Patterns of utilization and clinical adoption of 0.35 Tesla MR-guided radiation therapy in the United States - Understanding the transition to adaptive, ultra-hypofractionated treatments.

Purpose/Objective: Magnetic resonance-guided radiation therapy (MRgRT) utilization is rapidly expanding worldwide, driven by advanced capabilities including continuous intrafraction visualization, automatic triggered beam delivery, and on-table adaptive replanning (oART). Our objective was to describe patterns of 0.35Tesla(T)-MRgRT (MRIdian) utilization in the United States (US) among early adopters of this novel technology. Materials/Methods: Anonymized administrative data from all US MRIdian treatment systems were extracted for patients completing treatment from 2014 to 2020. Detailed treatment information was available for all MRIdian linear accelerator (linac) systems and some cobalt systems. Results: Seventeen systems at 16 centers delivered 5736 courses and 36,389 fractions (fraction details unavailable for 1223 cobalt courses), of which 21.1% were adapted. Ultra-hypofractionation (UHfx) (1-5 fractions) was used in 70.3% of all courses. At least one adaptive fraction was used for 38.5% of courses (average 1.7 adapted fractions/course), with higher oART use in UHfx dose schedules (47.7% of courses, average 1.9 adapted fractions per course). The most commonly treated organ sites were pancreas (20.7%), liver (16.5%), prostate (12.5%), breast (11.5%), and lung (9.4%). Temporal trends show a compounded annual growth rate (CAGR) of 59.6% in treatment courses delivered, with a dramatic increase in use of UHfx to 84.9% of courses in 2020 and similar increase in use of oART to 51.0% of courses. Conclusions: This is the first comprehensive study reporting patterns of utilization among early adopters of MRIdian in the US. Intrafraction MR image-guidance, advanced motion management, and increasing adoption of adaptive radiation therapy has led to a substantial transition to ultra-hypofractionated regimens. 0.35 T-MRgRT has been predominantly used to treat abdominal and pelvic tumors with increasing use of on-table adaptive replanning, which represents a paradigm shift in radiation therapy.

Technical Report: Diagnostic Scan-Based Planning (DSBP), A Method to Improve the Speed and Safety of Radiation Therapy for the Treatment of Critically Ill Patients.

PURPOSE: Treating critically ill patients in radiation oncology departments poses multiple safety risks. This study describes a method to improve the speed of radiation treatment for patients in the intensive care unit by eliminating the need for computed tomography (CT) simulation or on-table treatment planning using patients' previously acquired diagnostic CT scans. METHODS AND MATERIALS: Initially, a retrospective planning study was performed to assess the applicability and safety of diagnostic scan-based planning (DSBP) for 3 typical indications for radiation therapy in patients in the intensive care unit: heterotopic ossification (10), spine metastases (cord compression; 10), and obstructive lung lesions (5). After identification of an appropriate diagnostic CT scan, treatment planning was performed using the diagnostic scan data set. These treatment plans were then transferred to the patients' simulation scans, and a dosimetric comparison was performed between the 2 sets of plans. Additionally, a time study of the first 10 patients treated with DSBP in our department was performed. RESULTS: The retrospective analysis demonstrated that DSBP resulted in treatment plans that, when transferred to the CT simulation data sets, provided excellent target coverage, a median D95% of 96% (range, 86%-100%) of the prescription dose with acceptable hot spots, and a median Dmax108% (range, 102%-113%). Subsequently, DSBP has been used for 10 critically ill patients. The patients were treated without CT simulation, and the median time between patient check-in to the department and completion of radiation therapy was 28 minutes (range, 18-47 minutes.) CONCLUSIONS: This study demonstrates that it is possible to safely use DSBP for the treatment of critically ill patients. This method has the potential to simplify the treatment process and improve the speed and safety of treatment.

Contemporary analysis of pelvic and para-aortic metastasis in endometrial cancer using the SEER registry.

