scholarly journals Striving for better comunication - an audit

BJPsych Open ◽  
2021 ◽  
Vol 7 (S1) ◽  
pp. S10-S10
Author(s):  
Eleanor Breen
Keyword(s):  
Mental Health ◽  
Older Adult ◽  
Community Hospital ◽  
Small Sample Size ◽  
Physical Illness ◽  
Clinical Governance ◽  
Small Sample ◽  
Number Of Patients ◽  
Discharge Letter ◽  
Audit Cycle

AimsThe aim of this audit is to assess communication between the general and psychiatric hospital. This audit was prompted after a number of patients were transferred to Udston Hospital, a community hospital with two older adult acute mental health wards, with no written communication. This led to several significant issues including medication errors, ambiguity regarding patient escalation plans and uncertainty regarding what had been discussed with families.MethodOver the course of one month eight patients were identified who had been transferred from the acute site to Udston Hospital. Three were new admissions to Udston, four were returning after treatment for physical illness, and one returned following assessment in ED. Data were collected by examining paper and electronic notes, and analysed using Excel. The results of this audit were discussed at the local clinical governance meeting. A 2nd cycle was performed. Eight transfers were identified. Four were returning after an assessment in ED, two were new admissions to Udston and two were returning after treatment for physical illness.ResultInitial audit found that 38% of patients were transferred with their medical notes, 50% were transferred with no written documentation whatsoever, and none of the patients were transferred with a transfer letter. The second cycle found that 88% of patients had a transfer or discharge letter. 12% of patients came with no written documentation.ConclusionThe initial audit found significant deficiencies in communication. Highlighting the need for all patients to have a transfer letter at a local management meeting seems to have led to an improvement. However, differences between the samples in the 1st and 2nd audit cycle could be distorting the results. Further audits would be useful given the small sample size and due to the differences between the sample populations.

Abstract W P224: Higher Pre-Hospital Blood Pressure Prolongs Door to Needle Thrombolysis Times

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Digvijaya Navalkele ◽  
Chunyan Cai ◽  
Mohammad Rahbar ◽  
Renganayaki Pandurengan ◽  
Tzu-Ching Wu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Small Sample Size ◽  
Heart Association ◽  
Small Sample ◽  
Categorical Variables ◽  
Continuous Variables ◽  
Intravenous Tissue Plasminogen Activator ◽  
Number Of Patients

Background: Per American Heart Association guidelines, blood pressure (BP) should be < 185/110 to be eligible for intravenous tissue plasminogen activator (tPA). It is shown that door to needle (DTN) time is prolonged in patients who require anti-hypertensive medications prior to thrombolysis in the emergency department (ED). To our knowledge, no studies have focused on pre-hospital BP and its impact on DTN times. We hypothesize that DTN times are longer for patients with higher pre-hospital BP. Methods: We conducted a retrospective review of acute ischemic stroke patients who presented between 1/2010 and 12/2010 to our ED through Emergency Medical Services (EMS) within 3-hrs of symptom onset. Patients were identified from our registry and categorized into two groups: Pre-hospital BP ≥ 185/110 (Pre-hsp HBP) and < 185/110 (Pre-hsp LBP). BP records were abstracted from EMS sheets. Two groups were compared using two-sample t-test or Wilcoxon rank sum test for continuous variables and Chi-square test or Fisher’s exact test for categorical variables. Results: A total of 107 consecutive patients were identified. Out of these, 75 patients (70%) were treated with tPA. Among the patients who received thrombolysis, 35% had pre-hospital BP ≥ 185/110 (n= 26/75). Greater number of patients required anti-hypertensive medications in ED in high BP group compared to low BP group (Pre-hsp HBP n= 14/26, 54%; Pre-hsp LBP n= 13/49, 27%, p < 0.02). Mean door to needle times were significantly higher in Pre-hsp HBP group. (mean ± SD 87.5± 34.2 Vs. 59.7±18.3, p<0.0001). Analysis of patients only within the Pre-hsp HBP group (n= 26) revealed that DTN times were shorter if patients received pre-hsp BP medications compared to patients in the same group who did not receive pre-hsp BP medication (n= 10 vs 16; mean ± SD 76.5 ± 25.7 Vs. 94.3 ± 37.7, p = 0.20) Conclusion: Higher pre-hospital BP is associated with prolonged DTN times and it stays prolonged if pre-hospital high BP remains untreated. Although the later finding was not statistical significant due to small sample size, pre-hospital blood pressure control could be a potential area for improvement to reduce door to needle times in acute ischemic stroke.

