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.

Personal Update on my CLL: I am doing well with a near normal MR and no evidence of resistance to Ibrutinib at 42 months

I had MR imaging of my abdomen and pelvis earlier this week at St. Jude. The results were compared to my CT scans done on June 30, 2014 at Ohio State, about 16 months ago. 

I am now on my 42nd month on ibrutinib as part of the OSU clinical trial.

The abdomen showed no adenopathy. No abnormal nodes. None. No big nodes! 

WOW!

My pelvis did show one plump node in the left external iliac area (drains the lymph from the left side of GU tract) that was borderline enlarged and probably 2 millimeters bigger than it was before. 

Different techniques, different doctors, different times. I don't think the 2 mm. means anything and either does Dr. Byrd so I refuse to worry.

I switched to the less precise technique of MR to avoid the potential cancer causing risks of ionizing radiation of the many CT scans that are part and parcel of clinical trials.

When relapses happen with ibrutinib, they often start in the nodes. And that clearly is not happening in my case. And that is great news.

The other great news was that my blood tests done at OSU for the two common mutations that can lead to resistance to ibrutinib were negative, namely the downstream gain of function mutation of PLCγ2 or the C481S mutation at the BTK binding sites that prevents ibrutinib from irreversibly (covalently) binding. Either one of these mutations could turn back on the signaling. Blocking BTK signaling is the key to the success of ibrutinib in handling the CLL clone, so if the blockade is broken than will lead to resistance and eventually relapse

It is not a perfect test, but I had neither one at detectable levels.

Tomorrow I go for IVIG for my still dismal levels of immunoglobulins and to keep my auto-immune ITP at bay. I will also have routine labs drawn, but I am not expecting any surprises

A week later I am back at OSU for my 3 month check-up.

Flying to Ohio in the late fall and all winter is not predictable, but what I can predict is good care and what I can anticipate is more good good news as I am heading towards 4 years on ibrutinib.

UPDATE: My CBC at the infusion center Nov. 12, 2015 was basically normal. Hemoglobin was really normal at 14.5 so no anemia, platelets were very slightly above normal at 458,000 due to my splenectomy, ALC was at the low end of normal at 1.0 and that makes me most happy and my ANC was a healthy 8.1.  

All good. YEAH!

Hope to see you at our after ASH educational bash at City of Hope on Dec 12. Click here for the details.

ASCO 2014: Dr. O'Brien Discusses Improved Trial Designs, CT Scans and the role of Chemo-immunotherapy In Frontline Therapy in CLL (chronic lymphocytic leukemia)

I am back from ASH 2014 with some informative video interviews from Drs. Hillmen, Byrd, Burger, Wiestner, Kipps. Sharman, Roberts, Pagel, and Kay. The congress was a huge success and I will be reporting on the important abstracts and news over the next few months first here and then on our new website for the CLL Society Inc.

I also am very excited with the video interviews from ESH in Greece including ones with Furman, Porter, Hallek, Stilgenbauer, Wu, and Brown.

But first I have to share this fourth and final thoughtful audio interview with Dr. Susan O'Brien despite all its hisses and pops.

We pick up on the issue of ethical trial design from the third part of her interview on the issue of equipoise. If you missed part 3 or part 1 or 2, please enjoy by clicking on the numbers.

In this segment, Dr. O'Brien and I discuss the place of CT scans in clinical trials and in the real world of CLL therapy. Her answer is not black or white but is balanced and well considered.

Next Dr. O' Brien gives as a nuanced response to the question of what might be the possible role for chemo-immunotherapy in and out of trials.

Spoiler alert: Consider FCR frontline if you are young, healthy, mutated, and trisomy 12. But only under those circumstances>

 Here is Dr. O'Brien



More soon from ASH and ESH.

And thanks to the well over 300 of you that have completed our survey. If you haven't done it yet, please, take a few minutes to add your voice to the others as to what are your particular unmet needs in living with CLL. We are building the nonprofit CLL Society Inc. in response to those needs.

We will be taking the survey offline in one week on December 19, so please don't delay.

Here's the link.

And a very special thanks to those of you who have generously given a tax deductible donation to help us with our website construction and developing our CLL specific support groups.

More details to follow soon after we have analyzed the survey results.

We still are welcoming any contribution, large or small. At the suggestion of several of you, we have added a donate button at the top of the blog and on our placeholder website for the CLL Society Inc.

Thanks for all your help.

We are all in this together.

                                           

More Good News- Update on My Lab, CT Scans, and General CLL (chronic lymphocytic leukemia) Status

My blog has veered far away from the simple telling of my story to more telling of our stories with much B roll.

I am making plans to maybe bifurcate its content in the future, but for now it will continue its happy and diverse life as a personal health blog, a home for research news and video and audio interviews with leading researchers, and a whole bunch of personal analysis and advocacy on what it all means.

