We'll cover the general management principles for the more typical situation of patients with multiple brain metastases from lung cancer soon, but today we’ll cover the special situation of the patient who has a brain metastasis identified as the ONLY area of metastatic disease (generally referring to NSCLC, since SCLC has such a high tendency to spread distantly early in its history). Recall that metastatic, or stage IV, lung cancer, is treated with a palliative approach, due to the inability to achieve prolonged survival except in very rare cases. These patients are generally treated as a unique category for whom an aggressive treatment is often considered, not only for the brain metastasis but also for disease in the chest.
One important point is that finding an area of metastatic disease in the brain only represents the concept of a “precocious metastasis”, a metastatic deposit that somehow slipped out before the rest of the disease was readily shedding metastatic disease (not all of the discussion of this concept requires just a single brain metastasis – some consider this idea to also apply to up to three brain lesions that can be treated aggressively). A thorough staging workup, including a PET scan, is very important in this setting. If there is a brain metastasis and one liver metastasis or a second tumor in the lung opposite the main tumor, the brain lesion isn’t “precocious”: it’s now a cancer that has at least a couple of areas of distant spread. This doesn’t mean that the brain metastasis shouldn’t be treated aggressively, but the situation isn’t as favorable as having a stage I or II NSCLC cancer in the chest and a single brain metastasis. For that matter, many people also make the distinction between early stage NSCLC, especially stage I, in the chest and locally advanced NSCLC aside from the brain metastasis. The idea of the precocious metastasis doesn’t apply as well if the staging outside of the brain is IIIB. The most encouraging results have been in the patients with an early stage NSCLC tumor aside from a single brain metastasis. These are patients in whom surgery is often considered both for the lung disease and the brain metastasis.
There are two primary means of aggressive treatment for a solitary brain metastasis: surgery or stereotactic radiosurgery (SRS, also known as gamma knife, which is a brand name for the technique). The latter entails focusing a radiation beam very precisely on the target area, using a stereotactic frame to keep the skull in place, so the radiation obliterates the tumor in the brain but delivers very little radiation outside of the target area. There has never been a randomized controlled trial that directly compares neurosurgery to SRS, but the results of the two techniques have appeared to be quite comparable in terms of survival, local control in the brain, side effects, and treatment-related mortality (deaths). Because of this, they’ll be discussed as more or less interchangeable approaches in terms of providing local control of a single brain metastasis.
While there isn’t any suggestion that an aggressive approach for precocious brain metastasis should applies to any particular NSCLC subtype, outcomes have tended to be more favorable in younger patients and women, as well as those who develop a metastatic brain lesion some period of time after the lung tumor has been treated. The results also have a tendence to be more favorable in patients with a brain lesion less than 3 cm, compared with a larger tumor, and in those with lesions in the larger cerebral hemispheres compared with the cerebellum (the latter about 15%).
For patients in these situations, treated aggressively and with curative intent, survival far exceeds the general numbers for metastatic NSCLC. The five-year survival in many of these case series, which has involved a delay between lung tumor treatment and brain tumor treatment in about 2/3 of cases, hovers around 21%, with a range of around 16-30%. There is an approximately 2% mortality risk from aggressive, curative treatment, which historically has usually been surgery for both chest and brain.
One of the key questions is whether people should undergo whole brain irradiation after definitive treatment, whether neurosurgery or SRS, on a brain metastasis. This remains completely unclear, with one study showing no benefit (abstract here), and another showing a significant improvement in survival (abstract here). One study of 95 patients who underwent resection of a single brain metastases were randomized to receive post-operative WBI or observation (full article provided free here) and reported that WBI quite significantly reduced the rate of brain relapses (18% vs. 70%). Patients who received WBI were less likely to die of neurologic symptoms/complications (14% vs. 44%), but this didn’t translate into a significantly higher overall survival for recipients of WBI.
These trials have been conducted in a time in which adjuvant chemotherapy was not routinely administered for patients with early stage, resected chest disease. Now that post-operative chemotherapy is commonly recommended to reduce the risk of recurrence and death from lung cancer. This should only improve the long-term outcome for patients with a “precocious metastasis”, a high-risk situation but one in which we can see more and more patients surviving year after year to provide hope, another example of the benefit of tailoring treatment plans for different patients. This doesn’t apply for enough patients with advanced lung cancer, but it can certainly make a difference for the minority in whom it does apply.
We'll break from the subject of brain metastases and cover a few other issues, then get back to general management of brain metastases again very soon.