scholarly journals Discrepancy of Blast Percentage between the Bone Marrow Aspirate and Flow Cytometry and Its Impact on Survival Outcomes in Patients with Myelodysplastic Syndromes Excess Blast (MDS-EB)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5441-5441
Author(s):  
Meera Yogarajah ◽  
Phuong L. Nguyen ◽  
Rong He ◽  
Hassan B. Alkhateeb ◽  
Mithun Vinod Shah ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Small Sample Size ◽  
Scoring Systems ◽  
Standard Of Care ◽  
Risk Groups ◽  
Small Sample ◽  
International Prognostic Scoring System ◽  
P Value ◽  
Number Of Patients

Background MDS is a heterogeneous disease and the revised International Prognostic Scoring System (IPSS-R) is utilized in prognostication. The percentage (%) of blasts in the bone marrow is determined in the aspirate morphologically. Though the former is the standard of care the blast percentage is also reported by flow cytometry and biopsy which can many times be inconsistent. We previously presented the utilization of biopsy based blast percentage which showed meaningful prognostic groups compared to aspirate. In this study we compare the blasts as reported by the aspirate and flow cytometry in MDS-EB in calculating IPSS-R. Methods The MDS database was reviewed for cases of MDS-EB after due IRB approval at the Mayo clinic. We calculated IPSS-R scores based on the aspirate blast % (IPSS-RAsp) and flow blast% (IPSS-Rfl). The aspirate blast percentage was reported morphologically. Suboptimal aspirates were excluded from the study. The flow blast percentage was determined by immunophenotyping. The overall survival (OS) was determined by IPSS-RAsp and IPSS-RFl. OS estimates were calculated by Kaplan-Meier curves and log-rank testing using JMP v.13. Uno's concordance statistic was used to compare the 2 risk scoring systems. Results Of 1322 patients, 431 (33%) cases were identified with MDS-EB out of which 120 (29%) cases had blasts reported in the aspirate and flow. Based on aspirate MDS EB1: 54% (n=65), MDS EB2 46% (n=55). The hematological, cytogenetic and R-IPSS categories were compared between MDS-EB1 and MDS- EB 2. The blast percentage and hemoglobin levels was significantly different between MDS-EB1 and EB2 as seen in table 1, however the IPSS-R risk groups were not significantly different. The flow cytometry was concordant with aspirate in 66/120 (55%) cases. Out of the dis-concordant cases only 20% (11/54) was upstaged by flow cytometry with most of the patients being down staged as expected by the techniques used in processing the blood and hence not reliable when reported low (Figure 1). The OS outcomes based on the IPSS- R asp, IPSS-Rfl areshown in figure 2A,2B .The p value with aspirate based R-IPSS was more significant than flow cytometry based R-IPSS (p= 0.0007 vs 0.0174). We compared the two models for observed OS differences using the Uno model which was not statistically significant. (p= 0.6) Conclusions Both models did not show a difference which is likely due to the very small sample size. However flow cytometry did down stage more patients when disconcordant and may have less value in that setting. It would be ideal to compare all 3 models aspirate, biopsy and flow cytometry however we did not have enough number of patients to do the comparison. Disclosures Patnaik: Stem Line Pharmaceuticals.: Membership on an entity's Board of Directors or advisory committees. Al-Kali:Astex Pharmaceuticals, Inc.: Research Funding.

