Dosimetric Advantage Of Proton Therapy Research Articles

Proton therapy for reducing heart and cardiac substructure doses in Indian breast cancer patients.

Indians have a higher incidence of cardiovascular diseases, often at a younger age, than other ethnic groups. This higher baseline risk requires consideration when assessing additional cardiac morbidity of breast cancer treatment. Superior cardiac sparing is a critical dosimetric advantage of proton therapy in breast cancer radiotherapy. We report here the heart and cardiac-substructure doses and early toxicities in breast cancer patients treated post-operatively with proton therapy in India's first proton therapy center. We treated twenty breast cancer patients with intensity-modulated proton therapy (IMPT) from October 2019 to September 2022, eleven after breast conservation, nine following mastectomy, and appropriate systemic therapy, when indicated. The most prescribed dose was 40 GyE to the whole breast/chest wall and 48 GyE by simultaneous integrated boost to the tumor bed and 37.5 GyE to appropriate nodal volumes, delivered in 15 fractions. Adequate coverage was achieved for clinical target volume (breast/chest wall), i.e., CTV40, and regional nodes, with 99% of the targets receiving 95% of the prescribed dose (V95% > 99%). The mean heart dose was 0.78 GyE and 0.87 GyE for all and left breast cancer patients, respectively. The mean left anterior descending artery (LAD) dose, LAD D0.02cc, and left ventricle dose were 2.76, 6.46, and 0.2 GyE, respectively. Mean ipsilateral lung dose, V20Gy, V5Gy, and contralateral breast dose (Dmean) were 6.87 GyE, 14.6%, 36.4%, and 0.38 GyE, respectively. The dose to heart and cardiac substructures is lower with IMPT than published photon therapy data. Despite the limited access to proton therapy at present, given the higher cardiovascular risk and coronary artery disease prevalence in India, the cardiac sparing achieved using this technique merits consideration for wider adoption in breast cancer treatment.

Clinical Outcomes of Intensity Modulated Proton Therapy Reirradiation for Gynecologic Malignancies

Pelvic reirradiation (re-RT) for patients with gynecologic cancers remains a challenge because of toxicity concerns. Given the dosimetric advantages of proton therapy, we aimed to assess oncologic and toxicity outcomes of patients with re-RT to the pelvis/abdomen with intensity modulated proton therapy (IMPT) for gynecologic cancers. We performed a retrospective analysis of all patients with gynecologic cancer treated at a single institution between 2015 and 2021 with IMPT re-RT. Patients were included for analysis if the IMPT plan had at least partial overlap with the treated volume of a previous radiation treatment. A total of 29 patients were included for analysis, with 30 total courses of re-RT. The majority of patients had been treated previously with conventional fractionation to a median dose of 49.2 Gy (30-61.6 Gy). With a median follow-up of 23 months, 1-year local control was 83.5% and overall survival was 65.7%. Three patients (10%) developed acute and late grade 3 toxicity. One-year freedom from late grade 3+ toxicity was 96.3%. This is the first complete analysis of clinical outcomes for re-RT with IMPT for gynecologic malignancies. We demonstrate excellent local control and acceptable acute and late toxicity. IMPT should strongly be considered for treatments requiring re-RT for gynecologic malignancies.

A novel optimization algorithm for enabling dynamically collimated proton arc therapy

The advent of energy-specific collimation in pencil beam scanning (PBS) proton therapy has led to an improved lateral dose conformity for a variety of treatment sites, resulting in better healthy tissue sparing. Arc PBS delivery has also been proposed to enhance high-dose conformity about the intended target, reduce skin toxicity, and improve plan robustness. The goal of this work was to determine if the combination of proton arc and energy-specific collimation can generate better dose distributions as a logical next step to maximize the dosimetric advantages of proton therapy. Plans were optimized using a novel DyNamically collimated proton Arc (DNA) genetic optimization algorithm that was designed specifically for the application of proton arc therapy. A treatment planning comparison study was performed by generating an uncollimated two-field intensity modulated proton therapy and partial arc treatments and then replanning these treatments using energy-specific collimation as delivered by a dynamic collimation system, which is a novel collimation technology for PBS. As such, we refer to this novel treatment paradigm as Dynamically Collimated Proton Arc Therapy (DC-PAT). Arc deliveries achieved a superior target conformity and improved organ at risk (OAR) sparing relative to their two-field counterparts at the cost of an increase to the low-dose, high-volume region of the healthy brain. The incorporation of DC-PAT using the DNA optimizer was shown to further improve the tumor dose conformity. When compared to the uncollimated proton arc treatments, the mean dose to the 10mm of surrounding healthy tissue was reduced by 11.4% with the addition of collimation without meaningfully affecting the maximum skin dose (less than 1% change) relative to a multi-field treatment. In this case study, DC-PAT could better spare specific OARs while maintaining better target coverage compared to uncollimated proton arc treatments. While this work presents a proof-of-concept integration of two emerging technologies, the results are promising and suggest that the addition of these two techniques can lead to superior treatment plans warranting further development.

