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By Christian Sinclair (@ctsinclair)

The growth of palliative care in the community and outpatient settings has been one of the more popular stories in our field in the past few years. No longer is palliative care only available to serve in the intensive care units, but the demand for person-centered, family-oriented, symptom-based care with an emphasis on communication and decision-making is being heard in the earlier stages of illness. Serving patients and families in clinics and in their home is unleashing the true potential of palliative care. Even in my own work leading our outpatient efforts in an academic cancer center, we are very excited about our upstream involvement setting the stage for the 2016 ASCO Clinical Practice Guidelines on implementing palliative care into oncology practices. I have seen the positive impact of being involved early and it gets me excited to hear from my peers across the country doing the same thing.

But we have learned in the delivery of palliative care, to be wary of the overpromise of new medications and new technologies. We see the patient impact due to the hype around a new treatment lead to a widening of “eligible” patients which is often followed by a lack of impact compared to original trials. We hear the stories of medical bankruptcy because of expensive new treatments that never panned out for patients. And knowing this I have begun to worry about the Goldilocks principle as applied to palliative care; not too late while also being not too early. Unfortunately, not all the research is helping us define the right time to initiate palliative care, which is a crucial question because we still do not have the workforce to be undisciplined in what populations are served.

The Danish Palliative Care Trial (DanPaCT), published in Palliative Medicine this May by Groenvold et al, is just the kind of study which may help us begin to focus our efforts on this important question of timing. It is the first major European trial of SPC compared to all the other studies which have been based on North America. DanPaCT researchers looked at early referral to a specialist palliative care (SPC) team versus standard care. I came across this study because it was covered in the December Hospice and Palliative Medicine Journal Club (#hpmJC, @hpmJC on Twitter). The study population involved nearly 300 people with stage IV (metastatic) cancer at 5 Danish oncology centers. The SPC intervention took place over eight weeks and included in-person and telephone visits. The outcome studied was the change the single most distressing need for a patient using the EORTC QLQ-C30. And the results showed that early specialist palliative care made no difference in the most distressing issue. That is not heartening.

(Sidebar - Patient Selection - They looked at 1146 patients with metastatic cancer and after completing a palliative care screen (showing multiple high scores on EORTC QLQ-C30), they found 464 (40%) patients that they thought would benefit from SPC. That is a helpful metric to emphasize not everyone with metastatic cancer may have needs to be met by your palliative care team. Also, 30 of the 297 patients died during the eight-week study period, which is a pretty high mortality if this was designed to be a trial of EARLY palliative care.)

The study was well-designed and the publication is a must-read for anyone looking to make a case for upstream palliative care. I expect it will be featured in the state of the science at The Annual Assembly of Hospice and Palliative Care in 2018 even though it is a negative study There are some caveats to be made before you change course and tell your Stem Cell Transplant Team that you can’t see the patient BEFORE they get their transplant because you won’t make a difference.

The researchers looked at primary need, which was based on patient-reported outcomes (Good!) but picked because it was the highest score on the severity scale, not because the patient said it was the most important thing (Bad.) We all can imagine a patient who rates their anxiety a 7 and their pain a 5, but states that they would really be less anxious if they felt some control over their pain, so they feel pain control is the most important issue. Also picking one issue is a narrow view of the whole-person approach that defines palliative care, but to be fair when they looked at the improvement in other areas in the secondary outcomes analysis, there really was no major impact by SPC either. While not the focus of this first major DanPaCT publication, I hope to see other key areas of impact published like health care utilization (days at home, hospitalizations, ER visits, cost of care) and patient satisfaction with care.

It was not clear what professional disciplines were involved in delivering SPC, which is one of the most important factors in helping other clinicians decide how they can design their palliative care program. Many of the studies featured in the ASCO CPG were quite explicit in how their palliative care intervention was delivered, which helps program leaders decide what staff they need to hire.

My conclusions are:
1. This was a fantastic and well run trial
2. But they probably chose the wrong primary outcome
3. And underpowered given pragmatic approach#hpmJC

— Katherine Sleeman (@kesleeman) December 13, 2017

So this gets me back to the Goldilocks Principle. If we are going to properly balance our small but growing palliative care workforce and meet the needs of patients who would benefit most from our interventions, is there a problem with being involved with being too far upstream? We all know the problems involved with being called too late, now we might start developing a vocabulary around the challenge of being called too early.

