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Art Int Surg 2022;2:159-72. 10.20517/ais.2022.21 © The Author(s) 2022.
Open Access Systematic Review

Artificial intelligence for decision support in surgical oncology - a systematic review

1Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg 69120, Germany.

2Study Center of the German Society of Surgery (SDGC), Heidelberg University Hospital, Heidelberg 69120, Germany.

3National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg 69120, Germany.

4Department of Surgery, Cantonal Hospital Thurgau, Frauenfeld 8501, Switzerland.

5Division of Computer Assisted Medical Interventions (CAMI), German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.

6Department of Translational Surgical Oncology, National Center for Tumor Diseases (NCT) Dresden, Dresden 01307, Germany.

7Centre for Tactile Internet with Human-in-the-Loop (CeTI), Technical University Dresden, CeTI-Cluster of Excellence, Dresden 01062, Germany.

8Institute of Medical Informatics, Heidelberg University Hospital, Heidelberg 69120, Germany.

9Faculty of Mathematics and Computer Science, Heidelberg University, Heidelberg 69120, Germany.

10Medical Faculty, Heidelberg University, Heidelberg 69120, Germany.

Correspondence to: Prof. Beat Peter Müller-Stich, Deputy Medical Director, Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Im Neuenheimer Feld 420, Heidelberg 69120, Germany. E-mail: beat.mueller@med.uni-heidelberg.de

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    Academic Editors: Andrew A. Gumbs, Stephen Kavic | Copy Editor: Peng-Juan Wen | Production Editor: Peng-Juan Wen

    © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

    Abstract

    Aim: We systematically review current clinical applications of artificial intelligence (AI) that use machine learning (ML) methods for decision support in surgical oncology with an emphasis on clinical translation.

    Methods: MEDLINE, Web of Science, and CENTRAL were searched on 19 January 2021 for a combination of AI and ML-related terms, decision support, and surgical procedures for abdominal malignancies. Data extraction included study characteristics, description of algorithms and their respective purpose, and description of key steps for scientific validation and clinical translation.

    Results: Out of 8302 articles, 107 studies were included for full-text analysis. Most of the studies were conducted in a retrospective setting (n = 105, 98%), with 45 studies (42%) using data from multiple centers. The most common tumor entities were colorectal cancer (n = 35, 33%), liver cancer (n = 21, 20%), and gastric cancer (n = 17, 16%). The most common prediction task was survival (n = 36, 34%), with artificial neural networks being the most common class of ML algorithms (n = 52, 49%). Key reporting and validation steps included, among others, a complete listing of patient features (n = 95, 89%), training of multiple algorithms (n = 73, 68%), external validation (n = 13, 12%), prospective validation (n = 2, 2%), robustness in terms of cross-validation or resampling (n = 89, 83%), treatment recommendations by ML algorithms (n = 9, 8%), and development of an interface (n = 12, 11%).

    Conclusion: ML for decision support in surgical oncology is receiving increasing attention with promising results, but robust and prospective clinical validation is mostly lacking. Furthermore, the integration of ML into AI applications is necessary to foster clinical translation.

    INTRODUCTION

    Cancer is still a major problem in modern medicine[1], with surgery being an important part of curative multimodal treatment strategies for solid cancers[2]. Furthermore, operations on abdominal organs can be associated with many severe complications[3]. Choices regarding the optimal treatment for individual patients are made by multidisciplinary tumor boards that have to follow international guidelines[4-6], but even this multidisciplinary approach does not always guarantee treatment success[7].

    Attempts to improve curative surgical treatment increasingly involve the use of modern computational methods[8]. Digitalization, interconnectivity between technical equipment, and electronic health records offer chances to improve patient outcomes. With the introduction of machine learning (ML) and artificial intelligence (AI) into medicine, multiple new options for data analysis have arisen and could be used to facilitate decisions in surgical oncology[9]. AI is intelligence demonstrated by machines, which may be realized by the use of ML, i.e., the study of computer algorithms that can improve automatically through experience[10]. While a general AI that can transfer knowledge to other problems similar to human intelligence is not yet realized, ML algorithms can be used to solve specific problems[11], such as interpretation of electrocardiograms[12], detection of suspicious findings in chest radiographs[13], computer-assisted colonoscopy[14], and early detection of pancreatic cancer[15].

