Dose-escalated Prostate Radiotherapy Research Articles

Long-term outcome of biologically guided dose-escalated radiotherapy of localized prostate cancer

Background Biologically created subvolumes enable non-uniform dose distributions in prostate cancer radiotherapy (RT) thus potentially improving therapeutic ratio and reducing toxicity. We present the long-term outcome of men receiving focal boosting of carbon-11 acetate (ACE) PET-CT metabolically active areas in prostate carcinoma. Material and methods Thirty men with hormone naïve localized prostate carcinoma underwent ACE PET/CT for RT planning. There were five low-, 17 intermediate-, and eight high-risk patients. Based on thresholding of the standardized uptake values (SUVs) metabolic target volumes (MTVs) corresponding to intraprostatic lesions (IPLs) were contoured. Two planning target volumes (PTVs) were applied i.e., PTVlow-risk for the whole prostate with 8–10 mm margin and PTVhigh-risk for the MTV. Pelvic nodes were not irradiated. Late toxicity of biologically guided RT was reviewed after a median of 63 months and outcome after a median follow-up of 124 months. Results Median doses to PTVlow-risk, PTVhigh-risk, prostate, and MTV were 72.9 Gy, 79.4 Gy, 76.6 Gy, and 80.4 Gy, respectively, in 38 fractions. The 10-year cancer-specific survival was 86% and the biochemical failure-free ratio 68%, respectively. The median biochemical progression-free survival (PFS) was 37, 108, and 119 months in the high, intermediate, and low-risk groups, respectively, the difference being significant between high and intermediate-risk groups (p = 0.02). One patient (3%) presented with locoregional and 5 (17%) with distant nodal metastases. Five patients (17%) had a biochemical relapse. A larger MTV was associated with shorter PFS (r = −0.41, p = 0.02), but had no influence on OS. No other statistically significant differences in the dose painting parameters were observed between recurrence-free and recurring patients. Conclusions Biological guidance for dose-escalated prostate RT is feasible with ACE PET/CT. Since a larger MTV may be associated with a higher risk for progression, we encourage further study of dose-escalation to ACE-positive lesions considering the low toxicity of our protocol.

Effectiveness of rectal displacement devices during prostate external-beam radiation therapy: A review.

Dose-escalated prostate radiotherapy (RT) can improve treatment outcomes, but rectal toxicity is the main limiting factor for introducing dose-escalated RT. Pushing rectal wall away from the prostate reduces the volume of the rectum in high-dose region, which can decrease both short- and long-term rectal toxicities after RT. This review focuses on the literature using different rectal displacement devices such as endorectal balloons, tissue spacers, rectal retractor, and ProSpare during prostate External beam radiotherapy, with regard to dosimetric effects, clinical benefits, prostate motion, and postoperative RT setting.

Target miss using PTV-based IMRT compared to robust optimization via coverage probability concept in prostate cancer

Purpose: Cure- and toxicity rates of prostate IGRT can both be affected by ill-chosen planning target volume (PTV) margins. For dose-escalated prostate radiotherapy, we studied the potential for organ at risk (OAR) sparing and compensation of prostate motion with robust plan optimization using the coverage probability (CovP) concept compared to conventional PTV-based IMRT.Material and methods: We evaluated plan quality of CovP-plans for 27 intermediate risk prostate cancer patients treated in a prospective study (78 Gy/39 fractions). Clinical target volume (CTV) and OARs were contoured on three separate CTs to capture movement and deformation. To define the internal target volume (ITV), the union of CTV1-3 was encompassed by an isotropic margin of 7 mm for the planning process. CovP-dose distribution is optimized considering weight factors for IMRT constraints derived from probabilities of systematic organ displacement in the three CTs. CovP-dose volume histograms (DVHs) were compared with additionally calculated conventional PTV-based IMRT plans. PTV-based IMRT was planned on one-single CT with an isotropically expanded CTV to generate the PTV (i.e., CTV1 + 7mm) and was evaluated on the two other CTs.Results: The CovP-concept showed higher robustness in target volume coverage. Target miss was frequently observed with PTV-based IMRT, resulting in cold spots until 70 Gy with the CovP-concept. The target dose at 74 Gy was comparable, while further the dose–escalation (75–78 Gy) was improved with PTV-based IMRT. However, dose–escalation with PTV-based IMRT was associated with increased OAR-doses, especially in high-dose areas.Conclusions: Probabilistic dose-escalated IMRT was feasible in this prospective study. Comparison of the CovP-concept with PTV-based IMRT revealed superiority with regard to target-coverage and sparing of OARs. The CovP-concept implements a robust plan optimization strategy for organ deformation and motions and could, therefore, serve as a less demanding compromise on the way to adaptive IGRT avoiding daily time-consuming re-planning. SUMMARYWe evaluated the robustness of coverage probability (CovP)-based IMRT plans within a prospective study for prostate cancer radiotherapy. The treatment plans were compared with newly calculated conventional PTV-based IMRT plans. We were able to show that CovP led to a clearly more robust target coverage by avoiding hot spots at OARs compared to conventional PTV-based IMRT. In addition, negative consequences of an inflated PTV can be ameliorated by a more relaxed CovP-based dose prescription.

