Exact Binomial Confidence Intervals Research Articles

35 Efficacy of treatments post-lenvatinib in patients with advanced renal cell carcinoma (aRCC)

Abstract Background Lenvatinib is a tyrosine kinase inhibitor (TKI) that targets both vascular endothelial growth factor (VEGF) receptor and fibroblast growth factor receptor. It has demonstrated efficacy both in the upfront and refractory disease settings. However, there is a lack of data surrounding the efficacy of TKIs post-lenvatinib exposure. In this study, we investigate the activity of therapies post-lenvatinib in patients with aRCC. Methods We conducted a retrospective analysis utilizing the International Metastatic Database Consortium (IMDC). Patients having received treatment post-lenvatinib exposure were eligible and divided into two cohort: patients post-1st line lenvatinib (2nd line cohort) and patients post-2nd line lenvatinib (3rd line cohort). The primary objective was objective response rate (ORR) and time to treatment failure (TTF). ORR was summarized with 95% two-sided exact binomial confidence interval. TTF was defined as time from treatment initiation to drug cessation for any reason censored at the date of last follow-up. Results Overall, 84 patients received 1st line lenvatinib of whom 43 (51%) remain on therapy, 20 (24%) received 2nd line treatment, and 21 (25%) received no subsequent treatment. The median duration of prior lenvatinib was 9.7 months. All patients received 1st line pembrolizumab + lenvatinib (ORR 50%, median TTF 19.7 months). Reason for lenvatinib discontinuation was progression (50%), progression + toxicity (20%), toxicity (15%), or other (15%). For the 2nd line cohort, median age was 61 years, most patients were male (85%), had prior nephrectomy (75%), clear cell histology (85%), and were IMDC intermediate/poor risk (55%). 2nd line therapy regimens included TKI monotherapy (80%), TKI-IO (5%), and other (15%). The median follow up from 2nd-line treatment initiation was 4.9 months. The ORR to 2nd line treatment was 5% (95% CI 0.2-25) and median TTF was 5.8 months (95% CI 1.9-14.9). Of 2nd line lenvatinib-exposed patients (n=84), 24 (29%) remain on treatment, 34 (40%) received 3rd line treatment, and 26 (31%) did not receive additional therapy. The median duration of prior lenvatinib was 5.9 months. Most patients received 2nd line everolimus + lenvatinib (97%) (ORR 31%, median TTF 9.2 months). Reason for lenvatinib discontinuation was progression (59%), progression + toxicity (9%), toxicity (12%), or other (21%). For the 3rd line cohort, median age was 67 years, most patients were male (68%), had prior nephrectomy (88%), clear cell histology (68%), and were IMDC intermediate/poor risk (77%). 3rd line treatments included TKI alone (50%), IO-TKI (38%), and other (12%). The median follow up from 3rd-line treatment initiation was 14.9 months. The ORR to 3rd line treatment was 12% (95% CI 3.3-27) and median TTF was 2.8 months (95% CI 1.9-7.4). Conclusions In this analysis, we demonstrate modest activity of TKI-based therapy post-lenvatinib exposure. Our study highlights the need for improved treatment options for patients progressing on lenvatinib-based therapies.

Efficacy of post-lenvatinib treatments in patients (pts) with advanced renal cell carcinoma (aRCC).

4538 Background: Lenvatinib is a tyrosine kinase inhibitor (TKI) that targets both vascular endothelial growth factor (VEGF) receptor and fibroblast growth factor receptor. It has demonstrated efficacy both in the upfront and refractory disease settings. However, there is a lack of data surrounding the efficacy of TKIs post-lenvatinib exposure. In this study, we investigate the activity of post-lenvatinib therapies in pts with aRCC. Methods: We conducted a retrospective analysis utilizing the International Metastatic Database Consortium (IMDC). Pts having received treatment post lenvatinib exposure were eligible and divided into two cohort: pts post-1st line lenvatinib (2nd line cohort) and pts post-2nd line lenvatinib (3rd line cohort). The primary objective was objective response rate (ORR) and time to treatment failure (TTF). ORR was summarized with 95% two-sided exact binomial confidence interval. TTF was defined as time from treatment initiation to drug cessation for any reason censored at the date of last follow-up. Results: Overall, 84 pts received 1st line lenvatinib of whom 43 (51%) remain on therapy, 20 (24%) received 2nd line treatment, and 21 (25%) received no subsequent treatment. All pts received 1st line pembrolizumab + lenvatinib (ORR 50%, median TTF 9.7 months). Reason for lenvatinib discontinuation was progression (50%), progression + toxicity (20%), toxicity (15%), or other (15%). For the 2nd line cohort, median age was 61 years, most pts were male (85%), had prior nephrectomy (75%), clear cell histology (85%), and were IMDC intermediate/poor risk (55%). 2nd line therapy regimens included TKI monotherapy (80%), TKI-IO (5%), and other (15%). The ORR to 2nd line treatment was 5% (95% CI 0.2-25) and median TTF was 5.8 months (95% CI 1.9-14.9). Of 2nd line lenvatinib-exposed pts (n=84), 24 (29%) remain on treatment, 34 (40%) received 3rd line treatment, and 26 (31%) did not receive additional therapy. Most pts received 2nd line everolimus + lenvatinib (97%) (ORR 39%, median TTF 5.9 months). Reason for lenvatinib discontinuation was progression (59%), progression + toxicity (9%), toxicity (12%), or other (21%). For the 3rd line cohort, median age was 67 years, most pts were male (68%), had prior nephrectomy (88%), clear cell histology (68%), and were IMDC intermediate/poor risk (77%). 3rd line treatments included TKI alone (50%), IO-TKI (38%), and other (12%). The ORR to 3rd line treatment was 12% (95% CI 3.3-27) and median TTF was 2.8 months (95% CI 1.9-7.4). Conclusions: In this analysis, we demonstrate modest activity of TKI-based therapy post-lenvatinib exposure. Our study highlights the need for improved treatment options for pts progressing on lenvatinib-based therapies.

