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.

Twitter for oncologists: More reflections.

One thing is apparent. Twitter as a service, is for sharing links alone. The original premise was to get the overall perspective of how users discuss issues in “real time” and function as a “real-time” search engine. Google, at some point, listed Twitter results but it ended for reasons best known to them.

The more the people on any platform leads to an excessive banter. Separating the signal from the noise becomes even more difficult as informational deluge overwhelms us. While it is fanciful to have more Twitter (or Instagram) followers and show off as “influencers”, it doesn’t help much because of abysmal rates of engagement. While I may consistently get a large number of “Tweet impressions” (mumbo-jumbo of acronyms that Twitter is marketing), this is useless as it doesn’t translate to real life behavioural change.

It is evident from the fact that engagement with my shared links is abysmally poor. My idea of being on the social network is an academic exchange. Suppose I share in a link which is opened and read by another- it would foster a dialogue of information.

On the other extreme, I have come across “verified” accounts of “star-influencers” in Oncology community who push out links with annotations, pictures, survival curves and proper attribution to the authors. How do those “star-influencers” manage it?

I have a strong reason to believe that these links are pushed by dedicated teams using enterprise accounts. A lot of window dressing takes place and after “approval” is “tweeted” out. You have to see the pattern to understand it. It is impossible to juggle professional commitments with tweeting links all the time. There has to be a team involved.

The race for “followers” has polluted the ecosystem. Automated bots propel the specific “likes” making it impossible to differentiate legitimate traffic from bot sponsored and propagated traffic.

I am not cynical. I use Twitter for ideas to write on this blog here. I observe trends. I interact with virtual selves of humans, genteel people scattered all over the planet. It is fun to learn from there, to ping them and understand their perspectives. The trick is to moderate, turning off retweets which don’t concern you, muting specific words and staying focused on what you wish to gain. As a result, I have whittled down to less than half off my previous unread tweets on the timeline. It took time to cull away the deadwood and the fresh perspectives soak in. In the end, it was worth it.

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).

Financial Disclosure: Much more than meets the eye

I have always wondered what the disclosures mean. Financial disclosure, to my understanding, means that no sums of money are involved in the publishing of the manuscript.

If a funding organisation has offered grants to a researcher that leads to publication, is the researcher acting as an “agent” of that organisation by researching what the agency wants?

There’s always an agenda.

Conflicts of interest sound more fanciful. It is a philosophical argument that seems like more of an afterthought and a subtle print as a footnote. I believe that most readers have turned a blind eye to this relative obscurity. I am also surprised that people in conferences often highlight this, but I digress. It is a matter of personal preference.

I think that the time has now come to be more comprehensive about the research agendas as well as identify motivation behind publications. This post was triggered by an innocuous write up in one “prestigious journal” where the lead author had pushed for a particular technological breakthrough in the healthcare system (Disclosure: I don’t want to highlight it for fear of reprisals!). One of the names that caught my eye was a company I had previously aliased. I was keen to bring in the same technology in India and report it’s suitability for Indian conditions. The executives decided not to implement it (and that’s another story!)

But how many people aware that the company in disclosure has precisely the same division working to popularise the health care intervention listed in the article? I have my genuine doubts because it is very niche.

Hint: Most users are unaware of who manufactures the innards of mobile devices.

I think it is time to explain these disclosures comprehensively in the context of the article.

Apple health: The new age digital colonialism

Mobile ecosystems have now boiled down mostly to a duopoly- Android and iOS. Android portrays itself to be an open source but now increasingly locked down by Google with incremental updates. Apple promotes its iOS operating system- increasingly popular with the physicians and lay people in developed and developing economies.

I am not delving into technical nuances, but perceived benefits of Apple are its flawed privacy stance based on its marketing spin called “differential privacy”. Apple hasn’t shown any inclination towards having any independent advertisement networks, and this division doesn’t get any mention. It gets it’s revenues from superior hardware and locked in services (these revenues are never repatriated back to the country of origin). Apple also has controversial policies concerning foreign workers in China, and the manufactured debate about the privacy (it fought FBI) was frivolous. It did divide the tech community. Interestingly, it’s foray in China is opposite of what it does in the US. It has handed over the encryption keys to Chinese government citing the local laws (paywall).

