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.

Size does matter

The size of clinical trials has now become a raging issue. I came across it on Twitter, and I’d like to put in my perspective to it.

The Wall Street Journal article presents a reasonably nuanced view about the need for trials. What it leaves out in the process is that some diseases like those involving brain, because of their relative rarity, would always need a clinical trial. Likewise, for common cancers arising in breast and prostate, the opinion for long-term clinical trials is divided because it is a significant public health problem.

The treatment protocols for brain tumours like gliomas hasn’t changed much in the past 15+ years. For even rarer diseases like CNS lymphomas, the role of chemotherapy has expanded manifold. Patients present to different facilities with varying standard of care. Not everyone has access to the “research facilities”, and especially in developing countries, that conceptual framework is non-existent. The treatment protocols are often the trial and error in what “fits” in with the Indian subset of patients. It is true primarily because out of pocket expenditure is a significant public health issue.

Now comes the emerging role of “personalised medicine” where the opinion for big or small trials is even more sharply divided. What everyone secretly agrees but never speaks out in the open? It is more important to understand the need to publish negative trials. The focus of the oncological community is towards the big bang positive studies; especially for the “blockbuster” drugs. These are often intricately linked to prevailing stock prices. There are perverse incentives as well, not to take the financial risks. It is the pharma companies that decide on “treatment protocols” and the “standard of care” where conflicts of interest are given short shrift in the protocols. That is the reason why I insist on public funding of trials where a leeway has to be made to fail. Previously, I have also argued that “personalised medicine” is way too much in its infancy. We are only nibbling at the outliers and nowhere near the core of the problem.

It is also incredibly naive to assume that if a company is offering an “unrestricted educational grant”, it has no say in the outcomes. It gets them a seat on the board to be able to influence the reports indirectly.

So does size matter? More extensive trials, are time honed but require immense resources. I strongly feel that hair-splitting in current treatment options offers no means to an end. Instead of a clear focus on the outliers (like the drugs), protocols need to include radiation therapy as an inherent component of treatment.

Translational medicine needs to become the centre-stage, and public funding should avoid a substantial scale duplication of work. It comes with its caveats.

My Twitter journey so far

It is an honest confession about what I have been able to achieve and put it in perspective. Is the social microblogging website, beneficial?

  1. I have been lucky to come across many excellent individuals! Medical Physicists, Radiation Oncologists and the fraternity which gets together and deliberates on matters of mutual interest.
  2. I had to use a lot of muted words because most people don’t realise that Twitter is meant for “manufactured outrage”. It is lazy person’s means of “activism”.
  3. I follow many accounts, but some of them are muted because their tweets add no value to the discourse here.
  4. Some Twitter users are great. They read whats on their platter, but Twitter sorts out interaction based on algorithms. It means you are likely to miss out on a lot of important things. Your likes, re-tweets or other signals are factored in what you ultimately see. It isn’t educative nor informative.
  5. I participated in my first virtual conference for ESTRO. It was an enjoyable experience, and I have written and shared my ideas extensively. If you wish to factor in Twitter as part of an interactive platform, you need to have a coherent strategy. A generic hashtag adds little value to the overwhelming noise. I would, on any given day, have a Telegram channel, instead.
  6. I am dismayed by the constant barrage of advertisements by many organisations. It is good to promote diversity of thought; however, it is clear that these accounts have been outsourced to different agencies. It appears phoney; as if they are drunk of kool-aid. My bullshit filters typically go up at the very thought. I am not naming them, of course, but it gets my goat. Likewise, for a respected “physician-scientist”. It may be acceptable to make political statements, but it is like mixing wine with water. The result- academics+politics doesn’t make any sense.
  7. Gender politics on Twitter is too stupefying; I am gender neutral (if that is the term) and I prefer to see individuals as such. There is no meaning of gender for me (as far as academics is concerned). Using your Twitter account to wash your dirty linen in public (because you have a specific gender) is labelling your back with the tag of “stupid”. Ultimately, it is your choice as to what you wish to achieve with social media. I usually prefer to stick to a personal account on Twitter or better still; I prefer Telegram.
  8. The click-through rate for articles is abysmal. If you wish to see an improved version of click-throughs for the posted links, you will need to have a large number of followers.

