Wednesday, April 04, 2007

CT scans

When should a CLL patient have a CT scan?

The first thing to say is that for the past 30 years the staging of CLL has been carried out very satisfactorily without CT scans. Indeed all the predictive information that is based on Rai or Binet staging specifically excludes CT scanning. However, it stands to reason that some Rai stage 0 patients will in fact have enlarged retroperitoneal lymph nodes (this means nodes at the back of the tummy)undetectable by clinical examination, and these patients will have the prognosis of stage I patients rather than stage 0 patients, and that in some patients the glands will be of sufficient size as to justify immediate treatment.

If CT scanning is used to stage patients, then patients who are truly stage 0 will have a better prognosis than historical data shows, but we are in the dark about what happens to patients whose only evidence of enlarged lymph nodes is what is detectable by CT scanning.

A new paper from Professor Montserrat's group is about to be published in J C lin Oncol which helps to resolve this.

The Barcelona group did abdominal CT scan on 140 stage 0 patients. 27% had an abnormal CT scan. This correlated with increased bone marrow infiltration, high lymphocyte count, high ZAP-70 expression and short lymphocyte doubling time. Patients with an abnormal CT scan had a shorter time to first treatment than those with normal CT scans (median 3.5 years compared with median not yet reached). In a multivariate analysis only abnormal CT scan and high ZAP-70 correlated with disease progression. (Remember that the Barcelona ZAP-70 is one we believe in - it was published in NEJM under Crespo et al. It correlates very closely with unmutated VH genes).

In the light of this finding the International Working Group in CLL are minded to add to their advice on the management of CLL.

CT scans generally are not required for the initial evaluation, staging, or follow up. A recent study has found that patients in Rai stage 0 but with detectable abdominal disease by CT scans may have a more aggressive disease. Therefore, clinical studies evaluating the use of CT scans in CLL are strongly encouraged.

The IWCLL group are very conservative about changing recommendations, but I certainly think that there are situations where a CT scan would be indicated in the initial evaluation of patients in clinical practice.

Patients who are apparently stage 0 but have a lymphocyte count greater than 50,000 (possibly those greater than 30,000), overweight patients who are difficult to examine for lymph nodes, patients with 'B' symptoms, patients with lymphocyte doubling times of less than a year, patients with unmutated VH genes (or a reliable positive ZAP-70).

I know that some people who are worried by the radiation dose from a CT scan. This worry has been reinforced by an MRI specialist who has been writing on Medscape. I have to say that this is very much a lone view among medical imagers. Most, while recognizing that CT scanning does involve a large dose of radiation compared to that received from a chest X-ray, nevertheless agree that the risk of inducing a second cancer is very small compared to the risk of missing the correct diagnosis.

What about using ultrasound or MRI to diagnose retroperitoneal lymph nodes?

In some countries, the use of abdominal ultrasound is popular to assess the extent of lymphadenopathy and organomegaly in CLL. While it may be used in the clinical management of individual patients, this methodology is strongly investigator-dependent and should therefore not be used for the response evaluation in clinical trials. - so say IWCLL and I agree with them. Measurement of nodes on successive ultrasound scans is nigh on impossible, because you cannot really produce comparable views.

Similarly, the IWCLL view of MRI is this - "nuclear magnetic resonance imaging and other imaging techniques are generally not useful in the management of CLL." Again I agree, the view of lymph nodes is not precise enough.

While we are on the subject of imaging, the IWCLL say, "Positron emission tomography (PET) scans do not provide information that is useful in the management of CLL. PET scans, however, might become useful in the diagnostic evaluation and follow up of known or suspected Richter's transformation."

In clinical trials, the latest German trials demonstrate that the use of CT scans to evaluate how good a response is, is very worthwhile. Apparent complete remissions are nothing of the sort in many cases when CT scans are used to evaluate them. The IWCLL recommend, "In clinical trials where the treatment intent is to maximize complete remissions, neck, chest, abdominal and pelvic CT scans are recommended to evaluate the response to therapy. CT scans should be performed prior to the start of therapy and at the first restaging following therapy if previously abnormal".

Like all imaging examinations the doctor must first ask himselftheh question, "Why am I doing this?" and then answer the question, "How will it alter my management if I have this information?" If the answer to the first is, "Idon't know or because it is in the protocol" or the answer to the second is "Not at all or I don't know," then the CT scan should not be done.


Anonymous said...

