Radiation Doses- What to Worry about and What to Shrug Off when we have CLL (chronic lymphocytic leukemia)

No amount of radiation is good for us. Ionizing radiation damages DNA and increases cancer risk. No question about it. 

So avoid x-rays unless they are truly needed. Even more so for CT scans, that are rarely indicated for CLL under most normal circumstances. 

We have reviewed our increased cancer risk in prior posts when we have multiple CT scans. And Wayne Wells has written this extensive review for the CLL Society on our website. Here is a link to an article I wrote titled "The Risk Of Secondary Cancer Associated With > 8 CT Scans In Patients With NHL (Non Hodgkins Lymphoma)" Remember CLL is a type of NHL.

But what about the risk from a minor dental films or an x-ray of an extremity?  When should we worry?

My dentist has been bugging me for years to have some x-rays, and I finally said yes after he provided me with this sheet that compares a dental x-ray to a CT scan to Chernobyl. 

It gets complicated, but the bottom line is that what this chart is basically tells us is that if the x-ray machines are properly calibrated, and are used properly, and are functioning normally, we don't need to sweat the small stuff when it comes to getting imaging. Also with dental films, miscalibration, should it occur is less likely to be a big deal than it is with CT scans.

This chart is from my dentist. Click on it to expand it. Lots of good information so it is worth the squinting. Apologies for the small text.

One tiny blue box equal 0.5 μSV and that is roughly equivalent to the radiation exposure from eating 1/2 a banana. Pretty low risk. The sugar is probably more dangerous.

The unit SV or Sievert is a measure of the health effects of exposure to low dose radiation. The sievert represents the equivalent biological effect of the deposit of a joule of radiation energy or 1 gray or Gy in a kilogram of human tissue. μSV is 1 millionth (micro SV) of a Sievert. 

A chest x-ray is equal to 1 green box or 20 μSV. In the chart, there are 400 blue boxes in every green box. Next there are 500 blue boxes for each one orange box that is equivalent to 10 mSv or ten 1/thousandth of an SV or ten milli-SV. For reference 1 mSv is the average accumulated background radiation dose to an individual for 1 year, exclusive of radon, in the United States. 1 mSv is the dose produced by exposure to 1 milligray (mG) of radiation. 5000 - 8000 mG is exposure dose that kills about half of us, known as the LD50 though the damage is dependent on many factors including duration of exposure.

100 orange boxes equals one yellow box of 1 SV.  Remember that 5-8 SV  is a likely fatal dose. Ten minutes exposure next to the Chernobyl core after meltdown resulted in 50 SV, 6-10 times the usual killing dose.

Life is full of risks, but a dental x-ray is not one to worry about.

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.

http://www.cancernetwork.com/blog/lung-cancer-screening-shared-decision-making-session?GUID=4DA9CFB5-590D-4180-AC65-4071506DC6BF&XGUID&rememberme=1&ts=23012015 …

A Lung Cancer Screening “Shared Decision-Making” Session

Blog | January 16, 2015 | Screening, Lung Cancer

By Frederic W. Grannis, Jr, MD

Frederic W. Grannis, Jr, MD

A ONE-ACT PLAY

DRAMATIS PERSONAE

DR. KILDARE, a private practitioner of medicine named Sonny Kildare

PATIENT, a 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 a 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.

PATIENT. What?

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. 

REFERENCES

1. Proposed Decision Memo for Screening for Lung Cancer with Low Dose Computed Tomography (LDCT) (CAG-00439N). http://www.cms.gov/medicare-coverage-database/details/nca-proposed-decision-memo.aspx?NCAId=274. 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. http://nomograms.mskcc.org/Lung/Screening.aspx. 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.

- See more at: http://www.cancernetwork.com/blog/lung-cancer-screening-shared-decision-making-session?GUID=4DA9CFB5-590D-4180-AC65-4071506DC6BF&XGUID&rememberme=1&ts=23012015#sthash.sHKKeEg2.dpuf

ASCO 2013 Abstract: ABT-199 in Relapsed and Refractory CLL Patients

I have posted before on ABT-199. I like this drug because it works. And it is a pill, not an IV.

It is clearly a very potent therapy.

We know that not just from the impressive 85% response rates, even for those difficult to treat 17p del and F refractory patients where an amazing 88% and 75% respectively achieved at least a partial response (PR), but we also know it from its dark's side, namely tumor lysis syndrome (TLS).

Until the dosing was adjusted after the first cohort, the first three patients all had TLS, a life threatening complication (and one die did in this trial) from the massive killing of the cancer overloading the liver and especially the kidneys' ability to prevent all that toxic waste from cell death from building up to dangerous levels.

We need to move carefully, but I am glad that ABT-199 is back in trial after the studies were suspended due to deaths from TLS.

The present approved options for F-refractory and 17p deleted patients are severely limited and these results are very promising.

Complete responses (CR) are only 13%, but that's not bad for any mono therapy, especially in these tough patients.

Our future depends on the researchers taming both the disease and the drugs that we use to treat it.

