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Many patients with cancer experience cancer-related cognitive decline (CRCD). Previous studies have shown that elevated S100β, a calcium-binding protein commonly found in glial cells, can exhibit neurotoxic effects, including disruption of the blood-brain barrier (BBB). We studied changes in S100β levels in patients with breast cancer receiving chemotherapy, and the relationship to changes in cognitive function. A total of 505 women with breast cancer (mean (sd) age; 53.4 (53.6)) and 336 age-matched controls without cancer (52.8 (10.3)) were included from a nationwide study as part of the National Cancer Institute Community Oncology Research Program (NCORP). Both groups provided blood samples and completed neurocognitive assessments within 7 days before the patients with breast cancer received their first chemotherapy dose (pre-chemotherapy; T1) and within 1 month of their last chemotherapy administration (post-chemotherapy; T2). Utilizing a linear mixed model, multivariate linear regressions, and Spearman rank correlations (rs), we investigated longitudinal changes in serum S100β concentrations and their relationships to changes in neurocognitive outcomes over time. We observed an increase in S100β for patients with breast cancer (p = 0.002), but not for controls without cancer over time (p = 0.683). Additionally, we identified subtle relationships between increases in serum S100β and worsening in cognitive performance on the Backward Counting test (rs = 0.11, p = 0.041) and self-reported FACT-Cog Perceived Cognitive Abilities (rs = −0.10, p = 0.025). Regression analyses adjusted for age, race, body-mass index (BMI), education, menopausal status, anxiety, and depression revealed a trend remained for the relationship of S100β with Backward Counting. In conclusion, we found that patients with breast cancer experience a significant increase in concentration of serum S100β over the course of chemotherapy. This increase is correlated with worsening in some neurocognitive outcomes from pre-to post-chemotherapy, with trending results remaining following adjustment for covariates.

Patients with neuropathic pain often present with variable pain and nonpainful sensory qualities that could serve as outcomes in randomized clinical trials (RCTs). This study aimed to investigate the within-participant variability in the severity of these sensory qualities and whether the means of 7 daily pain quality assessments provide better assay sensitivity (ie, more sensitivity to treatment effects) than single-week recall-based assessments. This secondary analysis used data from an RCT of transcutaneous electrical nerve stimulation for chemotherapy-induced peripheral neuropathy (N = 142). Participants rated the severity of painful and nonpainful sensory qualities using 0 to 10 numeric rating scales daily for 1 week (24-hour recall) and 1 time at the end of each week (week recall) at trial baseline and endpoint (after 6 weeks of treatment). For pain quality assay sensitivity analyses, the 2 types of measures were used to 1) define the study sample (ie, how many participants met minimum baseline pain quality severity) and 2) calculate the observed effect sizes (ie, between-group differences in mean pain qualities) using analysis of covariances. The projected sample sizes required to detect the observed effect sizes in future clinical trials for hot/burning pain and cramping were substantially smaller using the daily mean outcome compared with week recall (ie, hot/burning pain: 153 vs 388, cramping: 121 vs 349), and only marginally larger for sharp/shooting pain (22 participants) with the daily mean outcome. Compared with single-week recall-based assessments of pain qualities, the mean of daily assessments may improve RCT assay sensitivity when used to define entry criteria and assess outcomes.

Very few treatments have demonstrated efficacy for CIPN in clinical trials. Patients with painful CIPN present with varying painful sensory qualities. We hypothesize that personalized endpoints that incorporate each participants’ most severe or bothersome painful qualities would provide a more assay sensitive endpoint than an endpoint that includes multiple pain qualities, regardless of whether all participants endorse them. This secondary analysis included data from participants who reported ³4 out of 10 severity for hot/burning pain, sharp/shooting pain, and/or cramping (N= 80) at baseline in a RCT of transcutaneous electrical nerve stimulation (TENS) for CIPN. The initial analyses suggested moderate effect sizes for TENS on each of these pain qualities. Analyses of covariance (ANCOVA) were used to estimate the TENS treatment effect on personalized outcomes that included the most severe or most bothersome of these three pain qualities at baseline for each participant or the mean of all three. Each pain quality was measured on a 0 – 10 numeric rating scale (NRS). For 73% of participants, the pain quality that was ranked as most bothersome was also rated as most severe at baseline. The adjusted mean difference between groups (i.e., effect size) for the personalized outcomes ranged from 1.21 to 1.40 NRS points. The mean outcome resulted in the lowest between group difference of 0.97. Personalized pain quality outcomes may increase assay sensitivity in future trials of painful CIPN. Repetition of these analyses is necessary to confirm this result. Funded by the National Institutes of Health (R21CA235389; UG1CA189961, K24NS126861).