We will be talking about this Wednesday, December 27th at 6p PT/9p ET on Twitter at #hpm chat. We hope you will join us!
Additional Info:

• Good short review by the Cicely Saunders Institute on PubMed Commons (PS would love to see more HPM Fellowship Programs make use of this for Journal Club Reviews. Steal this idea!)
• Nice detailed statistical analysis plan for this study published to help prevent bias during the analysis phase. I learned a lot about trial design in reading this.

Christian Sinclair, MD, FAAHPM, is an assistant professor at the University of Kansas Health System, editor-in-chief of Pallimed, and immediate past-president of the American Academy of Hospice and Palliative Medicine. You can find him on Twitter at @ctsinclair. 

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by Christian Sinclair

As a palliative care doctor who works in an outpatient cancer center, I have come to value the time I get to see the patient concurrently with the oncology team. I am able to learn much more about the particular individual case, so I can be more helpful to the patient. But in the long game, the added benefit is a more nuanced understanding of the oncologist-patient relationship. Hearing the language an oncologist speaks to a patient is much different than having an oncologist give me a 45-second summary of that same discussion and medical plan. Yet, I suspect my mere presence (even when non-participatory) changes the nature of these conversations, a la the Hawthorne effect.

Oh, to be a fly on the wall!
Dr. Sarguni Singh from the University of Colorado, Denver is the lead author (working with Dr. Toby Campbell's group out of the University of Wisconsin) performed a study, "Characterizing the Nature of Scan Results Discussions: Insights Into Why Patients Misunderstand Their Prognosis," which was published online early in the Journal of Oncology Practice. (OPEN ACCESS PDF!)

The researchers analyzed recordings of oncologists and patients with stage IIIA, IIIB, or IV non-small cell lung cancer in the outpatient setting. These recordings were from another large study and are over a decade old now. But as the authors pointed out, there is not strong evidence that outpatient communication strategies have changed wholesale in oncology, (although treatment options have changed drastically with the introduction of checkpoint inhibitors, but that's not relevant here.)

The basic info about the visits (time, structure and broad themes) I found the most interesting, and for most clinicians it leads to the strongest behavior changing items. More on that in a minute. The team spent much of the time doing Conversation Analysis (with capital letters), a very involved qualitative research method. A 10-minute conversation may take 10 hours to code as they listen for changes in pitch, volume, tone, pauses and prosody. Prosody, prosody...such a lovely word, you may be thinking, I should know what that means. Prosody, a term which here means pattern and tone to ascribe meaning to a spoken word or phrase.

For those many of you in palliative care who geek out on communication, make sure to read the Appendix, where they explain laudable event proposals, blocking, objectionable projections, appreciation sequences. I will be on the look out for these next week in clinic. Some even emerging from my own vocal cords, because these exist beyond the domain of oncologsts.

The Results
I knew instinctively my clinical conversations were structured, but I had not fully realized it until reading this paper. 77% of the conversations were structured in the following phases:

• symptom-talk (Any cough? How's your breathing?)
• scan-talk (So your labs and scans are back....things looks stable...)
• treatment-talk (I think that chemo has done all it can for you, let's look at something new)
• logistic-talk (You'll need to come in for labs before your first new chemo treatment...)

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1. Moore RA, Wiffen PJ, Derry S, McQuay HJ. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database of Systematic Reviews. 2011, Issue3, Art No.: CD007938. DOI: 10.1002/14651858.CD007938.pub2
2. Micromedex® Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Reuters (Healthcare) Inc. Updated periodically.
3. Moore RA, Straube S, Wiffen PJ, Derry S, McQuay HJ. Pregabalin for acute and chronic pain in adults. Cochrane Database of Systematic Reviews. 2009, Issue 3. Art. No.: CD007076. DOI: 10.1002/14651858.CD007076.pub2. Open Access PDF
4. Wiffen PJ, Derry S, Moore RA, McQuay HJ. Carbamazepine for acute and chronic pain in adults. Cochrane Database of Systematic Reviews.  2011, Issue 1. Art. No.: CD005451. DOI: 10.1002/14651858.CD005451.pub2.
5. Zakrzewska J, Linskey M. Trigeminal Neuralgia. Clinical Evidence. 2009; 3(1207). Retrieved Nov 15, 2011 from http://clinicalevidence.bmj.com/ceweb/conditions/nud/1207/1207.jsp
6. Finnerup NB, et al. Algorithm for neuropathic pain treatment: An evidence based proposal. Pain. 12005; 18:289-305.PMID: 16213659. Open Access PDF
7. Gill D, Derry S, Wiffen PJ, Moore RA. Valproic acid and sodium valproate for neuropathic pain and fibromyalgia in adults.Cochrane Database of Systematic Reviews. 2011, Issue 10. Art. No.: CD009183. DOI: 10.1002/14651858.CD009183.pub2.
8. Kochar DK, et al. Sodium valproate for painful diabetic neuropathy:  A randomized double-blind placebo-controlled study. Quarterly J Med. 2004; 97:33-8. PMID: 14702509 Open Access PDF
9. Finnerup NB, et al. The evidence for pharmacological treatment of neuropathic pain. Pain. 2010; 150: 573-581. PMID: 20705215

