Saturday, August 30, 2014

A new lymph node station in lung cancer?

Earlier this week in our morning didactics session we had an interesting discussion about advanced stage non-small cell lung cancer (NSCLC). Now, there is certainly a LOT to discuss about advanced stage NSCLC, and there is a lot of uncertainty in how to treat it with the multitude of new targetted agents coming on the market for mutations like ALK, KRAS, N-RAS, BRAF, EGFR, etc...  and the trials that have been run are often difficult to interpret because of changes in standard of care, stage migration due to novel imaging modalities (PET) and other things.

To add to all the uncertainty in treatment, the staging guidelines (AJCC in this case) can change. When I started my residency in 2009, we were on the 6th edition, and now it's the 7th. While the changes are usually small, they matter, because the trials that are now having results reported were often stratified using earlier editions of the staging guidelines, once again clouding the picture for patients needing treatment decisions today.

One thing that hasn't changed, and never will (?) however, is the location of nodal stations. Right? Maybe not! As a refresher, we care about a number of nodal stations when staging lung cancer. Here is the picture we all know and love (also available from the AJCC in poster form here):



Please direct your attention to the lymph node station labelled #7 - this is the sub-carinal station, and one that is often involved, and often biopsied because of the relative ease of access (bronchoscopically). Notice it is, by definition N2. However, it is also considered mediastinal. 

Now, this is all well and good, until you have a patient present, as we did at our cancer center several weeks ago with a Left sided T2 NSCLC with station 7 involved TO THE RIGHT OF MIDLINE. We went through the imaging carefully, it was NOT station 8R, it was station 7, creeping down and crossing midline to the RIGHT.

So, now the patient has, by one definition, T2N2 disease (there were no other contralateral nodes or other nodes to make him N3) by virtue of his involvement of station 7. HOWEVER, he could also have T2N3 disease by virtue of having contralateral mediastinal involvement! This is not a trivial difference as it is the difference between IIIA and IIIB, resectable and unresectable.

What to do? Well, he had poor performance status, so surgery was out either way, so we opted or combined, definitive chemo-radiation. However, this uncertainly raise the possibility of a need for more detail in the staging system. Sort of in jest, we proposed a change for the 8th edition - maybe we should have a station 7.5R/L dichotomy for significant involvement, or possibly a 7C/R/L trichotomy?

Saturday, August 2, 2014

Re-entry into the clinic and my first evolution paper!

Sorry for the long radio silence - I re-entered my residency after a 3 year hiatus to pursue full time research and things have been busier than anticipated. While I am on a light rotation (sarcoma), which requires only 50% of my time actually in clinic, I had forgotten what being a #resident is like, and more importantly, what having a pager is like!!!

My personal research efforts have slowed somewhat - with my efforts now divided between the clinic, being a dad and thesis writing. I've changed my focus to writing up what I have currently, rather than chasing after new results, so I haven't much to report. A student I'm working with, however, +Daniel Nichol , recently finished up a paper that he and I have been working on for some time. He is going to write a full blog post about the work, but this will take some time. In the mean time, I thought I'd at least let the community know we've finally submitted our paper to the +bioRxiv Preprints site, as well as a journal (contemporaneously), which you can find here:

http://www.biorxiv.org/content/early/2014/08/03/007542


In this paper, my first personal foray in theoretical #evolution we build on theory from some exciting theoretical and experimental papers from Steven Weinreich (Weinreich et al. Science) and +Jeff Gore (Tan et al. PRL) to explore the concept of 'steering' evolution as a method of preventing the emergence of resistant strains of bacteria (or cancer!).

I look forward to putting Dan's proper post up, but until then, enjoy the #preprint - we welcome comments!

We were flattered, as well, to see another blog pick up our preprint - yet another reason to use the bioRxiv or arXiv!

Thursday, June 26, 2014

Impact of vascular patterning on radiation response - contributed talk from ECMTB 2014

So - I meant to try to use +Camtasia Studio to record my voice during this talk, which would have made following along much easier, but somehow, the meeting was so chock-a-block with content and excellent social outings, that I failed to download and sort it out.  Next time...



