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Older adults with plasma cell disorders (PCDs) experience cognitive dysfunction that may be attributable to the disease and associated therapies. Yet, this has seldom been reported in the literature. Our objectives were to describe cognitive function (objective and patient-reported) in adults with PCDs and to explore clinical correlates of cognitive impairment.Participants completed a geriatric assessment between March 2018 and February 2020. Cognitive function was evaluated using two objective measures - Montreal Cognitive Assessment (MoCA, cutpoint26) and Blessed Orientation Memory Concentration Test (BOMC, cutpoint4) - and two patient-reported outcome (PRO) measures - Patient-Reported Outcomes Measurement Information System Cognitive Function (PROMIS-CF, cutpoint45) and European Organization for Research and Treatment of Cancer Cognitive Functioning subscale (EORTC-CF, cutpoint75). Spearman correlations examined relationships among these measures and log binomial regression was used to examine characteristics associated with cognitive impairment, as defined by the MoCA and PROMIS-CF measures.Among 86 participants with a mean age of 69 (range: 46-91), the prevalence of cognitive dysfunction was between 20% (BOMC) and 63% (MoCA). There was moderate correlation among objective measures (r = 0.51, p 0.0001), moderate to high correlation among PRO measures (r = 0.69, p 0.0001), but no correlation between objective and PRO measures. Factors associated with objective impairment included ≤ high school education (RR 1.46, p = 0.009), living alone (RR 1.42, p = 0.02), relapsed/refractory disease (RR 1.39, p = 0.04), empirically de-intensified induction therapy (RR 1.62, p = 0.008), frailty (RR 1.49, p = 0.04), and peripheral vascular disease (RR 1.54, p = 0.002). Factors associated with PRO impairment included social isolation (RR 3.43, p = 0.003), depression (RR 3.30, p = 0.004) and anxiety (RR 4.43, p = 0.0002), frailty (RR 3.60, p = 0.02), falls in the previous 6 months (RR 2.53, p = 0.02), and deficits in physical function (RR 4.44, p = 0.01). Older age was not associated with either objective or PRO impairment.Cognitive impairment, using objective and PRO screening measures, was relatively common in adults with PCDs. Cancer-related factors and medical comorbidities were associated with objective cognitive impairment whereas psychosocial and functional factors were associated with PRO impairment.

OBJECTIVES: Findings from a brief geriatric assessment (GA) in a cohort of adults with multiple myeloma (MM) are presented, with particular attention to the utility of the GA in identifying important deficits in adults judged to have a normal Karnofsky Performance Status (KPS ≥ 80). MATERIALS AND METHODS: Adults age 18 and older with MM were recruited into an observational study from 2018 to 2020. A modified Cancer and Aging Research Group (CARG) GA was administered at enrollment. Enrollees also completed the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life of Cancer Patients Core 30 questionnaire (QLQ-C30), with subscales of physical, social, role, and cognitive functioning (range 0-100; higher values indicate better function). Data were analyzed using descriptive statistics for the full cohort and stratified by concurrent KPS (score < 80 vs ≥ 80). RESULTS: Among 89 adults, the mean age was 69.1 years, 68% were aged ≥ 65 years, and 70% were white. In this cohort, 78% had KPS ≥ 80. Among those with KPS ≥ 80, functional impairments (Timed Up and Go ≥ 14 seconds and dependence in ≥ 1 instrumental activity of daily living) were seen in 30% and 21%, respectively, with 11% reporting ≥ 1 fall in the prior 6 months. At least two GA-identified deficits were detected in 50% of the overall cohort and in 41% of those with KPS ≥ 80. Among those with KPS ≥ 80, self-reported physical impairment on EORTC QLQ-C30 was noted by 34%. CONCLUSION: Using a modified CARG GA and EORTC questionnaire, functional impairments were identified among adults considered to have a good performance status based on a KPS (≥ 80). Future studies should focus on using GA measures for therapy assignment and identifying opportunities for intervening upon GA-identified deficits.

