Single-fraction 34 Gy Lung Stereotactic Body Radiation Therapy Using Proton Transmission Beams: FLASH-dose Calculations and the Influence of Different Dose-rate Methods and Dose/Dose-rate Thresholds

Marlen, Patricia van; Verbakel, WFAR; Slotman, Ben J.; Dahele, Max

doi:10.1016/j.adro.2022.100954

Cited by 7 publications

(7 citation statements)

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“…The elapsed time the patient spent on the treatment couch (including the time for patient setup and positioning, imaging, and FLASH treatment delivery) was an average (range) of 15.8 (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) minutes per treatment site and 18.9 (11-33) minutes per patient. The 2 patients who received treatment to 2 anatomical treatment sites were on the treatment couch for 32 and 33 minutes, respectively.…”

Section: Flash Treatment Workflow Feasibilitymentioning

confidence: 99%

Proton FLASH Radiotherapy for the Treatment of Symptomatic Bone Metastases

et al. 2023

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ImportanceTo our knowledge, there have been no clinical trials of ultra-high-dose-rate radiotherapy delivered at more than 40 Gy/sec, known as FLASH therapy, nor first-in-human use of proton FLASH.ObjectivesTo assess the clinical workflow feasibility and treatment-related toxic effects of FLASH and pain relief at the treatment sites.Design, Setting, and ParticipantsIn the FAST-01 nonrandomized trial, participants treated at Cincinnati Children’s/UC Health Proton Therapy Center underwent palliative FLASH radiotherapy to extremity bone metastases. Patients 18 years and older with 1 to 3 painful extremity bone metastases and life expectancies of 2 months or more were eligible. Patients were excluded if they had foot, hand, and wrist metastases; metastases locally treated in the 2 weeks prior; metal implants in the treatment field; known enhanced tissue radiosensitivity; and implanted devices at risk of malfunction with radiotherapy. One of 11 patients who consented was excluded based on eligibility. The end points were evaluated at 3 months posttreatment, and patients were followed up through death or loss to follow-up for toxic effects and pain assessments. Of the 10 included patients, 2 died after the 2-month follow-up but before the 3-month follow-up; 8 participants completed the 3-month evaluation. Data were collected from November 3, 2020, to January 28, 2022, and analyzed from January 28, 2022, to September 1, 2022.InterventionsBone metastases were treated on a FLASH-enabled (≥40 Gy/sec) proton radiotherapy system using a single-transmission proton beam. This is consistent with standard of care using the same prescription (8 Gy in a single fraction) but on a conventional-dose-rate (approximately 0.03 Gy/sec) photon radiotherapy system.Main Outcome and MeasuresMain outcomes included patient time on the treatment couch, device-related treatment delays, adverse events related to FLASH, patient-reported pain scores, and analgesic use.ResultsA total of 10 patients (age range, 27-81 years [median age, 63 years]; 5 [50%] male) underwent FLASH radiotherapy at 12 metastatic sites. There were no FLASH-related technical issues or delays. The average (range) time on the treatment couch was 18.9 (11-33) minutes per patient and 15.8 (11-22) minutes per treatment site. Median (range) follow-up was 4.8 (2.3-13.0) months. Adverse events were mild and consistent with conventional radiotherapy. Transient pain flares occurred in 4 of the 12 treated sites (33%). In 8 of the 12 sites (67%) patients reported pain relief, and in 6 of the 12 sites (50%) patients reported a complete response (no pain).Conclusions and RelevanceIn this nonrandomized trial, clinical workflow metrics, treatment efficacy, and safety data demonstrated that ultra-high-dose-rate proton FLASH radiotherapy was clinically feasible. The treatment efficacy and the profile of adverse events were comparable with those of standard-of-care radiotherapy. These findings support the further exploration of FLASH radiotherapy in patients with cancer.Trial RegistrationClinicalTrials.gov Identifier: NCT04592887

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Section: Flash Treatment Workflow Feasibilitymentioning

confidence: 99%

Proton FLASH Radiotherapy for the Treatment of Symptomatic Bone Metastases

et al. 2023

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“…There is also a potential reduction of conformality in regions that would normally receive dose. Planning studies should be used to compare the quality of transmission beam plans with the most appropriate clinical standard to ensure no such compromises are made [4, 23,52]. While the FLASH-RBE remains uncertain, care should be taken in assuming any levels of FLASH sparing within treatment plans to ensure dose to OARs does not look more favourable than in reality.…”

