Stereotactic Body Proton Therapy Research Articles

Stereotactic Body Proton Therapy Versus Conventionally Fractionated Proton Therapy for Early Prostate Cancer: A Randomized, Controlled, Phase 3 Trial

PurposeWe aimed to determine if ultrahypofractionated proton therapy delivered via stereotactic body proton therapy (SBPT) is noninferior to conventionally fractionated proton therapy (CFPT) in patients with early prostate cancer. Methods and MaterialsThis study was a multicenter, randomized, controlled, noninferiority phase 3 trial that included patients with histologically confirmed low-risk prostate adenocarcinoma defined by Gleason score grouping 1, Prostate-specific antigen <10 ng/mL, and clinical stage T1-T2a N0 M0 according to 7th edition of the American Joint Committee on Cancer tumor-node-metastasis cancer staging system. Eligible participants were randomly assigned initially at a 1:1 ratio and later at a 2:1 ratio to SBPT (38 Gy in 5 fractions) or CFPT (79.2 Gy in 44 fractions). The primary endpoint was freedom from failure (FFF) at 2 years from the date of randomization. Noninferiority for FFF was determined based on 1-sided confidence intervals. Toxicities were compared at different time points using Fisher's exact test. Health-related quality-of-life (HRQoL) was analyzed at different time points using a mixed-effects linear model. This trial is registered with ClinicalTrials.gov, NCT01230866, and is closed to accrual. ResultsBetween December 10, 2010, and September 29, 2020, 144 patients were enrolled and 135 were randomly assigned (90 to the SBPT group and 45 to the CFPT group). The median follow-up was 5 years (IQR, 3.9-5.2). The 2-year FFF was 100% for both groups, with the 1-sided 5-year risk difference in FFF between groups reported as 2.63% (90% CI, −1.70% to 6.96%), favoring the SBRT arm, thus fulfilling the prespecified criteria for noninferiority of SBPT compared with CFPT. Rates of gastrointestinal and genitourinary G2 and G3 toxicities did not differ significantly between groups. Further, HRQoL metrics did not differ significantly between groups over the study's median follow-up. ConclusionsSBPT is noninferior to CFPT regarding FFF, with similar long-term genitourinary and gastrointestinal toxicity rates and minimal impact in patient-reported HRQoL over time.

O 23 - Novel approach to three-dimensional image guidance to deliver prostate stereotactic body proton therapy (SBPT) in a fixed beam room

O 23 - Novel approach to three-dimensional image guidance to deliver prostate stereotactic body proton therapy (SBPT) in a fixed beam room

Final Analysis of a Phase III Controlled Randomized Study of Stereotactic Body Proton Therapy or Conventionally Fractionated Proton Therapy for Early Prostate Cancer: PCG GU002

