Effects of Specialist Palliative Care for Patients Undergoing Major Abdominal Surgery for Cancer: A Randomized Clinical Trial.

Importance: Specialist palliative care benefits patients undergoing medical treatment of cancer; however, data are lacking on whether patients undergoing surgery for cancer similarly benefit from specialist palliative care. Objective: To determine the effect of a specialist palliative care intervention on patients undergoing surgery for cure or durable control of cancer. Design, Setting, and Participants: This was a single-center randomized clinical trial conducted from March 1, 2018, to October 28, 2021. Patients scheduled for specified intra-abdominal cancer operations were recruited from an academic urban referral center in the Southeastern US. Intervention: Preoperative consultation with palliative care specialists and postoperative inpatient and outpatient palliative care follow-up for 90 days. Main Outcomes and Measures: The prespecified primary end point was physical and functional quality of life (QoL) at postoperative day (POD) 90, measured by the Functional Assessment of Cancer Therapy-General (FACT-G) Trial Outcome Index (TOI), which is scored on a range of 0 to 56 with higher scores representing higher physical and functional QoL. Prespecified secondary end points included overall QoL at POD 90 measured by FACT-G, days alive at home until POD 90, and 1-year overall survival. Multivariable proportional odds logistic regression and Cox proportional hazards regression models were used to test the hypothesis that the intervention improved each of these end points relative to usual care in an intention-to-treat analysis. Results: A total of 235 eligible patients (median [IQR] age, 65.0 [56.8-71.1] years; 141 male [60.0%]) were randomly assigned to the intervention or usual care group in a 1:1 ratio. Specialist palliative care was received by 114 patients (97%) in the intervention group and 1 patient (1%) in the usual care group. Adjusted median scores on the FACT-G TOI measure of physical and functional QoL did not differ between groups (intervention score, 46.77; 95% CI, 44.18-49.04; usual care score, 46.23; 95% CI, 43.08-48.14; P = .46). Intervention vs usual care group odds ratio (OR) was 1.17 (95% CI, 0.77-1.80). Palliative care did not improve overall QoL measured by the FACT-G score (intervention vs usual care OR, 1.09; 95% CI, 0.75-1.58), days alive at home (OR, 0.87; 95% CI, 0.69-1.11), or 1-year overall survival (hazard ratio, 0.97; 95% CI, 0.50-1.88). Conclusions and Relevance: This randomized clinical trial showed no evidence that early specialist palliative care improves the QoL of patients undergoing nonpalliative cancer operations. Trial Registration: ClinicalTrials.gov Identifier: NCT03436290.

Seven decades of chemotherapy clinical trials: a pan-cancer social network analysis.

Clinical trials establish the standard of cancer care, yet the evolution and characteristics of the social dynamics between the people conducting this work remain understudied. We performed a social network analysis of authors publishing chemotherapy-based prospective trials from 1946 to 2018 to understand how social influences, including the role of gender, have influenced the growth and development of this network, which has expanded exponentially from fewer than 50 authors in 1946 to 29,197 in 2018. While 99.4% of authors were directly or indirectly connected by 2018, our results indicate a tendency to predominantly connect with others in the same or similar fields, as well as an increasing disparity in author impact and number of connections. Scale-free effects were evident, with small numbers of individuals having disproportionate impact. Women were under-represented and likelier to have lower impact, shorter productive periods (P < 0.001 for both comparisons), less centrality, and a greater proportion of co-authors in their same subspecialty. The past 30 years were characterized by a trend towards increased authorship by women, with new author parity anticipated in 2032. The network of cancer clinical trialists is best characterized as strategic or mixed-motive, with cooperative and competitive elements influencing its appearance. Network effects such as low centrality, which may limit access to high-profile individuals, likely contribute to the observed disparities.

Empiric Therapy with BRAF and MEK Inhibitors in Metastatic Melanoma.

BRAF and MEK inhibitors are highly active in the setting of BRAF V600 mutant melanoma. Rarely, patients without previous testing present with fulminant progression necessitating emergent treatment prior to BRAF testing results. The safety and efficacy of empiric treatment in this setting is unclear. Herein, we present two patients treated with empiric BRAF and MEK inhibitors, resulting in dramatic clinical improvement in one patient later found to have a BRAF mutation, and lack of improvement (but no accelerated progression) in a patient lacking this mutation. Empiric BRAF and MEK inhibitor treatment should not be routinely pursued but may be given safely in rare, emergent situations.

Systematic review of infectious events with the Bruton tyrosine kinase inhibitor ibrutinib in the treatment of hematologic malignancies.

OBJECTIVE: Ibrutinib is an irreversible inhibitor of Bruton tyrosine kinase (BTK) in B lymphocytes as well as other kinases including interleukin-2-inducible T-cell kinase (ITK) in CD4+ Th2 regulatory T cells. Increased infections have been observed in patients taking ibrutinib. The overall incidence has not been systematically evaluated. METHODS: The published literature and conference abstracts of prospective clinical trials using ibrutinib in hematologic malignancies were identified and reviewed using PubMed, Google Scholar, and HemOnc.org per PRISMA guidelines. Infectious events with a focus on pneumonia were collated per the Common Terminology Criteria for Adverse Events Version 4.03 grading. RESULTS: Infectious complications are common, occurring in 56% of patients taking single-agent ibrutinib and 52% of those on combination therapy. Approximately one in 5 patients developed pneumonia, which was the major contributor to a 2% rate of death from infections. Many of the cases of pneumonia were due to opportunistic pathogens. CONCLUSIONS: Ibrutinib use requires prudent consideration of the impacts on host immunity. We identified a high rate of serious adverse infectious events within prospective clinical trials. Data suggest a role of both BTK and ITK inhibition for the increased events. There was considerable variability in the reporting of adverse events between trials, journals, and conference reports.

