A recent project, supported by the NCCN Young Investigator Award, has led to a longitudinal biobanking resource to quantify minimal residual disease in small cell lung cancer (SCLC), according to Wade Iams, MD, Assistant Professor of Medicine at Vanderbilt University Medical Center, who presented his team's findings during the 2022 National Comprehensive Cancer Network Annual Conference (Abstract YIA22-003).
"Small cell lung cancer is an aggressive neuroendocrine cancer that makes up about 10-15 percent of patients with lung cancer, and it's the most aggressive histology," explained Iams, while highlighting that biopsies are rarely performed among these patients, and when it does happen, they are often small, sparse, and necrotic. "And so, it's a disease histology within our cancer care that we have a huge unmet need for better longitudinal monitoring of tumor dynamics in these patients."
With this in mind, the researchers sought to use SCLC circulating tumor DNA to identify minimal residual disease among patients with limited-stage and extensive-stage SCLC.
"The stratification of SCLC patients into high- and low-risk groups based on minimal residual disease positivity or negativity, respectively, may allow more individualized treatment strategies-simultaneously improving outcomes through novel therapy applications in high-risk patients and lowering the risk of adverse events by avoiding unnecessary treatment in low-risk patients," the study authors noted.
Research Details
Iams and colleagues used a longitudinal, prospective blood-banking protocol approved by the Vanderbilt University Medical Center Institutional Review Board. All SCLC patients treated at the medical center are eligible. The researchers collect longitudinal blood samples up to every 3 weeks, which are stored in the facility's thoracic biorepository.
"In conjunction, we compile a clinically annotated database with which we are able to identify target cohorts for analysis. Through identification of salient clinical questions and collaborators, we are able to perform the most meaningful analyses of these precious samples," the study authors outlined. "Our goal is to build preliminary datasets that can guide the most appropriate integration of circulating tumor DNA into prospective clinical trials to guide treatment selection."
Of the currently 161 unique patients included in the repository, 40 percent have limited-stage disease and 60 percent have extensive-stage or Stage IV metastatic disease, according to Iams, who also noted that they have a median of three collections per patient. This allows the researchers to monitor the disease over time and gain further insights into tumor dynamics. Of the patients with limited-stage disease, 94 percent had undergone concurrent chemoradiation in the first-line.
The investigators have partnered with Guardant Health to analyze specimens from patients with limited-stage SCLC using the Reveal assay, according to Iams, and assess if the combination of circulating tumor DNA next-generation sequencing and epigenetic methylation profiling can detect minimal residual disease within this cohort.
As of this presentation, Iams and his colleagues have analyzed treatment-naive samples among patients with limited-stage SCLC. Five of the six patients had detectable circulating tumor DNA.
"Among all five patients who had tumor DNA detected by the assay, it was both seen in the epigenetic and our more typical next-generation sequencing profiling technologies," noted Iams, who is also the Director of Thoracic Clinical Trials. "The one patient in whom it was not detected had Stage Ia/II disease, so very small disease burden. And there has been some preliminary research demonstrating that the sensitivity of these assays is greater in situations where there is greater tumor burden."
These initial findings are very promising, according to Iams, and have led the researchers to advance to a broader analysis of patients. This includes an investigation of end-of-treatment samples of patients with limited-stage disease, as well as advancement of their minimal residual disease analysis among patients with extensive-stage disease.
With a 70 percent risk of recurrence, in the real-world most of these patients will recur, stated Iams, while noting that they hope to determine if they can detect recurrence with the assay. "And then, hopefully, can we design prospective trials using circulating tumor DNA as an integral biomarker to decide on treatment interventions and improve patient outcomes?"
Catlin Nalley is a contributing writer.