Commissioning a secondary dose calculation software for a 0.35 T MR-linac

Secondary external dose calculations for a 0.35 T magnetic resonance image-guided radiation therapy (MRgRT) are needed within the radiation oncology community to follow safety standards set forth within the field. We evaluate the commercially available software, RadCalc, in its ability to accurately perform monitor unit dose calculations within a magnetic field. We also evaluate the potential effects of a 0.35 T magnetic field upon point dose calculations. Monitor unit calculations were evaluated with (wMag) and without (noMag) a magnetic field considerations in RadCalc for the ViewRay MRIdian. The magnetic field is indirectly accounted for by using asymmetric profiles for calculation. The introduction of double-stacked multi-leaf collimator leaves was also included in the monitor unit calculations and a single transmission value was determined. A suite of simple and complex geometries with a variety field arrangements were calculated for each method to demonstrate the effect of the 0.35 T magnetic field on monitor unit calculations. Finally, 25 patient-specific treatment plans were calculated using each method for comparison. All simple geometries calculated in RadCalc were within 2% of treatment planning system (TPS) values for both methods, except for a single noMag off-axis comparison. All complex muilt-leaf collimator (MLC) pattern calculations were within 5%. All complex phantom geometry calculations were within 5% except for a single field within a lung phantom at a distal point. For the patient calculations, the noMag method average percentage difference was 0.09 ± 2.5% and the wMag average percentage difference was 0.08 ± 2.5%. All results were within 5% for the wMag method. We performed monitor unit calculations for a 0.35 T MRgRT system using a commercially available secondary monitor unit dose calculation software and demonstrated minimal impact of the 0.35 T magnetic field on monitor unit dose calculations. This is the first investigation demonstrating successful calculations of dose using RadCalc in the low-field 0.35 T ViewRay MRIdian system

A multi-institutional phase 2 trial of ablative 5-fraction stereotactic magnetic resonance-guided on-table adaptive radiation therapy for borderline resectable and locally advanced pancreatic cancer

PURPOSE: Magnetic resonance (MR) image guidance may facilitate safe ultrahypofractionated radiation dose escalation for inoperable pancreatic ductal adenocarcinoma. We conducted a prospective study evaluating the safety of 5-fraction Stereotactic MR-guided on-table Adaptive Radiation Therapy (SMART) for locally advanced (LAPC) and borderline resectable pancreatic cancer (BRPC). METHODS AND MATERIALS: Patients with LAPC or BRPC were eligible for this multi-institutional, single-arm, phase 2 trial after ≥3 months of systemic therapy without evidence of distant progression. Fifty gray in 5 fractions was prescribed on a 0.35T MR-guided radiation delivery system. The primary endpoint was acute grade ≥3 gastrointestinal (GI) toxicity definitely attributed to SMART. RESULTS: One hundred thirty-six patients (LAPC 56.6%, BRPC 43.4%) were enrolled between January 2019 and January 2022. Mean age was 65.7 (36-85) years. Head of pancreas lesions were most common (66.9%). Induction chemotherapy mostly consisted of (modified)FOLFIRINOX (65.4%) or gemcitabine/nab-paclitaxel (16.9%). Mean CA19-9 after induction chemotherapy and before SMART was 71.7 U/mL (0-468). On-table adaptive replanning was performed for 93.1% of all delivered fractions. Median follow-up from diagnosis and SMART was 16.4 and 8.8 months, respectively. The incidence of acute grade ≥3 GI toxicity possibly or probably attributed to SMART was 8.8%, including 2 postoperative deaths that were possibly related to SMART in patients who had surgery. There was no acute grade ≥3 GI toxicity definitely related to SMART. One-year overall survival from SMART was 65.0%. CONCLUSIONS: The primary endpoint of this study was met with no acute grade ≥3 GI toxicity definitely attributed to ablative 5-fraction SMART. Although it is unclear whether SMART contributed to postoperative toxicity, we recommend caution when pursuing surgery, especially with vascular resection after SMART. Additional follow-up is ongoing to evaluate late toxicity, quality of life, and long-term efficacy

Stereotactic MR-guided on-table adaptive radiation therapy (SMART) for borderline resectable and locally advanced pancreatic cancer: A multi-center, open-label phase 2 study

