What can particle therapy add to the treatment of prostate cancer?

doi:10.1016/j.ejmp.2016.03.017

Physica Medica

Volume 32, Issue 3, March 2016, Pages 485-491

https://doi.org/10.1016/j.ejmp.2016.03.017 Get rights and content

Highlights

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Thousands prostate cancer patients were treated with hadrontherapy (HT) in the past.
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Similar doses to photon therapy (XRT) have been delivered, with comparable clinical results.
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Developments in HT give the chance to match the recently improved results of XRT.
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HT for intra-GTV boost and lymphnodes irradiation can provide superior results to XRT.

Abstract

The treatment of prostate cancer with either protons or carbon ions is not a novelty, and several thousands of patients were treated with hadrontherapy in the past decades. The standard treatment approach consisted in two lateral opposed fields for both protons and carbon ions, mostly delivered with scattered beams and using conventional fractionation and hypofractionation for protons and carbon ions, respectively. Similar (RBE-weighted and BED) doses to photon therapy (XRT) have been delivered, with comparable results in terms of both local control and toxicity. The advancements in dose deposition and image guidance of the early ‘00s that improved the quality of XRT treatments and then allowed for hypofractionation, are being matched with some delay by hadrontherapy in these very years. Pencil beam scanning is now the norm in proton therapy, and volumetric image guidance is being developed in all new hadrontherapy facilities. There is therefore the possibility of truly taking advantage of superior dose distributions of hadrons and safely apply it to innovative treatment protocols, such as an intraprostatic boost and the treatment of larger volume for advanced stage disease. This full integration between the best of technology and new clinical approaches is probably necessary in order to obtain clinical results that are truly superior to the current state of the art of XRT.

Introduction

Hadrontherapy, i.e. the treatment with protons and heavier charged particles, can be seen as the next step of radiation therapy dose shaping with respect to photons. Even though the use of heavy charged particles has been proposed almost 70 years ago and the first patients were treated in the mid ‘50s, still today, if we look at the number of treatments, hadrontherapy is a tiny niche of radiotherapy. Things are slowly about to change, as in the affluent part of the world several ongoing projects are aimed at installing hadrontherapy facilities. In Europe, for instance, by 2020 there will be about 50 treatment rooms where hadrontherapy can be delivered.

It is therefore meaningful to analyze the role of hadrontherapy for the treatment of a disease with high incidence such as prostate cancer.

The use of proton therapy to treat prostate cancer on relatively large number of patients is as old as the first hospital-based proton therapy facilities, i.e. it dates back to the late ‘90s. This means that the first applications, and clinical results, of charged particle therapy to prostate happened when the reference photon therapy technique was 3D conformal radiotherapy (3D-CRT). Since then, the technological landscape has changed significantly, first in photon treatments and only afterwards in proton therapy, so starting from the early ‘00s photon treatments for prostate cancer could take advantage first of intensity modulated (IMXT) and then of image guidance (IGRT) techniques that became either only recently available in protons, or are now on the verge of being available.

As a consequence, protontherapy in general, and its application to prostate cancer in particular, has been at the forefront of heated discussions in the recent past about its cost-effectiveness, both in the scientific literature (e.g. [1], [2], [3]) and in the mainstream media.¹ As much as health economics is a crucial component in determining the success of a treatment technique, or lack thereof, in this article we will not discuss it. Here, we’ll focus on the dosimetric and technical aspects, starting from the assumption that economic issues are worth considering only if there is a convincing dosimetric and clinical rationale for hadrontherapy of prostate cancer.

Section snippets

Treatment techniques

Up until recently, the most common treatment technique of proton therapy for localized prostate cancer has been the application of passively scattered beams (often referred to as three-dimensional conformal proton therapy (3D-CPT)), typically two lateral and parallel-opposed fields, with a conventional fractionation regime (1.8–2.0 Gy (RBE)/fx), at total doses comparable to those applied in photon therapy in the curative setting (74–78 Gy (RBE)).

For a longtime, the use of passively scattered

Future perspectives

In the past 10–15 years photon radiotherapy techniques for prostate cancer have been evolving along some directions that are relevant for protons and carbon ions too:

(1)
Improved dose distributions, made possible by new plan optimization and beam delivery techniques. Photon therapy did greatly benefit in the early ‘00s from the introduction of IMXT, that allow to take full advantage of dose shaping capabilities of photons beams. A similar evolution occurred in particle therapy, albeit with some

Conclusion

Heavy charged particles have been used to treat prostate cancer on a relatively large number of patients. The clinical results show safety and effectiveness of this treatment approach, but they do not suggest significant improvements with respect to state of the art photon therapy.

