Association of urethral toxicity with dose exposure in combined high-dose-rate brachytherapy and intensity-modulated radiation therapy in intermediate- and high-risk prostate cancer

Introduction

To report acute and late toxicities in patients with intermediate- and high-risk prostate cancer treated with combined high-dose-rate brachytherapy (HDR-B) and intensity-modulated radiation therapy (IMRT).

Materials and methods

From March 2003 to September 2005, 64 men were treated with a single implant HDR-B with 21 Gy given in three fractions, followed by 50 Gy IMRT along with organ tracking. Median age was 66.1 years, and risk of recurrence was intermediate in 47% of the patients or high in 53% of the patients. Androgen deprivation therapy was received by 69% of the patients. Toxicity was scored according to the CTCAE version 3.0. Median follow-up was 3.1 years.

Results

Acute grade 3 genitourinary (GU) toxicity was observed in 7.8% of the patients, and late grades 3 and 4 GU toxicity was observed in 10.9% and 1.6% of the patients. Acute grade 3 gastrointestinal (GI) toxicity was experienced by 1.6% of the patients, and late grade 3 GI toxicity was absent. The urethral V₁₂₀ (urethral volume receiving ?120% of the prescribed HDR-B dose) was associated with acute (P = .047) and late ? grade 2 GU toxicities (P = .049).

Conclusions

Late grades 3 and 4 GU toxicity occurred in 10.9% and 1.6% of the patients after HDR-B followed by IMRT in association with the irradiated urethral volume. The impact of V₁₂₀ on GU toxicity should be validated in further studies.     

MRI-guided prostate radiation therapy planning: Investigation of dosimetric accuracy of MRI-based dose planning

Background and purpose

Dose planning requires a CT scan which provides the electron density distribution for dose calculation. MR provides superior soft tissue contrast compared to CT and the use of MR-alone for prostate planning would provide further benefits such as lower cost to the patient. This study compares the accuracy of MR-alone based dose calculations with bulk electron density assignment to CT-based dose calculations for prostate radiotherapy.

Materials and methods

CT and whole pelvis MR images were contoured for 39 prostate patients. Plans with uniform density and plans with bulk density values assigned to bone and tissue were compared to the patient’s gold standard full density CT plan. The optimal bulk density for bone was calculated using effective depth measurements. The plans were evaluated using ICRU point doses, dose volume histograms, and Chi comparisons. Differences in spatial uniformity were investigated for the CT and MR scans.

Results

The calculated dose for CT bulk bone and tissue density plans was 0.1 ± 0.6% (mean ± 1 SD) higher than the corresponding full density CT plan. MR bulk bone and tissue density plans were 1.3 ± 0.8% lower than the full density CT plan. CT uniform density plans and MR uniform density plans were 1.4 ± 0.9% and 2.6 ± 0.9% lower, respectively. Paired t-tests performed on specific points on the DVH graphs showed that points on DVHs for all bulk electron density plans were equivalent with two exceptions. There was no significant difference between doses calculated on Pinnacle and Eclipse. The dose distributions of six patients produced Chi values outside the acceptable range of values when MR-based plans were compared to the full density plan.

Conclusions

MR-alone bulk density planning is feasible provided bone is assigned a density, however, manual segmentation of bone on MR images will have to be replaced with automatic methods. The major dose differences for MR bulk density plans are due to differences in patient external contours introduced by the MR couch-top and pelvic coil.     

Analysis of biochemical control and prognostic factors in patients treated with either low-dose three-dimensional conformal radiation therapy or high-dose intensity-modulated radiotherapy for localized prostate cancer

PURPOSE: To identify prognostic factors and evaluate biochemical control rates for patients with localized prostate cancer treated with either high-dose intensity-modulated radiotherapy (IMRT) or conventional-dose three-dimensional conformal radiotherapy 3D-CRT. METHODS: Four hundred sixteen patients with a minimum follow-up of 3 years (median, 5 years) were included. Two hundred seventy-one patients received 3D-CRT with a median dose of 68.4 Gy (range, 66-71 Gy). The next 145 patients received IMRT with a median dose of 75.6 Gy (range, 70.2-77.4 Gy). Biochemical control rates were calculated according to both American Society for Therapeutic Radiology and Oncology (ASTRO) consensus definitions. Prognostic factors were identified using both univariate and multivariate analyses. RESULTS: The 5-year biochemical control rate was 60.4% for 3D-CRT and 74.1% for IMRT (p < 0.0001, first ASTRO Consensus definition). Using the ASTRO Phoenix definition, the 5-year biochemical control rate was 74.4% and 84.6% with 3D-RT and IMRT, respectively (p = 0.0326). Univariate analyses determined that PSA level, T stage, Gleason score, perineural invasion, and radiation dose were predictive of biochemical control. On multivariate analysis, dose, Gleason score, and perineural invasion remained significant. CONCLUSION: On the basis of both ASTRO definitions, dose, Gleason score, and perineural invasion were predictive of biochemical control. Intensity-modulated radiotherapy allowed delivery of higher doses of radiation with very low toxicity, resulting in improved biochemical control.     