I am back from Ohio State where I am still seeing the research team every 3 months and getting CT scans every six months for my clinical trial on ibrutinib. I have riffed on this being too much radiation before in this prior post that includes links to some of the basic research of radiation exposure and its risks, but Dr. Byrd argues that the few relapses he sees on ibrutinib show up first in the nodes, so he wants to monitor me with the scans.

True enough. When I relapsed post failed hematopoeitic stem cell transplant in 2008, the nodes were my canary in the coal mine showing slight growth months before my lymphocyte counts started to move up and my platelets down.

So twice a year CTs are still the plot line for my clinical trial at OSU.

Since diagnosed in 2005, I have probably had about two dozen CT scans!

Add to that the equivalent of the 20 chest X-rays annually I get from flying over 100,000 miles a year, and my risk of secondary cancer is significant. This link with a NASA produced video tells the air travel part of the story.

If you really want to worry, take a look at this article from Medscape on CT scans in NHL.

But this post is not about the danger of CT scans, but about what my last one showed and happily that was stable disease.

I still have enlarged lymph nodes but they have changed little since October of 2012, or for the last 20 of my total of 25 plus months on ibrutinib. My largest sentinel gut node near my liver was about 10 cm at its peak, 7.3 x 3.3 cm just before starting ibrutinib, 4.4 x 0.7 cm in October, 2012 after about 6 months on the medication, then it shrunk to its shortest 3.9 x 0.7 three months later and when last measured on June 30, 2014 was 4.4 x 0.4 which actually represents its lowest volume. It has been fluctuating and when you account for the difficulty of measuring mobile objects in the mesentery and near the liver, is mostly stable since its dramatic shrinking in the first 6 months of therapy. Its a long hot dog shaped node instead of the more common bean shape. The same early dramatic shrinking in the first six months and slight ups and downs since has been the tale for my other smaller sentinel nodes on the scans.

So I have pretty stable disease.

What does this mean to still have enlarged nodes and a touch of CLL in my blood (see this prior post from last April on my flow cytometry report to understand more about my numbers and disease burden)?

The CLL does not proliferate in our blood, so the disease in our nodes and bone marrow are the source of all our problems and I will ignore the blood for now.

There is good reason to believe that these enlarged nodes are still full of CLL, but that it is not proliferating, thanks to the signal blocking from ibrutinib preventing it from getting the messages from its nurse like cells and others to be fruitful and multiply. So chock full of CLL, but it's dormant.

The other more positive interpretation is that these enlarged nodes are just the scarred down skeletons of the cancerous nodes they once were, and there is no residual disease to be found. Unfortunately, I am skeptical of this more PolyAnna hypothesis, and short of a biopsy which is not going to happen, there is not way to know for sure.

So what to do to avoid waking the Kraken?

Hope my genomic instability as evidenced by my 17p and 11q deletions and my complex karyotype will continue to behave with the ibrutinib aboard and not mutate so that my magical bullet no longer covalently binds BTK and blocks its activity?

Knock down the residual disease by adding a second or even a third agent?

Be reactive or proactive?

That is the question du jour faced by many of us now and more in the future whose CLL is controlled but it is not gone now with the new medications such as ibrutinib and idelalisib.

I have probed this recurring and unanswered question in more detail a prior post, and will soon be updating my thoughts on how to avoid being left stranded on third base and not getting home to a cure.

The rest of my news is also good.

My blood counts are boring and despite dropping my cyclosporin to a token dose of only 25 mgs once a day and stretching my 40 grams of IVIG infusions to every 7-8 weeks, my ITP also remains dormant. I think the possible immune stabilizing activity of ibrutinib and my low disease burden may be the factors  that have given me this long ride with high normal platelet counts. I have not been anemic for many months now and my neutrophils and the rest of the CBC are all copasetic. My blood chemistries are in the normal range and only my very low immunoglobulins, namely IGA, IGM, and IGG give proof to that fact that I still have a B cell leukemia, albeit a very sleepy and well behaved one.

More personal clinical and general CLL news soon, nearly all of it good.

I will be posting some of my interviews from ASCO 2014, plus sharing some exciting advocacy news. Busy times.

ASH 2012: Dr. David P Steensma: Myelodysplastic Syndrome with a Focus on Secondary MDS in CLL

Dr. David Steensma is a world leader in not only basic laboratory and clinical research on MDS, but also in examining the impact that anemia has on the life of older patients.

MDS or myelodysplastic syndrome is bone marrow failure and in a minority cases, turns into an acute leukemia.

It is not an uncommon complication of CLL, both, as Dr. Steensma explains, secondary to the genetic and epigenetic changes inherent in the disease itself, and to the treatments, especially the alkylating agents that damage the DNA. In CLL, these included chlorambucil (Leukeran), cyclophosphamide (Cytoxan or the C in FCR), and bendamustine (Treanda).

