Recurrence patterns after maximal surgical resection and postoperative radiotherapy in anaplastic gliomas according to the new 2016 WHO classification

Authors: Jung Ho Im, Je Beom Hong, Se Hoon Kim, Junjeong Choi, Jong Hee Chang, Jaeho Cho, Chang-Ok Suh


Scientific Reports, 2018, Volume 8, Issue 1

Why is this paper so important?

However, recurrence patterns according to the histological subtypes have not been well studied. Most studies on recurrence patterns were mainly conducted before 1995

This is the reason why this paper is important because it focuses on the type III tumours (which hasn’t been explored in contemporary literature) and the first article to address this.

I am more interested to see how the molecular landscape varies across the different histologies. As you can see from the ensuing table, majority of them were MGMT methylated with IDH1 mutation and some gratifyingly 1p19q co-deleted (for the Anaplastic Oligodendroglioma) (which are known to have a good prognosis, anyway).

The recurrence patterns are more instructive. The following is a representational image of how they took the planning volumes (but more importantly, the way recurrent tumours were defined- they were “outside” the planning volumes.

Let’s talk about the vital survival curves; there’s not much difference between the PFS and OS (which anyway is a known factor for the Grade III tumours). There is nothing earth-shattering about this, in the first instance.

But look carefully at the following table which provides the low down of the molecular abnormalities in the tumours which were identified in the cohort.

Survival outcomes as per the molecular findings; of course, this confirms our biases 🙂 As always, the gross total resection offers the best results along with the mutated IDH and co-del tumours. Again, there’s nothing much to bleat about here because these are known “good prognosis factors”.

Median PFS and OS were 130 (range, 56–204 months) and 158 months, respectively. 5- and 10-year PFS rates were 60.4% and 56.3%, respectively, and 5- and 10-year OS rates were 65.4% and 56.6%, respectively

The authors had used the antibody to test for the IDH presence; although reasonably robust but I ALWAYS prefer to get the sequencing done to identify the mutation if any.

Antibody used was anti-human IDH1 R132H mouse monoclonal antibody (Clone H09L, 1:80 dilution; Dianova, Hamburg, Germany). When the cytoplasmic expression of IDH1 R132H was identifed in glioma cells, we considered the case as “mutant”/“positive.”

They had a pretty robust way to identify the 1p/19q status as well (as per the 2016 guidelines for identification of FISH criteria).

The table is demonstrating break up of the mutations in the cohort (which I feel is the most important table in the entire paper).

THIS IS THE MOST IMPORTANT FINDING.

 

 

 

 

 

 

 

 

 

 

 

Patterns of recurrence according to the 2016 WHO classification and extent of resection. Column 2 represents the number of patients in each subgroup with recurrence and their percentages are indicated in parentheses. GTV, Gross Tumor Volume; CTV, Clinical Target Volume; CSF, Cerebrospinal Fluid; WHO, World Health Organization; AO, Anaplastic Oligodendroglioma; IDH, isocitrate dehydrogenase gene; GTR, Gross Total Resection; STR, Subtotal Resection; PR, Partial Resection; Bx, Biopsy; AA, Anaplastic Astrocytoma.

If you look carefully, the ones that had the maximum out of field recurrences were IDH wild type. Is it possible that they had some pro-migratory characteristics right from the start? Are we missing something?

Recurrence rates for GTR or STR were similar but much lower than those for those who underwent partial resections or biopsy. In patients with GTR, most recurrences (12/13) occurred in the patients with AA, IDH-wildtype. 

The authors had followed the standard protocol.

We prescribed 46–50 Gy to CTV. Therefore, a higher radiation dose to CTV can be considered for AA, IDH-wildtype

I would concur with the above statement.

