Small cell lung cancer accounts for approximately 15 percent of all lung cancer diagnoses. It is found most often in patients with a substantial history of tobacco exposure. Small cell lung cancer is an aggressive cancer that grows and spreads quickly in the body. There are multiple approaches being tested in the U.S. and elsewhere to improve treatment options.
LUNGevity spoke with Charles Rudin, MD, PhD, professor and chief of the Thoracic Oncology Service at Memorial Sloan Kettering Cancer Center and chair of LUNGevity’s Scientific Advisory Board, to answer questions from our small cell lung cancer community and to discuss progress in small cell lung cancer treatments.
LUNGevity Foundation: How has treatment of limited-stage small cell lung cancer (LS-SCLC) evolved over the past ten years?
Dr. Charles Rudin: Small cell lung cancer is typically treated with a combination of chemotherapy and radiation. In particular, the technology for delivering radiation has improved significantly over the years. This has resulted in decreased toxicity and possibly even better efficacy. In limited-stage disease patients, radiation to the chest is used, and patients with a good response may also receive prophylactic cranial radiation.
What is prophylactic cranial radiation, and when is it appropriate to use?
After a patient with LS-SCLC has successfully completed their chemotherapy and radiation regimen for disease in the chest, the physician may opt to employ prophylactic cranial radiation, a series of radiation treatments that are applied diffusely to the brain. The rationale for this type of cranial radiation is that even if no disease is visible in the brain, there can be micro-metastatic disease—individual tumor cells—that have avoided chemotherapy by hiding behind the blood-brain barrier. These microscopic metastases can lead to disease recurrence. For limited-stage disease with successful treatment of the chest, it has been shown that the application of prophylactic cranial radiation can reduce the incidence of recurrent disease within the brain and improve survival.
How has treatment of extensive-stage small cell lung cancer (ES-SCLC) evolved over the past ten years?
For many years, a pairing of two chemotherapy drugs has been the first-line treatment for small cell lung cancer. In the last two years, we have seen two important clinical trials reporting a benefit when adding in immunotherapy for the treatment of ES-SCLC. Now, the first-line of treatment for ES-SCLC has shifted to chemotherapy with immunotherapy in many countries, including the United States.
Should extensive-stage small cell lung cancer patients consider testing their biopsy samples for driver mutations?
To a large extent, mutational profiling doesn’t currently influence treatment decisions for small cell lung cancer patients. I would say that mutational profiling in small cell lung cancer remains in the realm of research. It is important for us to continue this research to the explore the genomic landscape of small cell lung cancer. Although it may not help treat an individual today, mutational profiling of tumors as a part of a clinical trial or research project could help us think about new therapies for the future.
Why has immunotherapy progress been slower for small cell lung cancer patients than for non-small cell lung cancer patients?
We think about this question a lot! Small cell lung cancers typically have a lot of mutations. Generally, we might expect this to improve immunotherapy outcomes because it would provide a lot of “foreign” targets for the immune system to recognize and attack. However, small cell lung cancer has evolved so that it fails to present those mutations effectively to the immune system. The tumors can be large, which may limit the ability of immune effector cells to penetrate the mass. And we’re only beginning to understand the cells that typically hang in and around small cell tumors – these non-cancer cells in the tumor microenvironment may contribute to the difficulty in activating the immune system.
What are some exciting areas of research for small cell lung cancer treatment?
It’s hard to pick one or two. Although small cell lung cancer has historically been difficult to treat, laboratory research is giving us a better understanding of the biology of the cancer, and now we have a growing list of potential therapeutic targets. There has been a pretty amazing reinvigoration in small cell lung cancer research in the past few years. The challenge for us is that these targets haven’t yet translated into clinical efficacy. Over the next five years, many clinical trials will report out, and I am hoping some new targeted therapies will lead to improved outcomes for patients.
How has the prevalence of small cell lung cancer evolved in recent years?
Small cell lung cancer is the type of lung cancer most closely associated with heavy tobacco use. So, as smoking cessation programs have taken hold in the United States, we have seen a decrease in the frequency of small cell lung cancer. However, it is important to note that globally, small cell lung cancer continues to be a major public health problem. Some Asian countries in particular are continuing to report increases in small cell lung cancer incidence.
What is the future of diagnosis and treatment for small cell lung cancer patients and their families?
Well, we are beginning to recognize that there are subtypes of small cell lung cancer, not based on mutational differences but rather on differences in gene expression profiles. These cancer subtypes may react differently when confronted with particular targeted therapies or immunotherapies. Currently, we are using the same treatments for almost all small cell lung cancer patients—looking to the future as we learn more about how to treat each of these small cell lung cancer subtypes, I think we’ll get closer to delivering individualized care for patients.
This is a disease that is pretty notorious for dashing what seem like good ideas. But I do think now we have a singularly diverse range of novel therapeutic strategies on the horizon. I am sure some of these won’t hold up. But I am hopeful that others will play out to improve outcomes for our patients.
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Juhi Kunde, MA, is a science writer for LUNGevity.