This is a strong argument for younger patients to avoid those drugs known to damage the bone marrow, but Dr. Steensma offers some more subtle analysis and advice.

We also discuss the radiation risk of MDS from all those CT scans we get in clinical trials.

A good friend of mine is now more than two years out post transplant at MDACC for his CLL/MDS combo one-two knockout punch and he is doing great with no molecular evidence of either disease (MRD negative). And very little graft versus disease.  You can read his story at this link.

This is my last video interview from ASH 2012, but ASCO is just around the corner with more news and interviews.

Dr. Steensma clarifies and explains the risk of MDS in simple terms.

Einstein is quoted as saying: "Make things as simple as possible, but not simpler."

Dr. Steensma does exactly that.

ASH 2012: Dr. John Byrd Part 3 Accrual Issues in Clinical Trials, Transplant, CAR-T, the Rare Relapses, and Biological Combination

We are still in Ireland having an amazing time so I will be brief in posting the third of a four part ASH 2012 interview with Dr. Byrd.

In this segment we are  getting into some of the gritty details of treatment with ibrutinib. For the cognoscenti, this may add to your knowledge base. For those new to the ibrutinib story, I suggest you review my early ASH 2012 interviews with Dr. Pagel and the first two parts to this interview in my earlier posts.

To my non-CLL friends, I guarantee that soon I will share some amazing craic, photos, and video from Ireland. but right now, I am just having way too good a time to devote much attention to the internet.

The Risks of Too Much Testing in CLL

As those of you know who follow my chronicles know, I have been plagued by a cracking irritating noise in my right ear associated with a congested feeling for months now.

While steroids gave powerful if temporary relief, nothing has solved the problem. It seems each doctor who checks the ear sees something different. The diagnosis ranged from a serious infection to a completely normal tympanic membrane with a few stops in between at a dull and retracted eardrum.

Here I valued my family doctor’s evaluation more than that of the less experienced “ear-looker-at-er”, my CLL guru, and in the end, relied on the the findings of a otolaryngologist.

When we doctors look in your ear, we are using one eye therefore there is no depth perception. That can lead to a misreading of what the anatomical landmarks are telling us and as a consequence, a misdiagnosis. Minor findings seen on the otoscope can be over-interpreted and lead to unneeded therapies.

When I saw my ENT specialist, he told my ear looked great. So I asked “ Then why the crackly noises and stuffy feeling? ” He wasn’t sure but he also wasn’t worried. Often in medicine, it is much easier to tell a patient what they don’t have than what the do. We can reassure our patients and ourselves that the chest pain is not angina from the heart, but darned if we know what is the true cause.

This brings me to revisit another old theme.

Patients come to the office for two very distinct problems.

The first is that they want relief from the symptom- the pain or itch or nausea or depression or a thousands other “chief complaints.” Chief complaints or CC- that’s what we healthcare providers call them in your medical chart.

The second very different motivator that leads to a doctor visit is the need to know that the presenting symptom is not something serious. “ Doc, I don’t want you to remove that mole. It is not causing me any problems. Just tell me that it isn’t cancer.” Or  “ Is it normal to feel my heart beat in bed at night?” Or “ Why am I hearing this funny noise in my ear?” And a thousand more concerns and worries that need to be assessed and offered reassurance more than relieved.

These are disinct problems, and the wise practioner must recognize what the patient is asking for and meet that need or the encounter will not be satisfying for either party.

I wanted the reassurance. The noise itself is trivial, but was I missing a clue to a more occult issue?

Because of my CLL, my specialist did a tympanogram and demonstrated that my drums bilaterally were responding to changes in pressure in a normal and symmetrical way. That suggested no serious pathology. The big surprise was my hearing test. It was nearly perfect, at all frequencies, in both ears. This was a welcome and unexpected finding in a baby boomer. When I think of my teenage years when I stood inches away from the giant stage speakers at a Led Zeppelin or Janis Joplin concert, and woke up with ringing ears the next morning, I am truly amazed that I suffered no permanent damage.

The ears-nose-and-throat man can see where my internal auditory canal (IOC) ends at the eardrum with his otoscope and where it begins my looking up the nostril with a different specialized instrument, but he can not asses what is in between.

That is why he ordered an MRI of my IOC. With contrast to enhance any tumor.

And here is where my tale of too much knowledge gets interesting.

A few days ago after physical therapy, and before a memorial service where I gave the eulogy (see post Jennie Lynn Taylor) followed by a CLL support group meeting, and ending with packing for travel the next morning, I squeezed in my imaging test. The radiologist reading my study is an old pal, so he shared the results with me. Another of the unabashed perks of being a staff doctor.

My IOC was patent (open) with no tumor or inflammation or fluid.

Great news.

BUT…

My right mastoid that should be fully aerated and thus appear black on the scan as did the left side instead instead had a mottled appearance reflecting fluid and swelling in the air cells. It wasn’t subtle. It was obvious.