To determine if stereotactic body proton therapy (SBPT) is non-inferior to conventionally fractionated proton therapy (CFPT) in patients with early prostate cancer. Multicenter, randomized, controlled, open-label, non-inferiority phase 3 trial that included patients with histologically confirmed low-risk prostate adenocarcinoma defined by Gleason score ≤6, PSA <10 ng/mL, and clinical stage T1-2a N0 M0 by AJCC 7th Ed. Eligible participants were randomly assigned (initially 1:1 and later 2:1 ratio) to CFPT (79.2 Gy in 44 fractions for 9 weeks) or SBPT (38 Gy in 5 fractions for 1 week). Concurrent or adjuvant androgen deprivation therapy was not allowed. The primary endpoint was freedom from failure (FFF) at 2 years, defined as the first occurrence of local, regional, or distant recurrence, biochemical failure by the Phoenix definition (increase of PSA ≥2 ng/mL over the nadir PSA), or the start of salvage therapy including ADT. Secondary endpoints included GI and GU grade ≥2 toxicity according to CTCAE v4 criteria, as well as health-related quality of life (HRQoL) metrics assessed by AUASI and EPIC scores. Non-inferiority would be declared if the 1-sided 95% confidence interval limit for the difference in 2-year FFF rate was below 4.2% between both groups by Clopper-Pearson exact method. Between November 2010 and September 2020, 133 patients were enrolled and randomly assigned to CFPT (n = 45) or SBPT (n = 88). Median follow-up was 5 years (IQ 3.9-5.2), with the last patient enrolled followed for at least 2 years. The 2-year FFF was 100% for both groups, fulfilling the pre-specified criteria for non-inferiority of SBPT compared to CFPT. By KM estimates, 5-year FFF was 97.4% and 100% (P = 0.1), and the 5-year OS was 97.1% and 95.5% (P = 0.46) for patients treated with CFPT and SBPT, respectively. The cumulative incidence of any grade ≥3 toxicities at 5 years was 0% and 5.7% (P = 0.14) for patients treated with CFPT and SBPT, respectively. The frequency of GI grade ≥2 toxicity at 6 months was of 0% and 2.3% (P = 0.55), and at 2 years was of 6.7% and 3.4% (P = 0.69) for patients treated with CFPT and SBPT, respectively. The frequency of GU grade ≥2 toxicity at 6 months was of 2.2% and 5.7% (P = 0.42), and at 2 years was of 8.9% and 5.7% (P = 0.54) for patients treated with CFPT and SBPT, respectively. Changes in HRQoL scores at 2 years were similar between groups (Table). SBPT is non-inferior to CFPT regarding FFF and associated with similar long-term toxicity rates and HRQoL metric scores.

An Integrated Physical Optimization Framework for Proton Stereotactic Body Radiation Therapy FLASH Treatment Planning Allows Dose, Dose Rate, and Linear Energy Transfer Optimization Using Patient-Specific Ridge Filters

Patient-specific ridge filters provide a passive means to modulate proton energy to obtain a conformal dose. Here we describe a new framework for optimization of filter design and spot maps to meet the unique demands of ultrahigh-dose-rate (FLASH) radiation therapy. We demonstrate an integrated physical optimization Intensity-modulated proton therapy (IMPT) (IPO-IMPT) approach for optimization of dose, dose-averaged dose rate (DADR), and dose-averaged linear energy transfer (LETd). We developed an inverse planning software to design patient-specific ridge filters that spread the Bragg peak from a fixed-energy, 250-MeV beam to a proximal beam-specific planning target volume. The software defines patient-specific ridge filter pin shapes and uses a Monte Carlo calculation engine, based on Geant4, to provide dose and LET influence matrices. Plan optimization, using matRAD, accommodates the IPO-IMPT objective function considering dose, dose rate, and LET simultaneously with minimum monitor unit constraints. The framework enables design of both regularly spaced and sparse-optimized ridge filters, from which some pins are omitted to allow faster delivery and selective LET optimization. To demonstrate the framework, we designed ridge filters for 3 example patients with lung cancer and optimized the plans using IPO-IMPT. The IPO-IMPT framework selectively spared the organs at risk by reducing LET and increasing dose rate, relative to IMPT planning. Sparse-optimized ridge filters were superior to regularly spaced ridge filters in dose rate. Depending on which parameter is prioritized, volume distributions and histograms for dose, DADR, and LETd, using evaluation structures specific to heart, lung, and esophagus, show high levels of FLASH dose-rate coverage and/or reduced LETd, while maintaining dose coverage within the beam specific planning target volume. This proof-of-concept study demonstrates the feasibility of using an IPO-IMPT framework to accomplish proton FLASH stereotactic body proton therapy, accounting for dose, DADR, and LETd simultaneously.

Comparison of Patient-Reported Quality-of-Life between Spot Scanned Proton Stereotactic Body Radiation Therapy and Conventional Proton Therapy after Radiotherapy for Intermediate-Risk Prostate Cancer: A Single-Center Prospective Registry Experience

