Hypofractionated Radiotherapy For Prostate Cancer Research Articles

10-yr Results of Moderately Hypofractionated Postoperative Radiotherapy for Prostate Cancer Focused on Treatment Related Toxicity

IntroductionTo retrospectively report long term outcomes following postoperative hypofractionated radiotherapy (RT) for prostate cancer, emphasizing treatment related toxicity. Material and MethodsPatients for whom adjuvant or salvage RT was indicated after prostatectomy were treated with a course of moderate hypofractionation consisting in the delivery of 62.5 Gy in 25 fractions (2.5 Gy per fraction) on the prostate bed in 5 consecutive weeks (EQD21.5 = 70 Gy) by means of 3D-CRT in most of them. Androgen deprivation therapy (ADT) was allowed at physician's discretion. Patients were evaluated for urinary and rectal complications according to the Common Terminology Criteria for Adverse Events v4 (CTCAE v.4). Overall survival (OS), biochemical recurrence free survival (bRFS), and metastasis-free survival (MFS) were estimated using the Kaplan–Meier method. ResultsOne hundred and ten patients with a median age of 67 years (range 51-78) were enrolled. The majority of them (82%) had adverse pathologic features only, while 31 (28%) had early biochemical relapse. Median PSA level before RT was 0.12 ng/mL (range 0-9 ng/mL). Median time from surgery was 4 months (range 1-136 months). Twenty-eight patients (25.4%) also received ADT. At a median follow up of 103 months (range 19-138 months), late Grade 3 and Grade 4 rectal toxicity were 0.9% (1 case of hematochezia) and 0.9% (1 case of fistula), respectively, while late Grade 3 GU side effects (urethral stenosis) occurred in 9 cases (8%). No late Grade 4 events were observed, respectively. Ten-year OS, b-RFS and MFS were 77.3% (95%CI: 82.1%-72.5%), 53.3% (95%CI: 59.9%-47.6%), and 76.7% (95%CI: 81.2%-72.2%), respectively. ConclusionOur study provides long term data that a shortened course of postoperative RT is as safe and effective as a long course of conventionally fractionated RT and would improve patients’ convenience and significantly reduce RT department workloads.

Predicting Erectile Dysfunction after Highly Conformal, Hypofractionated Radiotherapy to the Prostate

Background: Erectile dysfunction (ED) is common after prostate cancer treatment. It has been studied for conventional radiotherapy, but associations in the hypofractionated radiotherapy context are less clear. This study aimed to determine which factors are predicted for worsening ED after highly conformal, modestly hypofractionated radiotherapy to the prostate. Methods: Two hundred and twelve patients treated with 6000 cGy in twenty fractions across four centers were included in this study. Demographic, clinical, and dosimetry factors were then evaluated for post-treatment declines in erectile function using logistic regression and an explainable machine learning-based neural network. Results: 212 patients with a median follow-up of 3.6 years were evaluated. A total of 104 (49%) patients received androgen deprivation therapy. Prior to treatment, 52 (25%) patients were on ED medication. Mean doses to the penile bulb, penile crus, and penile shaft were 2490 (IQR: 1529–3656) cGy, 2095 (1306–3036) cGy, and 444 (313–650) cGy, respectively. Fifty-nine (28%) patients had a worsening of ED after treatment. On multivariable analysis, only the mean dose to the penile shaft [OR >345 vs. ≤345: 4.47 (1.43–13.99); p = 0.010] and pretreatment use of ED medication [OR yes vs. no: 12.5 (5.7–27.5; p < 0.001)] predicted for worsening ED. The neural network confirmed that the penile shaft mean dose and pre-treatment ED medication use are the most important factors in predicting ED. Conclusions: Pre-treatment ED and penile shaft dosimetry are important predictors for ED after hypofractionated radiotherapy for prostate cancer.