A study of atherosclerosis in patients after radiation for early breast cancer.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 260-260
Author(s):  
V. G. Kirtani ◽  
M. Chang ◽  
A. M. Dobrescu ◽  
S. Zeldis ◽  
J. A. Haas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Coronary Arteries ◽  
Background Radiation ◽  
Small Sample Size ◽  
Screening Method ◽  
Calcium Score ◽  
Small Sample ◽  
Left Hemithorax ◽  
Asymptomatic Patients ◽  
Number Of Patients

260 Background: Radiation therapy (RT) is widely used as part of curative treatment of breast cancer. However, older studies have shown increased cardiac morbidity and mortality from breast RT. A screening method is needed to detect early cardiac damage in this population. Recent data have shown that Electron beam computed tomography (EBCT) can detect early atherosclerosis in coronary arteries by identifying the amount of calcification in the coronaries. In our study we employed this tool to detect occult atherosclerosis caused by breast RT. Methods: We evaluated 20 asymptomatic patients, less than 60 years of age, treated with RT at least 5 years prior to enrollment. Nine received RT to the left and 11 to the right hemithorax. Average interval between RT and CT was 7.7 years (5-14). All patients were treated with external beam RT using tangential technique. The breast was treated to a dose of 4500-5040 cGy and the tumor bed was boosted to a total dose of 6000-6600 cGy. All patients underwent EBCT to compute the volumetric and agatston calcium scores in the coronary arteries and the aorta. Results: Of the 11 patients who had RT to right hemithorax, 8 had calcium score of 0, 2 had very minimally elevated scores and 1 had significantly elevated score (patient 19, interval -14 years). Of the 9 patients who had RT to left hemithorax, 7 had calcium score of 0. None had significantly elevated scores. In the aorta, 11 patients had score of 0 and 8 had minimally elevated scores. Conclusions: Occult atherosclerosis was not detected using EBCT calcium scores in coronaries and aorta in a significant number of patients treated with RT for breast cancer. However, the study is limited by a small sample size. [Table: see text]

Cell cycle and apoptosis regulatory protein (CARP)-1 expression in neuroblastoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9578-9578
Author(s):  
Santosh S. Hanmod ◽  
Samantha Siegel ◽  
James Hatfield ◽  
Edi Levi ◽  
Marwan Zidan ◽  
...  
Keyword(s):  
Small Sample Size ◽  
Regulatory Protein ◽  
Tumor Biology ◽  
Progression Free Survival ◽  
Small Sample ◽  
Immune Histochemistry ◽  
Formalin Fixed Paraffin ◽  
Number Of Patients ◽  
Significant Difference ◽  
Formalin Fixed Paraffin Embedded

9578 Background: Neuroblastoma (NB) is the most common extra-cranial solid tumor in children. The prognosis for patients with high risk NB is still poor. Study of additional prognostic factors will enhance current understanding of the tumor biology and risk stratification. CARP-1 is a recently identified molecule mediating apoptosis signaling by agents like doxorubicin and etoposide. Since these agents are used in the front line treatment of NB, we tested whether CARP-1 expression could be another prognostic factor in NB. Methods: CARP-1 expression was examined by Western blot in a pair of NB cell lines, SK-N-SH and SK-N-SH Dox. We reviewed medical records of patients with NB at Children’s Hospital of Michigan from 2000-2009 and examined CARP-1 expression by immune-histochemistry in the archived, formalin fixed paraffin embedded NB tissues. CARP-1 expression was recorded as positive or negative. Correlation of CARP-1 expression and progression free survival (PFS) was calculated. Results: CARP-1 expression was detected in SK-N-SH but not SK-N-SH Dox, a doxorubicin-resistant derivative of SK-N-SH, suggesting that resistance to doxorubicin is associated with decreased level of CARP-1 expression in NB cells. Of the 30 cases studied, 53 % (16/30) expressed CARP-1. There was no significant difference in N-myc amplification status (13% vs.14%, p=0.3), or proportion of unfavorable Shimada histology (60% vs. 64%, p=0.5) between CARP-1 positive vs. negative groups. Twenty three percent (7/22) patients progressed or relapsed, including 2/16 (13%) in CARP-1 positive group vs. 5/14 (36%) in CARP-1 negative group (p=0.1). There was no significant difference in the PFS at 1 year (94% vs.79%, p=0.2) and 3 year (86% vs.71%, p=0.2) between CARP-1 positive vs. negative groups. Conclusions: CARP-1 expression was decreased in doxorubicin resistant NB cell line. CARP-1 expression was detected in approximately half (53%) of NB tumors. Patients with NB who expressed CARP-1 showed trend towards better 1- & 3-year PFS as compared to those who did not express CARP-1, however, the results are not statistically significant which could be due to the small sample size. Further study with a larger number of patients is warranted to clarify these findings.