OBJECTIVE: To determine the incidence of regional lymph node involvement for early-stage endometrial cancer by using the Surveillance, Epidemiology, and End Results (SEER) registry. METHODS: In a retrospective study, data were analyzed from patients who were diagnosed with stage IA-IIB endometrioid adenocarcinoma and were treated between 1998 and 2003. The incidence of pelvic and para-aortic lymph node involvement was determined. RESULTS: Data were analyzed from 4052 patients. Incidences of pelvic and para-aortic lymph node metastases were: 1% and 0% in stage IA, grade 1 disease; 2% and 0% in IA, grade 2; 2% and 1% in IA, grade 3; 2% and 0% in IB, grade 1; 3% and 1% in IB, grade 2; 3% and 2% in IB, grade 3; 7% and 3% in IC, grade 1; 8% and 5% in IC, grade 2; 12% and 8% in IC, grade 3; 7% and 3% in IIA, grade 1; 10% and 4% in IIA, grade 2; 10% and 5% in IIA, grade 3; 8% and 4% in IIB, grade 1; 13% and 8% in IIB, grade 2; and 19% and 12% in IIB, grade 3. CONCLUSION: Incidences of pelvic and para-aortic metastases were lower than previously reported. Patients at higher stages and grades had a 10% or higher risk of lymph node involvement and might benefit from aggressive therapy.

A margin-based analysis of the dosimetric impact of motion on step-and-shoot IMRT lung plans.

PURPOSE: Intrafraction motion during step-and-shoot (SNS) IMRT is known to affect the target dosimetry by a combination of dose blurring and interplay effects. These effects are typically managed by adding a margin around the target. A quantitative analysis was performed, assessing the relationship between target motion, margin size, and target dosimetry with the goal of introducing new margin recipes. METHODS: A computational algorithm was used to calculate 1,174 motion-encoded dose distributions and DVHs within the patient's CT dataset. Sinusoidal motion tracks were used simulating intrafraction motion for nine lung tumor patients, each with multiple margin sizes. RESULTS: D95% decreased by less than 3% when the maximum target displacement beyond the margin experienced motion less than 5 mm in the superior-inferior direction and 15 mm in the anterior-posterior direction. For target displacements greater than this, D95% decreased rapidly. CONCLUSIONS: Targets moving in excess of 5 mm outside the margin can cause significant changes to the target. D95% decreased by up to 20% with target motion 10 mm outside the margin, with underdosing primarily limited to the target periphery. Multi-fractionated treatments were found to exacerbate target under-coverage. Margins several millimeters smaller than the maximum target displacement provided acceptable motion protection, while also allowing for reduced normal tissue morbidity.

Feasibility of proton beam therapy for reirradiation of locoregionally recurrent non-small cell lung cancer.

BACKGROUND AND PURPOSE: Options are limited for patients with intrathoracic recurrence of non-small cell lung cancer (NSCLC) who previously received radiation. We report our 5-year experience with the toxicity and efficacy of proton beam therapy (PBT) for reirradiation. MATERIALS AND METHODS: Thirty-three patients underwent PBT reirradiation for intrathoracic recurrent NSCLC at a single institution. All patients had had RT for NSCLC (median initial dose 63 Gy in 33 fractions), with median interval to reirradiation of 36 months. Median reirradiation dose was 66 Gy (RBE) in 32 fractions. Toxicity was scored with CTCAE v4.0, and survival outcomes were estimated using Kaplan-Meier. RESULTS: Thirty-one patients (94%) completed reirradiation. At a median 11 months' follow-up, 1-year rates of overall survival, progression-free survival, locoregional control, and distant metastasis-free survival were 47%, 28%, 54%, and 39%. Rates of severe (grade ≥3) toxicity were 9% esophageal, 21% pulmonary; 1 patient had grade 4 esophagitis, and 2 had grade 4 pulmonary toxicity. Nine patients experienced a second in-field failure. CONCLUSIONS: PBT is an option for treating recurrent NSCLC. However, the rates of locoregional recurrence and distant metastasis are high and the potential for toxicity significant. The risks and benefits of PBT must be carefully weighed in each case.

A comparison of the dosimetric effects of intrafraction motion on step-and-shoot, compensator, and helical tomotherapy-based IMRT.