    Regarding a systematic analysis of available evidence in AI and ML for decision support, a recent systematic review investigated ML and regression analysis from an epidemiologist’s point of view, focusing on the algorithm performance and not on the clinical translation[16]. Another review assessed studies that used AI for analysis, detection, prediction, and pathology in gastric cancer[17]. A scoping review described the use of ML in metabolic surgery[18]. Other reviews focused on the application of data science methods to surgery[9] and general hurdles for clinical translation[19], or the use of ML in abdominal surgery[20] and surgical phase recognition[21].

    In contrast, this systematic review gives a detailed overview of AI for decision support in surgical oncology based on ML with a focus on clinical applications, methodological soundness, and performance evaluation, as well as the key steps for clinical translation.

    METHODS

    The systematic review was conducted according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA, see checklist in Supplementary Table 1)[22] and followed the recommendations of the Cochrane Handbook for Systematic Reviews and Interventions[23] and recommendations specific to systematic reviews in surgery[24]. A protocol for this systematic review was developed a priori and was registered in the PROSPERO database (CRD42021235515).

    Eligibility criteria

    Studies were selected following the criteria for population, intervention, control, and outcome (PICO criteria) described below. Animal studies, meeting abstracts, letters, comments, editorials, non-English literature, and publications for which the full text was irretrievable were excluded.

    For the population, inclusion criteria were to meet the conditions of all studies on surgical oncology, including patients with the following types of cancer: thyroid, esophagus, stomach, colorectal, gallbladder, liver, pancreas, kidney, spleen, or sarcomas. Patients were eligible for, received, or followed up after cancer surgery. Excluded were other cancer types or a treatment approach that did not involve surgery.

    For intervention, inclusion criteria were development, testing, and use of AI based on ML only for decision support to aid in diagnosis, prediction of tumor characteristics and prognosis, therapy planning, intraoperative, and postoperative problems. Excluded were decision support applications using imaging or biomarkers only without taking clinical characteristics into account, ML algorithms used for abdominal cancer screening only, and algorithm development without clinical application.

    For control, inclusion criteria were based on comparison with other ML algorithms and regression analysis, if described. These were not mandatory for inclusion without specific exclusion criteria.

    For outcome, inclusion criteria were descriptive characteristics of selected studies and analysis of quality for developing meaningful clinical decision support without specific exclusion criteria.

    Definition of machine learning and artificial intelligence

    There is no consensus on the definition of ML and AI, with some authors using the terms synonymously[25]. In this review, ML is defined “as a program that learns to perform a task or make a decision automatically from data”, according to Beam and Kohane[26]. Algorithms range from rule-based systems and regression analysis, which require more human input, to higher-ranking systems such as random forests or neural networks, which require less[26]. As ML has gained more popularity in medicine in recent years, the focus is on novel methods for decision support and excluded studies, which dealt with lower ranking regression analysis from the current review.

    Poole et al. used the term “computational intelligence” as a synonym for artificial intelligence (AI), which is intelligence demonstrated by machines that perceive their environment, adapt their actions accordingly, and learn from experience[27]. Based on this definition, we focus on learning systems, and, for the purpose of this review, we define AI in surgical oncology as a computer application that integrates ML into the clinical workflow to support surgical decision making. These applications integrate ML algorithms trained on clinical data and surgical experience in a graphical user interface that allows for quick capture and representation of data in the clinical routine or even provides a treatment recommendation.

    Information sources and search

    The search strategy involved the most relevant medical databases for surgical literature; MEDLINE (via PubMed), Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL)[24]. The exact search terms can be accessed in Supplementary Note 1. The search was performed on 31 January 2021 for papers published between 1 January 2011 and 31 December 2020, because previously published applications of ML methods would not have been compared to current methods and would be outdated.

    Study selection

    After the removal of duplicates, titles and abstracts were screened by one reviewer (Haselbeck-Köbler M) for relevance. Positively evaluated reports were further screened by Schulze A, who provided an independent decision on whether to perform full-text screening. Selected articles underwent a full-text screening by two independent reviewers (Haselbeck-Köbler M and Schulze A). Any disagreement among the reviewers was resolved by consensus or a third person (Wagner M).

