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.

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).

Research and biotech: Asking right questions

The Ken is a wonderful resource for myriad issues.The staff at The Ken is constantly churning out some of the highest quality journalistic write ups in India. Their focus is mostly on start ups, biotech and increasingly now on security of digital assets. The reason why I recommend it is to broad-base your reading sources and think laterally beyond our narrow confines. Financial crunching may not be everyone’s cup of tea but it has spurred me on to understand more about it’s complexity. In the end, it is a deep dive learning experience to write effectively. In the sea of otherwise hopeless mediocrity that Indian journalism has seeped itself, The Ken (and to some extent, Business Standard) redeem themselves.

Today’s post was motivated by an excellent coverage of biotech sector and this prodded me on to think about what the research goals ought to be. Biotech companies are chasing the end of the rainbow for the pot of gold. The reason why US remains the “gold standard” for these companies is because of a perverse incentive that pharmaceutical companies and hospital corporations have to milk the consumer. That’s where the big money is. And these companies are pushing themselves to crack the market in order to get the first mover advantage.

I will not name a few companies that I have worked with (due to non-disclosure agreements with them and that included not calling them names publicly). There were some great individuals, that I had the good fortune to learn from, as well. This aside, they are mostly floundering pushing their luck. In proverbial terms, trying to see what sticks to the wall.

In one presentation, they presented a “case scenario” which showed how the medical oncologist based his decision on genomic details for lung cancer. In another, they were keen to show for cool-rectal cancer. All laudable but with one significant omission. They did not have any follow up for outcomes! Not only this, none for any clinical trial, suitability for a vast majority or how the specific gene sets were chosen to be marketed.

Its stupidity compounded by idiocy. Over and over again.

Sadly, the translational science hasn’t made specific progress and now we have the buzz words like “precision medicine”. Pray, what is precision medicine?

Hype fuels another set of hype cycles. It is a good thing that all of this looks great on dossiers or fanning our collective egos in fancy conferences but they remain a collective effort for intellectual masturbation. We need hard core data sets and equally hard nosed questions before we thrust all of this in front of hapless patients.

The company mentioned in The Ken write up hasn’t specifically mentioned as to how they will find out the difference in the genetic mutations (from primary index lesion) to the current state. I had earlier explored this concept in an editorial arguing for liquid core biopsies as means to monitor the course of treatment in lung cancers because of the range of molecular mutations.

Rest assured, I have a healthy disdain for pharma company sponsored trials with results that appear too good to be true. When it is translated into actual clinical practise, it doesn’t live up to it’s hype. Remember the Cetuximab “landmark trial”? Or even for that matter, Bevacizumab?

Lets pause. Think.

There ought to be healthy skepticism. A side note to fellow radoncs- there is a lot that can be achieved in Radiation Therapy. We need to explore different fractionation schedules or even radiation sensitisers. Combination therapies do-not always work out. That is the subject for another blog post.

Inbox Zero: Fastmail for academics.

Who wants this?

It is simple.

Sign up for Fastmail.

Have a custom domain, if you want. Or else, existing domains offered by Fastmail work fine.

Have an alias for each website. For example, if you order pizzas, have one for that. For a travel website, have another. The trick is NOT to give out your actual email id but give the alias for that particular site.

This is how it plays out. Go to dominos and have an alias like (or whatever domain you want). It will immediately segregate your email. If you are spammed for that domain, it is a matter of deleting that alias. Simple. Quick. Painless.

I have folders for all incoming mail, and Fastmail allows setting up rules to sort them out automatically. For example, if I have a newsletter subscription, it is set to flow in that folder and marked as read. Or anything else that I wish to read later.

Achieve that today!

RANO: Working plan for the use of patient-reported outcome measures in adults with brain tumours

Lancet Oncology, 19 (2018) e173-e180. doi:10.1016/S1470-2045(18)30004-4

Why is this paper important?