<h3>Purpose/Objective(s)</h3> Proton stereotactic body proton therapy (SBPT) for prostate cancer takes advantage of biologic advantages with hypofractionation and the technical advances of spot scanning. We report toxicities and quality-of-life (QOL) in patients treated with SBPT versus conventional proton therapy (CPT) in a single-institution prospective registry. <h3>Materials/Methods</h3> Patients (Pt) with localized intermediate-risk prostate cancer (PC) were treated with proton radiation (RT) from 2016 to 2018 on an IRB approved prospective registry. Treatment included SBPT (≥6 Gy/fx) or CPT (<2 Gy/fx) per physician choice. Expanded Prostate Cancer Index Composite (EPIC), AUASI, SF-12, Promis10, FACIT-COST, and PRO-CTCAE QOL were administered pre-RT, end-of-treatment, 3, 6, 12 months post RT, and then annually. Toxicities were recorded according to CTCAE v5. Fisher's Exact and Kruskal-Wallis tests were utilized to compare pt characteristics between groups. Effect of treatment were analyzed using logistic regression (toxicity), Kaplan-Meier statistics, and repeated measure mixed models (QOL) with all events were baseline adjusted. <h3>Results</h3> 191 pts were included with a median follow-up of 43.2 months (SBPT:39.9, CPT: 44.9). SBPT (38 Gy/5 fxs) was used in 47 pts (24.6%) while CPT used in 144 pts (75.6%) ranged from 75.6-79.2 Gy in 39-44 fx. At baseline, SBPT pts, tended to be younger, higher BMI, lower Gleason score, lower T stage, less likely to have had prior or treatment concurrent ADT, and less likely to have had concurrent urinary medications. There was no significant difference between arms in terms of survival (p=0.22) and development of new primary cancers (p=0.63). At last follow-up, there were 1x failures for SBPT and 4x failure for CPT (p=0.92). Grade 2+ AE were experienced by 12.8% SBPT versus 11.1% CPT (p=0.76). When adjusted for baseline toxicity, neither acute (≤3 months) grade 2+ (p=0.3) nor chronic grade 2+ (p=0.24) AEs were significantly different between the arms. No significant differences occurred between the arms for Promis10 overall (p=0.76), Physical (p=0.75), or Social (p=0.79) domains, PRO-CTCAE (p>0.73), or FACIT-COST (p=0.92). In regard to EPIC domains, SBPT pts fared significantly (all p<0.05) better in: urinary, bowel, urinary function, urinary bother, urinary irritative/obstructive, bowel bother, and Mental SF12. All other domains did not approach statistical significance (all p>0.1). <h3>Conclusion</h3> There was no significant difference in PC patients treated with SBPT versus CPT except for an improvement in prostate specific QOL in SBPT patients. SBPT appears safe and effective, while providing improved QOL over CPT.

A Prospective Observational Study of Proton Stereotactic Body Radiation Therapy and Immunotherapy for Recurrent Metastatic Head and Neck Cancer: Initial Report of MC ROR1771 Survival Analysis and Toxicity

<h3>Purpose/Objective(s)</h3> Patients with recurrent head and neck squamous cell carcinoma (HNSCC) after previous platinum-based chemotherapy have a median survival of 6 months or less. CheckMate 141 demonstrated that nivolumab administration to this patient population led to a median 7.5-month survival vs. 5.1-months with standard therapy, with 36% 1-year overall survival. The effect of radiotherapy on tumor immunogenicity when combined with immunotherapy has been an area of interest in immuno-oncology. However, proton therapy's role in this space is not well understood. MC ROR1771 was designed as a multisite prospective observational study to evaluate the addition of stereotactic body proton therapy (SBPT) to nivolumab in a platinum-refractory population. <h3>Materials/Methods</h3> Patients with metastatic histologically confirmed HNSCC from any primary site were eligible. Two cycles of nivolumab every other week were followed by SBPT to 1-2 target lesion(s). Maintenance nivolumab continued every other week with follow-up for progression and treatment toxicity. Subsequent oligoprogression was treated with stereotactic body radiotherapy or SBPT as indicated. Objective criteria included target lesion response rate, overall survival, progression-free survival, time to distant metastasis, toxicity, and evaluation of potential predictive biomarkers. Survival analysis was conducted using the Kaplan-Meier method in statistical software. The focus of this report was survival and toxicity analyses. <h3>Results</h3> 15 patients enrolled with 13 receiving SBPT, after which one treated patient withdrew. Of the remaining twelve, 3 had laryngeal primary, 1 nasopharyngeal, and 8 oropharyngeal. 4 patients underwent one round of prior chemotherapy before enrollment, 3 patients two rounds, and 5 patients three rounds: 10 received concurrent chemoradiation in first line (5 definitive, 5 adjuvant), with 1 receiving neoadjuvant chemotherapy prior to chemoradiation, and one presenting with metastatic disease. SBPT dosing ranged from 35-50 Gy. From initiation of nivolumab, median overall survival was 12.5 months (1-year overall survival 67%), with median progression free survival of 4.5 months. Two patients presented with baseline grade 3 cancer pain; no ≥grade 3 toxicity specific to nivolumab nor SBPT was reported. One patient is still alive at 40 months from initiation of nivolumab. <h3>Conclusion</h3> In this highly pretreated population, overall and progression-free survival compare favorably with CheckMate 141, suggesting that SBPT co-treatment may be beneficial in this population. No ≥grade 3 toxicity occurred with nivolumab nor SBPT. Biochemical analysis and correlation with delineated local, regional, and distant radiographic response are forthcoming. Further prospective evaluation of combination SBPT and immunotherapy is needed.