Prevalence and predictors of virologic failure among HIV patients on antiretroviral therapy in Makueni County: a cross-sectional study

Background: The growing number of people on antiretroviral therapy in Kenya has led to a decrease in HIV morbidity and mortality. However, virologic failure (VF) threatens to reverse these gains. In Makueni County, existing data indicate challenges in achieving viral load (VL) suppression among persons living with HIV (PLHIV). Few studies have been carried out investigating VF in the region despite its high incidence of HIV infections. Methods: An analytical cross-sectional study was conducted among PLHIV in Makueni County to investigate the determinants and estimate the prevalence of VF. The prevalence of VF and its associated 95% exact binomial confidence interval was estimated, and a mixed-effects logistic regression model used to evaluate the relationship between the predictors and VF. Results: The estimated period prevalence of VF between October 2018 and June 2019 was 13.2% (95% CI: 12.7%–13.8%). Being 15 years or older (aOR=0.53; 95% CI: 0.44 – 0.645) and having blood samples tested for reasons other than baseline VL measurement was associated with lower odds of VF: breastfeeding mothers (aOR=0.1; 95% CI: 0.01 – 0.97); clinical failure (aOR=0.08; 95% CI: 0.01 – 0.44); confirmation of VF (aOR=0.2; 95% CI: 0.07 – 0.62); no VL data (aOR=0.06; 95% CI: 0.01 – 0.31); routine VL (aOR=0.04; 95% CI: 0.01 – 0.12); drug substitution (aOR=0.03; 95% CI: 0.01 – 0.08). Taking ABC-based, AZT-based, or other non-TDF-Based regimens increased the odds of VF (aOR=1.61; 95% CI: 1.34 – 1.94), (aOR=1.75; 95% CI: 1.52 - 2.01), and (aOR=1.55; 95% CI: 0.99 - 2.44) respectively. Conclusion: This study showed that over 13% of HIV patients on ART in Makueni County had VF between October 2018 and June 2019. The significant risk factors associated with VF were found to be age lower than 15 years, taking a non-TDF-based ART regimen, and blood sampling for baseline VL measurements.

Congenital Pulmonic Valve Dysfunction Treated With SAPIEN 3 Transcatheter Heart Valve (from the COMPASSION S3 Trial)

Significant pulmonary regurgitation (PR) and pulmonary stenosis are common after surgical repair of some congenital heart defects. This prospective, single-arm, multicenter trial enrolled patients who underwent transcatheter heart valve (THV) implantation with a SAPIEN 3 valve to treat dysfunctional right ventricular outflow tract (RVOT) conduits or pulmonic surgical valves (≥ moderate PR and/or mean RVOT gradient ≥35mm Hg). The primary end point was a nonhierarchical composite of THV dysfunction at 1year comprising RVOT reintervention, ≥ moderate total PR, and mean RVOT gradient >40mm Hg. A performance goal of <25% of upper confidence interval (CI) was prespecified for the primary end point, using a 95% exact binomial CI. Patients (n=58) were enrolled between July 5, 2016 and July 17, 2018, with mean age of 32years. Prestenting was performed in 53.4%. At discharge, the device success was 98.1% (single valve without explant, < moderate PR, gradient <35mm Hg). At 30days, there were no major adjudicated adverse clinical events. At 1year, the primary end point composite was 4.3% (95% CI 0.5 to 14.5). The composite components were 0% (0 of 56) RVOT reintervention, 2.1% (1 of 47) ≥ moderatePR, and 2.1% (1 of 48) mean RVOT gradient >40mm Hg. No mortality, endocarditis, thrombosis, or stent fracture were reported at 1year. In conclusion, the SAPIEN 3 THV was safe and effective in patients with dysfunctional RVOT conduits or previously implanted valves in the pulmonic position to 1 year. Clinical trial registration: NCT02744677; https://clinicaltrials.gov/ct2/show/NCT02744677.