Mastoiditis he said! A dreaded infection, usually of children, that can lead to major surgery, nerve damage, hearing loss, and life threatening abscesses and brain infections. I have not seen a case since I worked on the ENT floor of St. Justine pour Les Enfants in Montreal as a med student at McGill.

Could my suppressed immune system allowed some weird organism to slip into my bone and take up a hostile and damaging occupation?  

This demanded action. Or did it?

Read my last post on worrying to see how I was coping.

You see it just didn’t add up. My ear was pain free and functionally normal. I wasn’t sick and hadn’t been sick recently. There was no tenderness or redness or warmth or fever.

I called to consult the doctor who had ordered the scan and they arranged an appointment later that same day on my way home from the memorial service.

He took one look at the MRI and reassured me (exactly what I needed) that is a non-event that he sees all the time. Sure the mastoid air cells are different on the right, but this could represent old minor damage from childhood infections or allergies or nothing.  Not a chance that it is some weird bug because there is no involvement of my ear canal and no free fluid. Why the right side only? Why has become symptomatic now? He has no idea, but he also has no worries, so I won’t either. 

Apparently MRIs are notorious for over diagnosing mastoiditis. Who knew? My ENT colleague gets too many calls from the ER or worried neurologists or family doctors about exactly this same non-issue.

So here’s my point, as I try to decide about whether to go ahead with my CT scans next week. Will they find another red herring on all those scans that will demand further workup to “rule-out” that it is nothing to worry about. Well I wouldn’t ever have worried if you hadn’t done the imaging to begin with. Much ado about nothing.

You order enough labs, x-rays, and other tests and sooner or later you are bound to find something, but does it mean something. As my pseudo-mastoiditis case revealed, often it doesn’t.

This is another cost of knowing too much, and too little at the same time.

Moreover as to my upcoming CTs, the size of my internal lymph nodes measured by the scan will make absolutely no difference in my own care. My suspicion is that it will also make little in any difference in the final study data as long as I get the exit CT scans and bone marrow biopsy in a brief three months from now. Others might disagree. The scan might find an unexpected non CLL growth or problem. While the yield on secondary cancers is small, it can be life saving for those few. I can count a half a dozen friends among those who are alive today with exactly this scenario.

My tendency is not to look for trouble. I am no diagnostic nihilist, but how many CTs do I need?  This recent brief scare with my MRI  “finding” is another reason to think twice about this testing.

Tests need to be reasonably expected to make an impact on how the patient or the disease will be managed. There is no role for curiosity, especially when we are talking about procedures that care some  small long term risk (see prior post on CT scans and secondary cancer).

In the big picture, the fact that I can focus in on such passing details such as the risk/ benefit of imaging is testimony to the fact that I am doing so well on the ibrutinib.

Labs are rock stable and energy is picking.

Life is good. Off  to Ohio in a few days to pick up more magic grey pills.

A Personal Story of CLL and Secondary Cancer

Lynn is one of those fighting and beating two cancers, both CLL and a secondary lung cancer.

She has kindly permitted me to show how she has been coached by this double whammy.

She speaks to the advantages of the frequent CT scans and also give valuable information about her relatively benign experience of coming off the ibrutinib, also very helpful and encouraging.

Hi Brian,

Of course I follow your posts on various sites as well as your blog.  I think you saw that my end of 2nd cycle CT scan showed me with a right upper lobe and bronchus mass of 2.5 cm.  Biopsy revealed it was a cancer so I went off Ibrutinib and a great NIH surgeon, Dr. David Schrump, removed the upper right lobe and all of the tumor .. clean margins and nothing in the nodes removed, thus allowing me to avoid chemo.

During the first conscious sedation broncoscopy attempt to get a biopsy, the pulmonary doc couldn't get enough cells because of the easy bruising.  I mention this because I had lots of unexplained bruising while on Ibrutinib.  The second fully sedated biopsy didn't have the same bleeding issue and I had been off Ibrutinib for three days when that occurred.

I am VERY grateful I had the CT scan as part of my protocol.  My baseline showed nothing, and it was done in March while this tumor was present in July.  I think the tumor was perking just before I came to NIH and went on the protocol as I had a strange bronchitis with blood and then soon on the Ibrutinub I had lots of coughing with excessive bleeding.  Did the Ibrutinib allow it to bloom faster?  Who knows.  In a way, I'm glad it did so that it could be excised and considered a Stage I non-small cell adenomacarcinoma.  My surgeon said my tumor grew faster than would be expected for that type.

So .. I hope people won't throw out their CT scans.  I'm now a big believer and booster and hope that all should be aware of how important it is to find these secondary cancers.

