Plenary Session: Lung Cancer in Never Smokers
The day started if with Dr. Thun from the American Cancer Society. He reviewed environmental factors contributing to Lung Cancer in never smokers. He started by reminding us that although only 10% of lung cancer deaths in men and 15-20% of lung cancer deaths in women are due to nonsmoking cancer, the burden of suffering caused by non-smoking lung cancer is actually rather high. If non-smoking lung cancer were treated as its own disease, separate from smoking-driven lung cancer, it would rank eighth among the most common fatal cancers in America! He reviewed environmental factors known to cause lung cancer: secondhand smoke, radon, asbestos, certain metals, some organic chemicals, radiation, air pollution, tubercoulosis, and other chronic inflammatory conditions. Others exposures likely also play a role, but have yet to be proven: human papilloma virus and chronic inhalation of cooking fumes and incense. Indoor air pollution from cooking, coal burning, and smoking men may explain the extraordinarily high rate of nonsmoking lung cancer among women in some areas of Northern China.
Dr. Pierre Massion of Vanderbilt took the stage second to talk about the molecular pathogenesis of never smokers. He reminded us of the different histologic tendencies of never smokers—less SqCC, more adenocarcinoma including the multiple subtypes once called BAC. He reviewed genes associated with susceptibility including cyp1a1, gstm1, xrcc1, gpc5, and fam38b. He pointed out the role of genetic differences in key molecules in inflammatory pathways: IL-1b, IL6, and IL1RN. Finally, insults from the environment may be expressed differently based on variations in genetic susceptibility.
Dr. Massion then used the figure, reproduced below, from Pao et al, Lancet Oncology 2011 to remind us how far we have come in understanding the molecular drivers in nonsmoking cancer:
Studies have shown particular genomic signatures in never smokers. But not only is the DNA changed, but DNA modifiers (epigenetics) are also changed and we have defined specific genes whose expression is modified.
Dr. Pinder previously summarized the early story of the newly identified EML4-ALK mutation in NSCLC, which traces back only a couple of years. Amazingly, in that short time, treatments targeting this mutation have already been identified and administered to patients who are benefiting from these novel agents at this very moment. Still, one of the leading issues with this story of progress is that the EML4-ALK mutation appears to be present in less that 5 percent of the overall NSCLC population, so people may ask how valuable this discovery really is.
That really depends on a couple of factors. First, screening for an EML4-ALK mutation will be much more appealing and feasible if we have some hints of which pateints are more or less likely to have one of these mutations. Second, we need to have a treatment that helps the people we screen who have the ALK mutation.
The ASCO meeting I’m at right now is so insanely busy during the days and nights that it’s next to impossible to carve out the time to write posts during the meeting. While the talk show hosts just show re-runs while they’re on vacation, we’re at least going to put up some new content, even if it’s from work previously done (and this is far from a vacation).
This podcast features Dr. Suresh Ramalingam, Director of the Thoracic Oncology Program from Winship Cancer Institute at Emory University in Atlanta. We discussed recent data that have led to changes in our current treatment standards for first line treatment of advanced NSCLC, as well as emerging evidence leading to debates about maintenance therapy after a fixed amount of initial chemotherapy. The video version includes synchronized figures. The audio is an mp3 file.
I’ll add the figures and transcript very soon.