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Annals of Palliative Medicine Nov 2023Given its sharp dose fall off and ability to spare healthy surrounding tissue, proton beam therapy (PBT) has traditionally been used to treat various types of... (Review)
Review
Given its sharp dose fall off and ability to spare healthy surrounding tissue, proton beam therapy (PBT) has traditionally been used to treat various types of malignancies in the definitive setting, with strong, empirical data supporting its utility and safety. In the palliative setting, however, photon therapy has generally remained the standard of care in radiation treatment delivery due to lower cost, and greater availability. However, recent data suggest that the use of PBT may provide benefit in terms of symptom management and disease control in patients with locally advanced or recurrent disease who do not qualify for definitive therapy or with metastatic disease. Additionally, due to its unique dosimetric properties, PBT may confer less overall toxicity, thus helping preserve or improve the quality of life in this patient population, especially for those who are nearing end of life. While there is a need for further study, initial data analyzed from both retrospective and prospective single-institution and multi-institution trials are promising. This review aims to explore the efficacy and safety of PBT in the palliative setting among adults and to summarize pertinent studies that support its usage. To the authors' knowledge, this is the first review of the literature pertaining to PBT used in the palliative setting across multiple disease sites.
Topics: Adult; Humans; Proton Therapy; Retrospective Studies; Quality of Life; Prospective Studies; Neoplasms
PubMed: 37574582
DOI: 10.21037/apm-23-230 -
Ugeskrift For Laeger Jan 2024The general population is aging, which expectedly will lead to a future increase in older patients with cancer. This review summarises the recent advances in... (Review)
Review
The general population is aging, which expectedly will lead to a future increase in older patients with cancer. This review summarises the recent advances in radiotherapy. Technological advances have led radiotherapy to be an efficient and well-tolerated treatment option in older patient with cancer. Studies show no difference in toxicity and disease control rates compared with the ones in younger patients with cancer. MR-guided radiotherapy, proton therapy, and integration of artificial intelligence in treatment planning represent the latest advances in the field of radiotherapy and hold potential to further improve the treatment of older patients with cancer.
Topics: Humans; Aged; Artificial Intelligence; Neoplasms; Proton Therapy; Aging
PubMed: 38305322
DOI: 10.61409/V06230381 -
JAMA Network Open Aug 2023Radiotherapy plays an important role in the treatment of esophageal cancer. Proton therapy has unique physical properties and higher relative biological effectiveness.... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Radiotherapy plays an important role in the treatment of esophageal cancer. Proton therapy has unique physical properties and higher relative biological effectiveness. However, whether proton therapy has greater benefit than photon therapy is still unclear.
OBJECTIVE
To evaluate whether proton was associated with better efficacy and safety outcomes, including dosimetric, prognosis, and toxic effects outcomes, compared with photon therapy and to evaluate the efficacy and safety of proton therapy singly.
DATA SOURCES
A systematic search of PubMed, Embase, the Cochrane Library, Web of Science, SinoMed, and China National Knowledge Infrastructure databases was conducted for articles published through November 25, 2021, and updated to March 25, 2023.
STUDY SELECTION
For the comparison of proton and photon therapy, studies including dosimetric, prognosis, and associated toxic effects outcomes were included. The separate evaluation of proton therapy evaluated the same metrics.
DATA EXTRACTION AND SYNTHESIS
Data on study design, individual characteristics, and outcomes were extracted. If I2 was greater than 50%, the random-effects model was selected. This meta-analysis is reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.
MAIN OUTCOMES AND MEASURES
The main outcomes were organs at risk (OARs) dosimetric outcomes, prognosis (overall survival [OS], progression-free survival [PFS], and objective response rate [ORR]), and radiation-related toxic effects.