宫颈癌调强放疗中膀胱解剖结构变化及对其吸收剂量影响研究

目的 研究宫颈癌患者调强放疗中膀胱体积与位置变化及对其吸收剂量的影响.方法 随机选取20例接受宫颈癌根治性调强放疗患者,采集分次治疗前锥形束CT(CBCT)图像,与原始治疗计划CT图像实施基于骨性解剖结构的刚体配准.由同一医师在CBCT图像上勾画膀胱轮廓,并映射回原始治疗计划CT图像,分析分次治疗间膀胱体积与位置及其吸收剂量变化.结果 20例患者共采集451次CBCT图像进行分析.膀胱体积与位置变化较大,15例患者膀胱体积与V45无相关性(r=-0.225～0.473,P值均>0.05),4例呈负相关性(r=-0.564,P<0.05;r=-0.597,P<0.01;r=-0.942,P<0.01;r=-0.816,P<0.01),1例呈正相关性(r=0.662,P<0.01);治疗中超出标准(V45≤50%)次数共64次(14.2%).结论 宫颈癌调强放疗中大部分患者通过适当充盈膀胱处理后膀胱体积与位置变化仍较大,但对其剂量影响在临床可接受范围,对个别临床靶体积较大患者应密切观察其退缩情况,必要时进行在线或离线分析及时修改治疗计划.

Abstract：

Objective To investigate bladder anatomical changes and dose variation in patients with cervical cancer.Methods We analyzed 20 patients,undergoing external beam radiotherapy scanning cone beam CT(CBCT)before each fraction.Bladder was contoured on each CBCT,was projected onto the planning CT and assesses anatomical changes and dose variation.Results A total 451 CBCT images,for 20 patients were collected for analysis,show more change in bladder volume and position.In 15 cases bladder volume and V45 had no significant correlation(r=0.225 -0.473,all P>0.05),4 cases shows negative correlation(r=-0.564,P<0.05;r=-0.597,P<0.01;r=-0.942,P<0.01;r=-0.816,P<0.01),1 case shows positive correlation(r=0.662,P<0.01).Have more than the criteria(V45≤50%)number is 64/451(14.2%)in whole treatment.Conclusions For most patients by filling adequacy bladder,bladder dose variation is acceptable:CTV lager for individual patients should be closely observed its regression,implementation of the offline or online calibration.     

Systematic review of hypofractionated radiation therapy for prostate cancer

Prostate cancer is the second most prevalent solid tumor diagnosed in men in the United States and Western Europe. Conventionally fractionated external beam radiation therapy (1.8–2.0 Gy/fraction) is an established treatment modality for men in all disease risk groups. Emerging evidence from experimental and clinical studies suggests that the α/β ratio for prostate cancer may be as low as 1.5 Gy, which has prompted investigators around the world to explore moderately hypofractionated radiation therapy (2.1–3.5 Gy/fraction). We review the impetus behind moderate hypofractionation and the current clinical evidence supporting moderate hypofractionated radiation therapy for prostate cancer. Although hypofractionated radiation therapy has many theoretical advantages, there is no clear evidence from prospective, randomized, controlled trials showing that hypofractionated schedules have improved outcomes or lower toxicity than conventionally fractionated regimens. Currently, hypofractionated schedules should only be used in the context of clinical trials. High dose rate brachytherapy and stereotactic body radiation therapy (fraction size 3.5 Gy and greater) are alternative approaches to hypofractionation, but are beyond the scope of this report.     

Patient tolerance of rectal balloons in conformal radiation treatment of prostate cancer

PURPOSE: To evaluate patient tolerance of intrarectal balloons used during conformal prostate irradiation. METHODS AND MATERIALS: A retrospective analysis was performed on 3,561 patients who underwent conformal radiation for prostate cancer. Therapy consisted of proton irradiation of the prostate and seminal vesicles and X-ray treatment of the pelvis when warranted. The number of treatments in which the balloon was tolerated was recorded. Results were stratified according to method of irradiation (protons alone vs. combined proton/X-ray) and method of planning (2D vs. 3D planning of X-ray fields in patients undergoing combination treatment). RESULTS: Of all the patients evaluated, 3,474 (97.6%) tolerated the balloon throughout treatment; 87 (2.4%) declined the balloon for 1 or more treatments and tolerated the balloon for 85.5% of their treatments. Chi-square analysis revealed a significant tolerance advantage in those who received protons alone compared with combination treatment (99.5% vs. 95.7%; p < 0.001). In patients undergoing combination treatment, chi-square analysis did not reveal significant tolerance differences in patients undergoing 3D vs. 2D planning for pelvic X-ray fields (95.74% vs. 95.72%; p = 0.990). CONCLUSIONS: Intrarectal balloons are well tolerated over a course of conformal prostate irradiation.     