We also need to constantly recognize the sacrifice of those who bravely jumped into this "first-in-human" phase 1 trials. CLL is not for wimps.

The question I am asking myself is will ABT-199 offer enough of a therapeutic potency edge over the other novel oral therapies such as the gentler inhibitors of BTK and PI3K∂ that will justify its risks and earn a place in our therapeutic arsenal.

Or will its risks become acceptably manageable? Whatever that means.

Still is nice to have more viable choice options for those of us with bad disease.

I hope it move forward. I imagine a time that we will take a cocktail of oral pathway blockers to completely slay our dragon, much as is done today with HIV. Blocking BCL-2 is part of that vision.

Here is the abstract.

Updated results of a phase I first-in-human study of the BCL-2 inhibitor ABT-199 (GDC-0199) in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL).
John Francis Seymour, Matthew Steven Davids, John M. Pagel, Brad S. Kahl, William G. Wierda, Thomas P. Miller, John F. Gerecitano, Thomas J. Kipps, Mary Ann Anderson, David C.S. Huang, David E. Darden, Lori A. Gressick, Cathy E. Nolan, Jianning Yang, Todd A. Busman, Alison M. Graham, Elisa Cerri, Sari H. Enschede, Rod A. Humerickhouse, Andrew Warwick Roberts; Peter MacCallum Cancer Center, Melbourne, Australia; Dana-Farber Cancer Institute, Boston, MA; Fred Hutchinson Cancer Research Center, Seattle, WA; University of Wisconsin Carbone Cancer Center, Madison, WI; The University of Texas MD Anderson Cancer Center, Houston, TX; University of Arizona Cancer Center, Tucson, AZ; Memorial Sloan-Kettering Cancer Center, New York, NY; UC San Diego Moores Cancer Center, La Jolla, CA; Royal Melbourne Hospital; Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; AbbVie, Inc, North Chicago, IL; Royal Melbourne Hospital, Melbourne, Australia
Background: Targeting BCL-2 is a promising strategy for treating CLL, including disease refractory to fludarabine (F), or with (del(17p). ABT-199 is a selective BCL-2 inhibitor with >500-fold higher affinity for BCL-2 (Ki< 0.10 nM) than for BCL-XL (Ki = 48 nM). Methods: Objectives of this Ph I dose-escalation study include evaluations of safety, pharmacokinetics and preliminary efficacy of ABT-199 in patients (pts) with R/R CLL. A single oral dose was given followed by 6 days off drug, before continuous once daily dosing. After cohort 1, the initial dose was reduced and daily dosing modified to include a 2 or 3 step dose-escalation to the target dose for each cohort. Results: As of January 11, 2013, 56 pts have been enrolled; median age 67 y (range 36-86); 41 males; median 3.5 prior therapies (range 1-10). 16 (29%) had del(17p) and 18 (32%) F-refractory CLL. Median follow up is 6.3 months (range 0.03-16.5); 7 pts have been on study for more than 1 yr. 13 pts discontinued; 7 due to PD, 6 for other reasons: tumor lysis syndrome (TLS; 2), other illness (2), thromboembolic event (1), consent withdrawal (1). The most common non-hematological AEs (>15% pts) were nausea (36%), diarrhea (30%), fatigue (25%), upper respiratory tract infection (23%), and cough (16%). Grade 3/4 AEs occurring in > 5 pts were neutropenia 21(38%), thrombocytopenia 6 (11%) and TLS 5 (9%). TLS occurred in 3/3 pts in cohort 1 and 2/53 pts with the modified stepped dosing schedule (DLTs). Additionally, 1 fatal AE occurred within 48 hrs of dose- escalation to 1200 mg in a pt with laboratory evidence of TLS (DLT). 46 of 54 pts (85%) evaluable for efficacy achieved a response to ABT-199; 7 (13%) a CR or CR with incomplete count recovery and 39 (72%) a PR (30 confirmed by consecutive scans). 14/16 (88%) and 12/16 (75%) of pts with del(17p) and F-refractory CLL, respectively, achieved at least a PR. Conclusions: ABT-199 is highly active achieving a 85% overall response rate in R/R CLL, independent of high risk markers such as del(17p) and F-refractory disease. Additional dosing and scheduling modifications are currently being explored to minimize the risk of TLS. Clinical trial information: NCT01328626. 

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Dr. Richard Furman on Surprising Early Trial Results for Ibrutinib

We were all surprised, pleasantly surprised.

Dr. Furman did the first phase 1 study on ibrutinib. I remember him mentioning this trial to me years ago and it seemed to me such a long shot.

Not any more.

Thanks to those who had the courage to try something new. They were the real pioneers. We who are in the phase 2 and 3 trials are all in their debt.

And those who are eventually prescribed this drug or GS-1101 or others should look kindly on those of us who earlier make the decision, took a much lesser but still significant risk and entered a phase 2 or 3 trials.

Part 2 Is there a doctor on the plane?

It has too busy with travel and treatment and lectures and the Stanley Cup Finals (GO KINGS GO) to blog. I should be able to catch up more with lots of good news about me and ibrutinib from rainy Orlando real soon


But first when I last left you, I was walking to the back of the plane to see who needed medical attention.


