There's a general concept out there that chemo is ineffective in treating brain metastases, and in fact, I've mentioned it in some comments here in the past. The reasoning behind this is that we know there's a blood-brain barrier, and we've presumed that chemo is blocked from crossing it.

As I described in prior post, prophylactic cranial irradiation (PCI) is established as a treatment approach for patients with LD-SCLC who have had a complete or "good partial" response to chemo and radiation. Some physicians also recommend PCI for patients with ED-SCLC who have experienced a very good response, since about 10% of the patients on the PCI trials that led to our current recommendations had ED-SCLC.

Inhibitors of the epidermal growth factor receptor (EGFR), such as Iressa (gefitinib) and Tarceva (erlotinib) are generally known for being often minimally toxic, oral, targeted therapies that can occasionally produce dramatic and long-lasting responses in a minority of patients and more modest, minor responses or prolonged disease stabilization in a larger proportion of patients. They are not widely considered as a treatment for brain metastases, but there are many reports that describe responses, including prolonged ones, of brain metastases to Iressa or Tarceva.

I briefly mentioned the potential value of surgery for a solitary brain metastasis, where it is commonly used, in another post. Today I'll talk more specifically about where the role for surgery has been specifically tested for brain metastases in lung cancer.

A novel agent called motexafin gadolinium (MGd), with a marketed name of Xcytrin, has been studied as a potential neuroprotectant as well as radiosensitizer that may allow patients with brain metastases to do better when it as added to whole brain radiation therapy (WBRT) than they would with WBRT alone.

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.

While brain metastases are common, some patients seem to be at higher risk than others. As previously noted, SCLC has a very high risk of spread to the brain. For NSCLC subtypes, several studies have shown that patients with non-squamous lung cancers have a greater tendency to develop brain metastases than those with squamous cancers, which tend toward more local spread.

I'm going to cover the general concepts of management of brain metastases, a subject that is still evolving because of our growing technology, particularly with stereotactic radiosurgery (SRS), commonly referred to as gamma knife. In many cases, our practice has moved a bit ahead of the data. We'll start with some general issues and then, over several posts, cover issues from surgery to radiation to medical therapy.