RESULTS
A total of 45 studies were included in the meta-analysis. For dosimetric analysis, proton therapy was associated with significantly reduced OARs dose. Meta-analysis showed that photon therapy was associated with poor OS (hazard ratio [HR], 1.31; 95% CI, 1.07-1.61; I2 = 11%), but no difference in PFS was observed. Subgroup analysis showed worse OS (HR, 1.42; 95% CI, 1.14-1.78; I2 = 34%) and PFS (HR, 1.48; 95% CI, 1.06-2.08; I2 = 7%) in the radical therapy group with photon therapy. The pathological complete response rate was similar between groups. Proton therapy was associated with significantly decreased grade 2 or higher radiation pneumonitis and pericardial effusion, and grade 4 or higher lymphocytopenia. Single-rate analysis of proton therapy found 89% OS and 65% PFS at 1 year, 71% OS and 56% PFS at 2 years, 63% OS and 48% PFS at 3 years, and 56% OS and 42% PFS at 5 years. The incidence of grade 2 or higher radiation esophagitis was 50%, grade 2 or higher radiation pneumonitis was 2%, grade 2 or higher pleural effusion was 4%, grade 2 or higher pericardial effusion was 3%, grade 3 or higher radiation esophagitis was 8%, and grade 4 or higher lymphocytopenia was 17%.
CONCLUSIONS AND RELEVANCE
In this meta-analysis, proton therapy was associated with reduced OARs doses and toxic effects and improved prognosis compared with photon therapy for esophageal cancer, but caution is warranted. In the future, these findings should be further validated in randomized clinical trials.
Topics: Humans; Proton Therapy; Protons; Pericardial Effusion; Radiation Pneumonitis; Esophageal Neoplasms
PubMed: 37581887
DOI: 10.1001/jamanetworkopen.2023.28136 -
The British Journal of Radiology Mar 2020Range uncertainty is a much discussed topic in proton therapy. Although a very real aspect of proton therapy, its magnitude and consequences are sometimes misunderstood... (Review)
Review
Range uncertainty is a much discussed topic in proton therapy. Although a very real aspect of proton therapy, its magnitude and consequences are sometimes misunderstood or overestimated. In this article, the sources and consequences of range uncertainty are reviewed, a number of myths associated with the effect discussed with the aim of putting range uncertainty into clinical context and attempting to de-bunk some of the more exaggerated claims made as to its consequences.
Topics: Absorption, Radiation; Humans; Neoplasms, Radiation-Induced; Patient Positioning; Photons; Proton Therapy; Radiotherapy Dosage; Treatment Outcome; Uncertainty; Water
PubMed: 31778317
DOI: 10.1259/bjr.20190582 -
European Journal of Surgical Oncology :... Aug 2020Aim of the manuscript is to discuss how to improve margins in sacral chordoma. (Review)
Review
OBJECTIVE
Aim of the manuscript is to discuss how to improve margins in sacral chordoma.
BACKGROUND
Chordoma is a rare neoplasm, arising in half cases from the sacrum, with reported local failure in >50% after surgery.
METHODS
A multidisciplinary meeting of the "Chordoma Global Consensus Group" was held in Milan in 2017, focusing on challenges in defining and achieving optimal margins in chordoma with respect to surgery, definitive particle radiation therapy (RT) and medical therapies. This review aims to report on the outcome of the consensus meeting and to provide a summary of the most recent evidence in this field. Possible new ways forward, including on-going international clinical studies, are discussed.
RESULTS
En-bloc tumor-sacrum resection is the cornerstone of treatment of primary sacral chordoma, aiming to achieve negative microscopic margins. Radical definitive particle therapy seems to offer a similar outcome compared to surgery, although confirmation in comparative trials is lacking; besides there is still a certain degree of technical variability across institutions, corresponding to different fields of treatment and different tumor coverage. To address some of these questions, a prospective, randomized international study comparing surgery versus definitive high-dose RT is ongoing. Available data do not support the routine use of any medical therapy as (neo)adjuvant/cytoreductive treatment.
CONCLUSION
Given the significant influence of margins status on local control in patients with primary localized sacral chordoma, the clear definition of adequate margins and a standard local approach across institutions for both surgery and particle RT is vital for improving the management of these patients.
