Wednesday, March 25, 2015

Shared Decision Making, Cancer Risk Assessment, and The Doctor- Patient Relationship

Welcome to my world as a practicing physician. Here is your chance to learn of the secret sacrifices we doctors make in the inner sanctum of the temple of Evidence Based Based Medicine. 

The "joys" of mandated guideline-driven shared medical decision making come to life in a one act play.

Below Dr Kildare will welcome you to his world that we doctors and patients will increasingly inhabit as we worship at the altar of evidence based, cost effective care.

This article is about lung cancer, but the issues it raises apply to all healthcare including CLL: arbitrary guidelines, lies to game the system, the intrusiveness of the computer and electronic medical record, the farce that is "mandated" shared decision making, and the general loss of intimacy and trust in the patient-doctor relation as big government and big insurance and big medicine play a more and more invasive role in the clinic and hospital.

I am no Luddite.

I celebrate the use of technology and big data. I look at cost effectiveness when sharing decisions with my patients (or with my doctors when I am the patient), but we need to remember the human connection and to pay attention to the needs of the real person in front of us and not to some statistical metric.

This is a good read:

Here is the link and below I simply cut and pasted the text.

Thank you Dr. Grannis for feeling our pain. …

A Lung Cancer Screening “Shared Decision-Making” Session

Frederic W. Grannis, Jr, MD



PATIENTa patient named Hiram Wrisque
It is the near future. As the lights come up, a young physician, DR. KILDARE, is seated behind a desk working at a computer in consultation room. For dramatic emphasis, he is dressed in the white smock, pants, and shoes worn by interns during the mid-20th century. A stethoscope is draped over his shoulders.
There is a knock on the door.
DR. KILDARE. Come in.
The office door opens and PATIENT enters, stage left.
PATIENT. Good morning, Dr. Kildare.
DR. KILDARE. Please sit down, sir. For the record, what is your name and date of birth?
PATIENT. I am Hiram Wrisque. I have been a patient in this medical practice for almost 50 years; a patient of your granddaddy’s until his passing. I am not sure why this visit has been scheduled? I requested to be screened for lung cancer 3 months ago.
DR. KILDARE. Well, Mr. Wrisque…
PATIENT (interrupting). Mr. Wrisque was my daddy; please call me Hy.
DR. KILDARE. All right, Hy it is. We have scheduled this doctor–patient shared decision-making discussion because it is mandated in the Centers for Medicare and Medicaid Services—we call it CMS for short—decision of February 2015 for all patients who ask their doctors to order a screening CT scan.[1]
PATIENT. Seems like a waste of time, I have done a lot of reading on the subject, and given it a lot of thought. But if we must, then let’s get on with it.
DR. KILDARE. First thing is that we need to enter your eligibility information into this computer database. What is your age?
PATIENT. I am 65 years old.
DR. KILDARE types laboriously into his computer.
PATIENT (impatient). Look, doc, I have to get my wife to her chemotherapy, so why don’t you take this sheet of information I have prepared for you, and you can have your secretary type it into the computer later. That way you can make eye contact with me instead of that computer screen. Let me sum up what it says it for you.
First thing, I smoked two packs a day for 40 years, starting at age 10. I quit 15 years ago today, when your granddaddy convinced me that my bullous emphysema and COPD were caused by smoking, and that I was at high risk of lung cancer. I have worked since high school at the nuclear power plant maintaining the asbestos insulation. Mom and dad and my older sis all died of lung cancer. My own lung cancer was resected 7 years ago and the laryngeal cancer was radiated 6 years ago. They tell me there is no evidence of recurrence of either and that I am probably cured of both. I had pneumonia twice in the past 2 years. Almost forgot to mention that I had lots of exposure to second-hand smoke as well.
I am in otherwise good health and can even play two sets of doubles tennis a couple times a week.
DR. KILDARE. Thank you for organizing that risk information for me. It is very helpful and makes it clear to me that I must recommend that you are not a good candidate for screening.
DR. KILDARE. Yes, although you have a number of risk factors, Hy, you don’t meet the Medicare criteria for insurance coverage because you quit smoking 15 years ago.
PATIENT. Well first thing, doc, I asked to be screened 3 months ago, and it took all of this time to get the appointment.
