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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\u2013effect relationship. Data sets of consistent and reliable inter\u2010center dosimetry findings are required to characterize this relationship.<\/jats:p><\/jats:sec><jats:sec><jats:title>Purpose<\/jats:title><jats:p>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 <jats:sup>177<\/jats:sup>Lu\u2010DOTATATE (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\u2019 imaging data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Pretreatment and posttreatment data for 20 patients with NETs treated with <jats:sup>177<\/jats:sup>Lu\u2010DOTATATE were collected from two clinical centers. A total of 3412 radiomic and dosiomic features were extracted from the patients\u2019 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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 <jats:sup>68<\/jats:sup>Ga\u2010DOTATOC positron emission tomography (PET)\/CT and posttherapy <jats:sup>177<\/jats:sup>Lu\u2010DOTATATE single photon emission (SPECT)\/CT scans. \u03a4he 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 <jats:sup>68<\/jats:sup>Ga\u2010DOTATOC PET\/CT and any posttherapy <jats:sup>177<\/jats:sup>Lu\u2010DOTATATE treatment cycle SPECT\/CT scans as well as any <jats:sup>177<\/jats:sup>Lu\u2010DOTATATE SPECT\/CT treatment cycle and the consequent <jats:sup>177<\/jats:sup>Lu\u2010DOTATATE SPECT\/CT treatment cycle revealed mean absorbed dose differences ranges from \u22120.55 to 0.68\u00a0Gy. Incorporating radiodosiomics features from the <jats:sup>68<\/jats:sup>Ga\u2010DOTATOC PET\/CT and first <jats:sup>177<\/jats:sup>Lu\u2010DOTATATE 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%\u201396.12%). However, it's important to note that in three instances (i.e., Ga,C.1\u00a0\u2192\u00a0C3 in spleen and left kidney, and Ga,C.1\u00a0\u2192\u00a0C2 in right kidney) we did not observe an improvement (absolute differences of 0.17, 0.08, and 0.05\u00a0Gy, respectively). Wavelet\u2010based features proved to have high correlated predictive value, whereas non\u2010linear\u2010based ML regression algorithms proved to be more capable than the linear\u2010based of producing precise prediction in our case.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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\u2010making, especially regarding dose escalation issues.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mp.16746","type":"journal-article","created":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T00:19:28Z","timestamp":1695082768000},"page":"7222-7235","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["A radiomic\u2010 and dosiomic\u2010based machine learning regression model for pretreatment planning in <sup>177<\/sup>Lu\u2010DOTATATE therapy"],"prefix":"10.1002","volume":"50","author":[{"given":"Dimitris","family":"Plachouris","sequence":"first","affiliation":[{"name":"3DMI Research Group, Department of Medical Physics School of Medicine University of Patras  Rion 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