Patients with neuropathic pain present with different pain qualities. Each is usually assessed using single ratings in randomized clinical trials (RCTs). To our knowledge, no studies have investigated whether means of daily pain quality assessments would provide better assay sensitivity (i.e., more sensitive to treatment effects) than single week recall-based assessments. This secondary analysis used data from participants who reported ³4 out of 10 severity for hot/burning pain, sharp/shooting pain, and/or cramping at baseline in a RCT of transcutaneous electrical nerve stimulation for CIPN (N=88). Participants rated the severity of different pain qualities using 0-10 numeric rating scales daily for a week and a single-week recall-based outcome at baseline and endpoint. Effect sizes (differences in mean pain between placebo and active at endpoint) for the mean of the daily assessments and the single week recall assessments were computed using ANCOVAs. The sample sizes that would be required in future clinical trials to detect the observed effect sizes were calculated (alpha=0.5, power=80%). The effect sizes were greater for the mean of daily outcomes than the single week recall outcome in all cases except for sharp/shooting pain. For hot/burning pain and cramping, the projected sample sizes for the mean ratings were 114 and 126 fewer participants per group than with the week recall outcome. For sharp/shooting pain, the week recall outcome had a slightly lower (22 participants) projected sample size requirement than the mean outcome. Daily pain quality assessments may provide improved assay sensitivity than week recall-based assessments. Funded by NIH (R21CA235389; UG1CA189961; K24NS126861).

IMPORTANCE: Universal screening of patients with newly diagnosed cancer for hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV is not routine in oncology practice, and experts disagree about whether universal screening should be performed. OBJECTIVE: To estimate the prevalence of HBV, HCV, and HIV infection among persons with newly diagnosed cancer. DESIGN, SETTING, AND PARTICIPANTS: Multicenter prospective cohort study of patients with newly diagnosed cancer (ie, identified within 120 days of cancer diagnosis) at 9 academic and 9 community oncology institutions affiliated with SWOG (formerly the Southwest Oncology Group) Cancer Research Network, a member of the National Clinical Trials Network, with enrollment from August 29, 2013, through February 15, 2017. The data analysis was conducted using data available through August 17, 2017. MAIN OUTCOMES AND MEASURES: The accrual goal was 3000 patients and the primary end point was the presence of HBV infection (previous or chronic), HCV infection, or HIV infection at enrollment. Patients with previous knowledge of infection as well as patients with unknown viral viral status were evaluated. RESULTS: Of 3092 registered patients, 3051 were eligible and evaluable. Median (range) age was 60.6 (18.2-93.7) years, 1842 (60.4%) were female, 553 (18.1%) were black, and 558 (18.3%) were Hispanic ethnicity. Screened patients had similar clinical and demographic characteristics compared with those registered. The observed infection rate for previous HBV infection was 6.5% (95% CI, 5.6%-7.4%; n = 197 of 3050 patients); chronic HBV, 0.6% (95% CI, 0.4%-1.0%; n = 19 of 3050 patients); HCV, 2.4% (95% CI, 1.9%-3.0%; n = 71 of 2990 patients); and HIV, 1.1% (95% CI, 0.8%-1.6%; n = 34 of 3045). Among those with viral infections, 8 patients with chronic HBV (42.1%; 95% CI, 20.3%-66.5%), 22 patients with HCV (31.0%; 95% CI, 20.5%-43.1%), and 2 patients with HIV (5.9%; 95% CI, 0.7%-19.7%) were newly diagnosed through the study. Among patients with infections, 4 patients with chronic HBV (21.1%; 95% CI, 6.1%-45.6%), 23 patients with HCV (32.4%; 95% CI, 21.8%-44.5%), and 7 patients with HIV (20.6%; 95% CI, 8.7%-37.9%) had no identifiable risk factors. CONCLUSIONS AND RELEVANCE: Results of this study found that a substantial proportion of patients with newly diagnosed cancer and concurrent HBV or HCV are unaware of their viral infection at the time of cancer diagnosis, and many had no identifiable risk factors for infection. Screening patients with cancer to identify HBV and HCV infection before starting treatment may be warranted to prevent viral reactivation and adverse clinical outcomes. The low rate of undiagnosed HIV infection may not support universal screening of newly diagnosed cancer patients.