Variable Relative Biological Effectiveness of Proton Therapy Increases PET-Visible Mucosal Injury in Head and Neck Cancer Patients

Despite dosimetric advantages of proton therapy in head and neck cancers, there is concern for increased end of range relative biologic effectiveness (RBE) and subsequent dose enhancement and mucosal toxicity with proton therapy. Herein, we evaluated differences in mucosal PET avidity on post-treatment scans as a surrogate for mucosal injury between proton and photon therapy patients. We further assessed the relationship between PET changes and RBE. The cohort comprised 9 proton and 10 photon patients who received ≥50 Gy adjuvant radiotherapy to oropharyngeal mucosa who remained loco-regional disease free ≥6 months post-treatment. All patients underwent follow-up fluorodeoxyglucose (FDG) PET-CT scans 3 months post-radiotherapy. PET-CTs were fused to planning CTs using deformable registration. High- and low-uptake regions were auto-contoured using a ≥150% mean liver standard uptake value (SUV) threshold and intersected with mucosal targets with/without a 5mm margin. SUV maximum (SUVMAX) values, linear energy transfer (LET) statistics, and RBE statistics based on McNamara, Jones, and linear LET models were extracted and compared. The mucosal target SUVMAX values on post-treatment PET-CTs for proton patients averaged 6.78 compared to 4.83 for photon patients (p=0.0267). Near maximum (LETd1%) LET for mucosal targets with a 5mm margin averaged 5.232 keV/µm. RBE in high-uptake regions exceeded that of low-uptake regions (p=0.0039), with mean biologic dose exceeding clinical dose by 11.05%, 18.67%, and 15.65%, respectively, using different RBE models. Post-radiotherapy PET avidity was more commonly observed in proton patients. Within proton patient mucosal targets, the location of increased PET avidity corresponded to areas with higher RBE. This is the first report of differential PET findings based on RBE. These results suggest that elevated RBE was associated with PET avidity and mucosal injury.

Photon vs. Proton Whole Ventricular Radiotherapy for Non-Germinomatous Germ Cell Tumors

<h3>Purpose/Objective(s)</h3> The hypothesis is that dose to normal CNS structures is lower for children treated with proton therapy, as compared to photon therapy for children receiving whole ventricular radiotherapy (WVRT) for non-germinomatous germ cell tumors (NGGCT). We present data from patients enrolled in stratum 1 of the Children's Oncology Group study ACNS1123. <h3>Materials/Methods</h3> Dosimetric data for NGGCT patients on ACNS1123 who received 30.6 Gy WVRT were compared in a post-hoc analysis. Target segmentation was standardized using a contouring atlas as per the study protocol. The PTV was created by creating a 3-5mm geometric expansion from the CTV. Doses to cranial organs-at-risk (OARs) were compared between proton and photon treatments. Clinically relevant dose-volume parameters that were compared included mean dose and dose to 40% of the OAR volume (D40). A subgroup analysis of patients treated with 3 mm PTV margins was performed. Dosimetric comparisons between proton and photons plans were conducted using two-sided Wilcoxon's rank sum test for continuous variables. <h3>Results</h3> Fifty-eight patients had WVRT dosimetry available and were included; 13 (22%) received proton treatment and 45 (78%) received photon treatment. Median age was 10 years old (range 0-21). Mean and D40 doses to the supratentorial brain, cerebellum (see Table), and bilateral temporal, parietal and frontal lobes were statistically significantly lower amongst proton-treated patients compared to photon-treated patients. In a subgroup analysis of patients uniformly treated with a 3 mm planning target volume, patients who received proton therapy continued to have statistically significantly lower doses to brain OARs. <h3>Conclusion</h3> Children treated with proton therapy for WVRT had lower doses to normal brain structures when compared to those treated with photon therapy. Future work will help elucidate whether this dosimetric advantage of proton therapy translates to a reduction in toxicities for these patients.