Quality of life outcomes from a phase III trial exploring optimal sequencing of androgen deprivation therapy with external beam radiotherapy in localized prostate cancer.

315 Background: Dose-escalated prostate radiotherapy (PRT) with androgen deprivation therapy (ADT) is a standard curative treatment for localized prostate cancer (LPCa). The optimal sequencing of these therapies is unclear. We report the patient-reported health related quality of life (HR-QoL) outcomes from a phase III study exploring optimal sequencing of PRT with ADT in LPCa. Methods: Newly diagnosed LPCa patients with Gleason score ≤7, clinical stage T1b-T3a, and PSA < 30 ng/mL were randomized to receive PRT (76 Gy/38 fractions) with 6 months (mos) of ADT starting 4 mos prior to RT (NAHT arm) or concurrently with RT (CAHT arm). HR-QoL was assessed using EORTC QLQ-C30 and PR25 at baseline, q2 mos while on ADT, q4 mos for year 1 and 2 after ADT, q6 mos from year 3 to 5 and annually thereafter. Linear mixed modelling was applied to compare change in score (relative to baseline) over time. Wilcoxon rank-sum test was used to identify between-group difference in absolute scores, at 18, 36 and 60 mos. The statistical and clinical significance was set at p≤0.01 and 10-point threshold, respectively. Results: Overall 432 men were enrolled in the study and 393 (194 in NAHT and 199 in CAHT arm) were eligible for HR-QoL evaluation. There was a significant difference in the change in score of sleep disturbance due to urinary bother (least-squared mean: 3.9 vs. 7.6, P = 0.001) between the two arms. Although there were statistically significant differences in absolute scores of global QoL (18, 60 mos), cognitive (18, 60 mos), social and emotional functions (60 mo), sexual intimacy (18 mo) and fatigue (60 mo) favoring NAHT, the only clinically meaningful difference was noted in ejaculatory dysfunction at 18 (mean: 52.5 vs. 64.6), 36 (60.2 vs. 49.2) & 60 mos (61.4 vs. 50.9), respectively. Conclusions: We did not find any notable difference between the two arms with respect to score change over time in any of the HR-QoL metrics except sleep disturbance due to urinary bother. Clinically meaningful difference was noted only in the late absolute ejaculatory dysfunction score which favored the NAHT arm. Based on these findings, both NAHT and CAHT with PRT are reasonable standards of care for LPCa. Clinical trial information: DC-990-0082.

Rectal retractor application during image-guided dose-escalated prostate radiotherapy.

