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!!)

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!

Why blogging is essential

When you face an empty sheet, the hardest part is to define the direction you want to give to your words.

This post was in response to a brilliant blog post on 33charts, which is peddled by an influential paediatrician. I love the way he wraps up his ideas which is both a joy and a delight to read.

I have flirted and experimented with blogging consistently over the past few years (a decade or more). I am aware of how the blogging landscape evolved.

This neuroblog was set up later in response to many recommendations by those who had been there. Blogging is the best way to be able to get your ideas out. It showcases what is on your mind.

If you are clear in your mind, you can set out to do what you wish to achieve. Hence, this blogging platform is essential to categorise as well as firm up the opinion.

Twitter is sorely limited to express both the nuance as well as context. A blogging platform only explains the background, but spoken word or personal interactions best explain nuance.

Each one of these leads to a more vibrant diversity of opinion.

(Images are subject to copyright of their owners)

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)

Can we have a Spotify like model for academic publishing?

I have always disliked the idea of paywalls. If I have to borrow the cliche from silicon valley rags, it amounts to having “friction” in accessing the resources. It is a huge pain, especially, if you don’t have the resources.

Much has been written about the advent of scientific publishing in the internet era. And despite the monopolistic tendencies of publishers in erecting huge barriers, likes of Sci-Hub are winning. A few “pirate” websites have extended its support and currently houses the bulk of published scientific literature. Interestingly, the majority of access happens from university campuses where they have already paid for the access! It is a natural human tendency to look for the most comfortable way out!

This post is not about accessing Sci-Hub, but it reminds me of a bitter battle between pirates and Hollywood executives who had similar issues in 90’s with torrents. They are losing profits, as per their claims (despite mansions/big cars/lavish lifestyles) and are locked in pitched battles with telecom service providers to identify those who “pirate”. Paywalls and digital rights management system did not deter those who were determined to access content. Telegram, for example, has emerged as one of the largest piracy hubs for movie distribution on mobile because of its generous file limits.

This post is not to discuss these nuances, but it set me thinking. Why can’t we have a Spotify/Netflix like model for academic papers? At a monthly cost of around 10 USD with all publishers pooling in their resources, it can be a formidable challenge to a tendency to pirate. Technology has made DRM easier. Do we see pirated Netflix original content? Yes, true. But Netflix/Spotify offers a superior UI. The ratio of people paying up versus those who pirate is larger; hence these companies are profitable.

Publishing houses should accept the writing on the wall. I would be all for a Spotify like model for papers. Every stakeholder stands to gain.

Brain tumour advocacy:What is the role?

The Role of Brain Tumor Advocacy Groups

This is an excellent paper which I came across, and I find it is very pertinent. I have highlighted the most important aspects here. The full article is behind the paywall (another blog post coming up soon for this!). However, nevertheless, despite the repetitiveness, these are the essential highlights.

Brain tumor patients, caregivers, and loved ones realized that research is underfunded, which catalyzed the creation of nonprofit patient advocacy groups to bridge the gaps that the for-profit sector and the government have not addressed.

I agree here. Rare tumours are “rarely” the focus of researchers. Sadly, I have a strong feeling that bulk of current research in these tumours is dressed up to impress the charities. Because when the push comes to the shove, we hardly have moved the needle.

The challenges that brain tumor advocacy groups and organizations face and the role that they must play are reflective of the nature of their patient population. Individual efforts to combat the deadly disease are driven by a shared sense of urgency.

It is precisely my motivation to set up exclusive Telegram group and a public broadcast channel. It helps to gather all the information in one place with vetted links so that patients or their caregivers do not have to wade through the toxic Google searches.

As recently as fall of 2013, patient advocacy organizations were defined as providing “patient- and caregiver-oriented education,advocacy, and support services”

It is difficult to “define” them (advocacy groups), Definition, by its very nature, limits its scope. I would prefer to call them formal or informal support groups but more on that later.

This role may be sufficient in disease areas where there are effective treatments, but for brain tumors, where treatment options are limited and often ineffective, the community requires proactive research programs, as well as a host of advocacy and patient support services

Exactly. The issues are stark in developed economies while in most of other health care systems where research is either fledgeling or non-existent, brain tumours are likely to be axed. Breast cancer or even head and neck cancer are public health issues, and the bulk of biological research has been directed towards it. The idea is to define “targets” and spin it off to pharmaceutical companies. It does de-risk it but with it comes the high price of failure for other disease sites. Not every research leads to a breakthrough; like for example, in the case of Temozolomide. What next? Electric fields?