Clinical Outcomes of Medulloblastoma Patients Treated with Proton Radiotherapy: A Systematic Review

<h3>Purpose/Objective(s)</h3> The aim of this study was to comprehensively review all studies examining clinical outcomes of proton therapy for craniospinal irradiation of medulloblastoma, to determine whether theoretical dosimetric advantages of proton therapy have translated into superior clinical outcomes, including survival and toxicities. <h3>Materials/Methods</h3> We performed a systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, using the PubMed (Medline), EMBASE, and Cochrane Library databases (inception to December 2021). The study was registered with PROSPERO, CRD42022302455. Articles in the English language reporting on clinical outcomes of pediatric and/or adult medulloblastoma patients treated with proton therapy were included. Two independent authors screened all titles/abstracts, reviewed full texts and extracted relevant data, with discrepancies resolved by consensus. Individual study quality was scored using Newcastle Ottawa Scale and overall evidence base by GRADE scale. <h3>Results</h3> Thirty-five studies were included, representing 629 unique patients. Publication dates ranged from 2011 to 2021, with the majority (n=32) from the United States. None of the studies were randomized, 12 were comparative, 9 were prospective, 3 mixed and 22 retrospective. Average mean/median follow up was 5.0 years (range = 4 weeks to 12.6 years). The majority of studies (n=19) reported on treatment with passive scatter proton beams exclusively. Average study quality score was 6.08 out of 9 (SD 0.688, median 5). Seven studies scored ≥8/9 on the Newcastle Ottawa Scale; an overall "moderate" GRADE score was assigned. Well-designed comparative cohort studies with adequate follow-up demonstrate superior neurocognitive outcomes, lower incidence of hypothyroidism (23% vs 69%) and reduced acute toxicities (including myelosuppression, esophagitis, diarrhea, weight loss and nausea/vomiting) in patients treated with protons compared to photons. The 10-year cumulative incidence of secondary malignancy is also lower for proton cohorts (2.1-4.9% vs 8%), but did not reach statistical significance in any individual study. Overall survival (10-yr) (85.3-86.9% for standard-risk disease), progression-free survival (10-yr), patterns of failure, and other endocrine outcomes such as incidence of GH deficiency, adrenal insufficiency and precocious puberty were similar to those reported for photon therapy. Quality of life, ototoxicity and incidence of CNS injury were also found to be comparable between proton and photon cohorts, albeit with lower quality of evidence. Overall, quality of evidence was most robust in the domains of intellectual outcomes, endocrinopathies and acute toxicity. <h3>Conclusion</h3> Moderate grade evidence supports proton beam therapy as a preferred treatment for craniospinal irradiation of medulloblastoma based on equivalent disease outcomes and comparable-to-improved toxicity versus photon beam radiotherapy.

The dosimetric enhancement of GRID profiles using an external collimator in pencil beam scanning proton therapy.

The radiobiological benefits afforded by spatially fractionated (GRID) radiation therapy pairs well with the dosimetric advantages of proton therapy. Inspired by the emergence of energy-layer specific collimators in pencil beam scanning (PBS), this work investigates how the spot spacing and collimation can be optimized to maximize the therapeutic gains of a GRID treatment while demonstrating the integration of a dynamic collimation system (DCS) within a commercial beamline to deliver GRID treatments and experimentally benchmark Monte Carlo calculation methods. GRID profiles were experimentally benchmarked using a clinical DCS prototype that was mounted to the nozzle of the IBA-dedicated nozzle system. Integral depth dose (IDD) curves and lateral profiles were measured for uncollimated and GRID-collimated beamlets. A library of collimated GRID dose distributions were simulated by placing beamlets within a specified uniform grid and weighting the beamlets to achieve a volume-averaged tumor cell survival equivalent to an open field delivery. The healthy tissue sparing afforded by the GRID distribution was then estimated across a range of spot spacings and collimation widths, which were later optimized based on the radiosensitivity of the tumor cell line and the nominal spot size of the PBS system. This was accomplished by using validated models of the IBA universal and dedicated nozzles. Excellent agreement was observed between the measured and simulated profiles. The IDDs matched above 98.7% when analyzed using a 1%/1-mm gamma criterion with some minor deviation observed near the Bragg peak for higher beamlet energies. Lateral profile distributions predicted using Monte Carlo methods agreed well with the measured profiles; a gamma passing rate of 95% or higher was observed for all in-depth profiles examined using a 3%/2-mm criteria. Additional collimation was shown to improve PBS GRID treatments by sharpening the lateral penumbra of the beamlets but creates a trade-off between enhancing the valley-to-peak ratio of the GRID delivery and the dose-volume effect. The optimal collimation width and spot spacing changed as a function of the tumor cell radiosensitivity, dose, and spot size. In general, a spot spacing below 2.0 cm with a collimation less than 1.0 cm provided a superior dose distribution among the specific cases studied. The ability to customize a GRID dose distribution using different collimation sizes and spot spacings is a useful advantage, especially to maximize the overall therapeutic benefit. In this regard, the capabilities of the DCS, and perhaps alternative dynamic collimators, can be used to enhance GRID treatments. Physical dose models calculated using Monte Carlo methods were experimentally benchmarked in water and were found to accurately predict the respective dose distributions of uncollimated and DCS-collimated GRIDprofiles.

