December 2, 2024: 

A Big Ten Cancer Research Consortium (Big Ten CRC) study, BTCRC-LUN16-081, led by Greg Durm, MD, of IU Simon Comprehensive Cancer Center, was published in the Journal of Thoracic Oncology in October 2024. The article is titled, “Analysis of Circulating Tumor DNA Predicts Outcomes of Short-Course Consolidation Immunotherapy in Unresectable Stage III NSCLC.”

Congratulations to all co-authors and study teams whose hard work led to this publication.

Abstract:

The current standard of care for patients with inoperable stage III non-small cell lung cancer includes chemoradiotherapy (CRT) followed by 1 year of checkpoint inhibitor (CPI) therapy. Nevertheless, the optimal duration of consolidation CPI remains unknown. Here, we characterized the relationship between circulating tumor DNA (ctDNA), minimal residual disease (MRD), and clinical outcomes of patients with unresectable locally advanced non-small cell lung cancer treated on a phase 2 trial of short-course consolidation immunotherapy after CRT, with the goal of testing whether ctDNA may be able to identify patients who do not require a full year of treatment.

Plasma samples for ctDNA analysis were collected from patients on the Big Ten Cancer Research Consortium BTCRC-LUN16-081 trial after completion of CRT, before day 1 of cycle 2 (C2D1) of CPI (i.e., 1 mo after treatment start), and at the end of up to 6 months of treatment. Tumor-informed ctDNA MRD analysis was performed using cancer personalized profiling by deep sequencing. Levels of ctDNA at each time point were correlated with clinical outcomes.

Detection of ctDNA predicted significantly inferior progression-free survival after completion of CRT (24-mo 29% versus 65%, p = 0.0048), before C2D1 of CPI (24-mo 0% versus 72%, p < 0.0001) and at the end of CPI (24-mo 15% versus 67%, p = 0.0011). In addition, patients with decreasing or undetectable ctDNA levels after 1 cycle of CPI had improved outcomes compared with patients with increasing ctDNA levels (24-mo progression-free survival 72% versus 0%, p < 0.0001). Progression of disease occurred within less than 12 months of starting CPI in all patients with increasing ctDNA levels at C2D1.

Detection of ctDNA before, during, or after 6 months of consolidation CPI is strongly associated with inferior outcomes. Our findings suggest that analysis of ctDNA MRD may enable personalizing the duration of consolidation immunotherapy treatment.

Read the full article.

Authors:

Soyeong Jun (Stanford Cancer Institute), Nikhil A. Shukla (MD Anderson Comprehensive Cancer Center), Greg Durm (IU Simon Comprehensive Cancer Center), Angela B. Hui (Stanford Cancer Institute), Sha Cao (IU Simon Comprehensive Cancer Center), Apar Kishor Ganti (VA Nebraska Western Iowa Health Care System and University of Nebraska Medical Center), Salma K. Jabbour (Rutgers Cancer Institute of New Jersey), Christian Kunder (Stanford University), Ash A. Alizadeh (Stanford Cancer Institute), Nasser H. Hanna (IU Simon Comprehensive Cancer Center), Maximilian Diehn (Stanford Cancer Institute)

About the Big Ten Cancer Research Consortium: The Big Ten Cancer Research Consortium was created in 2013 to transform the conduct of cancer research through collaborative clinical trials and observational studies that seek to improve the lives of cancer patients in the diverse communities we serve by leveraging the scientific and clinical expertise of Big Ten universities. The Big Ten Cancer Research Consortium creates a unique team research culture to drive science rapidly from ideas to treatment and prevention. Within this innovative environment, today’s research leaders collaborate with and mentor the research leaders of tomorrow. Since its founding, the Big Ten CRC has activated nearly 40 clinical trials across a wide range of cancer types, more than 1,000 participants have enrolled in Big Ten CRC studies, and more than 500 researchers have joined Big Ten CRC Clinical Trial Working Groups.

About the Big Ten Conference: The Big Ten Conference is an association of world-class universities whose member institutions share a common mission of research, graduate, professional and undergraduate teaching and public service. Founded in 1896, the Big Ten has sustained a comprehensive set of shared practices and policies that enforce the priority of academics in the lives of students competing in intercollegiate athletics and emphasize the values of integrity, fairness and competitiveness. The broad-based programs of the 18 Big Ten institutions provide direct financial support for more than 11,000 participation opportunities on 350 teams in 42 different sports. The Big Ten sponsors 28 official conference sports, 14 for men and 14 for women. For more information, visit www.bigten.org.