Patient-related risk factors for late rectal bleeding after hypofractionated radiotherapy for localized prostate cancer: a single-center retrospective study

BackgroundSeveral studies have reported patient-related risk factors for late rectal bleeding following conventionally fractionated radiotherapy for prostate cancer. We investigated patient-related risk factors for late rectal bleeding after hypofractionated radiotherapy.MethodsA total of 231 patients with local or locally advanced prostate cancer treated with hypofractionated radiotherapy (70 or 67.2 Gy in 28 fractions) were evaluated retrospectively. All patients received intensity-modulated radiotherapy with daily image guidance. The relationships between late rectal bleeding and risk factors like diabetes, hypertension, cirrhosis, and anticoagulant use were analyzed.ResultsDuring a median follow-up of 23 months, the crude rates of grade ≥ 1, grade ≥ 2, and grade ≥ 3 late rectal bleeding were 23.8%, 16.9%, and 9.5%, respectively. Cirrhosis and anticoagulant use predicted an increased risk of grade ≥ 3 rectal bleeding in multivariable analyses (hazard ratio [HR] 14.37, 95% confidence interval [CI] 3.09–66.87, P = 0.001, and HR 2.93, 95% CI 1.14–7.55, P = 0.026, respectively). The non-anticoagulant group had a significantly superior 5-year freedom from grade ≥ 3 bleeding compared to the anticoagulant group in a propensity-weighted log-rank analysis (88.0% vs. 76.7%, P = 0.041). A receiver operating characteristic curve analysis revealed that rectal bleeding was minimized in the anticoagulant group if the equivalent dose at fractionation of 2 Gy (EQD2) V77 Gy of the rectum was < 4.5% or if the EQD2 V8.2 Gy was < 71.0%.ConclusionsPatients taking anticoagulants or those with cirrhosis had a significantly higher risk of severe late rectal bleeding than other patients after hypofractionated radiotherapy for prostate cancer in the present study. The bleeding risk could be lowered by minimizing hotspots in patients taking anticoagulants.

Clinical evaluation of the impact of rectal and bladder filling on prostate position during hypofractionated radiotherapy for prostate cancer

Objective: To evaluate the impact of rectal and bladder filling on prostate position during hypofractionated radiotherapy for prostate cancer. Methods: Three gold fiducials were implanted into the prostate in 25 patients. Each patient underwent CT scanning under four different conditions: full rectum and bladder, full bladder and empty rectum, full rectum and empty bladder, and empty rectum and bladder (primary image). The other three scans were aligned with the primary image by pelvic bone, then by the implanted fiducials. Prostate displacements were determined by computing the difference between these two alignments. The magnitude and directions of displacement were analyzed. Results: A full rectum shifted the prostate most significantly in the anterior (0.93 ± 0.31 cm) and superior directions (0.48 ± 0.30 cm). A full rectum was associated with anterior shifts ≥0.5 cm in 92.0% of the patients, ≥1 cm in 44.0%, while superior shifts ≥0.5 cm were observed in 48.0% and ≥1 cm in 8.0%. A full bladder shifted the prostate mildly in the superior direction (0.19 ± 0.30 cm). A full rectum and full bladder shifted the prostate more in the anterior (1.19 ± 0.37 cm) and superior directions (0.49 ± 0.50 cm). 100% and 56.0% had ≥0.5 cm of anterior and superior displacements. 68.0% and 16.0% had ≥1 cm of anterior and superior shift. Conclusions: Our study demonstrated that a full rectum shifted the prostate mainly anterosuperiorly. The rectal volume’s impact on prostate movement is much larger than that of the bladder.

Post-operative hypofractionated radiotherapy for prostate cancer: a mono-institutional analysis of toxicity and clinical outcomes.

As the use of hypofractionation has spread in the setting of curative prostate radiotherapy, few data are available in the post-operative scenario. This study reports a mono-institutional experience of moderate post-operative hypofractionated radiotherapy for prostate cancer. In February 2021, we retrospectively assessed the outcomes of 129 patients who received between April 2013 and May 2020 hypofractionated post-operative radiotherapy using Helical Tomotherapy. Toxicity was assessed using CTCAE criteria v4.0. Survival endpoints were calculated with Kaplan-Meier method. Median age and follow-up were, respectively, 67years and 43months. Adjuvant and salvage treatment were delivered to 63.5% and 36.4% of patients to a median total dose of 63.8Gy (61.6-65.25Gy) in 29 fractions (2.12-2.25Gy/fraction). Pelvic lymph-nodes irradiation was performed in 67.4% of cases. ADT was added in 50%. Acute toxicity was: G1 and G2 GU events in 36% and 9.3% of cases; G1 and G2 GI events in 29.4% and 13.9%. Late GU toxicity occurred in 12.4% of cases: 3.1% G1, 7.7% G2 and 1.5% G3 events; GI toxicity consisted of 1.5% G1 and 7.7% G2 events. Biochemical relapse occurred in 26.3% of cases, recording no significant differences between adjuvant and salvage (p = 0.67), with 4- and 5-years bRFS rates of 78.7% and 75.6%. Two patients died of progressive disease and eight for non-oncological causes resulting in 3-years overall survival and cancer-specific survival rates of 98% and 98.4%. Our experience supports the use of moderate hypofractionation for prostate bed radiotherapy, with minimal toxicity and promising results in terms of clinical outcomes.