Proton Therapy for Prostate Cancer: Challenges and Opportunities.

Simple SummaryReported clinical outcomes of proton therapy (PT) for localized prostate cancer are similar to photon-based external beam radiotherapy. Apparently, the dosimetric advantages of PT have yet to be translated to clinical benefits. The suboptimal clinical outcomes of PT might be attributable to inadequate dose prescription, as indicated by the ASCENDE-RT trial. Moreover, uncertainties involved in the treatment planning and delivery processes, as well as technological limitations in PT treatment systems, may lead to discrepancies between planned doses and actual doses delivered to patients. In this article, we reviewed the current status of PT for prostate cancer and discussed different clinical implementations that could potentially improve the clinical outcome of PT for prostate cancer. Various technological advancements under which uncertainties in dose calculations can be minimized, including MRI-guided PT, dual-energy photon-counting CT and high-resolution Monte Carlo-based treatment planning systems, are highlighted.The dosimetric advantages of proton therapy (PT) treatment plans are demonstrably superior to photon-based external beam radiotherapy (EBRT) for localized prostate cancer, but the reported clinical outcomes are similar. This may be due to inadequate dose prescription, especially in high-risk disease, as indicated by the ASCENDE-RT trial. Alternatively, the lack of clinical benefits with PT may be attributable to improper dose delivery, mainly due to geometric and dosimetric uncertainties during treatment planning, as well as delivery procedures that compromise the dose conformity of treatments. Advanced high-precision PT technologies, and treatment planning and beam delivery techniques are being developed to address these uncertainties. For instance, external magnetic resonance imaging (MRI)-guided patient setup rooms are being developed to improve the accuracy of patient positioning for treatment. In-room MRI-guided patient positioning systems are also being investigated to improve the geometric accuracy of PT. Soon, high-dose rate beam delivery systems will shorten beam delivery time to within one breath hold, minimizing the effects of organ motion and patient movements. Dual-energy photon-counting computed tomography and high-resolution Monte Carlo-based treatment planning systems are available to minimize uncertainties in dose planning calculations. Advanced in-room treatment verification tools such as prompt gamma detector systems will be used to verify the depth of PT. Clinical implementation of these new technologies is expected to improve the accuracy and dose conformity of PT in the treatment of localized prostate cancers, and lead to better clinical outcomes. Improvement in dose conformity may also facilitate dose escalation, improving local control and implementation of hypofractionation treatment schemes to improve patient throughput and make PT more cost effective.

Clinical Outcomes of Patients Treated With Intensity Modulated Proton Therapy (IMPT) Re-Irradiation for Gynecologic Malignancies