I'm hopeful to eventually get back on Ibrutinib, one way or another.  It did wonders for me .. I started at 342k wbc and when I went off the drug, was around 114K and my counts kept going down, even after stopping taking it. In two cycles, my CLL marrow went from 80% to 50%. After my surgery and 12 hospital nights (got pneumothorax and had to return to the OR for pleuradesis) the WBC bottomed out at 13k with Hgb at 6.6 so got first ever transfusion of two units.  Now all climbing except for the neuts so have had several neupogen shots and hope tomorrow's CBC will show me out of neutropenic-ville.  Anyway, I'm sharing all this with you as I think it's important that you as both a patient and a thoughtful doctor hear from those of us on the "fringes" of these studies.  I don't think enough has been tracked of those who had to stop taking Ibrutinib and my story certainly is not one of rapidly increasing counts or nodes.  I'll keep you in my loop and love being in yours.

All the best,
Lynn

Here is my response:

Hi Lynn,

Thanks you again for reaching out, staying in touch, and sharing your story.

I am so glad your lung cancer was caught early. In most cancers the paradigm is a quick and aggressive pre-emptive strike, so unlike the hard-to-wrap-your-head-around paradigm for CLL where biding time is the prevailing wisdom .

In my post on secondary cancers, I pointed out that one possible reason for the high prevalence of secondary cancers in CLL is our greater surveillance. Not only CTs, but mammos, PAPs. colonoscopy, PSAs and skin exams find cancers earlier and more often.

Your neutropenia surprises me. That has not been a recurrent issue with ibrutinib or with lung cancer for the matter.

Also your WBC continuing to drop after treatment stopped is not what I have heard from others. Usually what I have heard is that the nodes bounce back up again, sometimes within days, but I haven't heard much about the counts so appreciate your good news.

I would like to share your email on my blog as I believe others would benefit from your experience and counsel.

Would it be OK for me to post your email on my blog?

Thanks and be well.

We are all in this together.

Brian

My last reply suggested that she push hard to restart the ibrutinib as she needed no chemo and has had curative surgery. In effect, she is back to square one dealing with a single cancer.

I am sorry for what she has had to endure, but thankful for her willingness to share her instructive, cautionary, and ultimately upbeat story.

Finally, her idea of sharing the experiences of those that needed to stop their ibrutinib or GS-1101 is brilliant and should be explored. Patients and hematologists alike will need to know and be prepared for what they might expect when the drugs are discontinued. My guess is that the longer that you are on them and the lower the disease burden, the less the rebound. We are just starting to look at these issues in CML with imatinib and the early results are encouraging.

Honestly, for right now I am just so happy to have something that works so well and is so free of side effects, that I don't plan to worry about how to stop for a long long time.

It's Always Something: Secondary Cancer Risk with CLL and CT scans

CLL is bad enough, but about half of us will get a secondary cancer and when we get them our overall survival is inferior. Skin cancers occur to more than one in three and a whopping 16.5% of us must deal with a melanoma.

Here is the gut of an abstract from ASCO this year:

546 CLL patients were included in the study. Median age was 62.5 years. 84 (43%) were Stage 0 and 62 (32%) were Stage 1 RAI at diagnosis indicating earlier disease. 266 (49%) patients had a second or secondary malignancy. A total of 304 cancers were identified. 14% of patients had more than one malignancy. Melanoma was identified in 44 (16.5%) patients and non-melanoma skin cancer was identified in 54 (20%). Lung cancer was identified as the most frequent solid tumor malignancy with 36 (13.5%) cases, followed by prostate (35), breast (21), colorectal (15), and bladder (14). 10 patients had a Richter’s transformation of their CLL. 26 patients developed either myelodysplastic syndrome or acute myelogenous leukemia. Conclusions: Second malignancies are frequent in CLL patients. Immunosupression, increased UV light exposure, longer life expectancy in low risk CLL, and tertiary cancer center referral bias are likely reasons for these increased rates.


And here's the conclusion of the one on how aggressive those secondary cancers can be:

Conclusions: Several common cancers, including breast, colon, and lung, have inferior overall and cancer-specific survival when there is coexistent CLL. 


And our risk is high even when compared to other B-cell cancers such as follicular lymphoma (FL)


Here's part of a Canadian abstract:


CLL patients had a 1.8-fold higher relative risk of a 2nd cancer (95% CI 1.29-2.41) compared to FL patients. SIR (Standardized Incidence Ratio) was 1.9 when non-melanoma skin cancers were excluded. Patients with FL had a similar incidence of second malignancies, as did patients with other invasive cancers. The most common second cancer among CLL patients was non-melanoma skin cancer, followed by cancers of the digestive organs, prostate, breast and lung. Malignancy was the leading cause of death in CLL patients. In patients with a 2nd cancer, cancers of the digestive organs, lung and brain were the most common causes of death. However, in patients without a 2nd cancer, CLL was the primary cause of death. After cancer, cardiovascular complications and infections were the most common causes of death in CLL patients.