Pallimed Case Conference Disclaimer: This post is not intended to substitute good individualized clinical judgement or replace a physician-patient relationship. It is published as a means to illustrate important teaching points in health care.

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You drive down a busy expressway amidst thousands of other vehicles and a billboard jumps out at you.  In the font of confidence, it reads, ""The first step in fighting cancer should be a second opinion."  The billboard informs you of the location of the nearest Cancer Treatment Center of America (CTCA), "only" about 130 miles from the billboard.

When I saw this billboard, my initial response was to recall a recent article about CTCA which challenged their dubious centerpiece claim: Patients with cancer who receive treatment there survive longer than those who don't.  The article pointed out significant selection bias in CTCA's data.  Could individual patients have outcomes comparable to any other cancer center? If the center uses best practices in oncology (including appropriate provision of palliative care), then I have no doubt that some patients have a good experience at the center.  Even though, several patients or their relatives have asked me about the center, none of them have been evaluated or received treatment at CTCA.  At least a few of these patients (or a family member) have gone as far as calling CTCA but haven't gone any further.

Enter a salient point about my practice: I work at a safety net hospital where many patients either have Medicaid or no insurance.  They will never receive care at CTCA for this reason.  But they'll still see the billboards and hear the ads on TV or radio.  Patients in a safety net setting are more likely to present with advanced disease and a poor performance status.  The risks of cancer directed therapy sometimes outweigh the benefits at the time of diagnosis. The likelihood of "early" palliative care referral may increase.  Patients and their families face a double whammy.  You have a terminal cancer and cannot receive any cancer directed therapy.  Without any good way of independently verifying the latter news, how could you not wonder if perhaps CTCA would be a better option? Even though my patients have access to experts from an academic National Cancer Institute center and a full interdisciplinary palliative care team, I cannot fault them for wondering.

I won't debate CTCA's right to not-so-subtly suggest that all cancer care in my city is substandard and once you receive the diagnosis, the only acceptable approach is to make a nauseating three-plus hour car trip to another city, far away from the family, community, and spiritual support which the patient may already have locally.  At the same time, I reserve the right to be irritated.  If a patient asks me about a second opinion, I have several excellent options locally, thank you.  Ranting done, though.  Onto the kernel of opportunity.

An anxious daughter tells you she saw this billboard. She asks if it might be an option for her father who has advanced lung cancer and is hospitalized for hypercalcemia and delirium.  It's time to find a chair for her and yourself if you haven't already.  She trusted you enough to ask you about it.  You can win further trust and more.  How?  Turn it into an opportunity to educate, discuss and explore goals of care.

1. "No stone should be unturned": Acknowledge the desire to look into all possible therapies which may benefit the patient.
2. Ask her what she's found out about the center.  What specifically appeals to her?   Listen for information which provides further clues to how she views the goals of care. Resist the temptation to explain immediately why the approach wouldn't work. Reflect outloud those outcomes which seem most important to her.
3. Ask her to review what she knows about her father's condition and treatment approaches discussed previously by you or your colleagues.  There will likely be questions about why certain cancer directed therapies aren't appropriate for her father.  Make sure to address these questions.  Incorporate your recommendations for how to address the concerns raised in step 2.
4. Invite her to give your opinion on the center.  By now, some patients or family might not even need your opinion, but many still will want it.  Give your opinion- it's OK.  If you're not sure what to make of some of the claims the daughter heard, acknowledge that. If you are confident that you or your colleagues adhere to best practices in oncology care, it's also OK to say that.  While treatment may vary some from center to center, people sometimes assume that there's greater variation than actually exists.  You don't need to belabor the point, though. You're not here to defend yourself, your colleagues, or your institution.  You're here to help a woman who is in normative anticipatory grief.  She's yearning, which CTCA capitalizes on in their advertisements.  Of course, it's normal for her to want her father to receive the best care possible.
5. If the desire for a second opinion remains, offer to help arrange one locally, if appropriate.  If the patient can travel further, you may also mention other options if more appropriate.   I am obviously not suggesting there is no value in second opinions.  Sometimes, the value comes from reassurance that the first provider is "on target" and occasionally, the patient will benefit from a different treatment approach. 
6. If  the patient or family is on the verge of making a trip for a second opinion, help them think through the logistics of travel.
7. Above all, ensure non-abandonment and address emotion.  Even if the patient goes far, far away, you are still likely part of the patient's care team.  How might it be destructive for a patient or family to go to a second opinion and not be sure if the original providers will care for them when they come back?  

