Citations

Purpose. There are no known effective medical treatments for refractory MPNST. Inactivation of the NF1 tumor suppressor in MPNST results in upregulation of mTOR (mammalian target of rapamycin) signaling and angiogenesis, which contributes to disease progression. We conducted a phase II study for patients (pts) with refractory MPNST combining everolimus (10 mg PO once daily) with bevacizumab (10 mg/kg IV every 2 weeks) to determine the clinical benefit rate (CBR) (complete response, partial response (PR), or stable disease (SD) ≥ 4 months). Patients and Methods. Patients ≥18 years old with chemotherapy refractory sporadic or NF1 MPNST were eligible. Tumor response was assessed after every 2 cycles (the WHO criteria). A two-stage design targeting a 25% CBR was used: if ≥ 1/15 pts in stage 1 responded, enrollment would be expanded by 10 pts, and if ≥ 4/25 patients had clinical benefit, the combination would be considered active. Results. Twenty-five pts, 17 with NF1 and 8 with sporadic MPNST, enrolled. One of 15 pts in stage 1 had clinical benefit. Of 10 additional pts enrolled, 2 had clinical benefit. The median number of completed cycles was 3 (range 1–16). Adverse events were similar to those known for this combination. Conclusion. With a CBR of 12% (3/25), the combination of everolimus and bevacizumab did not reach the study’s target response rate and is not considered active in refractory MPNST.

AbstractBackgroundThe importance of change‐of‐shift handoffs in maintaining patient safety has been well demonstrated. Change‐of‐shift handoff is an important source of data used in surveillance, a nursing intervention aimed at identifying and preventing complications. Surveillance requires the nurse to acquire, process, and synthesize information (cues) encountered during patient care. Interruptions in handoff have been observed but there is a gap in the evidence concerning how interruptions during nurse‐to‐nurse handoff impact the change‐of‐shift handoff process.AimsTo describe registered nurses’ perceptions of interruptions experienced during change‐of‐shift handoff at the bedside in critical care units and analyze the number, type, and source of interruptions during change‐of‐shift handoff at the bedside.MethodsAn exploratory descriptive design was used. One hundred nurse‐to‐nurse handoffs were observed, and four focus groups were conducted. Observation data were analyzed with descriptive statistics and quantitative content analysis. Focus group data were analyzed with qualitative content analysis.Results and FindingsOf the 1,196 interruptions observed, 800 occurred in the communication between the two nurses involved in the handoff. Over 80% (645) of these interruptions were from the nurse receiving handoff and included questions or clarification of information received. About half of the nurses reported that interruptions occurred during handoff. Focus group findings revealed that whether or not something is an interruption is determined by the individual nurse’s appraisal of value added to their knowledge of the patient and/or plan of care at the time of handoff.Linking Evidence to ActionInterruptions during handoff are evaluated as useful or disruptive based on the value to the nurse at the time. Strict structuring or mandating of handoff elements may limit nurses’ ability to communicate information deemed most relevant to the care of a specific unique patient.

Purpose Despite increasing emphasis in medical school education on quality and systems improvement, many medical schools lack sufficient faculty with expertise to teach systems improvement. Using the pedagogical content knowledge framework, this study explores how faculty engage students in systems improvement work and faculty perceptions of the outcomes for the health system and students. Method In May–June 2017, the authors interviewed 12 of 13 invited faculty with experience in teaching and engaging first-year medical students in systems improvement work, the course of students’ systems improvement work over time, the impact of students’ projects on health systems, and students’ learning and attitudes about systems improvement. The authors conducted qualitative analysis iteratively with data collection to sufficiency. Results Six emergent themes characterized faculty’s approach to guiding students in systems improvement work: faculty–student relationship, faculty role, student role, faculty–student shared responsibility for projects, faculty and student content knowledge, and project outcomes. The faculty–student relationship was foundational for successful systems improvement work. Faculty roles included project selection, project management, and health systems interactions. Students engaged in systems improvement as their faculty leveraged their knowledge and skills and created meaningful student roles. Faculty and students shared responsibility and colearned systems improvement content knowledge. Faculty defined successful outcomes as students’ learning about the systems improvement process and interprofessional collaboration. Conclusions Findings highlight the critical importance of pedagogical content knowledge to engage early learners in systems improvement work, understand their learning interests and needs, and manage their projects longitudinally.

The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for consequences of cancer and cancer treatment to aid healthcare professionals who work with survivors of adult-onset cancer. Guidance is also provided to help promote physical activity, weight management, and proper immunizations in survivors and to facilitate care coordination to ensure that all needs are addressed. These NCCN Insights summarize some of the topics discussed by the NCCN Survivorship Panel during the 2019 update of the guidelines, including the survivorship population addressed, ways to improve care coordination, and pain management.

