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.

Goals of research

There has been an outpouring of dollars in basic molecular research. Many clinicians have joined in with their labs to push for “clinically relevant research”. It is evident that there would be a lot of duplication and overlap between it.

For example, look at IDH gene in the pathogenesis of gliomas. We know it carries a prognostic significance. We also know about the molecular pathogenesis. How does duplicating the research across different labs helps us or makes us any wiser?

The answer lies in the pharmaceutical business goldmine. Loath to spend on basic research in molecular pathways, the research, instead has been farmed out to a network of labs. It is easy for anyone to form a company and then sell out by being acquired. It is excellent for research ecosystem as it brings about new innovative ideas, but there are some serious issues here.

Public funded research gets outpriced for the end users who have contributed in no small measure to the same. They need to become more aware of these repercussions. Shrinking federal grants for public funded research means that there is no adequate oversight and auditing of the labs that are doing the same thing. These are potentially very high stakes, and patent awards can make individuals pretty rich.

I agree that these are generalisations and that this opinion isn’t set in stone. I have based the above assertion on my reading of the situation as well as verbal accounts.

What is urgently required is a partnership at all levels. It is to focus on one idea that has the potential to work in brain tumours. Pool in resources, under legal agreements, to work on the different aspects of the same problem. The idea above is more akin to a hub-and-spoke model of research. The goal is the identify molecular pathway and understand its implications for radiation therapy.

Let’s say, hypothetically, IDH gliomagenesis is the new pathway discovered. One team to work at a molecular level to identify potential inhibitory points, other to identify molecules that bring about this change. Another side to study the effect of radiation therapy and the pathway. Aggregated results would avoid duplication and overlap and lead to faster translational outcomes.

The problem is that they end up leaving radiation as an after-thought. It should change.

Twitter: Towards a slow spiral of death

Twitter is getting desperate after an increased focus and scrutiny of its actual number of users. While they use metrics like users who were online in the past month, Twitter knows that it is a sinking ship.

There was a lot of hoopla about Twitter making its first profit after consecutive losses. However, it seemed like a flash in the pan. It is yanking off the API’s (third party services which connect via desktop applications). It wants web-only services so that it can serve up “personalised” advertisements. The daily engagement with the service is declining.

It is a worrying trend. While the BTSM practitioners have linked and bonded over this microblogging service, it is easier to get lost in the din of rapid tweets which makes it impossible for any coherent discourse. I have seen posts from institutions- pictures shot from the OT about the cases that they have done. Why this kind of marketing?

The impact of social media ought to be real- like reaching out to potential donors, for example. However, that individual tweet is decidedly less likely to be seen by a specific person. Re-Tweets or Symplur impressions hardly have any bearing on the impact of “tweet”. It only states how many people could have possibly seen. Were they the correct target audience?

A vast majority of the population isn’t aware of nuances of Twitter which can be overwhelming. Mobile interface, like Telegram, needs to be explored in earnest. It should be linked to all the Telegram links (like URL’s). That is also a safe, secure service which doesn’t track you, unlike Twitter.

Whole Brain Radiotherapy: Is it valid?

The debate between whole brain radiation therapy and stereotactic radiation is spurious. One thumb rule that determines the “success” of stereotactic radiotherapy is the presence of extracranial disease. If it is still present, whatever lesions are being treated, are all likely to recur.

I strongly feel that motivation for stereotactic came in from higher billable for this modality. It isn’t valid and practical for most scenarios across the world. I am not going in for all defence of whole brain radiation which does have its drawbacks, like affecting the quality of life- but any robust psychometric testing hasn’t reliably quantified this. Likewise, the advantages touted for stereotactic don’t always hold water.

The “researchers” have pushed for statistical mumbo-jumbo with the “expert” committees that jump in to “bring order” to the mess of “confusion”. There is no uniform consensus, still, but it is slowly becoming the norm to push for stereotactic XRT (even for multiple mets) when a whole brain radiation therapy may suffice. I believe that the well was poisoned earlier on by papers pushing for many lesions to be treated via Gamma Knife. Cyberknife has only made things worse.

To top it all, multiple “universities” have overactive public relations department to push for “cutting edge treatment”. I was appalled to note that someone was pushing VMAT, for head and neck, as the “standard”. No Sir. Modulation is still not established on substantial evidence but is being only used for its perceived benefits.

This post was triggered because I had a lengthy discussion with a patient’s family about the use of stereotactic radiation for a solitary lesion versus the whole brain, even though she has an extensive extra-cranial disease. She was arguing from half-baked knowledge because she was concerned about the quality of life. Someone told her that the patient might not be able to do mental calculations. Well, is this reason valid in the socio-cultural context? Nope. Only if people are keen to promote “hippocampal sparing” (which adds to unnecessary complexity to treatment), which ultimately, in my opinion, offers no robust advantage. Likewise, scalp sparing again is fancy vanity metric which I call as intellectual masturbation. Good for the conferences to blow your trumpets but the poor practical application or impacting outcomes.

