Real-time Image-guided Adaptive-predictive Prostate Radiotherapy using Rectal Diameter as a Predictor of Motion

doi:10.1016/j.clon.2016.09.019

Clinical Oncology

Volume 29, Issue 3, March 2017, Pages 180-187

https://doi.org/10.1016/j.clon.2016.09.019 Get rights and content

Highlights

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A method for image-guided adaptive prostate radiotherapy is proposed.
•
Existing and widely available technologies are used.
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Possible normal tissue complication probability reductions for bladder and rectum.

Abstract

Aims

To investigate a relationship between maximum rectal diameter (MRD) on pre-treatment cone beam computed tomography (CBCT) and intra-fraction prostate motion, in the context of an adaptive image-guided radiotherapy (IGRT) method.

Materials and methods

The MRD was measured on 2125 CBCTs from 55 retrospective patient datasets and related to prostate displacement from intra-fraction imaging. A linear regression model was developed to determine a threshold MRD associated with a high probability of small prostate displacement. Standard and reduced adaptive margin plans were created to compare rectum and bladder normal tissue complication probability (NTCP) with each method.

Results

A per-protocol analysis carried out on 1910 fractions from 51 patients showed with 90% confidence that for a MRD ≤ 3 cm, prostate displacement will be ≤5 mm and that for a MRD ≤ 3.5 cm, prostate displacement will be ≤5.5 mm. In the first scenario, if adaptive therapy was used instead of standard therapy, median reductions in NTCP for rectum and bladder were 0.5% (from 9.5% to 9%) and 1.3% (from 6.6% to 5.3%), respectively. In the second scenario, the NTCP for rectum and bladder would have median reductions of 1.1% and 2.6%, respectively.

Conclusions

We have identified a potential method for adaptive prostate IGRT based upon predicting small prostate intra-fraction motion by measuring MRD on pre-treatment CBCT.

Introduction

Radiotherapy dose escalation for prostate cancer offers improved biochemical control, but may also lead to increasing toxicity, which is concerning for patients with long-term survival prospects [1]. Prostate cancer radiotherapy clinical target volumes most commonly include the prostate with or without the seminal vesicles. The rectum, bladder and penile bulb are organs at risk in immediate proximity to the prostate and are partially included in the planning target volume (PTV). Minimising PTV margins where possible would reduce the risk of toxicity and potentially allow safe dose escalation.

Historic inter-fraction and intra-fraction prostate motion data are commonly used to calculate PTV margins. These data take into account random treatment errors for all treatment fractions, many of which will not be present for each fraction. Two key components of prostate intra-fraction motion are the filling of the rectum and the duration of the treatment. Cine-magnetic resonance imaging has shown that patients who present with an empty rectum may be at much lower risk of intra-fraction prostate motion compared with patients who present with a full rectum [2], [3]. Several studies have also shown that the longer the fraction duration, the greater the risk of prostate motion [3], [4], [5].

To reduce the effect of random errors during prostate radiotherapy, intra-fraction monitoring using methods such as radiofrequency transponders, stereoscopic kV systems and using on-board imaging, may allow reductions of margins down to 5 mm or less [6], [7], [8]. Greatly reducing treatment times with volumetric modulated arc therapy (VMAT) and flattening filter free modes may also reduce the probability of intra-fraction motion [5]. For those without access to new technologies, alternative methods to reduce margins could be investigated.

Our data has shown intra-fraction motion of greater than 5 mm in only 4.7% of fractions [4], so identifying fractions with reduced motion is one possibility. Adaptive radiotherapy offers methods to reduce PTV margins when conditions are appropriate. Previous studies have outlined offline [9], [10], [11], hybrid [12], [13] and online protocols [14], [15], [16], [17], [18], [19] for adaptive prostate radiotherapy. None of these has predicted daily prostate motion based on cone beam computed tomography (CBCT) rectal presentation.

