects. Further study to improve the dosimetry of VBT for patients requiring small cylinders may be worthwhile.

Fractionated high-dose-rate brachytherapy as monotherapy in prostate cancer: Does implant displacement and its correction influence acute and late toxicity?

PurposeIn fractionated high-dose-rate brachytherapy (HDR-BT) for prostate cancer (PCa) with one implant for several fractions, dose delivery relies on reproducibility of catheter positions. However, caudal displacement of implanted catheters does occur between fractions and needs to be corrected. Our protocol prescribes correction of displacements > 3 mm. We investigated whether displacement and its corrections influence acute and late toxicity incidences. Methods and MaterialsWe analyzed 162 PCa patients treated with HDR-BT monotherapy between 2007 and 2013. The implant remained in situ between the 4 fractions. Catheter displacement was assessed before each fraction using lateral X-ray images and corrected if needed. Genitourinary (GU) and gastrointestinal (GI) acute and late toxicities were assessed using clinical record forms and patient self-assessment questionnaires. ResultsImplant displacement corrections (DC) were needed in 71 patients (43.8%) whereas no DCs were needed in 91 patients (56.2%). No statistically significant differences were seen in acute and late grade ≥ 2 GU and GI toxicity incidences between DC and no DC groups. The maximum displacement nor the number of corrections had any influence on toxicity. ConclusionsThe occurrence and subsequent correction of implant displacements exceeding 3 mm during fractionated HDR-BT monotherapy for PCa did not lead to increased incidences of acute or late GU and GI toxicity. This indicates that our clinical protocol to correct displacements > 3 mm results in safe treatment regarding organ at risk toxicity.

Hypofractionated intensity-modulated radiotherapy in patients with localized prostate cancer: a preliminary study.

PurposeThe aim of this work was to assess the efficacy and tolerability of hypofractionated intensity-modulated radiotherapy (IMRT) in patients with localized prostate cancer.Materials and MethodsThirty-nine patients who received radical hypofractionated IMRT were retrospectively reviewed. Based on a pelvic lymph node involvement risk of 15% as the cutoff value, we decided whether to deliver treatment prostate and seminal vesicle only radiotherapy (PORT) or whole pelvis radiotherapy (WPRT). Sixteen patients (41%) received PORT with prostate receiving 45 Gy in 4.5 Gy per fraction in 2 weeks and the other 23 patients (59%) received WPRT with the prostate receiving 72 Gy in 2.4 Gy per fraction in 6 weeks. The median equivalent dose in 2 Gy fractions to the prostate was 79.9 Gy based on the assumption that the α/β ratio is 1.5 Gy.ResultsThe median follow-up time was 38 months (range, 4 to 101 months). The 3-year biochemical failure-free survival rate was 88.2%. The 3-year clinical failure-free and overall survival rates were 94.5% and 96.3%, respectively. The rates of grade 2 acute genitourinary (GU) and gastrointestinal (GI) toxicities were 20.5% and 12.8%, respectively. None of the patients experienced grade ≥3 acute GU and GI toxicities. The grade 2-3 late GU and GI toxicities were found in 8.1% and 5.4% of patients, respectively. No fatal late toxicity was observed.ConclusionFavorable biochemical control with low rates of toxicity was observed after hypofractionated IMRT, suggesting that our radiotherapy schedule can be an effective treatment option in the treatment of localized prostate cancer.

Reducing radiation-associated toxicity using online image guidance (IGRT) in prostate cancer patients undergoing dose-escalated radiation therapy