Target motion mitigation promotes high-precision treatment planning and delivery of extreme hypofractionated prostate cancer radiotherapy: Results from a phase II study

Background and purposeWhile favourable long-term outcomes have been reported in organ-confined prostate cancer treated with 5 × 7–8 Gy extreme hypofractionation, dose escalation to 5 × 9–10 Gy improved local control but was associated with unacceptable rates of late rectal and urinary toxicities. The purpose of this study was to explore the feasibility of intra-fractional prostate immobilization in reducing toxicity, to promote dose escalation with extreme hypofractionated radiotherapy in prostate cancer. Material and methods207 patients received 5 consecutive fractions of 9 Gy. An air-inflated (150 cm3) endorectal balloon and an intraurethral Foley catheter with 3 beacon transponders were used to immobilize the prostate and monitor intra-fractional target motion. VMAT-IGRT with inverse dose-painting was employed in delivering the PTV dose and in sculpting exposure of normal organs at risk to fulfil dose-volume constraints. ResultsIntroduction of air-filled balloon induced repeatable rectum/prostate complex migration from its resting position to a specific retropubic niche, affording the same 3D anatomical configuration daily. Intra-fractional target deviations ≤1 mm occurred in 95% of sessions, while target realignment in ≥2 mm deviations enabled treatment completion as scheduled. Nadir PSA at median 54 months follow-up was 0.19 ng/mL, and bRFS was 100%, 92.4% and 71.4% in low-, intermediate- and high-risk categories, respectively. Late Grade 2 GU and GI toxicities were 2.9% and 2.4%, respectively. No adverse changes in patient-reported quality of life scores were observed. ConclusionThe unique spatial configuration of this prostate motion mitigation protocol enabled precise treatment planning and delivery that optimized outcomes of ultra-high 5 × 9 Gy hypofractionated radiotherapy of organ-confined prostate cancer.

Linac-based stereotactic body radiation therapy vs moderate hypofractionated radiotherapy in prostate cancer: propensity-score based comparison of outcome and toxicity.

Prostate cancer represents the second most common malignancy in the world and majority of patients have diagnosis of localized disease. The aim of the present study was to compare two cohorts of patients treated with moderate hypofractionation (MHRT) or stereotactic body radiation therapy (SBRT). We included patients treated between 2010 and 2015. Inclusion criteria were: adenocarcinoma of the prostate; class risks low or intermediate; WHO performance status 0-2. We evaluated rectal, gastrointestinal toxicity and genitourinary. Measures of outcome were biochemical disease-free survival and overall survival. Propensity score was used to approximate the balance in covariates. 209 patients were included, treated with MHRT (n = 109) or SBRT (n = 100). Median follow-up time was 37.4 months. Rates of biochemical disease-free survival at 1- and 3 years were 100 and 95%, respectively. There was no significant difference between the two groups (p = 0.868). Rates of overall survival at 1- and 3 years were 100 and 97.1%, respectively with no differences between the two groups (p = 0.312). After propensity scoring matching, no differences were observed in terms of acute and late rectal and gastrointestinal toxicity. While mild genitourinary side-effects were more common in SBRT group (45.5% vs 19.5 %), Grade 2 and 3 toxicity was increased after MHRT (11.7% vs 2.6 %; p = 0.029). Moderate hypofractionation and SBRT are two effective and safe options for the treatment of low- and intermediate-risk prostate cancer. The analysis showed no difference in terms of disease's control and survival but increased moderate and severe toxicity after MHRT. Moderate hypofractionation and SBRT are comparable in terms of efficacy while moderate and severe toxicity is more common in the first one.

Twice- vs. thrice-weekly moderate hypofractionated radiotherapy for prostate cancer: does overall treatment time matter?

