Deep Learning-Based Objective and Reproducible Osteosarcoma Chemotherapy Response Assessment and Outcome Prediction.

Osteosarcoma is the most common primary bone cancer, whose standard treatment includes pre-operative chemotherapy followed by resection. Chemotherapy response is used for prognosis and management of patients. Necrosis is routinely assessed after chemotherapy from histology slides on resection specimens, where necrosis ratio is defined as the ratio of necrotic tumor/overall tumor. Patients with necrosis ratio ≥90% are known to have a better outcome. Manual microscopic review of necrosis ratio from multiple glass slides is semiquantitative and can have intraobserver and interobserver variability. In this study, an objective and reproducible deep learning-based approach was proposed to estimate necrosis ratio with outcome prediction from scanned hematoxylin and eosin whole slide images (WSIs). To conduct the study, 103 osteosarcoma cases with 3134 WSIs were collected. Deep Multi-Magnification Network was trained to segment multiple tissue subtypes, including viable tumor and necrotic tumor at a pixel level and to calculate case-level necrosis ratio from multiple WSIs. Necrosis ratio estimated by the segmentation model highly correlates with necrosis ratio from pathology reports manually assessed by experts. Furthermore, patients were successfully stratified to predict overall survival with P = 2.4 × 10-6 and progression-free survival with P = 0.016. This study indicates that deep learning can support pathologists as an objective tool to analyze osteosarcoma from histology for assessing treatment response and predicting patient outcome.

Post-Operative Permanent Hypoparathyroidism and Preoperative Vitamin D Prophylaxis.

Permanent hypoparathyroidism, a feared thyroidectomy complication, leads to significant patient morbidity, medical treatment, and monitoring. This study explores whether preoperative high-dose vitamin D loading decreases the incidence of permanent hypoparathyroidism. In a subgroup analysis, the study examines the predictive utility of day 1 parathyroid hormone (PTH) in permanent hypoparathyroidism. Patients (n = 150) were previously recruited in the VItamin D In Thyroidectomy (VIDIT) trial, a multicentre, randomised, double blind, placebo-controlled trial evaluating the role of 300,000 IU cholecalciferol administered orally a week before total thyroidectomy. Patients were contacted postoperatively beyond six months through a telephonic questionnaire. The primary outcome was permanent hypoparathyroidism, strictly defined as the need for activated vitamin D six months postoperatively. Out of 150 patients, 130 (86.7%) were contactable. Permanent hypoparathyroidism occurred in 11/130 (8.5%) patients, with a lower incidence of 5.3% (3/57) in the cholecalciferol group compared to 11% (8/73) in the placebo group; however, this was non-significant (p = 0.34). In a subgroup analysis, no relationship between day 1 PTH level and the incidence of permanent hypoparathyroidism was found (p ≥ 0.99). There was a lower rate of permanent hypoparathyroidism in the cholecalciferol group, which was not significant. The predictive utility of day 1 postoperative PTH levels may be limited to transient hypoparathyroidism.