Abstract

We compared the accuracy of prediction of the response to neoadjuvant chemotherapy (NAC) in osteosarcoma patients between machine learning approaches of whole tumor utilizing fluorine−18fluorodeoxyglucose (18F-FDG) uptake heterogeneity features and a convolutional neural network of the intratumor image region. In 105 patients with osteosarcoma, 18F-FDG positron emission tomography/computed tomography (PET/CT) images were acquired before (baseline PET0) and after NAC (PET1). Patients were divided into responders and non-responders about neoadjuvant chemotherapy. Quantitative 18F-FDG heterogeneity features were calculated using LIFEX version 4.0. Receiver operating characteristic (ROC) curve analysis of 18F-FDG uptake heterogeneity features was used to predict the response to NAC. Machine learning algorithms and 2-dimensional convolutional neural network (2D CNN) deep learning networks were estimated for predicting NAC response with the baseline PET0 images of the 105 patients. ML was performed using the entire tumor image. The accuracy of the 2D CNN prediction model was evaluated using total tumor slices, the center 20 slices, the center 10 slices, and center slice. A total number of 80 patients was used for k-fold validation by five groups with 16 patients. The CNN network test accuracy estimation was performed using 25 patients. The areas under the ROC curves (AUCs) for baseline PET maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), metabolic tumor volume (MTV), and gray level size zone matrix (GLSZM) were 0.532, 0.507, 0.510, and 0.626, respectively. The texture features test accuracy of machine learning by random forest and support vector machine were 0.55 and 0. 54, respectively. The k-fold validation accuracy and validation accuracy were 0.968 ± 0.01 and 0.610 ± 0.04, respectively. The test accuracy of total tumor slices, the center 20 slices, center 10 slices, and center slices were 0.625, 0.616, 0.628, and 0.760, respectively. The prediction model for NAC response with baseline PET0 texture features machine learning estimated a poor outcome, but the 2D CNN network using 18F-FDG baseline PET0 images could predict the treatment response before prior chemotherapy in osteosarcoma. Additionally, using the 2D CNN prediction model using a tumor center slice of 18F-FDG PET images before NAC can help decide whether to perform NAC to treat osteosarcoma patients.

Highlights

  • Osteosarcoma is the most common primary malignant bone tumor, typically occurring in the metaphysis of the long bones and occurs mainly between the ages of 15 and 25, and occurs more frequently in men than in women [1]

  • The retrospective study was conducted in a cohort of 81 osteosarcoma patients who were diagnosed at the Korea Institute of Radiology and Medical Sciences from June 2006 to May 2014

  • Before neoadjuvant chemotherapy (NAC), only gray level size zone matrix (GLSZM) (AUC = 0.626, sensitivity = 0.579, specificity = 0.721, p-value = 0.045), an 18 F-FDG uptake heterogeneity feature reflecting the image intensity size zone, could predict the NAC response, while SUVmax (AUC = 0.532, sensitivity = 0.842, specificity = 0.302, p-value = 0.622), total lesion glycolysis (TLG) (AUC = 0.507, sensitivity = 0.763, specificity = 0.395, p-value = 0.918), and metabolic tumor volume (MTV) (AUC = 0.510, sensitivity = 0.816, specificity = 0.349, p-value = 0.881) could not; this prediction result is similar to the results of previous studies [16,20]

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Summary

Introduction

Osteosarcoma is the most common primary malignant bone tumor, typically occurring in the metaphysis of the long bones and occurs mainly between the ages of 15 and 25, and occurs more frequently in men than in women [1]. 5-year survival rate of osteosarcoma was as low as 20% [2]. Application of neoadjuvant chemotherapy (NAC) therapy significantly improves long-term survival in patients with high-grade osteosarcoma. The NAC protocol has been included before and after surgery for osteosarcoma patients [3]. NAC for osteosarcoma has a toxicity and ineffective problem [4,5,6]. Ineffective chemotherapy can cause drug resistance [7] and delayed tumor removal surgery can compromise clinical outcomes [8]. Predicting the histological response to NAC and determining whether to maintain treatment is important for managing osteosarcoma patients

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