Cancer-related cognitive impairment (CRCI) has been largely unstudied in patients with multiple myeloma (MM). This study describes patient-reported cognition over time and patient factors associated with adverse cognitive outcomes in MM.Participants enrolled in a registry in which they completed a geriatric assessment at study entry, and 36 months after entry. Cognitive function was assessed using the EORTC QLQ-C30 Cognitive Function subscale, with CRCI defined as scores75. Generalized estimating equation (GEE) models were used to fit longitudinal models to investigate differences by group and differences in changes over time by group, with adjustment for time since diagnosis.One hundred and four adults with MM had mean age of 67 years and 30% identified as Black. Patient-reported CRCI was present in 18% of participants at enrollment, 21% at 3 months, and 30% at 6 months. Worse cognitive function was reported in those with impairments in physical function (P = .002), IADLs (P = .02), and performance status (P = .04), as well as in those who were prefrail/frail (P = .02) and depressed (P = .049). Greater cognitive decline over time was observed in patients without CRCI at enrollment (P.0001) and those with lower levels of education (P = .04).This is one of the first studies to describe longitudinal changes in patient-reported cognition in patients with MM. Several potentially intervenable factors, including physical function impairment and depression, were associated with worse cognition at study entry, but only baseline CRCI status and education level were predictive of future decline.

Time at home is a critically important outcome to adults with acute myeloid leukemia (AML) when selecting treatment; however, no study to date has adequately described the amount of time older adults spend at home following initiation of chemotherapy. We queried records from a multi-institution health system to identify adults age ≥60 newly diagnosed with AML treated with azacitidine (AZA) or venetoclax (VEN) and evaluated the proportion of days at home (PDH) following diagnosis. Days were considered "at home" if patients were not admitted or seen in the emergency department or oncology/infusion clinic. Assessed covariates included demographics and disease risk. Associations between PDH and baseline characteristics were evaluated via linear regression, adjusted for log length of follow-up. From 2015-2020, 113 older adults were identified. Most received AZA+VEN (51.3%) followed by AZA monotherapy (38.9%). Mean PDH for all patients was 0.58 (95% confidence interval 0.54-0.63, median 0.63). PDH increased among survivors over time. PDH did not differ between therapy groups (adjusted mean, AZA+VEN: 0.68; AZA monotherapy: 0.66; p=0.64) or between disease risk categories (p=0.34). Compared to AZA monotherapy, patients receiving AZA+VEN had longer clinic visits (median minutes: 127.9 vs. 112.9, p.

Novel copolymers of vinyl acetate and oxy ring-substituted ethyl 2-cyano-3-phenyl-2-propenoates, RPhCH=C(CN)CO2C2H5 (where R is 2-methoxy, 3-methoxy, 4-methoxy, 2-ethoxy, 4-ethoxy, 4-propoxy, 4-butoxy, 2,3-dimethoxy, 2,4-dimethoxy, 2,5-dimethoxy, 3,4-dimethoxy, 2,3,4-trimethoxy, 2,4,5-trimethoxy, 2,4,6-trimethoxy, 3,4,5-trimethoxy) were prepared in solution with radical initiation at 70C. The propenoates were synthesized by the piperidine catalyzed Knoevenagel condensation of ring-substituted benzaldehydes and ethyl cyanoacetate, and characterized by CHN analysis, IR, 1H and 13C-NMR. The compositions of the copolymers were calculated from nitrogen analysis and the structures were analyzed by IR, 1H and 13C-NMR. Thermal behavior of the copolymers was studied by DSC (Tg) and TGA. Decomposition of the copolymers in nitrogen occurred in two steps, first in the 160-350ºC range with residue (2.2-25.3 wt%), which then decomposed in the 500-650ºC range.

