Citations

AbstractPurposeTo develop an online graphic processing unit (GPU)‐accelerated Monte Carlo‐based adaptive radiation therapy (ART) workflow for pencil beam scanning (PBS) proton therapy to address interfraction anatomical changes in patients treated with PBS.Methods and MaterialsA four‐step workflow was developed using our in‐house developed GPU‐accelerated Monte Carlo‐based treatment planning system to implement online Monte Carlo‐based ART for PBS. The first step conducts diffeomorphic demon‐based deformable image registration (DIR) to propagate contours on the initial planning CT (pCT) to the verification CT (vCT) to form a new structure set. The second step performs forward dose calculation of the initial plan on the vCT with the propagated contours after manual approval (possible modifications involved). The third step triggers a reoptimization of the plan depending on whether the verification dose meets the clinical requirements or not. A robust evaluation will be done for both the verification plan in the second step and the reopotimized plan in the third step. The fourth step involves a two‐stage (before and after delivery) patient‐specific quality assurance (PSQA) of the reoptimized plan. The before‐delivery PSQA is to compare the plan dose to the dose calculated using an independent fast open‐source Monte Carlo code, MCsquare. The after‐delivery PSQA is to compare the plan dose to the dose recalculated using the log file (spot MU, spot position, and spot energy) collected during the delivery. Jaccard index (JI), dice similarity coefficients (DSCs), and Hausdorff distance (HD) were used to assess the quality of the propagated contours in the first step. A commercial plan evaluation software, ClearCheck™, was integrated into the workflow to carry out efficient plan evaluation. 3D Gamma analysis was used during the fourth step to ensure the accuracy of the plan dose from reoptimization. Three patients with three different disease sites were chosen to evaluate the feasibility of the online ART workflow for PBS.ResultsFor all three patients, the propagated contours were found to have good volume conformance [JI (lowest‐highest: 0.833–0.983) and DSC (0.909–0.992)] but suboptimal boundary coincidence [HD (2.37–20.76 mm)] for organs‐at‐risk. The verification dose evaluated by ClearCheck™ showed significant degradation of the target coverage due to the interfractional anatomical changes. Reoptimization on the vCT resulted in great improvement of the plan quality to a clinically acceptable level. 3D Gamma analyses of PSQA confirmed the accuracy of the plan dose before delivery (mean Gamma index = 98.74% with a threshold of 2%/2 mm/10%), and after delivery based on the log files (mean Gamma index = 99.05% with a threshold of 2%/2 mm/10%). The average time cost for the complete execution of the workflow was around 858 s, excluding the time for manual intervention.ConclusionThe proposed online ART workflow for PBS was demonstrated to be efficient and effective by generating a reoptimized plan that significantly improved the plan quality.

Background: There is lack of data regarding impact of atherectomy on the length of stay (LOS) and cost of hospitalization in lower extremity arterial revascularization. Methods: HCUP’s Nationwide Inpatient Sample (NIS) 2012 was queried using the ICD-9- CM code for peripheral vascular disease and procedural codes 39.90 (bare metal stent - BMS), 00.55 (drug eluting stent - DES), 17.56 (peripheral atherectomy) and 39.50 for angioplasty. Only procedures performed in patients ≥18 years of age were included. Hierarchical mixed effects linear regression models were generated to evaluate multivariate predictors of LOS and hospitalization costs. Results: A total of 13,206 (weighted: 66,030) lower extremity arterial revascularizations were identified (43.8% female & 65.5% white). Out of these, atherectomy was utilized in 23.2%. Atherectomy utilization was associated with significant reduction in LOS (4.96 ± 0.11 days vs. 5.78 ± 0.07 days, p <0.001) but higher hospitalization cost ($ 25196 ± 359 vs. $ 23408 ± 185, p < 0.001). Multivariate analysis showed similar results with decrease in LOS (-0.71 days, -1.00 - - 0.43; p < 0.001) but higher hospitalization cost (+1875 $, +811 - +2940; p = 0.001) with atherectomy, which was matched by propensity score analysis. Additionally, emergent/urgent & weekend admissions and Charlson score ≥2 were further associated with increased LOS and hospitalization costs. (Figure) Conclusion: Our study demonstrates that atherectomy utilization is associated with significant reduction in length of stay, which was counterbalanced by a slight increase in hospitalization costs following lower extremity arterial revascularization.

