Selecting patients for proton beam therapy.
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ABSTRACT:
SUBMITTER: Ahern V
PROVIDER: S-EPMC7890916 | biostudies-literature | 2021 Mar
REPOSITORIES: biostudies-literature
Publications
Selecting patients for proton beam therapy.
Journal of medical radiation sciences 20201201 1
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. ...[more]
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Project description:Proton beam therapy (PBT) delivers less dose to nearby normal organs compared to X-ray therapy (XRT), which is particularly relevant for treating liver cancers given that both mean and low liver dose are among the most significant predictors of radiation induced liver disease (RILD). High-dose PBT has been shown to achieve excellent long-term tumor control with minimal toxicity in hepatocellular carcinoma (HCC) patients. Increasing data support ablative PBT for patients with unresectable cholangiocarcinoma or liver metastases, especially those with larger tumors not suitable for XRT.
| S-EPMC7052772 | biostudies-literature
Project description:This paper presents a concept for a proton therapy system capable of delivering intensity modulated proton therapy using a fan beam of protons. This system would allow present and future gantry-based facilities to deliver state-of-the-art proton therapy with the greater normal tissue sparing made possible by intensity modulation techniques.A method for producing a divergent fan beam of protons using a pair of electromagnetic quadrupoles is described and particle transport through the quadrupole doublet is simulated using a commercially available software package. To manipulate the fan beam of protons, a modulation device is developed. This modulator inserts or retracts acrylic leaves of varying thickness from subsections of the fan beam. Each subsection, or beam channel, creates what effectively becomes a beam spot within the fan area. Each channel is able to provide 0-255 mm of range shift for its associated beam spot, or stop the beam and act as an intensity modulator. Results of particle transport simulations through the quadrupole system are incorporated into the MCNPX Monte Carlo transport code along with a model of the range and intensity modulation device. Several design parameters were investigated and optimized, culminating in the ability to create topotherapy treatment plans using distal-edge tracking on both phantom and patient datasets.Beam transport calculations show that a pair of electromagnetic quadrupoles can be used to create a divergent fan beam of 200 MeV protons over a distance of 2.1 m. The quadrupole lengths were 30 and 48 cm, respectively, with transverse field gradients less than 20 T/m, which is within the range of water-cooled magnets for the quadrupole radii used. MCNPX simulations of topotherapy treatment plans suggest that, when using the distal edge tracking delivery method, many delivery angles are more important than insisting on narrow beam channel widths in order to obtain conformal target coverage. Overall, the sharp distal falloff of a proton depth-dose distribution was found to provide sufficient control over the dose distribution to meet objectives, even with coarse lateral resolution and channel widths as large as 2 cm. Treatment plans on both phantom and patient data show that dose conformity suffers when treatments are delivered from less than approximately ten angles. Treatment time for a sample prostate delivery is estimated to be on the order of 10 min, and neutron production is estimated to be comparable to that found for existing collimated systems.Fan beam proton therapy is a method of delivering intensity modulated proton therapy which may be employed as an alternative to magnetic scanning systems. A fan beam of protons can be created by a set of quadrupole magnets and modified by a dual-purpose range and intensity modulator. This can be used to deliver inversely planned treatments, with spot intensities optimized to meet user defined dose objectives. Additionally, the ability of a fan beam delivery system to effectively treat multiple beam spots simultaneously may provide advantages as compared to spot scanning deliveries.
| S-EPMC3799727 | biostudies-other
Project description:PurposeTo compare the dosimetric performances of intensity-modulated proton therapy (IMPT) plans generated with two different beam angle configurations (the Right-Left oblique posterior beams and the Superior-Inferior oblique posterior beams) for the treatment of distal esophageal carcinoma in the presence of uncertainties and interplay effect.Methods and materialsTwenty patients' IMPT plans were retrospectively selected, with 10 patients treated with the R-L oblique posterior beams (Group R-L) and the other 10 patients treated with the S-I oblique posterior beams (Group S-I). Patients in both groups were matched by their clinical target volumes (CTVs-high and low dose levels) and respiratory motion amplitudes. Dose-volume-histogram (DVH) indices were used to assess plan quality. DVH bandwidth was calculated to evaluate plan robustness. Interplay effect was quantified using four-dimensional (4D) dynamic dose calculation with random respiratory starting phase of each fraction. Normal tissue complication probability (NTCP) for heart, liver, and lung was calculated, respectively, to estimate the clinical outcomes. Wilcoxon signed-rank test was used for statistical comparison between the two groups.ResultsCompared with plans in Group R-L, plans in Group S-I resulted in significantly lower liver Dmean and lung V30Gy[RBE] with slightly higher but clinically acceptable spinal cord Dmax . Similar plan robustness was observed between the two groups. When interplay effect was considered, plans in Group S-I performed statistically better for heart Dmean and V30Gy[RBE] , lung Dmean and V5Gy[RBE] , and liver Dmean , with slightly increased but clinically acceptable spinal cord Dmax . NTCP for liver was significantly better in Group S-I.ConclusionsIMPT plans in Group S-I have better sparing of liver, heart, and lungs at the slight cost of spinal cord maximum dose protection, and are more interplay-effect resilient compared to IMPT plans in Group R-L. Our study supports the routine use of the S-I oblique posterior beams for the treatments of distal esophageal carcinoma.