Very interesting. My U.S. doc immediately sent me for a CT scan and told me he was looking for enlarged nodes. It came back negative and I was pronounced stage 0. My WBC at the time was 25K. I always assumed it was standard protocol to scan. In addition he did a bone marrow biopsy. I guess he was pretty thorough. Three years later I remain at stage 0 and was comforted that I had no nodes. As far as the bone marrow biopsy I was relieved that it was not diffuse infiltration.

Jenny Lou said...

CT Scans definately have their place in CLL. Very good post on this, Terry.

Anonymous said...

I continue to believe that it is unlikely that the risk to the patient from a CT scan - the equivalent of 400 chest X-rays - will balance the benefit in an early-stage, asymptomatic patient.

Of what value is it to know if a patient is a stage 1 verses stage 0? Very little if any.

A FISH and flow cytometry (which should be standard tests for suspected CLL) can give the clinician the gross chromosomal abnormality data (revealing, say 17p) as well as any adverse cell markers (say CD38). Couple this with an accurate ZAP-70 test (available at research labs such as UCSD or perhaps in the UK at your facility), I would submit that all of the necessary prognostic data will be available to accurately predict a patient's progress. Other prognostic factors may be soon proven that will provide even more data to fine-tune the definition of the risk of progression.

Symptoms that crop up may be cause for a CT scan at some point, but the chances that that would be necessary at diagnosis in a stage 0 or 1 patient is slim indeed, IMO.

As the patient progresses, there will be plenty of time for the physician to subject the patient to lots and lots of ionizing radiation.

Radiation that is a proven, well-known carcinogen.

Physicians like to pass out CT slips like candy. It is easier for them, but potentially deadly for the patient.

Anonymous said...

I am not so worried about the radiation as the price tag for a low priority test for CLLers. Prognostic blood tests should tell much more, much earlier about what is going on.
Our research clinicians in the states recognize this reality, but community oncs. must count on CT scans to keep their profit margins up.

David Arenson said...

My first hem/onc ordered a CT scan as part of the workup of diagnosis. At the time, only CD 38 was available to me as a prognostic test, so this did provide some additional information of value. I tend to think that, regardless, a CT at diagnosis may be helpful in uncovering problems, as this new study indicates. This may impact treatment decisions in an intelligent way. The more we know, the better we can fight. After the diagnosis stage, I agree that "routine" CT scans are unwarranted, but that they are useful in some situations: for example, before deciding to use Campath as a chemo chaser in an effort to eliminate MRD. What's the point of doing Campath if there are enlarged nodes that won't respond to it? Let's also remember that we have cancer, that sometimes we must take risks, even involving a little radiation, in the larger cause of fighting it.

Sreve Madden said...

Pam Sykes at The Flinders medical centre is doing some interseting research that seems to show that low dose radiation actually lowers the chance of DNA damage, so the conventional wisdom that radiation = bad is not neccesarily so.

Terry Hamblin said...

The figure of one CT scan equals 400 chest X-rays is a bit misleading because a chest X-ray deliveres such a minute dose. The chest is mostly air which does not stop the radiation at all. A better comparison is that a CT scan equals 6 abdominal X-rays. It certainly gives a lot more information than a hundred abdominal X-rays.

I certainly don't think that every stage 0 patient requires a CT scan, but it is advisable in selected cases. I think it is much more important to get teh molecular markers done. For example, I recently saw a patient with a lymphocyte count of 4.1 who was free of all signs and symptoms. Unfortunately she has unmutated VH genes, so although she does not actually have CLL according to the IWCLL definition, it is pretty sertain that she will eventually progress, and she will require close monitoring.

Professor Howdy said...

Wrong guess Terry - Try again:O)

It's a hard hidden image to locate...

Did you like any of the videos on my blog???

Best - -

Anonymous said...

If the chest is mostly air, why do an X-ray or CT scan at all? The answer, of course, is that there are solid tissues in front of, inside, and behind the lung. These are the tissues that absorb the high energy X-rays. That is where the damage to the DNA can occur.

If you talk about rems or millisieverts, no one is going to know what that means. Most everyone has at least heard of a chest X-ray. Conceptually, this is easier to understand.

Another factor is the amount of time this dose is administered. It's like running into a brick wall. It's different if you hit one time at 75 mile per hour one time, that hit it 75 times at one mile per hour.

That factor is missing in some of the discussions.

I don't think Dr. Hamblin would say that any X-ray is perfectly safe and represents no risk to the patient.

Again, it is a matter of balancing the need versus the risk. And the risk at diagnosis is very, very small that there are real problems that are asymptomatic.