Introduction: Use of transcatheter endovascular stenting has been increasing in the treatment of Coarctation of Aorta (CoA). The present study was undertaken on adults with CoA undergoing stent placement from the period of 2000 to 2011 to analyze the relationship of hospital volume to the outcomes of stenting in adults with CoA. Methods: We queried Healthcare Cost and Utilization Project (HCUP)’s Nationwide Inpatient Sample (NIS) database from 2000 to 2011. Patients with CoA were identified using ICD-9-CM diagnosis code of 747.10. Patients≥18 years of age undergoing endovascular stenting were identified using ICD-9-CM procedure code of 39.90. Hospital volume was divided into two groups with ≥3 and <3 procedures annually. The outcomes studied were procedure-related complications, length of stay (LOS), and cost in relation to the hospital volume. Complications were coded using specific patient safety indicator codes released by HCUP. Length of stay (≤1 and >1 days) and cost (≤ $13,830 and > $13,830) were divided at median and included in regression analysis. Results: No in-hospital death was reported in either group. Hospitals with ≥3 procedures annually had significantly lower incidence of complications (9.50% vs. 23.01%) compared to the hospitals with <3 procedures annually (p=0.002). After multivariate regression analysis, compared to hospitals with <3 procedures annually, the hospitals with ≥3 procedures annually had odds ratio (OR) of 0.40 (95% CI: 0.19-0.82, p=0.013) for having any complications, OR of 0.67 (95% CI: 0.39-1.17, p=0.15) for having LOS>1 day, and OR of 0.72 (95% CI: 0.45-1.13, p=0.15) for having cost>$13,830. Conclusion: Stenting in adults for aortic coarctation is remarkably safe and the outcomes of the procedure have improved in centers with annual hospital volume of ≥3 procedures, and there is also decreasing trend of procedure-related complications, shorter hospital stay, and lower costs compared to centers with annual volume <3 procedures.

Introduction: The data regarding use of different Mechanical Circulatory Support (MCS) devices in TAVR is limited. The present study was performed to analyze the complications and outcomes of different MCS in TAVR. Methods: The subjects under study were obtained from Nationwide Inpatient Sample (NIS) for the years 2011-12 using ICD-9-CM procedure codes for TAVR and MCS. The use of MCS was divided into Intra-aortic balloon pump (IABP), percutaneous ventricular assist devices (PVADs) including Impella and TandemHeart, Extracorporeal membrane oxygenation (ECMO) and percutaneous cardiopulmonary support and cardiopulmonary bypass (CBP) using ICD-9-CM codes. The incidence of in-hospital mortality and occurrence of procedure related complications were analyzed. Results: Out of total 1794 TAVR procedures, MCS was utilized in 190 (10.6%) procedures. CBP was the most commonly utilized 136 (71.6%) followed by IABP 36 (18.9%), ECMO 14 (7.4%) and 4 (2.1%). In-hospital mortality was highest with use of IABP (36.6%), followed by ECMO (14.3%), CBP (9.6%) and PVAD (0%) with p-value <0.01. The incidence of complications was similar in IABP and PVAD (100% each) followed by ECMO (85.7%) and CBP (59.4%) with p-value <0.01. Conclusion: Being retrospective in design, the present study has no information regarding indications and individual patient related variables in which each of the MCS devices used. Overall, CBP was observed as the most extensive used MCS modality with less mortality (9.6%) and least complications (59.4%).

