Background and Aims

To exemplify the potential and limitations of two approaches to FLASH treatment planning with protons by testing them on two clinically realistic scenarios and different FLASH-specific parameters

Methods

We selected two planning approaches to be delivered with a cyclotron: 3D range modulator (3DRM) and transmission beams(TB). (See Table below for details on the beam delivery parameters.) We associated each planning technique with a disease site and a clinically applied hypofractionation protocol ( 3DRM - liver - 3x25Gy, TB - lung - 3x20Gy). We evaluated the resulting dose distributions for different beam currents (200nA and 800nA at isocentre), two dose rate definitions (dose-averaged dose rate (DADR) and a sliding time window), two minimum dose thresholds and two dose rate thresholds for the FLASH effect (4Gy and 8Gy, 40Gy/s and 100Gy/s, respectively).

Results

Both techniques achieved acceptable dose distributions with a limited number of fields (liver - 1 field, lung - 3 fields) for FLASH proton plans. All combinations of beam intensity, dose rate definition, dose and dose rate threshold we investigated were associated with some level of FLASH dose, suggesting that these disease sites and dosimetric protocols are reasonable candidates for FLASH proton therapy. The figure below shows an example of the results for 200nA and 4Gy and 40Gy/s thresholds.

Conclusions

Treatment planning studies are a useful tool to test candidate disease sites, protocols and planning techniques for proton FLASH. The next step will be to include additional combinations of beam production systems, planning techniques, and patient anatomies.

Background and Aims

In conventional proton therapy, Bragg peaks are positioned inside the tumor and in a margin surrounding it. This causes uncertainties in LET, RBE and range, endangering critical structures distal from the tumor. To combat this, shoot-through flash beams position the Bragg peaks behind the patient. While potentially losing the dosimetric advantage of Bragg peak plans, the FLASH protective effect may compensate for this. A planning study was performed on 5 neuro cases to evaluate dose-averaged LET_D and robustness for both planning strategies.

Methods

5 neuro cases were planned using four 227 MeV Pencil Beam Scanning proton beams. LET_D was calculated for the clinical plan and the shoot-through plan, applying a 2Gy dose threshold (RayStation 10A & 9AR-IonPG). A FLASH protective factor of 1.5 was used for tissues outside the CTV. Robust evaluation was performed considering movement (0.1 cm, 14 directions) and density uncertainty (±3% throughout entire volume).

Results

Clinical plans showed large LET_D variations compared to shoot-through plans. For shoot-through plans, LET_D merely reflects stopping power ratio differences (Fig. 1,2) and the maximum LET_D in OAR is 2–6 times lower. Although less conformal, shoot-through plans met the same clinical goals as the clinical plans. The shoot-through plans are almost entirely robust to density uncertainties (Fig 3a). Considering both spatial and density uncertainties, the target coverage is less robust while the OAR D2% is in general more robust compared to clinical plans (Fig 3b).

Conclusions

Proton shoot-through flash beams avoid LET_D and range uncertainties, provide adequate target coverage, meet planning constraints and are robust.

Background and Aims

We explore potential benefits of combining proton conformal FLASH delivery with LET optimization to enhance high LET energy depositions in the target volume. While high dose rate reduces damage to healthy tissue elevated LET increases the therapeutic effect. Increasing target LET comes at the price of higher dose in the portal volumes. The goal of this work was to seek a sweat spot where an overall gain is achieved.

Methods

Oppose beam prostate MFO conformal FLASH plans with single energy layer beams (214 MeV) and beam specific 3D range modulators were produced by Monte Carlo based optimization. LET enhanced plans were created by adding LET maximizing functions and a dose limiting penalty on the portal dose.

Results

For one exemplar plan (α/β=3, 3 Gy(RBE)/fx, 200 nA beam current) target LET increased from 2 keV/μm to 3.4 keV/μm (RBE 1.14 to 1.17) while portal dose increased by 14%. For the LET enhanced plan characteristic high LET horns at the target periphery were reduced from 4 keV/μm to 2.5 keV/μm. About 80% of the portal dose was delivered at >40 Gy/s evaluated over a 100 ms sliding window.

Conclusions

To yield an RBE gain the fraction dose had to be kept modest which worked against onset of the FLASH effect. For the case studied no overall therapeutic gain is expected. The complete elimination of the peripheral LET horns is advantageous for robustness and for risk organ protection. This feature is independent of fraction dose or dose rate and should be considered for future clinical application.

Background and Aims

We present the rigorous commissioning of a modified LINAC to deliver ultrahigh dose-rate (UHDR) electron beam and implementation of its model in a widely adopted treatment planning system (TPS) with minimal changes to the clinical setting.

Methods

A Varian Clinac 2100C/D was converted to deliver UHDR beams by withdrawing the target and scattering foil in 10MV x-ray mode. Beam characteristics and stability were quantified by film, Cherenkov, and scintillation imaging. The Geant4 generated beam model was validated with film and implemented in Varian Eclipse TPS. Electron FLASH radiotherapy (eFLASH-RT) plans were generated for representative mammal and human patient cases accounting for complex geometries and anatomical inhomogeneities.

Results

The surface mean-dose-rate at the isocenter was >230Gy/s for all measured fields with adequate long-term stability (deviations of output <7%, symmetry/flatness <2%, spatial shift and FWHM <2mm). The TPS model was validated to clinical accuracy (average error <1.5% for lateral profiles and <2% for percent-depth-dose profiles). Treatments plans were generated and accurately delivered to normal porcine skin surface tissue and a melanoma tumor in a canine’s posterior oral cavity. A human eFLASH-RT plan comparable to a conventional electron plan was achieved by utilizing routine accessories, oblique gantry angle and couch kick.