Personally, I find that their stance on privacy as a PR stunt. When I read or hear about their foray into healthcare, I recoil with horror. My privacy stance will not be enough to oppose them, but I was alerted to a write up in Harvard Business Review, which in my opinion, was a plug for Apple.

I can only surmise that interoperability within the electronic health records is a significant pain point. I know this because, at some point in time, I had been privy to getting one for my department. At the same time, my employer was keen to move towards it. (It did not materialise- but that’s another story). The question about the data portability came in, and it was apparent that it relied on some obscure protocol which didn’t have any open source equivalent. It meant that once the company goes belly up, all data, even if exported out, would only disappear into thin air. Or become useless.

Now you can foresee similar issues with the current tech companies. They would push for their proprietary protocols because big money lies in locking up users in their ecosystems. While the initial enthusiasm is understandable (a familiar user interface to work with like messaging applications) but it’s cheerleaders are ignoring the longer and more sinister implications of this move.

When the authors dream up instances of voice assistants detailing health information, I can only roll up my eyes. Either it is naïveté or stupidity or a mixture of both. These ancilliary companies are circling in anticipation of emerging technology, to feed on spoils from the ecosystem.

Is it suitable for the patients? Let’s examine that.

Healthcare data is most valuable commodity in dark web. Primarily, it has been used to impersonate individuals to gain access to medications (further sold in black markets). More importantly, healthcare data is of paramount importance- patterns of diseases, required interventions etc. should strictly be the purview of the governments and not private companies. None of which can be made accountable. The authors have explicitly mentioned about access to the third party companies where individual users are signing away the rights. The same consumers have been signing off the terms of services for Facebook, for example, and are shocked and horrified if they realise that their data is being used for psychological manipulation. People don’t recognise the importance of “caveat emptor”. Most users are technologically averse with very little understanding of the nuances involved.

Therefore, giving up data to these companies is a bad idea. I also see thought leaders and influencers pushing this line on the social media, but then, they have a lot to gain. I guess, no one reads the financial disclosures or stakes in the companies that stand to benefit from this push.

Healthcare and technology are getting more intertwined and complex. Let the likes of Apple and Amazon be excluded from this.

Or else, this would be the new wave of digital colonialism.

Glioma research: Asking right questions

There is an arms race to find the next molecular target. The potential spin-offs are enormous. Royalty payments. Insurance payouts.

Despite insane profits, big pharma has lost its drive to push forward for drug discovery. The easy way is to buy out the biotechnology companies (startups) or chase the clinical conditions which have healthy fat margins (like hypertension). Rare diseases like brain tumours haven’t seen any incremental investments over the past few years because of poor outcomes. Tumour treating field is the only “breakthrough” in recent times for recurrent tumours.

Therefore, the onus lies on informal networks of universities and individual researchers for pushing this narrative forward. Despite the wasted research dollars, there is a lot of promise for translational research.

My proposal has the following (very broad/generic) outline here.

The problem, at the outset, is the cost of sequencing. But it is a necessary evil. Unless we know what type of a tumour we are dealing with or its genetic signature, we cannot hope for proper characterisation. This information needs to be mated to clinical follow up with standard protocols.

Is there any scope for in-vivo monitoring? If yes, what is going to be its timeline? How frequently are we going to see for the mutations? What is the rate of mutations? What is its timescale? When should we intervene?

Another favourite pet theory is the class distinction for stem cells. Do they exist? If yes, why can’t they be reliably identified? What are their niches and what is the best way to target them?

Each sequencing would reveal a wealth of clinical data (both genomics as well as radio-genomics) and spur on more deep dive into the molecular ontology. Yes, that might fulfil the wet dream for molecular targets as well. However, as a radiation oncologist, I am only keen to know whether I can reduce my tumour volumes, how we can reduce the dose to normal structures (brain) and combine efforts with patient-related outcomes.

Bring it on! Let us do it! (Have some laughs!!)