    Data collection process

    The data were extracted using a predefined extraction form which was refined after a pilot phase of data extraction for the first ten selected articles. Data extraction was performed by Haselbeck-Köbler M and Schulze A. Uncertainties were resolved by consensus or consultation of an independent third person (Wagner M).

    Data were extracted for the bibliographic information of the selected articles, including title, year of publication, and first author. Furthermore, tumor entities were extracted, as well as the prediction task for which decision support was developed.

    For the data used to construct ML algorithms, data origin (e.g., own clinical database or public registry database) was extracted, as well as the involvement of different facilities (single center or multiple centers), which categories of data were used (demographic, clinical, surgical data, laboratory, radiology, pathology, radiomics, and biomarker), and whether all variables used for machine learning were described. Studies were only defined as prospective studies if a fully developed ML algorithm for decision support was validated on new, incoming patients. Consequently, studies were defined as retrospective if the ML algorithms used prospectively collected data for training but were trained retrospectively.

    For the decision support, the developed algorithms were extracted, and for the best algorithm, the performance metric “area under the receiver operating characteristic curve” (AUC) was extracted. For the development process of the algorithms, the total number of patients and, as surrogate measures for robustness, number of patients for external validation, process for data splitting or resampling, handling of missing values, and whether class imbalance was mentioned and adjusted were extracted. In addition, whether the code was available as open source was extracted.

    For clinical translation, we extracted whether any kind of interface was developed and whether a demo was made accessible online to get an impression of the usability. In addition, whether a treatment recommendation was given instead of only a prediction that would not influence clinical decisions was extracted. A short summary of each paper was given with further specification of the clinical application.

    Data were extracted on whether the criterion was met. Due to study heterogeneity, quantitative data synthesis was not viable because multiple cancer types and different algorithm purposes were evaluated, which would not allow comparisons with each other. Additionally, no risk-of-bias assessment was conducted, because the aim of this review was not to give clinical recommendations but to outline the research field.

    Role of the funding source

    This work was funded by the National Center for Tumor Diseases (NCT) Heidelberg, Germany, within the cancer therapy program “Surgical Oncology”, the German Federal Ministry of Health within the “Surgomics” project (grant number BMG2520DAT82), and the German Research Foundation (DFG, Deutsche Forschungsgemeinschaft) as part of Germany’s Excellence Strategy [EXC 2050/1, Project ID 3900696704 - Cluster of Excellence “Centre for Tactile Internet with Human-in-the-Loop” (CeTI)]. The funding sources did not influence the study design, collection, analysis, and interpretation of data; writing of the report; or the decision to submit the paper for publication.

    RESULTS

    The results of this systematic review include information about combining the expertise from surgery, machine learning, and interaction design to create a clinically usable AI for decision support in surgical oncology [Figure 1]. Accordingly, the extracted information was aggregated into a checklist of key steps for scientific validation and clinical translation of AI for decision support in surgical oncology based on the CHARMS Checklist for a systematic review of prediction models[28], an epidemiological literature review on ML prediction models[16], and an extensive discussion among the authors. Table 1 gives an overview of the steps together with their fulfillment in the studies included in this review, examples of fulfilling studies, and the necessary expertise from surgery, machine learning, and interaction design.

    Figure 1. Necessary components for clinically usable artificial intelligence applications (AI). To create a clinically usable artificial intelligence application (AI) for decision support in surgical oncology, it is necessary to combine expertise from surgery, machine learning, and interaction design.

