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Making the grade

Dr. Geoff Wood, OVC Department of Pathobiology, discusses study results with Dr. Courtney Schott.

Dr. Geoff Wood, left, OVC Department of Pathobiology, discusses study results with Dr. Courtney Schott.

How well do canine osteosarcoma grading systems predict outcome?

Accurate predictions are a critical piece of the puzzle when studying diseases such as cancer. They help define prognosis and are vital when choosing the best treatment plan. 

For canine osteosarcoma, tumour grading systems are the standard method for determining the best approach for patients. 

However, a study from Dr. Courtney Schott, as part of her PhD research at the University of Guelph’s Ontario Veterinary College (OVC), found that neither of the two most common grading systems for canine osteosarcoma could reliably predict outcome. 

Histologic grading helps inform how badly cancer will behave by looking at it under a microscope, and is a common technique in human and veterinary pathology, explains Dr. Geoff Wood, Schott’s advisor and a pathologist in OVC’s Department of Pathobiology. 

Grading generally examines what the tumour cells look like, what they are doing and how fast they are dividing. Plus, it is a relatively simple and inexpensive test using samples typically collected during diagnosis. 

Osteosarcoma is the most common bone tumour in dogs. In fact, it is 10 times more common in dogs than in humans. It is also aggressive with the average survival time in dogs of about a year. Treatment usually includes limb amputation if possible followed by chemotherapy.

Schott had three veterinary pathologists grade 85 canine osteosarcoma tumours using two histologic grading systems. All the cases had similar tumour location and treatment consisting of limb amputation and chemotherapy. The aim, to evaluate the two systems’ prognostic value to determine if grade is correlated to survival time or time to cancer spread (metastasis).

Schott’s results were published in Veterinary Pathology in 2018 with an accompanying guest editorial which highlights the importance of the work and the need for better predictive tools for canine cancers.

Asked the editorial: How would two published grading systems for osteosarcoma perform when applied in real life? The answer: “not well”. 

These results question the validity of an established prognostic tool, histologic grading, and highlight the need for standardization and validation when developing tests for outcome prediction,” Schott notes.

The research results really demonstrate the need for a better system, Wood adds. “Grading is pretty standard in human and veterinary pathology, and it took a lot of work to disprove the widely-held assumption that osteosarcoma grade predicts disease outcome. This study shows that, in fact, it does not.”

“With better methods we may be able to predict who will do better and who will fail treatment early,” he adds. “We may be able to recommend if they should undergo palliative care rather than surgery.”

Work by the Dog Osteosarcoma Group – Biomarkers of Neoplasia or DOGBONe, is exploring better ways to predict outcome in canine osteosarcoma using non-invasive blood sampling. Along with Alicia Viloria-Petit from OVC’s Department of Biomedical Sciences, Wood is a co-lead of the group comprised of top osteosarcoma researchers from across OVC. 

“Not only do we want to be able to predict how well these animals will do but we also need to treat them better because the therapy for these dogs hasn’t changed in about two decades,” says Wood. 

Schott and Wood’s most recent study, published in PLoS ONE, is a first step towards this goal. They used dog osteosarcoma cell lines derived from OVC cases and tested the effect of standard chemotherapy combined with an inhibitor of autophagy, a cellular process that can protect cancer cells from chemotherapy. 

“What we found was that inhibition of autophagy increased the effectiveness of chemotherapy on cancer cell killing,” explains Wood. “While this study was conducted in cell lines, moving to clinical trials is not that large a step. There are human cancer trials currently underway that use this same combination approach.”

This new research, as well as the previous grading study, and the DOGBONe non-invasive blood sampling research, is funded by OVC Pet Trust.

The Veterinary Pathology editorial also called for more validation, testing and standardization for evaluating tumours; in other words, see if it works and change it if it doesn't.

Added the editors, this paper may stimulate editors of pathology and oncology journals to accept the challenge. “If they do, it should lead to better patient care.”