A radiomic- and dosiomic-based machine learning regression model for pretreatment planning in ¹⁷⁷Lu-DOTATATE therapy

Background: Standardized patient-specific pretreatment dosimetry planning is mandatory in the modern era of nuclear molecular radiotherapy, which may eventually lead to improvements in the final therapeutic outcome. Only a comprehensive definition of a dosage therapeutic window encompassing the range of absorbed doses, that is, helpful without being detrimental can lead to therapy individualization and improved outcomes. As a result, setting absorbed dose safety limits for organs at risk (OARs) requires knowledge of the absorbed dose–effect relationship. Data sets of consistent and reliable inter-center dosimetry findings are required to characterize this relationship. Purpose: We developed and standardized a new pretreatment planning model consisting of a predictive dosimetry procedure for OARs in patients with neuroendocrine tumors (NETs) treated with ¹⁷⁷Lu-DOTATATE (Lutathera). In the retrospective study described herein, we used machine learning (ML) regression algorithms to predict absorbed doses in OARs by exploiting a combination of radiomic and dosiomic features extracted from patients’ imaging data. Methods: Pretreatment and posttreatment data for 20 patients with NETs treated with ¹⁷⁷Lu-DOTATATE were collected from two clinical centers. A total of 3412 radiomic and dosiomic features were extracted from the patients’ computed tomography (CT) scans and dose maps, respectively. All dose maps were generated using Monte Carlo simulations. An ML regression model was designed based on ML algorithms for predicting the absorbed dose in every OAR (liver, left kidney, right kidney, and spleen) before and after the therapy and between each therapy session, thus predicting any possible radiotoxic effects. Results: We evaluated nine ML regression algorithms. Our predictive model achieved a mean absolute dose error (MAE, in Gy) of 0.61 for the liver, 1.58 for the spleen, 1.30 for the left kidney, and 1.35 for the right kidney between pretherapy ⁶⁸Ga-DOTATOC positron emission tomography (PET)/CT and posttherapy ¹⁷⁷Lu-DOTATATE single photon emission (SPECT)/CT scans. Τhe best predictive performance observed was based on the gradient boost for the liver, the left kidney and the right kidney, and on the extra tree regressor for the spleen. Evaluation of the model's performance according to its ability to predict the absorbed dose in each OAR in every possible combination of pretherapy ⁶⁸Ga-DOTATOC PET/CT and any posttherapy ¹⁷⁷Lu-DOTATATE treatment cycle SPECT/CT scans as well as any ¹⁷⁷Lu-DOTATATE SPECT/CT treatment cycle and the consequent ¹⁷⁷Lu-DOTATATE SPECT/CT treatment cycle revealed mean absorbed dose differences ranges from −0.55 to 0.68 Gy. Incorporating radiodosiomics features from the ⁶⁸Ga-DOTATOC PET/CT and first ¹⁷⁷Lu-DOTATATE SPECT/CT treatment cycle scans further improved the precision and minimized the standard deviation of the predictions in nine out of 12 instances. An average improvement of 57.34% was observed (range: 17.53%–96.12%). However, it's important to note that in three instances (i.e., Ga,C.1 → C3 in spleen and left kidney, and Ga,C.1 → C2 in right kidney) we did not observe an improvement (absolute differences of 0.17, 0.08, and 0.05 Gy, respectively). Wavelet-based features proved to have high correlated predictive value, whereas non-linear-based ML regression algorithms proved to be more capable than the linear-based of producing precise prediction in our case. Conclusions: The combination of radiomics and dosiomics has potential utility for personalized molecular radiotherapy (PMR) response evaluation and OAR dose prediction. These radiodosiomic features can potentially provide information on any possible disease recurrence and may be highly useful in clinical decision-making, especially regarding dose escalation issues.