And:

We demonstrated that CLL patients have a significantly increased risk of developing a 2nd cancer compared to FL patients, and this increase was similar in both genders and in all age groups. Thus, the poor relative survival of older men with CLL cannot be explained by an increased incidence of 2nd cancers. The increased incidence of malignancy in CLL may be related to the immune suppression in this disease or to an inherited predisposition to cancer.  

Five dear friends have had their CLL complicated by a secondary cancer is the last few months, two lung cancers, one breast, one prostrate, and one possibly renal.  Two are in ibrutinib trials and one is post transplant. Andrew Schorr, a well respected CLL patient and reporter has shared that he has developed MDS. I lost a friend a few years back to AML. And there are so many more.


Secondary cancers usually quickly vault into being the primary concern often demanding urgent therapy as the Canadian article notes. They are, after all, the leading cause of death in CLL.

I don't share this to depress you. I tell you because we are immune suppressed, many of us are on treatments that further compromise the ability of our immune systems to search and destroy potential and early cancers. A few of us must get EPO and other "growth" factors that might accelerate cancer growth. There is one possible positive. We often get more testing (see below re CT scans) that may facilitate finding new cancers sooner and more often.


And remember: we got CLL in the first place, which suggests at least a predisposition to one cancer. Maybe more?


So get your check-ups. See the dermatologist at least annually. Get our annoying choice of gender and age specific cancer screening tests: PAPs, mammos, PSAs, colonoscopies. We are not at normal risk. We are not the people at whom the recent relaxed recommendations for PSA screening were directed. We need to be more vigilant.


Next lab draw I get a PSA and I have a derm appointment scheduled. Colon is fine, thank you. It better be with all the fibrous veggies that I eat.


My news today from my ibrutinib/ofatumumab trial at OSU?  


Palpable nodes are slowly but surely getting smaller. Blood chemistries are completely normal including liver and kidney function and uric acid and LDH. ALC (absolute lymphocyte count) is down to a very normal 2.3, eosinophils are back to normal, platelets are just fine for someone with a history of ITP and single digit counts in the past at  a lofty 348,000, Hgb is almost normal at 13.0, reversing its prior slow downward drift. All good, very good.


So after four plus hours of my ofatumumab infusion, I will be leaving with my three bottles of ibrutinib. YEAH!


The trial protocol may be changing. Nothing is certain until there are written changes to the protocol approved by the independent IRB (Institutional Review Board) that is set up to safe guard us "subjects" from unethical or dangerous therapies.  


First the good news: After next month's and my last ofatumumab infusion, I probably only need to be here every 60 days. That makes perfect sense. 


Now the bad news which unfortunately is pertinent to today's topic of new cancers. I may no longer be able to opt out of the excessive CTs scan, every 60 - 90 days. Why do we need such frequent exposure to a proven cancer promoting procedure that is of questionable value in patients with CLL, already at higher risk for secondary malignancies? 


From the New England Journal of Medicine:


These considerations suggest that the estimated risks associated with CT are not hypothetical — that is, they are not based on models or major extrapolations in dose. Rather, they are based directly on measured excess radiation-related cancer rates among adults and children who in the past were exposed to the same range of organ doses as those delivered during CT studies. 


It is not that bad. The same journal does point out that the risk, while not insignificant, does dramatically decrease with age. Another advantage of being older; I am not likely to live the many decades it takes to get the secondary cancer. Dr. Rick Furman points out the data from that same article that states: " One article published (NEJM 2007;357:2277-2284) suggested that the increase risk for developing a cancer during their lifetime for a 40 year old was 0.02% from a single CT scan. Thus, it would take 50 scans to increase one's risk by 1% if they were 40 years old."


I don't want to overreact, but there is no safe minimum amount of radiation.  The radiation exposure from each set of three CT scans ordered here are roughly equivalent to 12 years of background radiation. Do I really need four or six a year? And it is reasonable to assume that the negative synergy of having CLL and a lot of ionizing radiation might make the risks higher for us.


As for the role and value in CLL, from an article that Dr. Bryd co-authored in JCO:
VOLUME 25 􏰆 NUMBER 35 􏰆 DECEMBER 10 2007.



"Current NCI-WG CLL response criteria are a significant predictor of PFS in previously treated CLL patients, with no additional benefit from the inclusion of CT scans."


But there are other ways to look at the issue.


Also from JCO earlier in 2007:
VOLUME 25 􏰆 NUMBER 12 􏰆 APRIL 20 2007

"In this series, an abnormal abdominal CT was a strong predictor of progression in patients with early-stage CLL. The inclusion of CT scans in the initial work-up of patients with early clinical stage on clinical grounds can, therefore, provide relevant clinical information. "

But those of us in this trial are much more similar to the previously treated patients in the first of those two study from JCO.

