Pencil-beam scanning (PBS) proton therapy (PT), particularly intensity modulated PT, represents the latest advanced PT technology for treating cancers, including thoracic malignancies. On the basis ...of virtual clinical studies, PBS-PT appears to have great potential in its ability to tightly tailor the dose to the target while sparing critical structures, thereby reducing treatment-related toxicities, particularly for tumors in areas with complicated anatomy. However, implementing PBS-PT for moving targets has several additional technical challenges compared with intensity modulated photon radiation therapy or passive scattering PT. Four-dimensional computed tomography–based motion management and robust optimization and evaluation are crucial for minimizing uncertainties associated with beam range and organ motion. Rigorous quality assurance is required to validate dose delivery both before and during the course of treatment. Active motion management (eg, breath hold), beam gating, rescanning, tracking, or adaptive planning may be needed for cases involving significant motion or changes in motion or anatomy over the course of treatment.
Dose uncertainty induced by respiratory motion remains a major concern for treating thoracic and abdominal lesions using particle beams. This Task Group report reviews the impact of tumor motion and ...dosimetric considerations in particle radiotherapy, current motion‐management techniques, and limitations for different particle‐beam delivery modes (i.e., passive scattering, uniform scanning, and pencil‐beam scanning). Furthermore, the report provides guidance and risk analysis for quality assurance of the motion‐management procedures to ensure consistency and accuracy, and discusses future development and emerging motion‐management strategies. This report supplements previously published AAPM report TG76, and considers aspects of motion management that are crucial to the accurate and safe delivery of particle‐beam therapy. To that end, this report produces general recommendations for commissioning and facility‐specific dosimetric characterization, motion assessment, treatment planning, active and passive motion‐management techniques, image guidance and related decision‐making, monitoring throughout therapy, and recommendations for vendors. Key among these recommendations are that: (1) facilities should perform thorough planning studies (using retrospective data) and develop standard operating procedures that address all aspects of therapy for any treatment site involving respiratory motion; (2) a risk‐based methodology should be adopted for quality management and ongoing process improvement.
Proton therapy can allow for superior avoidance of normal tissues. A widespread consensus has been reached that proton therapy should be used for patients with curable pediatric brain tumor to avoid ...critical central nervous system structures. Brainstem necrosis is a potentially devastating, but rare, complication of radiation. Recent reports of brainstem necrosis after proton therapy have raised concerns over the potential biological differences among radiation modalities. We have summarized findings from the National Cancer Institute Workshop on Proton Therapy for Children convened in May 2016 to examine brainstem injury.
Twenty-seven physicians, physicists, and researchers from 17 institutions with expertise met to discuss this issue. The definition of brainstem injury, imaging of this entity, clinical experience with photons and photons, and potential biological differences among these radiation modalities were thoroughly discussed and reviewed. The 3 largest US pediatric proton therapy centers collectively summarized the incidence of symptomatic brainstem injury and physics details (planning, dosimetry, delivery) for 671 children with focal posterior fossa tumors treated with protons from 2006 to 2016.
The average rate of symptomatic brainstem toxicity from the 3 largest US pediatric proton centers was 2.38%. The actuarial rate of grade ≥2 brainstem toxicity was successfully reduced from 12.7% to 0% at 1 center after adopting modified radiation guidelines. Guidelines for treatment planning and current consensus brainstem constraints for proton therapy are presented. The current knowledge regarding linear energy transfer (LET) and its relationship to relative biological effectiveness (RBE) are defined. We review the current state of LET-based planning.
Brainstem injury is a rare complication of radiation therapy for both photons and protons. Substantial dosimetric data have been collected for brainstem injury after proton therapy, and established guidelines to allow for safe delivery of proton radiation have been defined. Increased capability exists to incorporate LET optimization; however, further research is needed to fully explore the capabilities of LET- and RBE-based planning.