For now, here is a short presentation that I gave as a contributed talk at #ECMTB2014 in Goteborg.  It represents the meat of the second chapter of my growing (fingers crossed) DPhil thesis. My hope is that by finding a metric (Ripley's K) that predicts radiation response in our CA model (based on a simplification of a CA I worked on previously with +David Basanta which we published here), that we (or someone!) could translate this into histopathologic sections from patient samples.

This is essentially an extension to a poster I presented at the #PSOC meeting in DC in early April which I blogged about previously.  Please feel free to ask questions or make comments. I'll let everyone know once there is a proper #preprint available, and in the mean time I'll try to learn to use camtasia.

'Till then, here's the presentation:



Monday, June 23, 2014

ECMTB 2014 in Goteborg, Sweden

I've just returned from nearly two weeks in the UK and Sweden, visiting friends and colleagues in both countries. The impetus for the trip was the once-every-three-years meeting of the European Society of Mathematical and Theoretical Biology called the European Conference of Mathematical and Theoretical Biology (ECMTB).  I first attended this meeting in Krakow, Poland (thanks to the futuristic vision of +Alexander Anderson ), before I even began my DPhil, and found a true intellectual home. This is an unbelievable group of people - intelligent, kind, fun loving and open minded.

The scientific content for this meeting was excellent (and can be found here) and included many parallel sessions of contributed talks, a poster session as well as member organized minisymposia (I hosted two, which I will blog about separately). There was a lot of activity in the +Twitter sphere recording both the scientific content as well as much of the social activity of the meeting - which are both, I firmly believe, are equally important to the success of a meeting.

I have storified the tweetcast of the meeting and social events, and will embed it below, but I also wanted to take a moment to thank +Torbjörn Lundh and +Philip Gerlee and the rest of the organizers for a throughful and beautifully organized meeting. Everyone to whom I spoke had only nice things to say - the only complaint being that there wasn't enough time to see all the amazing content! Thank you so much for your hard work.

Take a moment to scan what's below - there is lots of linked content and interesting people. Also, keep your eyes out for a group (pro-con) post on tweetcasting on the WCMBlog in the coming days.




Sunday, May 25, 2014

A success story for Warburg's Lens

I've been travelling a lot of late, which I'll blog about on its own in a bit (including a 'best of the best' coffee machines post), but I heard a story from a friend, which triggered a memory which I want to share. It took a moment, but I realised that a whole chain of events that I was unaware of, yet intimately involved in) added up to a success story for Warburg's Lens, the theoretical oncology preprint discussion forum that some colleagues and I started to try to speed up the process of scientific discussion.

So the story goes like this:

I was trolling the qBio section of the arXiv, as you do on a Friday night, looking for interesting papers. For the record, I also always scan the +bioRxiv Preprints. On this night, I came across one from one of my favorite authors, +Arne Traulsen, who has an evolutionary theory group at the Max Planck Institute in Plon, Germany. The #preprint, entitled, Cancer initiation with epistatic interactions between driver and passenger mutations, seemed like a very interesting one, so I put it on Warburg's Lens for discussion. It generated some nice discussion on the site which even included the authors, who were able to defend some of the points, but also take on board some very relevant (non-anonymous) feedback.



Fast forward a bit, and I'm minding my own business trying to get a job, and I get a request from a journal to review an article.... lo and behold it is the same one we are talking about. For various reasons, I declined to review it, but I remembered that there were some very constructive criticisms from people on Warburg's Lens (people who have published significant works in this direct area), so I knew who I could suggest as a replacement reviewer, which I did. Readers won't have a problem guessing who any of the anonymous people are, but I will not divulge that here.

Fast forward again, and I'm visiting some colleagues in Boston (again, post to follow, there was wide #heterogeneity in coffee machines) and a friend mentioned that this great paper that he had reviewed just came out...  and on the same day, my colleague and supervisor, +Alex Fletcher sent me an email notifying me of the paper, which is now out, and you can find it online here, but of course, I can't get it at home without dropping $40. I am eager to read the paper and compare it to the #preprint.