Introduction: Over the past decade, Transcatheter Aortic Valve Replacement (TAVR) has emerged as a therapeutic option for treating severe aortic stenosis in high-risk patients. Patients with liver cirrhosis are at high risk for operative morbidity and mortality when they undergo cardiac surgery. In the present study, in-hospital outcomes are compared in cirrhotic patients undergoing TAVR vs. Surgical Aortic Valve Replacement (SAVR). Methods: The study population was derived from the National Inpatient Sample (NIS) for the years 2011 and 2012 using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) procedure codes 35.21 and 35.22 for SAVR, and 35.05 and 35.06 for TAVR. Patients<50 years of age and those with concomitantly other valvular procedures were excluded. ICD-9-CM diagnosis codes were used to identify patients with liver cirrhosis including those with other manifestations of cirrhosis such as portal hypertension and esophageal varices. Using propensity score matching, two matched cohorts were derived in which the outcomes were compared using chi-square test, fisher’s exact test, and student’s t-test. Results: There were 30 cirrhotic patients in the SAVR and TAVR group each after propensity score matching. Compared to the TAVR group, the patients in the SAVR group had higher mean cost of hospitalization ($79,263 vs. $63,913, p=0.12), mean post-procedural length of stay (14.3 days vs. 6.2 days, p<0.01), any complications rate (80.0% vs. 60.0%, p=0.09), rate of transfusion of blood or blood products (56.7% vs. 30.0%, p=0.037) and liver complications rate (20.0% vs. 10.0%, p=0.4). The in-hospital mortality rate was same in both the groups (6.7%). Conclusions: In high-risk cirrhotic patients, TAVR is a viable option for aortic valve replacement compared to SAVR.

Abstract Purpose To evaluate the accuracy of the RayStation Monte Carlo dose engine (RayStation MC) in modeling small‐field block apertures in proton pencil beam scanning. Furthermore, we evaluate the suitability of MCsquare as a second check for RayStation MC. Methods We have enhanced MCsquare to model block apertures. To test the accuracy of both RayStation MC and the newly enhanced MCsquare, we compare the dose predictions of each to in‐water dose measurements obtained using diode detectors and radiochromic film. Nine brass apertures with openings of 1, 2, 3, 4, and 5 cm and either 2 cm or 4 cm thickness were used in the irradiation of a water phantom. Two measurement setups were used, one with a range shifter and 119.7 MeV proton beam energy and the other with no range shifter and 147 MeV proton beam energy. To further test the validity of RayStation MC and MCsquare in modeling block apertures and to evaluate MCsquare as a second check tool, 10 small‐field (average target volume 8.3 cm 3 ) patient treatment plans were calculated by each dose engine followed by a statistical comparison. Results Comparing to the absolute dose measurements in water, RayStation MC differed by 1.2% ± 1.0% while MCsquare differed by −1.8% ± 3.7% in the plateau region of a pristine Bragg peak. Compared to the in‐water film measurements, RayStation MC and MCsquare both performed well with an average 2D‐3D gamma passing rate of 99.4% and 99.7% (3%/3 mm), respectively. A t ‐test comparing the agreement with the film measurements between RayStation MC and MCsquare suggested that the relative spatial dose distributions calculated by MCsquare and RayStation MC were statistically indistinguishable. Directly comparing the dose calculations between MCsquare and RayStation MC over 10 patients resulted in an average 3D‐3D gamma passing rates of 98.5% (3%/3 mm) and 94.1% (2%/2 mm), respectively. Conclusion The validity of RayStation MC algorithm for use with patient‐specific apertures has been expanded to include small apertures. MCsquare has been enhanced to model apertures and was found to be an adequate second check of RayStation MC in this scenario.

PURPOSE To improve the outcomes of patients with T-cell acute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphoma (T-LL), the proteasome inhibitor bortezomib was examined in the Children's Oncology Group phase III clinical trial AALL1231, which also attempted to reduce the use of prophylactic cranial radiation (CRT) in newly diagnosed T-ALL. PATIENTS AND METHODS Children and young adults with T-ALL/T-LL were randomly assigned to a modified augmented Berlin-Frankfurt-Münster chemotherapy regimen with/without bortezomib during induction and delayed intensification. Multiple modifications were made to the augmented Berlin-Frankfurt-Münster backbone used in the predecessor trial, AALL0434, including using dexamethasone instead of prednisone and adding two extra doses of pegaspargase in an attempt to eliminate CRT in most patients. RESULTS AALL1231 accrued 824 eligible and evaluable patients from 2014 to 2017. The 4-year event-free survival (EFS) and overall survival (OS) for arm A (no bortezomib) versus arm B (bortezomib) were 80.1% ± 2.3% versus 83.8% ± 2.1% (EFS, P = .131) and 85.7% ± 2.0% versus 88.3% ± 1.8% (OS, P = .085). Patients with T-LL had improved EFS and OS with bortezomib: 4-year EFS (76.5% ± 5.1% v 86.4% ± 4.0%; P = .041); and 4-year OS (78.3% ± 4.9% v 89.5% ± 3.6%; P = .009). No excess toxicity was seen with bortezomib. In AALL0434, 90.8% of patients with T-ALL received CRT. In AALL1231, 9.5% of patients were scheduled to receive CRT. Evaluation of comparable AALL0434 patients who received CRT and AALL1231 patients who did not receive CRT demonstrated no statistical differences in EFS ( P = .412) and OS ( P = .600). CONCLUSION Patients with T-LL had significantly improved EFS and OS with bortezomib on the AALL1231 backbone. Systemic therapy intensification allowed elimination of CRT in more than 90% of patients with T-ALL without excess relapse.