Automated robust SBPT planning using EUD-based prediction of SBRT plan for patients with lung cancer

PurposeTo evaluate the quality of robust stereotactic body proton therapy (RSBPT) plans generated by one-clicking scripting method for patients with lung cancer. Materials and methodsRetrospective analysis was performed on fifty lung cancer patients whose plan with robustly stereotactic body radiation therapy (SBRT). Thirty out of fifty patients were used for training to build a regression model, based on robust SBRT reference doses, to predict EUD values of ROIs for robust SBPT planning. Thereafter, robust SBPT plans with both automated EUD-Based mimicking (Automated Robust Proton ARP) and manual (Manual Robust Proton MRP) methods were evaluated in the remaining 20 patients. Plans were compared in terms of dosimetric parameters and planning time. ResultsA statistically significantly improvement in target dose fall off was observed for ARP plans compare to MRP plans (Dose fall off: 135 for MRP and 88 for ARP, p < 0.01), while no differences in target coverage and conformity. A statistically significantly reduce in normal lung tissue were observed for ARP plans compare to MRP plans (Lung [Dmean cGy (RBE)]: MRP: 478 vs. ARP: 351, p < 0.01; Lung [V5Gy (RBE) (%)]: MRP: 16.1 vs. ARP: 12.1, p < 0.01; Lung [V20Gy (RBE) (%)]: MRP: 8.5 vs. ARP: 6.8, p < 0.01). Planning time was reduced for ARP plans compare to MRP plans (optimization time: 12 min for MRP vs. 8 min for ARP; total plan time: 23 min for MRP vs. 18 min for ARP). ConclusionThe automated robust SBPT plans using EUD-Based mimicking of SBRT reference dose improve target dose fall off, reduced the radiation doses to the lungs, reduce planning time, which might be beneficial for patient with lung cancer in clinical.

A Beam-Specific Optimization Target Volume for Stereotactic Proton Pencil Beam Scanning Therapy for Locally Advanced Pancreatic Cancer

PurposeWe investigate two margin-based schemes for optimization target volumes (OTV), both isotropic expansion (2 mm) and beam-specific OTV, to account for uncertainties due to the setup errors and range uncertainties in pancreatic stereotactic pencil beam scanning (PBS) proton therapy. Also, as 2-mm being one of the extreme sizes of margin, we also study whether the plan quality of 2-mm uniform expansion could be comparable to other plan schemes. Methods and MaterialsWe developed 2 schemes for OTV: (1) a uniform expansion of 2 mm (OTV2mm) for setup uncertainty and (2) a water equivalent thickness–based, beam-specific expansion (OTVWET) on beam direction and 2 mm expansion laterally. Six LAPC patients were planned with a prescribed dose of 33 Gy (RBE) in 5 fractions. Robustness optimization (RO) plans on gross tumor volumes, with setup uncertainties of 2 mm and range uncertainties of 3.5%, were implemented as a benchmark. ResultsAll 3 optimization schemes achieved decent target coverage with no significant difference. The OTV2mm plans show superior organ at risk (OAR) sparing, especially for proximal duodenum. However, OTV2mm plans demonstrate severe susceptibility to range and setup uncertainties with a passing rate of 19% of the plans meeting the goal of 95% volume covered by the prescribed dose. The proposed dose spread function analysis shows no significant difference. ConclusionsThe use of OTVWET mimics a union volume for all scenarios in robust optimization but saves optimization time noticeably. The beam-specific margin can be attractive to online adaptive stereotactic body proton therapy owing to the efficiency of the plan optimization.