scholarly journals Multi-model mapping of phonemic fluency

2021 ◽  
Author(s):  
Lisa Cipolotti ◽  
Tianbo Xu ◽  
Bronson Harry ◽  
Joe Mole ◽  
Grace Lakey ◽  
...  
Keyword(s):  
Statistical Analysis ◽  
Small Sample Size ◽  
Small Sample ◽  
Anterior Cingulate ◽  
Functional Region ◽  
Phonemic Fluency ◽  
Number Of Patients ◽  
Lesion Symptom Mapping ◽  
Subcortical Regions ◽  
Over Time

Abstract The voluntary generation of non-overlearned responses is usually assessed with phonemic fluency. Like most frontal tasks, it draws upon different complex processes and systems whose precise nature is still incompletely understood. Many claimed aspects regarding the pattern of phonemic fluency performance and its underlying anatomy remain controversial. Major limitations of past investigations include small sample size, scant analysis of phonemic output and methodologically insufficient lesion analyses approaches. We investigated a large number of patients with focal unilateral right or left frontal (n = 110) or posterior (n = 100) or subcortical (n = 65) lesions imaged with magnetic resonance or computed tomography and compared their performance on the number of overall responses, words produced over time, extremely infrequent/unknown words and inappropriate words generated. We also employed, for the first time parcel-based lesion symptom mapping, tract-wise statistical analysis as well as Bayesian multivariate analysis based on meta-analytically defined functional region of interest, including their interactions. We found that left frontal damage was associated with greater impairment than right frontal or posterior damage on overall fluency performance, suggesting that phonemic fluency shows specificity to frontal lesions. We also found that subcorticals, similar to frontals, performed significantly worse than posteriors on overall performance suggesting that subcortical regions are also involved. However, only frontal effects were found for words produced over time, extremely infrequent/unknown and inappropriate words. Parcel-based lesion symptom mapping analysis found that worse fluency performance was associated with damage to the posterior segment of the left frontal middle and superior gyrus, the left dorsal anterior cingulate gyrus and caudate nucleus. Tract-wise statistical analysis revealed that disconnections of left frontal tracts are critical. Bayesian multivariate models of lesions and disconnectome maps implicated left middle and inferior frontal and left dorsomedial frontal regions. Our study suggests that a set of well localised left frontal areas together with subcortical regions and several left frontal tracts are critical for word generation. We speculate that a left lateralized network exists. It involves medial, frontal regions supporting the process of energization, which sustains activation for the duration of the task and middle and inferior frontal regions concerned with selection, required due to the competition produced by associated stored words, respectively. The methodology adopted represents a promising and empirically robust approach in furthering our understanding of the neurocognitive architecture underpinning executive processes.

scholarly journals Implementation and Evaluation of a Military–Civilian Partnership to Train Mental Health Specialists

2019 ◽  
Vol 184 (7-8) ◽  
pp. e184-e190
Author(s):  
Scott A Simpson ◽  
Matthew Goodwin ◽  
Christian Thurstone
Keyword(s):  
Mental Health ◽  
Patient Care ◽  
Small Sample Size ◽  
Safety Net ◽  
Small Sample ◽  
Training Experience ◽  
Training Environment ◽  
Army Reserve ◽  
Safety Net Hospital ◽  
The Military