Finally, again from Dr. Byrd referring to the demands to include CTs in clinical trials in an ASH publication in March 2011:

"The current requirement for CT scans remains problematic to interpreting new study results, as essentially all prior CLL clinical trials did not include CT scans. More importantly, these imaging tests add significant cost and potential morbidity to the very special patients who volunteer to be part of clinical trials exploring new treatment approaches. Reconsideration of the CT requirement in the setting of implementing detailed lymph node and spleen physical exams might offer an opportunity to match our new clinical trial approaches to methods best supported by evidence-based tumor assessment."

I know I am in a trial. It is to get important potentially life saving information, but as Dr. Byrd says so eloquently, trials are for patients, not the other way around.


If push comes to shove, and the imaging is a must to do to in order to receive my meds, then the choice is simple: it is a small risk for a big gain.


Moreover, if it helps get the drug approved sooner, so all those waiting for these game changing meds can benefit, then it is a small theoretical risk for a huge payoff.


Finally, small molecules such as ibrutinib and GS-1101, because they unanchor the B-cells from the safe home in the nodes and send them out in droves onto the less protected environment of the blood stream,  the ALC can shoot up.  That is normally a sign of disease progression with old school therapies, but is not usually the case with these new new drugs. Hence, the need to document shrinking nodes to prove that the therapy is working is even more critical with these treatments.


Still, isn't twice a year enough?


I even opt out of the total body scanners at the airports where the risks are at best minor and more honestly, unknown at this time, so I hope I can continue to opt out of my CTs here. TSA staff can get by with just patting me down at the airport to check for contraband. Why is essentially the same procedure for palpable nodes done by team of medical professionals not sufficient?  


A while back, I suggested to Dr. Byrd that he do a trial that once and for all compares the response to therapy of palpable nodes to that of the nodes seen on CT to see if we can eliminate need for all the scans. Seems even more urgent now.


Finished the airport at Phoenix waiting for my delayed flight home.

CT scans and knowing

CT scans. I hate them.

I hate how they slice me up like a salami every 5 mm and then use some mathematical wizardry to reconstruct my innards. What you get is shadows. What casts them is the different x-ray densities of the tissues being spied upon. It my case it is the mesenteric or gut nodes that will tell my story.

The radiation exposure is considerable. Maybe equivalent to 400 chest x-ray, And since the belly is nearly always shot with and without contrast, the exposure is doubled. Hence my decision to forego the viewing pleasure of my chest and neck. The gut is where the action is or isn't. Why redouble my exposure for little more data?

Some malfunctioning CT scans here in LA were delivering massive overdoses of x-rays, unbeknownst to patient and doctor alike. They weren't just imaging the cancer, they were frying it. More likely nudging it, tilting its already chaotic genetic balance to tumble down, who knows where. That however is not my worry.

I avoid them become I become despondent in the weeks before despite my best efforts.

I live now in the realm of all that is possible, including a miracle. On Friday, I sacrifice on the altar of science and the need to know, the infinitely plausible in order to tentatively grab at ,,,,, what? The reality of a fragile miracle happening in my gut and my marrow? A cancer saying goodbye? G-d willing! A confluence of bad boys covering each others' back like the worst street gang you ever saw? G-d forbid. A hint of remission or at least a significant retreat of my most persistent enemy in its favored hangout? Or no change? Or a tiny change or a little up or a little down or a little of both?

Forget the radiation risks, the barium, the clear liquids, the weird flush feeling from the IV dyes that carry the risk of allergic reactions and renal damage.

What bothers me is that it seems too prying, too invasive.

Too knowing.

It is the surrender of all possibilities that makes me hate CT scans.

But I must march headlong into knowing. Even Moses, with G-d on his side, sent scouts ahead to check out Canaan.

I am confident that I will get a better report than Moses. And although my ancestors did spend too long wandering the desert, largely as a result of their reaction to the spies' reports, we do know that they finally did enter the promised land.

I will not wander from my goal.

What to do, again? The same set of questions

Time to focus and bring my A game to the table. No more wishful thinking and pushing the tough issues aside. Lines are being drawn, and I better be aware of where I stand and what I must do.

It is always the same set of questions I must ask when staging my disease. Questions about when to keep my foot on the gas, when to brake, and when to change vehicles.

It helps me frame my plans if I lay them out here. This post will be of more interest to my CLL friends, as it is rather technical, though it does detail how I deconstruct my problems. And I always seem to get to the "big question" by the end.

In the next few days I will get my first CT scan in over a year and my latest of my many bone marrow biopsy, the last being in February.

Since that time I have had a reoccurrence of my ITP, controlled easily at first with just IVIG and nothing else for almost 10 months until June this year when my platelet count crashed again. Cyclosporin (CSP) and Rituximab (R) in about a week rescued my platelets from the 20,000s to the 300,000s.

