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Dr. Jack West is a medical oncologist and thoracic oncology specialist who is the Founder and previously served as President & CEO, currently a member of the Board of Directors of the Global Resource for Advancing Cancer Education (GRACE)

 

The Future of the Field: "Molecular Epidemiology" and SWOG Trial 0424
Author
Howard (Jack) West, MD

It's only been in the past few years that we have begun to appreciate that there may be many different subgroups of patients who fit within the broader lung cancer population. We now have begun to see differences in the safety and/or activity of certain drugs in never-smokers vs. smokers, patients with adenocarcinomas (and especially bronchioloalveolar carcinoma, or BAC)vs. squamous cell carcinomas or other subtypes, and even in women compared with men. This work has been primarily involved looking back retrospectively at how patients with different clinical characteristics did on various treatments. But we are also starting to move into a new era of collecting tumor tissue and blood on patients with different characteristics in order to learn about the molecular epidemiology (study of various factors in disease) to learn about the different genes and proteins that may define new subgroups of lung cancer, and how they may relate to gender, smoking status, and other factors we already recognize. SWOG trial 0424 is an important new type of research that we hope will move the field forward.

This national trial focuses on patients with a new diagnosis of stage I, II, IIIA, or IIIB NSCLC without a malignant pleural effusion -- in other words the patients with NSCLC that we can treat for a cure. The trial does not change treatment in patients receiving care for lung cancer, but rather just looks carefully at the correlation between multiple potentially relevant blood and tumor biological markers in men vs. women and smokers (current or former) vs. never-smokers, to see if there are differences in the biological variables of these different groups. It will also follow how patients do in terms of cancer progression and survival for up to five years after they enroll on the trial. The trial seeks to enroll a total of 720 patients, comprised of 120 female never-smokers (less than 100 cigarettes lifetime), 120 male never-smokers, 240 female ever-smokers, and 240 male ever-smokers. Patients who agree to enroll must be within 4 months of their diagnosis and staging and must not have received any whole body therapy (chemotherapy or targeted therapy) yet, and they submit several vials of blood and some tumor tissue from the biopsy or surgery, and complete a one-time questionnaire about exposure to carcinonogens (ranging from actual smoking passive smoke to other toxins), hormone therapy, and other factors that may relate to cancer risk.

The molecular studies that are being done include assessment of tobacco-related DNA changes, alterations in specific cancer genes ("oncogenes"), and expression of hormone receptors to see if they differ by patient sex or smoking status, and whether they predict for better or worse outcomes. The trial will allow study of lung tissue as well as blood cells to see whether DNA damage levels in different kinds of cells are overall higher in women than in men with a similar tobacco exposure. It will also look at the relationship of patient-reported factors like smoking exposure, other medications used, hormones and reproductive factors (age of starting periods or when first pregnancies were, etc.), and other variables, and whether they differ by patient sex and smoking status.

This is just the start of this type of research, but it is one of the key ways in which we hope to understand more about why some people develop lung cancer and others don't. It may lead to a better understanding of preventive mechanisms and identifying patients or groups of patients at higher risk that need screening. We may learn ways to predict how well or poorly patients may do based on clinical and/or molecular features. And we may learn ways to refine our treatment approaches for different groups of patients, rather than lumping patients with lung cancer together and considering them essentially the same.

If you are eligible and interested, further information is available here.

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