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.

Simulation of an HDR "Boost" with Stereotactic Proton versus Photon Therapy in Prostate Cancer: A Dosimetric Feasibility Study.

Purpose/ObjectivesTo compare the dose escalation potential of stereotactic body proton therapy (SBPT) versus stereotactic body photon therapy (SBXT) using high-dose rate prostate brachytherapy (HDR-B) dose-prescription metrics.Patients and MethodsTwenty-five patients previously treated with radiation for prostate cancer were identified and stratified by prostate size (≤ 50cc; n = 13, > 50cc; n = 12). Initial CT simulation scans were re-planned using SBXT and SBPT modalities using a prescription dose of 19Gy in 2 fractions. Target coverage goals were designed to mimic the dose distributions of HDR-B and maximized to the upper limit constraint for the rectum and urethra. Dosimetric parameters between SBPT and SBXT were compared using the signed-rank test and again after stratification for prostate size (≤ 50cm3 and >50cm3) using the Wilcoxon rank test.ResultsProstate volume receiving 100% of the dose (V100) was significantly greater for SBXT (99%) versus SBPT (96%) (P ≤ 0.01), whereas the median V125 (82% vs. 73%, P < 0.01) and V200 (12% vs. 2%, P < 0.01) was significantly greater for SBPT compared to SBXT. Median V150 was 49% for both cohorts (P = 0.92). V125 and V200 were significantly correlated with prostate size. For prostates > 50cm3, V200 was significantly greater with SBPT compared to SBXT (14.5% vs. 1%, P = 0.005), but not for prostates 50cm3 (9% vs 4%, P = 0.11). Median dose to 2cm3 of the bladder neck was significantly lower with SBPT versus SBXT (9.6 Gy vs. 14 Gy, P < 0.01).ConclusionSBPT and SBXT can be used to simulate an HDR-B boost for locally advanced prostate cancer. SBPT demonstrated greater dose escalation potential than SBXT. These results are relevant for future trial design, particularly in patients with high risk prostate cancer who are not amenable to brachytherapy.

A Novel Use of Hydrogel as a Dual-Buffer in Stereotactic Body Proton Therapy for Locally Advanced Pancreatic Cancer