AimTo determine the influence of IGRT in terms of toxicities compared to non-IGRT patients undergoing definitive RT. BackgroundImage-guided radiotherapy (IGRT) enables immediate correction of target movement by online imaging. For prostate cancer patients undergoing radiation therapy (RT), a geographical miss of the prostate may result in increased dose–volume effects in the rectum and bladder. MethodsA total of 198 prostate cancer patients treated between 2003 and 2013 were recruited randomly for this evaluation. The rates of genitourinary (GU) and gastrointestinal (GI) toxicity for 96 non-IGRT patients (total dose: 72/73.8Gy) were compared to those for 102 IGRT patients (total dose: 77.4Gy) according to the Common Toxicity Criteria Version 3.0 (CTCAEv3.0). Follow-up information included treatment-related symptoms and PSA relapse. ResultsAfter a median follow-up of 55.4 months, a statistically significant difference was noted for acute GI toxicities ≥1 in favour of IGRT. Significantly more patients treated by IGRT were free of acute GI symptoms (43% vs. 19%, p=0.0012). In the non-IGRT group, more patients experienced acute GU side effects (89% vs. 80%, p=0.07). Late toxicity scores were comparable for both cohorts. ConclusionsBased on the data, we demonstrated that despite dose escalation, IGRT enabled us to reduce the GI side effects of radiation. IGRT can therefore be considered to be the standard of care for dose-escalated RT of localized prostate cancer.

Dose-Escalated Stereotactic Body Radiation Therapy for Patients With Intermediate- and High-Risk Prostate Cancer: Initial Dosimetry Analysis and Patient Outcomes

To report the short-term clinical outcomes and acute and late treatment-related genitourinary (GU) and gastrointestinal (GI) toxicities in patients with intermediate- and high-risk prostate cancer treated with dose-escalated stereotactic body radiation therapy (SBRT). Between 2011 and 2014, 24 patients with prostate cancer were treated with SBRT to the prostate gland and proximal seminal vesicles. A high-dose avoidance zone (HDAZ) was created by a 3-mm expansion around the rectum, urethra, and bladder. Patients were treated to a minimum dose of 36.25Gy in 5 fractions, with a simultaneous dose escalation to a dose of 50Gy to the target volume away from the HDAZ. Acute and late GU and GI toxicity outcomes were measured according to the National Cancer Institute Common Terminology Criteria for Adverse Events toxicity scale, version4. The median follow-up was 25months (range, 18-45months). Nine patients (38%) experienced an acute grade 2 GU toxicity, which was medically managed, and no patients experienced an acute grade 2 GI toxicity. Two patients (8%) experienced late grade 2 GU toxicity, and 2 patients (8%) experienced late grade 2 GI toxicity. No acute or late grade ≥3 GU or GI toxicities were observed. The 24-month prostate-specific antigen relapse-free survival outcome for all patients was 95.8% (95% confidence interval 75.6%-99.4%), and both biochemical failures occurred in patients with high-risk disease. All patients are currently alive at the time of this analysis and continue to be followed. A heterogeneous prostate SBRT planning technique with differential treatment volumes (low dose: 36.25Gy; and high dose: 50Gy) with an HDAZ provides a safe method of dose escalation. Favorable rates of biochemical control and acceptably low rates of acute and long-term GU and GI toxicity can be achieved in patients with intermediate- and high-risk prostate cancer treated with SBRT.

Prediction of toxicities of prostate cancer radiotherapy.

We treated acohort of 116 patients with prostate cancer with three-dimensional conformal hypofractionated radiotherapy to atotal dose of 52.8 Gy in 16 fractions (3.3 Gy per fraction). The correlation between acute and late gastrointestinal (GI) and genitourinary (GU) toxicity and dose-volume parameters was analysed. Comparison of observed incidence of toxicity and normal tissue complication probability calculated from dose-volume histograms (DVH) of all patients using radiobiological Lyman-Kutcher-Burman model was performed. The results of our study suggest that acute gastrointestinal toxicity ≥ grade 2 (G2) is the significant predictor of late toxicity ≥ G2 (p=0.006). Observed incidence of acute and late GI toxicities ≥ G2 was 9.7% and 11.5%, respectively. NTCPs of acute and late GI complications ≥ G2 were 11.3% and 2.5%. Observed incidence of late GU toxicity ≥ G2 was 14.2%, NTCP was 0.8%. Comparison of calculated probability of acute GI toxicity ≥ G2 and observed incidence indicates that parameters of radiobiological models are set appropriately. Comparison of observed incidence of late GI and GU complications ≥ G2 and calculated NTCPs shows the need of refinement of LKB model parameters for acute and late GI and GU complications ≥ G2. prostate cancer, radiotherapy, acute and late toxicity, radiobiological modeling.

Predicting genitourinary toxicity in three-dimensional conformal radiotherapy for localized prostate cancer: A dose-volume parameters analysis of the bladder.