To evaluate the influence of overall treatment time (OTT) in disease control, acute, and long-term side effects with moderate hypofractionated external beam radiotherapy (RT) for prostate cancer (PCa) delivered either twice- or thrice-a-week. 157 patients with localized PCa were treated consecutively with 56Gy in 4Gy/fraction delivered either twice (86 patients, from 2003 to 2010, group-1) or thrice a week (71 patients, from 2010 to 2017, group-2) using IMRT or VMAT techniques. Gastrointestinal (GI) and genitourinary (GU) toxicities were scored according to the CTCAE v3.0 grading scale. Median follow-up was 110 and 56months for groups 1 and 2, respectively. At 6weeks, patients treated thrice-a-week experienced higher acute ≥ grade-2 GU toxicity compared to those treated twice a week (25.4% vs 5.8%, p = 0.001) even though none presented ≥ grade-3 GU or GI toxicity in the thrice-a-week group. The 5-year ≥ grade-2 late GU toxicity-free survival was higher in group-1 (95.9 ± 2.3%) than in group-2 (81.5 ± 4.9%, p = 0.003), while no differences in ≥ grade-2 late GI toxicity-free survival were observed between both groups (97.5 ± 1.7% vs. 97 ± 2.1% for groups 1 and 2, respectively). The 5-year biochemical relapse-free survival (bRFS) was not different for patients treated twice compared to those treated thrice-a-week (80.6 ± 4.5% vs. 85.3 ± 4.8%, respectively, p = 0.441), as much as for patients treated in > 5weeks vs. those treated in ≤ 5weeks (81.3 ± 4.4% vs. 84.4 ± 5.1%, respectively, p = 0.584). In this retrospective hypothesis-generating analysis, less vs. more than 5weeks OTT may increase acute and late GU toxicities without significantly improving bRFS in patients treated to high effective doses (> 80Gy) with moderate hypofractionated RT. Prospective trials evaluating the impact of OTT on hypofractionated schedules for PCa are warranted.

Tolerance doses for late adverse events after hypofractionated radiotherapy for prostate cancer on trial NRG Oncology/RTOG 0415

Purpose/objectiveHypofractionated radiotherapy (HRT) regimens for prostate cancer are emerging, but tolerance doses for late adverse events are scarce. The purpose of this study is to define dose–volume predictors for late gastrointestinal and genitourinary (GI and GU) toxicities after HRT in the multi-center NRG Oncology/RTOG 0415 low-risk prostate cancer trial (N = 521). Material/methodsTreatment in the studied HRT arm was delivered as 70 Gy at 2.5 Gy/fraction with 3D-CRT/IMRT (N = 108/413). At a median follow-up of 5.9 years, the crude late ≥Grade 2 GI and GU toxicities were 19% and 29%, respectively. For modeling, the complete HRT cohort was randomly split into training and validation (70% and 30%; preserved toxicity rates). Within training, dose–response modeling was based on dose–volume cut-points (EQD2Gy; bladder/rectum: α/β = 6 Gy/3Gy), age, acute ≥Grade 2 toxicity, and treatment technique using univariate and multivariate logistic regression on bootstrapping (UVA and MVA). Candidate predictors were determined at p ≤ 0.05, and the selected MVA models were explored on validation where model generalizability was judged if the area under the receiver-operating curve in validation (AUCvalidation) was within AUCtraining ± SD with p ≤ 0.05, and with an Hosmer–Lemeshow p-value (pHL) > 0.05. ResultsThree candidate predictors were suggested for late GI toxicity: the minimum dose to the hottest 5% rectal volume (D5%[Gy]), the absolute rectal volume <35 Gy, and acute GI toxicity (AUC = 0.59–0.63; p = 0.02–0.04). The two generalizable MVA models, i.e., D5%[Gy] with or without acute GI toxicity (AUCvalidation = 0.64, 0.65; p = 0.01, 0.03; pHL = 0.45–0.56), suggest that reducing late GI toxicity from 20% to 10% would require reducing D5%[Gy] from ≤65 Gy to ≤62 Gy (logistic function argument: 17+(0.24D5%[Gy])). Acute GU toxicity showed only a trend to predict late GU toxicity (AUCtraining = 0.57; p = 0.07). ConclusionLate GI toxicity, following moderate HRT for low-risk prostate cancer, increases with higher doses to small rectal volumes. This work provides quantitative evidence that limiting small rectal dose ‘hotspots’ in clinical practice of such HRT regimens is likely to further reduce the associated rates of GI toxicity.