DR. KILDARE (defensive). I am a very busy man and couldn’t get you in earlier.
PATIENT (exasperated). I have just about every risk factor for lung cancer imaginable and very clearly have a high risk of dying of lung cancer and yet you are telling me that I can’t be screened? That’s just plain nuts.
DR. KILDARE (irritated that this discussion is taking longer than anticipated). Here, Mr. Wrisque—sorry, Hy. I would like you to read this copy of an article from Chest by an eminent physician at Memorial Sloan Kettering named Dr. Peter Bach, who also wrote the guideline on lung cancer screening for the American College of Chest Physicians.[2] He explains how you don’t meet the criteria used in the National Lung Screening Trial and that it would be irresponsible to screen you without good evidence.[3]
PATIENT (cutting in). I told you I have read a lot on the subject. I read this article, and it makes no sense to me. Dr. Bach says elsewhere that if I get screened with CT scans and they find a lung cancer, that I have only a one out of five—20%—chance of survival,[4] but all studies, including the National Lung Screening Trial and International Early Lung Cancer Action Program show that the chance of survival with cancers detected by CT screening at 5 and even 10 years and beyond is between 60% to 90%.
DR. KILDARE. Hy, you need to leave this up to the experts.
PATIENT. Don’t be condescending with me, Sonny! I even went to the Web site at Memorial Hospital in New York and entered my personal information into their lung cancer risk calculator—I am told it was written by Dr. Bach himself. It told me that my risk of lung cancer is very high, that I have a 4% chance—that’s one out of twenty-five risk—of getting lung cancer in the next 6 years![5]
What’s more, this calculator didn’t ask if I had a previous cancer caused by cigarettes. Why, Dr. Bach himself has published data that indicates that because I had lung and laryngeal cancers in the past that my risk of lung cancer is at least 20%.[6]
DR. KILDARE (now flustered). Yes, all of that may be true, but since you had the good sense to quit smoking 15 years ago, your risk is now lower.
PATIENT. I understand that, but it’s still high enough that I am greatly concerned for my future. An article I read by Dr. Robert McKenna in Los Angeles, perhaps the busiest lung cancer surgeon in the country, informs me that more than half of the ex-smokers he operates on for lung cancer had quit more than 15 years earlier.[7]
DR. KILDARE. I am sorry that you are disappointed, Hy, but the Medicare rules are very clear.
PATIENT: This shared decision-making sure seems to happen on a one-way street.
DR. KILDARE. I suppose that you could pay for the CT out of pocket.
PATIENT. Look, doc, I am retired on a fixed income and have a lot of expenses for my wife’s medical care. It just isn’t possible for me to pay for screening. What’s more, it isn’t fair to put me in this bind when people with much lower risk will be covered by CMS or private insurance. On top of that, I asked at the hospital and they told me they can’t screen me without your say-so or they might lose their status as an expert center.
DR. KILDARE (whispering). You didn’t hear this from me, Hy, but if you, let’s say, revise your time estimate (he winks) on how long ago you quit, you would be eligible.
PATIENT. You mean if I lie to you. Sorry, but that’s not the way I was raised.
DR. KILDARE (worried). I was certainly not advising you to lie. That would not be ethical on my part.
PATIENT. But it is ethical for Medicare and Medicaid to ration access to a test that can save me and other people like me from suffering and premature death?
DR. KILDARE. Well, Hy, we seem to have reached an impasse, and I certainly don’t see this as rationing healthcare. I see no point in continuing this discussion further.
PATIENT reaches into his shirt pocket and takes out a pack, a brand recognizable by its prominent red logo, strips off the cellophane covering, opens the flip-top box and extracts a filtered cigarette.
OK, doc, you leave me with no alternative.
DR. KILDARE (agitated). Wait…what are you doing? You can’t do that here; it is against the law. Put out that match immediately or I will have to ask you to leave my office.
PATIENT (blowing a smoke ring from the cigarette he has just lit). I had no other choice, Sonny. Now that I am a current smoker again, I meet the damned Medicare criteria, so please just tell your computer to arrange for my screening CT scan ASAP. Now I have to be going. You have yourself a nice day.
DR. KILDARE shrugs resignedly and begins slowly typing the order into his computer as Hiram Wrisque exits stage left


