Importance Symptomatic adverse events (AEs) in cancer trials are currently reported by clinicians using the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE). To integrate the patient perspective, the NCI developed a patient-reported outcomes version of the CTCAE (PRO-CTCAE) to capture symptomatic AEs directly from patients. Objective To assess the construct validity, test-retest reliability, and responsiveness of PRO-CTCAE items. Design Participants completed PRO-CTCAE items on tablet computers in clinic waiting rooms at two visits 1-6 weeks apart. A subset completed PRO-CTCAE items during an additional visit one business day after the first visit. Setting Nine U.S. cancer centers and community oncology practices. Participants 975 adult cancer patients undergoing outpatient chemotherapy and/or radiation enrolled between January 2011 and February 2012. Eligibility required participants to read English and be without clinically significant cognitive impairment. Main Outcome(s) and Measure(s) Primary comparators were clinician-reported Eastern Cooperative Oncology Group Performance Status (ECOG PS) and the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30). Results 940/975 (96%) and 852/940 (91%) participants completed PRO-CTCAE items at each visit. 938/940 (99.8%) participants (53% female, median age 59, 32% high school education or less, 17% ECOG PS 2-4) reported having at least one symptom. All PRO-CTCAE items had at least one correlation in the expected direction with a QLQ-C30 scale (111/124 P<.05). Stronger correlations were seen between PRO-CTCAE items and conceptually-related QLQ-C30 domains. Scores for 94/124 PRO-CTCAE items were higher in the ECOG PS 2-4 versus 0-1 group (58/124 P<.05). Overall, 119/124 items met at least one construct validity criterion. Test-retest reliability was acceptable for 36/49 pre-specified items (median intra-class correlation coefficient .76; range .53-.96). Correlations between PRO-CTCAE item changes and corresponding QLQ-C30 scale changes reached statistical significance for 27 pre-specified items (median r=.43, range .10-.56; all P≤.006). Conclusions and Relevance Evidence demonstrates favorable validity, reliability, and responsiveness of PRO-CTCAE in a large, heterogeneous U.S. sample of patients undergoing cancer treatment. Studies evaluating other measurement properties of PRO-CTCAE are underway to inform further development of PRO-CTCAE and its inclusion in cancer trials.

This risk assessment model accurately stratified the medical risk of these patients using only clinical information available on the first day of their course. Low-risk patients are an appropriate population in which to study less intensive treatment strategies.

Metformin, one of most widely prescribed oral hypoglycemic agents, has recently received increased attention because of its potential antitumorigenic effects that are thought to be independent of its hypoglycemic effects. Several potential mechanisms have been suggested for the ability of metformin to suppress cancer growth in vitro and vivo: (1) activation of LKB1/AMPK pathway, (2) induction of cell cycle arrest and/or apoptosis, (3) inhibition of protein synthesis, (4) reduction in circulating insulin levels, (5) inhibition of the unfolded protein response (UPR), (6) activation of the immune system, and (7) eradication of cancer stem cells. There is also a growing number of evidence, mostly in the form of retrospective clinical studies that suggest that metformin may be associated with a decreased risk of developing cancer and with a better response to chemotherapy. There are currently several ongoing randomized clinical trials that incorporate metformin as an adjuvant to classic chemotherapy and aim to evaluate its potential benefits in this setting. This review highlights basic aspects of the molecular biology of metformin and summarizes new advances in basic science as well as intriguing results from recent clinical studies.

BackgroundPRO-CTCAE is a library of items that measure cancer treatment-related symptomatic adverse events (NCI Contracts: HHSN261201000043C and HHSN 261201000063C). The objective of this study is to examine the equivalence and acceptability of the three data collection modes (Web-enabled touchscreen tablet computer, Interactive voice response system [IVRS], and paper) available within the US National Cancer Institute (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) measurement system.MethodsParticipants (n = 112; median age 56.5; 24 % high school or less) receiving treatment for cancer at seven US sites completed 28 PRO-CTCAE items (scoring range 0–4) by three modes (order randomized) at a single study visit. Subjects completed one page (approx. 15 items) of the EORTC QLQ-C30 between each mode as a distractor. Item scores by mode were compared using intraclass correlation coefficients (ICC); differences in scores within the 3-mode crossover design were evaluated with mixed-effects models. Difficulties with each mode experienced by participants were also assessed.Results103 (92 %) completed questionnaires by all three modes. The median ICC comparing tablet vs IVRS was 0.78 (range 0.55–0.90); tablet vs paper: 0.81 (0.62–0.96); IVRS vs paper: 0.78 (0.60–0.91); 89 % of ICCs were ≥0.70. Item-level mean differences by mode were small (medians [ranges] for tablet vs. IVRS = −0.04 [−0.16–0.22]; tablet vs paper = −0.02 [−0.11–0.14]; IVRS vs paper = 0.02 [−0.07–0.19]), and 57/81 (70 %) items had bootstrapped 95 % CI around the effect sizes within +/−0.20. The median time to complete the questionnaire by tablet was 3.4 min; IVRS: 5.8; paper: 4.0. The proportion of participants by mode who reported “no problems” responding to the questionnaire was 86 % tablet, 72 % IVRS, and 98 % paper.ConclusionsMode equivalence of items was moderate to high, and comparable to test-retest reliability (median ICC = 0.80). Each mode was acceptable to a majority of respondents. Although the study was powered to detect moderate or larger discrepancies between modes, the observed ICCs and very small mean differences between modes provide evidence to support study designs that are responsive to patient or investigator preference for mode of administration, and justify comparison of results and pooled analyses across studies that employ different PRO-CTCAE modes of administration.Trial registrationNCT Clinicaltrials.gov identifier: NCT02158637