Section: Further Considerations For Flash Treatment Planningmentioning

confidence: 99%

Treatment planning considerations for the development of FLASH proton therapy

Rothwell

Lowe

Traneus

et al. 2022

Radiotherapy and Oncology

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“…[19][20][21][22] It is debated whether FLASH effects are observable only with doses above a certain threshold (ranging up to 5-10 Gy), or whether the FLASH effect increases with dose. 23 However, high doses should still be delivered with caution since they may still worsen normal tissue dose before any FLASH sparing is observed. 22 While a full spatio-temporal report (including frequency and length of pulses, energy switching, beam switching, etc.)…”

Section: Introductionmentioning

confidence: 99%

“…Studies have indicated that hypofractionation increases Monitor Unit (MU) and thus dose rate, and that the combination of high doses and dose rates improve normal tissue sparing 19–22 . It is debated whether FLASH effects are observable only with doses above a certain threshold (ranging up to 5–10 Gy), or whether the FLASH effect increases with dose 23 . However, high doses should still be delivered with caution since they may still worsen normal tissue dose before any FLASH sparing is observed 22 .…”

Section: Introductionmentioning

confidence: 99%

“…17 However, the duration of the spot scanning process may decrease the mean dose rate to 1-2 Gy/min, which inhibits the study of the FLASH effect with intensity-modulated proton therapy (IMPT) over large irradiation fields. 9,14 Another consideration for FLASH therapy is the fractionation scheme of a typical IMPT plan, which may deliver small doses (∼2 Gy) in multiple fractions (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). 18 Studies have indicated that hypofractionation increases Monitor Unit (MU) and thus dose rate, and that the combination of high doses and dose rates improve normal tissue sparing.…”

Section: Introductionmentioning

confidence: 99%

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Dose and dose rate objectives in Bragg peak and shoot‐through beam orientation optimization for FLASH proton therapy

Ramesh

Ruan

et al. 2022

Medical Physics

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Purpose The combined use of Bragg peak (BP) and shoot‐through (ST) beams has previously been shown to increase the normal tissue volume receiving FLASH dose rates while maintaining dose conformality compared to conventional intensity‐modulated proton therapy (IMPT) methods. However, the fixed beam optimization method has not considered the effects of beam orientation on the dose and dose rates. To maximize the proton FLASH effect, here, we incorporate dose rate objectives into our beam orientation optimization framework. Methods From our previously developed group‐sparsity dose objectives, we add upper and lower dose rate terms using a surrogate dose‐averaged dose rate definition and solve using the fast‐iterative shrinking threshold algorithm. We compare the dosimetry for three head‐and‐neck cases between four techniques: (1) spread‐out BP IMPT (BP), (2) dose rate optimization using BP beams only (BP‐DR), (3) dose rate optimization using ST beams only (ST‐DR), and (4) dose rate optimization using combined BP and ST (BPST‐DR), with the goal of sparing organs at risk without loss of tumor coverage and maintaining high dose rate within a 10 mm region of interest (ROI) surrounding the clinical target volume (CTV). Results For BP, BP‐DR, ST‐DR, and BPST‐DR, CTV homogeneity index and Dmax were found to be on average 0.886, 0.867, 0.687, and 0.936 and 107%, 109%, 135%, and 101% of prescription, respectively. Although ST‐DR plans were not able to meet dosimetric standards, BPST‐DR was able to match or improve either maximum or mean dose in the right submandibular gland, left and right parotids, constrictors, larynx, and spinal cord compared to BP plans. Volume of ROIs receiving greater than 40 Gy/s (Vγ0)${V_{\gamma 0}})$ was 51.0%, 91.4%, 95.5%, and 92.1% on average. Conclusions The dose rate techniques, particularly BPST‐DR, were able to significantly increase dose rate without compromising physical dose compared with BP. Our algorithm efficiently selects beams that are optimal for both dose and dose rate.

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Single-fraction 34 Gy Lung Stereotactic Body Radiation Therapy Using Proton Transmission Beams: FLASH-dose Calculations and the Influence of Different Dose-rate Methods and Dose/Dose-rate Thresholds

Cited by 7 publications

References 53 publications

Proton FLASH Radiotherapy for the Treatment of Symptomatic Bone Metastases

Proton FLASH Radiotherapy for the Treatment of Symptomatic Bone Metastases

Treatment planning considerations for the development of FLASH proton therapy

Dose and dose rate objectives in Bragg peak and shoot‐through beam orientation optimization for FLASH proton therapy

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