-
Advanced Drug Delivery Reviews Jan 2017In principle, proton therapy offers a substantial clinical advantage over conventional photon therapy. This is because of the unique depth-dose characteristics of... (Review)
Review
In principle, proton therapy offers a substantial clinical advantage over conventional photon therapy. This is because of the unique depth-dose characteristics of protons, which can be exploited to achieve significant reductions in normal tissue doses proximal and distal to the target volume. These may, in turn, allow escalation of tumor doses and greater sparing of normal tissues, thus potentially improving local control and survival while at the same time reducing toxicity and improving quality of life. Protons, accelerated to therapeutic energies ranging from 70 to 250MeV, typically with a cyclotron or a synchrotron, are transported to the treatment room where they enter the treatment head mounted on a rotating gantry. The initial thin beams of protons are spread laterally and longitudinally and shaped appropriately to deliver treatments. Spreading and shaping can be achieved by electro-mechanical means to treat the patients with "passively-scattered proton therapy" (PSPT) or using magnetic scanning of thin "beamlets" of protons of a sequence of initial energies. The latter technique can be used to treat patients with optimized intensity modulated proton therapy (IMPT), the most powerful proton modality. Despite the high potential of proton therapy, the clinical evidence supporting the broad use of protons is mixed. It is generally acknowledged that proton therapy is safe, effective and recommended for many types of pediatric cancers, ocular melanomas, chordomas and chondrosarcomas. Although promising results have been and continue to be reported for many other types of cancers, they are based on small studies. Considering the high cost of establishing and operating proton therapy centers, questions have been raised about their cost effectiveness. General consensus is that there is a need to conduct randomized trials and/or collect outcomes data in multi-institutional registries to unequivocally demonstrate the advantage of protons. Treatment planning and plan evaluation of PSPT and IMPT require special considerations compared to the processes used for photon treatment planning. The differences in techniques arise from the unique physical properties of protons but are also necessary because of the greater vulnerability of protons to uncertainties, especially from inter- and intra-fractional variations in anatomy. These factors must be considered in designing as well as evaluating treatment plans. In addition to anatomy variations, other sources of uncertainty in dose delivered to the patient include the approximations and assumptions of models used for computing dose distributions for planning of treatments. Furthermore, the relative biological effectiveness (RBE) of protons is simplistically assumed to have a constant value of 1.1. In reality, the RBE is variable and a complex function of the energy of protons, dose per fraction, tissue and cell type, end point, etc. These uncertainties, approximations and current technological limitations of proton therapy may limit the achievement of its true potential. Ongoing research is aimed at better understanding the consequences of the various uncertainties on proton therapy and reducing the uncertainties through image-guidance, adaptive radiotherapy, further study of biological properties of protons and the development of novel dose computation and optimization methods. However, residual uncertainties will remain in spite of the best efforts. To increase the resilience of dose distributions in the face of uncertainties and improve our confidence in dose distributions seen on treatment plans, robust optimization techniques are being developed and implemented. We assert that, with such research, proton therapy will be a commonly applied radiotherapy modality for most types of solid cancers in the near future.
Topics: Humans; Neoplasms; Proton Therapy; Quality of Life; Radiotherapy Planning, Computer-Assisted
PubMed: 27919760
DOI: 10.1016/j.addr.2016.11.006 -
International Journal of Molecular... Sep 2020FLASH radiotherapy is the delivery of ultra-high dose rate radiation several orders of magnitude higher than what is currently used in conventional clinical... (Review)
Review
FLASH radiotherapy is the delivery of ultra-high dose rate radiation several orders of magnitude higher than what is currently used in conventional clinical radiotherapy, and has the potential to revolutionize the future of cancer treatment. FLASH radiotherapy induces a phenomenon known as the FLASH effect, whereby the ultra-high dose rate radiation reduces the normal tissue toxicities commonly associated with conventional radiotherapy, while still maintaining local tumor control. The underlying mechanism(s) responsible for the FLASH effect are yet to be fully elucidated, but a prominent role for oxygen tension and reactive oxygen species production is the most current valid hypothesis. The FLASH effect has been confirmed in many studies in recent years, both and , with even the first patient with T-cell cutaneous lymphoma being treated using FLASH radiotherapy. However, most of the studies into FLASH radiotherapy have used electron beams that have low tissue penetration, which presents a limitation for translation into clinical practice. A promising alternate FLASH delivery method is via proton beam therapy, as the dose can be deposited deeper within the tissue. However, studies into FLASH protons are currently sparse. This review will summarize FLASH radiotherapy research conducted to date and the current theories explaining the FLASH effect, with an emphasis on the future potential for FLASH proton beam therapy.
Topics: Humans; Neoplasms; Proton Therapy; Protons; Radiotherapy; Radiotherapy Dosage; Reactive Oxygen Species
PubMed: 32899466
DOI: 10.3390/ijms21186492 -
The British Journal of Radiology Mar 2022Localized prostate cancer can be treated with several radiotherapeutic approaches. Proton therapy (PT) can precisely target tumors, thus sparing normal tissues and... (Review)
Review
OBJECTIVE
Localized prostate cancer can be treated with several radiotherapeutic approaches. Proton therapy (PT) can precisely target tumors, thus sparing normal tissues and reducing side-effects without sacrificing cancer control. However, PT is a costly treatment compared with conventional photon radiotherapy, which may undermine its overall efficacy. In this review, we summarize current data on the dosimetric rationale, clinical benefits, and cost of PT for prostate cancer.