Abstract Introduction Mental health specialists (MHS, or 68X) play a central role in meeting the growing demand for combat stress care among Service Members. Partnering with civilian institutions may enhance the MHS training experience beyond Advanced Individual Training (AIT). Methods We describe a novel military–civilian collaboration to train U.S. Army Reserve MHS’s in the psychiatric emergency service (PES) of a public, safety-net hospital. Details of implementation are described. The training rotation was evaluated after 1 year through a comprehensive chart abstraction of patients seen as well as surveys of MHS’s and civilian partners. Results The roles of MHS and physician officers in this rotation are described. Over 9 days in the PES, the MHS team evaluated 26 patients. MHS’s described a high-quality training environment (83% rated very good or excellent) in which they frequently saw high-risk patients relevant to military practice. Experience with a certain patient presentation was correlated with comfort assessing and managing that presentation (p < 0.01). Many civilian staff (40%) felt the PES operated better with the presence of the Army team and 50% of civilians agreed their impression of the U.S. Army Reserve improved as a result of the partnership. Hundred percent of specialists and 80% of civilians reported very good to excellent rapport between military and civilian staff. Two civilian respondents (11%) expressed concern that the military team’s presence impeded patient care. Conclusion This is the first military–civilian training collaboration for behavioral health specialists, who have already completed AIT. This program provided well-received and mission-relevant training for MHS’s without notable adverse effects on patient care or team functioning in a civilian environment. Our findings are based on a small sample size, and no other such programs exist against which to compare these results. We propose that such educational partnerships, which have long been effective for other clinical specialists, may benefit the military, civilian communities, and the country.

scholarly journals The effectiveness of interventions for reducing subjective and objective social isolation among people with mental health problems: a systematic review

2019 ◽  
Vol 55 (7) ◽  
pp. 839-876 ◽  
Author(s):  
Ruimin Ma ◽  
Farhana Mann ◽  
Jingyi Wang ◽  
Brynmor Lloyd-Evans ◽  
James Terhune ◽  
...  
Keyword(s):  
Mental Health ◽  
Systematic Review ◽  
Social Isolation ◽  
Mental Health Problems ◽  
Small Sample Size ◽  
Intervention Development ◽  
Health Problems ◽  
Small Sample ◽  
Current Evidence ◽  
Physical And Mental Health

Abstract Purpose Subjective and objective social isolation are important factors contributing to both physical and mental health problems, including premature mortality and depression. This systematic review evaluated the current evidence for the effectiveness of interventions to improve subjective and/or objective social isolation for people with mental health problems. Primary outcomes of interest included loneliness, perceived social support, and objective social isolation. Methods Three databases were searched for relevant randomised controlled trials (RCTs). Studies were included if they evaluated interventions for people with mental health problems and had objective and/or subjective social isolation (including loneliness) as their primary outcome, or as one of a number of outcomes with none identified as primary. Results In total, 30 RCTs met the review’s inclusion criteria: 15 included subjective social isolation as an outcome and 11 included objective social isolation. The remaining four evaluated both outcomes. There was considerable variability between trials in types of intervention and participants’ characteristics. Significant results were reported in a minority of trials, but methodological limitations, such as small sample size, restricted conclusions from many studies. Conclusion The evidence is not yet strong enough to make specific recommendations for practice. Preliminary evidence suggests that promising interventions may include cognitive modification for subjective social isolation, and interventions with mixed strategies and supported socialisation for objective social isolation. We highlight the need for more thorough, theory-driven intervention development and for well-designed and adequately powered RCTs.

P-450 Effects of rheumatoid arthritis and methotrexate therapy on ovarian reserve in infertile women

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
G Vlasova ◽  
S Perminova
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Ovarian Reserve ◽  
Small Sample Size ◽  
Genetic Material ◽  
Main Group ◽  
Small Sample ◽  
Control Group ◽  
Proliferating Cells ◽  
Number Of Patients

