How can we do better?, page-22

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Abscopal response concept
A simple concept, but one that can be challenging for the investor to grasp.

Take the example of a man with late-stage prostate cancer. He has been through all available forms of therapy and the cancer has progressed despite all of those therapies. He has essentially run out of treatment options and is facing some months of palliative therapy leading up to his death.

His cancer has spread to clusters of lymph nodes in his pelvic cavity and abdomen, and throughout his skeleton with dozens (even up to hundreds) of metastases in bones in his legs, arms, ribs and skull. The growing tumour load in his body is draining his health, and the tumours in his bones are causing considerable pain.

Palliative therapy at this point generally involves two main therapies. The first is pain relief. The second is radiotherapy to try and shrink one or two larger tumours that might be pressing on a vital organ or causing particularly bad pain.

Where radiotherapy is used in this palliative setting, it is designed to shrink the offending tumour by killing as many cancer cells as possible. The radiation is restricted to a narrow band because the aim is to limit the amount of damage to healthy tissues. That means that the effect of the radiation is limited just to the 1 or 2 tumours in that tight band of radiation. The tumours in the rest of the body will continue to grow unaffected. Shrinking 1 or 2 targeted tumours in a body containing dozens or even hundreds of tumours won’t be expected to have any effect on the patient’s overall survival time. As the term ‘palliative’ indicates, it is intended to make remaining life as comfortable as possible …. not to extend it.

That’s the blunt way of using radiotherapy. Recent experience shows that there is a smarter way of using radiotherapy in the palliative setting that can go well beyond just providing symptomatic relief, and end up providing a very significant anti-cancer effect and prolonging life to a considerable degree.

This smarter, light-handed approach relies on using a low dose of radiation that instead of seeking to destroy the tumour, seeks instead to inflame and irritate. This triggers an immune response with the aim of generating immune cells within the irradiated tumours now primed to kill the cancer cells. The aim is that these primed immune cells then leave the irradiated tumour, enter the bloodstream, and travel round the body seeking out and destroying other cancer cells.

This phenomenon of applying radiation to one discrete part of the body and then seeing tumours shrinking or disappearing altogether in distant parts of the body where the radiation did not reach is known as an abscopal response.

Low-dose radiation on its own is highly unlikely to result in an abscopal response. It needs help, and that help comes in the form of anti-cancer drugs (known as immuno-oncology drugs) that work by promoting the immune system. Radiation alone and immuno-oncology drugs alone don’t deliver an abscopal response. Together, they can. Not in every case, but hopefully in enough cases to make the effort worthwhile.