BACKGROUND AND PURPOSE: Radiation dose escalation may improve local control (LC) and overall survival (OS) in select pancreatic ductal adenocarcinoma (PDAC) patients. We prospectively evaluated the safety and efficacy of ablative stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) for borderline resectable (BRPC) and locally advanced pancreas cancer (LAPC). The primary endpoint of acute grade ≥ 3 gastrointestinal (GI) toxicity definitely related to SMART was previously published with median follow-up (FU) 8.8 months from SMART. We now present more mature outcomes including OS and late toxicity. MATERIALS AND METHODS: This prospective, multi-center, single-arm open-label phase 2 trial (NCT03621644) enrolled 136 patients (LAPC 56.6 %; BRPC 43.4 %) after ≥ 3 months of any chemotherapy without distant progression and CA19-9 ≤ 500 U/mL. SMART was delivered on a 0.35 T MR-guided system prescribed to 50 Gy in 5 fractions (biologically effective dose RESULTS: Mean age was 65.7 years (range, 36-85), induction FOLFIRINOX was common (81.7 %), most received elective coverage (57.4 %), and 34.6 % had surgery after SMART. Median FU was 22.9 months from diagnosis and 14.2 months from SMART, respectively. 2-year OS from diagnosis and SMART were 53.6 % and 40.5 %, respectively. Late grade ≥ 3 toxicity definitely, probably, or possibly attributed to SMART were observed in 0 %, 4.6 %, and 11.5 % patients, respectively. CONCLUSIONS: Long-term outcomes from the phase 2 SMART trial demonstrate encouraging OS and limited severe toxicity. Additional prospective evaluation of this novel strategy is warranted

Patient specific contouring region of interest for abdominal stereotactic adaptive radiotherapy

Contouring during adaptive radiotherapy (ART) can be a time-consuming process. This study describes the generation of patient specific contouring regions of interest (CRoI) for evaluating the high dose fall-off in stereotactic abdominal ART. An empirical equation was derived to determine the radius of a cylindrical patient specific CRoIs. These CRoIs were applied to 60 patients and their adaptive fractions (301 unique treatment plans). Out of the 301 unique treatment plans, 284 (94%) treatment plans contained the high dose fall-off within the CRoI. There was an expected predicted average timesaving of 2.9-min-per case. Patient specific CRoIs improves the efficiency of ART

Association between GDF-15 levels and changes in vascular and physical function in older patients with hypertension

Background: Growth differentiation factor-15 (GDF-15) may be a biomarker of disease, protective response and/or prognosis, in older people with hypertension. Aims: To correlate baseline GDF-15 levels with physical and vascular health data in this population. Methods: Baseline blood samples were analysed using a GDF-15 ELISA assay kit. Correlations with baseline and 12-month outcome data, including measures of physical and vascular function, were performed. Results: A total of 147 individuals, mean age 76.8 ± 4.7 years, were included. 77 (52 %) were male. Baseline log10GDF-15 showed significant correlations with age (r = 0.37, p < 0.001), total cholesterol (r = −0.33, p < 0.001) and 6-min walking distance (r = −0.37, p < 0.001). Age remained significantly associated with log10GDF-15 in multivariable analysis (beta = −0.29, p = 0.001). Baseline log10GDF-15 was significantly associated with decline in 6-min walk distance over 12 months (beta = −0.27, p = 0.01) in multivariable models. No significant correlations were seen with changes in vascular function over 12 months. Conclusion: Baseline GDF-15 predicts declining physical, but not vascular, function in our population

In silico trial of simulation-free hippocampal-avoidance whole brain adaptive radiotherapy

BACKGROUND AND PURPOSE: Hippocampal-avoidance whole brain radiotherapy (HA-WBRT) can be a time-consuming process compared to conventional whole brain techniques, thus potentially limiting widespread utilization. Therefore, we evaluated the MATERIALS AND METHODS: Ten patients previously treated for central nervous system cancers with cone-beam computed tomography (CBCT) imaging were included in this study. The CBCT was the adaptive image-of-the-day to simulate first fraction on-board imaging. Initial contours defined on the MRI were rigidly matched to the CBCT. Online ART was used to create treatment plans at first fraction. Dose-volume metrics of these simulation-free plans were compared to standard-workflow HA-WBRT plans on each patient CT simulation dataset. Timing data for the adaptive planning sessions were recorded. RESULTS: For all ten patients, simulation-free HA-WBRT plans were successfully created utilizing the online ART workflow and met all constraints. The median hippocampi D CONCLUSIONS: Simulation-free HA-WBRT, with commercially available systems, was clinically feasible via plan-quality metrics and timing

Development of ceftazidime resistance in an acute Burkholderia pseudomallei infection.