Alex Smith recently commented on it at Geripal, rightfully pointing out the paucity of information about palliative care on CTCA's graphically pleasing website.  I single out CTCA here, but they are not alone in the creation of unhealthy skepticism about local care.  I wrote about this topic a few years back.   Be irritated, if you are.  It's justified, in my opinion. Just don't take it out on your patients or their families when they bring up the possibility of a second opinion far, far away.  See it as an opportunity to educate, strengthen relationships, and provide support.  

Photo Credit: "Drought vs Irrigation" by Poizon Myst, licensed under Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.

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I read the ASCO Post when I’m on airplanes.  At least I do, below 10,000 feet… and after I have finished the Sudoku.

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Case:

Ms Emma N. is a 32 year old woman with type 1 diabetes who underwent a living related donor renal transplant and a subsequent pancreas transplant. Unfortunately, both transplants were complicated by rejection and graft failure requiring re-initiation of hemodialysis in 3 years ago. Since that time she has suffered with constant, intractable nausea with multiple episodes of vomiting throughout each day. Her symptoms were initially thought related to diabetic gastroparesis but they did not respond to metoclopramide, erythromycin or pylorus muscle botulinum toxin injections. An electrical gastric stimulator was to be placed but was aborted when a gastric emptying study was normal. Extensive workup, including laboratory studies, endoscopy, CNS imaging and abdominal imaging, was unrevealing. She received little or no benefit from adequate trials of domperidone, prochlorperazine, ondansetron, oral granisetron, promethazine, trimethobenzamide, scopolamine, mirtazapine, dronabinol, pancreatic enzymes and a proton pump inhibitor.

She underwent voluntary admission to a psychiatric hospital for treatment of any possible contributing eating disorder without any improvement. She has had more than 40 admissions to the hospital for nausea and vomiting. A feeding J-tube was placed to maintain adequate nutrition in 2 years ago. She presented to the Palliative Care clinic for further management of her nausea and vomiting. After a complete history and physical, the etiology of her symptoms remained somewhat elusive. She had nausea before her transplant and it had resolved when the kidney was working then recurred when it failed so the final conclusion was that her symptoms may be due to a poorly defined metabolic process related to her renal failure. Olanzapine was initiated on the first visit for refractory nausea and vomiting and the patient was referred to psychology and psychiatry to help with coping and to address underlying depression and anxiety. At the subsequent visit she noted some benefit so the olanzapine dose was increased and a granisetron transdermal patch was added. At the next visit her symptoms had improved dramatically with a clear temporal relation to starting the granisetron patch. She was only vomiting once or twice in the morning and was relatively asymptomatic through the day. In her first clinic visit she had vomited multiple times through the visit and appeared miserable.

At this visit she was asymptomatic, neatly dressed, wearing makeup and was thrilled at this new level of symptom control which was allowing her to re-engage her life.