To see if I could help?


To see if was putting myself at risk/


What I found in the last  row was a man in his early 50s acutely short of breath with an oxygen mask on, very afraid for his life.


Less than a minute after arrived, t was being asked should we divert  the plane to Las Vegas. (What power. I should have said that Hawaii was a better choice).


I took a brief medical history. Turns out my patient suffered from chronic inflammatory demyelinating polyneuropathy (CIDP). I had had one patient with that rare disorder years ago. It is a bit like MS in that the sufferers develop an auto-immunity against their own myelin sheaths so the nerves, especially the motor nerves getting weaker and weaker. If CIDP involves the respiratory muscles, life threatening shortness of breath is a rare but real possibility. Pneumonia can also occurs with a decrease cough reflex.


He denied chest pain. No calf swelling or tenderness. No cough or fever. No new new meds or foods. No history of asthma or severe allergic reactions. No other major medical issues.


I used the emergency stethoscope that the steward provided. I could hear no air moving in and out. A very very bad sign. Then I listen to the heart. Again I heard nothing. But my patient had a normal pulse.  And he was not turning blue or had any altered mentation. In fact there was none of the classic signs of respiratory distress- nasal flaring, using accessory muscles, tracheal tugging. Maybe the CIDP was obscuring them? I retrieved my own stethoscope from my seat. Still nothing. Then I listen to my own heart. Nothing. The problem of course was the volume of the ambient noise, not that my patient had no air entry into the lungs and that his heart had ceased beating. I didn't asked if they could turn the engines off for a few minutes so I could listen in the quiet, but the thought did cross my mind for a moment.


He had an infusion of IVIG the day before and was worried about the effect of flying so soon afterward. Now I have great personal familiarity with flying right after IVIG. I have done it dozens of time without a blink or blip. I plan my long foreign trips around my IVIG and try to get it just before I leave for  exotic lands. He was very reassured by this.
.
We chatted more. He was able to talk without gasping or halting. He was felling better, less air hungry. We walked up to first class. His gait was weak and his hands shaky. CPID has devastated his muscles.


No need to divert the plane.


We talked about his family, my leukemia, his treatment. The oxygen mask came off. He was smiling, relaxed, feeling OK again. I gave him my contact information.


His panic attack was over. I still had the paramedics meet the plane and take over his care. After all I had yet to really auscultate his lungs. I could have missed a pulmonary embolism or a cardiac issue or....


That afternoon back home at last, I got a call from a dear friend, a fellow family doctor with CLL living in Canada just admitted to the neuro-ICU with chronic inflammatory demyelinating polyneuropathy. Was it related to the weird immune system us CLLers share? Was it totally unrelated? Seeing as no-one knows the cause of CIDP, it is anyone'e guess.


What are the odds? Two cases of an exceedingly rare disorder on the same day. 


Synchroncity? Where is Dr. Jung when I need him?


I had done my doctorly thing. It ended well. I could talk to my Canadian friend with some fresh knowledge of CIDP from the research I did after I landed.


The steward asked for my frequent flier number as I was leaving the plane. Maybe I will even get some miles out of just doing what I do.


One last puzzle piece. When I got down to baggage claim, another doctor who was on our flight walked up to me too thank me for jumping in. He was being treated for cancer and didn't want to take the risk of offering to help due to his lowered immunity. 


Don't be judgmental.


We all make decisions. If the patient that I had found at the back of the plane had not had a panic attack on top of a rare neuromuscular disorder, but was suffering from a much more common condition such as severe asthmatic bronchitis, putting anyone such as me or the more reluctant doctor at grave danger and with little to offer in the way of help, his decision would have been the correct one, not mine.


It is good to be lucky.


I promise more lucky news soon from my ibrutinib trial at OSU.

The Grand Canyon Mule Ride: Taking a risk, doing something different, and facing our fears

I might also add descending more than a mile into the pit and reemerging impressed with what is possible and what is unknown and unknowable.

Taking a necessary risk and a break for poetry

Today I took what I knew was a foolish, but I deemed to be a necessary risk and today I won.

Taking a medicine could have been a fatal gamble. I am still edgy and overwhelmed. Let me sober up from the rush of staring at the void and the void blinked first. Let me wait and tell my story tomorrow. It will be less dramatic in the morning.

Time for a break from death defying antics, and let's hear a poem.

A friend, a fellow traveler, sent this from Portugal, from a balcony overlooking the Atlantic. I am lucky to have such unmet friends in my life.

I also want to share with you my favorite poet C. Cavafy's wonderful "Ithaca" because it so well describes our journeys:

"Hope your road is a long one,

full of adventure, full of discovery

...

as long as you keep your thoughts raised high,

as long as a rare excitement

stirs your spirit and your body.

Laistrygonians, Cyclops,

wild Poseidon - you won't encounter them

unless you bring them along inside your soul,

unless your soul sets them up in front of you..."

She also said "Horizons are important to both of us."

That's the raw truth.