BackgroundThe plasma cell disorders (PCDs), multiple myeloma (MM), and light-chain amyloidosis (AL) are disproportionately diseases of older adults, whose care may be complicated by frailty associated with advancing age. We sought to evaluate the prevalence of functional deficits and symptoms in a cohort of persons with PCDs and associations of demographic, disease-related, functional, and psychosocial measures with quality of life (QoL).Patients and MethodsAdults with PCDs were recruited into an observational registry in 2018-2020. Patients completed a functional assessment and European Organization for Research and Treatment of Cancer QoL questionnaire (QLQ-C30). Associations of covariates of interest with QoL were evaluated via univariate linear regression.ResultsAmong 121 adults, the mean age was 68.6. Diagnoses were 74% MM, 14% AL, 7% both MM and AL, and 5% other PCDs. The median time from diagnosis was 34.9 months. Median lines of therapy were 2, with 11% having received ≥4th-line therapy.Patients with functional deficits had lower mean QoL scores: dependence in IADLs (66.3 vs. 79.9, P = .001) and recent falls (56.7 vs. 76.8, P = .001). Patients ≤6 months from diagnosis had lower QoL (66.7) than those ≥2 years from diagnosis (77.3, P = .03). However, patients on later lines of therapy (≥4th-line) had lower QoL (62.2) than those on 1st-line treatment (76.0, P = .04).ConclusionsPatients with physical impairments and more advanced PCDs had lower QoL than those without deficits or earlier in their disease course. Early identification of physical impairments may facilitate interventions that mitigate these deficits and thereby improve QoL for patients with PCDs.

Background: Prior reports have demonstrated inferior outcomes for patients with right-sided colorectal cancer (CRC) compared to patients with left-sided disease, as well as differences in treatment response based on disease sidedness. Differences in prognosis remain even among patients with metastatic disease, indicating that anatomy or stage at diagnosis alone cannot explain all of these findings. While genetic differences between right- and left-sided CRC have long been described, the genetic and molecular drivers underlying differences in prognosis and treatment response remain incompletely understood. Methods: We compared mutation prevalence between right- (cecum to splenic flexure) and left-sided (descending colon to rectum) CRC among 38 genes in a retrospective review of next-generation sequencing data of CRC samples obtained in routine clinical practice at a single academic medical center. Results: Among 288 cases (167 left-sided, 103 right-sided, 18 synchronous or without clear primary), patients with left-sided primaries had a longer overall survival from pathologic diagnosis (median 1,823 days vs . 1,006 days for right-sided cases, P=0.004). Among the assessed genes, BRAF and CTNNB1 mutations were more prevalent in right-sided CRC. BRAF was mutated in 15.5% of right-sided CRC (95% CI: 8.5–22.5%) compared to 4.8% (95% CI: 1.6–8.0%) (P=0.003). CTNNB1 was mutated in 3.9% of right-sided CRC (95% CI: 0.2–7.6%) compared to no instances of CTNNB1 mutations in left-sided disease (P=0.01). Conclusions: This difference in mutation prevalence may implicate these genetic pathways in the mechanisms underlying the discrepant outcomes and treatment responses between right- and left-sided CRC described in this and prior studies.

Background: The KRAS oncogene is a driver mutation and is present in greater than 90% of pancreatic ductal adenocarcinomas (PDAC). A subset of these tumors, however, do not harbor mutations in KRAS (wild type KRAS ). Studies have shown that patients with mutated KRAS have a poorer survival on first- line gemcitabine-based chemotherapy compared to wild type KRAS . In this study, we examined a cohort of patients with PDAC at our institution who were either wild type or mutant for the KRAS gene and assessed for differences in survival and response to different chemotherapeutic regimens. Methods: We examined clinical records of patients treated at the Abramson Cancer Center of the University of Pennsylvania from 2013 to 2017. Patients with a pancreatic mass and a histologic diagnosis of pancreatic or pancreaticobiliary adenocarcinoma were identi ed. Thirty-nine patients with PDAC who underwent tumor sequencing at Penn Medicine’s Center for Personalized Diagnostics (CPD) were selected for further study. Twelve patients were identi ed whose tumors were KRAS wild type. Twenty-seven patients with PDAC whose tumors harbored KRAS mutations were selected as controls ( KRAS mutant). Results: We noted a longer overall survival (OS) among KRAS wild type patients compared to KRAS mutant patients (P=0.026). This was independent of the age at diagnosis, patient gender, stage of diagnosis, tumor morphology, mismatch repair (MMR) status, and chemotherapeutic regimen. Conclusions: Similar to previously reported studies, PDAC with a KRAS wild type mutational profile has a better prognosis with a longer OS. This improved prognosis is independent of the protocol utilized in therapy for these patients. Our ndings suggest that future clinical trials in pancreatic cancer should take into consideration the presence of KRAS mutations in their pre-planned analysis when assessing the ef cacy of a novel therapeutic approach. This may be a crucial factor in trial concepts and outcomes.