The Achilles heel of the paper? They had chosen the patients selectively for getting chemotherapy. Not everyone got the adjuvant TMZ.  I prefer to give TMZ to all patients irrespective of the mutational status; however, the bigger question is whether it ought to be for 6 months, 12 months or even up to 24 months. I think, in part, it depends on the performance scale of the patients as well as the MRI perfusion scans. If the perfusion value is less, I’d prefer to keep at it. But these are only anecdotal observations; not backed by the trial outcomes. Which gives me an idea for a study as well.

The role of TMZ has been assessed in a large international trial, CATNON. Interim analysis showed that adjuvant TMZ CTx was associated with significant survival benefits in patients with newly diagnosed 1p/19q non-co-deleted anaplastic glioma.

The authors have proposed increasing the size of the planning target volume. They do mention the newer 2HG MR spectroscopy which detects the abnormality over a wider area.

Metabolic imaging with MR spectroscopy to image the 2-hydroxyglutarate signal in the brain to detect oncogenic IDH1 mutations has been recently developed. It showed that the 2-hydroxyglutarate volume was larger than the FLAIR volume in approximately half of the IDH-mutant glioma patients

But the big question: How much normal brain can you really irradiate?

These are the broader issues that need to be debated.

Is research wasted?

How far is this true?

I would dispute the numbers but the questions raised here are extremely pertinent.

  • As always, we need to ask the right question. Design appropriate methodology.
  • Put it out in public domain.
  • And make the research accessible.

These are desirable goals but not the end points that we see in practise. Things have to change for meaningful outcomes.

Word Press blogging platform

The standard wordpress.com blogging platform is decent enough. I had been using the self hosted version for pretty long time but the maintenance had been done by someone else. My job was to blog. And I did experiment around with various plugins.

Despite the “free option”, wordpress.com does have a decent advantage when you pay up for it. One of the biggest hassles with self hosting is the recurring cost for a single website; it doesn’t help that way. In addition, adding media to the blogposts quickly adds up to the allotted storage space. Although there are ways to circumvent it, honestly, I don’t have time and patience to have all this set up.

My biggest grouse is that standard wordpress.com doesn’t allow one to install plugins and requires most expensive tier. I have highlighted the same to the customer care but sadly, they aren’t able to help me to go around the limitations. Its being greedy and a stupid limitation but thats the best I have around me. Other alternatives have too fancy interfaces that doesn’t help to deliver the goods as effectively.

I really hope some sun shines and they at least move the installable plugins to the middle paid tier. I might reconsider then. Lets hope for the best!

How to deliver a scientific talk: Or not kill your audience

 

I stumbled on this gem from Twitter! I am sharing this in entirety because I feel that it needs to be shared to a wider audience.

I am not having any claim to fame as far as the public speaking is concerned but I have had my fair share of run ins. The author is right about being able to engage the mental attention and it is a difficult task. Nevertheless, there are some common sensical pointers here that I’d like to share from the embedded document (please feel free to download and share) Thats one reason I usually dread going to the conferences. Its only because of the boring presentations (and sometimes tasteless food).

Be visual!

I prefer to have the pictures do the talking but if they are done to death, it makes for a disaster.

The goal is to have a visually streamlined talk where the audience is so engaged with your presentation that they forget you’re standing in front of them speaking.

Highlight the points and learn to do it!

The bulleted points! They should be banned.

Kill clutter. Remove text. Complete sentences are to be banished from your talk.

Be nice to your audience!

Many times I have seen the speaker pointing the laser as if to highlight the importance of a bullet. The pointer goes up and down and this makes for a perfect recipe for disaster because subconsciously, the audience is following the pointer.

Try not to use a laser pointer. They’re a crutch for you and are distracting to your audience. More to the point, there’s no need for one if your slides are properly designed (uncrowded).

No suspense! This is self explanatory

People really don’t like suspense if they’re not already invested in your talk, and they have bad memories. So tell them the main answer before going into the details. Rather than try to figure out where you’re going, they’ll be able to concentrate on the finer details of your talk.

Keep it brief!

Really! This helps.