Abstract Small pulmonary nodules are most often managed by surveillance imaging with computed tomography (CT) of the chest, but the optimal frequency and duration of surveillance are unknown. The Watch the Spot Trial is a multicenter, pragmatic, comparative-effectiveness trial with cluster randomization by hospital or health system that compares more- versus less-intensive strategies for active surveillance of small pulmonary nodules. The study plans to enroll approximately 35,200 patients with a small pulmonary nodule that is newly detected on chest CT imaging, either incidentally or by screening. Study protocols for more- and less-intensive surveillance were adapted from published guidelines. The primary outcome is the percentage of cancerous nodules that progress beyond American Joint Committee on Cancer seventh edition stage T1a. Secondary outcomes include patient-reported anxiety and emotional distress, nodule-related health care use, radiation exposure, and adherence with the assigned surveillance protocol. Distinctive aspects of the trial include: 1) the pragmatic integration of study procedures into existing clinical workflow; 2) the use of cluster randomization by hospital or health system; 3) the implementation and evaluation of a system-level intervention for protocol-based care; 4) the use of highly efficient, technology-enabled methods to identify and (passively) enroll participants; 5) reliance on data collected as part of routine clinical care, including data from electronic health records and state cancer registries; 6) linkage with state cancer registries for complete ascertainment of the primary study outcome; and 7) intensive engagement with a diverse group of patient and nonpatient stakeholders in the design and execution of the study.

Background Blood pressure ( BP ) varies over time within individual patients and across different BP measurement techniques. The effect of different BP targets on concordance between BP measurements is unknown. The goals of this analysis are to evaluate concordance between (1) clinic and ambulatory BP , (2) clinic visit‐to‐visit variability and ambulatory BP variability, and (3) first and second ambulatory BP and to evaluate whether different clinic targets affect these relationships. Methods and Results The SPRINT (Systolic Blood Pressure Intervention Trial) ambulatory BP monitoring ancillary study obtained ambulatory BP readings in 897 participants at the 27‐month follow‐up visit and obtained a second reading in 203 participants 293±84 days afterward. There was considerable lack of agreement between clinic and daytime ambulatory systolic BP with wide limits of agreement in Bland‐Altman plots of −21 to 34 mm Hg in the intensive‐treatment group and −26 to 32 mm Hg in the standard‐treatment group. Overall, there was poor agreement between clinic visit‐to‐visit variability and ambulatory BP variability with correlation coefficients for systolic and diastolic BP all <0.16. We observed a high correlation between first and second ambulatory BP ; however, the limits of agreement were wide in both the intensive group (−27 to 21 mm Hg) and the standard group (−23 to 20 mm Hg). Conclusions We found low concordance in BP and BP variability between clinic and ambulatory BP and second ambulatory BP . Results did not differ by treatment arm. These results reinforce the need for multiple BP measurements before clinical decision making.

The 2017 World Health Organization update introduced a new category of nodal peripheral T-cell lymphoma with T-follicular helper phenotype (PTCL-TFH) defined by expression of at least 2 or 3 TFH markers. Our study assesses the utility of an immunohistochemical panel of 5 TFH markers (CD10, BCL6, PD-1, CXCL13, and ICOS) for identification of TFH phenotype in angioimmunoblastic T-cell lymphoma (AITL) and PTCL not otherwise specified (NOS). Immunohistochemical for the 5 markers was performed on 22 cases of AITL and 29 cases of PTCL-NOS. Cases were reviewed for morphologic features characteristic of AITL. All AITL cases showed expression of ≥2 TFH markers. This panel resulted in reclassification of 41% PTCL-NOS cases to PTCL-TFH. Positive percent agreement for the TFH phenotype is 97% for PD1, 94% for ICOS, 44% for CD10 and CXCL13, and 29% for BCL6. Negative percent agreement for TFH phenotype is 100% for CD10, BCL6, and CXCL13, 82% for ICOS and 71% for PD1. AITL cases were more likely than PTCL-TFH cases to contain expanded CD21-positive follicular dendritic cell meshworks, clear cell cytology and polymorphous inflammatory background; however, there was a significant (P<0.005) Kruskal-Wallis trend in all morphologic variables between the 3 groups suggesting a continuum from PTCL-NOS to PTCL-TFH to AITL. The median number of morphologic features of AITL also correlated significantly with number of TFH markers positive (Spearman coefficient ρ=0.759). In summary, the stain panel chosen will have an impact on cases classified as PTCL-TFH. This entity may exist along a spectrum between PTCL-NOS and AITL.

Abstract Purpose: Protein kinases are known to play a prominent role in oncogenic progression across multiple cancer subtypes, yet their role in prostate cancer progression remains underexplored. The purpose of this study was to identify kinases that drive prostate cancer progression. Experimental Design: To discover kinases that drive prostate cancer progression, we investigated the association between gene expression of all known kinases and long-term clinical outcomes in tumor samples from 545 patients with high-risk disease. We evaluated the impact of genetic and pharmacologic inhibition of the most significant kinase associated with metastatic progression in vitro and in vivo. Results: DNA-dependent protein kinase (DNAPK) was identified as the most significant kinase associated with metastatic progression in high-risk prostate cancer. Inhibition of DNAPK suppressed the growth of both AR-dependent and AR-independent prostate cancer cells. Gene set enrichment analysis nominated Wnt as the top pathway associated with DNAPK. We found that DNAPK interacts with the Wnt transcription factor LEF1 and is critical for LEF1-mediated transcription. Conclusions: Our data show that DNAPK drives prostate cancer progression through transcriptional regulation of Wnt signaling and is an attractive therapeutic target in aggressive prostate cancer.