1. Proposed Decision Memo for Screening for Lung Cancer with Low Dose Computed Tomography (LDCT) (CAG-00439N). Accessed January 14, 2015. (Scenario assumes that Final CMS decision of February 2015 will be substantially unaltered.)
2. Detterbeck FC, Mazzone PJ, Naidich DP, Bach PB. Screening for lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143(5 Suppl):e78S-92S.
3. Mazzone P, Powell CA, Arenberg D, et al. Components Necessary for High Quality Lung Cancer Screening: American College of Chest Physicians and American Thoracic Society Policy Statement. Chest. 2014 Oct 30. [Epub ahead of print]
4. Bach PB, Gould MK. When the average applies to no one: personalized decision making about potential benefits of lung cancer screening. Ann Intern Med.2012;157:571-3.
5. Memorial Sloan Kettering Cancer Center: Lung Cancer Screening Decision Tool. Accessed January 14, 2015.
6. Lou F, Huang J, Sima CS, et al. Patterns of recurrence and second primary lung cancer in early-stage lung cancer survivors followed with routine computed tomography surveillance. J Thorac Cardiovasc Surg. 2013;145:75-81
7. Mong C, Garon EB, Fuller C, et al. High prevalence of lung cancer in a surgical cohort of lung cancer patients a decade after smoking cessation. J Cardiothorac Surg. 2011;6:19.
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Monday, March 23, 2015

Experience with Idelalisib (Zydelig) in CLL (chronic lymphocytic leukemia)? A chance to can help fellow patients in Canada.

I received this email today with a link to a survey for those of us who have had experience with idelalisib. It is a chance to help our fellow patients with CLL in Canada. 
The email speaks for itself. Please help if you can.
Hello Dr. Koffman,
My name is Elizabeth Lye and I am the Scientific Advisor with Lymphoma Canada. I am reaching out to you to see if you can help put us in touch with patients who may have experience with idelalisib (Zydelig) for CLL. This treatment is not currently available in Canada and Lymphoma Canada is working to help Canadians gain access to this treatment. 
If you are not familiar already, the pan-Canadian Oncology Drug Review (pCODR) makes recommendations to the provinces and territories to help them decide whether they will provide funding for new cancer drugs in Canada. Understanding the experiences of patients is a key element in the pCODR review process and pCODR allows patient groups to do this through "patient submissions".

In order for Lymphoma Canada to have a strong submission, we really need to have patients who have direct experience with idelalisib (Zydelig) to complete an online survey or to participate in an interview with one of our staff. To ensure patient privacy and confidentiality, individual responses will not be identifiable.
I am writing to see if you would be able to help us find patients to participate in our survey.  Given that not a lot of people in Canada have had experience with idelalisib, we are seeking input from patients internationally to complete our survey to support our government submission. 

Would it be possible to post the link to the survey on any of the patient forums you post to? Or perhaps you have some other ideas that may help us locate patients who have experience with idelalisib (Zydelig) for CLL.

As always, the timelines are very tight. The closing date for the surveys is April 7th. The link to the survey is:

Thank you in advance for your consideration of our request.

Kind regards,


image010Elizabeth Lye
Scientific Advisor
Lymphoma Canada
7111 Syntex Dr., Suite 351, Mississauga
ON, L5N 8C3
Phone 905.822.5135 x 3
Toll-Free 1-866-659-5556


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Sunday, March 15, 2015

ESH 2014: Dr. Cathy Wu Explains TUMOR HETEROGENEITY and CLONAL EVOLUTION in CLL (Chronic Lymphocytic Leukemia)

This is taken from the first of a two part interview with Dr. Cathy Wu in Greece where I spoke on the patients' perspective at a meeting of the Greek Hematology Professional Congress.

It is also a teaser of what is to come in the new website of the nonprofit The CLL Society. That CLL specific education and support site should launch in the next few weeks. It will offer much deeper and broader information and be more searchable than is possible with a blog. 

Be assured that my blog is not going away but may revert back to more of a personal blog and the place where I continue to host my candid and occasionally combative opinions and commentaries. 

Truth is that the plethora of news and emerging therapies in CLL have outgrown the capacity of my time linear blog to keep up. This new format also will offer the chances to hear other patient voices in what will be the only patient driven physician curated place on the web for CLL support and education.

I and the team of fellow volunteers are pretty excited. It's been a ton of work, but our mission is to address the unmet needs of the CLL community and we believe this new website will be a helpful piece of that effort. There is great information out there and we want to help everyone find it and explain it in our soon to be born strong and friendly CLL focused website.

Honestly, my efforts to help launch our nonprofit 510c3 and its website has consumed me, leaving less time to post here.

While we are still building phase 1 of the new website, I plan to continue to post news and interviews like this one here modified for this blog. The website will offer more links, a glossary, some surprise, and a whole lot more.

Stay tune, but I digress.

This clonal heterogeneity discussion is very important stuff on how our cancer evolves and what it means when we consider therapies.