Abstract Study question Do patients with infertility and rheumatoid arthritis (RA) treated with methotrexate (MTX) have ovarian reserve alterations? Summary answer Women with infertility and RA treated with MTX were found to have statistically significant decrease of ovarian reserve. What is known already Rheumatoid arthritis (RA) is one of the most prominent inflammatory diseases affecting women of child-bearing age [Brouwer J. et al, 2014]. RA and its treatment may interfere with the female reproductive physiology. The vast majority of patients with RA are treated with methotrexate (MTX) which is a folate antagonist that inhibits DNA synthesis. MTX, which is the anchor drug in RA, targets actively proliferating cells including the oocytes and granulosa cells which may impair the ovarian reserve [Min Tun Kyaw et al, 2020]. Study design, size, duration A prospective case-control study that enrolled 72 female patients with infertility was conducted in the 2-year time period of September 2018 to October 2020. Participants/materials, setting, methods The main group comprised 32 patients with infertility and RA; the control group consisted of 40 women with infertility only. Patients with RA were stratified into subgroups based on whether or not they received MTX. To investigate ovarian reserve measurement of serum anti-Müllerian hormone (AMH) was used. The level of AMH was evaluated concerning RA duration and activity, as well as the age at initiation of MTX therapy, dosage, and treatment duration. Main results and the role of chance The mean age of the study population was 36±3 years. The duration of RA was 4 [3;11] years. The low disease activity based on DAS28-ESR (disease activity score based on 28 joints using the erythrocyte sedimentation rate) prevailed(56.2%). In the main group 19(59.4%) women received MTX therapy. The MTX dosage was 15 [15;20]mg /wk, the duration of MTX therapy by the day of inclusion in the study was 18.7[1;15]months. The AMH level was significantly lower in the main group (2.1 n /ml vs 2.73ng /ml, p = 0.043). The number of patients with decreased ovarian reserve (AMH level&lt;1.0ng/ml) significantly prevailed in the group of patients with RA (25% vs 5%, p = 0.015). When assessing the AMH level in patients with RA who received MTX (n = 19) and patients in the control group, there was a tendency towards a decrease in the indicator in the first subgroup, but no statistically difference was found (p = 0.074). Correlation analysis of the dependence of AMH level on the patient age showed the most significant decrease in AMH in the patients with RA receiving MTX compared to the patients with RA who did not, and compared to all patients with RA regardless of the therapy received (rs=-0.563)(p &lt; 0.05). Limitations, reasons for caution The lack of statistically significant data in certain cases may be due to the small sample size. Wider implications of the findings RA and MTX administration are associated with a significant decrease in AMH levels. The age of initiation of the therapy is negatively correlated with the AMH level. In this regard, patients with already compromised reproductive function who are planning to receive MTX should be advised to preserve the genetic material. Trial registration number 567890

scholarly journals Why make the effort? Exploring recovery college engagement

2018 ◽  
Vol 22 (1) ◽  
pp. 27-33 ◽  
Author(s):  
Leanne Harper ◽  
Mick McKeown
Keyword(s):  
Mental Health ◽  
Social Factors ◽  
Design Methodology ◽  
Small Sample Size ◽  
Structured Interview ◽  
Small Sample ◽  
Mental Health Recovery ◽  
Valuable Contribution ◽  
Content Type ◽  
The Impact

Purpose Whilst there is growing evidence to suggest that the recovery college (RC) environment supports students towards their mental health recovery (Meddings et al., 2015b), students’ initial motivations for engagement, alongside factors that may hinder or support attendance, have yet to be exclusively explored. The paper aims to discuss these issues. Design/methodology/approach All new RC students were invited to take part in a semi-structured interview three months following their enrolment. Four participants completed an interview which were later analysed using thematic analysis. Findings Four themes emerged within analysis: making the effort; being “too unwell”; friendly environment; and glad I came. These are discussed alongside the literature, and it is proposed that whilst there is a substantial struggle involved in engagement with a RC, likely related to mental health and social factors, the RC environment, peer support and support of the tutors helps students to overcome the impact of this. Research limitations/implications Due to the small sample size and exploratory stance of this study, additional research into the complexities around engagement with RCs is strongly recommended. Only students who had attended at least one RC course chose to participate in this study, therefore an under-researched population of non-attendees may provide a valuable contribution to further understanding. Originality/value This is one of the first studies to qualitatively explore factors which may support, or hinder, initial and ongoing engagement with a RC. It is proposed that a greater understanding of these important issues could be used to increase RC accessibility and inclusion.