Keep methods brief. Most don’t care about methods, it’s a distraction from the story. Provide enough detail that they know what you did and have some confidence that you know what you are doing.

Finally; last but not the least!

Knowing your audience is the most important thing. You need to be able to tailor your talk depending on who is going to listen to what.

Know your audience. Present something that they will enjoy, for scientists this usually means tailoring the level of technical detail (and amount of introductory material) to your audience.

I hope this little list helps!

How I have refined my academic workflow?

(Estimated reading time: around 8 minutes).

I have been trying to establish an academic workflow for quite some time now. Writing about it helps me to organise my thoughts better. I’ll highlight what I have found useful. This list is by no means exhaustive. This is also in line with my idea of documenting everything as I hurtle towards the goal of academia. Its an ongoing struggle but I am hoping that someone more knowledgeable than me would take time out to point any obvious flaws. I also hope to spur on discussion about their own workflows.

Mind Map and how ideas could flow

Created in scapple; a basic mind map

Step 1: Creating a mind map.

I use Scapple for it. There are other alternatives available but I haven’t explored them. Stare at a blank canvas and start writing randomly. Identify the thoughts as they come to you. They help in brainstorming. This involves identifying the parameters that I have to use/cover, all the ideas I have to write about and how I need to be able to distinguish my write up from other published ones.

That, I believe, is the most important part, since the first part of any research is identifying the question and being able to coherently frame it. This is followed by supportive evidence (if any) and the strength of the protocol that you are out to write. If you don’t want to use Scapple from the outset, you can always write it down; see all the ideas that form a feedback loop, if any, and then take it forward.

Key takeaway: Identify the idea first!

Step 2: Pubmed

Once I have done it, I hit Pubmed. The search on Pubmed has improved vastly although a compelling use case exists for Quertle as well. Previously, Quertle had a free tier but its a paid option now. I haven’t used it recently though. Nevertheless, I use advanced search and booleans to drill down to the specifics on pubmed. Once I have identified my key words that give me adequate results, the fun starts.

A specific keyword is likely to give a river of publications. Most of them are usually contextually related and Pubmed has complex algorithms to sort them out. I prefer to subscribe the whole list by RSS feeds (which I covered recently). These RSS feeds then pipe into Inoreader. Few people might prefer to get email for it but this is easily lost in the sea of email that we get (I hit on a specific actionable inbox zero protocol long time back and its serving me very well). Email is a bad idea.

Step 3: Inoreader for RSS feeds

Inoreader is a fantastic resource. Apart from the specific Twitter searches, I can filter out the feeds.

Lets say, if the feed is showing up keywords for canine oligodendroglioma (which is irrelevant for me), it can be filtered out. Once its done, I can set up several other rules in conjunction with IFTTT.

Inoreader and IFTTT (If This, Then That) allows you to create applets that links various services. For example, I pipe articles related to specific keywords, IFTTT can be triggered each time the article comes in. I add specific hashtags to it and viola! All articles that are of relevance (from specific keywords/filtered) are pushed out to Twitter. A bit of human curation also occurs in this river of articles. I usually “star” the articles (things I have to follow) and IFTTT appends separate hash tag to it and pushes out to Twitter.

In this, specific write ups that are relevant to my work (starred articles, for example), are saved and downloaded (usually from Sci-Hub or through institutional paywalls).

Step 4: HighlightsApp on Mac

I use Highlights App on Mac (I think it was created by a PhD student himself). The coolest thing about it is the annotations come as a note (which now happens in Bookends as well). These notes are exported as TextBundle and opened up via Ulysses. I add meaning to these notes (needed to learn a little Markdown; enough for me to get going) and Ulysses pushes it to my publishing website on word press.com

Step 5: Using Ulysses to craft your ideas

The beauty about Ulysses (apart from the simplicity, writing long form, ability to preview in various formats etc) is stellar customer support. I faced an issue with Highlights app and Ulysses and it was addressed by the developer himself. They moved towards a subscription based model and I think it was a wise sensible decision.