In prostate cancer radiotherapy, the relationship between genitourinary (GU) toxicity and clinical-dosimetric parameters is debated. We report our analysis of the parameters associated with GU toxicity. Eighty-six consecutive patients treated with conformal radiotherapy for localized prostate cancer were retrospectively analyzed; the bladder was delineated both as "whole bladder" (WB: Defined in its entirety as a solid organ) and "inferior bladder" (IB: Corresponding to the distal part of the bladder). GU toxicity and dose-volume parameters were correlated using the point biserial correlation coefficient. The normal tissue complication probability (NTCP) cut-off volume model was fitted to toxicity data; univariate analysis between GU toxicity and clinical parameters was done. Acute GU toxicity was correlated to doses higher than 80 Gy (P < 0.05) while late GU was correlated to doses higher than 77 Gy for WB and from 77.5 Gy for IB. The NTCP cut-off volume model identified for both WB and IB a bladder volume of 6 cc receiving a dose ≥77 Gy corresponding to a 50% probability of GU toxicity. At univariate analysis, acute GU toxicity was correlated with smoke (P < 0.001). Bladder maximal doses quantified as hotspots show a correlation to GU toxicity.

Stereotactic Body Radiotherapy for Clinically Localized Prostate Cancer: Toxicity and Biochemical Disease-Free Outcomes from a Multi-Institutional Patient Registry.

Objectives: To report on initial patient characteristics, treatment practices, toxicity, and early biochemical disease-free survival (bDFS) of localized prostate cancer treated with stereotactic body radiotherapy (SBRT) and enrolled in the RSSearch® Patient Registry.Methods: A retrospective analysis was conducted on patients with clinically localized prostate cancer enrolled in RSSearch® from June 2006 - January 2015. Patients were classified as low-risk (PSA ≤ 10 ng/ml, T1c-T2a, Gleason score ≤ 6), intermediate-risk (PSA 10.1 - 20 ng/ml, T2b-T2c, or Gleason 7), or high-risk (PSA > 20 ng/ml, T3 or Gleason ≥ 8). Toxicity was reported using Common Toxicity Criteria for Adverse Events, version 3. Biochemical failure was assessed using the Phoenix definition (nadir + 2 ng/ml). The Kaplan-Meier analysis was used to calculate bDFS and association of patient and tumor characteristics with the use of SBRT.Results: Four hundred thirty-seven patients (189 low, 215 intermediate, and 33 high-risk) at a median of 69 years (range: 48-88) received SBRT at 17 centers. Seventy-eight percent of patients received 36.25 Gy/5 fractions, 13% received 37 Gy/5 fractions, 6% received 35 Gy/5 fractions, 3% received 38 Gy/4 fractions, and 5% received a boost dose of 19.5-29 Gy following external beam radiation therapy. Median follow-up was 20 months (range: 1–64 months). Genitourinary (GU) and gastrointestinal (GI) toxicities were minimal, with no acute or late Grade 3+ GU or GI toxicity. Late Grade 1 and 2 urinary frequency was 25% and 8%. Late Grade 1 and 2 proctitis was 3% and 2%. Median PSA decreased from 5.8 ng/ml (range: 0.3-43) to 0.88, 0.4, and 0.3 ng/ml at one, two, and three years. Two-year bDFS for all patients was 96.1%. Two-year bDFS was 99.0%, 94.5%, and 89.8% for low, intermediate, and high-risk patients (p < 0.0001). Two-year bDFS was 99.2%, 93.2%, and 90.4% for Gleason ≤ 6, Gleason 7, and Gleason ≥ 8 (p < 0.0001). Two-year bDFS was 96.4%, 97.2%, and 62.5% for PSA ≤ 10 ng/ml, PSA 10.1 - 20 ng/ml, and PSA > 20 ng/ml (p < 0.0001). Clinical T Stage was not significantly associated with bDFS. Conclusions: Early disease outcomes of SBRT for the treatment of clinically localized prostate cancer from a multicenter patient registry compare favorably with reports from single institutions. Acute and late GU and GI toxicities were minimal, and PSA response to SBRT was highly encouraging. Continued accrual and follow-up will be necessary to confirm long-term results.

