When I joined GRACE earlier this month, a question was posed by a reader regarding whether there is an increasing frequency of the diagnosis of lung cancer in women who have never smoked. This is a very interesting question that those of us who specialize in lung cancer frequently wonder about.

With all this recent talk about never-smokers with lung cancer, and the interest in stories of patients with so-called “oligometastatic” cancer (minimal metastatic burden to perhaps a single site), I thought I would describe a recent case in my clinic as an illustration of how I use this information in everyday decision making. Mrs. D, a very fit 36 year-old woman with a young child at home, presented to her family doctor last year with back pain. It didn’t seem to be getting better, so her doctor ordered an x-ray of the back which showed a very nasty-looking spot in the lower spine.

One of the principles of screening is that the likelihood of detecting a cancer depends greatly on the risk that a person being screen has for developing that cancer. Low risk means that it is very likely that any abnormality that is detected is more likely to be unrelated to cancer. And because of that, nearly all of the screening efforts thus far have focused on patients with a significant smoking history.

A quick point on the importance of biology over treatment. Years ago, I highlighted the results in the TRIBUTE trial of chemo with placebo or combined with erlotinib (tarceva) at the same time (biomarker study abstract here), which showed that patients with EGFR mutations had a much better survival whether they received an EGFR inhibitor or not:

Actually, it's some background information and your blood that's needed.

An interesting trial presented at ASCO 2008 came out of Japan, asking the question of whether there is an advantage to continuing first line platinum-based doublet chemo for up to six cycles or whether it might be better to give just three cycles and then switch from chemo right to the EGFR inhibitor iressa in Japanese patients with advanced NSCLC (abstract here).

The European Society for Medical Oncology (ESMO) Congress, similar to ASCO but based in Europe, has been going on in Stockholm, where the results of a study called the First Line Iressa versus Carboplatin/Paclitaxel in Asia Study (taking some liberties to force it into the acronym "IPASS") was presented in the Presidential Symposium by my friend and Hong Kong-based colleague Tony Mok.

We’re recognizing more and more that lung cancer in never-smokers (LCINS) is a distinct disease, with different patterns of who gets it, how the cancer behaves, and it responds to treatments. But this recognition is still a work in progress, coming from a background in which the party line has been that NSCLC is treated the same regardless of the histologic type (squamous, adenocarcinoma, large cell, or other), smoking history, or other factors.

In a recent issue of the Journal of Clinical Oncology, Dr. Vince Miller and colleagues published the results of an important trial of the EGFR inhibitor tarceva (erlotinib) in the unusual NSCLC subtype bronchioloalveolar carcinoma, or BAC (abstract here). This work was predicated on the observation, also by Dr.

As I've mentioned in some prior posts, there is increasing recognition that lung cancer in never-smokers may be a different disease. Some of this has been defined by working backward from treatment results, where we've seen that never-smokers are consistently among the greatest beneficiaries of EGFR inhibitor therapies like Iressa or Tarceva. But there are some general principles and recurring themes with regard to the genetics of lung cancer in never-smokers.