Clinical Outcomes of Stereotactic MR-Guided Adaptive Radiation Therapy for High-Risk Lung Tumors.

PURPOSE: Magnetic resonance (MR)-guided SABR was performed for patients with lung tumors in whom treatment delivery was challenging owing to tumor location, motion, or pulmonary comorbidity. Because stereotactic MR-guided adaptive radiation therapy (SMART) is a novel approach, we studied clinical outcomes in these high-risk lung tumors. METHODS AND MATERIALS: Fifty consecutive patients (54 lung tumors) underwent SMART between 2016 and 2018 for either a primary lung cancer (29 patients) or for lung metastases (21 patients). Eligible patients had risk factors that could predispose them to toxicity, including a central tumor location (n = 30), previous thoracic radiation therapy (n = 17), and interstitial lung disease (n = 7). A daily 17-second breath-hold MR scan was acquired in treatment position, and on-table plan adaptation was performed using the anatomy of the day. Gated SABR was delivered during repeated breath-holds under continuous MR guidance. RESULTS: All but 1 patient completed the planned SMART schedule. With daily plan adaptation, a biologically effective dose ≥100 Gy to 95% of the planning target volume was delivered in 50 tumors (93%). Median follow-up was 21.7 months (95% confidence interval, 19.9-28.1). Local control and overall and disease-free survival rates at 12 months were 95.6%, 88.0%, and 63.6%, respectively. Local failures developed in 4 patients: in 2 after reirradiation for a recurrent lung cancer and in 2 patients with a colorectal metastasis. Overall rates of any grade ≥2 and ≥3 toxicity were 30% and 8%, respectively. Commonest toxicities were grade ≥2 radiation pneumonitis (12%) and chest wall pain (8%). No grade 4 or 5 toxicities were observed. CONCLUSIONS: Use of MR-guided SABR resulted in low rates of high-grade toxicity and encouraging early local control in a cohort of high-risk lung tumors. Additional studies are needed to identify patients who are most likely to benefit from the SMART approach.

Stereotactic MR-guided adaptive radiation therapy for peripheral lung tumors.

BACKGROUND AND PURPOSE: We studied the benefits of using stereotactic MR-guided adaptive radiation therapy (SMART) for delivery of SABR in peripherally located lung tumors. METHODS AND MATERIALS: Twenty-three patients (25 peripheral lung tumors) underwent SMART in 3-8 fractions on an MR Linac or Cobalt-60 system. Before each fraction, a breath-hold MR scan was acquired, followed by on-table plan adaptation based on the anatomy-of-the-day. Breath-hold gated delivery was performed under continuous MR-guidance using an in-room monitor. Benefits of on-table adaptation were studied by comparing 112 «predicted¼ plans, which are the baseline plans recalculated on the anatomy-of-the-day, with the on-table reoptimized plans. RESULTS: The full SMART procedure took a median of 48 and 62 minutes on the MR Linac and Cobalt-60 system, respectively. Median SMART-PTVs were 9.5 cm3 (range, 3.1-55.6). In 14 patients who had undergone a free-breathing 4DCT, SMART-PTVs measured 53.7% (range, 31.9-75.0) of PTVs that would have been generated using a motion-encompassing internal target volume approach. On-table adaptation improved prescription dose coverage of the PTV from a median of 92.1% in predicted plans, to 95.0% in reoptimized ones, thereby increasing the proportion of fractions delivering ≥100 Gy (BED10Gy) to 95% of PTV, from 90.2% to 100.0%. CONCLUSION: Delivery of gated breath-hold SABR using MR-guidance resulted in significantly smaller target volumes than would have been the case with an ITV-based approach. Although on-table adaptation ensured delivery of ablative doses in all fractions, the dosimetric benefits were modest, suggesting that daily online plan adaptation may not benefit most patients with peripheral lung tumors.

Combined Inter- and Intrafractional Plan Adaptation Using Fraction Partitioning in Magnetic Resonance-guided Radiotherapy Delivery.

