Wednesday, June 28, 2017

Upstream Palliative Care and Dissecting Hope From Hype in Oncology

by Christian Sinclair

Working in an outpatient cancer center, I frequently encounter the conversation about whether the next cancer treatment regimen is ‘worth it.’ Patients and families consider may interpretations of worth; financial being one of course, but also physical side effects, the emotional toll of investing faith into ‘one more treatment’ and hoping that it works. These conversations are challenging as they weigh biological, medical, spiritual, social, personal, emotional and other issues, so there is no neat equation which can easily tell you if the benefits or the risks are greater.

These struggles were nicely summarized by Liz Szabo (@LizSzabo) in her article “Widespread Hype Gives False Hope to Many Cancer Patients.” From hospital billboards that emphasize eliminating cancer, to multitudes of ads for new drugs with new indications are we entering a hype boom in cancer care or have we really reached the next level? Szabo has this amazing quote form the CMO of the American Cancer Society:

“I’m starting to hear more and more that we are better than I think we really are,” said Dr. Otis Brawley, chief medical officer at the American Cancer Society. “We’re starting to believe our own bullshit.”

(A quick aside, I appreciate his frank assessment and swearing. This is not some vanilla, focused-group response. Also, thank you Kaiser Health News (and CNN) for actually publishing it without asterisks)

What is causing this new level of excitement in oncology? Jennifer Temel recently noted that the therapeutic nihilism started to change with the emergence of genotype targeted therapies like tyrosine kinase inhibitors in the mid-2000’s. Her opinion piece in JCO on the Prognostic Uncertainty in the Modern Era of Cancer Therapeutics echoes what I have heard at last year’s Palliative Oncology Symposium, and the Cancer Center Business Summit, as well as what my fellow oncologists are saying as we see patients. But cancer therapy has historically been through boom and bust cycles of hype, how is it possible to tell if this is any different?

Pinned Tweet of Dr Prasad
Another great voice to listen to is Dr. Vinay Prasad (@VinayPrasad82) who constantly applies the screws of scientific theory to poke holes in over-optimistic press releases from drug makers and academic medical centers about the next big drug. Follow him on Twitter and you’ll quickly learn a lot of the hype is not necessarily backed up by the strongest evidence, despite what you may see on TV or even in journals. I would imagine given the modest evidence-base in palliative care he would take the same approach to us, yet I have found his explanations helpful to me as a palliative care doctor working upstream in an academic cancer center where every week I am seeing patients on brand new drugs or relatively new drugs with new indications.

For those of you working in more upstream palliative care in outpatient settings or in the community, how are you keeping up with the latest therapeutic advances in oncology? I see that I have needed to learn a lot in the last two years in this new position and see a new challenge for upstream palliative care.

If you are interested in talking more about this, join the #hpm monthly tweetchat tonigth Juen 28, 2017 at 9p ET and join the Facebook Group started by journalist Liz Szabo 'Treating Cancer: Hope vs Hype.'

Dr. Christian Sinclair is a palliative care physician at the University of Kansas Cancer Center, editor of Pallimed. When not reading up on the latest imboblumimab, you can find him walking his dog Spud to the park.

Wednesday, June 28, 2017 by Christian Sinclair ·

Thursday, June 8, 2017

Perusing ASCO 2017 - AKA Time for Lorazepam

by Drew Rosielle


The Annual Meeting of the American Society of Clinical Oncology was last week. It’s been my observation over the years that much of the best palliative-oncology and supportive-oncology research is presented at ASCO each year, before it’s actually published (if it ever gets published).  So I always dig through the palliative/EOL/supportive/psychooncology abstracts each year to see what's happening. Below is a gently annotated list of the abstracts that caught my eye the most, for your perusal and edification. Undoubtedly, these are my idiosyncratic choices, and if you want to dig through all of them you can browse the abstracts by category here. A couple additional comments first.

One of the big headline trials was a supportive oncology trial showing that regular tablet-based symptom assessment in cancer patients prolongs survival.  Christian promises me he's going to do a deep dive into the symptom tablet trial so I won't really talk about it here.

It’s interesting however to compare it to one of the other major headlines which was about abiraterone for advanced prostate cancer. People went nuts for this study, although if you dig into the results they’re pretty modest (3 year survival 83% in the abiraterone vs 76% in the placebo group), but in cancer trials that’s typical. I’m not knocking the study, they are good results, I’d undoubtedly do abiraterone myself, but there’s often a big disconnect in the headline findings in cancer research and the actual, real, patient-relevant results. Lots of money to be made and spent on abiraterone, which is why it’s gotten so much press. Full paper here:http://www.nejm.org/doi/full/10.1056/NEJMoa1702900#t=abstract


The symptom-assessment trial got great press, to be fair, but far less than abiraterone (see this WaPo puff piece which totally ignores the symptom trial, but does talk about abiraterone and the gobs of industry money slushing around ASCO, which makes me, and I hope many, many oncologists, nauseated).  


Here are the other abstracts which caught my eye, loosely organized, and mildly annotated. (I should note that my annotations are summaries of the findings - keep in mind these are abstracts, not full publications that have been through peer review, we can't really look at the methods, so when I say that the abstract shows that X is effective for Y, that's me summarizing the abstract, not endorsing the veracity of the findings.) Also, if you're an author, and I misrepresented your findings, shame me in the comments and I'll append edits in the permanent post. 