Pelvic re-irradiation for patients with gynecologic cancers remains a challenge due to toxicity concerns. Given the dosimetric advantages of proton therapy, we aimed to assess oncologic and toxicity outcomes of patients treated with re-irradiation to the pelvis/abdomen with IMPT for gynecologic cancers.A single-institution retrospective IRB-approved analysis was conducted of all gynecologic cancer patients treated between 2015-2020 with IMPT re-irradiation with at least partial overlap with the treated volume of the prior treatment. Toxicities were graded according to CTCAE v5.0. The Kaplan-Meier (KM) method was used to estimate local control (LC), freedom from progression (FFP), overall survival (OS), and late toxicity with their 95% confidence interval (CI).A total of 29 patients received re-irradiation to the pelvis and/or abdomen with IMPT. One patient received a 2nd course of re-irradiation. Primary sites included endometrial (n = 15), cervical (n = 7), vaginal (n = 3), vulvar (n = 2) and ovarian cancer (n = 2). Twenty-five patients were treated for a recurrence of their gynecological cancer while 4 patients had re-irradiation for a new gynecological primary. Three patients were treated in the adjuvant setting, 6 patients received brachytherapy boost, and 3 patients received concurrent hyperthermia. Fifteen patients received systemic therapy associated with their course of re-irradiation, 11 of which was concurrent. The majority of patients received radiation (RT) to their pelvis only (n = 22), while 5 patients received RT to their pelvis + abdomen and 4 patients received RT to para-aortic field only. Median age at time of re-irradiation was 65 years (range 34-95). Median dose of prior RT was 45 Gy (range 30-59.4 Gy). Median time between initial RT and re-irradiation was 2 years (range 7 months - 39 years). Median re-irradiation dose was 49.2 Gy (range 30-61.6 Gy). Fractionation included conventional (n = 21), hyperfractionation (n = 7), and IMPT-SBRT (n = 2). Median follow-up was estimated at 17 months (range 1-34 months) using the inverse-Kaplan-Meier method; 11 patients had either local, regional, or distant progression. 12-month LC was 90% (95% CI 78%-100%), 12 month-OS was 62% (95% CI 42%-100%), and 12-month FFP was 57% (95% CI 35%-79%). Two patients developed acute grade 3+ toxicity (grade 3 diarrhea, grade 3 anemia). Two patients developed late grade 3+ toxicity (grade 3 sacral ulcer; 1 patient with grade 3 vulvar radiation necrosis and grade 3 radiation proctitis). 12-month freedom from toxicity was 96% (95% CI 88%-100%), and 24 month freedom from toxicity was 86% (95% CI 65%-100%).This is the first series to report on clinical outcomes for re-irradiation with IMPT for gynecological malignancies. While extended long term follow-up is needed, our study demonstrates excellent local control with acceptable acute and late toxicity.A.E. Pollock: None. H. Risher: None. S.M. Bentzen: Travel Expenses; University of Copenhagen. D.M. Roque: None. G. Rao: None. E.M. Nichols: Arrange consortium meetings, help lead multi-institutional trials; GammaPod Research Consortium. Medical Director of University of Maryland Medical Center practice; University of Maryland School of Medicine. Oversee clinical operations of all UMSOM Radiation Oncology practices; University of Maryland School of Medicine. P. Mohindra: The Executive Committee shall recommend to the Board of Directors overall Alliance policy and direction, as well as Alliance priorities and activities. It shall approve, by majority vote, appointments of chairs for scientific and administrative committee; Alliance for Clinical Trials in Oncology. Participate in various activities of the f.

COMPARISON OF THE EFFECTIVENESS OF PROTON AND PHOTON THERAPY IN PATIENTS WITH BRAIN TUMORS

Owing to the development of molecular genetics, the role of radiation therapy and chemotherapy in treatment of patients with glioma (WHO Grade I–IV) has become more understandable. The overall survival among glioma patients has increased. As overall survival increases, oncologists are more likely to detect manifestations of late radiation toxicity that has a huge impact on Quality of Life in patients who have undergone radiation therapy in the past. In this regard, the question of finding more adequate radiation therapy techniques remains relevant. photon radiation therapy is the standard method; however, considering dosimetric advantages of proton therapy over photon therapy, its widespread use can potentially lead to the increased overall survival, decreased number of late radiation-induced complications and improved quality of life in the post-radiation period. This article presents some comparative characteristics of proton and photon radiation therapy in patients with gliomas (WHO Grade I–IV). dosimetry characteristics of protons in tissues were compared, data showing differences in survival of patients treated with photons versus patients treated with protons were presented, and general information on early and late radiation-induced toxicity arising from the treatment by these methods was disclosed.

Proton therapy delivery method affects dose-averaged linear energy transfer in patients

The dosimetric advantages of proton therapy have led to its rapid proliferation in recent decades. This has been accompanied by a shift in technology from older units that deliver protons by passive scattering (PS) to newer units that increasingly use pencil-beam scanning (PBS). The biologic effectiveness of proton physical dose purportedly rises with increasing dose-weighted average linear energy transfer (LETD). The objective of this study was to determine the extent to which proton delivery methods affect LETD. We calculated LETD from simple, dosimetrically matched, and clinical treatment plans with TOPAS Monte-Carlo transport code. Simple treatment plans comprised single fields of PS and PBS protons in a water phantom. We performed simulations of matched and clinical treatment plans by using the treatment and anatomic data obtained from a cohort of children with craniopharyngioma who previously received PS or PBS proton therapy. We compared the distributions of LETD from PS and PBS delivery methods in clinically relevant ROIs. Wilcoxon signed-rank tests comparing single fields in water revealed that the LETD values from PBS were significantly greater than those from PS inside and outside the targeted volume (p < 0.01). Statistical tests comparing LETD-volume histograms from matched and clinical treatment plans showed that LETD was generally greater for PBS treatment plans than for PS treatment plans (p < 0.05). In conclusion, the proton delivery method affects LETD both inside and outside of the target volume. These findings suggest that PBS is more biologically effective than PS. Given the rapid expansion of PBS proton therapy, future studies are needed to confirm the applicability of treatment evaluation methods developed for PS proton therapy to those for modern PBS treatments to ensure their safety and effectiveness for the growing population of patients receiving proton therapy. This study uses data from two clinical trials: NCT01419067 and NCT02792582.