1095. Retrospective Review of SARS-CoV-2 Infection in Immunocompromised Children at a Single Pediatric Institution

Abstract Background Immunocompromised individuals are considered higher risk for severe COVID-19 disease. Much of this data was collected from adults with limited pediatric reporting, although a recent study showed no worse outcome in immunocompromised children. In this study, we characterize our experience of immunocompromised children who were hospitalized with acute SARS-CoV-2 infection and aimed to identify a sub-group of patients who had worse outcomes. Methods We reviewed charts of all immunocompromised children hospitalized with SARS-CoV-2 RT-PCR positive results at our hospital from March 2020-April 2022. Disease severity was characterized according to the NIH COVID-19 guidelines. Clinical characteristics and outcomes were assessed. Individuals were grouped into solid organ transplant recipients, solid tumors, liquid tumors, and stem cell transplant recipients. Proportions were calculated per group in addition to the exact binomial confidence intervals (95%). Results We identified 39 pediatric aged patients ranging from 7 months to 20 years of age with a median age of 10. 35.9% (14/39) of individuals were solid organ transplant recipients, 25.6% (10/39) had solid tumors, 33% (13/39) had liquid tumors, and 5% (2/39) were stem cell transplant recipients. 17.9% were asymptomatic, 66.7% had mild disease, and 15.4% had severe/critical COVID-19 disease. The median time of positive SARS CoV-2 RT-PCR was 32 days. Six children had prolonged SARS-CoV-2 RT-PCR positive testing between 29-97 days with a mean of 49 days. Viral strand specific RNA testing for replicating virus was also persistently positive. Six experienced severe/critical disease resulting in death of three. Most of the patients were treated with predominantly T cell depleting agents (∼74%). However, four patients who had prolonged active critical infection were treated with B cell depleting agents or had known B cell dysfunction. Conclusion The majority of the immunocompromised children in our cohort had mild COVID-19 disease. A subset of individuals experienced ongoing prolonged RT-PCR positivity and testing indicating persistent viral replication, with three demonstrating an inability to control the virus and resulting in death. Worse outcomes may be related to their immune dysfunction and use of B cell depleting agents. Disclosures All Authors: No reported disclosures.

Global burden and temporal trends of lower urinary tract symptoms: a systematic review and meta-analysis.

Lower urinary tract symptoms (LUTS) are common complaint in urology practice and affecting the quality of life for patients. This article aims to perform a systematic review and meta-analysis on the global prevalence of LUTS overall, and according to different patient characteristics. We searched MEDLINE and Embase for population-based epidemiological studies reporting the prevalence of LUTS from inception to 1 Jan 2021. Studies which: (1) have enough information on sample size and prevalence; (2) investigate individuals aged 15 or above; and (3) have clear diagnostic criteria for LUTS. We extracted the following information: year of publication; name of the first author; study period; region of recruitment; race; age range; sex; severity; symptoms; and criteria. We pooled rate estimates with exact binomial and test score-based confidence intervals (CIs) using proportions with a random-effects model. We included 222 studies from 36 countries involving 1,692,110 samples and 632,933 patients with LUTS. The overall prevalence of any and moderate-to-severe LUTS was 63.2% (95% CI = 58.0-68.1) and 31.3% (95% CI = 28.8-33.8), respectively. The most common symptom was storage symptoms (56.7%; 95% CI = 51.0-62.4), followed by voiding symptoms (36.4%; 95% CI = 27.8-45.4) and post-micturition symptoms (30.7%; 95% CI = 19.2-43.6). A higher prevalence of moderate-to-severe LUTS was observed in male subjects (35.2%; 95% CI = 32.1-38.5) and individuals aged ≥60 (39.0%; 95% CI = 33.4-44.8; I2 = 99.9%). Its prevalence increased from 27.4% (95% CI = 24.5-30.3) in 1990-1999, to 31.9% (95% CI = 27.3-36.7) in 2000-2009 and 36.2% (95% CI = 30.7-41.9) in 2010-2019. This study was the first comprehensive meta-analysis examining the global prevalence of LUTS. We identified a high level of LUTS prevalence in the general population, with a higher burden in male subjects, older individuals, and the Asian population. There has been an increasing trend in the prevalence of LUTS since the 1990s.

AML-108 SELECT-AML-1 Trial in Progress: A Phase 2 Study of Tamibarotene in Combination With Venetoclax and Azacitidine in Previously Untreated Adult Patients Selected for RARA-Positive AML who are Ineligible for Standard Induction Therapy

RARA-positive AML is a novel, genomically defined subset with an actionable target for treatment with tamibarotene, an oral and selective RARα agonist (McKeown 2017). In a previous trial in RARA-positive newly diagnosed (ND) AML patients ineligible for standard induction therapy, tamibarotene/azacitidine led to a CR/CRi rate of 61% with a rapid onset of response. The combination was generally well tolerated with no increase in myelosuppression compared to azacitidine alone (de Botton 2020). Responses were observed irrespective of mutations or cytogenetic risk. Approximately one-third of ND unfit AML patients do not respond to venetoclax, and nearly all patients eventually relapse (DiNardo 2020). Translational data suggest that RARA positivity, found in approximately 30% of patients in this AML subset (Vigil 2017), enriches for monocytic features reported to be associated with venetoclax resistance (Fiore 2020, Pei 2019). This suggests that the blood-based RARA biomarker selects for patients who may respond to tamibarotene and may be less likely to respond to venetoclax/azacitidine. The primary objectives are to characterize the safety of the combination and to compare the CR/CRi rate of tamibarotene/venetoclax/azacitidine versus venetoclax/azacitidine; the secondary objectives are to compare the CR rate, CR/CRh rate, duration of response, time to response, and overall survival. A phase 2, open-label, multi-center trial comparing the activity of tamibarotene/venetoclax/azacitidine with that of venetoclax/azacitidine in treatment-naive RARA+ unfit AML patients. This 3-part trial includes a safety lead-in, randomized efficacy study, and salvage arm. Following the safety lead-in, patients will be randomized 1:1 to receive tamibarotene/venetoclax/azacitidine or venetoclax/azacitidine. Clinical activity will be characterized by European LeukemiaNet criteria. Response rates and 95% exact binomial confidence intervals will be calculated by treatment group. In the salvage arm, tamibarotene will be added for patients randomized to venetoclax/azacitidine who experience progressive disease, treatment failure, or relapse. Patients will be treated with azacitidine at 75 mg/m2 IV/SC daily on days 1-7, venetoclax on days 1-28 per VENCLEXTA® (venetoclax) USPI, and tamibarotene 6 mg twice per day by mouth on days 8-28 of each 28-day cycle. SELECT-AML-1 (NCT04905407) opened in July 2021 with ongoing enrollment. U.S. and France.