The technological developments of the recent past enables however new possibilities. There is now the chance to take the best of existing beam delivery techniques (e.g. scanning system with small pencil beam size on a

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Cited by (9)

Mixed-beam approach for high-risk prostate cancer: Carbon-ion boost followed by photon intensity-modulated radiotherapy. Dosimetric and geometric evaluations (AIRC IG-14300)
2020, Physica Medica
Citation Excerpt :
Syngo TPS does not provide robust optimization, so intra and inter fraction uncertainties needed to be compensated with a robust beam configuration. To reach this goal, beam arrangement for CIRT consisted of two parallel-opposed lateral beams, which represents the standard beam geometry for prostate treatment with particles and allows to avoid the irradiation of the most critical OARs, namely rectum and bladder, considering the sharp lateral beam penumbra of carbon ions [19]. In addition, a rigid thermoplastic mask was employed for patient immobilization to limit setup errors and in room cone beam compute tomography (CBCT) imaging was used to evaluate inter-fraction variations, related to different bladder and organ filling.
The aim was to evaluate dosimetric uncertainties of a mixed beam approach for patients with high-risk prostate cancer (PCa). The treatment consists of a carbon ion radiotherapy (CIRT) boost followed by whole-pelvis intensity-modulated RT (IMRT).
Patients were treated with a CIRT boost of 16.6 Gy/4 fractions followed by whole-pelvis IMRT of 50 Gy/25 fractions, with consequent long term androgen deprivation therapy. Deformable computed tomography image registration (DIR) was performed and corresponding doses were used for plan sum. A comparative IMRT photon plan was obtained as whole-pelvis IMRT of 50 Gy/25 fractions followed by a boost of 28 Gy/14 fractions. DIR performances were evaluated through structure-related and image characteristics parameters.
Until now, five patients out of ten total enrolled ended the treatment. Dosimetric parameters were lower in CIRT + IMRT than IMRT-only plans for all organs at risk (OARs) except femoral heads.
Regarding DIR evaluation, femoral heads were the less deformed OAR. Penile bulb, bladder and anal canal showed intermediate deformation. Rectum was the most deformed. DIR algorithms were patient (P)-dependent, as performances were the highest for P3 and P4, intermediate for P2 and P5, and the lowest for P1.
CIRT allows better OARs sparing while increasing the efficacy due to the higher radio-biological effect of carbon ions. However, a mixed beam approach could introduce DIR problems in multi-centric treatments with different operative protocols. The development of this prospective trial will lead to more mature data concerning the clinical impact of implementing DIR procedures in dose accumulation applications for high-risk PCa treatments.
Monte Carlo study of out-of-field exposure in carbon-ion radiotherapy with a passive beam: Organ doses in prostate cancer treatment
2018, Physica Medica
Citation Excerpt :
As mentioned before, the active-scanning technique realizes high irradiation accuracy and flexible treatment planning as well as less doses in OARs compared to the passive technique. Schwarz et al. indicated that the active-scanning technique with small pencil beam size on a gantry has the chance to take the best among existing beam delivery techniques for prostate cancer treatment; however, they pointed out that it is probably necessary to integrate new technologies, such as image guidance techniques, and clinical approaches which photon radiotherapy has been evolving recently into the current ion-beam radiotherapy [41]. Such technologies and clinical approaches have been applied to ion-beam radiotherapy, and further reduction of doses to OARs were attempted [42,43].
The aim of this work was to estimate typical dose equivalents to out-of-field organs during carbon-ion radiotherapy (CIRT) with a passive beam for prostate cancer treatment. Additionally, sensitivity analyses of organ doses for various beam parameters and phantom sizes were performed.
Because the CIRT out-of-field dose depends on the beam parameters, the typical values of those parameters were determined from statistical data on the target properties of patients who received CIRT at the Heavy-Ion Medical Accelerator in Chiba (HIMAC). Using these typical beam-parameter values, out-of-field organ dose equivalents during CIRT for typical prostate treatment were estimated by Monte Carlo simulations using the Particle and Heavy-Ion Transport Code System (PHITS) and the ICRP reference phantom.
The results showed that the dose decreased with distance from the target, ranging from 116 mSv in the testes to 7 mSv in the brain. The organ dose equivalents per treatment dose were lower than those either in 6-MV intensity-modulated radiotherapy or in brachytherapy with an Ir-192 source for organs within 40 cm of the target. Sensitivity analyses established that the differences from typical values were within ∼30% for all organs, except the sigmoid colon.
The typical out-of-field organ dose equivalents during passive-beam CIRT were shown. The low sensitivity of the dose equivalent in organs farther than 20 cm from the target indicated that individual dose assessments required for retrospective epidemiological studies may be limited to organs around the target in cases of passive-beam CIRT for prostate cancer.
