ABSTRACT
BACKGROUND: Several cytotoxic chemotherapies have demonstrated efficacy in improving recurrence-free survival (RFS) following resection of Stage II-IV colorectal cancer (CRC). However, the temporal dynamics of response to such adjuvant therapy have not been systematically quantified. METHODS: The Cochrane Central Register of Trials, Medline (PubMed) and Web of Science were queried from database inception to February 23, 2023 for Phase III randomized controlled trials (RCTs) where there was a significant difference in RFS between adjuvant chemotherapy and surgery only arms. Summary data were extracted from published Kaplan-Meier curves using DigitizeIT. Absolute differences in RFS event rates were compared at matched intervals using multiple paired t-tests. RESULTS: The initial search yielded 1469 manuscripts. After screening, 18 RCTs were eligible (14 Stage II/III; 4 Stage IV), inclusive of 16,682 patients. In the absence of adjuvant chemotherapy, the greatest rate of recurrence was observed in the first year (mean RFS event rate; 0-0.5 years: 0.22 ± 0.21; 0.5-1 years: 0.20 ± 0.09). Adjuvant chemotherapy was associated with significant decreases in the RFS event rates for the intervals 0-0.5 years (0.09 ± 0.09 vs. 0.22 ± 0.21, p < 0.001) and 0.5-1 years (0.14 ± 0.11 vs. 0.20 ± 0.09, p = 0.001) after randomization, but not at later intervals (1-5 years). In Stage IV trials, RFS event rates significantly differed for the interval 0-0.5 years (p = 0.012), corresponding with adjuvant treatment durations of 6 months. In Stage II/III trials, which included therapies of 6-24 months duration, there were marked differences in the RFS event rates between surgery and chemotherapy arms for the intervals 0-0.5 years (p < 0.001) and 0.5-1 years (p < 0.001) with smaller differences in the RFS event rates for the intervals 1-2 years (p = 0.012) and 2-3 years (p = 0.010). CONCLUSIONS: In a systematic review of positive RCTs comparing adjuvant chemotherapy to surgery alone for Stage II-IV CRC, observed RFS improvements were driven by early divergences that occurred primarily during active cytotoxic chemotherapy. Late recurrence dynamics were not influenced by adjuvant therapy use. Such observations may have implications for the use of chemotherapy for micrometastatic clones detectable by cell-free DNA-based methodologies.
ABSTRACT
Introduction: Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) is a network fostering clinical research to optimize care for critically ill children. We aim to examine the efforts of the PALISI Network to increase gender parity in research, as evidenced by authorship. Methods: The first and senior authors of all published PALISI articles from 2002 to 2021 were analyzed for gender of presentation. Funding sources, impact factors, professional roles, and location were extracted. Results: We identified 303 articles, 61 published from 2002 to 2011, and 242 from 2012 to 2021. There were 302 first authors, representing 188 unique individuals, and 283 senior authors, representing 119 unique individuals. Over half (55.6%, n = 168) of the first authors were women. More women were first authors from 2012 to 2021 (n = 145, 60.2%) as compared to the years 2002-2011 [37.7%, n = 23, OR = 2.50 (95% CI: 1.40, 4.45, p = 0.002)]. Senior authors were 36.0% (n = 102) women, with no change over time. Women senior authors had a higher proportion of women first authors (67.7% vs. 32.4%, p = 0.017). No gender differences were noted based on article type or impact factor. The majority of authors came from institutions in the United States. Women had comparatively more NIH and CDC funding but received less funding from foundations and AHRQ. Discussion: In PALISI publications, first authorship by women has increased over time, such that it now exceeds both the proportion of women pediatric intensivists and women first authors in critical care publications. Senior authorship by women has been stagnant. A multifactorial approach by individuals, institutions, networks, and journals is needed to bring senior women authors to parity.