Burkholderia pseudomallei, a bacterium that causes the disease melioidosis, is intrinsically resistant to many antibiotics. First-line antibiotic therapy for treating melioidosis is usually the synthetic β-lactam, ceftazidime (CAZ), as almost all B. pseudomallei strains are susceptible to this drug. However, acquired CAZ resistance can develop in vivo during treatment with CAZ, which can lead to mortality if therapy is not switched to a different drug in a timely manner. Serial B. pseudomallei isolates obtained from an acute Thai melioidosis patient infected by a CAZ susceptible strain, who ultimately succumbed to infection despite being on CAZ therapy for the duration of their infection, were analyzed. Isolates that developed CAZ resistance due to a proline to serine change at position 167 in the β-lactamase PenA were identified. Importantly, these CAZ resistant isolates remained sensitive to the alternative melioidosis treatments; namely, amoxicillin-clavulanate, imipenem, and meropenem. Lastly, real-time polymerase chain reaction-based assays capable of rapidly identifying CAZ resistance in B. pseudomallei isolates at the position 167 mutation site were developed. The ability to rapidly identify the emergence of CAZ resistant B. pseudomallei populations in melioidosis patients will allow timely alterations in treatment strategies, thereby improving patient outcomes for this serious disease

Techno-Economic Feasibility Analysis of a Fully Mobile Radiation Oncology System using Monte Carlo Simulation

PURPOSEDisparities in radiation oncology (RO) can be attributed to geographic location, socioeconomic status, race, sex, and other societal factors. One potential solution is to implement a fully mobile (FM) RO system to bring radiotherapy to rural areas and reduce barriers to access. We use Monte Carlo simulation to quantify techno-economic feasibility with uncertainty, using two rural Missouri scenarios.METHODSRecently, a semimobile RO system has been developed by building an o-ring linear accelerator (linac) into a mobile coach that is used for temporary care, months at a time. Transitioning to a more FM-RO system, which changes location within a given day, presents technical challenges including logistics and quality assurance. This simulation includes cancer census in both northern and southeastern Missouri, multiple treatment locations within a given day, and associated expenditures and revenues. A subset of patients with lung, breast, and rectal diseases, treated with five fractions, was simulated in the FM-RO system.RESULTSThe FM-RO can perform all necessary quality assurance tests as suggested in national medical physics guidelines within 1.5 hours, thus demonstrating technological feasibility. In northern and southeastern Missouri, five-fraction simulations\u27 net incomes were, in US dollars (USD), $1.55 ± 0.17 million (approximately 74 patients/year) and$3.65 USD ± 0.25 million (approximately 98 patients/year), respectively. The number of patients seen had the highest correlation with net income as well as the ability to break-even within the simulation. The model does not account for disruptions in care or other commonly used treatment paradigms, which may lead to differences in estimated economic return. Overall, the mobile system achieved a net benefit, even for the most negative simulation scenarios.CONCLUSIONOur simulations suggest technologic success and economic viability for a FM-RO system within rural Missouri and present an interesting solution to address other geographic disparities in access to radiotherapy

Prospective in silico evaluation of cone-beam computed tomography-guided stereotactic adaptive radiation therapy (CT-STAR) for the ablative treatment of ultracentral thoracic disease

PURPOSE: We conducted a prospective, in silico study to evaluate the feasibility of cone-beam computed tomography (CBCT)-guided stereotactic adaptive radiation therapy (CT-STAR) for the treatment of ultracentral thoracic cancers (NCT04008537). We hypothesized that CT-STAR would reduce dose to organs at risk (OARs) compared with nonadaptive stereotactic body radiation therapy (SBRT) while maintaining adequate tumor coverage. METHODS AND MATERIALS: Patients who were already receiving radiation therapy for ultracentral thoracic malignancies underwent 5 additional daily CBCTs on the ETHOS system as part of a prospective imaging study. These were used to simulate CT-STAR, in silico RESULTS: Seven patients were accrued, 6 with intraparenchymal tumors and 1 with a subcarinal lymph node. CT-STAR was feasible in 34 of 35 simulated fractions. In total, 32 dose constraint violations occurred when the P CONCLUSIONS: CT-STAR widened the dosimetric therapeutic index of ultracentral thorax SBRT compared with nonadaptive SBRT. A phase 1 protocol is underway to evaluate the safety of this paradigm for patients with ultracentral early-stage NSCLC