Step 6: Always use a Bibliography manager for your papers!

Nevertheless, I have found peace with using Bookends. It is (I think) a one man show (Sonny Software) and is one of the most comprehensive solutions. Sente/Papers 3 are gasping but Bookends has thrived on a payment model (upgrade every 2 years) with stellar support; both on forums and email. Bookends serves as a bibliography tool (this deserves another blog post some day).

Step 7: Scrivener for writing papers. A must have and a life saver!

After annotations/note taking, I prefer to write using Scrivener; especially the long form. I break up the article in several parts and I can work on them at different intervals. This also requires another blog post!

Scrivener pipes out the output in rtf (for example) where Bookends can scan it, add the citations which then requires some more formatting to be pushed to journals for submission (and then hope that the anonymous reviewer would be nice to you!)

Starting from Pubmed, this train of thought may sound complex (but it isn’t) and is straightforward. Each one of them serves a specific purpose.

Ulysses works perfectly to write these blog posts since I prefer to use a distraction free environment. I use Vivaldi browser as my preferred software; has tons of shortcuts and muscle thats absolutely amazing.

Don’t forget cups of tea/coffee and some Spotify lists to keep things interesting! (meditative music helps me :))

Disclosure: None of them are affiliate links and I have paid for the software in full. They deserve to be highlighted! 

 

How to use Telegram chat app for academics

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This post is prompted by a discussion I had with a few people on Twitter recently.

Instant messaging applications abound; the most popular amongst them is WhatsApp. It relies on phone numbers to get the work done. By being dead simple, WhatsApp became the most popular application for majority of the users. I believe that it is only a SMS replacement and nothing else. Furthermore, other reason I don’t use it is because its now completely owned by Facebook. The wealth of data related to our social interactions is more important for the company (and thats the reason why its free). Nevertheless, I’ll come straight to the point. How I found Telegram to be better than any chat application and how I use it effectively.

  1. The most important aspect: Bots. They are small nifty software programs that run on the application and automate things. For example, in a group, a Group Butler bot will assist the administrator in welcoming users, make them aware about the rules, limit the media (from pre-arranged rules) and prevent users from flooding. There is a classical music bot that works like Spotify 🙂 The possibilities with bots are endless. Payment bots are maturing on the platform as well.
    bots
  2. Notifications: This is the biggest bane of chat applications and serves to distract us most of the time. As a result, we are hooked to the devices. In Telegram, I have muted all users/groups/channels. The group notifies me only when someone mentions me by my screen name (like Twitter). This indeed is a life saver!
  3. Instant view for articles. It loads up the article (for example from New York Times) inside the app itself. This ensures that I don’t have to jump to the browser.
    instant-view-telegram-updated
  4. Channels serve as a mechanism for one way flow of information. Channel owners can post in media (file limits of 1.5 GB are pretty generous); videos, files, pictures etc but the subscribers cannot comment on it. This avoids the hassles with comment moderation. Channels can have unlimited number of subscribers while groups can accommodate upto 50,000 users (easily managed by bots!) Channels with companion groups can serve as a decent platform for two way communication between users. I manage couple of channels (which are automated) and serve as an admin for several groups without breaking into a sweat.
    Telegram-Channels-List
  5. Last but the not the least. It is a cloud based platform which ensures complete cross platform availability. I can start the conversation on my desktop and continue the same on my mobile device. It can also be accessed via browser. A personal cloud storage comes with it that can store my files indefinitely. Numerous granular privacy controls ensure that I can restrict users from adding me to groups or controlling who can initiate voice calls with me.
    telegram-two-step-verification

Publishers should explore Telegram channels; they can have dedicated systems for payments for premium content (which is invite only link); instant view from the app can ensure filtered information. This app can serve as a distribution hub for media. Bots can be used to link Telegram channel with Twitter, for example. The possibilities, actually are endless! Better still, you get to control access to your busy schedules (Personal chats, except family, groups and channels are all muted).

