New Perspectives on Brain Metastasis

The UCLA Metastatic Brain Tumor Program treats metastatic disease focally so as to spare normal brain tissue and function. Focal treatment allows retreatment of local and new recurrences (whole brain radiation is once and done, cannot be used again). UCLA is equipped with X-knife and Novalis to treat tumors of all sizes and shapes. For patients with a large number of small brain metastases (more than 5), they offer whole brain radiotherapy.

http://neurosurgery.ucla.edu/Programs/BrainTu...

As reported in MD Anderson's OncoLog, in the past the only treatment for multiple metastases was whole brain radiation, which on its own had little effect on survival. There are now a variety of effective treatment modalities for people who have fewer than four tumors. Dr. Jeffrey Weinberg at the Department of Neurosurgery at MD Anderson has said "with a small, finite number of tumors, it may be better to treat the individual brain tumors themselves rather than the whole brain." Anderson is equipped with Linac Linear Accelerator. The critical idea is to focally treat all tumors.

http://www2.mdanderson.org/depts/oncolog/arti...

The results of a study at the University of Pittsburgh School of Medicine reported that treating four or more brain tumors in a single radiosurgery session resulted in improved survival compared to whole brain radiation therapy alone. Patients underwent Gamma-Knife radiosurgery and the results indicate that treating four or more brain tumors with radiosurgery is safe and effective and translates into a survival benefit for patients.

http://newsbureau.upmc.com/UPCI/GammaKnifeStu...

An editorial by Drs. Arlan Pinzer Mintz and J. Gregory Cairncross (JAMA 1998;280:1527-1529) described the morbidity associated with whole brain radiation and emphasized the importance of individualized treatment decisions and quality-of-life outcomes. Patients who avoided the neurologic side effects of whole brain radiation had an improvement in survival. There is no survival benefit or prolonged independence in patients who received postoperative whole brain radiation therapy. There may have been some less tumor recurrence but not more long-term survival.

Had fatigue, memory loss and other adverse effects of whole brain radiation been considered, and had quality of life been measured, it might be less clear that whole brain radiation is the right choice for all patients. These patients do not remain functionally independent longer, nor do they live longer than those that have surgery alone, said researchers in a report in an issue of The Journal of the American Medical Association.

Of course, surgical excision is the gold standard of treatment for surgically accessible lesions. Many studies in the medical literature clearly demonstrate the efficacy and superiority of surgical resection followed by focal radiation over whole brain radiation therapy as a first-line treatment for metastatic brain tumors. Doctors at UCLA and MD Anderson say that even for patients with up to four metastases, surgical excision of all intracranial disease has been shown to provide the long survival with good quality of life, and has the same prognosis as someone who has only one brain tumor.

New Perspectives on Brain Metastasis

Sometimes, symptoms of brain damage appear many months or years after radiation therapy, a condition called late-delayed radiation damage (radiation necrosis or radiation encephalopathy). Radiation necrosis may result from the death of tumor cells and associated reaction in surrounding normal brain or may result from the necrosis of normal brain tissue surrounding the previously treated metastatic brain tumor. Such reactions tend to occur more frequently in larger lesions (either primary brain tumors or metastatic tumors).

Radiation necrosis has been estimated to occur in 20% to 25% of patients treated for these tumors. Some studies say it can develop in at least 40% of patients irradiated for neoplasms following large volume or whole brain radiation and possibly 3% to 9% of patients irradiated focally for brain tumors that developed clinically detectable focal radiation necrosis. In the production of radiation necrosis, the dose and time over which it is given is important, however, the exact amounts that produce such damage cannot be stated.

Late effects of whole brain radiation can include abnormalities of cognition (thinking ability) as well as abnormalities of hormone production. The hypothalamus is the part of the brain that controls pituitary function. The pituitary makes hormones that control production of sex hormones, thyroid hormone, cortisol. Both the pituitary and the hypothalamus will be irradiated if whole brain radiation occurs. Damage to these structures can cause disturbances of personality, libido, thirst, appetite, sleep and other symptoms as well. Psychiatric symptoms can be a prominent part of the clinical picture presented when radiation necrosis occurs.

http://www2.mdanderson.org/depts/oncolog/pdfs...

Patients who received stereotactic radiosurgery for four or fewer contained metastases to the brain lived as long, and had comparable radiation side effects and mental functioning, as patients who were treated with whole brain radiation.

http://www.cancer.gov/clinicaltrials/results/...

Whole Brain Radiation Therapy vs. Stereotactic Radiosurgery on Brain Mets

I often thought about the problem of unintended self-interest bias which may be a factor in this problem.

Some years back, the government had asked Joseph P. Newhouse, a health policy professor at Harvard, and his colleagues to look into how the Medicare reimbursement system may affect how doctors prescribe chemotherapy.

His study "Does Reimbursement Influence Chemotherapy Treatment For Cancer Patients?" co-authored with Dr. Craig C. Earle, was finally published in Health Affairs in 2006. This joint Michigan/Harvard study added to the 'smoking gun' survey by Dr. Neil Love, "Patterns of Care."

I wrote to both of them to ask if their study methodology on reimbursements influencing chemotherapy treatments, could be applied to reimbursements influencing radiation treatment?

Before the days and widespread use of Stereotatic, Gamma-Knife, Cyber-Knife, and the like, the most expensive treatment for postoperative brain surgery for a solitary brain metastasis was whole brain radiation. With the newer treatments, whole brain radiation was abandoned because of the substantial neurological deficits that resulted with its use, sometimes appearing a considerable time after treatment. Today, cutting-edge clinical practices use a more "focused" radiation field.

During the last twenty years when the preponderance of cancer care shifted from the institution-based, inpatient setting to community-based, ambulatory sites for treating the majority of the nation's cancer patients, many of these community-based settings did not have the cutting-edge high-tech toys.

Was there an incentive for radiation oncologists at community cancer centers to chose whole brain radiation treatments, as these were the most expensive, for them? Could Newhouse's methodology collect data documenting a clear association between reimbursement to radiation oncologists for whole brain radiation treatment which is based on how much incentive occurs to the radiation oncologist?

They thought that there were similar issues, but their methodology would be different because radiation isn't something that individual doctors buy, sometimes at a discount, and then profit from if they're reimbursed more for it, as in the case with chemotherapy.

They relied upon price variation across regions in Medicare, which was pseudo-random and had been eliminated. To their knowledge, there was no comparable price variation in radiology that they could have used.

However, they did mention a radiation oncologist in Michigan, who had done some work looking at the number of palliative fractions of radiation given to patients with advanced lung cancer as being a situation in which there is a lot of discretion on the part of the physicians: one fraction is as good as 10, but 10 will reimburse more. I'm not sure if he ever published or presented his results? Interesting!