Stereotactic MR-Guided Online Adaptive Radiation Therapy (SMART) for Ultracentral Thorax Malignancies: Results of a Phase 1 Trial

Abstract

PurposeStereotactic body radiation therapy (SBRT) is an effective treatment for oligometastatic or unresectable primary malignancies, although target proximity to organs at risk (OARs) within the ultracentral thorax (UCT) limits safe delivery of an ablative dose. Stereotactic magnetic resonance (MR)–guided online adaptive radiation therapy (SMART) may improve the therapeutic ratio using reoptimization to account for daily variation in target and OAR anatomy. This study assessed the feasibility of UCT SMART and characterized dosimetric and clinical outcomes in patients treated for UCT lesions on a prospective phase 1 trial.Methods and MaterialsFive patients with oligometastatic (n = 4) or unresectable primary (n = 1) UCT malignancies underwent SMART. Initial plans prescribed 50 Gy in 5 fractions with goal 95% planning target volume (PTV) coverage by 95% of prescription, subject to strict OAR constraints. Daily real-time online adaptive plans were created as needed to preserve hard OAR constraints, escalate PTV dose, or both, based on daily setup MR image set anatomy. Treatment times, patient outcomes, and dosimetric comparisons were prospectively recorded.ResultsAll initial and daily adaptive plans met strict OAR constraints based on simulation and daily setup MR imaging anatomy, respectively. Four of the 5 patients received ≥1 adapted fraction. Ten of the 25 total delivered fractions were adapted. A total of 30% of plan adaptations were performed to improve PTV coverage; 70% were for reversal of ≥1 OAR violation. Local control by Response Evaluation Criteria in Solid Tumors was 100% at 3 and 6 months. No grade ≥3 acute (within 6 months of radiation completion) treatment-related toxicities were identified.ConclusionsSMART may allow PTV coverage improvement and/or OAR sparing compared with nonadaptive SBRT and may widen the therapeutic index of UCT SBRT. In this small prospective cohort, we found that SMART was clinically deliverable to 100% of patients, although treatment delivery times surpassed our predefined, timing-based feasibility endpoint. This technique is well tolerated, offering excellent local control with no identified acute grade ≥3 toxicity.

First prospective clinical evaluation of feasibility and patient acceptance of magnetic resonance-guided radiotherapy in Germany

“…A number of authors have reported on on-table adaption of treatment plans using MRgRT devices [11,[33][34][35][36][37] and also on assessing which patients benefit most from adaptive MRgRT [35,[38][39][40][41][42][43][44]. In the presented study, no online treatment plan adaptions were performed.…”

Development and evaluation of machine learning models for voxel dose predictions in online adaptive magnetic resonance guided radiation therapy

“…[6][7][8] Daily, online adaptive treatment with magnetic resonance image guided RT (MRgRT) can provide an opportunity to simultaneously escalate gross tumor volume (GTV) dose while meeting OAR constraints in these difficult cases. 9 Both modeling studies 3,10,11 and completed phase I clinical trials [12][13][14] have shown the feasability of ablative dose escalation without significant adjacent organ toxicity in the central thorax and abdomen. Such trials have shown an increase in both local control and overall survival while decreasing radiation-induced toxicity events, leading to a prospective clinical trial for further evaluation in pancreatic cancer (SMART: NCT03621644).…”

“…As the use of online adaptive MRgRT has grown recently across a variety of clinics, both the potential benefits and practical difficulties of its utilization are beginning to be understood. [12][13][14][15][16][17][18][19][20][21] But ample opportunity remains for assessment and improvement of online adaptive RT as this unique treatment method continues to develop clinically. Analysis of a collection of patient data and their treatment plans in order to better understand and improve a particular RT process can proceed in a variety of ways.…”

First 500 Fractions Delivered with a Magnetic Resonance-guided Radiotherapy System: Initial Experience

“…Early reports have demonstrated the successful implementation of these systems into a number of clinics world-wide. Today, also a number of retrospective outcome analyses and a smaller number of phase one and phase two prospective clinical trials suggest the clinical value of investing in this technology [5][6][7].…”