5 MYTHS ABOUT BRAIN METASTASES

It is time to address a series of myths or "historical misconceptions" about brain metastases that might be compromising the optimal care of patients, according to a report published in the July issue of Neurosurgery.

Brain metastases have often been subjected to a "nihilistic" approach from the oncology community for a variety of reasons, including the relatively short survival of affected patients, write the authors, led by Douglas S. Kondziolka, MD, MSc, director of the Gamma Knife Program in the Department of Neurosurgery at New York University Langone Medical Center in New York City.

"We are in an era of personalized medicine," Dr. Kondziolka said in press statement, "and we need to begin thinking that way [with brain metastases]."

Although research in the field has been insufficient overall, "gains have clearly been made" in a series of randomized trials, comparative cohort studies, registries, and guidelines, the authors assert.

So the team took the initiative to dust off and clear out 5 "key" misconceptions that linger and "commonly drive" clinicians' approaches to treatment.

An expert not involved with the report likes the list.

"The authors did a great job looking at the current issues with respect to the evidence and highlight 5 areas of controversy," said Arjun Sahgal, MD, associate professor of radiation oncology at the Sunnybrook Odette Cancer Centre in Toronto.

But the truth is, the list could be longer, he said. There are "many" areas of treatment and management that are based on misconceptions and are in need of clinical trials and evidence, he told Medscape Medical News in an email.

For now, the authors submit the following 5 misconceptions.

Misconception: All histologies are created equal

This "one size fits all" approach resulted in, among other things, randomized treatment trials of brain radiotherapy and/or surgical resection that pooled together different primary cancers. The "assumption" was that the "primary diagnosis was irrelevant."

This has produced clinical trial results that did not control for the factors "that most strongly affected outcomes," like the different drugs used in the different primary cancers. Such outcomes data need to be considered with a grain of salt, suggest the authors.

"Broad histological inclusion" is still the norm today in clinical trials, they add.

Correction: Clinicians should recognize that brain metastases are not all the same and will have biologic differences resulting from different types of the original extracranial cancer, such as those from the lung, breast, or skin.

Misconception: The number of brain metastases is the best indicator for guiding management

This "counting tumors" approach to stratify patients has spawned a number of clinical problems, say the authors. For instance, with this approach, an 8 mm diameter frontal lobe melanoma metastasis is given the same "weight" by clinicians as a 2 cm diameter thalamic tumor from non-small-cell lung cancer. That is not helpful because of the different symptomatic presentations that are likely with such different lesions, explain the authors.

Correction: Total tumor volume might be more predictive of survival, local control, and distant brain failure than the number of tumors.

"One cannot dismiss tumor number as being unimportant, but real tumor burden should be our new focus," the authors write.They cite a number of contemporary studies to back up this point.

For example, in a study of 251 patients with brain metastases who underwent radiosurgery, the number of brain metastases (1 to 9) was not predictive of survival, local control, or distant brain failure. Instead, total tumor volume greater than 2 mL was predictive of survival and local control, which was 94% at 1 year (Int J Radiat Oncol Biol Phys. 2013;85:656-661).

Dr. Kondziolka told Medscape Medical News that the myth about tumor number even influences insurance payments. "Payers often approve treatment of the brain depending on the number of tumors present, which may have little to do with outcome," he emphasized.

Misconception: When a metastatic brain tumor is present, micrometastases are also always present and in need of management

"It is still held that micrometastases...create a diffuse problem no matter how many [bigger] tumors might be visible on an imaging study," write the authors.

If this thinking was accurate, then whole-brain radiation therapy (WBRT) should improve survival when it is added to a focal therapy, such as stereotactic radiosurgery (SRS), the authors argue. That is not what happens. "In no large study does the addition of WBRT to SRS improve survival," they write.

Correction: "Blindly managing assumed metastases is no longer best practice when such tumors can be defined with serial images," the authors assert.

Micromets will surface if they are significant, they suggest. "If micrometastases are present and not treated, they should become apparent on later imaging."

WBRT is not needed for every patient, they note.

Indeed, "strong evidence" indicates that focal therapies for isolated metastatic lesions improve survival, compared with the more diffuse WBRT.

Citing 2010 guidelines, the authors explain that both single-dose SRS and WBRT are effective for treating patients with brain metastases, but single-dose SRS alone provides a survival advantage over WBRT alone for patients with as many as 3 metastases.

Misconception: WBRT is always harmful — eventually

The idea behind this myth is that WBRT is generally unjustified because it will cause cognitive dysfunction if a patient survives long enough.

Correction: The authors, who are certainly critical of WBRT in their writing about other misconceptions, point out some of the potential benefits of WBRT in this section of their report.

For example, "an argument can be made," they say, that patients with large volumetric tumor burdens actually have a delay in cognitive decline when receiving WBRT, compared with those who do not. (A counterargument can also be made — that SRS alone is enough therapy and reduces the risk for cognitive adverse effects, they also say.)

Ultimately, the authors call for a "balanced approach that allows for individualization" of treatment.

Cognitive deficits occur as a result of WBRT, but also occur in the absence of WBRT — because of tumor progression. Such progression can be slowed by WBRT, so "an appropriate balance" needs to be sought.

Examples of patients who should avoid WBRT are someone who is "high-functioning" and concerned about cognitive decline or those in whom extended survivals are expected, they write.

But Dr. Sahgal emphasized some of the potentially negative impacts of WBRT in his comments toMedscape Medical News.

"Clearly, we are learning that WBRT has adverse effects on quality of life and neurocognition," he said. And he asked about the impact on the estimated 50% of patients who have brain metastases but will not go on to develop distant brain mets. Such patients may not benefit from WBRT with respect to reducing the risk of new lesions developing, and the limited gain in local control with additional WBRT following SRS has to be put in context with the increased risk for radiation necrosis. The trade-off between the adverse events and potential benefits is questionable in that population, he suggested.

Misconception: Most brain metastases cause very obvious symptoms, making regular screening unnecessary

This misconception did not apply until recently and still is not a full-blown myth. In past years, imaging for neurologic screening was rare, and it is still not commonplace, the authors acknowledge. As a result, the majority of brain metastases have been found because of symptoms — headaches, seizures, or neurologic deficits.

But melanoma studies conducted in the late 1990s helped change the clinical landscape and are pushing these facts into the direction of myths, the authors suggest.

Correction: Melanoma patients who entered immunotherapy clinical trials in the 1990s needed "screening" MRIs to prove or disprove brain metastases, explain the authors.

As a result, MRI helped to identify many tumors in melanoma patients that were small and, importantly, asymptomatic.

Now, the authors say that in oncology in general, the goal of brain mets treatment is to "prevent neurological deterioration" while care for the extracranial cancer goes on.

Most oncologists now obtain an MRI at "any hint of neurological symptoms." Thus, the bar has been lowered for this imaging in cancer patients, from obvious symptoms to those that are just a "hint."

Dr. Kondziolka and Dr. Sahgal have disclosed no relevant financial relationships. A number of coauthors have financial ties with industry, as detailed in the report.

Neurosurgery. 2014;75:1-9. Abstract