Moderate Hypofractionated Protracted Radiation Therapy and Dose Escalation for Prostate Cancer: Do Dose and Overall Treatment Time Matter?

This was a retrospective study of 2 sequential dose escalation regimens of twice-weekly 4 Gy/fractions hypofractionated intensity modulated radiation therapy (IMRT): 56 Gy and 60 Gy delivered within a protracted overall treatment time (OTT) of 6.5 and 7 weeks, respectively. 163 prostate cancer patients with cT1c-T3a disease and nodal involvement risk ≤20% (Roach index) were treated twice weekly to the prostate ± seminal vesicles with 2 sequential dose-escalated IMRT schedules: 56 Gy (14 × 4 Gy, n=81) from 2003 to 2007 and 60 Gy (15 × 4 Gy, n=82) from 2006 to 2010. Patient repositioning was made with bone matching on portal images. Gastrointestinal (GI) and genitourinary (GU) toxicities were scored according to the Common Terminology Criteria for Adverse Events version 3.0 grading scale. There were no significant differences regarding the acute GU and GI toxicities in the 2 dose groups. The median follow-up times were 80.2 months (range, 4.5-121 months) and 56.5 months (range, 1.4-91.2 months) for patients treated to 56 and 60 Gy, respectively. The 5-year grade ≥2 late GU toxicity-free survivals with 56 Gy and 60 Gy were 96 ± 2.3% and 78.2 ± 5.1% (P=.001), respectively. The 5-year grade ≥2 late GI toxicity-free survivals with 56 Gy and 60 Gy were 98.6 ± 1.3% and 85.1 ± 4.5% (P=.005), respectively. Patients treated with 56 Gy showed a 5-year biochemical progression-free survival (bPFS) of 80.8 ± 4.7%, worse than patients treated with 60 Gy (93.2 ± 3.9%, P=.007). A trend for a better 5-year distant metastasis-free survival was observed among patients treated in the high-dose group (95.3 ± 2.7% vs 100%, P=.073, respectively). On multivariate analysis, only the 60-Gy group predicted for a better bPFS (P=.016, hazard ratio = 4.58). A single 4-Gy additional fraction in patients treated with a hypofractionated protracted IMRT schedule of 14 × 4 Gy resulted in a similar and minimal acute toxicity, in worse moderate to severe urinary and GI late effects, but a significantly better biochemical control.

Radiotherapy for early-stage prostate cancer in men under 70 years of age.

To demonstrate that radiotherapy (RT) is a valid alternative to surgery in men ≤70 years old with localized prostate cancer. From 1988 to 2009, 214 patients with T1-2 N0 M0 prostate cancer were treated with RT. The effects of patient- and treatment-related risk factors on toxicity were investigated. Median follow-up was 105 months (range 14.2-180). The 5-, 10-, and 15-year biochemical relapse-free survival for all 214 patients was 80%, 61.9%, and 57.5%, respectively. In bivariate analysis, age (≤65 vs 65-70 years) was not a significant factor for biochemical relapse, while radiation dose was (p = 0.05) in multivariate analysis. Cancer-specific survival rates at 5, 10, and 15 years were 98.4%, 93.2%, and 69.7%, respectively. Median overall survival (OS) was 167 months (95% confidence interval 147.3-186.7). The OS rates at 5, 10, and 15 years were 91.8%, 75.8%, and 42.5%, respectively. Acute genitourinary (GU) and gastrointestinal (GI) toxicities occurred in 105 (49%) and 98 patients (45.8%), respectively, with only 2 cases of grade III GI toxicity. Late GU and GI toxicities occurred in 17 (7.9%) and 20 (9.3%) patients, respectively, with 1 grade III GI toxicity and 2 grade III GU toxicities. Risk factors for late toxicity were age and RT dose and technique, which were unrelated to acute toxicity. Age ≤70 years does not consistently confer a negative prognosis for localized prostate cancer. Radiotherapy appears to be a viable alternative to surgery, offering excellent long-term cancer control.