METHODS
An extensive literature review of PT for prostate cancer was performed with emphasis on studies investigating dosimetric advantage, clinical outcomes, cost-effective strategies, and novel technology trends.
RESULTS
PT is safe, and its efficacy is comparable to that of standard photon-based therapy or brachytherapy. Data on gastrointestinal, genitourinary, and sexual function toxicity profiles are conflicting; however, PT is associated with a low risk of second cancer and has no effects on testosterone levels. Regarding cost-effectiveness, PT is suboptimal, although evolving trends in radiation delivery and construction of PT centers may help reduce the cost.
CONCLUSION
PT has several advantages over conventional photon radiotherapy, and novel approaches may increase its efficacy and safety. Large prospective randomized trials comparing photon therapy with proton-based treatments are ongoing and may provide data on the differences in efficacy, toxicity profile, and quality of life between proton- and photon-based treatments for prostate cancer in the modern era.
ADVANCES IN KNOWLEDGE
PT provides excellent physical advantages and has a superior dose profile compared with X-ray radiotherapy. Further evidence from clinical trials and research studies will clarify the role of PT in the treatment of prostate cancer, and facilitate the implementation of PT in a more accessible, affordable, efficient, and safe way.
Topics: Cost-Benefit Analysis; Forecasting; Humans; Male; Prostatic Neoplasms; Proton Therapy; Radiotherapy Dosage
PubMed: 34558308
DOI: 10.1259/bjr.20210670 -
Hematology/oncology Clinics of North... Dec 2019Proton therapy is a form of external beam radiotherapy that has several advantages over conventional photon (x-ray) radiotherapy. Protons are useful in 2 scenarios that... (Review)
Review
Proton therapy is a form of external beam radiotherapy that has several advantages over conventional photon (x-ray) radiotherapy. Protons are useful in 2 scenarios that apply to a large proportion of cancer patients: lack of exit dose allows for delivery of a therapeutic radiation dose to tumors in challenging anatomic locations, and reduction in integral dose (low-dose bath) to normal tissues that may reduce the risk of late toxicities and secondary cancers. The emergence of smaller, more economically viable single-room proton units has led to the expansion in use of this technology across the world.
Topics: Humans; Neoplasms; Organs at Risk; Proton Therapy; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted
PubMed: 31668216
DOI: 10.1016/j.hoc.2019.08.006 -
JCO Oncology Practice Jun 2024Expert commentary on the evolving role of proton therapy, discussing the current status and controversies of proton therapy in the modern era.
Expert commentary on the evolving role of proton therapy, discussing the current status and controversies of proton therapy in the modern era.
Topics: Proton Therapy; Humans; Neoplasms
PubMed: 38547434
DOI: 10.1200/OP.24.00132 -
Neuro-oncology Sep 2022
Topics: Brain Neoplasms; Brain Stem; Child; Humans; Proton Therapy; Protons; Radiometry
PubMed: 35512698
DOI: 10.1093/neuonc/noac121 -
The British Journal of Radiology Mar 2020
Topics: Humans; Neoplasms; Proton Therapy
PubMed: 32081045
DOI: 10.1259/bjr.20209004 -
JAMA Otolaryngology-- Head & Neck... Aug 2023
Topics: Humans; Proton Therapy; Osteoradionecrosis; Radiotherapy Dosage; Mandibular Diseases
PubMed: 37318819
DOI: 10.1001/jamaoto.2023.1302 -
JAMA Otolaryngology-- Head & Neck... Aug 2023
Topics: Humans; Proton Therapy; Osteoradionecrosis; Radiotherapy Dosage; Mandibular Diseases
PubMed: 37318798
DOI: 10.1001/jamaoto.2023.1301 -
Surgical Oncology Clinics of North... Jul 2023Esophageal cancer is the eighth most common cancer worldwide and is the sixth most common cause of cancer-related mortality. The paradigm has shifted to include a... (Review)
Review
Esophageal cancer is the eighth most common cancer worldwide and is the sixth most common cause of cancer-related mortality. The paradigm has shifted to include a multimodality approach with surgery, chemotherapy, targeted therapy (including immunotherapy), and radiation therapy. Advances in radiotherapy through techniques such as intensity modulated radiotherapy and proton beam therapy have allowed for the more dose homogeneity and improved organ sparing. In addition, recent studies of targeted therapies and predictive approaches in patients with locally advanced disease provide clinicians with new approaches to modify multimodality treatment to improve clinical outcomes.
Topics: Humans; Esophageal Neoplasms; Radiotherapy, Intensity-Modulated; Proton Therapy; Radiotherapy Dosage; Chemoradiotherapy
PubMed: 37182986
DOI: 10.1016/j.soc.2023.03.004