This study investigated the relationship between rectal diameter on pre-treatment CBCT as a predictor of small intra-fraction prostate motion, which could be used in an adaptive image-guided radiotherapy (IGRT) protocol. We also investigated other predictors of prostate motion, such as the presence of bowel gas within treatment fields or superior to the treated volume at CBCT. We assessed the image quality of CBCT and its effect on the adaptive method.

Section snippets

Dataset Selection

This study used retrospective datasets from 55 consecutive patients treated at the Townsville Cancer Centre between July 2011 and August 2012 with daily CBCT imaging before treatment and megavoltage electronic portal images (EPI) acquired during treatment delivery, which allowed analysis of intra-fraction prostate motion. We received ethics approval from the Townsville Hospital and Health Service Human Research Ethics Committee and the Peter MacCallum Cancer Centre Ethics Committee. Eligible

Data Exceptions

Of 55 patients included in this study, 45 received 39 treatment fractions, five received 38 and the remaining five received 37 fractions. Four patients had a misplaced fiducial marker (i.e. placed outside the prostate capsule), which appeared to affect the intra-fraction motion assessment and were excluded in a per-protocol analysis. In these datasets, we compared inter-marker distances on the planning scan to locations on the treatment scans by measuring the centroid of each fiducial marker.

Discussion

This study used MRD and intra-fraction prostate displacement data from 1910 treatment fractions (per-protocol analysis) to show a potential adaptive-predictive IGRT technique for prostate radiotherapy based upon pre-treatment CBCT MRD. MRD seems to be a fast, assessable and reliable metric for predicting a high probability of minimal intra-fraction prostate displacement. Combining this with selective use of an adaptive plan with smaller PTV expansion allows for small reductions in rectum NTCP

Conclusions

Our study has shown a potential method for adaptive-predictive prostate IGRT, predicting small prostate intra-fraction motion by measuring MRD on pre-treatment CBCT. Further research is required to show the precise relationship between MRD and prostate motion for safe clinical implementation and to explore individualised approaches such as individualised MRDs. This method uses existing technologies and, with further understanding of the dosimetric impacts of the method, it may be advantageous

Acknowledgements

The authors would like to acknowledge the support of the Department of Radiation Oncology at the Peter MacCallum Cancer Centre and the Townsville Cancer Centre. Special thanks to Christina Finlason for contouring guidance.

