Biomedical research, outcomes and survivorship

This post was the result of being tagged in an interesting discussion on Twitter about survivorship. I want to give in my viewpoint.

Survivorship isn’t just about a hard clinical outcome. It is about the functional autonomy of an individual. There are various issues tied up here; it wouldn’t be appropriate to discuss survivorship issues in isolation. I would, of course, take the example of brain tumours per se and weave in the narrative for various interconnected problems. I have been thinking about it for the past two weeks and here’s my observation.

I was lucky to attend Paediatric Neurooncology conference- which was my first trip to States. It had been a fantastic experience; great organisation as well as well attendees from different parts of the world. However, one thing stood out- the predominance of biomedical research. I wouldn’t hesitate to call it as vanity research because it is an arms race to practically nowhere. We have expended billions of dollars in hair-splitting pathways and identifying newer targets, but as an opportunity cost (investment versus tangible outcomes) it is a downward spiral and a wasted opportunity. I am not advocating less of research but one that has measurable practical results.

Let’s look at survivorship from three examples. Meningiomas, Medulloblastomas and DIPG (as the extreme). Meningiomas are mostly indolent but are considered “curable” after definitive surgery followed by an indication for radiation therapy. How and why the need for drugs has come in? What proportion of patients needs it? Are they effective? And if the disease is aggressive and progressive, when do we call it a day and suggest best supportive care for the patient? The hapless patient would need dependent care (based on what neurological functions have deteriorated). How do we define survivorship here? Have we made the patient functionally autonomous or helped the patient to adjust to the disabilities?

The “middle rung” (as I would call it because it has a decent prognosis) is medulloblastomas. Elegant research has divided this into various subtypes with the promise of “de-escalation” of treatment. How much, do we know that “less is less” and not “really less” of radiation therapy? Chemotherapy, from the classical radiobiological constructs, eliminates only the most active cell populations but still, the “spurters” remain in the cell pool. Reducing the radiation dose will, in all probability, really compromise with the eradication. The “myth” of radiation-induced side effects continues to this day without really accounting for the long-term neurocognitive effects of chemotherapy.

What is survivorship in this context?

The last but not the least is relative rare diffuse intrapontine glioma. This diagnosis is universally fatal, and despite an intense outpouring of research, the outcomes haven’t improved. They have drilled catheters to deliver drugs right at the source and have claimed “success”, but the overall scenario remains bleak. What is survivorship here for DIPG?

Hence, either way, you look at it, there are no easy answers. The spurt of biomedical research (often cornering the most significant resource) needs to be tempered with the realistic expectations of the pharmaceutical industry (that funnelled research into practical, actionable targets). There have been clamours, of course, for a “close collaboration” between the industry and academia but everyone is aware of the pot of gold. An actionable mutation followed by a drug and patent protection for about ten years is equal to profits. Insane profits. But, how has survivorship improved? Instead, we have newer metrics to measure “survival” like “progression-free intervals” which has no meaning because the disease is always present.

I feel that it is important to pay equal importance to the emerging role of technology and patient support. Like the innovative use of chat applications, the emergence of bots and various platforms that can make life easier to adjust with disabilities. Patient support is an ignored criterion that could get a better impetus and more funding to make lives more meaningful.

The central question remains- when to introduce “palliative care” and “hospice” in the evolution of the disease. These two questions determine the meaningful survivorship.

As from the preceding discussion, it is not easy to quantify survivorship. The goal of research should remain improvement in population outcomes. Cancer aetiology points out towards mostly preventable causes- air pollution, smoking etc. What are we doing to improve our score in that direction?

Last but not the least is cancer prevention. Sadly, it is not relevant for gliomas save for the fact that mobile phones are “probably” a risk factor. That opens up another can of worms because industry-sponsored research fails to show an association between exposure and disease. Oh well, I am not surprised there.

Lets put things in perspective. We are trapped in our web of confirmation biases. Let’s focus on better ideas (pardon my cliche) for “cross-pollination” of disciplines. Radiation Therapy is curative and is the most critical determinator of survivorship.