Alternative methods for intensity-modulated radiation therapy inverse planning and dose delivery

A large number of IMRT systems are currently being marketed. Many of these systems appear to be unique, and manufacturers often emphasize design differences as they argue the merits of their particular approach. This paper focuses on highlighting the underlying feature that is intrinsically part of all IMRT systems. On the other hand, major differences often appear at the implementation stage for dose delivery. Such variations are evident because each manufacturer has a unique approach to balancing the issues of treatment time, leakage radiation reaching the patient's total body, aperture approximation of the ideal intensity maps, increasing the angles of approach for the treatment fields, integration of on-line imaging, selection of treatment distance, availability of different photon energies, and overall system complexity (i.e., cost). How these different issues are handled in the process of system design affects the relative advantages and disadvantages that appear in the final product. This paper takes the approach of dividing the various IMRT methods into categories that are divided roughly along the lines of the technique used during dose delivery to approximate the intensity patterns. Other features of each system are included under these sub-sections.     

Urethral stricture following high dose rate brachytherapy for prostate cancer

Purpose

To evaluate the incidence, timing, nature and outcome of urethral strictures following high dose rate brachytherapy (HDRB) for prostate carcinoma.

Methods and materials

Data from 474 patients with clinically localised prostate cancer treated with HDRB were analysed. Ninety percent received HDRB as a boost to external beam radiotherapy (HDRBB) and the remainder as monotherapy (HDRBM). Urethral strictures were graded according to the Common Terminology Criteria for Adverse Events v3.0.

Results

At a median follow-up of 41 months, 38 patients (8%) were diagnosed with a urethral stricture (6-year actuarial risk 12%). Stricture location was bulbo-membranous (BM) urethra in 92.1%. The overall actuarial rate of grade 2 or more BM urethral stricture was estimated at 10.8% (95% CI 7.0-14.9%), with a median time to diagnosis of 22 months (range 10-68 months). All strictures were initially managed with either dilatation (n = 15) or optical urethrotomy (n = 20). Second line therapy was required in 17 cases (49%), third line in three cases (9%) and 1 patient open urethroplasty (grade 3 toxicity). Predictive factors on multivariate analysis were prior trans-urethral resection of prostate (hazard ratio (HR) 2.81, 95% CI 1.15-6.85, p = 0.023); hypertension (HR 2.83, 95% CI 1.37-5.85, p = 0.005); and dose per fraction used in HDR (HR for 1 Gy increase per fraction 1.33, 95% CI 1.08-1.64, p = 0.008).

Conclusions

BM urethral strictures are the most common late grade 2 or more urinary toxicity following HDR brachytherapy for prostate cancer. Most are manageable with minimally invasive procedures. Both clinical and dosimetric factors appear to influence the risk of stricture formation.     

Modeling positioning uncertainties of prostate cancer external beam radiation therapy using pre-treatment data

Purpose

To investigate the influence of treatment plan data and image guidance (IG) on positioning uncertainty during prostate cancer (PCa) radiotherapy (RT).

Methods

Body mass index (BMI), planning target volume (PTV), bladder volume (BV), and rectal cross section area (RCS) were collected for 267 consecutive PCa patients undergoing daily IGRT. Radiographic isocenter corrections to intra-prostatic fiducials for 12,490 treatment fractions were used to derive random (RE) and systematic (SE) inter-fraction uncertainties for the cardinal axes. These data were used to simulate RE and SE for weekly IG and Action Level (AL)-IG treatment protocols.

Results

SE and RE were 2–5 and 3–4 mm in the cardinal axes, respectively, during simulation of no IG. Without IG, positive correlations (p < 0.01) were noted for (1) anterior-posterior RE vs. RCS and BV and (2) cranio–caudal RE vs. RCS, BV and BMI. The RE increase was 3 mm for the highest quartile of RCS, BV and BMI. Daily IGRT eliminated this relationship. 3D IG corrections of 1 cm or more occured in 27% of treatment fractions and in 97% of patients.

Conclusion

PCa patients with elevated pre-treatment BV, RCS and BMI have increased inter-fractionation positioning uncertainty and appear the primary candidates for daily IGRT.     