Has there been any luck with getting people to switch over to Telegram? Nope. Nada. Zilch. It is because of my tacit understanding as follows- Twitter as a medium for beginners is intimidating. Many users prefer to stick with the known than to start with something new. It is not laziness, but everyone has a motive to be online using Twitter. Some wish to have a more significant exposure; some users want to interact with peers, some want to express outrage or crib about life’s not fair. There is no one reason. Telegram is much more personal compared to Twitter. I have a couple of groups and channels with me on Telegram. It is good to spend time by consuming content passively. Groups allow more fine-grained control and better-nuanced interaction. And the recent moves by Twitter to force users to access it through web-alone is a stupid move.

Twitter is a bitter-sweet experience. Yes, the constant stream can be tiring and distract you cognitively but it is fun in parts. On the flip side, you end up meeting amazing individuals and people from different departments across the world.

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.

Research in radiation oncology: Break the logjam

I came across this on Twitter (where else!) Despite the “weirdness” (pun intended), it was apparent that it raised substantial issues. I had responded to it, but it merited a blog post.

There has been an institutional push to observe and record in western countries. Higher disposable incomes with specific segments of society helped them to get a better education and as a result, better opportunities. It is not getting into a nuanced debate about the racial differences or affirmative action. Inequalities have always played a part but so is the ability to capitalise on opportunities that present itself.

A lot of research happens because of institutionalised mechanisms. The children have exposure to ideas from the school and paid internships, scholarships and grant opportunities. In India, the approach is entirely insular and works in silos. Medical science has grown incredibly complicated, and it is beyond the purview of anyone to grasp nuances of differentials.

As a result of those initiatives, a few developed economies have led and broken ground in “research” (whether it is transformational or applicable to real-world solutions is immaterial). It has spurred on the likes of China (an aspirational economy) to ape the same system led by the US, but rigid hierarchies stymie them. It is indeed laughable when Government of India decides to set up a “scientific officer for innovation” because it cannot happen in silos. Throwing money at central “research institutes” isn’t going to help because lack of real-world application has hardly moved the needle in any meaningful direction. Likewise, the research is mostly divorced from socio-cultural contexts.

We can only break the log-jam if we first identify the cause of the problem. Outsourced research to understand molecular pathways and then to apply developmental molecules for “blocking them” only perpetuates, what I call a scientific fraud of “monumental proportions” because of perverse incentives associated with “pharmaceuticals”.

(Radiation Therapy needs love- not in delivery methods but radiobiology and fractionation). It is sad that radiation oncologists have more faith and belief in “combination regimes”- altered fractionation schemes have been beneficial too. But progress is excruciatingly slow here.

It would be difficult to think beyond patent protections and intellectual property if someone else controls the purse strings.

Social media: Caveat emptor!

The debate about doctors being on social media hasn’t ended. Most people, I have spoken to, have very negative connotations about it. They feel, very strongly feel, that Twitter is nothing but an echo chamber of bigotry, lies and cussedness. It “might” be true but then technology is what you make it out to be!

Facebook is another different beast. Their claimed usage is about 2 billion users, but no has independently verified these numbers. They have been able to grow this because of powerful network effects. Most users feel comfortable here because it allows them to interact with “friends and family”. It also means that most users are reckless about it.

Facebook is a global surveillance system that gives dopamine fuelled high to be voyeuristic or exhibitionist. Their terms of service point towards collecting the data and being able to share it with “third party affiliates”. I often chuckle when people get horrified that the service they depend on its utility, for administrators, for psychological manipulation. What would it take to learn the lessons?

Social media is as good as we make it out to be. The best ideas for the blog post appear in my Twitter timeline. I get ideas, dwell on them and then write. One way out could be to learn from different specialities, see how they are using it and adapt it yours. The ideas take their shape and pretty soon, a rich interactive web form that enriches it even further.

(I prefer Telegram app).