Normal Tissue Injury Induced by Photon and Proton Therapies: Gaps and Opportunities.

Despite technological advances in radiation therapy (RT) and cancer treatment, patients still experience adverse effects. Proton therapy (PT) has emerged as a valuable RT modality that can improve treatment outcomes. Normal tissue injury is an important determinant of the outcome; therefore, for this review, we analyzed 2 databases: (1) clinical trials registered with ClinicalTrials.gov and (2) the literature on PT in PubMed, which shows a steady increase in the number of publications. Most studies in PT registered with ClinicalTrials.gov with results available are nonrandomized early phase studies with a relatively small number of patients enrolled. From the larger database of nonrandomized trials, we listed adverse events in specific organs/sites among patients with cancer who are treated with photons and protons to identify critical issues. The present data demonstrate dosimetric advantages of PT with favorable toxicity profiles and form the basis for comparative randomized prospective trials. A comparative analysis of 3 recently completed randomized trials for normal tissue toxicities suggests that for early stage non-small cell lung cancer, no meaningful comparison could be made between stereotactic body RT and stereotactic body PT due to low accrual (NCT01511081). In addition, for locally advanced non-small cell lung cancer, a comparison of intensity modulated RTwith passive scattering PT (now largely replaced by spot-scanned intensity modulated PT), PT did not provide any benefit in normal tissue toxicity or locoregional failure over photon therapy. Finally, for locally advanced esophageal cancer, proton beam therapy provided a lower total toxicity burden but did not improve progression-free survival and quality of life (NCT01512589). The purpose of this review is to inform the limitations of current trials looking at protons and photons, considering that advances in technology, physics, and biology are a continuum, and to advocate for future trials geared toward accurate precision RT that need to be viewed as an iterative process in a defined path toward delivering optimal radiation treatment. A foundational understanding of the radiobiologic differences between protons and photons in tumor and normal tissue responses is fundamental to, and necessary for, determining the suitability of a given type of biologically optimized RT to a patient or cohort.

Comparative photon and proton dosimetry for patients with mediastinal lymphoma in the era of Monte Carlo treatment planning and variable relative biological effectiveness

BackgroundExisting pencil beam analytical (PBA) algorithms for proton therapy treatment planning are not ideal for sites with heterogeneous tissue density and do not account for the spatial variations in proton relative biological effectiveness (vRBE). Using a commercially available Monte Carlo (MC) treatment planning system, we compared various dosimetric endpoints between proton PBA, proton MC, and photon treatment plans among patients with mediastinal lymphoma.MethodsEight mediastinal lymphoma patients with both free breathing (FB) and deep inspiration breath hold (DIBH) CT simulation scans were analyzed. The original PBA plans were re-calculated with MC. New proton plans that used MC for both optimization and dose calculation with equivalent CTV/ITV coverage were also created. A vRBE model, which uses a published model for DNA double strand break (DSB) induction, was applied on MC plans to study the potential impact of vRBE on cardiac doses. Comparative photon plans were generated on the DIBH scan.ResultsRe-calculation of FB PBA plans with MC demonstrated significant under coverage of the ITV V99 and V95. Target coverage was recovered by re-optimizing the PT plan with MC with minimal change to OAR doses. Compared to photons with DIBH, MC-optimized FB and DIBH proton plans had significantly lower dose to the mean lung, lung V5, breast tissue, and spinal cord for similar target coverage. Even with application of vRBE in the proton plans, the putative increase in RBE at the end of range did not decrease the dosimetric advantages of proton therapy in cardiac substructures.ConclusionsMC should be used for PT treatment planning of mediastinal lymphoma to ensure adequate coverage of target volumes. Our preliminary data suggests that MC-optimized PT plans have better sparing of the lung and breast tissue compared to photons. Also, the potential for end of range RBE effects are unlikely to be large enough to offset the dosimetric advantages of proton therapy in cardiac substructures for mediastinal targets, although these dosimetric findings require validation with late toxicity data.

Outcomes following proton therapy for Ewing sarcoma of the cranium and skull base.

