Background: To propose a personalized therapeutic approach in osteosarcoma treatment, we assessed whether sequential [¹⁸F]FDG PET/CT (PET/CT) could predict the outcome of patients with osteosarcoma of the extremities after one cycle and two cycles of neoadjuvant chemotherapy. Methods: A total of 73 patients with AJCC stage II extremity osteosarcoma treated with 2 cycles of neoadjuvant chemotherapy, surgery, and adjuvant chemotherapy were retrospectively analyzed in this study. All patients underwent PET/CT before (PET0), after 1 cycle (PET1), and after the completion of neoadjuvant chemotherapy (PET2), respectively. Maximum standardized uptake value (SUV_max) (corrected for body weight) and the % changes of SUV_max were calculated, and histological responses were evaluated after surgery. Receiver-operating characteristic (ROC) curve analyses and the Cox proportional hazards models were used to analyze whether imaging and clinicopathologic parameters could predict event-free survival (EFS). Results: A total of 36 patients (49.3%) exhibited a poor histologic response and 17 patients (23.3%) showed events (metastasis in 15 and local recurrence in 2). SUV_max on PET2 (SUV2), the percentage change of SUV_max between PET0 and PET1 (Δ%SUV01), and between PET0 and PET2 (Δ%SUV02) most accurately predicted events using the ROC curve analysis. SUV2 (relative risk, 8.86; 95% CI, 2.25–34.93), Δ%SUV01 (relative risk, 5.97; 95% CI, 1.47–24.25), and Δ%SUV02 (relative risk, 6.00; 95% CI, 1.16–30.91) were independent predicting factors for EFS with multivariate analysis. Patients with SUV2 over 5.9 or Δ%SUV01 over − 39.8% or Δ%SUV02 over − 54.1% showed worse EFS rates than others (p < 0.05). Conclusions: PET evaluation after 1 cycle of presurgical chemotherapy can predict the clinical outcome of extremity osteosarcoma. [¹⁸F]FDG PET, which shows a potential role in the early evaluation of the modification of timing of local control, can be a useful modality for early response monitoring of neoadjuvant chemotherapy.

Zoledronic acid is an effective radiosensitizer in the treatment of osteosarcoma

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.

Chemotherapy response and metastasis prediction play important roles in the treatment of pediatric osteosarcoma, which is prone to metastasis and has a high mortality rate. This study aimed to estimate the prediction model using gene expression and image texture features. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) images of 52 pediatric osteosarcoma patients were used to estimate the machine learning algorithm. An appropriate algorithm was selected by estimating the machine learning accuracy. ¹⁸F-FDG PET/CT images of 21 patients were selected for prediction model development based on simultaneous KI67 and EZRIN expression. The prediction model for chemotherapy response and metastasis was estimated using area under the curve (AUC) maximum image texture features (AUC_max) and gene expression. The machine learning algorithm with the highest test accuracy in chemotherapy response and metastasis was selected using the random forest algorithm. The chemotherapy response and metastasis test accuracy with image texture features was 0.83 and 0.76, respectively. The highest test accuracy and AUC of chemotherapy response with AUC_max, KI67, and EZRIN were estimated to be 0.85 and 0.89, respectively. The highest test accuracy and AUC of metastasis with AUC_max, KI67, and EZRIN were estimated to be 0.85 and 0.8, respectively. The metastasis prediction accuracy increased by 10% using radiogenomics data.