P492: TAMIBAROTENE IN COMBINATION WITH VENETOCLAX AND AZACITIDINE IN PREVIOUSLY UNTREATED ADULT PATIENTS SELECTED FOR RARA-POSITIVE AML WHO ARE INELIGIBLE FOR STANDARD INDUCTION THERAPY (SELECT AML-1)

Background: RARA-positive (RARA+) AML is a novel genomically defined patient subset with an actionable biological target for treatment with tamibarotene, an oral and selective RARα agonist (McKeown 2017). RARA+ patients can be selected by a blood-based biomarker test, with approximately 30% of newly diagnosed (ND) AML patients being RARA+ (Vigil 2017). As a biologically targeted agent for patients with RARA overexpression, tamibarotene has the potential to provide benefit irrespective of mutation or cytogenetic risk classification. In RARA+ ND AML patients ineligible for standard induction therapy, tamibarotene plus azacitidine (aza) led to a CR/CRi rate of 61% and a rapid onset of response (de Botton 2020). Approximately one-third of patients with ND unfit AML do not respond to front-line standard of care venetoclax (ven)/aza (DiNardo 2020). Translational data suggest RARA positivity enriches for monocytic features reported to be associated with ven resistance (Fiore 2020, Pei 2020). This data suggests the RARA biomarker selects for patients who may respond to tamibarotene and may be less likely to respond to ven/aza. Given that tamibarotene plus aza has been generally well tolerated, with no increase in myelosuppression compared to single agent aza (de Botton 2020), it is anticipated that tamibarotene can be administered safely in combination with ven/aza. Aims: This is a Phase 2, open-label, multi-center study in the U.S. and France comparing the clinical activity of tamibarotene/ven/aza to ven/aza in treatment-naive RARA+ AML patients ineligible for standard induction chemotherapy. The primary objectives are to characterize the safety of the combination and to compare the CR/CRi rate of tamibarotene/ven/aza vs. ven/aza, with secondary objectives to compare CR rate, CR/CRh rate, duration of response, and time to response. The overall response rate using tamibarotene/ven/aza following ven/aza treatment failure will be explored. Clinical activity will be characterized by ELN criteria (Dohner 2017). Methods: This 3-part trial includes a safety lead-in, randomized efficacy study, and salvage arm. Following the safety lead-in, approximately 80 patients will be randomized 1:1 to receive tamibarotene/ven/aza or ven/aza. In the salvage arm, tamibarotene will be added for study patients randomized to ven/aza who experience progressive disease, relapse, or treatment failure. Patients will be treated with aza at 75 mg/m2 IV/SC daily on days 1-7, ven on days 1-28 per VENCLEXA USPI, followed by tamibarotene at 6 mg twice per day by mouth on days 8-28 of each 28-day cycle. Results: Response rates and 95% exact binomial confidence intervals will be calculated by treatment group. Summary/Conclusion: The SELECT AML-1 trial (NCT04905407) opened in July 2021 with ongoing enrollment.

Tamibarotene in combination with venetoclax and azacitidine in previously untreated adult patients selected for RARA-positive AML who are ineligible for standard induction therapy (SELECT AML-1).