    Table 1

    Checklist of key steps for scientific validation and clinical translation

    StepDescriptionFulfilled in studies (n = 107)ExamplesNecessary expertise[Figure 1]
    Full feature setDescribe all patient characteristics used for building the algorithm, even before the selection of features for ML. For optimal comprehensibility, state whether the features were categorical or continuous, how they were transformed and describe at which point in time they were assessed and how89 % (n = 95)Stojadinovic et al. 2013 (CRC)[29] + Ting et al. 2020 (CRC)[30] + Velez-Serrano et al. 2017 (pancreas)[31]Surgery
    Handling of missing featuresDescribe how missing features and values in the patient data sets were handled, e.g. excluded or imputed34 % (n = 36)Bhandari et al. 2020 (kidney)[32] + Mourad et al. 2020 (thyroid)[33] + Smith and Mezhir 2014 (pancreas)[34]Machine learning
    Split or resamplingDescribe how the data was split or resampled for training, validation and testing83 % (n = 89)Stojadinovic et al. 2013 (CRC)[29] + Ting et al. 2020 (CRC)[30] + Velez-Serrano et al. 2017 (pancreas)[31]Machine learning
    Class imbalanceMake sure the data has a balanced outcome, or use mathematical measures to optimize your dataset in case of imbalance12 % (n = 13)Bolourani et al. 2020 (esophagus)[35] + Bhandari et al. 2020 (kidney)[32] + Schoenberg et al. 2020 (liver)[36]Machine learning
    Multiple algorithmsCompare multiple algorithms to find the optimal one for a certain task68 % (n = 73)Nilsaz-Dezfouli et al. 2017 (stomach)[37] + Ting et al. 2020 (CRC)[30] + Xu et al. 2020 (CRC)[38]Machine learning
    MulticenterCollect data for building the algorithms from different facilities42 % (n = 45)Bhandari et al. 2020 (kidney)[32] + Mourad et al. 2020 (thyroid)[33] + Stojadinovic et al. 2013 (CRC)[29]Surgery
    External validation setMake use of an external validation set to assess the performance of the algorithm. This external validation set is curated from data outside the clinical environment in which the algorithm was trained12 % (n = 13)Rahman et al. 2020 (esophagus)[39] + Kudo et al. 2020 (CRC)[40] + Li et al. 2020 (CRC)[41]Surgery
    Prospective validationProspectively validate decision support with new patients after training of ML algorithm was finished2 % (n = 2)van Soest et al. 2017 (CRC)[42] + Adams and Papagrigoriadis 2014 (CRC)[43]Surgery
    Treatment recommendationUse ML to provide a treatment recommendation. A mere prediction of complication rate is not considered a treatment recommendation8 % (n = 9)Ichimasa et al. 2018 (CRC)[44] + Liu et al. 2019 (stomach)[45] + Kang et al. 2020 (pancreas)[46]Surgery, machine learning, interaction design
    Interface developedDevelop a user interface for clinicians and provide (online) access for other researchers11 % (n = 12)

    Schoenberg et al. 2020 (liver)[36] + Han et al. 2020 (pancreas)[47] + Rahman et al. 2020 (esophagus)[39]Surgery, interaction design
    Open sourceMake your code open source online for other researchers3 % (n = 3)Rahman et al. 2020 (esophagus)[39] + Zhou et al. 2020 (stomach)[48] + Lei et al. 2020 (liver)[49]Machine learning

    Study selection

    In total, 11,876 articles were identified through database searching. After the removal of duplicates and initial screening for title and abstract, 195 articles were eligible for full-text screening. In total, 107 articles met our eligibility criteria and information was extracted. The other articles were excluded for various reasons. A PRISMA flow chart of the selection process is given in Figure 2.

    Figure 2. PRISMA flow chart.

    Study characteristics

    In total, 107 studies were selected to be assessed in this systematic review; a summary for each of the selected studies can be found in Supplementary Table 2. Overall, 105 of 107 studies were conducted in a retrospective setting (98%), while only two were conducted prospectively (2%), i.e. they validated the retrospectively trained ML algorithms in a prospective cohort. No studies evaluated continuous learning of the models, i.e. investigated improvement of algorithm performance with an increasing amount of data collected during clinical use of the algorithms. Overall, 45 studies (42%) used data collected in a multicenter approach, while 23 studies (22%) used public databases such as SEER[50], ACS NSQIP[51], and SRTR[52]. External validation was performed in 13 studies (12%), with a median of 164 patients (IQR = 104-387) included in the external validation. Studies used demographic data most often (n = 98, 92%), followed by clinical data (n = 92, 86%), pathological data (n = 58, 54%), surgical data (n = 56, 52%), laboratory data (n = 55, 51%), radiological data (n = 46, 43%), biomarkers/genetics (n = 6, 6%), and radiomics (n = 2, 2%). A full list of the variables on which selection and training of ML algorithms were performed was presented by 95 studies (89%).