To investigate efficacy of arectal retractor (RR) on rectal dose during image-guided dose-escalated prostate three-dimensional conformal radiotherapy (3DCRT). In all, 21patients with localized prostate cancer were treated with aRR for 3DCRT in 40 × 2 Gy. Patient underwent two scans for radiotherapy planning, without and with RR. RR was used for the first half of the treatment sessions. Two plans were created for each patient to compare the effect of RR on rectal doses. PTW-31014 Pinpoint chamber embedded within RR was used for in vivo dosimetry in 6of 21patients. The patient tolerance and acute rectal toxicity were surveyed during radiotherapy using Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. Patients tolerated the RR well during 20fractions with mild degree of anal irritation. Using aRR significantly reduced the rectal wall (RW), anterior RW and posterior RW dose-volume parameters. The average RW Dmean was 29.4 and 43.0 Gy for plans with and without RR, respectively. The mean discrepancy between the measured dose and planned dose was -3.8% (±4.9%). Grade1 diarrhea, rectal urgency and proctitis occurred in 4, 2 and 3 cases, respectively. There were no grade ≥2 acute rectal toxicities during the treatment. Rectal retraction resulted in asignificant reduction of rectal doses with asafe toxicity profile, which may reduce rectal toxicity. Dosimeter inserted into the RR providing apractical method for in vivo dosimetric verification. Further prospective clinical studies will be necessary to demonstrate the clinical advantage of RR.

Target Localization and Toxicity in Dose-Escalated Prostate Radiotherapy with Image-Guided Approach using Daily Planar Kilovoltage Imaging

Dose escalation with intensity-modulated radiation therapy (IMRT) for carcinoma of the prostate has augmented the need for accurate prostate localization prior to dose delivery. Daily planar kilovoltage (kV) imaging is a low-dose image-guidance technique that is prevalent among radiation oncologists. However, clinical outcomes evaluating the benefit of daily kV imaging are lacking. The purpose of this study was to report our clinical experience, including prostate motion and gastrointestinal (GI) and genitourinary (GU) toxicities, using this modality. A retrospective analysis of 100 patients treated consecutively between December 2005 and March 2008 with definitive external beam IMRT for T1c-T4 disease were included in this analysis. Prescription doses ranged from 74-78 Gy (median, 76) in 2 Gy fractions and were delivered following daily prostate localization using on-board kV imaging (OBI) to localize gold seed fiducial markers within the prostate. Acute and late toxicities were graded as per the NCI CTCAEv3.0. The median follow-up was 22 months. The magnitude and direction of prostate displacement and daily shifts in three axes are reported. Of note, 9.1% and 12.9% of prostate displacements were ≥ 5 mm in the anterior-posterior and superior-inferior directions, respectively. Acute grade 2 GI and GU events occurred in 11% and 39% of patients, respectively, however no grade 3 or higher acute GI or GU events were observed. Regarding late toxicity, 2% and 17% of patients developed grade 2 toxicities, and similarly no grade 3 or higher events had occurred by last follow-up. Thus, kV imaging detected a substantial amount of inter-fractional displacement and may help reduce toxicity profiles, especially high grade events, by improving the accuracy of dose delivery.

Rectal dose reduction with IMRT for prostate radiotherapy

Dose escalation in radiation therapy has led to increased control rates with some clinical trial evidence that rectal toxicity may be reduced when using intensity-modulated radiotherapy (IMRT) over 3D conformal radiotherapy (3DCRT) for dose-escalated prostate radiotherapy. However, IMRT for prostate patients is not yet standard in many Australian radiation oncology centres. This study investigates dosimetric changes that can be observed between IMRT and 3DCRT in prostate radiotherapy. Fifteen patients were selected for analysis. Two target definitions were investigated--prostate-only and prostate plus seminal vesicles (p + SVs). A five-field 3DCRT and seven-field IMRT plan were created for each patient and target definition. The planning target volume coverage was matched for both plans. Doses to the rectum, bladder and femoral heads were compared using dose volume histograms. The rectal normal tissue complication probabilities (NTCPs) were calculated and compared for the 3DCRT and IMRT plans. The delivery efficiency was investigated. The IMRT plans resulted in reductions in the V25, V50, V60, V70 and V75 Gy values for both the prostate-only and p + SVs targets. Rectal NTCP was reduced with IMRT for three different sets of model parameters. The reductions in rectal dose and NTCP were much larger for the p + SVs target. Delivery of IMRT plans was less efficient than for 3DCRT plans. IMRT resulted in superior plans based on dosimetric and biological endpoints. The dosimetric gains with IMRT were greater for the more complex p + SVs target. The gains made came at the cost of decreased delivery efficiency.