| S-EPMC7700921 | biostudies-literature
Project description:Proton beam therapy (PBT) is a promising modality for the management of thoracic malignancies. We report our preliminary experience of treating esophageal cancer patients with concurrent chemotherapy (CChT) and PBT (CChT/PBT) at MD Anderson Cancer Center.This is an analysis of 62 esophageal cancer patients enrolled on a prospective study evaluating normal tissue toxicity from CChT/PBT from 2006 to 2010. Patients were treated with passive scattering PBT with two- or three-field beam arrangement using 180 to 250 MV protons. We used the Kaplan-Meier method to assess time-to-event outcomes and compared the distributions between groups using the log-rank test.The median follow-up time was 20.1 months for survivors. The median age was 68 years (range, 38-86). Most patients were males (82%) who had adenocarcinomas (76%) and Stage II-III disease (84%). The median radiation dose was 50.4 Gy (RBE [relative biologic equivalence]) (range, 36-57.6). The most common grade 2 to 3 acute toxicities from CChT/PBT were esophagitis (46.8%), fatigue (43.6%), nausea (33.9%), anorexia (30.1%), and radiation dermatitis (16.1%). There were two cases of grade 2 and 3 radiation pneumonitis and two cases of grade 5 toxicities. A total of 29 patients (46.8%) received preoperative CChT/PBT, with one postoperative death. The pathologic complete response (pCR) rate for the surgical cohort was 28%, and the pCR and near CR rates (0%-1% residual cells) were 50%. While there were significantly fewer local-regional recurrences in the preoperative group (3/29) than in the definitive CChT/PBT group (16/33) (log-rank test, p = 0.005), there were no differences in distant metastatic (DM)-free interval or overall survival (OS) between the two groups.This is the first report of patients treated with PBT/CChT for esophageal cancer. Our data suggest that this modality is associated with a few severe toxicities, but the pathologic response and clinical outcomes are encouraging. Prospective comparison with more traditional approach is warranted.
| S-EPMC3923631 | biostudies-literature
Project description:PurposeProton beam therapy is a commonly accepted treatment for intraocular melanomas, but the literature is lacking in descriptions of patient preferences of clinical outcomes and economic impact. In addition, no economic evaluations have been published regarding the incremental cost-effectiveness of proton beam therapy compared with enucleation or plaque brachytherapy, typical alternative treatments. We, therefore, conducted a cost-utility analysis of these three approaches for the treatment of intraocular melanomas.Materials and methodsA Markov model was constructed. Model parameters were identified from the published literature and publicly available data sources. Cost-effectiveness of each treatment was calculated in 2011 US Dollars per quality-adjusted life-year. Incremental cost-effectiveness ratios were calculated assuming enucleation as reference. One-way sensitivity analyses were conducted on all model parameters. A decision threshold of $50,000/quality-adjusted life-year was used to determine cost-effectiveness.ResultsEnucleation had the lowest costs and quality-adjusted life-years, and plaque brachytherapy had the highest costs and quality-adjusted life-years. Compared with enucleation, the base-case incremental cost-effectiveness ratios for plaque brachytherapy and proton beam therapy were $77,500/quality-adjusted life-year and $106,100/quality-adjusted life-year, respectively. Results were highly sensitive to multiple parameters. All three treatments were considered optimal, and even dominant, depending on the values used for sensitive parameters.ConclusionBase-case analysis results suggest enucleation to be optimal. However, the optimal choice was not robust to sensitivity analyses and, depending on the assumption, both plaque brachytherapy and proton beam therapy could be considered cost-effective. Future clinical studies should focus on generating further evidence with the greatest parameter uncertainty to inform future cost-effectiveness analyses.
| S-EPMC4436277 | biostudies-literature
Project description:Proton radiotherapy has clear dosimetric advantages over photon radiotherapy. In contrast to photons, which are absorbed exponentially, protons have a finite range dependent on the initial proton energy. Protons therefore do not deposit dose beyond the tumor, resulting in great conformality, and offers the promise of dose escalation to increase tumor control while minimizing toxicity. In this review, we discuss the rationale for using proton radiotherapy in the treatment of upper abdominal tumors-hepatocellular carcinomas, cholangiocarcinomas and pancreatic cancers. We also review the clinical outcomes and technical challenges of using proton radiotherapy for the treatment of these malignancies. Finally, we discuss the ongoing clinical trials implementing proton radiotherapy for the treatment of primary liver and pancreatic tumors.