261 Association of T-cell–inflamed gene expression profile and PD-L1 status with efficacy of pembrolizumab in patients with esophageal cancer from KEYNOTE-180

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A285-A285
Author(s):  
Manish Shah ◽  
Takashi Kojima ◽  
Daniel Hochhauser ◽  
Peter Enzinger ◽  
Judith Raimbourg ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Sample Size ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Small Sample Size ◽  
Gastroesophageal Junction ◽  
Small Sample ◽  
Link Type ◽  
Number Of Patients

BackgroundKey biomarkers under investigation for the ability to predict response to monotherapy PD-1 inhibitors such as pembrolizumab include PD-L1, TMB, MSI, and T-cell–inflamed gene expression profile (GEP). The KEYNOTE-180 trial (NCT02559687) was a single-arm phase 2 study of pembrolizumab as third-line or greater therapy in advanced/metastatic esophageal/gastroesophageal junction adenocarcinoma or squamous cell carcinoma (SCC). ORR was 9.9% and median DOR was NR at the primary analysis. We investigated the relationship in KEYNOTE-180 between response to pembrolizumab and T-cell–inflamed GEP or PD-L1 expression by histology.MethodsPatients received pembrolizumab 200 mg Q3W for ≤2 years until disease progression, toxicity, or withdrawal. The end points for this analysis were ORR, DOR, and PFS per RECIST v1.1 by central review and OS in the SCC and adenocarcinoma populations by GEP (non-low [≥–1.540] or low [<–1.540]; cutoff prespecified) and PD-L1 (CPS ≥10 or <10). Tumor GEP was determined using the NanoString nCounter Analysis System. PD-L1 expression was characterized using PD-L1 IHC 22C3 pharmDx. Data cutoff date was July 30, 2018.ResultsOf 121 total patients, 118 had an evaluable GEP score and 121 had an evaluable PD-L1 CPS. Fifty-one patients (42.1%) had GEPnon-lowtumors, 58 (48.0%) had CPS ≥10 tumors, and 31 (25.6%) had GEPnon-low/CPS ≥10 tumors; 63 patients (52.1%) had SCC and 58 (47.9%) had adenocarcinoma. ORR was 15.4% with GEPnon-low and 13.5% with GEPlow among patients with SCC and 12% and 0% among patients with adenocarcinoma, respectively (table 1). ORR was 20% with CPS ≥10 and 7.1% with CPS <10 among patients with SCC and 4.3% and 5.7%, respectively, among patients with adenocarcinoma (table 2). Median OS was slightly higher among patients with SCC in the GEPnon-low subgroup and the CPS ≥10 subgroup versus GEPlow and CPS <10 subgroups, respectively (tables 1, 2); this trend was reversed among patients with adenocarcinoma (tables 1, 2). Median PFS ranged from 1.9 to 2.1 across histology/biomarker subgroups. Median DOR was NR regardless of GEP or CPS status (tables 1, 2).Abstract 261 Table 1Response by GEP status and histologyaAnalysis by biomarker status was not possible because of the small sample size.Abstract 261 Table 2Response by PD-L1 status and histologyaAnalysis by biomarker status was not possible because of the small sample size.ConclusionsIn KEYNOTE-180, data in a small number of patients suggested that measures of inflammation, like PD-L1 and GEP, may enrich for responses to pembrolizumab. In SCC, some trends toward enrichment were observed for both biomarkers, although the trend was stronger for PD-L1 CPS ≥10. In adenocarcinoma, a trend was observed for GEP but not for PD-L1; the small number of responders is limiting, and further studies are needed to understand molecular correlates in adenocarcinoma.AcknowledgementsMedical writing and/or editorial assistance was provided by Tim Peoples, MA, ELS, and Holly C. Cappelli, PhD, CMPP, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.Trial RegistrationClinicalTrials. gov, NCT02559687Ethics ApprovalThe study and the protocol were approved by the institutional review board or ethics committee at each site.ConsentAll patients provided written informed consent to participate in the clinical trial.

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