Improved Clinical Outcomes With High-Dose Image Guided Radiotherapy Compared With Non-IGRT for the Treatment of Clinically Localized Prostate Cancer

doi:10.1016/j.ijrobp.2011.11.047

International Journal of Radiation OncologyBiologyPhysics

Volume 84, Issue 1, 1 September 2012, Pages 125-129

https://doi.org/10.1016/j.ijrobp.2011.11.047 Get rights and content

Purpose

To compare toxicity profiles and biochemical tumor control outcomes between patients treated with high–dose image-guided radiotherapy (IGRT) and high–dose intensity-modulated radiotherapy (IMRT) for clinically localized prostate cancer.

Materials and Methods

Between 2008 and 2009, 186 patients with prostate cancer were treated with IGRT to a dose of 86.4 Gy with daily correction of the target position based on kilovoltage imaging of implanted prostatic fiducial markers. This group of patients was retrospectively compared with a similar cohort of 190 patients who were treated between 2006 and 2007 with IMRT to the same prescription dose without, however, implanted fiducial markers in place (non-IGRT). The median follow-up time was 2.8 years (range, 2–6 years).

Results

A significant reduction in late urinary toxicity was observed for IGRT patients compared with the non-IGRT patients. The 3-year likelihood of grade 2 and higher urinary toxicity for the IGRT and non-IGRT cohorts were 10.4% and 20.0%, respectively (p = 0.02). Multivariate analysis identifying predictors for grade 2 or higher late urinary toxicity demonstrated that, in addition to the baseline Internatinoal Prostate Symptom Score, IGRT was associated with significantly less late urinary toxicity compared with non-IGRT. The incidence of grade 2 and higher rectal toxicity was low for both treatment groups (1.0% and 1.6%, respectively; p = 0.81). No differences in prostate-specific antigen relapse-free survival outcomes were observed for low- and intermediate-risk patients when treated with IGRT and non-IGRT. For high-risk patients, a significant improvement was observed at 3 years for patients treated with IGRT compared with non-IGRT.

Conclusions

IGRT is associated with an improvement in biochemical tumor control among high-risk patients and a lower rate of late urinary toxicity compared with high–dose IMRT. These data suggest that, for definitive radiotherapy, the placement of fiducial markers and daily tracking of target positioning may represent the preferred mode of external-beam radiotherapy delivery for the treatment of prostate cancer.

Introduction

Intensity-modulated radiotherapy (IMRT) for prostate cancer has facilitated the delivery of high radiation doses to the prostate and is associated with excellent biochemical tumor control outcomes for patients with localized disease (1). Given the highly conformal nature of this form of therapy, surrounding normal tissues such as the rectum and bladder can be effectively spared from being exposed to high prescription doses, leading to fewer treatment complications. A recent report of our long-term toxicity outcomes with IMRT corroborated a lower morbidity profile after high–dose IMRT, with an observed incidence of grade 2 rectal and urinary toxicities at 2% and 15%, respectively (2).

Image-guided radiotherapy (IGRT) for prostate cancer takes advantage of intraprostatic fiducial marker placement and imaging of the target before the daily dose or via daily pretreatment cone-beam imaging. This allows for the adjustment and positional correction of the radiation beams based on daily imaging to account for the variability of the target position. In addition to correction of interfractional motion with the use of fiducial markers or pretreatment imaging, commercially available systems can also track prostate motion during the delivered fraction (intrafractional motion correction) to further enhance accuracy of the therapy. IGRT potentially represents a more accurate form of dose delivery for patients receiving radiotherapy for prostate cancer. Given the more targeted nature of these treatments, margins routinely used around the clinical target volume to account for organ motion and variability of the target position can be further reduced if daily target positional correction is done.

In 2007 we initiated IGRT at our institution with the implantation of fiducial markers for all patients receiving definite radiotherapy for prostate cancer. We decided at that time not to alter our clinical target volume margins, and these margins were maintained as 1 cm circumferentially except at the prostate–rectal interface, where a 6-mm margin was used. We hypothesized that the use of IGRT should be associated with less toxicity, given its enhanced accuracy. To this end, we retrospectively compared the outcomes of a cohort of patients treated with definitive IGRT using implanted fiducial markers to the outcomes in a cohort treated with the same dose and margins with IMRT without daily target position correction (non-IGRT). In this report we compare the toxicity and tumor control outcomes of these two patient cohorts. Our findings are consistent with a lower incidence of late urinary toxicity and improved early biochemical tumor control for high-risk patients in the IGRT-treated patients compared with the non-IGRT cohort.