    Of the selected studies, 73 (68%) used more than one ML algorithm. Neural networks (n = 52, 49%) were by far the most popular ML algorithm, only outnumbered by regression analyses (n = 56, 52%), which were used as a control method in comparison to ML methods. Neural networks (n = 45, 42%) were also the ML method most often deemed best by the authors of the respective studies. For treatment recommendations, only nine studies (8%) used ML to explore predictions that would directly influence surgical decision making. To visualize these data, Figure 3 summarizes the used ML methods, tumor entities, prediction tasks, and the origin of data.

    Figure 3. Summary of study characteristics: (A) Number of machine learning algorithms investigated in selected studies; (B) number of cancer entities investigated in selected studies; (C) number of different prediction tasks performed in selected studies; and (D) origin of data in selected studies.

    Patient numbers ranged from 45 to 188,336 (median of 565 patients, IQR = 267.5-1729.5). Figure 4 gives an overview of the different patient numbers of selected studies grouped by respective tumor entities.

    Figure 4. Patient numbers of selected studies grouped by tumor entity. Tumor entities subsumed as “Other” are intrahepatic cholangiocarcinoma (n = 2), gallbladder cancer (n = 1), kidney cancer (n = 1), and peritoneal carcinomatosis (n = 1).

    Methods of data splitting or resampling for validation were a single-random-split (n = 57, 53%), k-fold cross validation (n = 21, 20%), bootstrapping (n = 10, 9%), and leave-one-out-cross validation (n = 1, 1%), while 18 studies (17%) did not describe any. Only 13 studies (12%) acknowledged the problem of class balancing explicitly, and 10 (9%) of them described how they addressed it. The developed ML models were evaluated with different statistical measurements. AUC (n = 76, 71%) was the most common, followed by sensitivity (n = 45, 42%), accuracy (n = 41, 38%), and specificity (n = 41, 38%). Additional measurements encompassed positive predictive values (n = 25, 23%) and negative predictive values (n = 19, 18%). Other metrics such as F1-Score (n = 9, 8%) or c-index (n = 7, 7%) were only reported rarely; various others, such as Brier-Score, Youden-Index, and Hosmer-Lemeshow-Test, were only reported by single studies.

    For visualization and a possible clinical application, five studies (5%) developed a nomogram and twelve studies (11%) developed an interactive interface for their chosen ML method, which was accessible online in seven cases (7%) at the time of this review. Only three studies (3%) published their code to make the methods behind their ML models accessible open source for other researchers.

    DISCUSSION

    AI for decision support in surgical oncology

    Modern medicine generates masses of data every day, generating “big data” not only in terms of volume but also in terms of variety (e.g., demographic, clinical pathological, and surgical data), velocity (e.g., intraoperative sensor data and vital monitoring on intensive care unit), veracity (e.g., uncertainty of findings in radiological imaging), and value (for doctors, nurses, hospitals, insurance companies, etc.)[53]. However, the data themselves are useless. They have to be analyzed and interpreted, and ML has proven to be a powerful tool[54]. This systematic review gives an overview of the state of the art in use of ML and clinical application of AI for surgical oncology. Here, a broad spectrum of tumor entities investigated with various endpoints are addressed. In addition, numerous different ML algorithms are compared.

    However, major drawbacks are revealed in the systematic analysis of key steps for scientific validation and clinical translation. Basic rules of machine learning were followed by most studies, such as feature set description and data splitting and resampling. Fewer studies compared multiple algorithms. Only about half of the selected studies used data from multiple centers, which is important to increase heterogeneity, reduce bias, and improve generalizability[11], as in the case of multicenter clinical trials. Moreover, up until now, prospective, external validation of ML algorithms and the development of user interfaces for clinical application of AI are limited to very few studies. The following paragraphs give an overview of how studies on AI in surgical oncology should be designed to perform an “ideal” ML study in surgical oncology based on our findings in this systematic review. These key steps lead to the path of successfully using “big data” in surgical oncology. Our checklist thus complements the DECIDE-AI guidelines that focus on early evaluation of AI systems as an intervention in live clinical settings[55]

