Abstract

PurposeTheoretical studies have shown that dose‐painting‐by‐numbers (DPBN) could lead to large gains in tumor control probability (TCP) compared to conventional dose distributions. However, these gains may vary considerably among patients due to (a) variations in the overall radiosensitivity of the tumor, (b) variations in the 3D distribution of intra‐tumor radiosensitivity within the tumor in combination with patient anatomy, (c) uncertainties of the 3D radiosensitivity maps, (d) geometrical uncertainties, and (e) temporal changes in radiosensitivity. The goal of this study was to investigate how much of the theoretical gains of DPBN remain when accounting for these factors. DPBN was compared to both a homogeneous reference dose distribution and to nonselective dose escalation (NSDE), that uses the same dose constraints as DPBN, but does not require 3D radiosensitivity maps.MethodsA fully automated DPBN treatment planning strategy was developed and implemented in our in‐house developed treatment planning system (TPS) that is robust to uncertainties in radiosensitivity and patient positioning. The method optimized the expected TCP based on 3D maps of intra‐tumor radiosensitivity, while accounting for normal tissue constraints, uncertainties in radiosensitivity, and setup uncertainties. Based on FDG‐PETCT scans of 12 non‐small cell lung cancer (NSCLC) patients, data of 324 virtual patients were created synthetically with large variations in the aforementioned parameters. DPBN was compared to both a uniform dose distribution of 60 Gy, and NSDE. In total, 360 DPBN and 24 NSDE treatment plans were optimized.ResultsThe average gain in TCP over all patients and radiosensitivity maps of DPBN was 0.54 ± 0.20 (range 0–0.97) compared to the 60 Gy uniform reference dose distribution, but only 0.03 ± 0.03 (range 0–0.22) compared to NSDE. The gains varied per patient depending on the radiosensitivity of the entire tumor and the 3D radiosensitivity maps. Uncertainty in radiosensitivity led to a considerable loss in TCP gain, which could be recovered almost completely by accounting for the uncertainty directly in the optimization.ConclusionsOur results suggest that the gains of DPBN can be considerable compared to a 60 Gy uniform reference dose distribution, but small compared to NSDE for most patients. Using the robust DPBN treatment planning system developed in this work, the optimal DPBN treatment plan could be derived for any patient for whom 3D intra‐tumor radiosensitivity maps are known, and can be used to select patients that might benefit from DPBN. NSDE could be an effective strategy to increase TCP without requiring biological information of the tumor.

Highlights

  • Dose-painting-by-numbers (DPBN) could potentially lead to a more effective radiation treatment than conventional treatment plans

  • We found that a theoretical gain of DPBN of on average 0.2 reduced to on average 0.03 compared to nonselective dose escalation (NSDE) when variations in patient anatomy and 3D radiosensitivity distributions were accounted for

  • Based on a large range of patient anatomies and 3D radiosensitivity maps, our results suggest that the gains of DPBN can be considerable compared to a 60 Gy reference dose distribution, but small (0.03 in tumor control probability (TCP)) compared to NSDE for most patients

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Summary

Introduction

Dose-painting-by-numbers (DPBN) could potentially lead to a more effective radiation treatment than conventional treatment plans (see[1] and references therein). Two categories of methods can be distinguished to use these images to steer the dose painting treatment planning. The first method assigns a priori desired dose levels to different regions or voxels of the tumor based on imaging data. The treatment planning strategy aims to minimize the difference between the desired and planned dose distribution for each voxel. A pragmatic approach is to define a boost region based on tracer uptake, assign a desired boost dose level, and optimize the treatment plan using a conventional simultaneous integrated boost technique.[15] Others converted 3D tracer maps to assign a prescription dose or escalation factor to each voxel individually.[16,17,18]

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