Abstract Background: Partial breast irradiation (PBI) is an established option for selected patients with early stage breast cancer. The optimal technique, target volume and dose/fractionation for PBI has yet to be defined. The most studied regimen in North America (38.5 Gy in 10 fractions twice daily) has been associated with cosmetic deterioration. We hypothesized that condensing treatment and reducing the total administered dose could improve the therapeutic ratio in luminal breast cancer and DCIS based on emerging evidence that breast cancer is more sensitive than surrounding normal tissues to high dose fractions. Herein, we report cosmetic, tolerability, disease control, and patient reported outcomes of a novel ultra-accelerated PBI regimen. Methods: We conducted a single arm, three cohort trial of photon, proton, and brachytherapy PBI. Technique was selected at physician and patient discretion. Eligible women were age ≥ 50 years with estrogen receptor positive (ER+), sentinel lymph node negative invasive or in-situ breast cancer measuring ≤ 2.5 cm. The regimen was designed to have comparable biologically equivalent effect as 40 Gy in 15 fractions, assuming an α/β ratio of 3.5. Intracavitary brachytherapy target volume was lumpectomy cavity plus 1 cm and prescribed 21 Gy in 3 fractions. Photon and proton target volumes were post-operative tumor bed plus 1 cm and a 3 mm setup uncertainty margin, prescribed 21.9 Gy (RBE) in 3 fractions, and delivered with image guidance. The primary outcome was the percentage difference in patients with adverse cosmesis (defined as fair or poor cosmesis) at 3 years compared to baseline pre-PBI, as assessed by trained nurses using the 4-point Harvard breast cosmesis scale. Patients also completed quality of life surveys and self-reported cosmesis using the 4-point scale. Locoregional and distant recurrence-free survival was determined using the Kaplan-Meier method. Adverse events were assessed using CTCAE, v 4.0. Results: Between 2015 and 2017, 163 patients were treated: photons in 58, protons in 48, and brachytherapy in 57. Median patient age was 66 years. 129 (79%) patients had invasive breast cancer (all ER+) and 34 (21%) had DCIS (83% ER+). Median tumor size was 1.1 cm. Grade was 2-3 in 102 (63%). The median mean heart/ipsilateral lung doses were photons 0.1/1.6 Gy, protons &lt;0.001/0.1 Gy, and brachytherapy 0.5/0.9 Gy. Median follow-up was 4.1 years (IQR 3.9-5.0). The proportion of patients with adverse cosmesis (by RN assessment) was 14.3% at baseline and 3.8% at 3 years, with four patients (1 photon, 1 proton, 2 brachytherapy) experiencing cosmetic deterioration at 3 years from baseline. The proportion with adverse cosmesis by self-report at 3 years was 2.4%, with three patients (1 photon, 1 proton, 1 brachytherapy) reporting cosmetic deterioration. Four patients developed locoregional recurrence (1 photons, 2 protons, 1 brachytherapy); three were local only and one was local and distant. 4-year locoregional recurrence and distant metastasis-free survival were 97.9% and 97.4%, respectively. There were 2 treatment related ≥ grade 2 late events (grade 2 fibrosis and grade 2 seroma, both brachytherapy associated), and no evidence of deterioration in patient-reported pain, fatigue, breast related or overall quality of life, as assessed by the patient reported outcomes version of the CTCAE, 10-point linear analog scales, and the breast cancer treatment outcomes scale. Conclusions: Ultra-accelerated 3-fraction PBI exquisitely spared normal tissues and was associated with favorable cosmetic outcomes, disease control, and excellent long-term tolerability. This ‘precision-radiotherapy’ approach may optimize the therapeutic ratio over more aggressive radiotherapy options as well as radiotherapy omission, particularly in patients with long life expectancies. Citation Format: Robert Mutter, Tina Hieken, Todd DeWees, Arslan Afzal, Stephanie Kenison, Laura Vallow, Christopher Deufel, Nicholas Remmes, Kathryn Ruddy, Judy Boughey, Keith Furutani, Amy Degnim, James Jakub, Tamara Vern-Gross, Dean Shumway, William Wong, Samir Patel, Lisa McGee, Minetta Liu, Carlos Vargas, Daniel Visscher, Bradley Stish, Deanna Pafundi, Mark Waddle, Michael Golafshar, Michele Halyard, Kimberly Corbin, Sean Park. Ultra-accelerated photon, proton, and brachytherapy partial breast irradiation: Primary results of the Mayo 3-fraction trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD7-03.

