Randomized Controlled Trials (RCT) are the gold standard for estimating treatment effects but some important situations in cancer care require treatment effect estimates from observational data. We developed “Proxy based individual treatment effect modeling in cancer” (PROTECT) to estimate treatment effects from observational data when there are unobserved confounders, but proxy measurements of these confounders exist. We identified an unobserved confounder in observational cancer research: overall fitness. Proxy measurements of overall fitness exist like performance score, but the fitness as observed by the treating physician is unavailable for research. PROTECT reconstructs the distribution of the unobserved confounder based on these proxy measurements to estimate the treatment effect. PROTECT was applied to an observational cohort of 504 stage III non-small cell lung cancer (NSCLC) patients, treated with concurrent chemoradiation or sequential chemoradiation. Whereas conventional confounding adjustment methods seemed to overestimate the treatment effect, PROTECT provided credible treatment effect estimates.

Objective Analysis of textural features of pulmonary nodules in chest CT, also known as radiomics, has several potential clinical applications, such as diagnosis, prognostication, and treatment response monitoring. For clinical use, it is essential that these features provide robust measurements. Studies with phantoms and simulated lower dose levels have demonstrated that radiomic features can vary with different radiation dose levels. This study presents an in vivo stability analysis of radiomic features for pulmonary nodules against varying radiation dose levels. Methods Nineteen patients with a total of thirty-five pulmonary nodules underwent four chest CT scans at different radiation dose levels (60, 33, 24, and 15 mAs) in a single session. The nodules were manually delineated. To assess the robustness of features, we calculated the intra-class correlation coefficient (ICC). To visualize the effect of milliampere-second variation on groups of features, a linear model was fitted to each feature. We calculated bias and calculated the R2 value as a measure of goodness of fit. Results A small minority of 15/100 (15%) radiomic features were considered stable (ICC > 0.9). Bias increased and R2 decreased at lower dose, but shape features seemed to be more robust to milliampere-second variations than other feature classes. Conclusion A large majority of pulmonary nodule radiomic features were not inherently robust to radiation dose level variations. For a subset of features, it was possible to correct this variability by a simple linear model. However, the correction became increasingly less accurate at lower radiation dose levels. Clinical relevance statement Radiomic features provide a quantitative description of a tumor based on medical imaging such as computed tomography (CT). These features are potentially useful in several clinical tasks such as diagnosis, prognosis prediction, treatment effect monitoring, and treatment effect estimation. Key Points • The vast majority of commonly used radiomic features are strongly influenced by variations in radiation dose level. • A small minority of radiomic features, notably the shape feature class, are robust against dose-level variations according to ICC calculations. • A large subset of radiomic features can be corrected by a linear model taking into account only the radiation dose level.