Intrafraction motion during intensity-modulated radiation therapy can cause differences between the planned and delivered patient dose. The magnitude of these differences is dependent on a number of variables, including the treatment modality. This study was designed to compare the relative susceptibility of plans generated with three different treatment modalities to intrafraction motion. The dosimetric effects of motion were calculated using computational algorithms for seven lung tumor patients. Three delivery techniques - MLC-based step-and-shoot (SNS), beam attenuating compensators, and helical tomotherapy (HT) - were investigated. In total 840 motion-encoded dose-volume histograms (DVHs) were calculated for various combinations of CTV margins and sinusoidal CTV motion including CTV offsets. DVH-based metrics (e.g., D95% and D05%) were used to score plan degradations. For all three modalities, dosimetric degradations were typically smaller than 3% if the CTV displacement was smaller than the CTV margin. For larger displacements, technique and direction-specific sensitivities existed. While the HT plans show similar D95% degradations for motion in the SI and AP directions, SNS and compensator plans showed larger D95% degradations for motion in the SI direction than for motion in the AP direction. When averaged over all motion/margin combinations, compensator plans resulted in 0.9% and 0.6% smaller D95% reductions compared to SNS and HT plans, respectively. These differences were statistically significant. No statistically significant differences in D95% degradations were found between SNS and HT for data averaged over all margin and motion track combinations. For CTV motion that is larger than the CTV margin, the dosimetric impact on the CTV varies with treatment technique and the motion direction. For the cases presented here, the effect of motion on CTV dosimetry was statistically smaller for compensator deliveries than SNS and HT, likely due to the absence of the interplay effect which is present for the more dynamic treatment deliveries. The differences between modalities were, however, small and might not be clinically significant. As expected, margins that envelop the CTV motion provide dosimetric protection against motion for all three modalities.

Real-time tumor tracking in the lung using an electromagnetic tracking system.

PURPOSE: To describe the first use of the commercially available Calypso 4D Localization System in the lung. METHODS AND MATERIALS: Under an institutional review board-approved protocol and an investigational device exemption from the US Food and Drug Administration, the Calypso system was used with nonclinical methods to acquire real-time 4-dimensional lung tumor tracks for 7 lung cancer patients. The aims of the study were to investigate (1) the potential for bronchoscopic implantation; (2) the stability of smooth-surface beacon transponders (transponders) after implantation; and (3) the ability to acquire tracking information within the lung. Electromagnetic tracking was not used for any clinical decision making and could only be performed before any radiation delivery in a research setting. All motion tracks for each patient were reviewed, and values of the average displacement, amplitude of motion, period, and associated correlation to a sinusoidal model (R(2)) were tabulated for all 42 tracks. RESULTS: For all 7 patients at least 1 transponder was successfully implanted. To assist in securing the transponder at the tumor site, it was necessary to implant a secondary fiducial for most transponders owing to the transponder's smooth surface. For 3 patients, insertion into the lung proved difficult, with only 1 transponder remaining fixed during implantation. One patient developed a pneumothorax after implantation of the secondary fiducial. Once implanted, 13 of 14 transponders remained stable within the lung and were successfully tracked with the tracking system. CONCLUSIONS: Our initial experience with electromagnetic guidance within the lung demonstrates that transponder implantation and tracking is achievable though not clinically available. This research investigation proved that lung tumor motion exhibits large variations from fraction to fraction within a single patient and that improvements to both transponder and tracking system are still necessary to create a clinical daily-use system to assist with actual lung radiation therapy.

Aortic dose constraints when reirradiating thoracic tumors.

BACKGROUND AND PURPOSE: Improved radiation delivery and planning has allowed, in some instances, for the retreatment of thoracic tumors. We investigated the dose limits of the aorta wherein grade 5 aortic toxicity was observed after reirradiation of lung tumors. MATERIAL AND METHODS: In a retrospective analysis, 35 patients were identified, between 1993 and 2008, who received two rounds of external beam irradiation that included the aorta in the radiation fields of both the initial and retreatment plans. We determined the maximum cumulative dose to 1 cm(3) of the aorta (the composite dose) for each patient, normalized these doses to 1.8 Gy/fraction, and corrected them for long-term tissue recovery between treatments (NIDR). RESULTS: The median time interval between treatments was 30 months (range, 1-185 months). The median follow-up of patients alive at analysis was 42 months (range, 14-70 months). Two of the 35 patients (6%) were identified as having grade 5 aortic toxicities. There was a 25% rate of grade 5 aortic toxicity for patients receiving composite doses ≥120.0 Gy (vs. 0% for patients receiving <120.0 Gy) (P=0.047). CONCLUSIONS: Grade 5 aortic toxicities were observed with composite doses ≥120.0 Gy (NIDR ≥90.0 Gy) to 1cm(3) of the aorta.