A primer on treatment planning aspects for temporally modulated pulsed radiation therapy

TL;DR

Temporally modulated pulsed radiotherapy (TMPRT) delivers conventional fraction doses as discrete pulses to exploit tumor hypersensitivity, achieving a fraction-effective rate near $6.7$ cGy/min. The paper provides a practical primer on TMPRT treatment planning, presenting VMAT and 3DCRT planning recipes, evaluation metrics, and deliverability verification to support the NRG CC-017 trial. It reports three planning recipes (VMAT single-arc, 3D-DCA two half arcs, and static 3DCRT) for conventional and hypofractionated regimens, with target coverage and organ-at-risk sparing quantified by HI and CI metrics, and plan deliverability confirmed by in-phantom and EPID-based measurements across multiple LINACs. The findings demonstrate that TMPRT planning is feasible with current technology, with VMAT offering the best balance of homogeneity, conformality, and sparing, while deliverability remains robust on both modern and legacy systems, enabling broader clinical adoption.

Abstract

Temporally modulated pulsed radiotherapy (TMPRT) delivers conventional fraction doses of radiation using temporally separated pulses of low doses (<30 cGy) yielding fraction-effective dose rates of around 6.7 cGy/min with the goal to exploit tumor radiation hypersensitivity, which was observed in both, preclinical models and in human clinical trials. To facilitate TMPRT, volumetric modulated arc therapy (VMAT) and 3D-CRT planning techniques were developed following the guidelines of the proposed NRG CC-017 trial. Plans were evaluated with respect to homogeneity, conformality, and adherence to dose constraints. Deliverability of plans was assessed using in-phantom measurements for absorbed dose accuracy at low dose rates and using EPID for isodose verification. For VMAT only single arc plans were found to be acceptable due to otherwise unacceptably heterogeneous field doses, while for dynamic conformal arcs machine limtations on the number of monitor units per degree require the use of partial arcs for each pulse. Delivery of plans at low dose rates (< 100 MU/min) was accurate with high Gamma pass rates on modern LINACs and moderate pass rates on legacy LINACs, in line with their general performance. Generally, VMAT is preferred to achieve optimal homogeneity, conformality, and organ-at-risk sparing, while the use of 3D-CRT can increase the availability of TMPRT for more patients and clinics.

Figures (5)

• Figure 1: Example dose distributions of single-arc VMAT (left) and DCA (center) plans to 4600, and a static 3DCRT (right) plan to 1400. For each two separate axial planes are shown in rows. Structures delineated in red and light blue are PTV4600 and PTV6000, respectively. Colorwash levels are chosen as 110;105;100;95;90;50 of the respective prescription doses; yellow corresonds to 100.
• Figure 2: Dose profiles for single- and two-arc VMAT (top and middle) and DCA (bottom) showing the plan total (blue) and field (red, green) dose profiles in three directions through isocenter. Note that any profile alignment across different plans are coincidental. AP: anterior-posterior; RL: right-left; SI: superior-inferior.
• Figure S1: Field doses and profiles for an example two-arc VMAT plan. Arcs one and two are shown in the top and bottom row with HI of 1.47;1.60, respectively. To deliver 4600 total, each arc is supposed to contribute 2300; levels in the colorwash are chosen as 200;150;120;100;80;50 of 2300.
• Figure S2: Field doses and profiles for an example two-arc DCA plan. Arcs one and two are shown in the top and bottom row with HI of 0.28;0.27, respectively. To deliver 4600 total, each arc is supposed to contribute 2300; levels in the colorwash are chosen as 200;150;120;100;80;50 of 2300.
• Figure S3: Field doses and profiles through isocenter for an example three-field 3DCRT boost plan using wedges and MLC with HI of 0.38;0.52;0.44. Levels in the colorwash are chosen as 200;150;120;100;80;50 of 467.