BACKGROUNDPatients with renal cell carcinoma (RCC) brain metastases are frequently treated with immune checkpoint inhibitors (ICIs) and stereotactic radiosurgery (SRS). However, data reporting on the risk of developing radiation necrosis (RN) are limited.METHODSRN rates were compared for concurrent therapy (ICI/SRS administration within 4 weeks of one another) and nonconcurrent therapy with the χ2 test. Univariable logistic regression was used to identify factors associated with developing RN.RESULTSFifty patients (23 concurrent and 27 nonconcurrent) with 395 brain metastases were analyzed. The median follow‐up was 12.1 months; the median age was 65 years. The median margin dose was 20 Gy, and 4% underwent prior whole‐brain radiation therapy (WBRT). The median treated tumor volume was 3.32 cm3 (range, 0.06‐42.38 cm3); the median volume of normal brain tissue receiving a dose of 12 Gy or higher (V12 Gy) was 8.42 cm3 (range, 0.27‐111.22 cm3). Any‐grade RN occurred in 17.4% and 22.2% in the concurrent and nonconcurrent groups, respectively (P = .67). Symptomatic RN occurred in 4.3% and 14.8% in the concurrent and nonconcurrent groups, respectively (P = .23). Increased tumor volume during SRS (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.01‐1.19; P = .04) was associated with developing RN, although V12 Gy (OR, 1.03; 95% CI, 0.99‐1.06; P = .06), concurrent therapy (OR, 0.74; 95% CI, 0.17‐2.30; P = .76), prior WBRT, and ICI agents were not statistically significant.CONCLUSIONSSymptomatic RN occurs in a minority of patients with RCC brain metastases treated with ICI/SRS. The majority of events were grade 1 to 3 and were managed medically. Concurrent ICI/SRS does not appear to increase this risk. Attempts to improve dose conformality (reduce V12) may be the most successful mitigation strategy in single‐fraction SRS.

Abstract BACKGROUND Intensity‐modulated proton therapy (IMPT) demonstrates superior dose distribution over volumetric‐modulated arc therapy (VMAT) for sparing organs‐at‐risk (OARs) in ipsilateral radiotherapy. To determine a clinical benefit, assessment of patient‐reported outcomes (PRO) and physician‐reported toxicities alongside a dosimetric analysis is needed. METHODS Plans were analyzed for dosimetric differences. PROs were compared for patients undergoing ipsilateral curative‐intent radiotherapy for tonsil and salivary gland cancers with VMAT or IMPT from 2015 to 2020. Physician‐reported toxicities were compared. RESULTS In 40 patients, IMPT was associated with decreased dose to multiple OARs and less deterioration in the following PROs: pain, swallowing function, dry mouth, sticky saliva, sensory change, cough, speech, feeling ill, and social eating. Physician‐reported toxicities demonstrated less oral pain. CONCLUSION IMPT is associated with decreased dose to OARs and less patient‐reported acute deterioration in multiple head and neck domains. A strong consideration for IMPT in ipsilateral head and neck patients with cancer is warranted.