Those who have followed my writings over time will know that I haven’t been inclined to adopt a reflexive strategy of ordering molecular testing without good evidence that having this information will improve outcomes. Testing tumors for EGFR mutations is advocated by a vocal minority of lung cancer experts in Boston and New York City, but this hasn’t been advocated by the broader lung cancer community yet, or adopted as routine clinical practice.
Circulating Tumor Cells from Lung Cancer as a Window into the Tumor: Important Proofs of Principle Published in NEJM
In a recent issue of the New England Journal of Medicine, a research group from Massachusetts General Hospital in Boston published some very promising results from their work showing that they can now detect circulating tumor cells (CTCs) from most patients with lung cancer and even detect EGFR mutations and other molecular findings from these cells collected just from patient blood samples (
Continuing on the subject from my last post of gene signatures to predict clinical behavior, another ASCO presentation came from Poland (abstract here), with the goal of validating a couple of different kinds of gene signatures that have been presented before.
I had described earlier this week (prior post here) how the long-term follow up of one of the more important adjuvant chemotherapy trials for early stage resected NSCLC patients showed that there may be long-term adverse effects of chemotherapy. My last post also suggested that the benefit of pre-operative chemotherapy in another trial appeared to be limited to the patients with stage IIB and IIIA disease and wasn’t present for stage IB and IIA patients.
The issue of population-based differences in response to lung cancer treatments was essentially introduced with the EGFR inhibitors, so it’s appropriate to introduce racial differences overall with this work. Mention of more favorable results with EGFR inhibitors iressa and tarceva emerged with the earliest clinical studies and have since become a well established truism. Let’s explore what we know now and how we got here.
Infused throughout the website is a constant recognition that "patients are different", but while we know this intuitively, we're really not moved to a point of individualizing treatment on the basis of this. There are many lines of clinical research that are moving in that direction, and one of the key elements is pharmacogenomics, the study of the genetic underpinnings of the differences among people in response to a medication, both in terms of response and side effects.
As I described in my prior post, the marker ERCC1 (excision-repair cross complementing group 1) is a prognostic variable that is associated with a more favorable survival in patients who aren't treated with chemo after surgery for early stage NSCLC. But this marker also appears to be predictive of resistance to cisplatin and a worse survival in patients treated with platinum-based chemo after surgery.
Although I’ve described this concept in a few posts over the past year, it’s time for me to dedicate some real discussion to the concept of individualizing treatment with the ERCC1 marker. ERCC1 stands for excision repair cross-complementing group 1, and it helps repair damage to DNA.
NOTE: ALL FIGURES CAN BE SEEN BY DOUBLE-CLICKING ON THEM, EVEN THOUGH NOT ALL APPEAR AS THUMBNAIL VIEWS PROPERLY.