TPS7065 Background: RARA-positive (RARA+) AML is a novel genomically defined patient subset with an actionable biological target for treatment with tamibarotene, an oral and selective RARα agonist (McKeown 2017). RARA+ patients can be selected by a blood-based biomarker test, with approximately 30% of newly diagnosed (ND) AML patients being RARA+ (Vigil 2017). As a biologically targeted agent for patients with RARA overexpression, tamibarotene has the potential to provide benefit irrespective of mutation or cytogenetic risk classification. In RARA+ ND AML patients ineligible for standard induction therapy, tamibarotene plus azacitidine (aza) led to a CR/CRi rate of 61% and a rapid onset of response (de Botton 2020). Approximately one-third of patients with ND unfit AML do not respond to front-line standard of care venetoclax (ven)/aza (DiNardo 2020). Translational data suggest RARA positivity enriches for monocytic features reported to be associated with ven resistance (Fiore 2020, Pei 2020). This data suggests the RARA biomarker selects for patients who may respond to tamibarotene and may be less likely to respond to ven/aza. Given that tamibarotene plus aza has been generally well tolerated, with no increase in myelosuppression compared to single agent aza (de Botton 2020), it is anticipated that tamibarotene can be administered safely in combination with ven/aza. Methods: This is a Phase 2, open-label, multi-center study in the U.S. and France comparing the clinical activity of tamibarotene/ven/aza to ven/aza in treatment-naive RARA+ AML patients ineligible for standard induction chemotherapy. The primary objectives are to characterize the safety of the combination and to compare the CR/CRi rate of tamibarotene/ven/aza vs. ven/aza, with secondary objectives to compare CR rate, CR/CRh rate, duration of response, and time to response. The overall response rate using tamibarotene/ven/aza following ven/aza treatment failure will be explored. Clinical activity will be characterized by ELN criteria (Dohner 2017). This 3-part trial includes a safety lead-in, randomized efficacy study, and salvage arm. Following the safety lead-in, approximately 80 patients will be randomized 1:1 to receive tamibarotene/ven/aza or ven/aza. Response rates and 95% exact binomial confidence intervals will be calculated by treatment group. In the salvage arm, tamibarotene will be added for study patients randomized to ven/aza who experience progressive disease, relapse, or treatment failure. Patients will be treated with aza at 75 mg/m2 IV/SC daily on days 1-7, ven on days 1-28 per VENCLEXA USPI, followed by tamibarotene at 6 mg twice per day by mouth on days 8-28 of each 28-day cycle. The SELECT AML-1 trial opened in July 2021 with ongoing enrollment. Clinical trial information: NCT04905407.

Preliminary Research on a COVID-19 Test Strategy to Guide Quarantine Interval in University Students

Following COVID-19 exposure, the Centers for Disease Control (CDC) recommends a 10–14-day quarantine for asymptomatic individuals and more recently a 7-day quarantine with a negative PCR test. A university-based prospective cohort study to determine if early polymerase chain reaction (PCR) negativity predicts day 14 negativity was performed. A total of 741 asymptomatic students in quarantine was screened and 101 enrolled. Nasopharyngeal swabs were tested on days 3 or 4, 5, 7, 10, and 14, and the proportion of concordant negative results for each day versus day 14 with a two-sided 95% exact binomial confidence interval was determined. Rates of concordant negative test results were as follows: day 5 vs. day 14 = 45/50 (90%, 95% CI: 78–97%); day 7 vs. day 14 = 47/52 (90%, 95% CI: 79–97%); day 10 vs. day 14 = 48/53 (91%, 95% CI:79–97%), with no evidence of different negative rates between earlier days and day 14 by McNemar’s test, p &gt; 0.05. Overall, 14 of 90 (16%, 95% CI: 9–25%) tested positive while in quarantine, with seven initial positive tests on day 3 or 4, 5 on day 5, 2 on day 7, and none on day 10 or 14. Based on concordance rates between day 7 and 14, we anticipate that 90% (range: 79–97%) of individuals who are negative on day 7 will remain negative on day 14, providing the first direct evidence that exposed asymptomatic students ages 18–44 years in a university setting are at low risk if released from quarantine at 7 days if they have a negative PCR test prior to release. In addition, the 16% positive rate supports the ongoing need to quarantine close contacts of COVID-19 cases.

Profile of orthoptic clinic patients at a tertiary care Government Medical University in North India: A 6-year review

Aim: This study aims to study clinicodemographic profile of patients presenting to orthoptic clinic over the previous 6 years. Methods: Records of all new patients registered at the orthoptic clinic over 6 years' (January 1, 2014, to December 31 2019) were retrieved. Details of patient demographics, clinical presentation and management were studied in this hospital-based descriptive observational study after obtaining institutional ethical clearance. Records that were incomplete and those of patients with a history of strabismus surgery at presentation were excluded from analysis. Exact binomial confidence intervals (CIs) were calculated for the estimates of proportion. The results were reported as percentage (95% CIs). Descriptive statistics were used for subtypes of strabismus and amblyopia. Results: Out of 1548 patients, 896 were male (57.88%) and 652 (42.12%) were female. Mean age at presentation was 18.53 ± 10.41 years. Comitant strabismus was seen in 1083 (69.96%) and incomitant in 203 (13.11%). Among comitant deviations exotropia (XT) was commonest (n = 511, 47.18%), 6th nerve palsy (34%) was the most common cause among incomitant deviations, Duane retraction syndrome (DRS) constituted 24% of restrictive strabismus and amblyopia was present in 16.71% (n = 331) of patients. The left eye (LE) was more frequently involved in unilateral amblyopia (P < 0.0001). Conclusions: In our study, male to female ratio was 1.37. XT, 6th Nerve palsy, and DRS were the commonest types of comitant, paralytic and restrictive deviations respectively. Prevalence and severity of different types of amblyopia have also been described.

EUS-guided hepaticogastrostomy in patients with obstructive jaundice after failed or impossible endoscopic retrograde drainage: A multicenter, randomized phase II Study.