    Key steps for scientific validation

    To validate ML algorithms during their development, the dataset is usually split into training and test sets. Most of the studies described their strategy for this. However, there was an inconsistent use of the terms “validation set” and “test set”, which were used as synonyms to build the algorithm. Although in many studies internal or external validations were included, they often did not describe the performance evaluation to their full extent, as reported similarly by van Soest et al.[42]. The confusing terminology and reporting lead to considerable effort in understanding the process of building surgical decision support with ML algorithms. Here, a visualization, such as a flow chart, should be used to visualize the complex process of development and validation [16]. Another weakness in the selected studies is the lack of reports on class imbalance and measures to avoid a wrongful training process. If class imbalance is not accounted for, predicting rare events or outcomes such as mortality after surgery may be distorted because, if a dataset is not equally distributed, then the ML algorithm may not predict the event but rather the majority class of “no event”.

    An external validation set or independent test set is curated from data outside the clinical environment used for algorithm training and can be used to test the algorithm. External validation is a key step to demonstrate generalizability, i.e. a tool for surgical decision support cannot just be applied to the population it was designed for. However, only a few studies included in this review performed external validation.

    When assessing the performance of the decision support, AUC was mostly used. Closely linked to the AUC are sensitivity, specificity, positive-predictive value, and negative predictive value. Surprisingly, results for the latter metrics are reported much less frequently, leading to considerable bias in overestimating the performance of ML algorithms in practical clinical applications of AI. A full performance analysis as well as a risk of bias analysis was not included in this systematic review as there was a lot of heterogeneity and different methods of reporting the algorithms’ performance. Instead, the data extracted on AUC - if available - for each of the selected papers can be accessed in Supplementary Table 2. The complete set of extracted performance data, including the heterogeneous metrics and methods, is available from the authors upon reasonable request. The data extracted on comprehensive performance evaluation for each selected paper is available in the Appendix. Furthermore, comparability of the studies was limited by the heterogeneity of tumor entities and predicted outcomes of the algorithms.

    Multiple algorithms were compared based on about two thirds of selected papers. This approach is of utmost importance to investigate which of many different algorithms achieves the best performance for a certain prediction task and whether simpler models can achieve even better results than complicated neural networks[11,41,56].

    In addition, to provide further validation after successfully developing a model, the source code should be provided online or in the supplementary material to make the surgical decision support reproducible for fellow researchers. Unfortunately, the vast majority of studies failed to provide their code.

    Key steps for clinical translation

    Most selected studies covered prediction purposes with no direct clinical consequence, such as predicting survival when a surgical resection was already performed. Only a few studies predicted certain outcomes that are directly linked to treatment consequences and can therefore be regarded as clinically relevant decision support. Examples include the prediction of pathological complete response after neoadjuvant chemoradiotherapy of rectal cancer that justifies the decision about a watch-and-wait-strategy[57] or the prediction of malignant intraductal papillary mucinous neoplasms of the pancreas that justifies the decision about surgical resection[46]. It has to be noted that this clinically relevant decision support renders the software used a medical product falling under the respective legal regulations.

    In addition, the majority of studies described their full feature set before final feature selection. However, upon closer inspection, it was not always evident when applied features (laboratory values, results of staging, etc.) were assessed. Assessment before or after surgery influences the possible utilization for decision support: if features are only available after surgery, their application to support decisions for or against a surgical approach is limited.

    Despite AI is highly acclaimed in medicine and surgery, there is a lack of tools that allow clinicians to enter patient data and then recommend individual treatment paths[8,58,59]. A famous example of that is IBM’s Watson for Oncology which gives individual advice for chemotherapy regimes for certain types of cancer. While a few studies on IBM’s Watson for Oncology have been published, the comparison with multidisciplinary tumor boards lacks the resounding success promised[59-61]. Moreover, even a seemingly strong AI can fail simply because certain chemotherapeutics are not available in the country where the system was launched[59].

    Apart from that, the promising results reported in selected papers almost always lack a prospective, external validation, which is a key requirement for the transition into the clinical routine and external generalizability[35]. Often, even a randomized, controlled trial would be necessary to prove the superiority of AI-supported decisions compared to those without AI. While in this review, only a few studies on decision support in surgical oncology validated their algorithm externally, AI for imaging is two steps ahead, as these applications have not only been tested externally and prospectively but also prospectively compared with clinicians in randomized controlled trials[62].