It is because there are no reliable means of patient-reported outcomes (PRO). These metrics are an essential part of monitoring the course of treatment as well as quantifying the impact of the same. For years, we have been relying on metrics like Mini-Mental State Examination. I have found that examination to be sorely limited because it is full of biases and highly dependent on the cognition/mood status of patients. There has to be a more robust metric.

Hence, the great blurb from this paper:

The first step would be to provide an overview of the guidelines of previous initiatives on the collection, analysis, interpretation, and reporting of PRO data

It is the step in the right direction because of it an acknowledgement of what we don’t know. I have attempted to involve formal psychometric testing, but it usually takes hours and have limited clinical utility. The existing tests have undergone validation in different “trials” (most of which are either single author led studies or institutional trials) leading to much confusion. Do we have a standard way of reporting them?

Not yet.

It leads us to the second step.

The second step would be to identify what PRO measures have been applied in brain tumour studies so far. As mentioned, several PRO measures are already used frequently (e.g., MD Anderson Symptom Inventory Brain Tumor Module, Functional Assessment of Cancer Treatment-Br, EORTC Quality of Life Questionnaire C30 and BN20, and the Barthel Index)

Content validity should also be culturally sensitive. What applies in one geography doesn’t translate in another part of the world (which adds to the complexity of the task).

Therefore, I feel that the third step is the most crucial question in patient-reported outcomes.

The third step would be to establish the content validity of the existing PRO measures identified in the second step. Are all essential aspects of functioning and health for patients with brain tumours covered by these instruments?

The next excerpt nails this in the right direction. It is not the patient defined outcomes alone but has to be validated by physician scoring system as well.

How is this going to shape up?

This framework refers to a patient’s functioning at three distinct levels. The most basic level is a patient’s impairment in body function, such as muscle weakness. Assessment of these impairments can be done with PRO measures, such as a symptom questionnaire, but also with clinician-reported outcome measures such as a neurological examination

Last but not the least is the psychometric properties-it has to prove its reliability as well! This, of course, applies to reproducibility across different domains.

The fourth step is to identify the psychometric properties of the detected PRO measures. How valid and reliable are these instruments for patients with brain tumours

To achieve this goal, the committee proposes to use COSMIN taxonomy and defines it as such:

The COSMIN taxonomy distinguishes three quality domains: reliability, validity, and responsiveness, each of which includes one or more measurement properties. Reliability refers to the degree in which the measurement is without measurement error, whereas validity refers to the degree in which an instrument truly measures the construct intended to measure. Responsiveness refers to the ability of an instrument to detect (clinically relevant) changes over time.

These criteria will help to shape up the course of treatment beyond the survival outcomes and focus on preservation of quality of life.

More on that later.

Why a Telegram channel for brain tumours was created?

The idea behind setting up a Telegram channel and a group was inspired by holding a Twitter-based discussion with a colleague. I am placing this on record here.

The central premise is a straightforward thing. If I were to face a similar situation, what would have been my state of mind? What is the ideal way to go about this? So, I decided to set up something in a way which I would have wanted. The first and foremost is the platform wherein I could access psychological support. These issues hit from nowhere, and it is essential to know that I am not vulnerable nor alone. While a lot of emphases has been placed on breaking bad news by the oncologists, handling the aftermath of emotional distress by a patient is an unaddressed issue. Having access to psychological resources or a support group becomes imperative at that moment.

How do I choose a support group? Ideally, one that has an active involvement of a clinician in some capacity. Most patients hit Google with a furious pace to know more about the disease. It is essential to guide them efficiently to informed sources about what we are dealing with, the likely side effects and estimated financial impact. Like a multi-disciplinary set up in a hospital, it should reflect some of it’s moving parts in a chat group as well. Patients should reasonably be expected to be guided through a simple workflow; a place where their queries are answered.

That, in simple terms, is the purpose of having a dedicated Telegram group. It is envisaged that patients would find others who have gone through similar experiences, interact with rehabilitation specialists (the medium should allow exchanging large files like videos or multimedia content) and access all old messages about the same thread (through a global search or use of hashtags). These are the broad contours to get the project off the ground and fine tune it as we go along.

