Deep Domain Adversarial Learning for Species-Agnostic Classification of Histologic Subtypes of Osteosarcoma

Osteosarcomas (OSs) are aggressive bone tumors with many divergent histologic patterns. During pathology review, OSs are subtyped based on the predominant histologic pattern; however, tumors often demonstrate multiple patterns. This high tumor heterogeneity coupled with scarcity of samples compared with other tumor types render histology-based prognosis of OSs challenging. To combat lower case numbers in humans, dogs with spontaneous OSs have been suggested as a model species. Herein, a convolutional neural network was adversarially trained to classify distinct histologic patterns of OS in humans using mostly canine OS data during training. Adversarial training improved domain adaption of a histologic subtype classifier from canines to humans, achieving an average multiclass F1 score of 0.77 (95% CI, 0.74-0.79) and 0.80 (95% CI, 0.78-0.81) when compared with the ground truth in canines and humans, respectively. Finally, this trained model, when used to characterize the histologic landscape of 306 canine OSs, uncovered distinct clusters with markedly different clinical responses to standard-of-care therapy.