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      Explainable machine learning model for predicting skeletal muscle loss during surgery and adjuvant chemotherapy in ovarian cancer

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          Abstract

          Background

          Skeletal muscle loss during treatment is associated with poor survival outcomes in patients with ovarian cancer. Although changes in muscle mass can be assessed on computed tomography (CT) scans, this labour‐intensive process can impair its utility in clinical practice. This study aimed to develop a machine learning (ML) model to predict muscle loss based on clinical data and to interpret the ML model by applying SHapley Additive exPlanations (SHAP) method.

          Methods

          This study included the data of 617 patients with ovarian cancer who underwent primary debulking surgery and platinum‐based chemotherapy at a tertiary centre between 2010 and 2019. The cohort data were split into training and test sets based on the treatment time. External validation was performed using 140 patients from a different tertiary centre. The skeletal muscle index (SMI) was measured from pre‐ and post‐treatment CT scans, and a decrease in SMI ≥ 5% was defined as muscle loss. We evaluated five ML models to predict muscle loss, and their performance was determined using the area under the receiver operating characteristic curve (AUC) and F1 score. The features for analysis included demographic and disease‐specific characteristics and relative changes in body mass index (BMI), albumin, neutrophil‐to‐lymphocyte ratio (NLR), and platelet‐to‐lymphocyte ratio (PLR). The SHAP method was applied to determine the importance of the features and interpret the ML models.

          Results

          The median (inter‐quartile range) age of the cohort was 52 (46–59) years. After treatment, 204 patients (33.1%) experienced muscle loss in the training and test datasets, while 44 (31.4%) patients experienced muscle loss in the external validation dataset. Among the five evaluated ML models, the random forest model achieved the highest AUC (0.856, 95% confidence interval: 0.854–0.859) and F1 score (0.726, 95% confidence interval: 0.722–0.730). In the external validation, the random forest model outperformed all ML models with an AUC of 0.874 and an F1 score of 0.741. The results of the SHAP method showed that the albumin change, BMI change, malignant ascites, NLR change, and PLR change were the most important factors in muscle loss. At the patient level, SHAP force plots demonstrated insightful interpretation of our random forest model to predict muscle loss.

          Conclusions

          Explainable ML model was developed using clinical data to identify patients experiencing muscle loss after treatment and provide information of feature contribution. Using the SHAP method, clinicians may better understand the contributors to muscle loss and target interventions to counteract muscle loss.

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          Most cited references39

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            A Unified Approach to Interpreting Model Predictions

            Understanding why a model makes a certain prediction can be as crucial as the prediction's accuracy in many applications. However, the highest accuracy for large modern datasets is often achieved by complex models that even experts struggle to interpret, such as ensemble or deep learning models, creating a tension between accuracy and interpretability. In response, various methods have recently been proposed to help users interpret the predictions of complex models, but it is often unclear how these methods are related and when one method is preferable over another. To address this problem, we present a unified framework for interpreting predictions, SHAP (SHapley Additive exPlanations). SHAP assigns each feature an importance value for a particular prediction. Its novel components include: (1) the identification of a new class of additive feature importance measures, and (2) theoretical results showing there is a unique solution in this class with a set of desirable properties. The new class unifies six existing methods, notable because several recent methods in the class lack the proposed desirable properties. Based on insights from this unification, we present new methods that show improved computational performance and/or better consistency with human intuition than previous approaches. To appear in NIPS 2017
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              Definition and classification of cancer cachexia: an international consensus.

              To develop a framework for the definition and classification of cancer cachexia a panel of experts participated in a formal consensus process, including focus groups and two Delphi rounds. Cancer cachexia was defined as a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. Its pathophysiology is characterised by a negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism. The agreed diagnostic criterion for cachexia was weight loss greater than 5%, or weight loss greater than 2% in individuals already showing depletion according to current bodyweight and height (body-mass index [BMI] <20 kg/m(2)) or skeletal muscle mass (sarcopenia). An agreement was made that the cachexia syndrome can develop progressively through various stages--precachexia to cachexia to refractory cachexia. Severity can be classified according to degree of depletion of energy stores and body protein (BMI) in combination with degree of ongoing weight loss. Assessment for classification and clinical management should include the following domains: anorexia or reduced food intake, catabolic drive, muscle mass and strength, functional and psychosocial impairment. Consensus exists on a framework for the definition and classification of cancer cachexia. After validation, this should aid clinical trial design, development of practice guidelines, and, eventually, routine clinical management. Copyright © 2011 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                kpwu@nycu.edu.tw
                sinus.5706@mmh.org.tw
                Journal
                J Cachexia Sarcopenia Muscle
                J Cachexia Sarcopenia Muscle
                10.1007/13539.2190-6009
                JCSM
                Journal of Cachexia, Sarcopenia and Muscle
                John Wiley and Sons Inc. (Hoboken )
                2190-5991
                2190-6009
                12 July 2023
                October 2023
                : 14
                : 5 ( doiID: 10.1002/jcsm.v14.5 )
                : 2044-2053
                Affiliations
                [ 1 ] Institute of Biomedical Informatics National Yang Ming Chiao Tung University Taipei Taiwan
                [ 2 ] Department of Obstetrics and Gynecology MacKay Memorial Hospital Taipei Taiwan
                [ 3 ] Department of Medicine MacKay Medical College New Taipei City Taiwan
                [ 4 ] Department of Radiology MacKay Memorial Hospital Taipei Taiwan
                [ 5 ] Department of Radiation Oncology Changhua Christian Hospital Changhua Taiwan
                [ 6 ] Department of Obstetrics and Gynecology Changhua Christian Hospital Taipei Taiwan
                [ 7 ] Department of Medical Research MacKay Memorial Hospital Taipei Taiwan
                [ 8 ] Department of Radiation Oncology MacKay Memorial Hospital Taipei Taiwan
                Author notes
                [*] [* ] Correspondence to: Jie Lee, Department of Radiation Oncology, MacKay Memorial Hospital, No. 92, Section 2, Chung Shan North Road, Taipei 104217, Taiwan. Email: sinus.5706@ 123456mmh.org.tw

                Kun‐Pin Wu, Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, No. 155, Section 2, Li‐Nong St, Beitou District, Taipei 112304, Taiwan. Email: kpwu@ 123456nycu.edu.tw

                Author information
                https://orcid.org/0000-0003-1445-2393
                Article
                JCSM13282 JCSM-D-22-00595
                10.1002/jcsm.13282
                10570082
                37435785
                f67229ab-15fd-4705-a74b-5e8a41ff5c85
                © 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 30 March 2023
                : 25 August 2022
                : 22 May 2023
                Page count
                Figures: 4, Tables: 3, Pages: 2053, Words: 4085
                Funding
                Funded by: Ministry of Science and Technology, Taiwan , doi 10.13039/501100004663;
                Award ID: MOST 110‐2314‐B‐A49A‐506‐MY3
                Award ID: MOST 110‐2314‐B‐195‐033
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                October 2023
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.3.4 mode:remove_FC converted:12.10.2023

                Orthopedics
                machine learning,muscle loss,ovarian cancer,shapley additive explanations
                Orthopedics
                machine learning, muscle loss, ovarian cancer, shapley additive explanations

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