Over the last two decades, EUS-guided hepaticogastrostomy (EUS-HGS) has emerged as a therapeutic alternative for patients with biliary obstruction and failed ERCP. Percutaneous transhepatic biliary drainage (PTBD) as the gold standard is associated with relevant morbidity and need for re-intervention. The aim of our work was to evaluate in a phase II study the safety and efficacy profile of EUS-HGS. A PTBD arm was considered a control group. We conducted a prospective, randomized, noncomparative phase II study in three French tertiary centers involving patients with benign or malignant obstructive jaundice after failure of ERCP. Patients were randomized to either PTBD or EUS-HGS. Fifty-six patients (mean age 64 years) have been included between 2011 and 2015. Twenty-one underwent PTBD and thirty-five were drained using EUS-HGS. An interim analysis after the inclusion of 41 patients revealed an unexpected high 30-day morbidity rate for PTBD (13 out of 21 patients), justifying to stop randomization and inclusion in this control arm in 2013. The primary objective was reached with 10 out of the 35 EUS-HGS patients (28.6%) having observed complications (90%-level bilateral exact binomial confidence interval [CI] [16.4%-43.6%], left-sided exact binomial test to the objectified 50% unacceptable rate P = 0.0083). Both methods achieved comparable technical success rate (TSR) and clinical success rate (CSR) (TSR: PTBD 100% vs. EUS-HGS 94.3%, P = 0.28; CSR: PTBD 66.7% vs. EUS-HGS 80%, P = 0.35). Long-term follow-up showed EUS-HGS patients being at lower risk for re-intervention (relative risk = 0.47, 95% CI [0.27-0.83]). In cases of ERCP failure, EUS-HGS is a valuable alternative for biliary drainage with a high TSR and CSR. PTBD is associated with an unacceptable 30-day morbidity rate, whereas EUS-HGS seems to have a decent safety profile, suggesting that it may be the treatment of choice in appropriately selected patients.

The impact of a universal inpatient palliative care consultation protocol for patients with gynecologic cancer: a quality improvement project

The impact of a universal inpatient palliative care consultation protocol for patients with gynecologic cancer: a quality improvement project

Videos improve patient understanding of misunderstood chemotherapy terms in a rural population.

7022 Background: Rural communities can have low health literacy, which impacts the adequacy of informed consent, adherence to treatment, and outcomes. We had previously created and tested educational videos about basic chemotherapy terminology for use in an underserved population at our inner-city hospital. This study aimed to determine if these videos increased understanding of these terms in rural communities. Methods: Through patient and provider interviews in an underserved urban setting, 20 basic cancer treatment terms were identified as frequently misunderstood. As a pilot, 6 of these terms were explained in short, animated one-minute videos using VideoScribe (Sparkol).To determine if these videos improved understanding in the rural setting, 50 rural patients, specified as patients living in a county ranked 4-9 on the USDA Rural Urban Continuum Code (RUCC) scale, were asked to define each term before and after viewing the video. All answers were audiotaped and double coded for correctness of definition pre and post video screening, using the video definition as the correct definition. Before video and after video correct definition rates were calculated, along with 95% exact binomial confidence intervals using the Clopper-Pearson method. The videos for all 20 terms can be viewed on CancerQuest ( https://www.cancerquest.org/media-center/videos/cancer-treatment-terms ). Results: Participants were mostly white (79%), female (52%), resided in the more rural counties RUCC ranked 6-9 (62%), had &lt; a high school degree (56%) and had a family income of &lt;$40K (59%). Conclusions: Improving health literacy is a critical component in improving care. Our study establishes that a simple and easily disseminated intervention can significantly increase patient understanding of basic chemotherapy terminology in a rural setting. [Table: see text]

P047: Emergency department practice patterns of UTI investigation among the delirious elderly: a retrospective chart review

Introduction: Delirium is a common emergency department (ED) presentation in elderly patients. Urinary tract infection (UTI) investigation and treatment are often initiated in delirious patients in the absence of specific urinary symptoms, despite a paucity of evidence to support this practice. The purpose of this study is to describe the prevalence of UTI investigation, diagnosis and treatment in delirious elderly patients in the ED. Methods: We performed a retrospective chart review of elderly patients presenting to the ED at The Ottawa Hospital between January 15-July 30, 2018 with a chief complaint of confusion or similar. Exclusion criteria were pre-existing and current UTI diagnosis, Glasgow Coma Scale &lt;13, current indwelling catheter or nephrostomy tube, transfers between hospitals, and leaving without being seen. The primary outcome was the proportion of patients for whom urine tests (urinalysis or culture) or antibiotic treatment were ordered. Secondary outcomes were associations between patient characteristics, rates of UTI investigation, and patient outcomes. Descriptive values were reported as proportions with exact binomial confidence intervals for categorical variables and means with standard deviations for continuous variables. Comparisons were conducted with Fischer's exact test for categorical variables and t-tests for continuous variables. Results: After analysis of 1039 encounters with 961 distinct patients, 499 encounters were included. Urine tests were conducted in 324 patients (64.9% [60.6-69.1]) and antibiotics were prescribed to 176 (35.2% [31.1-39.6]). Overall 57 patients (11.4% [8.8-14.5]) were diagnosed with UTI, of which only 12 (21.1% [11.4-33.9]) had any specific urinary symptom. For those patients who had no urinary symptoms or other obvious indication for antibiotics (n = 342), 199 (58.2% [52.8-63.5]) received urine tests and 62 (18.1% [14.2-22.6]) received antibiotics. Patients who received urine tests were older (82.4 ± 8.8 vs. 78.3 ± 8.4 years, p &lt; 0.001) but did not differ in sex distribution from those than those who did not. Additionally, patients who received antibiotics were more likely to be admitted (OR = 2.6 [1.48-4.73]) and had higher mortality at 30 days (OR = 4.2 [1.35-12.91]) and 6 months (OR = 3.2 [1.33-7.84]) than those who did not. Conclusion: Delirious patient without urinary symptoms in the ED were frequently investigated and treated for UTI despite a lack of evidence regarding whether this practice is beneficial.