Conclusions

Treatment planning and accurate delivery of eFLASH-RT were feasible in minimally modified radiation oncology clinical settings. The modifications and open-source TPS model are readily transferable to facilitate clinical translation of eFLASH-RT.

Acknowledgment: This work was supported by the Norris Cotton Cancer Center (grant P30CA023108) and Thayer School of Engineering (seed funding and grant R01EB024498).

Background and Aims

With a sizeable patient population, a target largely comprising healthy tissue, and clinically relevant late effects, FLASH whole breast irradiation (WBI) merits consideration. Transmission beams provide a practical way to deliver ultra-high dose rate proton therapy. However, the large WBI volumes make it harder to achieve FLASH dose rates with pencil-beam-scanning (PBS). We therefore performed a simulation study to identify PBS machine characteristics needed for such treatments.

Methods

For a left-sided breast case (861cc) a single-field spot-reduced plan was generated using 250MeV transmission beams. ‘PBS dose rates’ were calculated, considering the total time (including dead-times) to deliver 95% of the dose in each voxel. We varied maximum beam current at isocenter (200, 400, 800nA), energy-layer-wise or spot-wise current, minimum spot duration (0.5, 1, 2ms), and fraction dose (5x5.7Gy, 2x9.74Gy; equivalent BED₃). The percentage of dose delivered above FLASH thresholds was evaluated, considering dose rate thresholds of 40Gy/s and 100Gy/s, and dose thresholds of 4Gy and 8Gy.

Results

For 40Gy/s dose rate threshold, spot-wise currents generally provided >70% of dose delivered above FLASH thresholds, with little dependence on beam current and spot duration (Figure 1). When using energy-layer-wise currents, comparable FLASH dose was achieved only for 9.74Gy fraction dose and 0.5ms minimum spot duration. For 100Gy/s dose rate threshold, substantial FLASH dose was obtained only with extreme machine settings (i.e. 800nA, spot-wise, <=1ms).

Conclusions

Assuming large fields do not necessarily preclude a FLASH effect, FLASH WBI is theoretically achievable, but may require large fraction sizes, and may be (too) demanding for current PBS machines.

Background and Aims

To investigate the clinical potential of FLASH-RT for improving high-dose sparing of OAR, to enable SBRT/SRS that could otherwise fail to meet dose constraints with CONV-RT.

Methods

CONV-RT (via Bragg peaks (BP)) and FLASH-RT (via transmission beams (TB)) are compared with PBS proton therapy, i.e., CONV-RT planned with IMPT-BP, and FLASH-RT planned respectively with IMPT and SDDRO of TB. While IMPT only optimizes the dose distribution, SDDRO also optimizes the FLASH effect, i.e., to maximize the normal tissue volume receiving dose rate and dose thresholds pertinent to the FLASH effect, which was set to be 40Gy/s and 8Gy. The plan evaluation is based on the effective dose (d_e), i.e., the product of the physical dose (d) and FLASH dose modifying factor, which was set to be 0.7 when normal tissues meet both dose rate and dose thresholds.

Results

CONV-RT (IMPT-BP) was compared with FLASH-RT (IMPT and SDDRO). In terms of effective dose, (1) conformal index (CI) values show that SDDRO had the best target dose conformality; (2) mean doses at PTV-10mm (10mm expansion of PTV) suggest that SDDRO had the fastest high-dose falloff for normal tissues adjacent to the target.

Conclusions

Compared to CONV-RT (IMPT-BP), FLASH-RT via SDDRO improved high-dose sparing of OAR, which can potentially enable proton SBRT/SRS that could otherwise fail to meet dose constraints, e.g., the reduction of V12Gy from 44cc to 14cc to meet V12Gy≤15cc for this case to be eligible for brain SRS.

Background and Aims

This work aims to study transmission proton pencil beam scanning (PBS) FLASH radiotherapy (RT) planning for liver cancer cases based on the parameters of a commercially available proton system under FLASH mode.

Methods

An in-house TPS was developed to perform intensity-modulated proton therapy (IMPT) FLASH RT planning. Single-energy transmission PBS plans of 4.5 Gy x 15 fractions were optimized for seven hepatocellular carcinoma patients, using 2 and 5 fields combined with 1) the highest minimum MU/spot from 100-400, and minimum spot time (MST) of 2 ms; 2) the minimum MU/spot of 100, and MST of 0.5 ms. Then, the 3D average dose rate (ADR) distribution and major OARs' dose metrics were characterized to evaluate the plan quality for different combinations of field numbers and MSTs.

Results

Shorter MST are generally associated with better dose quality while more fields are only associated with better target uniformities. Fewer fields will allow higher OAR FLASH coverage with 2 ms MST compared to the 0.5 ms. For 2-field plans, dose metrics and V_40Gy/s of some OARs have large variations due to selecting beam angles and the distance to the target. The transmission plans yield inferior dose quality to the conventional IMPT plans.

Conclusions

For the challenging hypofractionation liver case with smaller fractional doses (4.5Gy/fraction), using fewer fields can allow higher minimum MU/spot, resulting in higher OARs FLASH dose rate coverages while achieving similar plan quality compared to plans with more fields. Shorter MST can achieve better plan quality and comparable or even better FLASH dose rate coverage.