Estimation and inference on the partial volume under the receiver operating characteristic surface.

measures of biomarker accuracy that employ the receiver operating characteristic surface have been proposed for biomarkers that classify patients into one of three groups: healthy, benign, or aggressive disease. The volume under the receiver operating characteristic surface summarizes the overall discriminatory ability of a biomarker in such configurations, but includes cutoffs associated with clinically irrelevant true classification rates. Due to the lethal nature of pancreatic cancer, cutoffs associated with a low true classification rate for identifying patients with pancreatic cancer may be undesirable and not appropriate for use in a clinical setting. In this project, we study the properties of a more focused criterion, the partial volume under the receiver operating characteristic surface, that summarizes the diagnostic accuracy of a marker in the three-class setting for regions restricted to only those of clinical interest. We propose methods for estimation and inference on the partial volume under the receiver operating characteristic surface under parametric and non-parametric frameworks and apply these methods to the evaluation of potential biomarkers for the diagnosis of pancreatic cancer.

First-Line Immunotherapy with Check-Point Inhibitors: Prospective Assessment of Cognitive Function.

Approximately 40% of patients with cancer are eligible for check-point inhibitor (CPI) therapy. Little research has examined the potential cognitive impact of CPIs. First-line CPI therapy offers a unique research opportunity without chemotherapy-related confounders. The purpose of this prospective, observational pilot was to (1) demonstrate the feasibility of prospective recruitment, retention, and neurocognitive assessment for older adults receiving first-line CPI(s) and (2) provide preliminary evidence of changes in cognitive function associated with CPI(s). Patients receiving first-line CPI(s) (CPI Group) were assessed at baseline (n = 20) and 6 months (n = 13) for self-report of cognitive function and neurocognitive test performance. Results were compared to age-matched controls without cognitive impairment assessed annually by the Alzheimer's Disease Research Center (ADRC). Plasma biomarkers were measured at baseline and 6 months for the CPI Group. Estimated differences for CPI Group scores prior to initiating CPIs (baseline) trended to lower performance on the Montreal Cognitive Assessment-Blind (MOCA-Blind) test compared to the ADRC controls (p = 0.066). Controlling for age, the CPI Group's 6-months MOCA-Blind performance was lower than the ADRC control group's 12-months performance (p = 0.011). No significant differences in biomarkers were detected between baseline and 6 months, although significant correlations were noted for biomarker change and cognitive performance at 6 months. IFNγ, IL-1ß, IL-2, FGF2, and VEGF were inversely associated with Craft Story Recall performance (p < 0.05), e.g., higher levels correlated with poorer memory performance. Higher IGF-1 and VEGF correlated with better letter-number sequencing and digit-span backwards performance, respectively. Unexpected inverse correlation was noted between IL-1α and Oral Trail-Making Test B completion time. CPI(s) may have a negative impact on some neurocognitive domains and warrant further investigation. A multi-site study design may be crucial to fully powering prospective investigation of the cognitive impact of CPIs. Establishment of a multi-site observational registry from collaborating cancer centers and ADRCs is recommended.

Epidermal Growth Factor Receptor Inhibitor Treatment Timing does not Impact Survival in Stage 4 Colon Cancer Treatment: A Retrospective Study.

Introduction: Colon cancer impacts the lives of Kansans and those across the United States. Epidermal growth factor receptor (EGFR) inhibitors, such as panitumumab and cetuximab, have gained popularity as first-line treatment for stage 4 colon cancer despite their toxicities and have been used by clinicians in later lines of therapy. EGFR inhibitors have been proven to be an efficacious first-line treatment for stage 4 colon cancer, but no study has investigated outcomes comparing EGFR inhibitors as first-line treatment to its use as second- or third-line treatment. This study investigated EGFR inhibitor therapy estimated overall survival when used as first-, second-, and third-line treatment for stage 4 colon cancer. Methods: A retrospective review was done for patients with stage 4 colon cancer who underwent EGFR inhibitor treatment at a large academic center from November 2007 to August 2021. The patients were stratified into five groups by the line in which they received the EGFR inhibitor treatment. A log-rank test was used to analyze the groups, and the median survival for each group was determined. Results: A total of 68 patients were reviewed; 18 received first-line, 23 received second-line, 18 received third-line, 6 received fourth-line, and 3 received sixth-line treatment with an EGFR inhibitor. Fourth- and sixth-line therapies were excluded due to small patient size. There was no significant difference in estimated survival time between any of the lines. Median survival of the therapies was found. Conclusions: There was no statistical difference in survival between the first-, second-, or third-line groups, which may provide justification for its use as a second- or third-line therapy.