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External beam radiation therapy to the prostate is typically delivered after verification of prostatic position with image guidance. Prostate motion can occur during the delivery of each radiation treatment between the time of localization imaging and completion of treatment. The objective of this work is to review the literature on intrafraction motion (IFM) of the prostate during radiation therapy and offer clinical recommendations on management.
A comprehensive literature review was conducted on prostate motion during prostate cancer radiation therapy. Information was organized around 3 key clinical questions, followed by an evidence-based recommendation.
IFM of the prostate during radiation therapy is typically ≤3 mm and is unlikely to compromise prostate dosimetry to a clinically meaningful degree for men treated in a relatively short treatment duration with planning target volume (PTV) margins of ≥3 to 5 mm. IFM of 5 mm or more has been observed in up to ∼10% of treatment fractions, with limited dosimetric effect related to the infrequency of occurrence and longer fractionation of therapy. IFM can be monitored in continuous or discontinuous fashion with a variety of imaging platforms. Correction of IFM may have the greatest value when tighter PTV margins are desired (such as with stereotactic body radiation therapy or intraprostatic nodule boosting), ultrahypofractionated courses, or when treatment time exceeds several minutes.
This focused review summarizes literature and provides practical recommendations regarding IFM in the treatment of prostate cancer with external beam radiation therapy.
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A scoping literature review was conducted to identify gastrointestinal (GI) factors most likely to influence prostate motion during radiotherapy. We proffer that patient specific measurement of these GI factors could predict motion uncertainty during radiotherapy, facilitating personalised care by optimising treatment technique e.g., daily adaption or via bespoke patient pre-habilitation and preparation.
The scoping review was undertaken as per JBI guidelines. Searches were conducted across four databases: Ovid Medline®, EMBASE, CINAHL and EBSCO discovery. Articles written in English from 2010-present were included. Those pertaining to paediatrics, biological women exclusively, infectious and post-treatment GI morbidity and diet were excluded.
Common GI factors impacting men were identified and related symptoms, incidence and measurement tools examined. Prevalence among persons with prostate cancer was explored and suitable assessment tools discussed.
A preliminary search identified four prominent GI-factors: mental health, co-morbidity and medication, physical activity, and pelvic floor disorder. The scoping search found 3644 articles; 1646 were removed as duplicates. A further 1249 were excluded after title and abstract screening, 162 remained subsequent to full text review: 42 mental health, 53 co-morbidity and medication, 39 physical activity and 28 pelvic floor disorder.
Six GI factors prevalent in the prostate cancer population and estimated most likely to influence prostate motion were identified: depression, anxiety, diabetes, obesity, low physical activity, and pelvic floor disorder. Reliable, quick, and easy to use tools are available to quantify these factors.
A comprehensive GI factor assessment package suitable to implement into the radiotherapy clinic has been created. Unveiling these GI factors upfront will guide improved personalisation of radiotherapy.
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Citation Excerpt :
Despite methodological differences, both on-line and off-line methods need information about the potential movements of the irradiated region relative to the anatomy from treatment planning and the dose delivered relative to planned dose. Methodology of prediction of intra-fraction motion of prostate showed by Oates et al. [43] seems to be an optimal method that connects the on-line and off-line strategies. While it allows to set an adequate CTV-to-PTV margin (just like the off-line strategies), it is implemented in the on-line regime.
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A systematic literature search was carried out using the PubMed engine, based upon the following terms: adaptive radiotherapy, intensity modulated radiotherapy, volumetric modulated arc therapy and image-guided and dose-guided radiotherapy. Overall, 58 relevant studies were included: 31 about on-line strategies of adaptation, 6 about off-line strategies, and 21 that highlighted the technical aspects of CBCT usage.
The off-line strategies provide a statistical prediction for each individual patient for the rest of treatment. The on-line strategies aim to resolve the potential disagreements between a planned and delivered dose directly before the specific fraction. Both strategies need information about the movements of the irradiated region relative to the target from treatment planning and the dose delivered relative to the planned dose. Quality of CBCT is very important for the accuracy of the adaptation procedures. While the errors caused by the insufficient quality of anatomy visualisation with CBCT are currently minimized, there are still problems with the proper dose computation. The most accurate methods are able to minimize the calculation error to 3%.
CBCT plays a significant role in each step of adaptive radiation therapy of prostate cancers, starting from registration procedures through setting an appropriate CTV-to-PTV margin to fraction dose recalculations, and its cumulation/monitoring relative to the planned dose.
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Aim of this paper is to investigate the plan quality of a tri-Co-60 MRI-Hybrid system for intensity-modulated radiation therapy (IMRT) in patients affected by locally advanced rectal cancer (LARC) undergoing neo-adjuvant radiotherapy.
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B_on and B_off tri-Co-60 IMRT plans showed no relevant differences. Mean values of PTV1 and PTV2 receiving at least 95% of the D_p (V_95%) were higher than 95% in all treatment plans. All plans met the V_105% constraint for the PTV1. Mean values of V_105% for the PTV2 were 14.8, 5.0, and 7.3% respectively for tri-Co-60, VMAT and IMRT. Mean Wu’s HI values were similar in all plans (7.4–7.8%). All plans met the V_45Gy constraint for small bowel, but mean V_45Gy value was higher with tri-Co-60.
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Original ArticleReal-time Image-guided Adaptive-predictive Prostate Radiotherapy using Rectal Diameter as a Predictor of Motion

Highlights

Abstract

Aims

Materials and methods

Results

Conclusions

Introduction

Section snippets

Dataset Selection

Data Exceptions

Discussion

Conclusions

Acknowledgements

Clin Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Radiother Oncol

Urology

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Eur Urol

Original Article
Real-time Image-guided Adaptive-predictive Prostate Radiotherapy using Rectal Diameter as a Predictor of Motion