Thursday, May 21, 2009

The message of medians

Stephen J Gould's article, "The Median is not the Message" is a must read for everyone with any sort of cancer.

Results of particular treatments are usually reported as median survivals. This means the time at which 50% of people are dead and 50% are still alive. Medians are sensible figures when calculated on populations based on a normal distribution as represented by my second curve. But survival curves, as can be seen from the first illustration, do not look like this. They are extremely right skewed.

The median of the whole population is pressed up against the left hand edge of the graph at zero days because the normal distribution would contain all those who were going to get the cancer that we don't (and can't) know about. So we start on the downward slope from the time that the cancer is diagnosed. But that is a time some way into the disease. Some people are only diagnosed on the day that they die, having had the disease for many years undiagnosed. For CLL, we know that virtually all cases have had a long period when they had MBL before the diagnosis was makeable, and even when the diagnosis was makeable with a blood test, most people don't have blood tests.

On the survival curve, those with the most advanced and drug-resistant disease die soonest. By the time you get to the median survival the survivors are mainly those who had good prognostic factors at the beginning: low white count, no lymph nodes or spleen, mutated IgVH genes, low ZAP-70, low CD38 and del 13q14 on one chromosome. We know that some patients with these characteristics live out beyond 20 years and that they tend to die from old age. Indeed the ACOR list reported a man in New Mexico who had had the disease for 52 years. That survival curve had a very long tail indeed. As far as CLL is concerned the tail is abbreviated by the fact that everybody dies and that CLL patients cannot live longer than life itself. It is also a snapshot of the time it was drawn and it cannot take account of treatments that will appear in the next 20 years.

As far as my cancer is concerned, the median survival on this treatment is given as 22 months. But the 50% who die in this time are those who are really ill when they present, including those with massive liver secondaries, ascites, and bowel obstruction. I have all the good prognostic features: a primary so small as to be unfindable, localized spread, no liver involvement and no ascites, a well differentiated histology, low CEA levels, no symptoms and a 6 month observation which showed no progression on the CT scan. I should be on the right hand edge of the tail of that survival curve.


Burke said...

What is the median survival for cll patients today, Doctor Hamblin?

(Hope you feel better.)

Richard said...

Sorry to learn about your cancer. I hope the chemo side effects ease with time.

You helped so many of us when we were worried about our CLL be assured that we are all thinking of you now and wishing you the very best of outcomes. You deserve a survival at least 3 standard deviations above the mean.

You should start planning you trip to Minehead via the SWCP now!

Anonymous said...

Here's to the right! Your posts - regardless of subject - are always a treat. Your wisdom is so appreciated, your humor is delightful, and your willingness to share your knowledge is a blessing. You continue to be in my prayers.
Deb in Chicagoland (CLL)

Terry Hamblin said...

No-one really knows because the new definition has not been running long enough.

Marcia said...

Thanks for the reminder of how to think about medians and the normal distribution. I'm glad to hear your prognosis is far to the right of the curve.

Marilyn said...

Thank you, Dr. Hamblin. You gave a new perspective to this and some things to think about.

We so enjoyed seeing your video presentation at the CLL Conference in Niagara Falls last month. Thank you for that, too!

Hope your current course of treatment is effective and you are soon free to pursue your interests with your former strength.

Geroge said...

Along with the good prognostics, one del 13q14 seems to be normally sited. In my case all the usual prognostics are good, but my FISH and CGH indicate normal karotype. As far as I have been able to learned this means that the probes did not detect any abnormalities. I have never seen anything written about prognosis for normal karotype. Are you aware of any data on this class or the significance of this result?

Thanks for sharing your knowledge and expertise.

Best wishes for your treatment and recovery.


Terry Hamblin said...

Normal karyotypes usually have a prety good prognosis.

Anonymous said...

Hi Dr Terry,
It is heartening to hear of your very favourable prognostic factors and it is good to remind oneself of these. I attend my hematologist tomorrow re ?SMZL - pathology should be in from my splenectomy. Prognosis is certainly top of mind! Thanks for the helpful interpretation of "median survival". Wishing you the best.