I really hope academicians and fellow professionals explore this application in right earnestness!

5 ways how Twitter helps: How I embraced Twitter (and learned to stop worrying)

I had been social media averse because of privacy concerns. I am much happier to pay for a service than have a company muck around with my personal data. I had been on Twitter way before “fake news” became a phenomenon and much before presidential tweets became the new normal.

As an individual, its easier to get lost in the stream of work, cynicism and unmet goals. This plays out in professional domain as well since its impossible to keep personal life segregated completely. However, those seeking care from us require more emergent solutions that requires us to “divorce” our personal problems, cast them aside and have a smiling face. Social awkwardness has its own set of limitations though; it becomes difficult to open up to a colleague , at times, to discuss issues like marriage or issues with boss etc (problems which are universal).

As a result, we wear a thick coat of cynicism. We look at the issues (as they are happening) through a narrow perspective. While we are attending to patients, it appears as if we are merely going through the motions of it; almost like a robot. This needed a change.

Much has changed over the past few years (ever since I quit Twitter in the first instance). I have matured, become more patient and accommodating. However, I couldn’t feel the inner connect with my drive; I knew I am capable of far better output!

Twitter, as a platform, has become better than previous iteration. I discovered a whole community of very interesting people and indeed a revelation! In no specific order, Twitter interactions with them definitely helped me both personally and professionally (and I have just started!) by helping me to see what people are doing; what they have achieved and what I can aim at.

  1. First and foremost is the patient advocacy. This is extremely important because patients need a voice of their own and they need to look up to their clinicians. I have always been empathic to this cause and realised early on that their individual voices need to be channelised. Many organisations are now harnessing the power of social media and its important to amplify this good cause. Once I got used to the interface, I made a specific twitter list for various patient advocates. There’s a whole community out there which touches the lives of individuals in a profound way; makes them one of their own. This is important aspect in their recovery and coping up mechanisms.

2.Overcoming my “writers block”. I have always been blogging and writing about everything else except my own profession! This step was important and I owe it to some individuals who are prolific writers in their own right! The breath of ideas and thoughts has deeply impacted me and motivated me to get on with my own writing.

3. I have always been interested about technology and how deeply it impacts our day to day lives. I am more keen for the privacy aspect; especially the deluge of data being analysed by unknown entities. Big data has entered our lexicon that brings forth new set of challenges for professionals. “Shape up or ship out” is the new mantra; healthcare professionals are being tasked with administrative issues which requires this domain expertise. The inter-connectedness of diverse health care streams and cross pollination of ideas is bound to affect the rich heterogeneity of radiation oncology community. I was very happy to find people with similar interests there!

4. I was extremely happy to learn about other disciplines; especially Pathology! It was something that I dread during med school days but it is only because I couldn’t appreciate or go beyond the routine “stains”. However, much water has flowed since then! Molecular diagnostics has made a roaring presence and “clinico-radio-pathological” diagnosis (as part of the comprehensive joint neuro-oncology meet ups) is the new norm. Nothing beats the thrill of a diagnosis and a debate between diverse fields! I have a renewed respect for my colleagues pursuing it! (Bonus tip: I love the #pathart so much!)

5. Last but not the least. Its an amazing community to be with. Ignore the “politics” and you’ll find more meaning in it. I did some things to automate tweets, use RSS feeds to push new updates (which in turn have been sliced and diced using complex rules), follow timeline with muted words and hashtags (to improve signal from the noise) and created multiple private lists to avoid being overwhelmed with information. Its worthwhile intellectually fulfilling exercise!

More importantly, it has become a go-to place to see whats being discussed and I get more ideas to write about; blogging is actively being shaped by my Twitter experience in order to get my voice out. I owe to each one of them!

Thats how I embraced Twitter and stopped worrying about it!