A substantial barrier to the single- and multi-institutional aggregation of data to supporting clinical trials, practice quality improvement efforts, and development of big data analytics resource ...systems is the lack of standardized nomenclatures for expressing dosimetric data. To address this issue, the American Association of Physicists in Medicine (AAPM) Task Group 263 was charged with providing nomenclature guidelines and values in radiation oncology for use in clinical trials, data-pooling initiatives, population-based studies, and routine clinical care by standardizing: (1) structure names across image processing and treatment planning system platforms; (2) nomenclature for dosimetric data (eg, dose–volume histogram DVH-based metrics); (3) templates for clinical trial groups and users of an initial subset of software platforms to facilitate adoption of the standards; (4) formalism for nomenclature schema, which can accommodate the addition of other structures defined in the future. A multisociety, multidisciplinary, multinational group of 57 members representing stake holders ranging from large academic centers to community clinics and vendors was assembled, including physicists, physicians, dosimetrists, and vendors. The stakeholder groups represented in the membership included the AAPM, American Society for Radiation Oncology (ASTRO), NRG Oncology, European Society for Radiation Oncology (ESTRO), Radiation Therapy Oncology Group (RTOG), Children's Oncology Group (COG), Integrating Healthcare Enterprise in Radiation Oncology (IHE-RO), and Digital Imaging and Communications in Medicine working group (DICOM WG); A nomenclature system for target and organ at risk volumes and DVH nomenclature was developed and piloted to demonstrate viability across a range of clinics and within the framework of clinical trials. The final report was approved by AAPM in October 2017. The approval process included review by 8 AAPM committees, with additional review by ASTRO, European Society for Radiation Oncology (ESTRO), and American Association of Medical Dosimetrists (AAMD). This Executive Summary of the report highlights the key recommendations for clinical practice, research, and trials.
Abstract
Background. Proton therapy offers superior low and intermediate radiation dose distribution compared with photon-based radiation for brain and skull base tumors; yet tissue within and ...adjacent to the target volume may receive a comparable radiation dose. We investigated the tolerance of the pediatric brainstem to proton therapy and identified prognostic variables.
Material and methods. All patients < 18 years old with tumors of the brain or skull base treated from 2007 to 2013 were reviewed; 313 who received > 50.4 CGE to the brainstem were included in this study. Brainstem toxicity was graded according to the NCI Common Terminology Criteria for Adverse Events v4.0.
Results. The three most common histologies were ependymoma, craniopharyngioma, and low-grade glioma. Median patient age was 5.9 years (range 0.5-17.9 years) and median prescribed dose was 54 CGE (range 48.6-75.6 CGE). The two-year cumulative incidence of toxicity was 3.8% ± 1.1%. The two-year cumulative incidence of grade 3 + toxicity was 2.1% ± 0.9%. Univariate analysis identified age < 5 years, posterior fossa tumor location and specific dosimetric parameters as factors associated with an increased risk of toxicity.
Conclusion. Utilization of current national brainstem dose guidelines is associated with a low risk of brainstem toxicity in pediatric patients. For young patients with posterior fossa tumors, particularly those who undergo aggressive surgery, our data suggest more conservative dosimetric guidelines should be considered.
Proton therapy has been shown to reduce radiation dose to organs at risk (OAR) and could be used to safely escalate the radiation dose. We analyzed outcomes in a group of phase 2 study patients ...treated with dose-escalated proton therapy with concurrent chemotherapy for stage 3 non-small cell lung cancer (NSCLC).
From 2009 through 2013, LU02, a phase 2 trial of proton therapy delivering 74 to 80 Gy at 2 Gy/fraction with concurrent chemotherapy for stage 3 NSCLC, was opened to accrual at our institution. Due to slow accrual and competing trials, the study was closed after just 14 patients (stage IIIA, 9 patients; stage IIIB, 5 patients) were accrued over 4 years. During that same time period, 55 additional stage III patients were treated with high-dose proton therapy, including 7 in multi-institutional proton clinical trials, 4 not enrolled due to physician preference, and 44 who were ineligible based on strict entry criteria. An unknown number of patients were ineligible for enrollment due to insurance coverage issues and thus were treated with photon radiation. Median follow-up of surviving patients was 52 months.