Section snippets

Methods and Materials

Beginning in 2007, IGRT was initiated at our institution as part of the routine treatment of patients with definitive radiotherapy for prostate cancer using implanted fiducial markers. From that time until October 2009, 186 patients were treated with IGRT to a dose of 86.4 Gy using implanted prostatic fiducial markers for Stages T1–T3 prostate cancer at Memorial Sloan-Kettering Cancer Center (MSKCC). The 86.4-Gy prescription dose was the standard dose delivered to patients receiving monotherapy

Results

Table 2 compares the incidence of acute rectal and urinary toxicities observed in the IGRT and non-IGRT treatment groups. No differences were observed between the treatment groups for grade 2 and higher acute GI toxicity rates (p = 0.30). However, for genitourinary acute toxicity, a significantly higher incidence of acute grade 2 and higher toxicities was observed for the non-IGRT cohort than in the IGRT group (p = 0.05).

Figure 1 demonstrates a significant difference in late urinary toxicity

Discussion

To our knowledge, this is the first report to compare outcomes in patients with localized prostate cancer treated with IMRT and IGRT and to demonstrate a difference in toxicity and tumor control outcomes. The comparison is unique in that both groups were treated with the same radiation dose and with similar margins for the PTV. Indeed, the only difference between the two groups was whether daily positional corrections were used via imaging of implanted fiducial markers. We nevertheless observed

References (5)

M.J. Zelefsky et al.
Long-term outcome of high dose intensity modulated radiation therapy for patients with clinically localized prostate cancer
J Urol
(2006)
M.J. Zelefsky et al.
Clinical experience with intensity modulated conformal radiotherapy (IMRT) in prostate cancer
Radiother Oncol
(2000)

There are more references available in the full text version of this article.