Evaluation of transperineal ultrasound imaging as a potential solution for target tracking during hypofractionated radiotherapy for prostate cancer

BackgroundEmerging hypofractionated prostate radiotherapy regimens require solutions for accurate target tracking during beam delivery. The goal of this study is to evaluate the performance of the Clarity ultrasound monitoring system for prostate motion tracking.MethodsFive prostate patients underwent continuous perineum ultrasound imaging during their daily treatments. Initial absolute 3D positions of fiducials implanted in the prostate were estimated from the KV images. Fiducial positions in MV images acquired during beam delivery were compared with predicted positions based on Clarity 3D tracking. The uncertainty in the comparison results was evaluated in a phantom validation study.ResultsContinuous real-time ultrasound motion tracking was recorded in 5 patients and 167 fractions for overall of 39.7 h. Phantom validation of the proposed procedure demonstrated that predicted and observed fiducial positions agree within 1.1 mm. In patients agreement between predicted and actual fiducial positions varied between 1.3 mm and 3.3 mm. On average ultrasound tracking reduced the maximum localization error in patients by 20% on average. With the motion corrected, the duration prostate beyond 1 mm from its initial treatment position can be reduced from 37 to 22% of the total treatment time.ConclusionReal-time ultrasound tracking reduces uncertainty in prostate position due to intra-fractional motion.Trial registrationIRB Protocol #27372. Date of registration of trial: 12/17/2013.

EP-1349: Adjuvant hypofractionated radiotherapy for prostate cancer: acute toxicity

EP-1349: Adjuvant hypofractionated radiotherapy for prostate cancer: acute toxicity

PO-0724: Moderate hypofractionated radiotherapy in prostate cancer: a meta-analysis from randomized trials

PO-0724: Moderate hypofractionated radiotherapy in prostate cancer: a meta-analysis from randomized trials

Hypofractionated radiation therapy for prostate cancer: The McGill University Health Center experience

PurposeIn 2002, at the McGill University Health Centre, we began a program of hypofractionated radiotherapy for patients with low risk prostate cancer as an alternative to conventionally fractionated radiotherapy. Material and methodsOur initial hypofractionation regimen was 66Gy given in 22 fractions, prescribed to the isocenter, delivered with 3D-conformal radiotherapy plan. The clinical target volume was the prostate gland and the planning target volume consisted of the clinical target volume plus a 7-mm margin in all directions. Hormonal therapy was not given to any patient. ResultsThe long-term results for this group of patients confirmed the feasibility, good tolerance and excellent disease control of the regimen with the extra-benefit of being convenient to both patients and the health system by shortening treatment duration. The outcomes of this approach stimulated us to use hypofractionation in patients with intermediate-risk. Analysis of 100 intermediate-risk patients receiving our hypofractionated radiotherapy regimen (no hormones) shows, at median follow-up of 75 months, 8-year biochemical recurrence free and cancer specific survival rates of 90% and 95%, respectively, with acceptable toxicity. DiscussionOur technique changed from 3D to intensity modulated radiotherapy with the dose adjusted to 60Gy in 20 fractions. Lastly, we have expanded the program to high-risk patients where IMRT treatments are given to the pelvic nodes (44Gy in 20 fractions) with a simultaneous integrated boost delivery to the prostate (60Gy in the same 20 fractions). Our long-term results have shown that moderate hypofractionated radiotherapy for prostate cancer is safe and provides good tumor control comparable to high-dose conventionally fractionated radiotherapy. This hypofractionated regimen has been routinely used in our institution.

On Voxel-by-voxel Accumulated Dose for Prostate Radiation Therapy using Deformable Image Registration

Since delivered dose is rarely the same with planned, we calculated the delivered total dose to ten prostate radiotherapy patients treated with rectal balloons using deformable dose accumulation (DDA) and compared it with the planned dose. The patients were treated with TomoTherapy using two rectal balloon designs: five patients had the Radiadyne balloon (balloon A), and five patients had the EZ-EM balloon (balloon B). Prostate and rectal wall contours were outlined on each pre-treatment MVCT for all patients. Delivered fractional doses were calculated using the MVCT taken immediately prior to delivery. Dose grids were accumulated to the last MVCT using DDA tools in Pinnacle3 TM (v9.100, Philips Radiation Oncology Systems, Fitchburg, USA). Delivered total doses were compared with planned doses using prostate and rectal wall DVHs. The rectal NTCP was calculated based on total delivered and planned doses for all patients using the Lyman model. For 8/10 patients, the rectal wall NTCP calculated using the delivered total dose was less than planned, with seven patients showing a decrease of more than 5% in NTCP. For 2/10 patients studied, the rectal wall NTCP calculated using total delivered dose was 2% higher than planned. This study indicates that for patients receiving hypofractionated radiotherapy for prostate cancer with a rectal balloon, total delivered doses to prostate is similar with planned while delivered dose to rectal walls may be significantly different from planned doses. 8/10 patients show significant correlation between rectal balloon anterior-posterior positions and some VD values.