Topics: Chordoma; Humans; Margins of Excision; Proton Therapy; Radiotherapy Dosage; Sacrum
PubMed: 32402509
DOI: 10.1016/j.ejso.2020.04.028 -
Radiation Oncology (London, England) May 2020The targeting accuracy of proton therapy (PT) for moving soft-tissue tumours is expected to greatly improve by real-time magnetic resonance imaging (MRI) guidance. The... (Review)
Review
BACKGROUND
The targeting accuracy of proton therapy (PT) for moving soft-tissue tumours is expected to greatly improve by real-time magnetic resonance imaging (MRI) guidance. The integration of MRI and PT at the treatment isocenter would offer the opportunity of combining the unparalleled soft-tissue contrast and real-time imaging capabilities of MRI with the most conformal dose distribution and best dose steering capability provided by modern PT. However, hybrid systems for MR-integrated PT (MRiPT) have not been realized so far due to a number of hitherto open technological challenges. In recent years, various research groups have started addressing these challenges and exploring the technical feasibility and clinical potential of MRiPT. The aim of this contribution is to review the different aspects of MRiPT, to report on the status quo and to identify important future research topics.
METHODS
Four aspects currently under study and their future directions are discussed: modelling and experimental investigations of electromagnetic interactions between the MRI and PT systems, integration of MRiPT workflows in clinical facilities, proton dose calculation algorithms in magnetic fields, and MRI-only based proton treatment planning approaches.
CONCLUSIONS
Although MRiPT is still in its infancy, significant progress on all four aspects has been made, showing promising results that justify further efforts for research and development to be undertaken. First non-clinical research solutions have recently been realized and are being thoroughly characterized. The prospect that first prototype MRiPT systems for clinical use will likely exist within the next 5 to 10 years seems realistic, but requires significant work to be performed by collaborative efforts of research groups and industrial partners.
Topics: Humans; Magnetic Fields; Magnetic Resonance Imaging; Online Systems; Proton Therapy; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Image-Guided; Workflow
PubMed: 32471500
DOI: 10.1186/s13014-020-01571-x -
The British Journal of Radiology Mar 2020It is recognized that the use of a single plan calculated on an image acquired some time before the treatment is generally insufficient to accurately represent the daily... (Review)
Review
It is recognized that the use of a single plan calculated on an image acquired some time before the treatment is generally insufficient to accurately represent the daily dose to the target and to the organs at risk. This is particularly true for protons, due to the physical finite range. Although this characteristic enables the generation of steep dose gradients, which is essential for highly conformal radiotherapy, it also tightens the dependency of the delivered dose to the range accuracy. In particular, the use of an outdated patient anatomy is one of the most significant sources of range inaccuracy, thus affecting the quality of the planned dose distribution. A plan should be ideally adapted as soon as anatomical variations occur, ideally online. In this review, we describe in detail the different steps of the adaptive workflow and discuss the challenges and corresponding state-of-the art developments in particular for an adaptive strategy.
Topics: Humans; Neoplasms; Organs at Risk; Photons; Proton Therapy; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Conformal; Workflow
PubMed: 31647313
DOI: 10.1259/bjr.20190594 -
Scientific Reports May 2022The objective of this study was to improve the precision of linear energy transfer (LET) measurements using [Formula: see text] optically stimulated luminescence...
The objective of this study was to improve the precision of linear energy transfer (LET) measurements using [Formula: see text] optically stimulated luminescence detectors (OSLDs) in proton beams, and, with that, improve OSL dosimetry by correcting the readout for the LET-dependent ionization quenching. The OSLDs were irradiated in spot-scanning proton beams at different doses for fluence-averaged LET values in the (0.4-6.5) [Formula: see text] range (in water). A commercial automated OSL reader with a built-in beta source was used for the readouts, which enabled a reference irradiation and readout of each OSLD to establish individual corrections. Pulsed OSL was used to separately measure the blue (F-center) and UV ([Formula: see text]-center) emission bands of [Formula: see text] and the ratio between them (UV/blue signal) was used for the LET measurements. The average deviation between the simulated and measured LET values along the central beam axis amounts to 5.5% if both the dose and LET are varied, but the average deviation is reduced to 3.5% if the OSLDs are irradiated with the same doses. With the measurement procedure and automated equipment used here, the variation in the signals used for LET estimates and quenching-corrections is reduced from 0.9 to 0.6%. The quenching-corrected OSLD doses are in agreement with ionization chamber measurements within the uncertainties. The automated OSLD corrections are demonstrated to improve the LET estimates and the ionization quenching-corrections in proton dosimetry for a clinically relevant energy range up to 230 MeV. It is also for the first time demonstrated how the LET can be estimated for different doses.
