11019 Background: There is growing awareness of the challenges of retaining oncologists engaged in research, and this leaky academic pipeline is most notable for women in medicine. Studying academic oncologists is challenging due to their many affiliations, but with an estimated attendance of over 30,000 oncologists, the ASCO annual meeting is a highly sought-after stage for presenting new research. To better understand the continued research engagement of oncologists active in research, we used public data from ASCO annual meetings to follow a cohort of oral abstract presenters over 5 years. Methods: To define our initial cohort of oncologists engaged in research, we used the 2016 ASCO Annual Meeting Digital Program to identify first author oral abstract presenters. We tracked if each presenter was subsequently listed as an author of any research type (oral abstract session, poster session, education session, etc.) at the 2017, 2018, 2019, 2020 and 2021 ASCO conferences. We then filtered out researchers who were not listed as authors at ASCO in consecutive years to look at only those researchers who continued to have active ASCO involvement. To evaluate by gender, each presenter’s name was referenced with the publicly available Wiki-Gendersort tool for an unbiased assignment. Results: 209 first author oral abstract presenters were identified at the 2016 ASCO conference. We found that 67.9% of the initial 209 researchers were listed as authors at ASCO in 2017, 55.5% continued to be authors in 2018, 46.9% in 2019, 42.6% in 2020, and only 38.3% were still listed as authors 5 years later in 2021. When looking at sustained first authorship, 8.1% of the initial 209 research cohort continued to be listed as first authors for 5 consecutive years through 2021. We also looked at the breakdown of other types of ASCO presentations and found that 122 of the initial 209 research cohort presented posters in 2016. Of these 122 researchers, 60 (49.2%) remained authors of posters throughout the consecutive 5 years. This is significantly higher than the number of researchers who continued to author oral abstracts in 2021 49.2% vs. 3.8% (P < 0.0001). When evaluating the differences between gender, there were approximately twice as many men presenters as women (122 men vs 65 women; 22 names were unisex or unknown). The rate of retention was similar for men (47 of the initial 122 males, 38.5%) and women (25 of the initial 65 females, 38.5%) at 5 years (P = 1). Conclusions: We conducted a descriptive study evaluating the rate of sustained activity in academic oncology over 5 years. Our research suggests that about one-third of ASCO presenters will continue to have sustained yearly authorship at 5 years post-oral abstract presentation. Compared to men, the leaky academic pipeline is comparable for women in the 5 years following an oral abstract presentation at ASCO.

Background

In preclinical studies of pancreatic ductal adenocarcinoma (PDAC), ibrutinib improved the antitumor efficacy of the standard of care chemotherapy. This led to a phase 1b clinical trial to determine the safety, tolerability, and immunologic effects of ibrutinib treatment in patients with advanced PDAC.

Methods

Previously untreated patients with PDAC were enrolled in a phase 1b clinical trial (ClinicalTrials.gov) to determine the safety, toxicity, and maximal tolerated dose of ibrutinib when administered with the standard regimen of gemcitabine and nab-paclitaxel. To study the immune response to ibrutinib alone, the trial included an immune response arm where patients were administered with ibrutinib daily for a week followed by ibrutinib combined with gemcitabine and nab-paclitaxel. Endoscopic ultrasonography-guided primary PDAC tumor biopsies and blood were collected before and after ibrutinib monotherapy. Changes in abundance and functional state of immune cells in the blood was evaluated by mass cytometry by time of flight and statistical scaffold analysis, while that in the local tumor microenvironment (TME) were assessed by multiplex immunohistochemistry. Changes in B-cell receptor and T-cell receptor repertoire were assessed by sequencing and analysis of clonality.

Results

In the blood, ibrutinib monotherapy significantly increased the frequencies of activated inducible T cell costimulator⁺(ICOS⁺) CD4⁺ T cells and monocytes. Within the TME, ibrutinib monotherapy led to a trend in decreased B-cell abundance but increased interleukin-10⁺ B-cell frequency. Monotherapy also led to a trend in increased mature CD208⁺dendritic cell density, increased late effector (programmed cell death protein 1 (PD-1^-) eomesodermin (EOMES⁺)) CD8⁺ T-cell frequency, with a concomitantly decreased dysfunctional (PD-1⁺ EOMES⁺) CD8⁺ T-cell frequency. When ibrutinib was combined with chemotherapy, most of these immune changes were not observed. Patients with partial clinical responses had more diverse T and B cell receptor repertoires prior to therapy initiation.

Conclusion

Ibrutinib monotherapy skewed the immune landscape both in the circulation and TME towards activated T cells, monocytes and DCs. These effects were not observed when combining ibrutinib with standard of care chemotherapy. Future studies may focus on other therapeutic combinations that augment the immunomodulatory effects of ibrutinib in solid tumors.

Trial registration number

NCT02562898.

Background

Although specific interventions previously demonstrated benefit in patients with ARDS, use of these interventions is inconsistent, and patient mortality remains high. The impact of variability in center management practices on ARDS mortality rates remains unknown.

Research question

What is the impact of treatment variability on mortality in patients with moderate to severe ARDS in the United States?

Study design and methods

We conducted a multicenter, observational cohort study of mechanically ventilated adults with ARDS and Pao₂ to Fio₂ ratio of ≤ 150 with positive end-expiratory pressure of ≥ 5 cm H₂O, who were admitted to 29 US centers between October 1, 2016, and April 30, 2017. The primary outcome was 28-day in-hospital mortality. Center variation in ventilator management, adjunctive therapy use, and mortality also were assessed.

Results

A total of 2,466 patients were enrolled. Median baseline Pao₂ to Fio₂ ratio was 105 (interquartile range, 78.0-129.0). In-hospital 28-day mortality was 40.7%. Initial adherence to lung protective ventilation (LPV; tidal volume, ≤ 6.5 mL/kg predicted body weight; plateau pressure, or when unavailable, peak inspiratory pressure, ≤ 30 mm H₂O) was 31.4% and varied between centers (0%-65%), as did rates of adjunctive therapy use (27.1%-96.4%), methods used (neuromuscular blockade, prone positioning, systemic steroids, pulmonary vasodilators, and extracorporeal support), and mortality (16.7%-73.3%). Center standardized mortality ratios (SMRs), calculated using baseline patient-level characteristics to derive expected mortality rate, ranged from 0.33 to 1.98. Of the treatment-level factors explored, only center adherence to early LPV was correlated with SMR.

Interpretation

Substantial center-to-center variability exists in ARDS management, suggesting that further opportunities for improving ARDS outcomes exist. Early adherence to LPV was associated with lower center mortality and may be a surrogate for overall quality of care processes. Future collaboration is needed to identify additional treatment-level factors influencing center-level outcomes.

Trial registry

ClinicalTrials.gov; No.: NCT03021824; URL: www.clinicaltrials.gov.