Is Biochemical Relapse-free Survival After Profoundly Hypofractionated Radiotherapy Consistent with Current Radiobiological Models?

AimsThe α/β ratio for prostate cancer is thought to be low and less than for the rectum, which is usually the dose-limiting organ. Hypofractionated radiotherapy should therefore improve the therapeutic ratio, increasing cure rates with less toxicity. A number of models for predicting biochemical relapse-free survival have been developed from large series of patients treated with conventional and moderately hypofractionated radiotherapy. The purpose of this study was to test these models when significant numbers of patients treated with profoundly hypofractionated radiotherapy were included. Materials and methodsA systematic review of the literature with regard to hypofractionated radiotherapy for prostate cancer was conducted, focussing on data recently presented on prostate stereotactic body radiotherapy. For the work described here, we have taken published biochemical control rates for a range of moderately and profoundly fractionated schedules and plotted these together with a range of radiobiological models, which are described. ResultsThe data reviewed show consistency between the various radiobiological model predictions and the currently observed data. ConclusionCurrent radiobiological models provide accurate predictions of biochemical relapse-free survival, even when profoundly hypofractionated patients are included in the analysis.

Hypofractionated External-Beam Radiotherapy for Prostate Cancer

There are radiobiological rationales supporting hypofractionated radiotherapy for prostate cancer. The recent advancements in treatment planning and delivery allow sophisticated radiation treatments to take advantage of the differences in radiobiology of prostate cancer and the surrounding normal tissues. The preliminary results from clinical studies indicate that abbreviated fractionation programs can result in successful treatment of localized prostate cancer without escalation of late toxicity.

Helical tomotherapy-based hypofractionated radiotherapy for prostate cancer: A report on the procedure, dosimetry and preliminary clinical outcome

Hypofractionated intensity-modulated radiotherapy (IMRT) under image guidance using helical tomotherapy for prostate cancer improves therapeutic ratio. To report on clinical and dosimetric experience using hypofractionated helical tomotherapy for prostate cancer. Prospective consecutive case series as feasibility study approved by Institutional Review Board (IRB) (2007-11). The staging work-up, risk stratification, simulation, contouring, planning, online matching and treatment delivery methodology are described in detail. The doses to (prostate and nodal) PTV and organs at risk (bladder, rectum, bowel and femoral heads) are described. The audit of online matching was used to determine set-up errors, PTV margins and resultant translational vector. We also report the outcomes in terms of biochemical relapse-free survival and acute toxicity. Fifty-three consecutive patients were included. The baseline PSA was 23 ng/ml (1.60-100.37). The prostate BED3 ranged from 110-129 Gy (α/β for prostate 1.5-3 Gy) and nodal 72-87.68 Gy. The required PTV margin by van Hark's formula for lateral, longitudinal and vertical axes were 11.30, 9.95 and 13.49 mm, respectively with resultant vectors 3-15 mm. There was 7% to 8% chance of missing part of CTV in absence of image guidance. There was only one patient requiring premature conclusion at 45 Gy due grade 3 genitourinary toxicity. At median follow-up of 23 months, biochemical relapse-free survival rate is 95.2%. Hypofractionated IMRT under image guidance using helical tomotherapy for prostate cancer is feasible with acceptable acute toxicity and may be advantageous in high throughput centers.