| S-EPMC7066948 | biostudies-literature
Project description:Cancer is a major cause of childhood death, with central nervous system (CNS) neoplasms being the second most common pediatric malignancy, following hematological cancer. Treatment of pediatric CNS malignancies requires multimodal treatment using a combination of surgery, chemotherapy, and radiotherapy, and advances in these treatments have given favorable results and longer survival. However, treatment-related toxicities have also occurred, particularly for radiotherapy, after which secondary cancer, reduced function of irradiated organs, and retarded growth are significant problems. Proton beam therapy (PBT) is a particle radiotherapy with excellent dose localization that permits treatment of liver and lung cancer by administration of a high dose to the tumor while minimizing damage to surrounding normal tissues. Thus, PBT has the potential advantages for pediatric cancer. In this context, we review the current knowledge on PBT for treatment of pediatric CNS malignancies.
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Project description:BackgroundThere are few comparative outcomes data regarding the therapeutic delivery of proton beam therapy (PBT) versus the more widely used photon-based external-beam radiation (EBRT) and brachytherapy (BT). We evaluated the impact of PBT on overall survival (OS) compared to EBRT or BT on patients with localized prostate cancer.Patients and methodsThe National Cancer Data Base (NCDB) was queried for 2004-2015. Men with clinical stage T1-3, N0, M0 prostate cancer treated with radiation, without surgery or chemotherapy, were included. OS, the primary clinical outcome, was fit by Cox proportional hazard model. Propensity score matching was implemented for covariate balance.ResultsThere were 276,880 eligible patients with a median follow-up of 80.9 months. A total of 4900 (1.8%) received PBT, while 158,111 (57.1%) received EBRT and 113,869 (41.1%) BT. Compared to EBRT and BT, PBT patients were younger and were less likely to be in the high-risk group. On multivariable analysis, compared to PBT, men had worse OS after EBRT (adjusted hazard ratio [HR] = 1.72; 95% confidence interval [CI], 1.51-1.96) or BT (adjusted HR = 1.38; 95% CI, 1.21-1.58). After propensity score matching, the OS benefit of PBT remained significant compared to EBRT (HR = 1.64; 95% CI, 1.32-2.04) but not BT (adjusted HR = 1.18; 95% CI, 0.93-1.48). The improvement in OS with PBT was most prominent in men ≤ 65 years old with low-risk disease compared to other subgroups (interaction P < .001).ConclusionIn this national data set, PBT was associated with a significant OS benefit compared to EBRT, and with outcomes similar to BT. These results remain to be validated by ongoing prospective trials.
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Project description:Protons interact with human tissue differently than do photons and these differences can be exploited in an attempt to improve the care of lung cancer patients. This review examines proton beam therapy (PBT) as a component of a combined modality program for locally advanced lung cancers. It was specifically written for the non-radiation oncologist who desires greater understanding of this newer treatment modality. This review describes and compares photon (X-ray) radiotherapy (XRT) to PBT. The physical differences of these beams are described and the clinical literature is reviewed. Protons can be used to create treatment plans delivering significantly lower doses of radiation to the adjacent organs at risk (lungs, esophagus, and bone marrow) than photons. Clinically, PBT combined with chemotherapy has resulted in low rates of toxicity compared to XRT. Early results suggest a possible improvement in survival. The clinical results of proton therapy in lung cancer patients reveal relatively low rates of toxicity and possible survival benefits. One randomized study is being performed and another is planned to clarify the clinical differences in patient outcome for PBT compared to XRT. Along with the development of better systemic therapy, newer forms of radiotherapy such as PBT should positively impact the care of lung cancer patients. This review provides the reader with the current status of this new technology in treating locally advanced lung cancer.
| S-EPMC4129522 | biostudies-literature
Project description:Despite the conformality of modern X-ray therapy limiting high dose received by normal tissues the physical properties of X-rays make it impossible to avoid dose being delivered distal to the target. This "exit dose" is likely clinically significant especially for patients with gastrointestinal (GI) cancers when considering that even low dose received by the heart, lungs, bowel, and other radiosensitive structures can lead to morbidity and even may affect long-term tumor control. In contrast, proton beam therapy (PBT) delivers no "exit dose" and a growing body of literature suggests that this may improve clinical outcomes by reducing toxicity and even allowing for safe dose intensification to enhance tumor control. While there are not yet robust prospective data demonstrating the role of PBT for GI cancers, emerging retrospective data provide a strong rationale for continued study of how PBT may improve the therapeutic ratio for these patients. Here we review these data as well as discuss ongoing clinical trials of PBT for GI cancers.
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