Senator Kennedy's Brain Cancer Followed a Typical Course

Zosia Chustecka

August 28, 2009

August 28, 2009 — The malignant glioma that resulted in the death of the remarkable Senator Edward Kennedy earlier this week appears to have followed a distinctly unremarkable course, cancer experts say.

Brain cancer experts interviewed by Medscape Oncology speculated that the Senator had the most aggressive form of the disease, glioblastoma multiforme, and commented that his survival for 15 months after diagnosis is "right on the median" for this type of tumor.

Senator Kennedy was diagnosed with a malignant glioma in May 2008, after being hospitalized following a seizure. A month later, he underwent what was described as "successful" surgery at Duke University Medical Center, Durham, North Carolina, and then received both chemotherapy and radiation after returning home to Massachusetts.

Six months after the diagnosis, Senator Kennedy had returned to the Capitol and was working part-time while still continuing with treatment.

However, in January 2009, he collapsed during the inaugural luncheon for the new president Barack Obama and appeared to be having a seizure as he was helped from the room by medical personnel.

Although he was absent from Senate for much of this year, he continued with political campaigning, which included advocacy for healthcare reform.

Earlier this month, however, his absence at the funeral services for his sister prompted speculation about his failing health. Just last week, he wrote a letter to legislative leaders asking for an action that — without mentioning himself or his brain cancer — would effectively ensure that his views would be heard even if he was not able to be present himself. In the letter, described by the Boston Herald as a "stunning admission of his frailty," he asked for a temporary gubernatorial appointment to his seat.

Most Aggressive of Gliomas

The time-line suggest that the tumor was a glioblastoma multiforme, the most common and the most aggressive of gliomas, commented Keith Black, MD, chairman and professor of neurosurgery at the Cedars-Sinai Medical Center. These tumors have a bimodal distribution, with a peak at 50 years and another at 70 years of age, he added.

Gliomas are a broad category, Dr Black explained. They include grade 1 and 2 tumors that are regarded as precancerous, although about 70% of these go on to become malignant, and also include grade 3 anaplastic astrocytomas and grade 4 glioblastomas.

In the United States, about 30,000 primary brain tumors are diagnosed annually, he added. Of these, 15,000 are gliomas and 8,000 are glioblastomas.

The median survival for glioblastoma multiforme is about 15 months, Dr Black commented, adding that the Senator was "right on the median."

Very Good Treatment

Another expert, Gregory Riggins MD, PhD, professor of neurosurgery and oncology at John Hopkins University School of Medicine, agreed that the Senator's survival was "right on the average" for this type of tumor. "This suggests that he received very good treatment," he added.

Surgery followed by both radiation and chemotherapy is the current standard of treatment, Dr Riggins added. "The surgery was apparently pretty extensive," he commented, adding that this would be "fairly typical. These tumors are very invasive, and they spread locally. They look like fingers pushing their way into the surrounding brain tissue."

Two chemotherapy regimens have been shown in clinical trials to extend survival in glioblastoma multiforme, Dr Riggins explained – temozolomide (Temodar, Schering) and the Gliadel wafer (polifeprosan with carmustine implant). Both have a similar effect of extending survival by a few extra months, he added, but temozolomide is the more commonly used of the 2, he said, adding that it was probably this that Senator Kennedy received.

Dr Black agreed that temozolomide was probably used, but he suspects that the anti-angiogenesis agent bevacizumab (Avastin) was also used. This drug was approved 3 months ago for use as a second-line in the treatment of glioblastoma, as reported at the time by Medscape Oncology.

"Whether or not it extends survival is controversial, but it clearly has benefit in improving MRI scans – it decreases the enhancement on the MIRI scan, which means that the blood/brain barrier is less leaky," Dr Black commented. "My own personal opinion is that it does extend survival, and it definitely improves quality of life for these patients, as they can reduce the dose of steroid because bevacizumab reduces the swelling on the brain."

Dr Black also commented that the radiation Senator Kennedy received was likely to have been proton beam radiation at the Massachusetts General Hospital. This is different from the more standard fractionated linear acceleration radiation that would be given to such patients, but there is no data to suggest that either form of radiation is better than the other, he commented, although the benefit of radiation in this tumor is proven.

Both experts commented that seizures are very commonly the first symptoms on presentation, and added patients are frequently given anti-convulsive medication throughout their treatment.

"This phenomenon is very common, as it appears that there may be a mechanism by which the tumor stimulates seizures," Dr Riggins explained. Typically, such patients would receive anti-seizure medication, but these seizures can be hard to control, he added.

Passionate Health Care Advocate

Since his death tributes from many United States medical organisations have been pouring in, praising Senator' Kennedy's passionate advocacy for better health care, and highlighting in particular his achievements in the fields of cancer and mental health legislation.

"Over the last half century, Senator Kennedy has stood as a tireless champion in the fight against cancer and was the driving force behind improving health care and research policy in the US Senate," noted a statement from the American Association for Cancer Research (AACR).

The Senator became a cancer advocate in 1971, when he helped create the National Cancer Act, the AACR noted. Over the last 2 years, he was working closely with the association to create the 21st Century Cancer ALERT Act, which aims to speed up research and translation from lab to bedside.

"It's a cruel irony that the Senator's life was taken by cancer," commented Dana-Farber Cancer Institute president and CEO Edward Benz, Jr, MD, as "there are countless cancer survivors who are alive today because of the Senator's passionate and tireless efforts to support cancer research, to ensure better access to cancer care, and to promote cancer prevention."

The American Psychiatric Association (APA) praised his "passion and commitment to health care issues during his long career in the Senate. Even as he was fighting for his life, he put patients and their care first, and fought for the 46 million Americans who are uninsured."

According to the APA, after his treatment for cancer, the Senator's "dramatic return to the Senate" led to the "passing of a landmark legislative reform bill for mental health." This mental health insurance parity law is one of the "most significant victories of the past 10 years for people who live with mental illness," said Michael Fitzpatrick, executive director of the National Alliance on Mental Illness.

Senator Kennedy was also "instrumental in reducing the disparity of the 50% Medicare coinsurance requirement for mental health services, thus ensuring those who have a mental disorder are provided with access to care on an equal level," the APA noted.

In total, Senator Kennedy authored more than 2500 bills during his time in the US senate, many hundred of which have gone on to become laws (


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