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Ultra-hypofractionated prostate cancer radiotherapy: Dosimetric impact of real-time intrafraction prostate motion and daily anatomical changes
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To retrospectively assess the differences between planned and delivered dose during ultra-hypofractionated (UHF) prostate cancer treatments, by evaluating the dosimetric impact of daily anatomical variations alone, and in combination with prostate intrafraction motion.
Prostate intrafraction motion was recorded with a transperineal ultrasound probe in 15 patients treated by UHF radiotherapy (36.25 Gy/5 fractions). The dosimetric objective was to cover 99 % of the clinical target volume with the 100 % prescription isodose line. After treatment, planning CT (pCT) images were deformably registered onto daily Cone Beam CT to generate pseudo-CT for dose accumulation (accumulated CT, aCT). The interplay effect was accounted by synchronizing prostatic shifts and beam geometry. Finally, the shifted dose maps were accumulated (moved-accumulated CT, maCT).
No significant change in daily CTV volumes was observed. Conversely, CTV V_100% was 98.2 ± 0.8 % and 94.7 ± 2.6 % on aCT and maCT, respectively, compared with 99.5 ± 0.2 % on pCT (p < 0.0001). Bladder volume was smaller than planned in 76 % of fractions and D_5cc was 33.8 ± 3.2 Gy and 34.4 ± 3.4 Gy on aCT (p = 0.02) and maCT (p = 0.01) compared with the pCT (36.0 ± 1.1 Gy). The rectum was smaller than planned in 50.3 % of fractions, but the dosimetric differences were not statistically significant, except for D1cc, found smaller on the maCT (33.2 ± 3.2 Gy, p = 0.02) compared with the pCT (35.3 ± 0.7 Gy).
Anatomical variations and prostate movements had more important dosimetric impact than anatomical variations alone, although, in some cases, the two phenomena compensated. Therefore, an efficient IGRT protocol is required for treatment implementation to reduce setup errors and control intrafraction motion.
Decision-making processes in image guided radiotherapy: A think aloud study
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3D Image Guided Radiotherapy (IGRT) using Cone Beam Computer Tomography (CBCT) has been implemented for a range of treatment sites across the UK in the last decade. A paucity of evidence exists to understand how radiation therapists (RTTs) make clinical decisions during image interpretation as part of the IGRT process. The aim of this study was to investigate the decision-making processes used by RTTs during image interpretation of IGRT.
Case study methodology was adopted utilising a think aloud observational method with follow-up interviews. 12 RTTs were observed and interviewed across three UK radiotherapy centres. Participants were observed reviewing and making clinical decisions in a simulated environment using clinical scenarios developed in partnership with each centres’ Clinical Imaging Lead. Protocol analysis was used to analyse the observational data and thematic analysis was used to analyse the interview data.
A range of approaches to decision-making was observed which varied in length from nine phrases to 57 (mean 24) per case. Six themes emerged from the data: Set Sequence, Site Specific Clinical Priorities, Initial Gross Review, Decision to treat, Compromise and experience. In addition, three cognitive decision-making processes were identified: Simple linear, Linear repeating and Intuitive decision-making process. The findings of the study align with general principles of expert performance, whereby experience in a specific scope of practice is more beneficial in developing expertise than overall experience.
This study has provided new and original insight in the decision-making processes of RTTs. The study has highlighted three process models to explain how RTTs make decisions during IGRT: Simple linear, Linear repeating and Intuitive decision-making process. Intuitive processes are widely accepted to be error prone and linked to bias. When using this process, some RTTs followed this with a confirmation phase. This second phase of the process should be encouraged when teaching IGRT. The results of the study support the concept of expert performance, where performance and expertise are only improved by exposing individuals to specific types of experiences. RTTs, managers and Higher Education Institutions are encouraged to review these models and implement them into IGRT training. It is clear from the evidence base that understanding how we make decisions, enables us to develop expertise and reduce errors during the decision-making process.
La radiothérapie 3D guidée par l'image (IGRT) utilisant la tomographie à faisceau conique a été mise en œuvre dans un certain nombre de sites de traitement à travers le Royaume-Uni au cours de la dernière décennie. Il existe peu de données permettant de comprendre comment les radiothérapeutes (RTT) prennent des décisions cliniques lors de l'interprétation des images dans le cadre du processus de radiothérapie guidée par l'image. L'objectif de cette étude était d'examiner les processus décisionnels utilisés par les RTT pendant l'interprétation des images de l'IGRT.
La méthodologie de l'étude de cas a été adoptée en utilisant une méthode d'observation à haute voix avec des entretiens de suivi. 12 RTT ont été observées et interrogées dans trois centres de radiothérapie britanniques. Les participants ont été observés en train d'examiner et de prendre des décisions cliniques dans un environnement simulé à l'aide de scénarios cliniques élaborés en partenariat avec le responsable de l'imagerie clinique de chaque centre. L'analyse des protocoles a été utilisée pour analyser les données d'observation et l'analyse thématique a été utilisée pour analyser les données des entretiens.
Un éventail d'approches de la prise de décision a été observé, dont la longueur variait de neuf phrases à 57 (moyenne de 24) par cas. Six thèmes ont émergé des données : Séquence définie, Priorités cliniques spécifiques au site, Examen brut initial, Décision de traiter, Compromis et expérience.
En outre, trois processus cognitifs de prise de décision ont été identifiés : Linéaire simple, Linéaire répétitif et Processus décisionnel intuitif. Les résultats de l'étude s'alignent sur les principes généraux de la performance des experts, selon lesquels l'expérience dans un domaine de pratique spécifique est plus bénéfique au développement de l'expertise que l'expérience globale.
Cette étude a apporté un éclairage nouveau et original sur les processus décisionnels des RTT. Elle a mis en évidence trois modèles de processus pour expliquer comment les RTT prennent des décisions pendant l'IGRT : le processus décisionnel linéaire simple, le processus décisionnel linéaire répétitif et le processus décisionnel intuitif. Il est largement admis que les processus intuitifs sont sujets à l'erreur et liés à la partialité. Lorsqu'elles utilisent ce processus, certains RTT le font suivre d'une phase de confirmation. Cette deuxième phase du processus devrait être encouragée lors de l'enseignement de l'IGRT. Les résultats de l'étude soutiennent le concept de performance experte, selon lequel la performance et l'expertise ne sont améliorées qu'en exposant les individus à des types d'expériences spécifiques. Les RTT, les responsables et les établissements d'enseignement supérieur sont encouragés à examiner ces modèles et à les mettre en œuvre dans la formation à l'IGRT. Il est clair, d'après les données disponibles, que comprendre comment nous prenons des décisions nous permet de développer notre expertise et de réduire les erreurs au cours du processus de prise de décision.