No, whole brain radiation isn’t out of “fashion”. It has more utility in the face of progressive extracranial disease. Stereotactic radiotherapy may be kept in reserve for recurrence or local failure. Whole brain with concomitant boost might serve the same purpose. I prefer SIB, to be honest, which for me, hasn’t shown any sign of failure.

Always keep some steroids handy, taper them down and patients do well to go to receive definitive chemotherapy. I believe, whole brain XRT will hold more importance in the setting of oligometastatic disease that is likely to impact survival. It is an anecdotal observation- liver Mets have a profound impact on survival. Lung Mets or bone Mets end up with a relatively prolonged course.

Social Media: Falsehoods

I was alarmed to read about falsehoods about health spreading through WhatsApp. It is a Facebook-owned application which has millions of users worldwide. It is impossible to get the actual numbers but suffice to say that it is prevalent in emerging economies.

The alarm went off with an excellent article from The Wired which has chronicled the rise in Yellow Fever epidemic in Brazil and the falsehoods surrounding the vaccination. I reproduce some essential bits here.

In recent weeks, rumours of fatal vaccine reactions, mercury preservatives, and government conspiracies have surfaced with alarming speed on the Facebook-owned encrypted messaging service, which is used by 120 million of Brazil’s roughly 200 million residents. The platform has long incubated and proliferated fake news, in Brazil in particular.

The phenomenon of fake news isn’t peculiar to Brazil, but these spread rapidly through the social networks.

“These videos are very sophisticated, with good editing, testimonials from experts, and personal experiences,” Sacramento says. It’s the same journalistic format people see on TV, so it bears the shape of truth. And when people share these videos or news stories within their social networks as personal messages, it changes the calculus of trust.

If you wish to have a scientific basis to why this happens, Science published a great resource.

We classified news as true or false using information from six independent fact-checking organisations that exhibited 95 to 98% agreement on the classifications. Falsehood diffused significantly farther, faster, deeper, and more broadly than the truth in all categories of information, and the effects were more pronounced for false political news than for false news about terrorism, natural disasters, science, urban legends, or financial information. We found that false news was more novel than true news, which suggests that people were more likely to share novel information.

This is an example of a rumour cascade:

The purpose of this post is that physicians should step up their game and have an active social media presence. A lot of sane voices will go a long way to dispel myths and fears about public health initiatives.

That is the reason why I set up Telegram channel to have physician vetted information and a one-stop solution for brain tumour affected patients. We owe people more!

Twitter for oncologists: Beyond 280 characters

I had my disdain for social media. It had been in the news for all wrong reasons. This post isn’t going to add to a growing and mounting evidence that social media is practically useless for politics because it amplifies our echo chambers and fuelling our confirmation biases. In the past few months, I have learned enough to hand hold a few tech-phobic colleagues and discover the positive side instead.

The hashtag: Twitter revolves around hash-tags. This is akin to a large room where people are discussing a topic; they come, and they leave the room. By having an open door policy, anyone can join in the conversation. It is like a large town-hall. Twitter usually lists trending hash-tags, but there are numerous third-party services which reveal global hashtags; not large enough to trend but essential nevertheless.

For example, #btsm is the hashtag for brain tumours social media. Often, patient advocates invite many thought leaders to debate and discuss on brain tumours. Anyone can use the hashtag to follow the process.

You guessed it right. The signal to noise ratio is very low, which makes it difficult to follow the conversation, meaningfully.

Username by @: They enduring symbol “@“ when prepended in front of a username, alerts the person (via notification) that he/she has been called out in the noisy room. You can either use the hashtag in the conversation (when the chats are being conducted) or individually if you wish to draw someone’s attention to their Twitter stream.

Twitter stream: Algorithms usually determine the endless “tweets” you see. Therefore, when you start out, with an empty slate, the number of tweets tend to be overwhelming as you start following various users. It happens because, Twitter, as a service, uses, the number of signals (your community engagement or number of re-tweets etc.) to determine what you are going to see there. The idea is to stay focused on what your goals are.

Direct Message: This works like an inbox system; you can restrict the users who can reach out to you.

It can quickly get overwhelming on this service. You will have to make several modifications to the way you are notified- via email, desktop or mobile clients. I prefer to get a notification only on a direct message from people who follow me. For everything else, it is switched off.