Effects of Plasma Exchange and Heparin Concentration on the Serotonin Release Assay in Heparin-Induced Thrombocytopenia.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a hypercoagulable state caused by a transient antibody to heparin-bound platelet factor 4 (PF4). Treatment involves discontinuing heparin and administering a nonheparin anticoagulant. Procedures requiring heparin, such as cardiopulmonary bypass, are preferably delayed until the offending antibody is no longer detectable. For patients with a high-titer anti-PF4-heparin antibody and who require exposure to heparin, therapeutic plasma exchange (TPE) has been used to remove the antibody. Recent work indicates that a functional assay for detecting platelet-activating antibodies in HIT patients, the serotonin release assay (SRA), is preferable to ELISAs for anti-PF4-heparin antibodies for following the effectiveness of plasma exchange. METHODS: Two cases of acute heparin-induced thrombocytopenia managed with plasma exchange before emergent cardiac surgery were evaluated with SRAs using a range of heparin concentrations that included those used in cardiopulmonary bypass. RESULTS: We observed that a single round of plasma exchange led to greater reduction in platelet reactivity at heparin concentrations between 1 and 3 U/mL than at lower concentrations, consistent with the impression that heparin-PF4-antibody complexes form optimally within a limited heparin concentration range. CONCLUSIONS: The findings suggest there may be a range of heparin concentration in which cardiac surgery may be safely performed in HIT patients, and that a single TPE in an emergent setting may lower antibody concentration sufficiently to lower platelet reactivity in the presence of heparin.

The immunophenotype of pre-TALL/LBL revisited.

Flow cytometric analysis of cluster of differentiation (CD) markers in abnormal lymphocyte populations is crucial in the diagnosis of precursor T cell acute lymphoblastic leukemia (T-ALL)/lymphoblastic lymphoma (LBL). The World Health Organization (WHO) suggested immunophenotype for pre-T ALL/LBL typically includes the expression of TdT, cCD3, and CD7, while CD2, CD3, CD4, CD5, CD8, and CD10 are variably expressed. The myeloid antigens CD13 and CD33 are usually positive, whereas CD117 and cCD79a are infrequently expressed. Furthermore, there is frequent dual expression of CD4 and CD8. In the present investigation, 19 cases of pre-TALL/LBL were analyzed for selected CD marker expression. Fifteen of 19 cases studied were evaluated for TdT, cCD3, and cCD79a expression. Eleven (73.3%) positively expressed TdT, 15 (100%) positively expressed cCD3, and 9 (60%) positively expressed cCD79a. Of the 17 cases analyzed for CD7, CD5, and CD10 expression, CD7 and CD5 were positive in all 17 (100%) cases, whereas CD10 was positive in 8 (47.1%) cases. Of the 18 cases evaluated for CD2, CD3, CD4, CD8, and dual expression of CD4 and CD8, CD2 was expressed in 14 (77.8%), while CD3 was expressed in 7 (38.9%) cases. CD4 was positive in 11 (61.1%), and CD8 was expressed in 9 (50%). Dual expression of CD4 and CD8 occurred in only 4 (22.2%) of the cases. Of the 16 analyzed for CD13, CD33, and CD117, only 1 case (6.3%) expressed CD13, while 2 (12.5%) cases expressed CD33 and CD117. Thus, these data point to the need for a more extensive study to reevaluate the current WHO defined immunophenotype used in the diagnosis of pre-TALL/LBL.

Antigenic transformation in plasma cell dyscrasia.

The WHO immunophenotype for plasma cell myeloma is deletion of CD19 and CD20, usual expression of CD38, CD138, and CD56, and occasional expression of CD10. Of the 39 cases of plasma cell dyscrasia in our study, the mean fluorescence intensities (MFI) of CD38, CD138, CD56, and CD19 were quantified in 30 cases. CD19 was absent in 38 of the cases (97.4%), whereas CD138 and CD38 were expressed in all 39 cases (100%). Most cases expressed CD38 and CD138 brightly with MFI values greater than 501, whereas all other marker expression was moderate with MFI greater than 301. Whereas CD38/CD56 dual expression was observed in 25 cases (64.1%), 14 failed to express CD56 (35.9%). CD56 expression was bright in 16 cases (53.3%), moderate in 2 cases (6.7%), and negative in the remaining 12 cases (40%) with MFI values of 200 or less. CD117 expression was positive in 9 of 24 cases (37.5%). In 32 of 39 cases, 27 were negative for CD20 (84.4%) and 28 were negative for CD10 (87.5%). Our results point to the value of quantitative fluorescence intensity in the flow cytometric evaluation of CD molecular expression or deletion in the diagnosis of hematopathologic disorders, such as plasma cell dyscrasia.