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The purpose of this study was to first characterize the prevalence of recall, recognition, and knowledge of colon cancer screening tests and guidelines (collectively, "awareness") among non-Hispanic black (NHB) and NH white (NHW) urban colon cancer patients. Second, we sought to examine whether awareness was associated with mode of cancer detection. Low awareness regarding colon cancer screening tests and guidelines may explain low screening rates and high prevalence of symptomatic detection. We examined recall, recognition, and knowledge of colorectal cancer (CRC) screening tests and guidelines and their associations with mode of cancer detection (symptomatic versus screen-detected) in 374 newly diagnosed NHB and NHW patients aged 45-79. Patients were asked to name or describe any test to screen for colon cancer (recall); next, they were given descriptions of stool testing and colonoscopy and asked if they recognized each test (recognition). Lastly, patients were asked if they knew the screening guidelines (knowledge). Overall, awareness of CRC screening guidelines was low; just 20% and 13% of patients knew colonoscopy and fecal test guidelines, respectively. Awareness of CRC screening tests and guidelines was especially low among NHB males, socioeconomically disadvantaged individuals, and those diagnosed at public healthcare facilities. Inability to name or recall a single test was associated with reduced screen-detected cancer compared with recall of at least one test (36% vs. 22%, p = 0.01). Low awareness of CRC screening tests is a risk factor for symptomatic detection of colon cancer.

Gemcitabine is widely utilized in the treatment of pancreatic, ovarian, and non small cell lung cancers. Gemcitabine is associated with a wide spectrum of lung toxicities, ranging from dyspnea 25% of patients to severe pulmonary toxicity in up to 5% of patients. There is a dearth of information specific to pulmonary toxicity in the setting of gemcitabine combination chemotherapy. Given the potential severity, it is important to identify it early by excluding more common etiologies. We share two case reports of patients with pancreatic cancer who developed severe pulmonary toxicity during gemcitabine combination chemotherapy. Both cases emphasize the heightened risk of pulmonary toxicity in patients receiving gemcitabine chemotherapy combinations, and a need to be vigilant to initiate appropriate therapies immediately.

BackgroundClinical trials establish the standard of care for cancer and other diseases. While social network analysis has been applied to basic sciences, the social component of clinical trial research is not well characterized. We examined the social network of cancer clinical trialists and its dynamic development over more than 70 years, including the roles of subspecialization and gender in relation to traditional and network-based metrics of productivity.MethodsWe conducted a social network analysis of authors publishing chemotherapy-based prospective trials from 1946-2018, based on the curated knowledge base HemOnc.org, examining: 1) network density; 2) modularity; 3) assortativity; 4) betweenness centrality; 5) PageRank; and 6) the proportion of co-authors sharing the same primary cancer subspecialty designation. Individual author impact and productive period were analyzed as a function of gender and subspecialty.FindingsFrom 1946-2018, the network grew to 29,197 authors and 697,084 co-authors. While 99.4% of authors were directly or indirectly connected as of 2018, the network had very few connections and was very siloed by cancer subspecialty. Small numbers of individuals were highly connected and had disproportionate impact (scale-free effects). Women were under-represented and likelier to have lower impact, shorter productive periods (PInterpretationThe network of cancer clinical trialists is best characterized as a strategic or “mixed-motive” network, with cooperative and competitive elements influencing its appearance.Network effects e.g., low centrality, which may limit access to high-profile individuals, likely contribute to ongoing disparities.FundingVanderbilt Initiative for Interdisciplinary Research; National Institutes of Health; National Science FoundationResearch in contextEvidence before this studyWe reviewed the literature on social networks from the 1800’s to 2018. Additionally, MEDLINE was searched for (“Social Networking”[Mesh] OR “Social Network Analysis”) AND (“Clinical Trials as Topic”[Mesh] OR “Hematology”[Mesh] OR “Medical Oncology”[Mesh]) without date restriction. The MEDLINE search yielded 43 results, of which 8 were relevant; none considered gender nor temporality in their analyses. To our knowledge, there has not been any similar study of the dynamic social network of clinical trialists from the inception of the fields of medical oncology and hematology to the present.Added value of this studyThis is the first dynamic social network analysis of cancer clinical trialists. We found that the network was sparse and siloed with a small number of authors having disproportionate impact and influence as measured by network metrics such as PageRank; these metrics have become more disproportionate over time. Women were under-represented and likelier to have lower impact, shorter productive periods, less network centrality, and a greater proportion of co-authors in their same cancer subspecialty.Implications of all the available evidenceWhile gender disparities have been demonstrated in many fields including hematology/oncology, our analysis is the first to show that network factors themselves are significantly implicated in gender disparity. The increasing coalescence of the network by traditional cancer type and around a small number of high-impact individuals implies challenges when the field pivots from traditionally disease-oriented subspecialties to a precision oncology paradigm. New mechanisms are needed to ensure diversity of clinical trialists.