Nondiagnostic Fine-Needle Aspiration Biopsy of Thyroid Nodules: Outcomes and Determinants.

Background: Nondiagnostic results are common following fine-needle aspiration biopsy (FNAB) of thyroid nodules, but recommendations for the management of these patients vary. We sought to determine the outcomes and predictors of nondiagnostic FNABs in a single-center cohort of patients undergoing thyroid nodule evaluation. Methodology: We identified all first time ultrasound-guided FNABs performed between May 2007 and June 2013 at the Beth Israel Deaconess Medical Center Thyroid Nodule Clinic and examined demographic data, follow-up ultrasounds, repeated FNABs, and histopathologic findings. We examined the likelihood of diagnostic findings and of cancer with increasing numbers of nondiagnostic evaluations with their exact binomial confidence intervals [CIs] and potential predictors of nondiagnostic status using generalized estimating equations. Results: During the six-year period, 2234 unique individuals underwent ultrasound-guided FNAB of a thyroid nodule. The probability of obtaining a diagnostic biopsy declined from 84.4% [95% CI 82.8-85.8%] for initial FNABs to 57.6% [CI 50.8-64.2%] for the first re-FNAB and further to 42.4% [CI 25.5-60.8%] for second re-FNABs. Adjusted risk of nondiagnostic FNAB strongly increased with increasing numbers of previous biopsies and was also higher among whites. The overall rate of diagnosis of malignancy after a nondiagnostic FNAB was 8.1% [CI 4.2-13.7%] and was similar regardless of the number of previous nondiagnostic aspirations. Conclusion: Following an initial nondiagnostic FNAB, the probability of yielding a diagnostic result declines with each sequential repeat FNAB. Nonetheless, a tangible possibility of malignancy remains even after repeated nondiagnostic FNABs.

Prevalence and risk factors for low back pain among university teaching staff in Nairobi, Kenya: a cross-sectional study

Background: To date, there are few studies carried out on low back pain (LBP) among university teaching staff in developing countries despite academics being a high-risk group for LBP. In Kenya, to the best of our knowledge, there are no published studies that have investigated risk factors for LBP among teaching staff. The objectives of this study were to estimate the prevalence of LBP among teaching staff of the University of Nairobi (UoN), during the period June 2016 – May 2017, and to identify its socio-demographic and work-related risk factors. Methods: An analytical cross-sectional study design was used to estimate the prevalence and investigate the risk factors for LBP among 136 teaching staff of UoN. A semi-structured questionnaire was used to collect data on LBP history, work-related and socio-demographic characteristics of the study participants. The 12-month prevalence of LBP and its associated 95% exact binomial confidence interval were estimated. A mixed-effects logistic regression model was used to evaluate the relationship between the predictors and LBP. Results: The estimated 12-month prevalence of LBP was 64% (95% CI: 55.3%–72.0%). From the multivariable analysis, physical inactivity (aOR: 6.0; 95% CI: 1.2–29.6), office chairs without lumbar supports (aOR: 3.3; 95% CI: 0.1–0.9) and high workplace stress (aOR: 4.4; 95% CI: 1.1–17.5) were identified as significant risk factors for LBP among the respondents. Conclusions: This study has revealed a high burden of LBP among teaching staff of the UoN and undoubtedly mimics the situation in other higher learning institutions in Kenya. Physical inactivity, sitting on chairs without lumbar supports and workplace stress have been identified as modifiable risk factors for LBP among teaching staff. This suggests a need to strengthen advocacy for regular physical activity, team-building activities and investment in office infrastructure to mitigate the effects of LBP within learning institutions.

NEXT: A phase II, open-label study of nivolumab adjuvant to chemoradiation in patients (pts) with localized muscle invasive bladder cancer.

TPS605 Background: In pts with localized muscle invasive bladder cancer (MIBC), trimodality bladder preserving therapy (TMT), with transurethral resection of bladder tumor, radio-sensitizing chemotherapy and definitive radiation, has up to a 50% risk of local and systemic relapse during the 2-year post treatment phase. We hypothesize that by inhibiting immune checkpoints, chemo-radiation induced tumor specific immune response will be enhanced both locally and abscopally, resulting in better failure-free survival (FFS). In the NEXT trial, we evaluate the efficacy of nivolumab after completion of the TMT in this setting. Methods: Pts with localized MIBC who have completed standard TMT are eligible. Pts receive nivolumab 480 mg intravenously every 4 weeks for up to 12 doses. Treatment with nivolumab begins within 90 days of completion of TMT. Subjects undergo surveillance cystoscopic and scan based assessments on study. Archived tumor tissue at baseline and at relapse is obtained for correlative studies. The primary endpoint is 2-year FFS. Secondary endpoints include FFS at 2 years in patients with intact bladder, rate of radical cystectomy (RC), cystoscopic local control, distant FFS in patients with intact bladder and those that undergo RC, overall survival, toxicity and quality of life. Exploratory endpoints include to characterize changes in immune cell subsets that can be correlated with clinical outcome and to assess the correlation of response to PD-L1 expression in pretreatment tumor tissue in the study subjects. The planned sample size for this single arm, open label trial is 28 pts. Kaplan-Meier methods will be used to plot survival endpoints and cystoscopic local control rates. Exact binomial methods will be used to provide 6 months, 1-year and 2-year estimates for these endpoints. The sample size justification is based on the maximum width of a two-sided 95% binomial confidence interval for 2 year FFS. With 28 evaluable subjects, a 95% exact binomial confidence interval, estimated using the method of Clopper-Pearson, will extend no more than 20% from the observed FFS. Clinical trial information: NCT03171025.