Intensity modulated radiation therapy (IMRT) in the management of prostate cancer

Intensity modulated radiation therapy (IMRT) is gaining widespread use in the radiation therapy community. Prostate cancer is the ideal target for IMRT due to the growing body of literature supporting dose escalation and normal tissue limitations. The need for dose escalation and the limits of conventional radiation therapy necessitate precise patient and prostate localization as well as advanced treatment delivery. The treatment of prostate cancer has been dramatically altered by the introduction of technology that can focus on the target while avoiding normal tissue. IMRT is evolving as the treatment of the future for prostate cancer.     

Urinary toxicity after high dose intensity modulated radiotherapy as primary therapy for prostate cancer

Background and purpose

Urinary toxicity plays a major role in the quality of life (QOL) of patients treated with external beam radiotherapy as primary therapy for prostate cancer.In this study we report on:(1) Incidence of acute and late GU toxicity after intensity modulated radiotherapy (IMRT) for prostate cancer at Ghent University Hospital (GUH).(2) Time evolution of pre-IMRT and IMRT-induced acute and late GU toxicity.

Materials and methods

At GUH, 260 patients with a follow-up of ?12 months were treated with IMRT for prostate cancer. The incidence and evolution of GU toxicity were recorded.

Results

Acute grades 3, 2 and 1 GU toxicity occurred in 8%, 42% and 42% of the patients, respectively. Late grades 3, 2 and 1 GU toxicity occurred in 3%, 19% and 40% of the patients, respectively.During therapy baseline grade 1 symptoms increased into grade 2 acute GU toxicity in 48%. After 1 and 2 years, 60% and 70% of the patients, respectively, had less GU symptoms when compared to the pre-treatment status.

Conclusion

IMRT induces mild GU toxicity. There is an improvement in pre-IMRT obstructive miction disorders.     

A significant decrease in rectal volume and diameter during prostate IMRT

Purpose

To record changes in rectal volume (RV) and diameter (RD) of patients with prostate adenocarcinoma prior to and at an interim period during radiotherapy, which could potentially affect treatment toxicity and tumor control.

Methods

Three hundred and fifteen patients treated with intensity modulated radiotherapy (IMRT) underwent planning CT scans before radiation and after 45 Gy. For each scan, RV and RD were recorded and compared using a two-tailed paired t-test. Robust linear regression analysis assessed correlation between initial RV and percent RV change.

Results

The mean change in RV was −8.62 cm³ and in RD was −0.19 cm³, (p < 0.05). A decrease ?10% in RV and RD was seen in 159 patients (50.5%) and 117 patients (37.1%), respectively. Patients with ?10% volume change had larger initial RVs than those with <10% decrease, (78.1 vs. 50.8 cm³, p < 0.0001).

Conclusions

A significant decrease in RV and RD occurs during prostate IMRT delivery. More than half of patients had decreased RV and over a third had decreased RD. This observation is pertinent to prostate localization, planning margins, and implies that dose-volume histogram (DVH) analysis of rectal irradiation based on pre-treatment CT scanning may inaccurately estimate the risk of rectal toxicity when the initial RV is larger than 70 cm³.     

Data handling in radiation therapy in the age of image-guided radiation therapy

Image-guided radiation therapy (IGRT) in the modern sense includes large volumetric image sets and high-resolution planar images. In addition to the issue of the sheer size of the data under consideration in IGRT is the critical need for the data to be available in the necessary situation in a timely and reliable fashion. Standards exist for the format of much of the data needed to perform IGRT, but the information workflow is not "standardized" (formal or ad hoc) and details of the use of the standards are only recently being constrained to ensure interoperability. Depending on the interpretation of the scope of IGRT or the desired workflow of the IGRT system, not all of the information that needs to be exchanged between systems is yet standardized nor is the means to exchange the information. The organization of the different types of data needed for IGRT for easy navigation is addressed by commercially available products from multiple vendors; however, this is also an area in which standards and consistency in the clinical environment are catching up to the market. The critical questions a clinician needs answers to include the following: (1) What kinds of data will I need to store and communicate between the pieces of my IGRT system? (2) How much storage will I need to address the volumes of data produced? (3) How long do I need to store (and be able to access) the data? (4) How will the pieces of my IGRT system communicate the necessary information between them (what standards or technical frameworks apply and do the pieces conform or adhere to them)? (5) What are the time constraints on getting information from "where it is" to "where it needs to be"? and (6) Is my IGRT system as a whole capable of providing me with the workflow necessary for my clinical environment or, alternatively, what do the providers of my IGRT system need to do to enable my required workflow? The body of this article examines these issues in greater detail to enable clinicians and clinical support personnel to frame the questions in a practical manner and develop answers that assist in the successful deployment of IGRT.