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Can Polymetastatic Disease Be ARRESTed Using SABR? A Dosimetric Feasibility Study to Inform Development of a Phase 1
Mark T Corkum1, Hatim Fakir2, David A Palma1
1Division of Radiation Oncology, Department of Oncology.
Purpose:
Phase 2 randomized trials suggest that stereotactic ablative radiation therapy improves progression-free and overall survival in patients with oligometastatic cancer, with phase 3 trials currently testing stereotactic ablative radiation therapy in up to 10 metastases. Whether stereotactic radiation therapy could provide similar benefits in polymetastatic disease (>10 metastases) is unknown. We sought to evaluate the dosimetric feasibility of using stereotactic radiation therapy in polymetastatic disease in preparation for a phase 1 trial.
Methods And Materials:
Five craniospinal computed tomography simulations were used to simulate 24 metastatic targets (n = 2 patients), 30 targets (n = 2 patients), and 50 targets (n = 1 patient) that were not present on the initial scan. Creation of radiation therapy plans was attempted for doses up to 30 Gy in 5 fractions, with de-escalation to 24 Gy/4, 18 Gy/3, 12 Gy/2, or 6 Gy/1 if not feasible based on standardized dose constraints. Plans were created using Raystation for delivery on linear accelerators using volumetric modulated arc therapy and validated using Mobius 3D.
Results:
A stereotactic radiation therapy treatment plan was generated for each simulated patient. Dose constraints were met to a dose of 30 Gy in 5 fractions for the patients with 24 and 30 lesions. For the patient with 50 targets, dose de-escalation to 12 Gy in 2 fractions was required to meet lung constraints. Estimated beam-on time varied between 18 and 29 minutes per fraction of 6 Gy. Median D95 planning target volume dosimetry ranged from 96.6% to 97.7% of the prescription dose. The conformity index (R100) range was 0.89 to 0.95, and R50 range was 6.84 to 8.72.
Conclusions:
Stereotactic radiation therapy treatment plans meeting standardized dose constraints could be created in the setting of 24 to 50 metastatic lesions using volumetric modulated arc therapy. This safety of this approach is being evaluated in a phase 1 trial (NCT04530513).
Insights
Stereotactic radiation therapy (SRT) planning is feasible for polymetastatic disease (>10 metastases). This study demonstrates that SRT can be safely delivered to 24-50 metastatic lesions, paving the way for further clinical trials.
Area of Science:
- Radiation Oncology
- Medical Physics
Background:
- Stereotactic ablative radiation therapy (SABR) has shown efficacy in oligometastatic cancer.
- Its application in polymetastatic disease (>10 metastases) remains unexplored.
- This study investigates the dosimetric feasibility of SABR for extensive metastatic burden.
Purpose of the Study:
- To evaluate the dosimetric feasibility of stereotactic radiation therapy (SRT) for polymetastatic cancer.
- To prepare for a Phase 1 clinical trial assessing SRT in patients with numerous metastases.
- To determine if SRT can be safely delivered within established dose constraints for >10 metastatic lesions.
Main Methods:
- Utilized computed tomography (CT) simulations to model 24, 30, and 50 metastatic targets.
- Developed radiation therapy plans using Raystation software on linear accelerators with volumetric modulated arc therapy (VMAT).
- Assessed plan feasibility based on standardized dose constraints, with dose de-escalation if necessary, and validated using Mobius 3D.
Main Results:
- Successful generation of SRT treatment plans for all simulated polymetastatic scenarios (24-50 lesions).
- Standard dose constraints were met for 24 and 30 lesions at 30 Gy/5 fractions.
- Dose de-escalation to 12 Gy/2 fractions was required for 50 lesions to meet lung constraints.
- Achieved excellent target volume coverage (median D95: 96.6%-97.7%) and plan conformity (R100: 0.89-0.95).
Conclusions:
- Volumetric modulated arc therapy-based SRT plans are dosimetrically feasible for treating 24 to 50 metastatic lesions.
- These findings support the potential of SRT in managing polymetastatic disease.
- The safety of this approach is currently under investigation in an ongoing Phase 1 clinical trial (NCT04530513).
