High Dose per Fraction, Hypofractionated Treatment Effects in the Clinic (HyTEC): An Overview

Grimm, Jimm; Marks, Lawrence B.; Jackson, Andrew; Kavanagh, Brian D.; Xue, Jiangyu; Yorke, Ellen

doi:10.1016/j.ijrobp.2020.10.039

Cited by 77 publications

(54 citation statements)

References 38 publications

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“…The OAR planning constraints followed SBRT/SRS recommendations from recent HyTEC reports and others 40,42–44 . FLASH via SDDRO was able to meet some OAR constraints that CONV (IMPT‐BP) failed to meet.…”

Section: Resultsmentioning

confidence: 97%

Simultaneous dose and dose rate optimization (SDDRO) of the FLASH effect for pencil‐beam‐scanning proton therapy

et al. 2021

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Purpose Compared to CONV‐RT (with conventional dose rate), FLASH‐RT (with ultra‐high dose rate) can provide biological dose sparing for organs‐at‐risk (OARs) via the so‐called FLASH effect, in addition to physical dose sparing. However, the FLASH effect only occurs, when both dose and dose rate meet certain minimum thresholds. This work will develop a simultaneous dose and dose rate optimization (SDDRO) method accounting for both FLASH dose and dose rate constraints during treatment planning for pencil‐beam‐scanning proton therapy. Methods SDDRO optimizes the FLASH effect (specific to FLASH‐RT) as well as the dose distribution (similar to CONV‐RT). The nonlinear dose rate constraint is linearized, and the reformulated optimization problem is efficiently solved via iterative convex relaxation powered by alternating direction method of multipliers. To resolve and quantify the generic tradeoff of FLASH‐RT between FLASH and dose optimization, we propose the use of FLASH effective dose based on dose modifying factor (DMF) owing to the FLASH effect. Results FLASH‐RT via transmission beams (TB) (IMPT‐TB or SDDRO) and CONV‐RT via Bragg peaks (BP) (IMPT‐BP) were evaluated for clinical prostate, lung, head‐and‐neck (HN), and brain cases. Despite the use of TB, which is generally suboptimal to BP for normal tissue sparing, FLASH‐RT via SDDRO considerably reduced FLASH effective dose for high‐dose OAR adjacent to the target. For example, in the lung SBRT case, the max esophageal dose constraint 27 Gy was only met by SDDRO (24.8 Gy), compared to IMPT‐BP (35.3 Gy) or IMPT‐TB (36.6 Gy); in the brain SRS case, the brain constraint V12Gy≤15cc was also only met by SDDRO (13.7cc), compared to IMPT‐BP (43.9cc) or IMPT‐TB (18.4cc). In addition, SDDRO substantially improved the FLASH coverage from IMPT‐TB, e.g., an increase from 37.2% to 67.1% for lung, from 39.1% to 58.3% for prostate, from 65.4% to 82.1% for HN, from 50.8% to 73.3% for the brain. Conclusions Both FLASH dose and dose rate constraints are incorporated into SDDRO for FLASH‐RT that jointly optimizes the FLASH effect and physical dose distribution. FLASH effective dose via FLASH DMF is introduced to reconcile the tradeoff between physical dose sparing and FLASH sparing, and quantify the net effective gain from CONV‐RT to FLASH‐RT.

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Section: Resultsmentioning

confidence: 97%

Simultaneous dose and dose rate optimization (SDDRO) of the FLASH effect for pencil‐beam‐scanning proton therapy

et al. 2021

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“…The large doses applied and low reliability of the linear-quadratic model at such levels, in addition to a lacking clinical validation, led us to omit its application. The linear-quadratic model itself carries certain flaws when assessing large doses per fraction; however, it has been widely adopted to allow comparisons between treatment schemes and pool data, even in settings like this (26). We suggest deeming all available factors when considering IORT-boosting.…”

