Thursday, May 22, 2008

Prognostication of Brain Tumors in the Spotlight

Most people with any access to any media probably could not escape the story about Ted Kennedy's seizure and eventual diagnosis with a glioblastoma these past few days. The very public disclosure of a diagnosis in a public figure deflates any presumption of 'keeping information' from the patient which is an occasional conflict in medical care. Imagine as a non-public figure you did not want to hear a lot of information about your diagnosis or prognosis and you try to escape by watching some TV. Flip on the TV and on CNN you get Sanjay Gupta telling you everything you did not want to hear.

Of course any illness in significant celebrity can be a 'teachable moment' as we have seen with Randy Pausch and pancreatic cancer, Elizabeth Edwards & Betty Ford and breast cancer, Ronald Reagan and Alzheimer's dementia, Magic Johnson and HIV, Katie Couric's husband and colonoscopies, Art Buchwald and hospice, and so on. (I wonder if palliative care will ever have a celebrity champion?) This public disclosure of an illness can provide a focus for patients and families going through the same situation, but it also can bring out lots of misleading information about 'miracle cures' without any demonstrated efficacy beyond anecdote. Events like this also make such unfortunate things like celebrity death pools come to light.

A particular influence in this situation is "survivor bias", in which the people who will likely call into the radio shows or write letters to the editors are alive. The survivors of often fatal illnesses therefore skew the perceived bias of survival. Dead people don't have that ability and families may not have as much incentive to write/call in and say, "My husband had a brain tumor and died 1 month after being diagnosed." Hopefully the media will strive to keep this balance right. Dr. Barron H. Lerner wrote a book that sounds like it strikes the right balance called When Illness Goes Public: Celebrity Patients and How We Look at Medicine. He spoke on NPR this week and counterbalanced some callers with skilled firm diplomacy.

A curious and morbid observation in discussing the medical care of public figures is the focus on prognostication which conversely is commonly avoided or glossed over for 'non-public figures' with life-threatening illness. The LA Times ("Kennedy's tumor prognosis is weakened by age") and my local Kansas City Star ("A grim prognosis for Kennedy") had articles discussing general information about glioblastomas, and both focused on prognosis in the title and the article. How does knowledge of a public figure's prognosis affect us as citizens? Maybe we are treating that person as part of our own circle of family and friends since we have seen them in our lives more than some of our family or friends.

In some talks on prognosis, I covered prognosis of survival in glioblastomas with the help of my colleague Mike Salacz. Here is one of the slides from that talk with references at the end. As you can see temozolamide plus radiation improved survival, but the real point of this slide is that it really depends on what study you are looking at to base your prognosis. Understanding the selection criteria for these studies to see if it matches your patient is important.

The NEJM has a free pdf of a 2005 review article of treating giloblastomas with radiation and temozolamide. The Kaplan-Meier survival curve is what I find most helpful in understanding disease progression (click picture for NEJM site view - free registration). The curves get steepest in the 6-12 month range which is also where you cross the median. That information together helps paint a likely picture for patients and families to prepare for if no other significant co-morbidities exist. But this is still a serious illness that requires plenty of planning (advance directives, living will, financial planning) and focus for how the next 6-12 months might be.


References:
Stupp R et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96.

Athanassiou H et al. Randomized phase II study of temozolomide and radiotherapy compared with radiotherapy alone in newly diagnosed glioblastoma multiforme.J Clin Oncol. 2005 Apr 1;23(10):2372-7.

Mirimanoff RO et al. Radiotherapy and temozolomide for newly diagnosed glioblastoma: recursive partitioning analysis of the EORTC 26981/22981- NCIC CE3 phase III randomized trial. J Clin Oncol. 2006 Jun 1;24(16):2563-9.

Gaspar L et al. Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys. 1997 Mar 1;37(4):745-51.

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