1. A RCT of pretty high doses of lorazepam vs placebo, plus haloperidol for EOL agitation, showing that the addition of lorazepam helped. This got a lot of chatter on Twitter, especially about how it compared to the RCT of low dose haloperidol/risperidol for delirium.  I think it’s validation of the idea that it’s imperative to keep in mind the therapeutic goals with regard to delirium and agitation. Ie are we trying to sedate someone (=suppress the agitation behavior) or are we trying to improve the delirium? The first we can do, as this abstract shows, quite easily with a good dose of a benzodiazepine; the second we still lack any convincing data about any effective strategy in our late-stage patients, despite the widespread observation (belief?) that haloperidol & similar agents help.  Good stuff and I hope it's published in full soon:  http://abstracts.asco.org/199/AbstView_199_181607.html
  
2. A study looking at chemotherapy and palliative consultation in ICUs:  http://abstracts.asco.org/199/AbstView_199_192587.html 

3. Another study showing helpful effects of early palliative consultation in hospitalized cancer patients:   http://abstracts.asco.org/199/AbstView_199_190938.html 

4. A study looking at the relative stability of treatment preferences in advanced cancer patients over time:  http://abstracts.asco.org/199/AbstView_199_192725.html 

5. A study looking at Latinos & EOL preferences, including the generational effects after immigration: http://abstracts.asco.org/199/AbstView_199_193461.html 

6. A study about patient-caregiver agreement about goals: http://abstracts.asco.org/199/AbstView_199_192587.html 

6. A study looking at the natural history of fatigue in breast cancer survivors for 6 months. I wished they followed for even longer and hope they come out with data at years 1, 2, 3 and beyond: http://abstracts.asco.org/199/AbstView_199_182648.html 

7. A mobile CBT app for anxiety in cancer patients does very little: http://abstracts.asco.org/199/AbstView_199_194370.html 

8. A study looking at what healthy people say about whether they'd want 'palliative' vs curative chemo for AML, hypothetically speaking. Interestingly, responses seemed to be more fixed (fixed beliefs about whether chemo is worth it or not) than based on the information provided about different levels of side effects. This sort of research is fascinating, but I always worry that what healthy people say in a survey about a hypothetical question is very different from what they do when actually facing a life-threatening disease. The same problem with statements people make when they are healthy, and even put into health care directives. "Uncle Joe would never want to go to a nursing home." That sort of stuff - ie does it actually mean Uncle Joe would rather choose to die this month than go to a nursing home - how do we actually interpret the prior statements, etc. Anyway:  http://abstracts.asco.org/199/AbstView_199_192439.html 

9. A fascinating study about potential interactions between depression, and depression treatment, and length of stay in  hospitalized cancer patients:  http://abstracts.asco.org/199/AbstView_199_188306.html 

10. A cocoa-based balm for onycholysis in chemo patients. There were 2 onycholysis abstracts this year. Why not?  http://abstracts.asco.org/199/AbstView_199_186790.html 

11. A mildly promising pilot study lactoferrin for chemo dysgeusia:  http://abstracts.asco.org/199/AbstView_199_191178.html 

12. Several studies of olanzapine for chemo nausea/vomiting (CINV). One showing it's more effective for emesis than nausea?:  http://abstracts.asco.org/199/AbstView_199_185558.html. More data for olanzapine: http://abstracts.asco.org/199/AbstView_199_181353.html. And in case there was any doubt, here's a metaanalysis of olanzapine for CINV demonstrating its effectiveness:  http://abstracts.asco.org/199/AbstView_199_187470.html 

13. A follow-up, with longer term data, from the RCT of palliative care for stem cell transplant patients showing improvements in depression and PTSD, but not other outcomes, at 6 mo: http://abstracts.asco.org/199/AbstView_199_188285.html. Earlier publication here: https://www.ncbi.nlm.nih.gov/pubmed/27893130 

14. Predictors of aberrant drug behavior in a cancer center population (helpful, and it’s exactly what you’d expect it to be, because they are the same predictors in the healthy population): http://abstracts.asco.org/199/AbstView_199_192505.html  

15. Yes, transbuccal fentanyl helps for dyspnea: http://abstracts.asco.org/199/AbstView_199_181614.html 

16. A RCT of minocycline for chronic myeloma pain (!) which showed promising results (phase II, better trials are needed). I vaguely had a sense minocycline had antiinflammatory effects, but apparently it could have analgesic effects too. Really looking forward to a study which hopefully looks at long-term safety and efficacy: http://abstracts.asco.org/199/AbstView_199_186197.html 

17. I hadn’t known this but there is actually a RCT showing that l-carnitine WORSENS taxane CIPN. Ugh. I have never used it due to lack of data showing efficacy, but hadn't realized it was probably toxic and still see patients on it sometimes. If one needed reminding that all these herbs, supplements, and so-called alternative treatments aren't these bland, safe, anodynes this is a good reminder. Science-based medicine is what our patients need and deserve. This abstract is a follow-up to the study showing it was poison:  http://abstracts.asco.org/199/AbstView_199_184547.html 

18. A deeper look at the truly nasty neurotoxicities of anti-PDL1 drugs (the major class of cancer immunotherapies). Little is known about this (I've now seen one case) and we will see more and more of this as these drugs are more widely used:  http://abstracts.asco.org/199/AbstView_199_191534.html 

19. Finally, and whoa -- single fraction is as good as multi-fraction radiation for cord compression. At least in patients with poor long-term survival (median survival was 12 weeks in this cohort). I look forward discussing this with my rad onc colleagues, as it would be a very welcome option for patients with less than 3 months to live so they didn't have to spend 2+ weeks of that time getting radiation: http://abstracts.asco.o/199/AbstView_199_186591.html

Thursday, June 8, 2017 by Drew Rosielle MD ·

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