According to the ‘Surveillance, Epidemiology, and End Results’ (SEER) Program of the National Cancer Institute (NCI), it is estimated that there will be more than 224,000 patients in the US in 2016 with newly diagnosed cancer of the lung and bronchus, which is 13.3 % of all new cancer cases. An estimated 158,000 people will die of this disease in the same year. Although lung cancer is not the cancer type with the highest incidence, that would be breast cancer for women and prostate cancer for men, it is the cancer with the highest death rate. 17.7 % of lung cancer patients survive 5 years after diagnosis overall. Depending on the extend of the cancer in the body, the 5 year survival can be higher: localized disease 55.2 % (confined to primary site), regional disease 28 % (cancer has spread to lymph nodes), distant disease 4.3 % (cancer has metastasized). The hope is that these numbers will change in the very near future with new therapies (e.g. in the area of immune-oncology) in development and other innovative therapeutics being or soon-to-be approved by the FDA, EMA and other regulatory agencies since lung cancer is a significant healthcare concern world-wide.
Lung cancer is more common in men than in women. Median age at diagnosis is 70 years. Smoking is the leading cause of cancer and the number of lung cancer patients increased drastically with smoking habits between 1940 and 1960 with a 20 year time lap after cigarette consumption increased in the US beginning of the 20th century. Yet, some lung cancer patients are much younger, never touched a cigarette and have not been exposed to cigarette smoke much either. Other causes for lung cancer include among others pollution, asbestos, toxic gases, radiation, high alcohol consumption, inferior nutrition, lack of exercise and inherited genetic factors. Asbestos can cause a special type of cancer that is different from lung cancer called mesothelioma, which will be discussed in a special post of this blog series.
Needless to say that all patients deserve the same optimal treatment regardless what caused their cancer. Knowing that smoking causes lung cancer, less and less people are smoking and smoking is banned from most working places, restaurants, bars etc. Thanks to this, rates of new lung cancer cases have been slowly declining by 1.8% since the late nineties. However, cancer incidence in absolute numbers including lung cancer is increasing and the need for new therapies is tremendous.
Lung cancer is a very heterogeneous disease from a genetic and consequently histologic point of view. Lung cancer treating oncologists and pulmonologists distinguish between two main groups of lung cancer, Non Small Cell Lung Cancer (85%: NSCLC) and Small Cell Lung Cancer (SCLC). Rare types like bronchial gland carcinomas and others will not be discussed in this blog. NSCLC can be a adenocarcinoma or non-squamous carcinoma (≈40% of all lung cancers) or squamous cell carcinoma (≈30%) or a large cell type of carcinoma (≈10%). Combinations of different histologies have been seen in individual patients and there are probably numerous subtypes as well.
Genetic drivers, characteristics, prognosis and thus, treatment strategies are very different between those three types and include surgery, radiation, chemotherapy, targeted therapy and immune-therapy and combinations of those.
Because lung cancer symptoms are not recognized as such early on, most patients present with a late stage, metastasized disease at diagnosis (70%), which also affects treatment decisions.
Genetic drivers of lung cancer include activated proto-oncogenes like K-RAS (10-30%), mutations in the EGF receptor (10-40% depending on geography – big differences between Northamerica, Europe and Asia), fusion genes like EML4-ALK (≈4-5%) or inactived tumor suppressors through epigenetic changes like DNA methylation and/or histone deacetylation. Not all drivers are targetable directly and several therapeutic strategies are still under investigation. Other gene mutations and amplifications that are less frequent have been seen in ROS1, HER2/NEU, c-MET, BRAF, PIK3CA. Some of them are developed by cancer cells as escape mechanisms or resistance to applied therapies e.g. EGFR or ALK inhibitors that have been greatly advanced in the recent past. Most recent findings will be discussed in the posts to come in this blog.
One theme that all genetic modification have in common is the need for testing at time of diagnosis and progression. Like it has been recognized for breast cancer patients, all lung cancer patients should be tested not only for their histologic type but also for genetic aberrations. A lung cancer gene array that makes sense is currently discussed and researched by lung cancer clinicians and pathologists and how to make it happen without putting too much distress on patients and payers. A solution could include blood testing and analysis of circulating tumor DNA (ctDNA). Some ctDNA assays are already available and used by community and approved by regulatory agencies.
- Molina, J. R., Yang, P., Cassivi, S. D., Schild, S. E., & Adjei, A. A. (2008). Non–Small Cell Lung Cancer: Epidemiology, Risk Factors, Treatment, and Survivorship. Mayo Clinic Proceedings. Mayo Clinic, 83(5), 584–594.