The goals of public policy advocacy include improving treatment options and access for brain tumor patients, supporting research funding and innovation, and optimizing conditions for drug development and approval.

As above. It is essential to raise the voice and create awareness. When this was published, using Twitter by patient advocates was not mainstream. However, in light of recent developments, it is essential that physicians also join in patient advocacy. Here’s the shocker. Very few oncologists pursue brain tumours as a career pathway. It is either because of limited treatment options (which is a fact) or restricted interest in putting efforts for what is a uniformly fatal disease. More importantly, it is likely to lead to high burnout rates. However, most of them do agree- it is intensely academically and emotionally challenging.

Owing to the nature of the disease and its treatment(s), the burden on caregivers is often very high, both emotionally and financially. Patients and their caregivers benefit from a variety of support services.

It is true.

Brain tumor treatment is expensive. Brain surgery, radiation therapy, chemotherapy, and targeted drugs all add up to a steep medical bill

Moreover, this leads to financial toxicity. It is true for most of the healthcare systems across the world.

Beyond its steep financial cost, brain tumor treatment is incredibly complicated. Coordinating care requires managing appointments, connecting with the right physicians, and finding the appropriate care services. This burden often falls on the caregiver because of the impact that the disease and treatment have on the brain tumor patient

This is what I dread the most. It is because advocacy groups are far and few in-between. Most general practitioners have a low threshold for diagnosis (which is also okay because these are rare tumours with a low index for suspicion). By the time it is understood in its context, it is usually too late. This issue is more pronounced for childhood cancers (and that breaks me entirely).

By funding research and changing the research system, advocacy groups today strive to identify a cure and transform a deadly disease into a manageable, treatable condition.

More importantly, funding the caregiver system because that is the urgent need. Basic biological research in gliomagenesis will take a long time to mature. I propose that advocacy groups should work with policymakers to push for public funding (because of a high risk of failure/difficulty in reproducing ideal lab conditions to in-vitro conditions) and at the same time, invest in support infrastructure to provide succour to affected families.

Today, the median survival for patients with GBM is approximately 15 months, with a 5-year-survival rate of less than 5% In spite of the money poured into research and although some targets and pathways have been identified, brain tumors such as these are still poorly understood in terms of causal and maintenance mechanisms. If this is a war against brain tumors, few (if any) would say that we are winning.

This is the most realistic statement. (emphasis mine)

Is this paucity of treatment options a question of a broken brain tumor drug discovery and development pipeline?
Is this a question of the research environment generally being inadequate?
What are the real barriers to advance research to treatments?
And which stakeholders are responsible for addressing these barriers? The true role of the advocacy group is to address the issues that the government and for-profit sectors cannot, or will not.

I agree, and these are the set of questions that advocacy groups should ask. (emphasis mine)

Instead, as patient groups have become more sophisticated, there has been a shift from funding research that increases scientific knowledge of the disease to targeting funding to specific points along the drug discovery and development pipeline that will provide incentives for others (such as pharmaceutical and biotechnology companies) to invest in the field.

This is one aspect. I still hold that advocacy groups should push for basic public funded research and invest in support groups on the other. It is a collaborative effort. Individual patients don’t have a voice. However, groups can collectively raise their voice- in mainstream media, social network and align with research charities.

Finally, it gets me to define the patient advocacy groups as a bridge between the policymakers to push for funding and caregivers to provide resources or access to them.

This area has not yet been fully explored by brain tumor advocacy groups, but advances in citizen science and computational platforms have opened the door to leveraging new communities of researchers. Interdisciplinary efforts in systems and computational biology have the potential to translate “big data” into meaningful analyses that further translate into clinical impact

The big data (machine learning/artificial intelligence) is still a way far off, and despite being the catchword of press releases, it is still very much in its infancy. Indeed, I get riled up because of the hype factor built in “tailored research” (which is dressing up done to squeeze in more funding). (Personalised medicine remains an elusive goal).