Unfortunately, patients with lung cancer often develop brain metastases.  Once discovered, brain metastases are most often treated with radiation therapy, sometimes preceded by surgery.

For non-small cell lung cancer (NSCLC) patients with a solitary brain metastasis, that is, only one identifiable “spot” in the brain, surgery is often used in combination with radiation therapy.  For NSCLC patients with multiple brain metastases, surgery offers less benefit.  However, if the diagnosis is not clear, or if one of multiple lesions in particular is causing symptoms, surgery can helpful for both diagnosis and relief of symptoms.  Relieving symptoms with surgery depends on the location of the lesion in regard to accessibility and function.  If the lesion is in a non-critical brain area, it often may be surgically removed; however, if it is in a critical area (for example, the brain area that controls motor function of the right leg), surgery can lead to even worse function (of the right leg).

After surgery for NSCLC brain metastasis, radiation therapy is used to decrease the risk of brain metastases reoccurring or causing symptoms.  Multiple options for radiotherapy treatment exist - mainly, whole brain irradiation and stereotactic radiosurgery.  They can be used alone or together.  For decades, standard treatment for lung cancer brain metastases has been whole brain irradiation.  In more recent years, stereotactic radiosurgery has increased in availability and has been used increasingly.

Choosing the right treatment depends dramatically on patient circumstances.  Let me describe a few situations:

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Here’s the second part of the webinar, co-sponsored with LUNGevity Foundation, by Dr. Minesh Mehta, Professor of Radiation Oncology and renowned expert in management of brain metastases.  Though his talk was very comprehensive, the topic of brain metastases is so relevant that there were a wide range of questions in a Q&A session that ended up lasting about half an hour, and even then, we weren’t able to get to every question.

Here’s the audio and video versions of the podcast (not really much video here, just in this format to have it go to the people subscribed to the video channel on iTunes, YouTube, etc.), as well as the transcript.

dr-mehta-brain-mets-qa-session-audio-podcast

dr-mehta-brain-mets-qa-session-transcript

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Dr. Minesh Mehta is a Professor of Radiation Oncology at Northwestern University, and he is also a world leader in the study and management of brain metastases.  He was kind enough to join us for a webinar several weeks ago in which he discussed the evidence about the benefits as well as the acute and longer term risks of various treatments that might prevent the development brain metastases or treat them if they’re identified.

Here is the podcast of his presentation in both audio and video form.  Along with them, you’ll find below the transcript and figures associated with this program.

dr-minesh-mehta-prevention-and-treatment-of-brain-mets-audio-podcast

dr-minesh-mehta-prevention-and-treatment-of-brain-mets-transcript

dr-minesh-mehta-prevention-and-treatment-of-brain-mets-figs

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Podcast: Play in new window | Download

   Re-treatment of brain metastases is one of the most difficult of cancer treatment problems.  It is also an area where the art of medicine supersedes the science by a long way.  The good news is that it is likely easier and safer as we shift from whole brain radiation therapy (WBRT) as standard for the first line treatment of brain metastases to stereotactic treatment (SRS).  The bad news is that our ability to look to the medical literature for guidance of risks and benefits is less.

   There are some studies looking at re-irradiation of the whole brain using altered radiation fractionation schedules (abstract here) after patients received standard WBRT.  The rationale for that is that the brain is an example of a tissue that is very sensitive to the size of the radiation treatment fraction.  So, giving smaller doses (fewer centiGray or rads) with each treatment and then treating twice a day to get the necessary total dose in a reasonable time, is an approach with solid theoretical rationale.  The study linked above treated 15 patients and none had significant side effects while on treatment, but median survival was 3.2 months, with 2 longer term survivors, out past 9 months.  Sixty percent (9 patients) had improvement from the re-irradiation. 

   A larger, though older, study (abstract here) looked at re-irradiation using standard fraction size after WBRT first line.  Median survival was 4 months, though the longest survival was 72 months.  Of the 86 patients reported on in this study, twenty-three patients (27%) had resolution of neurologic symptoms, 37 patients (43%) had partial improvement of neurologic symptoms, and 25 patients (29%) had either no change or worsened after re-irradiation.  Another retrospective study, this one from Princess Margaret Hospital in Toronto, Canada (abstract here) of 72 patients showed similar outcomes, with median survival of 4.1 months after re-irradiation.  Thirty-one percent responded, 27% were stable and 32% deteriorated post re-irradiation (though it is not stated if this is likely radiation or disease related, but clearly the re-irradiation provided no benefit).  The similarity of the results is noteworthy given that in Canada it is more common to use larger doses per fraction of radiation and shorter courses of treatment than in the US.  Therefore, it confirms for us that the effects from two courses of whole brain radiation are that roughly 1/3-2/3 of patients will benefit.