Either way, congrats to +Arne Traulsen et al. on the nice paper and thanks to all who contribute to the discussion on Warburg's Lens - and it's inspiration website, Haldane's Sieve. Keep submitting your #preprints to repositories like the arXiv and +bioRxiv Preprints, keep doing good #openscience. This seems like a win for everyone.

Also, lest I forget, cheers to the Journal of Theoretical Biology for being cool with preprints. Let's keep adding to the list.  This is a tangible example of how preprint servers help EVERYONE, even the journals. We got faster, more on target review, because of the preprint. A list of journals and their preprint policies can be found here:

http://en.wikipedia.org/wiki/List_of_academic_journals_by_preprint_policy

Wednesday, April 30, 2014

My visit to the Mathematical Neuro-Oncology group at NorthWestern and the talk I gave about glioblastoma evolutionary dynamics and metastasis

I recently was honored by an invitation to visit Chicago and present some of my recent research to my friends and collaborators in a new group formed there by +Kristin Swanson called Mathematical Neuro-Oncology. I spent my time visiting their new, beautiful lab;



celebrating +Russ Rockne's transition;



having some coffee;







visiting my roots;



finding out that a paper long in the works, based on an opinion piece I wrote a few years ago about the effects of the #IDH1 mutation in secondary #glioblastoma, is finally in press at Neuro-Oncology (aside: Somehow there is an editorial written about it that is available (if you PAY, which I haven't yet), but the article is not yet itself available); listening to +Kristin Swanson practice for her +TEDx talk, which I've heard went well, but haven't seen yet (more info here: http://www.tedxuchicago.com/kristin-swanson); and actually giving a talk.



I couldn't decide what to talk about, and since the audience was going to be half computational neuro-oncologists (casual dress) and half general scientific/medical folks (white coast, ties, scrubs), I decided to give a talk in two parts - about a half an hour each.

I spent the first half hour talking about an exciting (to me at least) extension to previous work I've done here at IMO with +Alexander Anderson and +David Basanta and others on glioblastoma stem cells. I've blogged on this topic before, from posts about our recent paper in PLoS Comp Biology to a recent grant we submitted - which, frustratingly didn't get scored due to a very prototypical reviewer #3 (reviewers 1 and 2 gave us 1's 2's and 3's and reviewer #3 gave us 7's, 8's and 9's).

The second half I talked about the work I've done with +Philip Gerlee and +Alexander Anderson and others to understand how a filter-flow paradigm of metastatic spread can help us understand (and intervene) in the process of #metastasis itself. We've published most of this work as a perspective piece in Nature Reviews Cancer, a test of the self-seeding hypothesis in J. Roy. Soc. Interface, a review in a Springer textbook (pre-print here) and recently, a more clinically oriented piece under review at Clinical and Experimental Metastasis (you can see a pre-print here on the +bioRxiv Preprints site). Both I and Philip Gerlee have blogged about it (including a shared post here in response to a Cancer Research UK blog post which we took exception to (at least to parts of it)) in the past as well.

So - anyways, here are the slides. The first half is work in progress, and we're pretty excited about it. I'd love to know if anyone has any feedback.


Sunday, April 6, 2014

5th Annual (final?) Physical Sciences in Oncology Centers meeting at the NCI

I just got back from 3 days at the National Cancer Institute for the (final?) meeting of the Physical Science in Oncology Centers. It hopefully isn't the REAL final meeting, but it is the final one as we know the PSOCs, as they are changing drastically in the way that they fund folks - in ways that haven't been entirely decided yet.  Either way, I've been attending these meetings since the beginning, and they have been quite important as formative experiences for me: showing me that outside the box thinking is OK (even encouraged) in cancer research, and that being a non-standard cancer biologists can be a way forward.

Anyways, it was a great meeting, with interesting talks ranging from origin of life, to mouse modeling to evolutionary game theory. There was a young investigator session (which I missed, but heard was really good) and a poster session, where I gave this poster -
As always, there were lots of great opportunities for networking, catching up with old friends, and making new ones. I storified the tweetcasting under the hashtag #PhysOnc (it was lively) to give you a flavor of the meeting. So, here that is: