Tuesday, May 27, 2008

Senator Kennedy's Cancer Family History


Dr Lubin, my partner at Helix Health of Connecticut asked me this question.

"Am I the only one to think about this? Ted Kennedy Junior had Osteosarcoma. His other son Patrick had a Spinal Tumor (I'd love to see the path on that). Ted Senior has a Glioma.....Likely GBM. In addition, his daughter had lung cancer at 43 (Was she a smoker?) and breast. So what this tells me is that the Kennedy family may have Li-Fraumeni or Li Fraumeni Like."

Well, perhaps we should call Dana Farber. Why? Because, Dr Rosenthal over there does not seem to be impressed. from the Globe:


Dr. David S. Rosenthal, former president of the American Cancer Society and the medical director of the Leonard P. Zakim Center for Integrated Therapies at the Dana-Farber Cancer Institute, said that while he is not familiar with the details of the Kennedys' medical history, he considers it "unlikely that the cancers are related." Given the young age at which some of the Kennedys' cancers occurred, and the fact that they were found in different organs, it is unlikely, but not impossible, that there is a common genetic thread linking them.


Hmm, let's see what a little GeneTests search can do. BTW the article was written by a Dana Farber genetic counselor.


Disease characteristics. Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome associated with soft-tissue sarcoma, breast cancer, leukemia, osteosarcoma, melanoma, and cancer of the colon, pancreas, adrenal cortex, and brain. Individuals with LFS are at increased risk for developing multiple primary cancers.


Hmmmm....


Genetic counseling. LFS is inherited in an autosomal dominant manner. Offspring of an affected individual have a 50% chance of inheriting the disease-causing mutation. Predisposition testing for at-risk family members is available in families in which the disease-causing mutation has been identified.


Two forms of Li-Fraumeni syndrome are recognized: classic Li-Fraumeni syndrome (LFS) and Li-Fraumeni-like syndrome (LFL).
Classic LFS is defined by the following criteria:


A proband with a sarcoma diagnosed before 45 years of age AND


A first-degree relative with any cancer under 45 years of age AND


A first- or second-degree relative with any cancer under 45 years of age or a sarcoma at any age [Li & Fraumeni 1969].


LFL shares some, but not all of the features listed for LFS.

Warmer.....


Birch's definition of LFL [Birch et al 1994]:


A proband with any childhood cancer or sarcoma, brain tumor, or adrenal cortical tumor diagnosed before 45 years of age (Ted Junior) AND


A first- or second-degree relative with a typical LFS cancer (sarcoma, breast cancer, brain tumor, adrenal cortical tumor, or leukemia) at any age (Ted Sr) AND


A first- or second-degree relative with any cancer under the age of 60 years (Daughter age 43)


Well Harvard. Looks like you were scooped by Helix Health of Connecticut.......

To the Kennedys, feel free to call for a full evaluation with Dr Murray up there, if someone at Harvard hasn't had the sense to send you already!




2 comments:

Alberto said...

Is there any effective strategy for preventing tumors in Li-Fraumeni positive individuals?
If oncologists don't know all the syndromes (ok, maybe Lynch, FAP, ecc are more common) wouldn't a good idea be to have a clinical genetist in every oncology group? Don't know how it works in the US.

Steve Murphy MD said...

From Gene Clinics

No surveillance measures, with the possible exception of breast cancer monitoring, have been shown to be effective in reducing morbidity or mortality among individuals with LFS or LFL. Routine mammograms and clinical breast exams are effective in women over age 40 years, but have not been proven to be beneficial for younger women with LFS or LFL.

Surveillance strategies have been suggested for individuals at risk for LFS or LFL [Varley, Evans et al 1997; NCCN 1999].

For at-risk children, on an annual basis:

Complete physical examination

Urinalysis

Complete blood count

Abdominal ultrasound examination

Additional organ-targeted surveillance based on family history (e.g., imaging studies of the head if a relative has had a childhood brain tumor)

For at-risk adults:

Complete physical examination every 12 months

Dermatologic examination every 12 months

Urinalysis and complete blood count every 12 months

Women only: clinical breast examination every six months

Women only: annual mammograms and annual breast MRI examination starting at age 20-25 years. Controversy exists regarding the use of routine mammograms in women with LFS, because of possible radiation sensitivity associated with TP53 mutations [Varley, Evans et al 1997; Eng et al 2001].

Additional organ-targeted surveillance based on family history (e.g., colonoscopies at regular intervals if a relative has had colorectal cancer)

Full-body MRI examination or PET scan has been suggested. However, no evidence supporting the benefit of such testing exists; in fact, it is possible that such testing leads to unnecessary biopsies or other follow-up tests.

Perhaps most importantly, at-risk individuals and their physicians are urged to pay greater attention to lingering symptoms and illnesses, particularly headaches, bone pain, or abdominal discomfort, and to schedule diagnostic tests promptly.

As for putting counselors or geneticists in Oncologists offices.....Way too many Oncs, way too few counselors. But it could be a start.

-Steve