    This limitation is closely linked to the development of user interfaces that facilitate adoption into the clinical workflow[63] and allow other physicians to benefit from the findings[64]. Only when decision support is easy to comprehend as well as to operate and allows for integration into the clinical routine can it contribute to patient benefit[65,66]. On the contrary, AI and surgical decision support are not to replace physicians but to equip them with tools that may improve patient outcomes and time utilization in clinical processes. Despite popular claims that AI will solve most problems in medicine, up until now, most algorithms train models that only solve one specific problem[11].

    Strengths and weaknesses

    An extensive literature research of the last ten years was conducted. A large variety of different algorithms and databases was covered, yet there was still the possibility that some articles were missed. ML algorithms may not necessarily be published in clinical journals but in pre-print services, online code repositories (e.g., GitHub), or conferences[58]. It is because of the focus on the clinical translation of ML and AI that these services were not explicitly searched. Furthermore, we excluded articles investigating image analysis and only focused on surgical decisions instead of radiological decisions. This exclusion criterion may have led to the exclusion of surgical imaging methods important for surgical oncology, such as those described[67].

    An in-depth bias analysis of the selected studies was not performed because of the heterogeneity of studies that rendered further clinical recommendations impossible. Nevertheless, several items, such as the description of missing features, presentation of the full feature set for data, strategy for splitting the data, class imbalance, and access to the methods online (open source), can be considered as indicators of bias.

    In conclusion, this systematic review provides a detailed summary and quality checklist of AI for decision support in surgical oncology with a focus on clinical translation. There is increasing activity in this field with multiple cancer entities and different ML algorithms investigated to predict various endpoints.

    Whereas most studies follow basic rules of machine learning, such as feature set description and data splitting and resampling, fewer studies compare multiple algorithms or use data from multiple centers. Moreover, until now, there are only very few studies on prospective, external validation and the development of user interfaces; however, both are necessary before clinical translation occurs and will pave the road for randomized controlled studies comparing surgeons with surgical decision support to those without such support.

    DECLARATIONS

    Authors’ contributions

    Conceptualized the study: Wagner M, Dugas M, Maier-Hein L, Speidel S, Mehrabi A, Büchler MW, Müller-Stich BP

    Defined the search strategy: Probst P, Brandenburg JM, Kalkum E

    Developed the methodology: Wagner M, Schulze A, Klotz R, März K, Bodenstedt S, Dugas M

    Performed data curation: Schulze A, Haselbeck-Köbler M

    Performed data analysis: Schulze A, Majlesara A, Ramouz A

    Provided funding for the study: Büchler MW, Maier-Hein L, Mehrabi A, Müller-Stich BP

    Supervised the data analysis: Probst P, Nickel F, Klotz R

    Wrote the original draft: Wagner M, Schulze A, Haselbeck-Köbler M, Brandenburg JM

    All authors reviewed and edited the manuscript.

    Availability of data and materials

    Template data collection forms, data extracted from included studies and data used for analyses are available from the authors upon reasonable request.

    Financial support and sponsorship

    This work has been funded by the National Center for Tumor Diseases (NCT) Heidelberg, Germany within the cancer therapy program “Surgical Oncology” and by the German Federal Ministry of Health within the “Surgomics” project (grant number BMG2520DAT82), and by the German Research Foundation (DFG, Deutsche Forschungsgemeinschaft) as part of Germany’s Excellence Strategy - EXC 2050/1 - Project ID 3900696704 - Cluster of Excellence “Centre for Tactile Internet with Human-in-the-Loop” (CeTI).

    Conflicts of interest

    All authors declared that there are no conflicts of interest.

    Ethical approval and consent to participate

    Not applicable.

    Consent for publication

    Not applicable.

    Copyright

    © The Author(s) 2022.

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    Cite This Article

    Wagner M, Schulze A, Haselbeck-Köbler M, Probst P, Brandenburg JM, Kalkum E, Majlesara A, Ramouz A, Klotz R, Nickel F, März K, Bodenstedt S, Dugas M, Maier-Hein L, Mehrabi A, Speidel S, Büchler MW, Müller-Stich BP. Artificial intelligence for decision support in surgical oncology - a systematic review. Art Int Surg 2022;2:159-72. http://dx.doi.org/10.20517/ais.2022.21

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