Optimizing Tissue Use: A Step-wise Approach to Diagnosing Squamous Cell Lung Carcinoma on Small Biopsies.

Background:Histologic subtyping of lung cancer has significant implications for treatment planning. Accurate diagnosis based on cytology/small biopsy specimens is challenging and frequently determined by morphology, as material is often not sufficient for immunohistochemical studies (IHC). We investigated the concordance between the rates of diagnosis from cytology/small biopsies compared with surgical specimens in patients with squamous cell lung cancer (SCC) and the utility of IHC for diagnostic precision in lung cancer subtyping.Methods:We conducted a 5-year retrospective analysis identifying cases of SCC diagnosed on cytology/small biopsies ± IHC and compared them with subsequent surgical specimens when available. The number of patients with SCC on surgical biopsy and the concordance between cytology ± IHC was determined.Results:Over the 5-year period (2011-2015), 231 cases were identified. Surgery was performed on 66 cases (28.5%), of which 87.9% concurred with cytological diagnosis (95% exact binomial confidence interval [CI] = 77.5%-94.6%). There were 36 cases diagnosed in 2014 and 2015 with IHC data. Of those cytology cases with IHC (n = 12), SCC was confirmed by surgery in 91.7% (95% CI = 61.5%-99.8%). Of those without IHC (n = 24), 95.8% were confirmed SCC by surgery (95% CI = 78.9%-99.9%). These rates were not different (Fisher exact test). All cases with IHC were morphologically squamous.Conclusions:Our data demonstrate that diagnostic precision of identifying SCC by cytology/small biopsy is comparable with or without additional IHC studies. We recommend judicious use of IHC on cytology specimens, reserving it for cases where cytomorphology is equivocal. Tissue should be preserved for molecular analysis, which may have therapeutic implications.

Abstract CT212: Combining pembrolizumab with locally delivered radiation therapy for the treatment of metastatic esophageal cancer

Abstract BACKGROUND Intraluminal brachytherapy for advanced esophageal cancer allows durable control of tumor-related obstructive symptoms by safely delivering large local doses of radiation over just one or a few sessions. Localized, intense doses of hypofractionated radiotherapy elicits more effective anti-tumor immune response than standard doses. In addition, abscopal effect of radiation in distant metastases may be augmented by addition of immune checkpoint inhibitor. Pembrolizumab is approved for treatment of PD-L1 positive gastroesophageal cancer. We therefore propose to evaluate the combination of brachytherapy and pembrolizumab in patients with advanced esophageal cancer. Correlative studies of this study aim to identify predictive biomarkers of response and to characterize the immune response before and after brachytherapy and pembrolizumab to assess immunologic parameters associated with the abscopal effect. METHODS This is a single institution, open-label, single-dose-level phase I study combining hypofractionated brachytherapy with standard dose pembrolizumab. Primary objective of this trial is to determine the tolerability of localized esophageal hypofractionated brachytherapy administered in two fractions when combined with pembrolizumab in patients with metastatic esophageal cancer. Secondary objective is to assess the antitumor efficacy of the combination. Exploratory objectives are to determine the expression profile of immunologic biomarkers and to annotate the local and distant immune response before and after treatments.Brachytherapy is delivered using a high-dose-rate iridium-192 afterloader via a dedicated esophageal applicator at 16 Gy in 2 fractions, 7-10 days apart. Pembrolizumab is given 1 week after completion of brachytherapy at 200 mg IV every 3 weeks. Endoscopic biopsies are performed before and after brachytherapy, and optionally after 8 weeks on pembrolizumab. Peripheral blood is collected at the same time points, at 3, 6, and 12 months on pembrolizumab, and at the time of progression. Patients with metastatic esophageal cancer who are candidates for brachytherapy for treatment of dysphagia are considered eligible for this trial. Exclusion criteria included prior treatment with PD-(L)1 targeting agent, symptomatic brain metastases, or other contraindication to pembrolizumab, such as active autoimmune disease. We plan to enroll 18 patients which will provide a reasonable ability to detect serious adverse event rates as well as early efficacy signals. There is at least 85% chance of observing at least 1 protocol-specified event if the true rate is 0.1 or greater. We will estimate 95% exact binomial confidence interval of true response rate based on observed responses. 80% of patient accrual is complete as of January 2019. NCT02642809. Citation Format: Haeseong Park, Tanner M. Johanns, A. Craig Lockhart, Jeffrey Bradley, Michael Roach, Gregory Vlacich, Manik Amin, Rama Suresh, Nusayba Bagegni, Clifford G. Robinson. Combining pembrolizumab with locally delivered radiation therapy for the treatment of metastatic esophageal cancer [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 CT212.