Two-year overall survival and progression-free survival rates were 57% and 25%, respectively. Median lengths of overall survival and progression-free survival were 33 months and 14 months, respectively. There were no acute grade 3 toxicities related to proton therapy. Late grade 3 gastrointestinal toxicity and pulmonary toxicity each occurred in 1 patient.
Dose-escalated proton therapy with concurrent chemotherapy was well tolerated with encouraging results among a small cohort of patients. Unfortunately, single-institution proton studies may be difficult to accrue and consideration for pragmatic and/or multicenter trial design should be considered when developing future proton clinical trials.
This study describes the early clinical outcomes of a prospective phase 2 study of consolidative involved-node proton therapy (INPT) as a component of combined-mode therapy in patients with stages I ...to III Hodgkin lymphoma (HL) with mediastinal involvement.
Between September 2009 and June 2013, 15 patients with newly diagnosed HL received INPT after completing chemotherapy in an institutional review board-approved protocol comparing the dosimetric impact of PT with those of three-dimensional conformal radiation therapy (3DCRT) and intensity modulated RT. Based on 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) response, 5 children received 15 to 25.5 cobalt Gy equivalent (CGE) of INPT after receiving 4 cycles of Adriamycin, Bleomycin, Vincristine, Etoposide, Prednisone, Cyclophosphamide or Vincristine, adriamycin, methotrexate, Prednisone chemotherapy, and 10 adults received 30.6 to 39.6 CGE of INPT after 3 to 6 cycles of Adriamycin, Bleomycine, Vinblastine, Dacarbazine. Patients were routinely evaluated for toxicity during and after treatment, using Common Terminology Criteria for Adverse Events, version 3.0, and for relapse by physical examination and routine imaging. Relapse-free survival (RFS) and event-free survival (EFS) rates were calculated using the Kaplan-Meier method from the time of diagnosis.
The median follow-up was 37 months (range, 26-55). Two events occurred during follow-up: 1 relapse (inside and outside the targeted field) and 1 transformation into a primary mediastinal large B cell lymphoma. The 3-year RFS rate was 93%, and the 3-year EFS rate was 87%. No acute or late grade 3 nonhematologic toxicities were observed.
Although decades of follow-up will be needed to realize the likely benefit of PT in reducing the risk of radiation-induced late effects, PT following chemotherapy in patients with HL is well-tolerated, and disease outcomes were similar to those of conventional photon therapy.
To compare three-dimensional conformal proton radiotherapy (3DCPT), intensity-modulated photon radiotherapy (IMRT), and 3D conformal photon radiotherapy (3DCRT) to predict the optimal RT technique ...for retroperitoneal sarcomas.
3DCRT, IMRT, and 3DCPT plans were created for treating eight patients with retroperitoneal or intra-abdominal sarcomas. The clinical target volume (CTV) included the gross tumor plus a 2-cm margin, limited by bone and intact fascial planes. For photon plans, the planning target volume (PTV) included a uniform expansion of 5 mm. For the proton plans, the PTV was nonuniform and beam-specific. The prescription dose was 50.4 Gy/Cobalt gray equivalent CGE. Plans were normalized so that >95% of the CTV received 100% of the dose.