·     Cancer by its nature is genomically unstable.
·     Over time it acquires more mutations.
·     New clones and sub-clones can arise over time.
·     Therapy can influence the balance and evolution of the clonal and sub-clonal populations.
·     Those changes may have significant implications for how to best manage our cancer.


Hematology in general and CLL specifically are full of jargon and acronyms that can be both overwhelming and daunting.  With time and experience, you'll become familiar with the terminology and acronyms.  We will try to explain each medical term the first time it appears in an article, but we will use the true terminology so that you gain comfort and familiarity with the medical terms that you will see in your lab reports and in medical articles. We will also provide a glossary for your reference.


Dr. Cathy Wu out of Dana-Farber starts at the basics.

In the first of our two part interview from the International Conference on New Concepts in B Cell Malignancies: From molecular pathogenesis to personalized treatment in Greece in November 2014 she reminds us that while the concept that any cancer is made of multiple populations of different cells dates back to the 70s, it is our recent ability to look deeply and quickly at the genome with next generation genetic sequencing that has really cracked open our understanding of how huge a factor this is in one’s particular CLL aggressiveness and its ability to become resistance to therapy.

We now know that questions about the presence or absence of a good or bad prognostic indicator often should not be answered with a simple yes or no.

More importantly we know that our population of our cancer cells evolves over time. Hence the need to repeat FISH and other tests when the contemplating therapy.

An analogy: In most good movies the lead protagonist has an arc to his or her character. We see how he or she changes and evolves in response to the support received or the challenges faced.

So too it is with our cancer. Unfortunately CLL is much more like a movie than a snapshot. Dr. Wu explains our cancer may evolve over time in response to therapy and other selection pressures.

Please enjoy our video interview with Dr. Cathy Wu.

If you want to dig deep, take a look at this Blood Journal abstract or this abstract from ASH 2014 or this older full text from the Journal of Clinical Oncology or this on the evolution of resistance to BTK inhibitors such as ibrutinib as just a few of the many examples of the explosion of research in this field.

Our understanding of this complicated concept is itself evolving.

I believe it is critical research with enormous implications for how we should treat our cancer. 

More to come.

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Friday, March 13, 2015

The Kindness of Strangers: Getting my IVIG to Control my CLL (chronic lymphocytic leukemia) induced ITP

" I have always depended on the kindness of strangers."

Blanche DuBois from A Streetcar Named Desire

As did Blanche,  I too have depended on the kindness of strangers.

For the last nine years, every few weeks I show up at the cancer infusion center to sit for hours to receive intravenous immune globulin or IVIG. Recently I have stretched the interval between IVs to 7 weeks. 

By mechanisms that are not fully understood, it blocks my stupid auto-immune antibodies from attacking my own platelets that in the past has lead to multiple hospitalizations and fearful encounters with my own mortality when my platelet counts crashed and I was at risk for major bleeds. Thankfully, that is all behind me now.

I  have gradually and cautiously been able to taper off all the other meds for my ITP (immune thrombocytopenia) and my platelets have not fallen. 

Perhaps my ibrutinib helps turn off my auto-immune triggers. As seen in this recent post there is good reason to be hopeful. There are case reports of ACP-196, another promising BTK inhibitor helping too.

Perhaps I no longer need the IVIG, but I am not brave enough to stop it to find out. ITP is scary.

There is another reason not to quit.

My infusion 7 or 8 x year may also protect me from all sorts of infections. And that is important in my work as a doctor and in my fun as a grandfather where I exposed to lots of germs.

Due to the recent measles scare, all the doctors at the hospital where I work were ordered to have blood work to confirm their immunity. I objected for several reasons:
  1. I had had measles as a child
  2. Due to my CLL, I couldn't take the live vaccine even if my test came back negative.
  3. My antibody levels are not my own.
This last one is because of the IVIG that I receive. It is a pooled blood product from 1000s of strangers and by definition contains their antibodies against everything they have either had or been vaccinated against.

No wonder I was immune to everything that I was tested for.

But am I really?

Truth is that it's not me. It is the kindness of strangers' blood that is protecting me. It is known as "passive" immunity as I played no role in forming the antibodies. When the IVIG disappears as measured by the IGG level in my blood dropping after a few weeks as it must, my immunity fades too. IVIG does not boost IGA or IGM, two other important antibody classes, only IGG. 

Compare this to a vaccination where we attempt to mount an "active" immune response that is remembered and always ready to respond. Sadly in CLL, this is usually a barren effort. Flu shots and  other immunizations don't usually work well for us. And we must never risk getting a live vaccine as it might run amok in our bodies due to out immune-incompetence. We are notoriously lousy at making healthy antibodies.

