Robust dose‐painting‐by‐numbers vs. nonselective dose escalation for non‐small cell lung cancer patients

Abstract

Theoretical 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 (i) variations in the overall radio-sensitivity of the tumor, (ii) variations in the 3D distribution of intra-tumor radio-sensitivity within the tumor in combination with patient anatomy, (iii) uncertainties of the 3D radio-sensitivity maps (iv) geometrical uncertainties and (v) temporal changes in radio-sensitivity. 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 non-selective 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 inhouse developed treatment planning system (TPS), that is robust to uncertainties in radio-sensitivity and patient positioning. The method optimized the expected TCP based on 3D maps of intra-tumor radio-sensitivity, while accounting for normal tissue constraints, uncertainties in radio-sensitivity and set-up uncertainties. Based on FDG-PETCT scans of twelve non-small cell lung cancer (NSCLC) patients, data of 324 virtual patients was created synthetically with large variations in the Accepted ArticleThis article is protected by copyright. All rights reserved 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 radio-sensitivity 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 radio-sensitivity of the entire tumor and the 3D radio-sensitivity maps. Uncertainty in radio-sensitivity 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 radio-sensitivity 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.

Positron emission tomography guided dose painting by numbers of lung cancer: Alanine dosimetry in an anthropomorphic phantom

“…Robust optimization strategies, as opposed to target volume based, has been proposed to deal with these issues [21] , [22] , [23] . Also, robust optimization has been introduced for dose painting [24] . Still, target volume based optimization is currently the standard approach in photon based DP radiotherapy planning [22] .…”

Hypoxia-guided treatment planning for lung cancer with dose painting by numbers

“…This is, however, a limitation when considering the implementation of lung cancer. Only one related method was found for DPBN used in patients with lung cancer [11]. The study has focused on optimizing the expect tumor control probability (TCP) for DPBN plan to achieve robustness for TCP and associated dose volume parameters for organs at risk (OARs).…”

Rethinking the potential role of dose painting in personalized ultra-fractionated stereotactic adaptive radiotherapy

“…Dose painting is a technique that entails tailoring the radiation dose delivered to a specific area within a tumor (31)(32)(33)(34)(35)(36). Instead of uniformly irradiating the entire tumor volume, dose painting allows for the adjustment of radiation doses to different regions inside the tumor based on factors such as the tumor's biological/functional characteristics and response to treatment.…”