Use of single‐energy proton pencil beam scanning Bragg peak for intensity‐modulated proton therapy FLASH treatment planning in liver‐hypofractionated radiation therapy

Abstract

Purpose The transmission proton FLASH technique delivers high doses to the normal tissue distal to the target, which is less conformal compared to the Bragg peak technique. To investigate FLASH radiotherapy (RT) planning using single‐energy Bragg peak beams with a similar beam arrangement as clinical intensity‐modulated proton therapy (IMPT) in a liver stereotactic body radiation therapy (SBRT) and to characterize the plan quality, dose sparing of organs‐at‐risk (OARs), and FLASH dose rate percentage. Materials and methods An in‐house platform was developed to enable inverse IMPT‐FLASH planning using single‐energy Bragg peaks. A universal range shifter and range compensators were utilized to effectively align the Bragg peak to the distal edge of the target. Two different minimum MU settings of 400 and 800 MU/spot (Bragg‐400 MU and Bragg‐800 MU) plans were investigated on 10 consecutive hepatocellular carcinoma patients previously treated by IMPT–SBRT to evaluate the FLASH dose and dose rate coverage for OARs. The IMPT–FLASH using single‐energy Bragg peaks delivered 50 Gy in five fractions with similar or identical beam arrangement to the clinical IMPT–SBRT plans. NRG GI003 dose constraint metrics were used. Three dose rate calculation methods, including average dose rate (ADR), dose threshold dose rate (DTDR), and dose‐ADR (DADR), were all studied. Results The novel spot map optimization can fulfill the inverse planning using single‐energy Bragg peaks. All the Bragg peak FLASH plans achieved similar results for the liver‐gross tumor volume (GTV) Dmean and heart D0.5cnormalm3${D_{0.5\,{\rm{c}}{{\rm{m}}^3}}}$, compared to SBRT–IMPT. The Bragg‐800 MU plans resulted in 18.3% higher clinical target volume (CTV) D2cnormalm3${D_{2\,{\rm{c}}{{\rm{m}}^{\rm{3}}}}}$ compared with SBRT (p < 0.05), and no significant difference was found between Bragg‐400 MU and SBRT plans. For the CTV Dmax, SBRT plans resulted in 10.3% (p < 0.01) less than Bragg‐400 MU plans and 16.6% (p < 0.01) less than Bragg‐800 MU plans. The Bragg‐800 MU plans generally achieved higher ADR, DADR, and DTDR dose rates than Bragg‐400 MU plans, and DADR mostly led to the highest V40 Gy/s compared to other dose rate calculation methods, whereas ADR led to the lowest. The lower dose rate portions in certain OARs are related to the lower dose deposited due to the farther distances from targets, especially in the penumbra of the beams. Conclusion Single‐energy Bragg peak IMPT–FLASH plans eliminate the exit dose in normal tissues, maintaining comparable dose metrics to the conventional IMPT–SBRT plans, while achieving a sufficient FLASH dose rate for liver cancers. This study demonstrates the feasibility of and sufficiently high dose rate when applying the Bragg peak FLASH treatment for a liver cancer hypofractionated FLASH therapy. The advancement of this novel method has the potential to optimize treatment for liver cancer patients.

Feasibility study of hybrid inverse planning with transmission beams and single‐energy spread‐out Bragg peaks for proton FLASH radiotherapy

“…The voxels receiving a dose > 0.1 Gy from each beam of a plan were extracted for the DRVH calculation,and the DRVHs of the plan were sampled from all the beams. 22,39 The FLASH dose rate coverage of ∼42% for the lung was achieved in all three plans. The FLASH dose rate coverage for the target in the TB-only plans (∼73%) was statistically higher than that in the two hybrid beam plans (∼50%).…”

“…21 The feasibility of using single-energy BPs with FLASH dose rate for planning has been explored in recent studies. 22,23 In these studies, the uniform range shifters (RSs) and patientspecific universal range compensators were employed to align the BPs of the high-energy proton beams to the distal edge of the target from multiple beam directions, which demonstrated improved OAR sparing with sufficient target dose coverage and comparable FLASH dose rate coverage compared to the TB-only planning. Alternative approaches have been proposed for FLASH planning using spread-out single-energy proton beams, in which patient-specific range compensators were used to pull back the BPs to the target exit edge and pin-shaped ridge filters (RFs) were customized to spread out the BPs to the proximal edge of the target.…”

“…Moreover, the LET effect could potentially be boosted by the BPs with FLASH dose rate to further improve tumor control as well as reduce toxicity 21 . The feasibility of using single‐energy BPs with FLASH dose rate for planning has been explored in recent studies 22,23 . In these studies, the uniform range shifters (RSs) and patient‐specific universal range compensators were employed to align the BPs of the high‐energy proton beams to the distal edge of the target from multiple beam directions, which demonstrated improved OAR sparing with sufficient target dose coverage and comparable FLASH dose rate coverage compared to the TB‐only planning.…”

Dose rate and dose robustness for proton transmission FLASH-RT treatment in lung cancer

“…Here we chose a feasible cyclotron current for the Varian ProBeam system, and under this current, the FLASH coverage for both plans is close. We demonstrated earlier in (7,8) that a less minimum spot time in the FLASH spot map delivery will allow smaller MUs in the treatment plans at the fixed beam current, likely resulting in superior plan quality to ones with greater minimum spot times.…”

“…As proton beams shoot through the body instead of being stopped as in the conventional proton treatment plans, the dosimetric performances are also expected to be very different. Several studies have investigated proton pencil beam scanning (PBS) transmission planning in the lung ( 1 , 2 ), head and neck ( 4 , 5 ), brain ( 6 ), and liver patients ( 7 , 8 ). All of those studies have shown promising dosimetric outcomes using transmission beams, which helps to inform the characteristics of proton transmission beams for treatment planning.…”