An algorithm for thoracic re-irradiation using biologically effective dose: a common language on how to treat in a “no-treat zone”

Abstract

Background Re-irradiation (re-RT) is a technically challenging task for which few standardized approaches exist. This is in part due to the lack of a common platform to assess dose tolerance in relation to toxicity in the re-RT setting. To better address this knowledge gap and provide new tools for studying and developing thresholds for re-RT, we developed a novel algorithm that allows for anatomically accurate three-dimensional mapping of composite biological effective dose (BED) distributions from nominal doses (Gy). Methods The algorithm was designed to automatically convert nominal dose from prior treatment plans to corresponding BED value maps (voxel size 2.5 mm3 and α/β of 3 for normal tissue, BED3). Following the conversion of each plan to a BED3 dose distribution, deformable registration was used to create a summed composite re-irradiation BED3 plan for each patient who received two treatments. A proof-of-principle analysis was performed on 38 re-irradiation cases of initial stereotactic ablative radiotherapy (SABR) followed by either re-SABR or chemoradiation for isolated locoregional recurrence of early-stage non-small cell lung cancer. Results Evaluation of the algorithm-generated maps revealed appropriate conversion of physical dose to BED at each voxel. Of 14 patients receiving repeat SABR, there was one case each of grade 3 chest wall pain (7%), pneumonitis (7%), and dyspnea (7%). Of 24 patients undergoing repeat fractionated radiotherapy, grade 3 events were limited to two cases each of pneumonitis and dyspnea (8%). Composite BED3 dosimetry for each patient who experienced grade 2–3 events is provided and may help guide development of precise cumulative dose thresholds for organs at risk in the re-RT setting. Conclusions This novel algorithm successfully created a voxel-by-voxel composite treatment plan using BED values. This approach may be used to more precisely examine dosimetric predictors of toxicities and to establish more accurate normal tissue constraints for re-irradiation.

Salvage percutaneous high-dose-rate brachyablation after stereotactic body radiation therapy for early-stage non-small cell lung cancer

“…Finally, considering any re-irradiation treatment option, a thorough assessment of cumulative dose affecting both the target and surrounding normal tissue is crucial, including time interval between radiotherapy courses and individual patient-related factors in determining the risk-to-benefit ratio. Retrospective data from a single large academic center suggests composite BED 3 (α/β of 3 for normal tissue) as a useful tool to predict for toxicity following thoracic re-irradiation [ 24 ]. Established dose guidelines for re-irradiation in the thorax have been outlined by the American Radium Society (ARS) and American College of Radiology (ACR) appropriateness criteria [ 25 ].…”

Technical note: Optimization functions for re‐irradiation treatment planning

“…During the recent ESTRO Physics workshop on re-irradiation, 8 such dose accumulation capability (together with visualization) was identified as one of the highest priorities when scoring potential software tools to support safe clinical re-irradiation. Although some previous studies have reported similar approaches for the evaluation of re-irradiation treatments, 19,20 few have incorporated such functionalities into re-irradiation planning using commercially available software. [3][4][5] For the fictitious RI scenario in this study, the three re-planning strategies performed equally well (Table 2, Figure 2, Figure 3a,b), which was expected due to the large distances between PTV and relevant OARs associated with RI treatments.…”

“…During the recent ESTRO Physics workshop on re‐irradiation, 8 such dose accumulation capability (together with visualization) was identified as one of the highest priorities when scoring potential software tools to support safe clinical re‐irradiation. Although some previous studies have reported similar approaches for the evaluation of re‐irradiation treatments, 19,20 few have incorporated such functionalities into re‐irradiation planning using commercially available software 3–5 …”

Review and recommendations on deformable image registration uncertainties for radiotherapy applications

“…Dose from previous treatments can be deformed to the current anatomy to evaluate potential dose overlap (Meijneke et al 2013 , Nix et al 2022 ). Thereby, being used to define safe dose tolerances in those previously treated regions (Embring et al 2021 , Andratschke et al 2022 , Brooks et al 2022 , Nix et al 2022 ). In addition, DIR-facilitated dose warping can be used to correlate places of local failure with previously planned and/or delivered dose distributions (Boman et al 2017 , McVicar et al 2018 , Skjøtskift et al 2018 , Embring et al 2021 , Nix et al 2022 ).…”

“…The lack of standardised toxicity scoring or cumulative DVHs over multiple treatments, partially influenced by DIR uncertainty remain reasons why the recovery of organs over time is not well quantified. The calculation of biologically effective dose can improve the understanding of normal tissue responses over time (Brooks et al 2022 , Nix et al 2022 ) and allow a better estimation of safe dose constraints during re-irradiation.…”