Despite the dosimetric advantages of proton therapy, little data exist on patients who receive proton therapy for Ewing sarcoma of the cranium and skull base. This study reports local disease control and toxicity in such patients. We reviewed 25 patients (≤21 years old) with nonmetastatic Ewing sarcoma of the cranium and skull base treated between 2008 and 2018. Treatment toxicity was graded per the Common Terminology Criteria for Adverse Events v4.0. The Kaplan-Meier product limit method provided estimates of disease control and survival. Median patient age was 5.9 years (range, 1-21.7). Tumor subsites included the skull base (48%), non-skull-base calvarial bones (28%), paranasal sinuses (20%), and nasal cavity (4%). All patients underwent multiagent alkylator- and anthracycline-based chemotherapy; 16% underwent gross total resection (GTR) before radiation. Clinical target volume (CTV) 1 received 45 GyRBE and CTV2 received 50.4 GyRBE following GTR or 54-55.8 GyRBE following biopsy or subtotal resection. Median follow-up was 3.7 years (range, 0.26-8.3); no patients were lost. The 4-year local control, disease-free survival, and overall survival rates were 96%, 86%, and 92%, respectively. Two patients experienced in-field recurrences. One patient experienced bilateral conductive hearing loss requiring aids, two patients developed intracranial vasculopathy, and 6 patients required hormone replacement therapy for neuroendocrine deficits. None developed a secondary malignancy. Proton therapy is associated with a favorable therapeutic ratio in children with large Ewing tumors of the cranium and skull base. Despite its high conformality, we observed excellent local control and no marginal recurrences. Treatment dosimetry predicts limited long-term neurocognitive and neuroendocrine side effects.

45 GyRBE for group III orbital embryonal rhabdomyosarcoma

Purpose: Despite widespread concerns of radiotherapy toxicity in children with head and neck tumors, recent Children’s Oncology Group (COG) findings suggest that the use of 45 Gy results in an unacceptably high rate of local recurrences in patients with low-risk orbital rhabdomyosarcoma. We therefore evaluated outcomes in our pediatric patients who received 45 GyRBE using proton therapy.Material and methods: To assess disease control and toxicity, we reviewed the medical records of 30 children (≤21 years old) with COG stage 1, group III embryonal orbital rhabdomyosarcoma enrolled on a prospective outcome study and treated with proton therapy between 2007 and 2018.Results: Median age at the time of radiation was 4.8 years old. Twenty-one and nine patients received ifosfamide- and cyclophosphamide-based chemotherapy according to their respective cooperative group regimens. Median duration between the start of induction chemotherapy and radiation was 12 weeks. Two patients had a complete response to induction chemotherapy and two had stable disease. Twenty-six patients had a partial response to induction chemotherapy, with a median volume reduction of 66%. With a median follow-up of 4.0 years (range, 0.5–9.5 years), we observed 1 local failure 6 months following treatment in a patient who had a partial response to cyclosphophomide-based induction chemotherapy. The 5-year local control, progression-free survival, and overall survival rates were 97%, 97%, and 100%, respectively. Serious late toxicities included 18 patients with cataracts, 4 with exposure keratoconjunctivitis resulting in permanently reduced visual acuity, and 1 with chronic sinusitis.Conclusion: 45 GyRBE offers effective local control for most patients with group III orbital rhabdomyosarcoma. The delivery of proton therapy to the postinduction tumor volume plus a small margin can mitigate early- and intermediate-term toxicity, but side effects still occur and long-term data are needed to demonstrate the dosimetric advantage of proton therapy.

TH‐D‐BRC‐01: Panel Member

Interest in proton therapy has increased dramatically in the past couple of years, especially in the United States. There certainly is an important place for proton therapy in the arsenal of cancer treatments. Its dosimetric advantage and potential for low toxicity makes it the perfect partner for photons and other cancer treatment modalities.Often there is a belief that the new technology ought to be better but many believe that they should be widely adopted in the clinic only after evidence has shown that they are at least as safe and efficacious as existing technologies, which are often less expensive. This is the case for proton radiotherapy.This session being both educational and debate will provide a good review of basics and technological advancement as well as a comprehensive clinical update for both proton and photon therapy.Future technology developments and how they will impact the potential dosimetric advantage of proton therapy will be discussed. Particularly the debate will focus on whether these developments will close or widen the gap between photon and proton therapy. Learning Objectives: To review challenges, limitations, and recent and future developments in proton therapy. To review challenges, limitations, recent and future developments in photon radiotherapy. To review current clinical trials and challenging clinical cases.C. Yu, No company or organization that my presentation mentions provided me with financial support. I am the Founder and CEO of Xcision Medical Systems, LLC. However, my presentation will not mention any product or technology developed by Xcision.

