Role of the Technical Aspects of Hypofractionated Radiation Therapy Treatment of Prostate Cancer: A Review

doi:10.1016/j.ijrobp.2014.08.006

International Journal of Radiation OncologyBiologyPhysics

Volume 91, Issue 1, 1 January 2015, Pages 182-195

https://doi.org/10.1016/j.ijrobp.2014.08.006 Get rights and content

The increasing use of moderate (<35 fractions) and extreme (<5 fractions) hypofractionated radiation therapy in prostate cancer is yielding favorable results, both in terms of maintained biochemical response and toxicity. Several hypofractionation (HF) schemes for the treatment of prostate cancer are available, although there is considerable variability in the techniques used to manage intra-/interfraction motion and deliver radiation doses. We performed a review of the published studies on HF regimens as a topic of interest for the Stereotactic Ablative Radiotherapy working group, which is part of the Italian Association of Medical Physics. Aspects of organ motion management (imaging for contouring, target volume definition, and rectum/bladder preparation) and treatment delivery (prostate localization, image guided radiation therapy strategy and frequency) were evaluated and categorized to assess outcome relative to disease control and toxicity. Despite the heterogeneity of the data, some interesting trends that emerged from the review might be useful in identifying an optimum HF strategy.

Introduction

Hypofractionated (HF) radiation therapy of prostate cancer has garnered increasing attention owing to its proposed low α/β value, which is close to 1.5 Gy 1, 2. Hypofractionated treatments increase the therapeutic ratio and ameliorate logistical inconveniences for both patients and their providers 2, 3, 4.

Supporting data have recently been summarized in a systematic review by Tree et al (5). Importantly, extreme (EHF) and moderate (MHF) hypofractionated regimens do not lead to higher toxicity to the nearby rectum and bladder than conventional regimens (2 Gy per fraction) and have the additional benefit of biochemical control.

The effect of geometric uncertainties is known to be one of the major concerns in radiation dose delivery in prostate cancer (6). These uncertainties are mostly due to patient setup errors and extensive motion of the rectum and bladder that is dependent on organ filling. In this regard, an augmented impact of geometric uncertainties is expected when high doses per fractions are adopted. This could occur because in HF treatments, any single targeting error causes a greater biologic impact by consistently underdosing the target organ at greater expense of the organs at risk (OARs) (7).

Several technological innovations have boosted the high-precision localization of the prostate during treatment, allowing the delivery of highly conformed dose fractions to a well-defined target with sharp dose fall-off toward the bladder and rectum (8). However, multiple technical parameters and operational variables can affect the correct localization of the prostate and the reproducibility of the procedures. For this reason, we focused our attention on these features to investigate the potential correlation/association with clinical outcome in prostate cancer patients treated with EHF and MHF schemes.

We performed a search of the available literature on the PubMed database, concentrating on technical and dosimetric aspects such as delivery techniques, immobilization devices, setup position, rectum and bladder preparation, imaging, margins, localization imaging on-line systems, dose prescriptions, dose constraints, and clinical outcome.

Section snippets

Search strategy

An extensive PubMed search was performed on April 31, 2014, including the search terms (((“Prostatic Neoplasms/radiotherapy”[Mesh] AND “Radiosurgery”[Mesh])) OR ((Prostat* AND (hypofraction* OR SBRT OR “stereobody radiotherap*” OR stereotactic OR radiosurger*))) NOT proton* NOT ion* NOT metastases) and using the filters: published in the last 10 years, English. A reference list of 433 articles resulted from the database according to this criterion. The list of articles was screened by 2

Results

In total, 275 reports were retrieved from the initial PubMed search. As a result of the abstracts reading, 236 were excluded because they did not fit exactly with the inclusion criteria. There was no discrepancy between the 2 reviewers.

We reviewed the data from 733 and 3454 patients from 15 EHF 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24 MHF 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47 reports, respectively.

Discussion

The aim of this study was to describe the state of the art on technical strategies used in HF radiation therapy treatments and their potential correlation with clinical outcome. Targeting this goal, a review of published studies on HF regimens in prostate cancer patients treated with EHF and MHF schemes was performed.

We would like to point out that our work may be not a comprehensive and exhaustive analysis of the known literature; neither is it a systematic review, but it can be considered a

Conclusions

Recent clinical data support a low value for α/β ratio as predicted by radiobiological models; hence, large doses per fraction should result in a higher probability of tumor control together with a reduced probability of complications for healthy tissue. Nevertheless, in the evaluation of the cost-effectiveness of the treatment, it is mandatory to also consider the associated morbidity. In this review, we focused on the technical parameters and treatment strategies adopted in the analyzed HF

Acknowledgments

The authors thank Simona Marzi; Raffaella Marconi for the English revision of the manuscript; and the staff of the Library of the National Cancer Institute Regina Elena (Gaetana Cognetti, Fabio D'Orsogna, and Francesca Servoli) for helping in the PubMed search.

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Hypofractionated (HF) radiation therapy protocols have shown their effectiveness in treating prostate cancer patients [1,2]. However, these protocols require a high level of accuracy in dose delivery to allow reducing treatment margins because of an increased risk of toxicity to the surrounding organs at risk (OARs) [3]. The use of reduced clinical target volume to planning target volume (CTV-to-PTV) margins for HF versus conventional fractionated treatments has shown to lead to similar late effects between the 2 cohorts whereas early side effects were more pronounced for HF treatments [4].
To investigate the impact on dose distribution of intrafraction motion during moderate hypofractionated prostate cancer treatments and to estimate minimum non-isotropic and asymmetric (NI-AS) treatment margins taking motion into account.
Prostate intrafraction 3D displacements were recorded with a transperineal ultrasound probe and were evaluated in 46 prostate cancer patients (876 fractions) treated by moderate hypofractionated radiation therapy (60 Gy in 20 fractions). For 18 patients (346 fractions), treatment plans were recomputed increasing CTV-to-PTV margins from 0 to 6 mm with an auto-planning optimization algorithm. Dose distribution was estimated using the voxel shifting method by displacing CTV structure according to the retrieved movements. Time-dependent margins were finally calculated using both van Herk’s formula and the voxel shifting method.
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NI-AS margins would be required to optimally take into account intrafraction motion.
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: Conflict of interest: none.

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Clinical InvestigationRole of the Technical Aspects of Hypofractionated Radiation Therapy Treatment of Prostate Cancer: A Review

Introduction

Section snippets

Search strategy

Results

Discussion

Conclusions

Acknowledgments

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Clin Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Radiother Oncol

Int J Radiat Oncol Biol Phys

Radiother Oncol

Int J Radiat Oncol Biol Phys

Clin Oncol (R Coll Radiol)

Radiat Oncol

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

Urol Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Radiother Oncol

Int J Radiat Oncol Biol Phys

Radiother Oncol

Radiother Oncol

Radiother Oncol

Radiother Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Clinical Investigation
Role of the Technical Aspects of Hypofractionated Radiation Therapy Treatment of Prostate Cancer: A Review