Not surprisingly, my CLL was raising its ugly head at the same moment with the leukemic clone showing up for the first time in almost two years, the first time since my transplant. Not a welcomed repeat visitor to my blood stream. My palpable nodes were also slowly growing. The cancer was definitely back and on the march.

Today I am still on the same dose of cyclosporin (150 mg 2 x a day) that has raised my BP, made my muscles ache, and slightly challenged my renal function, but is doing its job. Last platelet count was 291,000.

I had rituximab 375/M2 six times between June 2 and July 8. My absolute lymphocytes that had risen just beyond the normal level to 4.8 when the flow cytometry showed my cancer before the R , quickly fell to 0.8 and my palpable nodes shrank to 1 cm at the most and have stabilized there.

It is now more than two months since my last rituximab, so it is time to check the marrow. R when it is effective, is still working its magic for at least two months after its last dose so I need to wait to assess its success.

Assess what? If I need more rituximab? If I should consider other therapy?

Here's how I see it.

If there is no evidence of disease, in other words, the marrow is no longer 5-10% CLL as it was seven months ago, but has become MRD neg, and more importantly the largest mesenteric cluster of nodes that was 3 cm a year ago and all its CLL friends have shrunk to less that 1 cm.

The odds of that are small, but not impossible. The last time I had my idiosyncratic CSP and R mixture my marrow went from 90% infiltrated to 3%, and my palpable nodes all shrank to nothing. Unfortunately I did not have a CT scan to measure the disease until months after my last R then and by the time I did, it revealed a 5 cm mesenteric node. Had it shrunk from much bigger to that size? Maybe. More likely it had both shrunk and re-grown. But how much and how fast? This time I am starting with a much lower disease burden, less work for the drugs, but has my CLL toughened up in the two years since my last encounter? R on its own is wimpy, but the CSP seems to add extra oomph in my case, especially in the marrow.

This is the result that I am hoping for. Praying for.

Another reason for no more R soon would be the other extreme. Many big mesenteric nodes well over 5 cm and/or heavy marrow involvement, say >70%. R on its own is not that great in cleaning out big nodes or the marrow. CSP has little track record and even less clinical data as a CLL drug.

I am not going there in my mind or heart, but that unlikely finding would mean time to move on to bigger guns and tougher questions. What to do when the R and CSP are losing their mojo? Likely Revlimid and Ofatuzamb, maybe FCR. That all means transplant redux in a year or so, but more about that later, G-d willing much much later.

Almost any finding in between those extremes, MRD neg. versus big tumor burden would seem to suggest more treatment with R. Not rituxan maintenance, another of my controversial trailblazing path, but more actual standard treatment. The distinction is not just a nicety for insurance reasons, but a considered plan to push back the CLL as far as possible.

My friend Chaya says I need to stop worrying about my ITP and pay attention to my CLL, especially the size of the mesenteric nodes. (I asked to have the CT of only the abdomen as that halves the radiation exposure and it is the mesenteric nodes that have always been where I have the worst disease.) Let's examine what Chaya calls my opportunity cost. If my nodes are too big, then waiting or fussing around with more R makes little sense and might actually be ill advised. Because if they get too big, getting them down to size will be very difficult with fewer option. Getting them down to size will always be crucial in insuring the success of my next transplant.

I face the identical questions about node size that I did a over two years ago. Say my nodes are the same or a touch bigger than a year ago. Surely they were even bigger before I started CSP + R in June. After all, my palpable nodes shrunk so my gut nodes must have followed suit. Yet I had no palpable nodes and a hidden 5 cm mesenteric node pre-transplant, so there is no tight guarantee. Never is.

I will have the CT scan next Friday with my own medical group in Fullerton so I'll have my results within minutes, all this just a few hours before the call of Kol Nidre. The bone marrow biopsy is a week from Tuesday with Dr Kipps at UCSD, so results will only be available some three weeks later. Waiting, again, one of my weakness.

Truth be told, the big drama is next Friday.

Will I be sealed in the book of life?

I am asking this same question for the fifth time since my diagnosis. I am thrilled and grateful to be here and able to pose it.

I plan to be asking it for decades to come.

To Life, L'Haim

I am swinging back into my more ponderous mood as I face my upcoming  CT scan. It has been almost 6 months since the last one showed  small but definite growth of my mesenteric nodes.

The daily joys of life linger less time in the front of my brain. Instead the small pocket of dread from the back of my head creeps forward to leave a thin but unmistakeable scent of fear in my nostrils.

The unrevealed will soon be exposed.  Will it be a clarion call to action, or a long OHMMM to pause and savor the success?  Will I  scream with joy or will I grit my teeth, prepare my weapons, and climb back in the ring for another round with the dragon?

Or will there be no clarity. Just more questions. 

It is all about the journey after all.

I remain confident with not a palpable node to be found and all normal labs. Surely my CT will confirm what my loudest inner voice tells me. 

I am healthy. 

I am well. 

I am winning the war.

To life

L'Haim.