To evaluate the dosimetric efficacy of using hydrogel as a dual buffer, namely to suppress the dose to duodenum and boost the plan robustness in stereotactic body proton therapy for locally advanced pancreatic cancer. The dosimetric advantages of hydrogel spacer is quantitatively evaluated by a proposed quantity, full-width-half-maximum (FWHM) of dose spread function (DSF), which is defined as the distance needed to dwindle dose 50% off to the duodenum. The dose spread function is the derivative of dose falloff profile along the neighboring of 100% isodose line and critical organ. A proof-of-concept study was implemented on one of the previously treated pancreatic patients with prescribed dose of 33 Gy (RBE) in 5 fractions using spot scanning proton beam. The gross target volume is expanded with 2 mm using on-board volumetric imaging system to an optimization target volume (OTV). The proton plan dose profile in the abutment region between 100% isodose line and duodenum is sampled. The dose falloff is differentiated to obtain the FWHM distance to lower the dose to a 50% level. For all voxels representing the surface of duodenum, the mean values of FWHMs is therefore determined as the required spacing from hydrogel injection. An organ deformation method is developed to simulate the hydrogel spacer included in the post-injection plan, which is compared dosimetrically with pre-injection plan. The plan robust evaluation of the target coverage was assessed with 2 mm setup and 3.5% range uncertainties, defined as the percentage of the disturbed scenarios meeting the goal of more than 95% of target covered by at least 100% of the prescribed dose. The target coverages of both pre-injection and post-injection plans are able to achieve D98% with about 99% of the prescription. The required hydrogel spacing FWHM (mean distance for duodenum dose dropping to 50%) is determined as 14.1 mm. The average dose for duodenum in the hydrogel pre-injection plan is 7.35 Gy (RBE), while for post-injection plan is 4.61 Gy (RBE). By simulating the organ deformation induced by hydrogel spacing using the pre-determined value of FWHM, the dose covering 50% volume of the duodenum is lowered from 3.67 Gy (RBE) of pre-injection plan to 1.77 Gy (RBE) in the simulated post-injection plan, which is consistent with estimation using FWHM value. The high dose region to duodenum is also lowered for D2cc from 28 Gy (RBE) to 20.9 Gy (RBE). The robustness evaluation indicates that the passing rate of pre-injection plan is only 7%, while for the simulated post-injection plan is 21%. This study indicates that a hydrogel in SBPT can function dual roles as decreasing the dose to duodenum and improving the robustness of the post-injection pancreatic plan. With the knowledge of FWHM from DSF, the required spacing from hydrogel is determined. The dose level in post-injection plan match the desired dose level. The post-injection plan also demonstrates the improved immunity to range uncertainties and setup errors.

A proton primer to stereotactic lung radiotherapy

Stereotactic body radiation therapy (SBRT) is regarded as a safe and effective treatment for early stage non-small cell lung cancer (NSCLC). However, the safety of SBRT has been questioned, specifically in the treatment of central tumors abutting critical organs at risk (OARs), when treating large or multiple tumors or when re-irradiating. Due to these concerns, radiation with stereotactic body proton therapy (SBPT) has emerged as a possible alternative due to its potential to decrease dose to OARs. The Particle Therapy Cooperative Group (PTCOG) recommends consideration of SBPT for large or multiple tumors, central tumors and those close to critical OARs. However, proton irradiation can be associated with significant uncertainty due to tumor motion, tissue heterogeneity, set up error, or changes in patient anatomy, as well as variations in distal range linear energy transfer values. In this review, we discuss clinical outcomes data from prospective and retrospective studies evaluating the benefits and risks of SBPT, methods to address uncertainties associated with PBT, and future directions for research.

Stereotactic body proton therapy for liver tumors: Dosimetric advantages and their radiobiological and clinical implications.

Background and PurposePhoton Stereotactic Body Radiotherapy (SBRT) for primary and metastatic tumors of the liver is challenging for larger lesions. An in silico comparison of paired SBRT and Stereotactic Body Proton Therapy (SBPT) plans was performed to understand the potential advantages of SBPT as a function of tumor size and location.Methods and materialsTheoretical tumor volumes with maximum diameter of 1–10 cm were contoured in the dome, right inferior, left medial, and central locations. SBRT and SBPT plans were generated to deliver 50 Gy in 5 fractions, max dose <135%. When organs-at-risk (OAR) constraints were exceeded, hypothetical plans (not clinically acceptable) were generated for comparison. Liver normal tissue complication probability (NTCP) models were applied to evaluate differences between treatment modalities.ResultsSBRT and SBPT were able to meet target goals and OAR constraints for lesions up to 7 cm and 9 cm diameter, respectively. SBPT plans resulted in a higher integral gross target dose for all lesions up to 7 cm (mean dose 57.8 ± 2.3 Gy to 64.1 ± 2.2 Gy, p < 0.01). Simultaneously, SBPT spared dose to the uninvolved liver in all locations (from 11.5 ± 5.3 Gy to 8.6 ± 4.4 Gy, p < 0.01), resulting in lower NTCP particularly for larger targets in the dome and central locations. SBPT also spared duodenal dose across all sizes and positions (from 7.3 ± 1.1 Gy to 1.1 ± 0.3 Gy, p < 0.05).ConclusionThe main advantages of SBPT over SBRT is meeting plan goals and constrains for larger targets, particularly dome and central locations, and sparing dose to uninvolved liver. For such patients, SBPT may allow improvements in tumor control and treatment safety.