Proceedings of the National Cancer Institute Workshop on Charged Particle Radiobiology
2018, International Journal of Radiation Oncology Biology Physics
Citation Excerpt :
These aspects could increase the therapeutic window for slow-growing tumors. For normal tissues, they seem to counterbalance the other potential advantages of high LET radiation that generally support the use of hypofractionated regimens for this type of radiation (7, 143, 144). CSCs are thought to be responsible for tumor initiation, recurrence, metastasis formation, and resistance to any common cancer therapies, including RT (145).
In April 2016, the National Cancer Institute hosted a multidisciplinary workshop to discuss the current knowledge of the radiobiological aspects of charged particles used in cancer therapy to identify gaps in that knowledge that might hinder the effective clinical use of charged particles and to propose research that could help fill those gaps. The workshop was organized into 10 topics ranging from biophysical models to clinical trials and included treatment optimization, relative biological effectiveness of tumors and normal tissues, hypofractionation with particles, combination with immunotherapy, “omics,” hypoxia, and particle-induced second malignancies. Given that the most commonly used charged particle in the clinic currently is protons, much of the discussion revolved around evaluating the state of knowledge and current practice of using a relative biological effectiveness of 1.1 for protons. Discussion also included the potential advantages of heavier ions, notably carbon ions, because of their increased biological effectiveness, especially for tumors frequently considered to be radiation resistant, increased effectiveness in hypoxic cells, and potential for differentially altering immune responses. The participants identified a large number of research areas in which information is needed to inform the most effective use of charged particles in the future in clinical radiation therapy. This unique form of radiation therapy holds great promise for improving cancer treatment.
The role of medical physics in prostate cancer radiation therapy
2016, Physica Medica
Citation Excerpt :
Another relevant new approach for delivering PCa RT concerns heavy charged particles: in particular, the use of protons is increasing although there is, as yet, no clear evidence of net clinical benefit. The question around what protons can add compared to photons is well discussed in the paper by Schwarz and Molinelli [16]. Independently on the delivery techniques, probably one the major advancement in the field of PCa RT of the last 10–15 years has been the large-scale implementation of in-room image-guidance, after the clear recognition of the dramatic impact of geometric uncertainties on the outcome, mainly due to prostate motion.
Medical physics, both as a scientific discipline and clinical service, hugely contributed and still contributes to the advances in the radiotherapy of prostate cancer. The traditional translational role in developing and safely implementing new technology and methods for better optimizing, delivering and monitoring the treatment is rapidly expanding to include new fields such as quantitative morphological and functional imaging and the possibility of individually predicting outcome and toxicity. The pivotal position of medical physicists in treatment personalization probably represents the main challenge of current and next years and needs a gradual change of vision and training, without losing the traditional and fundamental role of physicists to guarantee a high quality of the treatment. The current focus issue is intended to cover traditional and new fields of investigation in prostate cancer radiation therapy with the aim to provide up-to-date reference material to medical physicists daily working to cure prostate cancer patients. The papers presented in this focus issue touch upon present and upcoming challenges that need to be met in order to further advance prostate cancer radiation therapy. We suggest that there is a smart future for medical physicists willing to perform research and innovate, while they continue to provide high-quality clinical service. However, physicists are increasingly expected to actively integrate their implicitly translational, flexible and high-level skills within multi-disciplinary teams including many clinical figures (first of all radiation oncologists) as well as scientists from other disciplines.
Ultrahypofractionated radiotherapy for localized prostate cancer with simultaneous boost to the dominant intraprostatic lesion: a plan comparison
2022, Tumori
Dosimetric Impact of Inter-Fraction Anatomical Changes in Carbon Ion Boost Treatment for High-Risk Prostate Cancer (AIRC IG 14300)
2021, Frontiers in Oncology

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Review PaperWhat can particle therapy add to the treatment of prostate cancer?

Highlights

Abstract

Introduction

Section snippets

Treatment techniques

Future perspectives

Conclusion

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Review Paper
What can particle therapy add to the treatment of prostate cancer?