Genetic analysis has ushered in a new era for non-small cell lung cancer management, enabling researchers and clinicians to diagnose and deploy more targeted treatments, lowering mortality rates.
Over the past two decades, the field of thoracic oncology has seen improved patient outcomes and extended survival rates for patients with non-small cell lung cancer (NSCLC), bringing hope to many where there was very little before.
“Twenty years ago, there was no cure. There was not even a race for a cure,” said Professor Michael Thomas, head of thoracic oncology at Thoraxklinik‑University of Heidelberg. “Nine out of ten patients [with metastatic non-small cell lung cancer] would not be alive after two years.”
Thankfully, the landscape has changed, and mortality rates for NSCLC have steeply dropped, Professor Thomas explained in a webinar given on April 18, 2023, The Evolving Landscape of Lung Cancer Treatment. Population-level mortality from NSCLC in the United States fell sharply from 2013 to 2016, and survival after diagnosis improved substantially.
The reason? The introduction of therapies that target genetic alterations in NSCLC has improved outcomes for these patients significantly. The underlying driver of this approach, genetic analysis, has allowed for additional insight at diagnosis that can be harnessed toward more targeted treatment.
The impact of detecting genetic alterations in NSCLC and deploying targeted treatments
There are several different genetic mutations that may arise in NSCLC tumors, and some may be more likely to cause the cancer cells to spread to other parts of the body. As an example, mutations of epidermal growth factor receptor (EGFR) have been identified as key drivers of metastasis, and safe, efficacious therapies have been developed to target EGFR mutations and inhibit cancer spread.
Targeted therapies for NSCLC represent a rapidly growing area of research, and many new targeted therapies are being studied in clinical trials.
NGS can provide a complete overview of molecular alterations, which can be especially critical in exploring a patient’s tissues at the beginning of clinical management. Patients with NSCLC can have their tumors studied for alterations known to drive cancer spread, so that their clinicians may prescribe treatments that target those alterations, and hopefully curb further progression of the disease.
For patients with a defined alteration of NSCLC (like EGFR), researchers and clinicians may want to track its presence over time. In these cases, clinicians may use a less invasive technique known as liquid biopsy – a non-invasive medical test that involves analyzing various biomolecules found in bodily fluids, such as blood or urine, to detect and diagnose diseases. It offers a less painful alternative compared to traditional solid tissue biopsies, which often involve invasively extracting a small sample of tissue for examination.
One application of liquid biopsy is the detection of cancer. Tumor cells shed cancer-specific molecules called circulating tumor DNA (ctDNA) into the bloodstream. By analyzing ctDNA through genetic analysis techniques like quantitative PCR (qPCR); digital PCR (dPCR) and next-generation sequencing (NGS), physicians can identify specific genetic mutations associated with cancer growth and monitor its progression.
Liquid biopsy also has potential applications for monitoring treatment effectiveness and even guiding personalized treatment plans by detecting drug resistance mutations in real-time. In addition, it could be used to screen populations at risk of developing certain types of cancers or infectious diseases before symptoms appear.
The evolving landscape of lung cancer treatment
Advances in genetic analysis have enabled researchers and clinicians to pinpoint alterations in some patients’ tumors, and to deploy more targeted treatments for NSCLS, extending survival rates significantly. Along with this introduction of targeted therapies, new treatment modalities like immunotherapy are vastly improving outcomes for patients with lung cancer. Combined, these advances represent an exciting new approach towards achieving precision medicine through early disease detection, targeted therapy options and tailored monitoring based on individual patients’ needs and a strong step forward in the cancer research field.
Professor Thomas believes that further innovation is just around the corner.
“We never could have expected the progress we’ve seen today 15 years from ago. We have a bright future.”
About the presenter
Professor Michael Thomas is the head of the department of thoracic oncology at the Thoraxklinik‑University of Heidelberg and is a member of the board of directors of the National Center on Tumor Diseases in Heidelberg. He designed and conducted large-scale Phase III trials in the trimodality treatment setting of NSCLC. His translational research activities focus on the assessment of molecular features and prerequisites of the tumor microenvironment indicating predictive and prognostic impact in the locally advanced and metastatic treatment setting.
 Howlader N, Forjaz G, Mooradian MJ, Meza R, Kong CY, Cronin KA, Mariotto AB, Lowy DR, Feuer EJ. The Effect of Advances in Lung-Cancer Treatment on Population Mortality. N Engl J Med. 2020 Aug 13;383(7):640-649. doi: 10.1056/NEJMoa1916623. PMID: 32786189; PMCID: PMC8577315.