Stereotactic Body Radiotherapy for Centrally Located Non-small Cell Lung Cancer

已有的少数研究表明，早期不可手术非小细胞肺癌立体定向放射治疗肿瘤局控率可超过90%，患者中位生存时间和总生存率接近外科手术治疗。近年来立体定向放射治疗已成为Ⅰ期不可手术周围型非小细胞肺癌患者的推荐治疗。但中央型肺癌因其解剖位置多毗邻纵隔内重要脏器，常可伴有更明显的放疗副反应。中央型肺癌是否能进行立体定向放射治疗目前尚无统一定论，本文主要对中央型非小细胞肺癌立体定向放射治疗的定义、适应症、剂量分割方式、危及器官剂量-体积限制、放疗技术支持、副反应及立体定向质子治疗进行综述。

(OA03) A Phase II Study of Stereotactic Body Radiotherapy and Stereotactic Body Proton Therapy for High-Risk Medically Inoperable Early-Stage Non-Small Cell Lung Cancer

We sought to compare the toxicity and efficacy of stereotactic body radiotherapy (SBRT) versus stereotactic body proton therapy (SBPT) for high-risk medically inoperable early-stage non-small cell lung cancer (NSCLC). We randomly assigned patients with medically inoperable NSCLC with high-risk features (centrally located or <5 cm-T3 tumor or isolated lung parenchymal recurrences) to SBRT or SBPT. Radiation dose was 50 Gy(RBE) in four 12.5-Gy(RBE) fractions prescribed to the planning target volume. SBRT was given as 3-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT), and SBPT was given as passive scattering. Consistency in patient setup was ensured with on-board cone-beam computed tomography for the SBRT group and with orthogonal X-rays for the SBPT group. The study closed early owing to poor accrual, largely because of patient preference, insurance coverage, and lack of volumetric imaging in SBPT group. Ultimately, 21 patients were enrolled, and 19 patients who received 50 Gy in 4 fractions were included for analysis (9 SBRT, 10 SBPT). At a median follow-up time of 32 months, median overall survival (OS) time was 28 months in the SBRT group and not reached in the SBPT group. Three-years OS were 27.8% and 90%, 3-year local control (LC) were 87.5% (8/9) and 90.0% (9/10) and 3-years regional control (RC) were 47.6% (5/9) and 90% (9/10) in SBRT and SBPT respectively. One patient in the SBPT group developed grade 3 skin fibrosis. No patients experienced grade 4/5 toxicity. This is the first randomized phase II study to compare SBRT with SBPT for high-risk medically inoperable early-stage NSCLC. Although poor accrual led to early closure of the trial and precluded assessment of efficacy, both techniques seemed to have acceptable toxicity, and outcomes after SBPT were no worse than those after SBRT.

Phase 2 Study of Stereotactic Body Radiation Therapy and Stereotactic Body Proton Therapy for High-Risk, Medically Inoperable, Early-Stage Non-Small Cell Lung Cancer

To report the feasibility of conducting a randomized study to compare thetoxicity and efficacy of stereotactic body radiation therapy (SBRT) versus stereotactic body proton therapy (SBPT) for high-risk, medically inoperable, early-stage non-small cell lung cancer (NSCLC). Patients with medically inoperable NSCLC with high-risk features (centrally located or <5cm T3 tumor or isolated lung parenchymal recurrences) were randomly assigned to SBRT or SBPT. Radiation dose was 50Gy(relative biological effectiveness [RBE]) in 4 12.5-Gy(RBE) fractions prescribed to the planning target volume. Stereotactic body radiation therapy was given using 3-dimensional conformal radiation therapy or intensity modulated radiation therapy, and SBPT was given using passive scattering. Consistency in patient setup was ensured with on-board cone beam computed tomography for the SBRT group and with orthogonal X rays for the SBPT group. The study closed early owing to poor accrual, largely because of insurance coverage and lack of volumetric imaging in the SBPT group. Ultimately, 21 patients were enrolled, and 19 patients who received 50Gy in 4 fractions were included for analysis (9SBRT, 10 SBPT). At a median follow-up time of 32months, median overall survival time was 28months in the SBRT group and not reached in the SBPT group. Three-year overall survival was 27.8% and 90%, 3-year local control was 87.5% (8 of 9) and 90.0% (9 of 10), and 3-year regional control was 47.6% (5 of 9) and 90% (9 of 10) in the SBRT and SBPT groups, respectively. One patient in the SBPT group developed grade 3 skin fibrosis. No patients experienced grade 4/5 toxicity. Poor accrual, due to lack of volumetric imaging and insurance coverage for proton therapy, led to early closure of the trial and precluded accurate assessment of efficacy and toxicity. Comparable maturity of 2 radiation therapy modalities, particularly on-board imaging, and better insurance coverage for SBPT should be considered for future studies.