Hypofractionated helical intensity-modulated radiotherapy of the prostate bed after prostatectomy with or without the pelvic lymph nodes - the PRIAMOS trial

BackgroundWhile evidence on safety and efficacy of primary hypofractionated radiotherapy in prostate cancer is accumulating, data on postoperative hypofractionated treatment of the prostate bed and of the pelvic lymph nodes is still scarce. This phase II trial was initiated to investigate safety and feasibility of hypofractionated treatment of the prostate bed alone or with the pelvic lymph nodes.Methods/designA total of 80 prostate cancer patients with the indication for adjuvant radiotherapy will be enrolled, where 40 patients with a low risk of lymph node involvement (arm 1) and another 40 patients with a high risk of lymph node involvement (arm 2) will each receive 54 Gy in 18 fractions to the prostate bed. Arm 2 will be given 45 Gy to the pelvic lymph nodes additionally. Helical Tomotherapy and daily image guidance will be used.DiscussionThis trial was initiated to substantiate data on hypofractionated treatment of the prostate bed and generate first data on adjuvant hypofractionated radiotherapy of the pelvic lymph nodes.Trial registrationClinicalTrials.gov; NCT01620710

3D geometric gel dosimetry verification of intraprostatic fiducial guided hypofractionated radiotherapy of prostate cancer

This pre-study is aimed to investigate the feasibility of a normoxic polyacrylamide gel (nPAG) dosimeter with implanted gold fiducials to evaluate the geometric precision, including setup correction strategies, in the delivery of hypofractionated treatments. For this purpose a phantom consisting of three parts was constructed: (1) the patient simulating volume, providing realistic scatter conditions and weight, (2) a bottle containing the active dosimetric volume and (3) the gold fiducials and the fiducial support structure. A 6.1 Gy prostate IMRT treatment was delivered to the phantom using the sliding-window technique. The phantom was positioned prior to the treatment using the implanted fiducials and kV on-board imaging. An overlay of the 95% isosurface of the TPS calculated dose distribution and the measured dose distribution using gel showed good agreement. The clinical target volume (CTV) was well centred inside the 95% isodose surface of the measured volume. It was shown for the evaluated case that the use of on-board imaging and integrated setup correction tools could be used to compensate for a deliberately introduced offset in CTV position. The study showed that MRI based nPAG gel dosimetry can be used to verify setup correction procedures using implanted gold fiducials.

Acute toxicity of image-guided hypofractionated radiotherapy for prostate cancer: Nonrandomized comparison with conventional fractionation

Objectives To compare acute toxicity of prostate cancer image-guided hypofractionated radiotherapy (hypo-IGRT) with conventional fractionation without image-guidance (non-IGRT). To test the hypothesis that the potentially injurious effect of hypofractionation can be counterbalanced by the reduced irradiated normal tissue volume using IGRT approach. Materials and methods One hundred seventy-nine cT1-T2N0M0 prostate cancer patients were treated within the prospective study with 70.2 Gy/26 fractions (equivalent to 84 Gy/42 fractions, α/β 1.5 Gy) using IGRT (transabdominal ultrasound, ExacTrac X-Ray system, or cone-beam computer tomography). Their prospectively collected data were compared with data of 174 patients treated to 80 Gy/40 fractions with non-IGRT. The difference between hypo-IGRT and non-IGRT cohorts included fractionation (hypofractionation vs. conventional fractionation), margins (hypo-IGRT margins: 7 mm and 3 mm, for all but posterior margins; respectively; non-IGRT margins: 10 and 5 mm, for all but posterior margins, respectively), and use of image-guidance or not. Multivariate analysis was performed to define the tumor-, patient-, and treatment-related predictors for acute toxicity. Results All patients completed the prescribed radiotherapy course. Acute toxicity in the hypo-IGRT cohort included rectal (G1: 29.1%; G2: 11.2%; G3: 1.1%) and urinary events (G1: 33.5%; G2: 39.1%; G3: 5%). Acute toxicity in the non-IGRT patients included rectal (G1: 16.1%; G2: 6.3%) and urinary events (G1: 36.2%; G2: 20.7%; G3: 0.6%). In 1 hypo-IGRT and 2 non-IGRT patients, radiotherapy was temporarily interrupted due to acute toxicity. The incidence of mild (G1-2) rectal and bladder complications was significantly higher for hypo-IGRT ( P = 0.0014 and P < 0.0001, respectively). Multivariate analysis showed that hypo-IGRT ( P = 0.001) and higher PSA ( P = 0.046) are correlated with higher acute urinary toxicity. No independent factor was identified for acute rectal toxicity. No significant impact of IGRT system on acute toxicity was observed. Conclusions The acute toxicity rates were low and similar in both study groups with some increase in mild acute urinary injury in the hypo-IGRT patients (most probably due to the under-reporting in the retrospectively analyzed non-IGRT cohort). The higher incidence of acute bowel reactions observed in hypo-IGRT group was not significant in the multivariate analysis. Further investigation is warranted in order to exclude the bias due to the nonrandomized character of the study.