Philip C. Mack

Supplementary Table 3. Patient Characteristics for those with and without assay results

Supplementary Table 2. Representativeness of Study Participants

Supplementary Figure 1. Progression-Free Survival and Overall Survival in patients with cancers with TP53 co-mutations, and STK11 co-mutations.

Supplementary Table 1. Dose Modifications for Docetaxel and Trametinib

Purpose: ctDNA is a powerful diagnostic companion to tissue profiling. Tumor fraction (TF) is a global assessment of an individual’s ctDNA burden. We evaluated the impact of plasma TF on mutation detection and clinical outcomes in patients with previously treated, advanced non–small cell lung cancer on the Lung Master Protocol (Lung-MAP). Experimental Design: Paired tumor tissue and plasma were collected prospectively from patients on the Lung-MAP study. Plasma was collected within 30 days of a new biopsy with no intervening therapies. Tissue and ctDNA genomic profiling and ctDNA TF levels were assessed by Foundation Medicine. TF was primarily calculated from tumor aneuploidy, defaulting to fragmentomics and maximum somatic allele frequencies when aneuploidy was not detectable. The effect of TF on tissue–plasma mutation concordance, overall survival, and its relation to variant allele frequencies was assessed using linear regression, Lin's coefficient, and Cox modeling/log-rank testing. Results: A total of 194 patients were eligible for analysis. TF ≥1% was significantly associated with improved positive percent agreement between ctDNA and tissue across multiple alteration types with the exception of copy-number gains. For short variants, positive percent agreement improved from 51% when TF <1% to 95% when TF ≥1%. TF showed a significant robust correlation with variant allele frequency for KRAS, STK11, and TP53—the three most common mutations. TF <1% was significantly associated with improved patient overall survival compared with TF ≥1% or TF ≥10%. Conclusions: TF provides an accurate, clinically useful assessment of ctDNA plasma levels from patients with refractory, advanced non–small cell lung cancer. TF levels ≥1% are associated with significantly worse overall survival but improved mutation detection in liquid biopsies.

The COVID-19 pandemic created the urgent need to monitor risk of SARS-CoV-2 infection and mortality and to evaluate immune responses to novel vaccines. A foremost concern was the unknown risks to patients with cancer, considering their overall health, immune status, and interactions with cancer therapies. The US National Cancer Institute, in partnership with the National Institute of Allergy and Infectious Diseases, established the SARS-CoV-2 Serological Sciences Network as the nation’s largest coordinated effort to identify and establish standardized serology tests to study immune responses against SARS-CoV-2. Serological Sciences Network–sponsored institutions established cohort studies in 2020 and 2021 across the nation to prospectively follow more than 3000 patients with solid and hematologic malignancies. Concerted efforts were launched to define common data elements for self-reported and clinicopathological data as well as standardized approaches for serological, cellular, and molecular assays. However, the urgency of the situation, the pace of scientific evolution, and the changing public health landscape presented unique challenges to this effort. Here, we discuss these challenges, including regulatory and institution-specific requirements, enrollment of participants, data and biospecimen collection and harmonization, and the need to adapt study designs to align with the ever changing landscape. This information is critical to the continuance of research on SARS-CoV-2 and provides a roadmap for combatting the emergence of future pathogens with pandemic potential.

Supplementary Figure 1. Progression-Free Survival and Overall Survival in patients with cancers with TP53 co-mutations, and STK11 co-mutations.

Supplementary Figure 1. Progression-Free Survival and Overall Survival in patients with cancers with TP53 co-mutations, and STK11 co-mutations.

Supplementary Table 2. Representativeness of Study Participants