Terry Hamblin said...

The proof of the pudding is in the eating. There is little to suggest that in practice necessary CT scans to any harm to patients

Anonymous said...

Well I suppose the medical profession can cover itself by noting that most cancer patients will die early, so effects won't be known!

To trivialize the danger is unfortunate, since a small amount of research on the internet gives quite a bit of information. And it has been shown that most doctors (including radiologists!) have no idea the amount of radition a CT scan delivers.

As to the lunacy of comparing a CT scan exposure to an airplane flight, go to and calculate how many round-trip trips from LA to NYC equal an abdominal CT scan. It's over 400 trips!!! Not the one or two a doctor will tell you.

And the exposure time is a factor. This sizable dose of ionizing radiation is done in a few seconds, if that. That means that damage will be done.

Even the government, which loves to downplay risks, says that CT scans will increase the number of people who will get cancer. And if you factor in the higher rate of secondary malignancies in CLL patients, this risk is doubled. So, out of a 100 people, perhaps one or two MORE people will get cancer, according to the US government's own data! And that may be understated, we don't know.

One thing to remember, radiation is not innocuous. It is a proven cancer-causing agent.

It's interesting to note that the Japanese who were bombed with atomic weapons had increased rates of cancer, in particular, leukemia (before Dr. Hambling heads to the blogger machine, yes, we know that wasn't CLL but acute leukemias).

Most people have heard of radon, which is a radioactive gas that can collect in buildings and represent a health hazard. It's a health hazard because of (ta da!) radiation.

As has been pointed out, sometimes X rays and CT scans are necessary. However, at diagnosis with CLL, it almost always isn't.

And wouldn't YOU hate to the the one or two out of a hundred who died pointlessly???

Jenny Lou said...

Happy Easter
Jenny Lou

Terry Hamblin said...

I don't think there is any evidence that of every 100 people getting a CT scan 1 or 2 will die of a cancer he or she would not otherwise have got. Then you have to say that the CT was unnecessary. I can certainly think of patients who would not have died if they had had a timely CT scan.

Here is another statistic to make you sit up and think. Would you rather let your child play with a friend whose house contained a) a revolver, b) a swimming pool?

Answer, the swimming pool is far more dangerous.

As a famous paediatrician in England recently discovered, we should not go around quoting statistics unless we really understand them; but it is always worth applying the common-sense test to any that we come across.

Anonymous said...

You miss the point.

We should not expose ourselves to UNNECESSARY risks.

This thread concerns CT scans at diagnosis. No one argues that a CT scan is sometimes necessary and imperative.

Let's agree on that.

As far as the swimming pool argument, this is disingenuous. There are millions of children who swim without incident. However, there are few who play with guns.

Therefore, if you compare exposures to deaths, I'd argue that a child is much more likely to be harmed playing with guns, PER INCIDENT, than while swimming.

Of course, proper decision-making regarding pools, guns, and CT scans will reduce risks even further.

Terry Hamblin said...

I absolutely agree that most stage 0 patients don't need a CT scan at diagnosis; I have been saying so for years. What the Montserrat paper was doing was pointing out that some patients with apparent stage 0 CLL have large retroperitoneal lymph nodes, and may go untreated when they really need treatment. The question then is which patients do need a CT scan for this purpose.

Anonymous said...

Hospitals are concerned about CT radiation. Why shouldn't I be?

Here's a relevant press release from the University of California, Davis Health Care System:

April 12, 2007


(SACRAMENTO, Calif.) -- James F. Holmes, associate professor of emergency medicine at UC Davis Health System, has received a three-year, $1.3 million grant to develop criteria for determining when computed tomography (CT) should be used on children with intra-abdominal injuries.

The study aims to generate clinical guidelines for identifying children at high risk and near-zero risk of intra-abdominal injuries in need of acute intervention.

These guidelines are intended to achieve safer and more efficient and effective use of abdominal CT in children at risk for intra-abdominal injuries.

Although CT is the standard for diagnosing intra-abdominal injuries, the procedure has serious risks, primarily that of developing radiation-induced cancer.

For every 1,500 children who undergo abdominal CT scanning, approximately one child will die from a cancer caused by the radiation, and up to three additional children will develop non-fatal cancers from the exposure. Less than 10 percent of the abdominal CT scans currently performed on children with trauma show intra-abdominal injuries...

Public Affairs
UC Davis Health System
4900 Broadway, Suite 1200
Sacramento, CA 95820

Terry Hamblin said...

You should be aware that children are especially vulnerable.