The CTV was covered adequately by all techniques. The median conformity index was 0.69 for 3DCPT, 0.75 for IMRT, and 0.51 for 3DCRT. The median inhomogeneity coefficient was 0.062 for 3DCPT, 0.066 for IMRT, and 0.073 for 3DCRT. The bowel median volume receiving 15 Gy (V15) was 16.4% for 3DCPT, 52.2% for IMRT, and 66.1% for 3DCRT. The bowel median V45 was 6.3% for 3DCPT, 4.7% for IMRT, and 15.6% for 3DCRT. The median ipsilateral mean kidney dose was 22.5 CGE for 3DCPT, 34.1 Gy for IMRT, and 37.8 Gy for 3DCRT. The median contralateral mean kidney dose was 0 CGE for 3DCPT, 6.4 Gy for IMRT, and 11 Gy for 3DCRT. The median contralateral kidney V5 was 0% for 3DCPT, 49.9% for IMRT, and 99.7% for 3DCRT. Regardless of technique, the median mean liver dose was <30 Gy, and the median cord V50 was 0%. The median integral dose was 126 J for 3DCPT, 400 J for IMRT, and 432 J for 3DCRT.
IMRT and 3DCPT result in plans that are more conformal and homogenous than 3DCRT. Based on Quantitative Analysis of Normal Tissue Effects in Clinic benchmarks, the dosimetric advantage of proton therapy may be less gastrointestinal and genitourinary toxicity.
We investigated the dosimetric impact of proton therapy (PT) on various cardiac subunits in patients with Hodgkin lymphoma (HL).
From June 2009 through December 2010, 13 patients were enrolled on an ...institutional review board-approved protocol for consolidative involved-node radiotherapy (INRT) for HL. Three separate treatment plans were developed prospectively by using three-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), and PT. Cardiac subunits were retrospectively contoured on the 11 patients with intravenous-contrast simulation scans, and the doses were calculated for all treatment plans. A Wilcoxon paired test was performed to evaluate the statistical significance (p < 0.05) of 3DCRT and IMRT compared with PT.
The mean heart doses were 21 Gy, 12 Gy, and 8 Gy (relative biologic effectiveness RBE) with 3DCRT, IMRT, and PT, respectively. Compared with 3DCRT and IMRT, PT reduced the mean doses to the left and right atria; the left and right ventricles; the aortic, mitral, and tricuspid valves; and the left anterior descending, left circumflex, and right circumflex coronary arteries.
Compared with 3DCRT and IMRT, PT reduced the radiation doses to all major cardiac subunits. Limiting the doses to these structures should translate into lower rates of cardiac toxicities.
Purpose
To investigate the dosimetric impact of prostate intrafraction motion on proton double‐scattering (DS) and uniform scanning (US) treatments using electromagnetic transponder‐based prostate ...tracking data in simulated treatment deliveries.
Methods
In proton DS delivery, the spread‐out Bragg peak (SOBP) is created almost instantaneously by the constant rotation of the range modulator. US, however, delivers each entire energy layer of the SOBP sequentially from distal to proximal direction in time, which can interplay with prostate intrafraction motion. This spatiotemporal interplay during proton treatment was simulated to evaluate its dosimetric impact. Prostate clinical target volume (CTV) dose was obtained by moving CTV through dose matrices of the energy layers according to prostate‐motion traces. Fourteen prostate intrafraction motion traces of each of 17 prostate patients were used in the simulated treatment deliveries. Both single fraction dose‐volume histograms (DVHs) and fraction‐cumulative DVHs were obtained for both 2 Gy per fraction and 7.25 Gy per fraction stereotactic body radiotherapy (SBRT).
Results
The simulation results indicated that CTV dose degradation depends on the magnitude and direction of prostate intrafraction motion and is patient specific. For some individual fractions, prescription dose coverage decreased in both US and DS treatments, and hot and cold spots inside the CTV were observed in the US results. However, fraction‐cumulative CTV dose coverage showed much reduced dose degradation for both DS and US treatments for both 2 Gy per fraction and SBRT simulations.
Conclusions
This study indicated that CTV dose inhomogeneity may exist for some patients with severe prostate intrafraction motion during US treatments. However, there are no statistically significant dose differences between DS and US treatment simulations. Cumulative dose of multiple‐fractions significantly reduced dose uncertainties.
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