So while I take my IVIG to protect my platelets, it is clearly helping me in other ways.

Thank you kind strangers. Your generous gift of your own blood has touched so many lives that you will never know.

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Saturday, March 7, 2015

ITP In CLL (Chronic Lymphocytic Leukemia): Personal And Clinical Reflections

Another great discussion courtesy of ONCLIVE with 4 top CLL experts, from left to right: Drs. Byrd, Furman, Ma, and Kipps.

This time they discuss immune thrombocytopenia (immune mediated low platelet count) or ITP.

ITP is where our immune system attacks our platelets. Just our luck, our wimpy inadequate immune system that can't alway respond to an infection or a vaccine or a secondary cancer, whips into high gear to attack its own cells.

In extreme cases it can lead to live threatening bleeding. It is well recognized complication of CLL occurring in < 5% of us, but as the doctors imply, I suspect many mild cases go unrecognized.

When the same process attacks our red blood cells, sometime leading to a dangerous anemia, it is called AIHA for the auto-immune hemolytic anemia. ITP is the platelet version of the same issue. Attacks on the neutrophils and multiple blood cells lineages also occur, but are more rare.

ITP is a subject near and dear to my heart.

About one year after my diagnosis with CLL, I remember being on call for my medical group and waking to the phone in the middle of the night. It was my exchange. I had asked my family doctor to order a CBC that morning because I had noticed some easy bruising and petechiae (tiny red dots caused by small hemorrhages often associated with low platelets) on my legs.

MEDICAL EXCHANGE: Dr. Koffman please.

ME: Yes. It's me.

MEDICAL EXCHANGE: We have a critical lab result ........ on Brian Koffman. A platelet count on 9.

ME: Thanks. I will definitely follow-up on this.

And I did. It was 6 they next morning and I was hospitalized for IVIG and steroids. It bounced up in 48 hours but because of my recurrently dangerously low platelets I would go on to five emergency admissions in the next year,  multiple outpatient infusions, and an urgent laparoscopic splenectomy where I lost half my blood. I failed steroids, rituximab, IVIG, cyclosporin and the splenectomy.

What finally worked post splenectomy was a combination of cyclosporin (an immune suppressing drug used today mostly to prevent rejection of kidney and other transplants) and rituximab that was recommended by Dr. Byrd. The combo's effects were nothing short of amazing, especially  considering that both drugs on their own had had no benefit in raising my counts. On the combo my platelets climbed from single digits to above normal (not uncommon when you have no spleen).

And the combination of cyclosporin and rituximab had the surprising and joyous bonus of reducing my bone marrow involvement with CLL down from 90% to 3%.

There are some case reports in the medical literature of cyclosporin having antileukemic activity, but it generally avoided due to the fact we are already immune suppressed and it can cause significant problems including renal disease, hypertension and aggressive gout.

It was my dangerous and refractory ITP more than my CLL that drove me to a first remission transplant.

That didn't work either, and my ITP was back one year post HSCT.

That were difficult times.

Despite the risks and side effects, it was only about none months ago, after almost two years on ibrutinib and with years of normal platelet counts under my belt, that I finally had the courage to taper off my cyclosporin. I feel it had helped save my life and I worried about stopping it.

But I did and I have done great since.

A few comments from one who's been there and done that. Yes, I know that one case is not data, but it can be a cautionary and instructive tale.

For obvious reason and because it is part of some of the guidelines, I would ask the doctors in the panel to add cyclosporin to their list of second line options for ITP. I would certainly use it well before the extremely immune suppressive alemtuzumab (CAMPATH) that knocks out both T and B cells for a very long time or splenic radiation that has a host of short and long term complications.

I would also remind us all that the surgery does not always go well, though laparoscopic is clearly the way to go. The research tells us that the best predictor of outcome is the experience of the surgeon. Though it didn't work for me, I have no regrets about my surgery.

I would also ask my colleagues to comment on just how difficult it can be to get us off steroids and not have the ITP return.

The data on ibrutinib is encouraging and makes sense from a biological point of view, but it is not 100% effective.

Overall, a very helpful and well considered discussion on a very important and scary topic. As we might expect, while there is much consensus, there is significant polite disagreement on how to proceed.

It is such a blessing to not have to live in fear of what my weekly or twice weekly blood test would reveal.  Showing up at the lab,  not  knowing whether I was OK or I was headed to the hospital.

That's all in my distant past now.

Still, as all of us with cancer know, we are always looking over our shoulder, wary of the return of our past tormentors,

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