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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 -
International Journal of Radiation... Oct 2021Radiation therapy plays an important role in the multidisciplinary management of breast cancer. Recent years have seen improvements in breast cancer survival and a... (Review)
Review
Radiation therapy plays an important role in the multidisciplinary management of breast cancer. Recent years have seen improvements in breast cancer survival and a greater appreciation of potential long-term morbidity associated with the dose and volume of irradiated organs. Proton therapy reduces the dose to nontarget structures while optimizing target coverage. However, there remain additional financial costs associated with proton therapy, despite reductions over time, and studies have yet to demonstrate that protons improve upon the treatment outcomes achieved with photon radiation therapy. There remains considerable heterogeneity in proton patient selection and techniques, and the rapid technological advances in the field have the potential to affect evidence evaluation, given the long latency period for breast cancer radiation therapy recurrence and late effects. In this consensus statement, we assess the data available to the radiation oncology community of proton therapy for breast cancer, provide expert consensus recommendations on indications and technique, and highlight ongoing trials' cost-effectiveness analyses and key areas for future research.
Topics: Breast; Breast Neoplasms; Consensus; Cost-Benefit Analysis; Female; Humans; Linear Energy Transfer; Neoplasm Recurrence, Local; Proton Therapy; Radiotherapy Planning, Computer-Assisted; Relative Biological Effectiveness
PubMed: 34048815
DOI: 10.1016/j.ijrobp.2021.05.110 -
Oral Oncology Jan 2019Radiation therapy plays an integral role in the management of head and neck cancers (HNCs). While most HNC patients have historically been treated with photon-based... (Review)
Review
Radiation therapy plays an integral role in the management of head and neck cancers (HNCs). While most HNC patients have historically been treated with photon-based radiation techniques such as intensity modulated radiation therapy (IMRT), there is a growing awareness of the potential clinical benefits of proton therapy over IMRT in the definitive, postoperative and reirradiation settings given the unique physical properties of protons. Intensity modulated proton therapy (IMPT), also known as "pencil beam proton therapy," is a sophisticated mode of proton therapy that is analogous to IMRT and an active area of investigation in cancer care. Multifield optimization IMPT allows for high quality plans that can target superficially located HNCs as well as large neck volumes while significantly reducing integral doses. Several dosimetric studies have demonstrated the superiority of IMPT over IMRT to improve dose sparing of nearby organs such as the larynx, salivary glands, and esophagus. Evidence of the clinical translation of these dosimetric advantages has been demonstrated with documented toxicity reductions (such as decreased feeding tube dependency) after IMPT for patients with HNCs. While there are relative challenges to IMPT planning that exist today such as particle range uncertainties and high sensitivity to anatomical changes, ongoing investigations in image-guidance techniques and robust optimization methods are promising. A systematic approach towards utilizing IMPT and additional prospective studies are necessary in order to more accurately estimate the clinical benefit of IMPT over IMRT and passive proton therapy on a case-by-case basis for patients with sub-site specific HNCs.
Topics: Head and Neck Neoplasms; Humans; Photons; Proton Therapy; Radiodermatitis; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated; Retreatment; Stomatitis; Survival Rate; Treatment Outcome
PubMed: 30616799
DOI: 10.1016/j.oraloncology.2018.11.015 -
The British Journal of Radiology Mar 2020
Topics: Humans; Neoplasms; Proton Therapy
PubMed: 32081045
DOI: 10.1259/bjr.20209004 -
Neuro-oncology Sep 2022
Topics: Brain Neoplasms; Brain Stem; Child; Humans; Proton Therapy; Protons; Radiometry
PubMed: 35512698
DOI: 10.1093/neuonc/noac121 -
Physics in Medicine and Biology Feb 2021The treatment of cancer with proton radiation therapy was first suggested in 1946 followed by the first treatments in the 1950s. As of 2020, almost 200 000 patients have... (Review)
Review
The treatment of cancer with proton radiation therapy was first suggested in 1946 followed by the first treatments in the 1950s. As of 2020, almost 200 000 patients have been treated with proton beams worldwide and the number of operating proton therapy (PT) facilities will soon reach one hundred. PT has long moved from research institutions into hospital-based facilities that are increasingly being utilized with workflows similar to conventional radiation therapy. While PT has become mainstream and has established itself as a treatment option for many cancers, it is still an area of active research for various reasons: the advanced dose shaping capabilities of PT cause susceptibility to uncertainties, the high degrees of freedom in dose delivery offer room for further improvements, the limited experience and understanding of optimizing pencil beam scanning, and the biological effect difference compared to photon radiation. In addition to these challenges and opportunities currently being investigated, there is an economic aspect because PT treatments are, on average, still more expensive compared to conventional photon based treatment options. This roadmap highlights the current state and future direction in PT categorized into four different themes, 'improving efficiency', 'improving planning and delivery', 'improving imaging', and 'improving patient selection'.
Topics: Biology; Humans; Neoplasms; Photons; Physics; Proton Therapy; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted
PubMed: 33227715
DOI: 10.1088/1361-6560/abcd16 -
Journal of Medical Radiation Sciences Mar 2021A transparent and equitable process for selecting patients who will benefit most from treatment at the Australian Bragg Centre for Proton Therapy as well as providing...
A transparent and equitable process for selecting patients who will benefit most from treatment at the Australian Bragg Centre for Proton Therapy as well as providing cost benefit for the investment made by government for this valuable resource, needs to be in place as soon as the Centre becomes operational, particularly for patients with more common cancers. Markov modelling is one method of patient selection and an example is provided in this issue of the Journal of Medical Radiation Sciences.
Topics: Cost-Benefit Analysis; Humans; Patient Selection; Proton Therapy
PubMed: 33259660
DOI: 10.1002/jmrs.454 -
Physics in Medicine and Biology Nov 2018Motion and uncertainty in radiotherapy is traditionally handled via margins. The clinical target volume (CTV) is expanded to a larger planning target volume (PTV), which... (Review)
Review
Motion and uncertainty in radiotherapy is traditionally handled via margins. The clinical target volume (CTV) is expanded to a larger planning target volume (PTV), which is irradiated to the prescribed dose. However, the PTV concept has several limitations, especially in proton therapy. Therefore, robust and probabilistic optimization methods have been developed that directly incorporate motion and uncertainty into treatment plan optimization for intensity modulated radiotherapy (IMRT) and intensity modulated proton therapy (IMPT). Thereby, the explicit definition of a PTV becomes obsolete and treatment plan optimization is directly based on the CTV. Initial work focused on random and systematic setup errors in IMRT. Later, inter-fraction prostate motion and intra-fraction lung motion became a research focus. Over the past ten years, IMPT has emerged as a new application for robust planning methods. In proton therapy, range or setup errors may lead to dose degradation and misalignment of dose contributions from different beams - a problem that cannot generally be addressed by margins. Therefore, IMPT has led to the first implementations of robust planning methods in commercial planning systems, making these methods available for clinical use. This paper first summarizes the limitations of the PTV concept. Subsequently, robust optimization methods are introduced and their applications in IMRT and IMPT planning are reviewed.
Topics: Humans; Motion; Proton Therapy; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated
PubMed: 30418942
DOI: 10.1088/1361-6560/aae659