   What about re-treatment after stereotactic treatment front line?  If the tumors are distant from each other, there is no difficulty or concern on treating the new brain mets with radiosurgery, as that area of the brain hasn’t received much or potentially any radiation dose so far.  What if the tumors are close together or recurrent in the same area?  Here the data are thin soup- ie, sketchy.  Data from the group at the  University of Pittsburgh group (abstract here), which is one of the best and most experienced in the world, shows that it can be safe even if in the same area, depending upon dose used and volume treated, but keep in mind, most places do not have the expertise that U. Pitt does.  Also, as the volume of retreatment increased, so did the neurologic decline of the patient.

   More difficult still is the question of when to move from repeated stereotactic treatments to whole brain radiation therapy.  For that, there is no clear answer and falls very much under the rubric of “clinical judgment”.  In the ASTRO (American Society for Therapeutic Radiation and Oncology) abstract discussed in a previous posting, there are many patients who now never move from stereotactic to whole brain treatment, despite repeated intracranial metastases.  Factors to consider when deciding on whole brain vs. stereotactic re-treatment are how many metastases, the overall functioning of the patient and the status of disease outside the skull. 

   Having been involved in this forum with patients and their families, I would add that side effects from whole brain radiation therapy can be more disabling than is often reported in the medical literature, and so it seems that we will likely continue to see a clinical practice shift away from this option as SRS permeates more of the local cancer treatment centers.  In my opinion, WBRT continues to have a valuable role in cancer treatment, but at this point, in the situation of recurrent brain metastases it is probably best suited for patients with many (>4) brain mets, and/or limited survival, though, in the interest of full disclosure, many of my colleagues would disagree.  There is little consensus about “how many brain metastases are too many” for SRS in actual clinical practice. 

We’ve previously discussed whole brain radiation therapy (WBRT) has been the historical cornerstone of treatment for brain metastases, and how surgery is sometimes employed in certain cases, but stereotactic radiosurgery (SRS) has dramatically changed the treatment of brain metastases. SRS involves using a high dose of extremely focused radiation to a small area, most commonly in the brain tissue. Several machines can be used for this approach, most commonly Gamma Knife, potentially Cyber Knife, but sometimes other machines.

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It has been best studied in the setting of just 1-3 brain metastases, but it’s being used increasingly in patients with many brain metastases, a setting in which we have no real data, and there’s a good deal of controversy around whether patients are better served by whole brain radiation in that setting. Read the rest of this entry »

Up to a few years ago, whole brain radiation therapy (WBRT) was the clear standard intervention for patients with lung cancer and brain metastases. Although median survival after WBR has been typically measured as a several months, that clearly exceeded the survival without treatment (typically in the range of weeks). There are several schedules, but the most common one has been 30 Gray (Gy) delivered in 10 three-Gy fractions over a two week period (Mon-Fri x 2 weeks) (abstract here). In addition to improving survival, WBRT also has a good likelihood of improving symptoms. Generally, about 60% of patients experience a complete or partial response to WBRT in terms of tumor shrinkage and/or improvement in neurologic symptoms. The dose is not likely to be enough to definitely control disease in the brain long-term, but the dose and schedule evolved as a compromise of trying to reduce the duration, minimize side effects, and control lung cancer in the brain for reasonably well. All too often, disease outside of the brain is progressing as well, so pushing the brain metastases onto the back burner has been the main achievement. It has remained the cornerstone of treatment for multiple brain mets, and particularly so for SCLC, where patients are particularly likely to have multiple lesions in the brain.

The other setting where WBRT is commonly recommended is after either surgery or radiosurgery (”gamma knife”) for one or a few lesions, in order to reduce the risk for further brain metastases. Studies have shown that on MRI patients with a brain metastasis have an 80% likelihood of an additional lesion, 50% have more than three, and over 70% of patients will develop recurrence in the brain if WBRT is not included after resection or radiosurgery (reference here).

The downside is that there is a real risk of developing significant symptoms from WBRT itself, including dementia or even, rarely, death (abstract here). It has actually been quite hard to assess the degree of neurocognitive decline in patients who receive WBRT, because detailed cognitive testing has often demonstrated a subtle deficits before starting WBRT, presumably as a function of their brain metastases. One study shows that memory (delayed recall) initially declines by three months after WBRT but then improves, even beyond pre-WBRT baseline (abstract here):

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