Erratum to: Image guided dose escalated prostate radiotherapy: still room to improve

We regret to report that a proofreading error caused an incorrect legend and description of the contents of table 6 to appear in our original publication of this work. The correct description of table 6 is: Univariate analysis of prognostic factors for 5-year nadir + 2 biochemical outcome for men presenting with intermediate risk factors.

Image guided dose escalated prostate radiotherapy: still room to improve

BackgroundProstate radiotherapy (RT) dose escalation has been reported to result in improved biochemical control at the cost of greater late toxicity. We report on the application of 79.8 Gy in 42 fractions of prostate image guided RT (IGRT). The primary objective was to assess 5-year biochemical control and potential prognostic factors by the Phoenix definition. Secondary endpoints included acute and late toxicity by the Radiotherapy Oncology Group (RTOG) scoring scales.MethodsFrom October/2001 and June/2003, 259 men were treated with at least 2-years follow-up. 59 patients had low, 163 intermediate and 37 high risk disease. 43 had adjuvant hormonal therapy (HT), mostly for high- or multiple risk factor intermediate-risk disease (n = 25). They received either 3-dimensional conformal RT (3DCRT, n = 226) or intensity modulated RT (IMRT) including daily on-line IGRT with intraprostatic fiducial markers.ResultsMedian follow-up was 67.8 months (range 24.4-84.7). There was no severe (grade 3-4) acute toxicity, and grade 2 acute gastrointestinal (GI) toxicity was unusual (10.1%). The 5-year incidence of grade 2-3 late GI and genitourinary (GU) toxicity was 13.7% and 12.1%, with corresponding grade 3 figures of 3.5% and 2.0% respectively. HT had an association with an increased risk of grade 2-3 late GI toxicity (11% v 21%, p = 0.018). Using the Phoenix definition for biochemical failure, the 5 year-bNED is 88.4%, 76.5% and 77.9% for low, intermediate and high risk patients respectively. On univariate analysis, T-category and Gleason grade correlated with Phoenix bNED (p = 0.006 and 0.039 respectively). Hormonal therapy was not a significant prognostic factor on uni- or multi-variate analysis. Men with positive prostate biopsies following RT had a lower chance of bNED at 5 years (34.4% v 64.3%; p = 0.147).ConclusionIGRT to 79.8 Gy results in favourable rates of late toxicity compared with published non-IGRT treated cohorts. Future avenues of investigation for toxicity reduction include IMRT, margin reduction, and dose modulation targeted to sites of disease burden. Further work is required to maximize efficacy beyond that achieved through radiation dose escalation alone.

The Impact of Dose Escalated Radiotherapy for Prostate Cancer

Introduction: Four randomised trials have shown that dose escalated prostate radiotherapy (DEPRT) improves tumour related outcomes, using additional fractions (3 photons, 1 proton) to deliver the boost (additional dose 11–15.6%). Two of the three trials performing a subgroup analysis did not show an advantage in their low-risk group patients. The aim of this study was to estimate the additional number of fractions required to implement DEPRT locally.

826 POSTER Impact of internal fiducial markers with daily on-line realignment on TCP and rectal toxicity for dose-escalated prostate radiotherapy: Monte Carlo simulation with Dose-Population Histogram analysis

826 POSTER Impact of internal fiducial markers with daily on-line realignment on TCP and rectal toxicity for dose-escalated prostate radiotherapy: Monte Carlo simulation with Dose-Population Histogram analysis

92 Dosimetric feasibility of a two — phase versus a simultaneous integrated boost technique for dose escalated prostate radiotherapy

92 Dosimetric feasibility of a two — phase versus a simultaneous integrated boost technique for dose escalated prostate radiotherapy

184 Dose-escalated prostate radiotherapy: Planning strategy based on overlap volumes between targets and critical structures

184 Dose-escalated prostate radiotherapy: Planning strategy based on overlap volumes between targets and critical structures

262 Oral A quality assurance phantom for treatment planning, dosimetry and portal imaging for participating centres in the MRC RT-01 trial in dose escalated prostate radiotherapy (ISRCTN 47772397)

262 Oral A quality assurance phantom for treatment planning, dosimetry and portal imaging for participating centres in the MRC RT-01 trial in dose escalated prostate radiotherapy (ISRCTN 47772397)