Background: PAC-1 is a small molecule that directly activates procaspase-3 and induces apoptosis of cancer cells. PAC-1 crosses the blood-brain-barrier. This first-in-human, phase I, multicenter study consists of 2 components. Component 1 evaluated safety, pharmacokinetics (PK), and preliminary clinical activity of single agent PAC-1 in patients with solid tumors or lymphoma. Component 2 combines PAC-1 with temozolomide in patients with refractory high-grade astrocytomas. Methods: Patients with metastatic solid tumors or lymphomas were enrolled in component 1 and patients with refractory high-grade astrocytomas were enrolled in component 2. A modified- Fibonacci dose-escalation 3+3 design was used in both components. The primary objective was to assess maximum tolerated dose (MTD). In component 1, PAC-1 was dosed from 75 to 750 mg daily orally (7 dose levels (DL)) on days 1-21 on 28 days cycle. For all dose cohorts, PAC-1 PK was assessed following doses administered on days 1 and 21 of the first cycle. In component 2, PAC-1 is dosed from 375 to 750 mg daily (up to 4 DL) plus temozolomide orally 150 mg/m2 daily for 5 days. PAC-1 PK was assessed following doses administered on days 7 and 12 and temozolomide PK is performed on Day 12 of the first cycle. Disease assessment was done every 2 cycles. Neurologic and neurocognitive function (NNCF) tests were performed throughout the study due to concern for neurotoxicity. Results: Forty-four patients were enrolled in part 1 and 12 in component 2. In part 1, at DL 1-5 no dose-limiting toxicities (DLTs) were observed. DL 6 was expanded to 6 patients due to one episode of intracranial bleed that occurred during cycle 4 of treatment, assessed initially as possibly related to study drug, but later attributed to new brain metastasis and unrelated to PAC-1. Grade 1 and 2 neurological adverse events such as ataxia and hallucinations were noted in DL 7 and this DL was expanded to 9 patients to assure safety. All other serious adverse events were determined to be unrelated or unlikely related to the study drug. Eleven patients (25%) did not complete 2 cycles of treatment due to rapid progression or withdrawal. Eight patients (18%) had stable disease for at least 2 cycles. One patient (2%) had partial response. In component 2 treating refractory high-grade astrocytomas, 7 patients were accrued to DL 1, and 5 patients to DL 2. No DLT was observed. Nine patients were evaluable for response. Five patients (42 %) had disease progression. Two patients (16%) had stable disease for at least 2 cycles, and two (16%) had partial response. Review of NNCF testing showed a consistent pattern of stable neurologic and cognitive evaluations. The PK data demonstrated satisfactory systemic delivery of PAC-1 following oral administration and acceptable absorption and elimination profiles. Conclusions: Single agent PAC-1 is well tolerated and 750 mg was determined to be the MTD. The combination of PAC-1 plus temozolomide continues to enroll patients in this study. Citation Format: Oana C. Danciu, M. Kelly Nicholas, Matthias Holdhoff, Richard A. Peterson, Neeta Venepalli, Rozina Chowdhery, Paul J. Hergenrother, Theodore M. Tarasow, Arkadiusz Z. Dudek. Phase I study of procaspase activating compound -1 (PAC-1) in the treatment of advanced malignancies and in combination with temozolomide in refractory high-grade astrocytomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT027.