Besides, regular updates and events about brain tumours need to be disseminated. A stream of messages in the proper group would become too overwhelming for every participant. Telegram offers a mechanism to copy the link of a particular message in the channel and share it anywhere (each exchanged message has a unique link available for the administrators). This would make it more efficient to share content across the application.

As with any application, users would need time to get used to the user interface. Twitter isn’t intuitive but is most widely used (along with Facebook). Twitter is meant for the immediacy of events, as they unravel. Hence, it becomes difficult (or even overwhelming) for a vast majority of users to get used to it. Like for example, no one subscribes to public lists of patient advocates that I have curated and collected, because most users aren’t aware of how to use Twitter effectively. As a result, their timelines are cluttered forcing them to spend more time. Due to process improvements, I usually skip over my timeline (using Mac desktop version) in less than 15 minutes because everything I need to focus on is there.

I hope that users find Telegram a vital addition to their daily lives.

Research in Radiation Oncology: Unanswered questions


Paper identified:

Current and Future Initiatives for Radiation Oncology at the National Cancer Institute in the Era of Precision Medicine

Charles A. Kunos, C. Norman Coleman

International Journal of Radiation Oncology Biology Physics, 2018

I have always wondered about the processes that fuel the current research programs. In fact, its fascinating to understand and learn how the various processes work in a different cultural context. Herein, I present an editorial recently published in the Red Journal (2018) and have highlighted the excerpts of what I feel are the most pertinent issues.

Current NCI Cancer Therapy Evaluation Program (CTEP) initiatives for radiation therapy devote resources and study to novel combination radiation plus agent study. Here, CTEP defines a radiation plus agent study as any-type radiation therapy given in close proximity (same line of treatment [first-, second-,etc]) before, during, or after therapeutic drugs or biologic agents

It is obvious that bulk of funding goes in identification of “targets”. They are important but not the only goal. Therefore, I am seeing bulk of money going in “biological agents”.

By investigating radiation plus agent combinations at the outset, there is an opportunity to broaden clinical utility.

While this sounds good in theory, the problem with the targeted approach is that we have no idea of how the cancer mutagenesis takes place. Radiation Therapy may also alter the tumour micro-environment and the biological agents may or may not be “effective” in this scenario. If you may remember the famously infamous Bonner trial for Cetuximab and XRT; the benefit was most with the conventional radiation using “field-in-field” (almost analogous to the SIB of today) (a type of altered fractionation) and follow up trials haven’t really shown the cetuximab to be “stellar”. I am not getting in the specifics (its a different sub-site altogether) but these issues have also rankled me.

Overview of the XRT combination

Proposed areas of research in radiation oncology

This is an important pertinent issue:

For example, it is suggested that up to 10 logs of tumor cell kill are needed to sterilize a single targeted tumor, which is a level of cytotoxicity possibly attained by radiation therapy alone, but better achieved when an agent is co-administered during radiation therapy

Bulk of what we know is primarily empiricism. The authors have also highlighted this aspect. For example, the XRT combination with Cisplatin, wherein the earlier trials were motivated by see “whatever-sticks-to-the-wall” approach. We as a community have wisened over the years and now it has been proposed that the newer agents “prove” their efficacy in the “cell lines”

CTEP endorses a preclinical approach that analyzes and emphasizes relevant cell lines (at least 2) and then cell-derived or patient derived (preferably) xenografts orgenetically engineered mouse models of cancer

My beef with it is the issue related to “in-vivo” versus the “in-vitro” model. Like really? Nope, the real time conditions faced inside the cellular environment can never be replicated outside in the petri-dish. But the “hope” is it would be safe (in animal models) with proven efficacy in the cell lines. What do we get in return? Progression Free Survival? Is that the end goal for a hopeless scenario? Is that progress and innovation in cancer?

