Advancing Combined Modality Therapy for Early-Stage, Screen-Detected Disease: Adjuvant/Neoadjuvant Therapy

Advancing Combined Modality Therapy for Early-Stage, Screen-Detected Disease: Adjuvant/Neoadjuvant Therapy

Lung Cancer Screening
May 06, 2021
David Yankelevitz, MD
James L. Mulshine, MD
David Yankelevitz, MD, and James L. Mulshine, MD

During the 17th annual Quantitative Imaging Workshop held in late Fall 2020, the Initiative for Early Lung Cancer Research on Treatment (IELCART) offered two sessions with panel discussions exploring the curative potential and challenges of managing early-stage, screen-detected lung cancer. IELCART investigators with well-established screening programs are recognizing a shift in the proportion of early-stage compared to advanced lung cancers accrued at their institutions (an example of this referral dynamic at Mount Sinai Health System institutions is shown in the Figure). IELCART looks to further advance its mission by collaborating with additional institutions, as well as with industry.

About IELCART

The IELCART group, led by Raja Flores, MD, and Claudia Henschke, PhD, MD, was recognized as the type of group that could be successful in enrolling participants into a trial such as this. The IELCART was established in 2016 to improve the treatment of early-stage lung cancer and came about as a natural extension of the International Early Lung Cancer Action Program’s (I-ELCAP’s) work over the last 3 decades on lung cancer screening research. Although the primary goal of I-ELCAP was related to early diagnosis, IELCART now focuses on the treatment aspects of early-stage lung cancer. The consortium includes the major healthcare systems in New York City and the surrounding areas, including the Mount Sinai Health System, Northwell Health, New York University, Valley Hospital System, and Vassar Brothers Medical Center. It also includes Stony Brook Medicine in Long Island, Swedish Health Services in Seattle, Lahey Hospital and Medical Center in Massachusetts, and Erasmus MC in the Netherlands, as well as major academic centers in Poland and Pamplona, Spain. This international consortium benefits from a highly efficient management system to collect data including clinical, pathologic, and imaging, through a web-based infrastructure that is stored in a central database. The consortium has enrolled approximately 1,400 patients with stage I disease. With several sites now coming up to speed, the group is on track to enroll 1,000 new patients annually. The initial objectives of the consortium were to focus on primary issues related to the treatment of stage I lung cancer that, despite years of study, remain unresolved. These include sublobar versus lobar resection, extent of nodal dissection, radiation versus surgery, and management of subsolid lesions. With several of these projects nearing completion, the consortium is now moving toward the larger goal of considering adjuvant and neoadjuvant trials for stage I lung cancers.

Updates on Projects for Stage I

It was highlighted during a panel discussion in the first of the two IELCART sessions, that one of the main challenges in performing clinical trials of early-stage lung cancers is reliably identifying the high-risk cases that would not be cured with surgical resection alone. Therefore, a critical component is to identify those stage I cancers that are at higher likelihood for recurrence. Two observations that have now been reported to be associated with a higher recurrence rate include lymphovascular invasion and spread through airspaces. The panel discussions identified numerous possible approaches for this identification, including blood-based markers, molecular pathology evaluation, immunophenotyping, clinical factors, and radiologic features. Ultimately moderator Nasser Altorki, MD, and panelists Harvey Pass, MD; Ignacio Wistuba, MD; Christopher Amos, PhD; and Matthijs Oudkerk, PhD, MD; agreed that considerable work remains to be done, and they noted that there is no leading approach at this point. PET scanning was also considered, but it was felt to be too unreliable for smaller lesions, and in the context of a clinical trial for stage I lesions, obtaining this examination would add an extra layer of complexity. The panel ultimately concluded that the simplest measure, tumor volume doubling rate, is at this time the most reliable approach; however, obtaining two high-quality time-separated CT scans also has challenges. The second session focused specifically on the feasibility of performing clinical trials for stage I disease, including a discussion of the ADAURA trial, which included patients with IB-IIIA disease. The panel discussion was led by James Mulshine, MD, and included: Fred Hirsch, MD, PhD; Phillip Dennis MD, PhD; Roy Herbst, MD, PhD; and Natasha Leighl, MMSC, MD. The discussion centered on the potential design of such a trial, acknowledging the already high cure rates for stage I disease. The possibility of performing a basket or umbrella trial where multiple targets were identified was a strong consideration, as this type of trial has already been shown to have great success in the context of squamous cell lung cancer. Here, the need to identify those patients at high risk for recurrence who will also have targets for treatment was the main consideration. The challenge of delaying surgery in the neoadjuvant setting was felt to be an important barrier to enrollment. Overall, the panel agreed that an adjuvant trial would likely be better able to accrue, but the information that could be added in the neoadjuvant setting would be useful. The consensus for the group was that a trial focusing on early-stage disease would be highly useful, although there are logistical challenges that would have to be effectively addressed.

The date for the next IELCART meeting is to be determined. We will be continuing discussions on approaches to identify those stage I lung cancers likely to recur, including an update of the review of the already accrued data as well as a review of approaches published by other groups. We will also continue discussions regarding moving forward with a clinical trial and will be inviting potential sponsors to attend. IELCART remains open for those who wish to join the collaboration.

Disclosure: Dr. Yankelevitz is a named inventor on multiple patents and patent applications related to the evaluation of chest diseases, including measurements of chest nodules. He has received financial compensation for the licensing of these patents. In addition, he is a consultant and co-owner of Accumetra, a private company developing tools to improve the quality of CT imaging, and is on the medical advisory board of Carestream, a company that develops radiography equipment and has consulted for AstraZeneca, Genentech, and Pfizer. 

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About the Authors

David Yankelevitz, MD

David Yankelevitz, MD

Dr. Yankelevitz is professor of Radiology, Icahn School of Medicine, The Mount Sinai Health System.
James L. Mulshine, MD

James L. Mulshine, MD

Dr. Mulshine is a professor in the Department of Internal Medicine, Rush Medical College.