A Phase I Trial of Stereotactic Body Proton Therapy (SBPT) for Liver Metastases

A Phase I Trial of Stereotactic Body Proton Therapy (SBPT) for Liver Metastases

Spot-scanned pancreatic stereotactic body proton therapy: A dosimetric feasibility and robustness study

PurposeWe explored the dosimetric potential of spot-scanned stereotactic body proton therapy (SBPT) for pancreatic cancer. MethodsWe compared SBPT to stereotactic body intensity-modulated radiotherapy (SB-IMRT) in 10 patients. We evaluated 3 variables in SBPT planning: (1) 4 and 6 mm spot size; (2) single vs. multi-field optimization (SFO vs. MFO); and (3) optimization target volume (OTV) expansion. Robustness analysis was performed with unidirectional isocenter shifts of ±3 mm in x, y, and z and ±3% stopping power uncertainties. ResultsSBPT plans had lower V10Gy for the stomach and small and large bowels. Under static robustness, a 5 mm OTV and SFO-6 mm spot size represented the best compromise between target and normal structure. A 4-mm spot-size and 3 mm OTV resulted in significant target underdosing with deformable dose accumulation analysis. ConclusionsThis study provides a critical basis for clinical translation of spot size, optimization technique, and OTV expansion for pancreatic SBPT.

Aggregated Plan Robustness Analyses for Spot-Scanned Pancreatic Stereotactic Body Proton Therapy

minimum dose of at least 39.2 GyE was achieved in 95% of the plans. Multicomparative and 2-sample t-tests were used. Results: The median GTV and CTV volumes were 43.9 and 56.9 cc, respectively. With median minimum separation from GTV of 0.15 cm (range, 0.0-1.6 cm), the duodenum was the most difficult organ-at-risk (OAR) for meeting dosimetric constraints, especially in the CTV+7 mm cases. For CTV+5 mm planning, selected IMRT and SBPT dosimetric values are shown in Table; P-values were calculated across all 4 proton groups. The integral dose was significantly better for proton vs. IMRT plans (V5Gy, 1663 vs. 3285 cc, P Z 0.0064), as for multiple other OARs. While most proton plans were acceptable, 4-mm spot plans gave slightly less dose to the OAR structures owing to a smaller spot size, but the binary differences (vs. 6-mm spot) were not statistically significant in most cases. Conclusions: Benchmarked against IMRT planning, pancreatic SBPT offers comparable duodenal sparing with significant improvements in most OAR dosimetric metrics considered, which represents an attractive therapeutic option. Under static proton planning considerations, MFO vs. SFO differences were generally not statistically significant. As expected, smaller spot size trended for better OAR sparing. Further proton plan robustness evaluations are warranted to determine the optimal combination of spot size, optimization technique, and target volume for spot placement in spotscanned SBPT. Author Disclosure: T.T. Sio: None. E.J. Tryggestad: None. J.B. Ashman: None. C.J. Beltran: None. W.S. Harmsen: None. K.A. Hoeft: None. S.K. Wurgler: None. R.C. Miller: None.

Individualized altered fractionation as a more effective radiotherapy for non-small cell lung cancer.

Individualized altered fractionation as a more effective radiotherapy for non-small cell lung cancer.