I prefer and recommend a desktop application (TweetBot for Mac). But you are forewarned. The developers do not bother to reply to your queries, and it lacks several customisation features. It gets the job done because I can filter out the advertisements on the web service. I also prefer to have a Tweetmarker service to go through the unread tweets. You can also turn off retweets from specific followers or mute them indefinitely.

Should you use Twitter or Facebook? In my opinion, both are bad. Even though the masses are there, but it represents too much of concentration of “power” in the hands of an algorithm. That’s why I prefer, the simple and straightforward Telegram. Groups work precisely that ways- you can quickly set up hashtags to organise the chats. Not many people follow this. Channels work exactly like a public broadcast. You can always set up links to discuss issues in the groups. As usual, there is a going to be a vast majority of people who will not speak up.

Closing thoughts: Twitter represents a dominant social media with numerous warts. I call it robust, only because of the sheer number of users, who have flocked to this medium. Most users are technology agnostic. People usually go by word of mouth recommendation or something which they have heard is “popular”.

It is time to take the leap of faith and contribute to the positive side of social media. As well as, try out something different and better! (Hint: Telegram)

How Twitter enriched me professionally as a radiation oncologist

I am a recent convert to Twitter but have flirted with it in its earlier days of inception when 140 characters were the norm. It wasn’t apparent as to why this service came into existence in the first place. Facebook started off with a similar pretence of “connecting dorm mates”, and it grew viral pretty fast from an invite-only platform to connect a majority of the online population.

I will not go in its politics or how toxic it has become. Its algorithms are an opaque science, and Facebook is a platform for social and psychological manipulation (despite public claims to the contrary). For this write-up, I’ll focus only on Twitter since I am engaging with it on a daily basis.

Twitter offers a place for discussion, sharing links, some media (pictures) and a medium to reach out to other users for marketing. Advertisers see some value in it (because Twitter offers granular options for targeting users). Beyond that, most scientists and doctors have discovered this as a platform to articulate their viewpoints. There’s life beyond academia as well, and most events affect us collectively. However, it blurs lines between personal and professional lives, often. This has prompted several professional organisations coming in with their “recommendations”, but social media is like any other platform which is public.

There is no inherent privacy if you get online. Period. Likewise, all this serves as a construct to showcase or to interact (like presenting a paper in conference or hanging out with colleagues post lunch). This also leads to a considerable scope for confusion because of the inherent limitation of characters. Like any written word, it cannot offer tone, tenor and contextual meanings which leaves things open to interpretation. However, Twitter provides only a limited scope of interaction via “re-tweet” or “like” which signals the intent. Beyond this engagement, it is a very limited platform.

With these caveats, Twitter offers a rich experience in professional interaction. I chanced on pathology colleagues, for example, who could reach out others in the world for a rapid “second opinion”. Pathological inferences usually require objective criteria, and it is not possible to be swayed by “wisdom of the crowd”. It makes it easier to nail the diagnosis for anything that’s obscure. Likewise, I interacted with a radiation oncologist, who advocated “shining the light in the basement”- exhorting fellow oncologists to embrace this medium. Another instance wherein I interacted with someone from the US to discuss the QA for a newer gamma knife machine. The follow-up comments were interesting, and I learned a lot in the process.

Similarly, it was fun to interact with professionals from down under! They are using social media in a very positive way (by dancing!) to target cancer and bring about an attitudinal change for radiation oncology (unstated and underused, like anywhere else in the world). I love their imaginative use of “targeting cancer” pin-ups with the backdrop of landmarks. Cats and dogs are also a part of it, for good measure! The idea is to get the word out to patients, who shouldn’t ever feel that they are alone. We are all a part of the team to take care of them.

These advocacy efforts on behalf of professionals are in addition to a lot of other patient advocates- one who has gone through the trauma of diagnosis and treatment and have lived to tell their stories.It is instructive for us to learn, as doctors, to understand and be empathic to their fears, concerns and how cancer diagnosis fundamentally changes their lives. A prominent patient advocate, for example, even suggested having “lego based models” to show what patients would be going through (radiation therapy mockups). A brilliant idea indeed!

Scientists have also joined in this chorus and have added their might to it. I follow their efforts to bring science to the public domain, how they navigate through government bureaucracy and how translational science can become the cornerstone of “cure”.

So yes, there are multiple positive attributes to being here on social media! For those who are starting out, a quick re-cap. You can follow specific “hashtags” like #btsm (brain tumour social media) or #radonc which are widely used around. Topical conversation happens around these hashtags. If you suffix the character “@“ before anyone’s username, it is like a “shout-out” to draw their attention. (Similar technique works in Telegram).

Join in here for the conversation and enjoy! Remember, you have only one life to make a difference!