Radiation-induced recto-urinary fistula: A dreaded complication with devastating consequences
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This study was undertaken to evaluate our 16-year experience with fistulas between the rectum and urethra or urinary bladder, collectively called recto-urinary fistulas (RUFs), and their devastating consequences in patients treated with radiation for prostate cancer.
We downloaded the records of all patients with radiation-related RUFS from 2004 to 2020 at our institution using the electronic medical record system. Details concerning patient demographics, clinical presentation, diagnostic approaches and surgical management were obtained and assessed.
We identified a total of seven patients with radiation-induced RUFS: all were male and had an average age of 66 at diagnosis. Each had a history of prostate cancer that was treated with external, internal (i.e.brachytherapy), or combination radiation therapy. No fistulas were noted in patients treated with radiation for another malignancy. Radiation proctitis with rectal ulcer formation occurred in 6 of 7 patients. Common symptoms included fecaluria, pneumaturia, urine leakage via rectum, rectal pain and urinary tract infection. CT scanning was the most useful diagnostic tool. Once confirmed, fistula management included both urinary and fecal diversion in all patients. Only one patient received definitive repair of the fistula. Five others either died before repair could be attempted or had prohibitive co-morbid diseases. One patient declined repair.
Although rare, the development of a recto-urinary fistula is a dreaded complication. Our results indicate that radiation proctitis with rectal ulcer formation precedes fistula formation in most patients and must be aggressively managed. While fecal and urinary diversion can manage fistula symptoms in the majority of patients, definitive fistula repair is only possible in selected individuals.
Targeting Education as a Barrier to Implement Hypofractionation: Results of a Country-Wide Training Program
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Access to radiation therapy in low- and middle-income countries (LMICs) could be improved with modern hypofractionated radiation therapy schedules, although their adoption remains limited. We aimed to evaluate perceptions regarding hypofractionation and the effect of a dedicated curriculum in an LMIC.
We developed a pilot e-learning hypofractionation curriculum focused on breast, prostate, rectal cancer, and high-grade glioma in Colombia. International educators taught 13 weekly, 90-minute sessions. Participants completed pre- and postcurriculum questionnaires regarding hypofractionation attitudes, 1 to 5 Likert-scale self-confidence, and practices for 12 clinical scenarios. Physicians’ responses were categorically scored “1” (for hypofractionation or ultrahypofractionation) or “0” (for conventional fractionation). We used the paired t test to measure pre- versus postcurriculum differences in self-confidence and the McNemar test to detect differences in hypofractionation selection.
Across 19 cities in Colombia, 147 clinicians enrolled: 61 radiation oncologists, 6 radiation oncology residents, 59 medical physicists, 18 physics residents, and 3 other staff. Among physicians, education was the greatest barrier to select hypofractionation, common in ultrahypofractionation for prostate (77.6%) and breast cancer (74.6%) and less common for moderate hypofractionation of prostate (61.2%) and breast cancer (52.2%). Additional perceived barriers included unfamiliarity with clinic protocols (7%-22%), clinical experience (5%-15%), personal preference (3%-16%), and lack of technology (3%-20%), with variation across different clinical settings. After the curriculum, paired (n = 38) physicians’ selection of hypofractionation increased across all disease sites (mean aggregate score 6.2/12 vs 8.2/12, P <.001). Self-confidence among paired clinicians (n = 87) increased for prostate ultrahypofractionation (+0.45), rectal ultrahypofractionation (+0.43), breast hypofractionation (+0.38), and prostate hypofractionation (+0.23) (P ≤ .03).
In an LMIC with a bundled payment system, lack of education and training was a perceived barrier for implementation of hypofractionation and ultrahypofractionation. A targeted e-learning hypofractionation curriculum increased participant confidence and selection of hypofractionated schedules.
A new target localization method for image-guided radiation therapy of prostate cancer
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In imaged-guided radiation therapy (IGRT), target localization is usually done with rigid-body registration based on anatomy matching. Problems arise when the target volume can only be matched partially due to inter-fractional organ motion and deformation, resulting in deteriorated target coverage and critical structure sparing. A new target localization method is investigated in which the treatment target volume is aligned with the prescription isodose surface. Our study included 15 prostate patients previously treated with intensity-modulated radiation therapy (IMRT). Patient setup and target localization were performed using a CT-on-rails system before and after the IMRT treatment. IMRT plans were generated on the original simulation CTs (15) and the same MUs and leaf sequences were used to compute the dose distributions on post-treatment CTs (98) with the isocenter adjustments based on either anatomical structure matching or prescription isodose surface alignment. When patients were aligned with the traditional anatomy matching method, the dose to 95% of the CTV, D₉₅, received 74.0 – 77.6 Gy and the minimum CTV dose, D_min, was 61.9 – 71.6 Gy, respectively, in the cumulative dose distributions. The rectal dose-volume constraints were violated in 35.7% of the treatment fractions. When patients were aligned using the new localization method, the dose to 95% of the CTV, D₉₅, received 74.0 – 78.2 Gy and the minimum CTV dose, D_min, was 68.4 – 71.6 Gy, respectively, in the cumulative dose distributions. The rectal dose-volume constraints were violated in 17.3% of the treatment fractions. Traditional IGRT target localization based on anatomy matching is effective for population-based PTV margins but not ideal for those patients with large inter-fractional prostate rotation/deformation due to large rectal and bladder volume variation. The new method using the prescription isodose surface to align the target volume could improve the target coverage and rectal sparing for these patients, which can be implemented clinically to improve target dose delivery accuracy.
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: Note—An online CME test for this article can be taken at http://astro.org/MOC.

: Conflict of interest: none.

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Clinical InvestigationImproved Clinical Outcomes With High-Dose Image Guided Radiotherapy Compared With Non-IGRT for the Treatment of Clinically Localized Prostate Cancer

Purpose

Materials and Methods

Results

Conclusions

Introduction

Section snippets

Methods and Materials

Results

Discussion

J Urol

Radiother Oncol

Clinical Investigation
Improved Clinical Outcomes With High-Dose Image Guided Radiotherapy Compared With Non-IGRT for the Treatment of Clinically Localized Prostate Cancer