Section: Discussionmentioning

confidence: 99%

Dosimetric Comparison of Upfront Boosting With Stereotactic Radiosurgery Versus Intraoperative Radiotherapy for Glioblastoma

et al. 2021

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PurposeTo simulate and analyze the dosimetric differences of intraoperative radiotherapy (IORT) or pre-operative single-fraction stereotactic radiosurgery (SRS) in addition to post-operative external beam radiotherapy (EBRT) in Glioblastoma (GB).MethodsImaging series of previously treated patients with adjuvant radiochemotherapy were analyzed. For SRS target definition, pre-operative MRIs were co-registered to planning CT scans and a pre-operative T1-weighted gross target volume (GTV) plus a 2-mm planning target volume (PTV) were created. For IORT, a modified (m)GTV was expanded from the pre-operative volume, in order to mimic a round cavity as during IORT. Dose prescription was 20 Gy, homogeneously planned for SRS and calculated at the surface for IORT, to cover 99% and 90% of the volumes, respectively. For tumors > 2cm in maximum diameter, a 15 Gy dose was prescribed. Plan assessment was performed after calculating the 2-Gy equivalent doses (EQD2) for both boost modalities and including them into the EBRT plan. Main points of interest encompass differences in target coverage, brain volume receiving 12 Gy or more (V12), and doses to various organs-at-risk (OARs).ResultsSeventeen pre-delivered treatment plans were included in the study. The mean GTV was 21.72 cm3 (SD ± 19.36) and mGTV 29.64 cm3 (SD ± 25.64). The mean EBRT and SRS PTV were 254.09 (SD ± 80.0) and 36.20 cm3 (SD ± 31.48), respectively. Eight SRS plans were calculated to 15 Gy according to larger tumor sizes, while all IORT plans to 20 Gy. The mean EBRT D95 was 97.13% (SD ± 3.48) the SRS D99 99.91% (SD ± 0.35) and IORT D90 83.59% (SD ± 3.55). Accounting for only-boost approaches, the brain V12 was 49.68 cm3 (SD ± 26.70) and 16.94 cm3 (SD ± 13.33) (p<0.001) for SRS and IORT, respectively. After adding EBRT results respectively to SRS and IORT doses, significant lower doses were found in the latter for mean Dmax of chiasma (p=0.01), left optic nerve (p=0.023), right (p=0.008) and left retina (p<0.001). No significant differences were obtained for brainstem and cochleae.ConclusionDose escalation for Glioblastoma using IORT results in lower OAR exposure as conventional SRS.

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“…As with QUANTEC, the HyTEC introductory article features a table summarizing the major dose/ volume outcome findings from each site-specific report. 4 Similar dose/volume guidance for SBRT treatment planning has been previously provided by AAPM's Task Group 101 and by other works. [5][6][7] Although the growing availability of clinical data prompted the HyTEC effort, these data remain suboptimal.…”

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confidence: 96%

“…The basic strategy of Emami 1 and its companion modeling paper 3 and of QUANTEC 2 is continued by HyTEC: to provide risk organ tolerances for treatment planning, based on both published clinical dose‐outcome data and statistical dose‐response modeling. As with QUANTEC, the HyTEC introductory article features a table summarizing the major dose/volume outcome findings from each site‐specific report 4 …”

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confidence: 99%

The HyTEC Project

et al. 2021

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High Dose per Fraction, Hypofractionated Treatment Effects in the Clinic (HyTEC): An Overview

Cited by 77 publications

References 38 publications

Simultaneous dose and dose rate optimization (SDDRO) of the FLASH effect for pencil‐beam‐scanning proton therapy

Simultaneous dose and dose rate optimization (SDDRO) of the FLASH effect for pencil‐beam‐scanning proton therapy

Dosimetric Comparison of Upfront Boosting With Stereotactic Radiosurgery Versus Intraoperative Radiotherapy for Glioblastoma

The HyTEC Project

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