Toxicity and quality of life after high-dose-rate brachytherapy as monotherapy for low- and intermediate-risk prostate cancer

Background and purposeThe use of HDR brachytherapy (HDR-BT) as monotherapy for prostate cancer (PC) is increasing worldwide with good tumour control rates and acceptable toxicity. We report our results on toxicity and quality of life (QoL) after HDR-BT monotherapy for PC patients. Materials and methods166 low- and intermediate-risk localized PC patients were treated with HDR-BT to a total dose of 38Gy in four fractions. Genitourinary (GU) and gastrointestinal (GI) toxicities were prospectively assessed using EORTC-RTOG questionnaires and physicians charts. QoL was evaluated using EORTC QLQ-PR25 questionnaires. ResultsThree months after treatment, acute GU and GI toxicities were reported in 10.8% and 7.2%. Acute toxicity resolved within two months in the majority of patients (61%). Late grade ⩾2 GU and GI toxicity were reported in 19.7% and 3.3% of patients 12months after HDR-BT. Mean QLQ-PR25 scores showed clinically relevant changes from baseline for urinary symptoms and sexual functioning. With a mean follow-up of 35months, biochemical failure was observed in 2.4%. Overall survival at 60months was 93.6% and cancer-specific survival was 100%. ConclusionsHDR-BT monotherapy for localized PC showed excellent clinical outcome and acceptable acute and late toxicity. Urinary symptoms and sexual function QoL decreased after treatment.

The impact of prostate gland dimension in genitourinary toxicity after definitive prostate cancer treatment with moderate hypofractionation and volumetric modulated arc radiation therapy.

To analyze clinical-dosimetric predictors of genitourinary (GU) toxicity in a cohort of prostate cancer (PC) patients treated with moderate hypofractionation and simultaneous integrated boost (SIB) using volumetric modulated arc therapy (VMAT) technique. 60 patients were selected. Patients were stratified into low (43 %), intermediate (30 %) and high-risk (27 %) groups. Low-risk patients received 73.5 Gy to PTV1; intermediate-risk received 73.5 Gy to PTV1 and 60 Gy to PTV2; high-risk received 73.5 Gy to PTV1, 60 Gy to PTV2, and 54 Gy to PTV3. All patients were treated in 30 fractions. Androgen deprivation therapy (ADT) was prescribed upfront in intermediate and high-risk categories. Toxicity was scored according to Common Terminology Criteria for Adverse Events v4.0 scoring system. Median follow-up was 30 months (range 16-36 months). GU acute toxicity was recorded as followS: G0 = 16/60 (27 %), G1 = 18/60 (30 %); G2 = 26/60 (43 %). GU late toxicity was recorded as follows: G0 = 20/60 (34 %); G1 = 29/60 (48 %); G2 = 11/56 (18 %). The risk of acute G2 GU toxicity was three times higher for prostate volume ≥80 cc. In 60 % of the patients with a prostate volume ≥80 cc, the first 3 weeks are at particular risk for toxicity onset. In the late setting, no statistical significance was found between GU toxicity and prostate gland dimension. Prostate volume ≥80 cc resulted a predictive factor of acute G2 GU toxicity, in moderate hypofractionation and volumetric modulated arc radiation therapy for definitive PC.

Ethnic difference in risk of toxicity in prostate cancer patients treated with dynamic arc radiation therapy.

The objective of this study was to assess the influence of ethnicity on toxicity in patients treated with dynamic arc radiation therapy (ART) for prostate cancer (PC). From June 2006 to May 2012, 162 cT1-T3 cN0 cM0 PC patients were treated with ART (primary diagnosis, n = 125; post-prostatectomy/brachytherapy biochemical recurrence, n = 26; adjuvant post-prostatectomy, n = 11) at 2 institutions. Forty-five patients were Latin Americans and 117 were Europeans. The dose prescribed to the prostate ranged between 68 Gy and 81 Gy. The median age was 69 years (range 43-87 years). The median follow-up was 18 months (range 2-74 months). Overall, only 3 patients died, none due to a cancer-related cause. Biochemical recurrence was seen in 7 patients. The rates of acute grade 2 gastrointestinal (GI) and genitourinary (GU) toxicities were 19.7% and 17%, respectively. Only 1 patient experienced acute grade 3 GI toxicity, whereas 11 patients (6.7%) experienced acute grade 3 GU toxicity. Multivariate analysis showed that undergoing whole pelvic lymph node irradiation was associated with a higher grade of acute GI toxicity (OR: 3.46; p = 0.003). In addition, older age was marginally associated with a higher grade of acute GI toxicity (OR: 2.10; p = 0.074). Finally, ethnicity was associated with acute GU toxicity: Europeans had lower-grade toxicity (OR: 0.27; p = 0.001). Our findings suggest an ethnic difference in GU toxicity for PC patients treated with ART. In addition, we found that ART is associated with a very low risk of severe toxicity and a low recurrence rate.

