Validation of a Diagnostic Model to Differentiate Multiple Myeloma from Bone Metastasis

Abstract

Phichayut Phinyo,1– 4,* Nutcha Jarupanich,2 Lalita Lumkul,2,4 Areerak Phanphaisarn,3,5 Thanate Poosiripinyo,6 Sermsak Sukpanichyingyong,6 Pichaya Thanindratarn,7 Yodsawee Pornmeechai,8 Taweechok Wisanuyotin,9 Rapin Phimolsarnti,10 Ekarat Rattarittamrong,11 Dumnoensun Pruksakorn3– 5,* 1Department of Family Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 2Center for Clinical Epidemiology and Clinical Statistics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 3Musculoskeletal Science and Translational Research (MSTR), Chiang Mai University, Chiang Mai, Thailand; 4Center of Multidisciplinary Technology for Advanced Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 5Department of Orthopaedics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 6Department of Orthopaedics, Khon Kaen Hospital, Khon Kaen, Thailand; 7Chulabhorn Hospital, Princess Srisavangavadhana College of Medicine, Chulabhorn Royal Academy, Bangkok, Thailand; 8Department of Orthopedics, Queen Savang Vadhana Memorial Hospital, Chonburi, Thailand; 9Department of Orthopaedics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; 10Department of Orthopaedic Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; 11Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand*These authors contributed equally to this workCorrespondence: Phichayut Phinyo, Department of Family Medicine, Faculty of Medicine, Chiang Mai University, 110 Intawaroros Road, Si Phum, Muang, Chiang Mai, 50200, Thailand, Tel [phone], Fax [phone], Email [email protected]; [email protected] Dumnoensun Pruksakorn, Department of Orthopaedics, Faculty of Medicine, Chiang Mai University, 110 Intawaroros Road, Si Phum, Muang, Chiang Mai, 50200, Thailand, Tel [phone], Fax [phone], Email [email protected]; [email protected]: A diagnostic model to differentiate multiple myeloma (MM) from bone metastasis (BM) in patients with destructive bone lesions (MM-BM DDx) was developed to promote timely and appropriate referral of patients with MM to hematologists. External validation has never been conducted. This study aims to externally validate the performance of the MM-BM DDx model.Patients and Methods: This multi-center external validation study was conducted using retrospective data of patients over 45 years old diagnosed with MM or BM at six university-affiliated hospitals in Thailand from 2016 to 2022. The MM-BM DDx development dataset, including patients from 2012 to 2015, was utilized during external validation. Diagnostic indicators for MM included in the MM-BM DDx model are serum creatinine, serum globulin, and serum alkaline phosphatase (ALP). MM and BM diagnosis was based on the documented International Classification of Diseases 10th Revision codes. Model performance was evaluated in terms of discrimination, calibration, and accuracy.Results: A total of 3018 patients were included in the validation dataset (586 with MM and 2432 with BM). Clinical characteristics were similar between the validation and development datasets. The MM-BM DDx model’s predictions showed an AUC of 0.89 (95% CI, 0.87, 0.90). The predicted probabilities of MM from the model increased concordantly with the observed proportion of MM within the validation dataset. The estimated sensitivity, specificity, and LR for each odds class in the validation dataset were similar to those of the development dataset.Conclusion: The discriminative ability and calibration of the MM-BM DDx model were found to be preserved during external validation. These findings provide support for the practical use of the MM-BM DDx model to assist clinicians in identifying patients with destructive bone lesions who are likely to have MM and enable them to arrange timely referrals for further evaluation by hematologists.Keywords: diagnosis, primary care, clinical prediction model, referral, bone metastases, multiple myeloma

Keywords

• diagnosis
• primary care
• clinical prediction model
• referral
• bone metastases
• multiple myeloma