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Make cancer treatment more flexible, game theory experts recommend

Considering cancer treatment through the lens of game theory could improve outcomes for patients, a study by a multidisciplinary group of researchers has suggested.

Game theory is the field of mathematics concerned with modelling logical behaviour of decision makers. The field, which is applied widely in computer science and social science, may also prove useful for decision making in healthcare.

According to the new study, published in JAMA Oncology, game theory could be used to identify flaws in current approaches to cancer treatment and to suggest new strategies to improve outcomes from patients suffering from metastatic cancer.

This requires cancer treatment to be considered as a “game” between the oncologist and the cancer cells.

While continually using the same drugs at the maximum tolerated dose (MTD) is the standard, decades-old treatment for metastatic cancers, the study suggests that clinicians adhering to this approach may not be making the most of their informed position, and would do better at the game by considering flexible treatment plans.

“Current treatments for metastatic cancers, by giving the same drug repeatedly at the MTD can inadvertently increase the speed with which cancer cells can evolve effective counter measures and then regrow,” said Dr Robert Gatenby, co-director of Moffitt Cancer Centre’s Center of Excellence in Evolutionary Therapy, Florida. “Today, therapy is usually changed only when the tumour progresses. By using this strategy, the physician cedes control to the cancer. Although standard practice for decades, administering drugs at MTD until progression is rarely the optimal game theoretic strategy for metastatic cancers.”

According to the Moffitt researchers, clinicians have two major advantages over the cancer in this game; being a rational actor capable of predicting responses, and the ability to take the first move. Cancer cannot develop resistance until a drug is administered, and it does not have the ability to predict the future. This means that the ‘game’ follows the basic form of a Stackelberg game, in which the leader of a game can gain advantage by using their first move to limit subsequent responses, and by using their knowledge to anticipate the behaviour of its opponent (in this case, the cancer’s resistances and vulnerabilities).

The study recommends that the clinician should take advantage of their position by monitoring the cancer’s response to their treatment, and adjusting types of drugs and their doses in order to hinder the progression of cancer as it develops resistance. These adjustments are informed by the evolutionary response of the tumour to each treatment cycle; combining this knowledge – which could come in the form of After Action Reports’ – with a mathematical model could provide information to improve the outcomes of subsequent treatments and eventually move towards personalising treatment.

The authors also suggest that the clinician begins by defining the goal of the treatment; for instance, to cure the patient or prolong survival. Having a specific goal would likely help the clinicians to balance the possible benefit of treatments with their painful side effects.

“As we develop the mathematics in conjunction with cancer therapies, we expect that our analyses will uncover novel game-theoretic, evolutionary strategies that may increase the probability of curing even aggressive and heterogeneous cancers,” said Dr Katerina Stankova, a game theory expert at Maastricht University.

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