Magnetic resonance-guided radiation therapy (MRgRT) not only allows for superior soft-tissue setup and online MR-guidance during delivery but also for inter-fractional plan re-optimization or adaptation. This plan adaptation involves repeat MR imaging, organs at risk (OARs) re-contouring, plan prediction (i.e., recalculating the baseline plan on the anatomy of that moment), plan re-optimization, and plan quality assurance. In contrast, intrafractional plan adaptation cannot be simply performed by pausing delivery at any given moment, adjusting contours, and re-optimization because of the complex and composite nature of deformable dose accumulation. To overcome this limitation, we applied a practical workaround by partitioning treatment fractions, each with half the original fraction dose. In between successive deliveries, the patient remained in the treatment position and all steps of the initial plan adaptation were repeated. Thus, this second re-optimization served as an intrafractional plan adaptation at 50% of the total delivery. The practical feasibility of this partitioning approach was evaluated in a patient treated with MRgRT for locally advanced pancreatic cancer (LAPC). MRgRT was delivered in 40Gy in 10 fractions, with two fractions scheduled successively on each treatment day. The contoured gross tumor volume (GTV) was expanded by 3 mm, excluding parts of the OARs within this expansion to derive the planning target volume for daily re-optimization (PTVOPT). The baseline GTVV95% achieved in this patient was 80.0% to adhere to the high-dose constraints for the duodenum, stomach, and bowel (V33 Gy <1 cc and V36 Gy <0.1 cc). Treatment was performed on the MRIdian (ViewRay Inc, Mountain View, USA) using video-assisted breath-hold in shallow inspiration. The dual plan adaptation resulted, for each partitioned fraction, in the generation of PlanPREDICTED1, PlanRE-OPTIMIZED1 (inter-fractional adaptation), PlanPREDICTED2, and PlanRE-OPTIMIZED2 (intrafractional adaptation). An offline analysis was performed to evaluate the benefit of inter-fractional versus intrafractional plan adaptation with respect to GTV coverage and high-dose OARs sparing for all five partitioned fractions. Interfractional changes in adjacent OARs were substantially larger than intrafractional changes. Mean GTV V95% was 76.8 ± 1.8% (PlanPREDICTED1), 83.4 ± 5.7% (PlanRE-OPTIMIZED1), 82.5 ± 4.3% (PlanPREDICTED2),and 84.4 ± 4.4% (PlanRE-OPTIMIZED2). Both plan re-optimizations appeared important for correcting the inappropriately high duodenal V33 Gy values of 3.6 cc (PlanPREDICTED1) and 3.9 cc (PlanPREDICTED2) to 0.2 cc for both re-optimizations. To a smaller extent, this improvement was also observed for V25 Gy values. For the stomach, bowel, and all other OARs, high and intermediate doses were well below preset constraints, even without re-optimization. The mean delivery time of each daily treatment was 90 minutes. This study presents the clinical application of combined inter-fractional and intrafractional plan adaptation during MRgRT for LAPC using fraction partitioning with successive re-optimization. Whereas, in this study, interfractional plan adaptation appeared to benefit both GTV coverage and OARs sparing, intrafractional adaptation was particularly useful for high-dose OARs sparing. Although all necessary steps lead to a prolonged treatment duration, this may be applied in selected cases where high doses to adjacent OARs are regarded as critical.

Dose calculations accounting for breathing motion in stereotactic lung radiotherapy based on 4D-CT and the internal target volume.

PURPOSE: The purpose of this study was to determine the 4D accumulated dose delivered to the CTV in stereotactic radiotherapy of lung tumours, for treatments planned on an average CT using an ITV derived from the Maximum Intensity Projection (MIP) CT. METHODS: For 10 stage I lung cancer patients, treatment plans were generated based on 4D-CT images. From the 4D-CT scan, 10 time-sorted breathing phases were derived, along with the average CT and the MIP. The ITV with a margin of 0mm was used as a PTV to study a worst case scenario in which the differences between 3D planning and 4D dose accumulation will be largest. Dose calculations were performed on the average CT. Dose prescription was 60Gy to 95% of the PTV, and at least 54Gy should be received by 99% of the PTV. Plans were generated using the inverse planning module of the Pinnacle(3) treatment planning system. The plans consisted of nine coplanar beams with two segments each. After optimisation, the treatment plan was transferred to all breathing phases and the delivered dose per phase was calculated using an elastic body spline model available in our research version of Pinnacle (8.1r). Then, the cumulative dose to the CTV over all breathing phases was calculated and compared to the dose distribution of the original treatment plan. RESULTS: Although location, tumour size and breathing-induced tumour movement varied widely between patients, the PTV planning criteria could always be achieved without compromising organs at risk criteria. After 4D dose calculations, only very small differences between the initial planned PTV coverage and resulting CTV coverage were observed. For all patients, the dose delivered to 99% of the CTV exceeded 54Gy. For nine out of 10 patients also the criterion was met that the volume of the CTV receiving at least the prescribed dose was more than 95%. CONCLUSIONS: When the target dose is prescribed to the ITV (PTV=ITV) and dose calculations are performed on the average CT, the cumulative CTV dose compares well to the planned dose to the ITV. Thus, the concept of treatment plan optimisation and evaluation based on the average CT and the ITV is a valid approach in stereotactic lung treatment. Even with a zero ITV to PTV margin, no significantly different dose coverage of the CTV arises from the breathing motion induced dose variation over time.

Modeling kinematics and dynamics of human arm movements.

A central problem in motor control relates to the coordination of the arm's many degrees of freedom. This problem concerns the many arm postures (kinematics) that correspond to the same hand position in space and the movement trajectories between begin and end position (dynamics) that result in the same arm postures. The aim of this study was to compare the predictions for arm kinematics by various models on human motor control with experimental data and to study the relation between kinematics and dynamics. Goal-directed arm movements were measured in 3-D space toward far and near targets. The results demonstrate that arm postures for a particular target depend on previous arm postures, contradicting Donders's law. The minimum-work and minimum-torque-change models, on the other hand, predict a much larger effect of initial posture than observed. These data suggest that both kinematics and dynamics affect postures and that their relative contribution might depend on instruction and task complexity.