TH‐D‐BRC‐03: Panel Member

Interest in proton therapy has increased dramatically in the past couple of years, especially in the United States. There certainly is an important place for proton therapy in the arsenal of cancer treatments. Its dosimetric advantage and potential for low toxicity makes it the perfect partner for photons and other cancer treatment modalities.Often there is a belief that the new technology ought to be better but many believe that they should be widely adopted in the clinic only after evidence has shown that they are at least as safe and efficacious as existing technologies, which are often less expensive. This is the case for proton radiotherapy.This session being both educational and debate will provide a good review of basics and technological advancement as well as a comprehensive clinical update for both proton and photon therapy.Future technology developments and how they will impact the potential dosimetric advantage of proton therapy will be discussed. Particularly the debate will focus on whether these developments will close or widen the gap between photon and proton therapy. Learning Objectives: To review challenges, limitations, and recent and future developments in proton therapy. To review challenges, limitations, recent and future developments in photon radiotherapy. To review current clinical trials and challenging clinical cases.C. Yu, No company or organization that my presentation mentions provided me with financial support. I am the Founder and CEO of Xcision Medical Systems, LLC. However, my presentation will not mention any product or technology developed by Xcision.

TH‐D‐BRC‐04: Panel Member

Interest in proton therapy has increased dramatically in the past couple of years, especially in the United States. There certainly is an important place for proton therapy in the arsenal of cancer treatments. Its dosimetric advantage and potential for low toxicity makes it the perfect partner for photons and other cancer treatment modalities.Often there is a belief that the new technology ought to be better but many believe that they should be widely adopted in the clinic only after evidence has shown that they are at least as safe and efficacious as existing technologies, which are often less expensive. This is the case for proton radiotherapy.This session being both educational and debate will provide a good review of basics and technological advancement as well as a comprehensive clinical update for both proton and photon therapy.Future technology developments and how they will impact the potential dosimetric advantage of proton therapy will be discussed. Particularly the debate will focus on whether these developments will close or widen the gap between photon and proton therapy. Learning Objectives: To review challenges, limitations, and recent and future developments in proton therapy. To review challenges, limitations, recent and future developments in photon radiotherapy. To review current clinical trials and challenging clinical cases.C. Yu, No company or organization that my presentation mentions provided me with financial support. I am the Founder and CEO of Xcision Medical Systems, LLC. However, my presentation will not mention any product or technology developed by Xcision.

TH‐D‐BRC‐00: Educational Point Counter/Point: Has Photon RT Hit the Limits?

Interest in proton therapy has increased dramatically in the past couple of years, especially in the United States. There certainly is an important place for proton therapy in the arsenal of cancer treatments. Its dosimetric advantage and potential for low toxicity makes it the perfect partner for photons and other cancer treatment modalities.Often there is a belief that the new technology ought to be better but many believe that they should be widely adopted in the clinic only after evidence has shown that they are at least as safe and efficacious as existing technologies, which are often less expensive. This is the case for proton radiotherapy.This session being both educational and debate will provide a good review of basics and technological advancement as well as a comprehensive clinical update for both proton and photon therapy.Future technology developments and how they will impact the potential dosimetric advantage of proton therapy will be discussed. Particularly the debate will focus on whether these developments will close or widen the gap between photon and proton therapy. Learning Objectives: To review challenges, limitations, and recent and future developments in proton therapy. To review challenges, limitations, recent and future developments in photon radiotherapy. To review current clinical trials and challenging clinical cases.C. Yu, No company or organization that my presentation mentions provided me with financial support. I am the Founder and CEO of Xcision Medical Systems, LLC. However, my presentation will not mention any product or technology developed by Xcision.

TH‐D‐BRC‐02: Panel Member

Interest in proton therapy has increased dramatically in the past couple of years, especially in the United States. There certainly is an important place for proton therapy in the arsenal of cancer treatments. Its dosimetric advantage and potential for low toxicity makes it the perfect partner for photons and other cancer treatment modalities.Often there is a belief that the new technology ought to be better but many believe that they should be widely adopted in the clinic only after evidence has shown that they are at least as safe and efficacious as existing technologies, which are often less expensive. This is the case for proton radiotherapy.This session being both educational and debate will provide a good review of basics and technological advancement as well as a comprehensive clinical update for both proton and photon therapy.Future technology developments and how they will impact the potential dosimetric advantage of proton therapy will be discussed. Particularly the debate will focus on whether these developments will close or widen the gap between photon and proton therapy. Learning Objectives: To review challenges, limitations, and recent and future developments in proton therapy. To review challenges, limitations, recent and future developments in photon radiotherapy. To review current clinical trials and challenging clinical cases.C. Yu, No company or organization that my presentation mentions provided me with financial support. I am the Founder and CEO of Xcision Medical Systems, LLC. However, my presentation will not mention any product or technology developed by Xcision.