Multigene Profiling of Circulating Tumor Cells (CTCs) for Prognostic Assessment in Treatment-Naïve Metastatic Hormone-Sensitive Prostate Cancer (mHSPC).

The substantial biological heterogeneity of metastatic prostate cancer has hindered the development of personalized therapeutic approaches. Therefore, it is difficult to predict the course of metastatic hormone-sensitive prostate cancer (mHSPC), with some men remaining on first-line androgen deprivation therapy (ADT) for several years while others progress more rapidly. Improving our ability to risk-stratify patients would allow for the optimization of systemic therapies and support the development of stratified prospective clinical trials focused on patients likely to have the greatest potential benefit. Here, we applied a liquid biopsy approach to identify clinically relevant, blood-based prognostic biomarkers in patients with mHSPC. Gene expression indicating the presence of CTCs was greater in CHAARTED high-volume (HV) patients (52% CTChigh) than in low-volume (LV) patients (23% CTChigh; * p = 0.03). HV disease (p = 0.005, q = 0.033) and CTC presence at baseline prior to treatment initiation (p = 0.008, q = 0.033) were found to be independently associated with the risk of nonresponse at 7 months. The pooled gene expression from CTCs of pre-ADT samples found AR, DSG2, KLK3, MDK, and PCA3 as genes predictive of nonresponse. These observations support the utility of liquid biomarker approaches to identify patients with poor initial response. This approach could facilitate more precise treatment intensification in the highest risk patients.

The changing landscape of phase II/III metastatic NSCLC clinical trials and the importance of biomarker selection criteria.

Over the last decade, new cytotoxic treatments and targeted therapies have altered treatment paradigms for patients with metastatic non-small cell lung cancer (NSCLC). We sought to analyze the impact of histology and biomarker selection criteria on outcomes of clinical trials in metastatic NSCLC reported over the last decade at the American Society of Clinical Oncology (ASCO) Annual Meeting. Data were collected from ASCO abstracts of Phase II-IV clinical trials for patients with metastatic NSCLC from 2004-2014. 770 of 2,989 identified metastatic NSCLC category abstracts met selection criteria. Despite a decline in the number of abstracts from 107 to 46 abstracts annually over this period, the proportion of trials with positive progression free survival (PFS) and overall survival (OS) outcomes has increased significantly. Trials with histology selection (6%) or molecular biomarker (15%) criteria were more likely to result in an improvement in PFS than those without selection criteria (21% vs. 8%, p = 0.0001 and 31% vs. 10%, p < 0.0001, respectively). These data demonstrate profound changes in the clinical trial landscape over the last 10 years with significantly increasing proportion of trials with positive outcomes. These changes are likely attributed to the use of histology and biomarker selection criteria in clinical trial design.

Bevacizumab in advanced NSCLC: chemotherapy partners and duration of use.

OPINION STATEMENT: Bevacizumab is an effective targeted therapy with demonstrated survival benefits for many patients with advanced nonsquamous non-small cell lung cancer (NSCLC). Some patient populations are at higher risk for bleeding complications and bevacizumab should be avoided, but advanced age should not be used as the sole exclusion criterion for use. Bevacizumab is generally a well-tolerated therapy that can be safely given in combination with multiple chemotherapy agents in the induction and maintenance phases of therapy. The optimal maintenance strategy is yet to be determined and is the focus of ongoing trials, such as ECOG 5508. Early use of bevacizumab in the adjuvant setting and continued use in the second-line setting are being investigated in current clinical trials.

Teleoncology for Veterans: High Patient Satisfaction Coupled With Positive Financial and Environmental Impacts.

PURPOSE: There was rapid adoption of teleoncology care in the Veterans Health Administration during the COVID-19 pandemic. One third of 9 million Veterans Health Administration enrolled Veterans live in rural areas. Although digital solutions can expand capacity, enhance care access, and reduce financial burden, they may also exacerbate rural-urban health disparities. Careful evaluation of patients' perceptions and policy tradeoffs are necessary to optimize teleoncology postpandemic. METHODS: Patients with ≥ 1 teleoncology visit with medical, surgical, or radiation oncology between March 2020 and June 2020 were identified retrospectively. Validated, Likert-type survey assessing patient satisfaction was developed. Follow-up survey was conducted on patients with ≥ 1 teleoncology visit from August 2020 to January 2021. Travel distance, time, cost, and carbon dioxide emissions were calculated based on zip codes. RESULTS: A hundred surveys were completed (response rate, 62%). Patients overall were satisfied with teleoncology (83% Agree or Strongly Agree) but felt less satisfied than in-person visits (47% Agree or Strongly Agree). Audiovisual component improved patient perception of involvement in care, ability to self-manage health or medical needs, and comparability to in-person visits. Follow-up survey demonstrated similar satisfaction. Total travel-related savings are as follows: 86,470 miles, 84,374 minutes, $49,720 US dollars, and 35.5 metric tons of carbon dioxide. CONCLUSION: Veterans are broadly satisfied with teleoncology. Audiovisual capabilities are critical to satisfaction. This is challenging for rural populations with lack of technology access. Patients experienced financial and time savings, and society benefitted from reduced carbon emissions. Continued optimization is needed to enhance patient experience and address secondary effects.

Implementation of a Multidisciplinary Care Pathway via an Emergency Department-ICU to Improve Care of Emergency Department Patients Presenting With Leukostasis.

Leukostasis is a life-threatening complication of acute hyperleukocytic leukemia, and is associated with substantial mortality. Management of leukostasis requires time-sensitive diagnostics and therapeutics, and leukapheresis remains a mainstay of treatment in select patients. Leukapheresis requires coordination of multi-disciplinary resources, which can prove challenging in the emergency department setting, and delays in treatment due to the complexity and coordination required are common. The objective of this study was to assess the effect of utilization of an emergency department-ICU and a multidisciplinary care pathway on outcomes of critically ill leukostasis patients presenting to the emergency department. DESIGN: Retrospective cohort study. SETTING: Single large academic medical center in the United States. PATIENTS: Adult emergency department patients with signs and symptoms of leukostasis requiring emergent leukapheresis from 2012-2019. INTERVENTIONS: Implementation of a hybrid emergency department-ICU setting (emergency critical care center) and a multidisciplinary care pathway with members from Emergency Medicine, Hematology, Blood Bank, and Clinical Pathology. MEASUREMENTS AND MAIN RESULTS: A total of 70 patients were identified and included for analysis: 14 preemergency critical care center; 32 postemergency critical care center, premultidisciplinary care pathway; and 24 postemergency critical care center, postmultidisciplinary care pathway. A statistically significant reduction in the time from emergency department presentation to initiation of leukapheresis was observed from preemergency critical care center to postemergency critical care center, premultidisciplinary care pathway and postemergency critical care center, postmultidisciplinary care pathway (11.5 vs 7.9 vs 7.7 hr; p = 0.004). Statistically significant reductions in in-hospital mortality were observed from preemergency critical care center to postemergency critical care center, premultidisciplinary care pathway and postemergency critical care center, postmultidisciplinary care pathway (64.3% vs 21.9% vs 25.0%; p = 0.01). A trend toward decreased inpatient ICU utilization was observed, although was not statistically significant (35.7% vs 12.5% vs 25.0%; p = 0.14.). CONCLUSIONS AND RELEVANCE: Implementation of a multidisciplinary care pathway via use of an emergency department-ICU for critically ill patients with leukostasis was associated with statistically significant reductions in time to leukapheresis and in-hospital mortality. These findings suggest an emergency department-ICU model may allow for maximal resource and care coordination at the point of contact with critically ill patients and improved clinical outcomes.