Topics: Linear Energy Transfer; Luminescence; Proton Therapy; Protons; Radiometry
PubMed: 35585205
DOI: 10.1038/s41598-022-10575-4 -
International Journal of Radiation... Mar 2022This study aimed to highlight the value and key findings of on-site proton audits.
PURPOSE
This study aimed to highlight the value and key findings of on-site proton audits.
METHODS AND MATERIALS
The authors performed 38 on-site measurement-based peer reviews of proton centers participating in National Cancer Institute-funded clinical trials. The reviews covered beam calibration, lateral and depth measurements, mechanical checks, treatment planning and clinical practice, and quality assurance (QA) practices. Program deficiencies were noted, and recommendations were made about ways institutions could improve their practices.
RESULTS
Institutions received an average of 3 (range, 1-8) recommendations for practice improvements. The number of deficiencies did not decrease over time, highlighting the continued need for this type of peer review. The most common deficiencies were for Task Group-recommended QA compliance (97% of centers), computed tomography number (CTN) to relative linear stopping power conversion (59%), and QA procedures (53%). In addition, 32% of institutions assessed failed at least 1 lateral beam profile measurement (<90% of pixels passing 3% [global]/3 mm; 10% threshold), despite passing internal QA measurements. These failures occurred for several different plan configurations (large, small, shallow, and deep targets) and at different depths in the beam path (proximal to target, central, and distal). CTN to relative linear stopping power conversion curves showed deviations at low, mid, and high CTNs and highlighted areas of inconsistency between proton centers, with many centers falling outside of 2 sigma of the mean curve of their peers. All deficiencies from the peer review were discussed with the institutions, and many implemented dosimetric treatment planning and practice changes to improve the accuracy of their system and consistency with other institutions.
CONCLUSIONS
This peer review program has been integral in confirming and promoting consistency and best practice across proton centers for clinical trials, minimizing deviations for outcomes data.
Topics: Calibration; Clinical Audit; Humans; National Cancer Institute (U.S.); Proton Therapy; Quality Assurance, Health Care; Radiometry; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; United States
PubMed: 34780973
DOI: 10.1016/j.ijrobp.2021.10.145 -
The British Journal of Radiology Mar 2020Proton therapy has shown dosimetric advantages over conventional radiation therapy using photons. Although the integral dose for patients treated with proton therapy is... (Review)
Review
Proton therapy has shown dosimetric advantages over conventional radiation therapy using photons. Although the integral dose for patients treated with proton therapy is low, concerns were raised about late effects like secondary cancer caused by dose depositions far away from the treated area. This is especially true for neutrons and therefore the stray dose contribution from neutrons in proton therapy is still being investigated. The higher biological effectiveness of neutrons compared to photons is the main cause of these concerns. The gold-standard in neutron dosimetry is measurements, but performing neutron measurements is challenging. Different approaches have been taken to overcome these difficulties, for instance with newly developed neutron detectors. Monte Carlo simulations is another common technique to assess the dose from secondary neutrons. Measurements and simulations are used to develop analytical models for fast neutron dose estimations. This article tries to summarize the developments in the different aspects of neutron dose in proton therapy since 2017. In general, low neutron doses have been reported, especially in active proton therapy. Although the published biological effectiveness of neutrons relative to photons regarding cancer induction is higher, it is unlikely that the neutron dose has a large impact on the second cancer risk of proton therapy patients.
Topics: Humans; Monte Carlo Method; Neoplasms, Radiation-Induced; Neoplasms, Second Primary; Neutrons; Photons; Proton Therapy; Radiometry; Radiotherapy Dosage; Relative Biological Effectiveness
PubMed: 31868525
DOI: 10.1259/bjr.20190412