Further, luckily this article does mention pushing for altered fractionation- hypo fractionation here. At least, there’s an awareness that it might be something better than the “conventional” methodology. I strongly feel that these are motivated by primary concerns of “finishing” off radiation therapy than exploring the true benefit of giving large doses per fraction. I am reminded of a beautiful issue of Seminars in Radiation Oncology about the fractionation and whether the venerated LQ model is applicable to giving large doses per fraction. Hopefully, with the trails that are being encouraged to explore the fractionation schedules, we might have a better clarity about the effect of radiation fractionation on tumour micro-enviroment. I remain hopeful about a better understanding on this important pertinent issue.

Reasonable number to initiate clinical trials, although the larger the enhancement the better, especially when considering hypofractionation, because there are few fractions to enhance compared with standard fractionation (2 Gy per day)

A lot of funding is also being made available for immunotherapy and in particular, abscopal effect, if any. This remains an exciting area of research and hopefully, we might have better insight in this. Is XRT having “only-local” effects or does it extend beyond the narrow confines of planning target volume? Interesting!

A proof-of-principle trial utilized local radiation therapy and granulocyte-macrophage colony-stimulating factor to potentially induce an abscopal response among treatment refractory solid tumor cancer patient. A trial evaluating high versus low radiation dose and immunotherapy is underway (NCT02888743) (emphasis mine)

Ah, the heavy particles. This opens another can of worms, isn’t it? Protons/Carbon Ions versus the Photons (traditional). Meta-analysis hasn’t been kind on its use but it probably represents an arms race to push for the lingering effect of higher OER/presumed benefit versus lower rate of side effects. I haven’t been exposed to the working but it remains subject of much interest. The countries listed here are indeed in a technological arms race. My only interest would be in radio-biology; more than the Bragg peak 🙂

The heavier particles, such as carbon ions, already in clinical use in Japan, Germany, Austria, Italy, and China, might offer further radiobiological advantages beyond protons

Radiogenomics offers the best insight. This is closest to the “personalised medicine” that we are talking about and is perhaps the sum combination of what all I have discussed above. I strongly feel that in sensitive patients; i.e. the ones have the driver mutations, there ought to be an “intensification” of treatment with a higher chance of more prolonged remission/local control, rather than the de-escalation of treatment schedules (as is currently in HPV positive oropharyngeal trials). Nope, we want to hit it hard when it matters the most and not otherwise. I think in the entire editorial, this is the most pertinent issue that’s been highlighted.

Single-arm design umbrella trial that aims to test whether patients with a specific tumor mutation, amplification, or translocation of genes in a driver molecular pathway derive clinical benefit if treated by radiation therapy or by radiation-agent combinations specifically targeting the driver molecular pathway. Such a study is akin to the NCI Molecular Analysis for Therapy Choice trial (NCT02465060) (emphasis mine).

Further aside in the ongoing discussion about the “personalised medicine”:

New radiation therapy trials are taking a first step to identify tumor mutation, amplification, or translocation of genes that drive radiation therapy sensitivity or resistance (NCT02888743,NCT01096368) (emphasis mine) 

The bureaucratic nightmare! The process of drug discovery and final clinical trials!

Last but not the least, the authors have not forgotten about the most important subset of patients: kids! It breaks my heart to see them in the hospital but someone has to care for them! Its important though to keep the fundamentals in place here. Delayed developmental milestones are a huge problem because of the human opportunity cost as well as the burden on the healthcare where costs are spiralling out of control. Research, here, would need to identify where paediatric patients need to be treated and how much treatment regimes need to be identified. With a whole different universe of molecular mutations, this area is ripe for disruption.

Whether radiation therapy could be delayed until developmental milestones are reached or whether radiation therapy could be omitted altogether remain important clinical questions for the radiation oncology field. Improving pediatric patient selection for radiation therapy, perhaps through molecular prognostic factors, is a good example of future radiation therapy science better anticipating needs for intensive local therapy or for intensive systemic therapy.