Very elderly (>80 years), frail patients with muscle-invasive bladder cancer and comorbidities: is curative irradiation feasible?

To evaluate clinical results in elderly and frail patients with bladder cancer treated with curative conformal irradiation alone. The records of ambulatory frail elderly patients, age &gt;80 years, Charlson Comorbidity Index (CCI) &gt;5, with invasive bladder cancer, were retrospectively analyzed. The patients were irradiated with curative intent. Acute and late toxicities were evaluated. A total of 27 ambulatory patients were treated. Median age was 84.5 years and a median CCI of 6.5 was recorded. Median delivered radiation dose was 64 Gy. All patients completed the planned treatment. Grade 1-2 gastrointestinal (GI) and genitourinary (GU) toxicities were observed in 55.5% of patients (15/27). At the last follow-up, no late G3+ toxicities have been observed, with G1-2 toxicities reported in 11.1% of patients (3/27). Higher values of CCI were associated with higher acute GU/GI toxicities; there was a correlation between CCI and acute GU toxicity (r = 0.43, p = 0.027). The mean survival time was 23.5 months (95% confidence interval 20.9-26.1) and no median was reached. Locoregional disease-free events and metastasis-free survival showed a 2-year actuarial rate of 90% and 87%, respectively, with an actuarial 2-year overall survival of 84.5%. Our results demonstrate safety and feasibility of curative radiation therapy in very elderly and frail patients with bladder cancer using 3D conformal radiation therapy.

The early result of whole pelvic radiotherapy and stereotactic body radiotherapy boost for high-risk localized prostate cancer.

Purpose: The rationale for hypofractionated radiotherapy in the treatment of prostate cancer is based on the modern understanding of radiobiology and advances in stereotactic body radiotherapy (SBRT) techniques. Whole-pelvis irradiation combined with SBRT boost for high-risk prostate cancer might escalate biologically effective dose without increasing toxicity. Here, we report our 4-year results of SBRT boost for high-risk localized prostate cancer.Methods and Materials: From October 2009 to August 2012, 41 patients newly diagnosed, high-risk or very high-risk (NCCN definition) localized prostate cancer were treated with whole-pelvis irradiation and SBRT boost. The whole pelvis dose was 45 Gy (25 fractions of 1.8 Gy). The SBRT boost dose was 21 Gy (three fractions of 7 Gy). Ninety percent of these patients received hormone therapy. The toxicities of gastrointestinal (GI) and genitourinary (GU) tracts were scored by Common Toxicity Criteria Adverse Effect (CTCAE v3.0). Biochemical failure was defined by Phoenix definition.Results: Median follow-up was 42 months. Mean PSA before treatment was 44.18 ng/ml. Mean PSA level at 3, 6, 12, 18, and 24 months was 0.94, 0.44, 0.13, 0.12, and 0.05 ng/ml, respectively. The estimated 4-year biochemical failure-free survival was 91.9%. Three biochemical failures were observed. GI and GU tract toxicities were minimal. No grade 3 acute GU or GI toxicity was noted. During radiation therapy, 27% of the patient had grade 2 acute GU toxicity and 12% had grade 2 acute GI toxicity. At 3 months, most toxicity scores had returned to baseline. At the last follow-up, there was no grade 3 late GU or GI toxicity.Conclusions: Whole-pelvis irradiation combined with SBRT boost for high-risk localized prostate cancer is feasible with minimal toxicity and encouraging biochemical failure-free survival. Continued accrual and follow-up would be necessary to confirm the biochemical control rate and the toxicity profiles.