Discussion: There were many factors that likely contributed to the dramatic improvement in Ms Emma N’s refractory nausea and vomiting. Better psychiatric care through the palliative care psychologist and psychiatrist almost certainly played a role in her overall clinical turn-around. The close attention, serial visits and supportive counseling she received in the Palliative Care clinic could also have been therapeutic. Up-titration of her olanzapine also likely was helpful. Olanzapine is an atypical antipsychotic that works on multiple receptors including dopaminergic, serotonergic, adrenergic, histaminergic and muscarinic receptors. Of particular interest is its antagonism of 5HT2 receptors which are located in the vomiting center and are not well targeted by other traditional antiemetics. Multiple small trials have demonstrated efficacy of olanzapine for chemotherapy-induced nausea and vomiting.¹ Many palliative care practitioners are now also starting to use olanzapine for refractory nausea and vomiting in patients with advanced cancer and other life-limiting conditions.^2-4

Even with all of these possible contributors to her improvement, there still seemed to be a clear benefit that came with initiation of the granisetron patch. While intravenous and oral granisetron have been available for some time, transdermal granisetron (Sancuso© - prescribing insert) is a relatively new addition to the practitioner’s toolbox for difficult to control nausea and vomiting. Transdermal granisetron was approved by the FDA for chemotherapy-induced nausea and vomiting (CINV) in September of 2008 based largely on a trial of 582 patients receiving multi-day moderately or highly emetogenic chemotherapy. Patients received either oral or transdermal granisetron and achieved equally good control of their symptoms with either method (approximately 60% in each group achieving complete symptom control). The most common side effect in both groups was constipation.⁵ The patch is an 8x6cm clear, plastic-backed patch and is worn for 7 days. Pharmacokinectic studies suggest that the patch delivers a dose equivalent to 2 mg of oral granisetron each day it is worn.⁶

It is thought to exert its antiemetic effect through antagonism of 5HT3 receptors in the gut and chemoreceptor trigger zone.⁷ Experience with the patch outside of CINV, however, is limited. This case suggests that transdermal granisetron may have a role in other cases of refractory nausea and vomiting. It is unclear why the transdermal form of the drug worked so much better than the oral version in this case. It could reflect absorption issues, especially if she was unable to keep the pills down. It could also reflect compliance issues and may bring into question the adequacy of her prior trial of oral granisetron. Whatever the mechanism, however, the result was dramatic. Further study of this agent in settings other than CINV is clearly needed. Hopefully these results can be replicated and other patients with difficult-to-control nausea and vomiting can achieve life-changing results similar to those achieved by this case.

References:
1. Navari RM, Einhorn LH, Loehrer PJ Sr, Passik SD, Vinson J, McClean J, Chowhan N, Hanna NH; Johnson CS (2007). A phase II trial of olanzapine, dexamethasone, and palonosetron for the prevention of chemotherapy-induced nausea and vomiting: a Hoosier oncology group study. Supportive Care in Cancer, 15 (11), 1285-91 PMID: 17375339

2.  Srivastava M, Brito-Dellan N, Davis MP, Leach M, Lagman R (2003). Olanzapine as an antiemetic in refractory nausea and vomiting in advanced cancer. Journal of Pain and Symptom Management, 25 (6), 578-82 PMID: 12782438

3.  Jackson WC, Tavernier L (2003). Olanzapine for intractable nausea in palliative care patients. Journal of Palliative Medicine, 6 (2), 251-5 PMID: 12854942

4.  Passik SD, Lundberg J, Kirsh KL, Theobald D, Donaghy K, Holtsclaw E, Cooper M, Dugan W (2002). A pilot exploration of the antiemetic activity of olanzapine for the relief of nausea in patients with advanced cancer and pain. Journal of Pain and Symptom Management, 23 (6), 526-32 PMID: 12067777

5.  Boccia RV, Gordan LN, Clark G, Howell JD, Grunberg SM, on behalf of the Sancuso Study Group (2010). Efficacy and tolerability of transdermal granisetron for the control of chemotherapy-induced nausea and vomiting associated with moderately and highly emetogenic multi-day chemotherapy: a randomized, double-blind, phase III study. Supportive Care in Cancer PMID: 20835873 - Open Access PDF

6.  Howell J, Smeets J, Drenth HJ, Gill D (2009). Pharmacokinetics of a granisetron transdermal system for the treatment of chemotherapy-induced nausea and vomiting. Journal of Oncology Pharmacy Practice, 15 (4), 223-31 PMID: 19304880

7. Wood, G., Shega, J., Lynch, B., Von Roenn, J. (2007). Management of Intractable Nausea and Vomiting in Patients at the End of Life: "I Was Feeling Nauseous All of the Time . . . Nothing Was Working" JAMA: The Journal of the American Medical Association, 298 (10), 1196-1207 DOI: 10.1001/jama.298.10.1196




Pallimed Case Conference Disclaimer: This post is not intended to substitue good individualized clinical judgement or replace a physician-patient relationship. It is published as a means to illustrate important teaching points in health care.