Introduction The prognosis for older adults with acute myeloid leukemia (AML) is poor. Of approximately 12,000 adults age ≥ 60 diagnosed with AML in the U.S. annually, less than 40% survive 1 year from diagnosis. Prior research has shown that adults with AML feel time at home is a critical consideration in treatment selection. However, to date, no study has adequately described the amount of time older adults can expect to spend at home following initiation of AML therapy. In this study, we aimed to (1) quantify this time and (2) assess the impact of venetoclax (VEN) combination therapy on time at home for older adults with AML. Methods We queried records from University of North Carolina Health to identify individuals age ≥ 60 newly diagnosed with AML from 2015 to 2020. First-line AML therapy was identified, and those receiving azacitidine (AZA) and/or VEN were included. Dates of diagnosis, first remission, death, last follow up, and all oncology clinic / emergency department (ED) / inpatient encounters were captured. Patients with incomplete records were excluded. The primary outcome was proportion of days at home (PDH). PDH was calculated for each patient by subtracting the number of care days (days hospitalized or seen in an ED / oncology clinic / infusion center) from the total days of follow up, divided by total days of follow up. Overall survival (OS) was calculated via the Kaplan-Meier method. Covariates including demographics and disease risk (per European Leukemia Net 2017) were captured. PDH was evaluated via summary statistics for the full cohort and stratified by each categorical variable, both for the full follow up period and on a month-by-month basis among survivors. Associations between PDH and covariates were further assessed via linear regression with adjustment for length of follow up, with significance assessed via Wald Chi-square test. Results From 2015-2020, 137 older adults receiving first-line AZA and/or VEN were identified. 24 were excluded due to incomplete records. Among the remaining 113, mean age was 76 (range 60-99), 80.4% were white, and 43.4% were female. Most received AZA+VEN (51.3%) followed by AZA monotherapy (39.0%) and other VEN-containing combinations (9.7%). The majority had adverse-risk AML (61.3%). Baseline covariates including age and ELN risk were similar across therapy groups. Over the full follow up period, mean PDH was 0.58 (95% confidence interval 0.54-0.63) with a median of 0.63. PDH was similar among those with adverse-risk (mean 0.55, CI 0.49-0.61) and intermediate-risk AML (0.64, CI 0.56-0.72). PDH did not differ among therapy groups: AZA+VEN (0.60, CI 0.54-0.66), AZA alone (0.57, CI 0.49-0.66), and other VEN-containing regimens (0.54, CI 0.40-0.69). When adjusted for length of follow up, no covariate had a significant association with PDH (all p > 0.05). When evaluated month-by-month, the proportion of days at home rose over time among survivors. For example, of patients who survived the full month, mean PDH was 0.51 (CI 0.47-54, n = 105) in month 1 following diagnosis and 0.77 (CI 0.72-0.82, n = 57) in month 6. Figure 1 summarizes person-days at home or engaged in care for 12 months following diagnosis (including contributions from those who did not survive the full month). 34.5% of patients achieved composite complete remission, with higher rates among those receiving AZA+VEN (51.7%) than AZA alone (13.6%) (OR 6.8, p = 0.0002). Median OS was 0.64 years (CI 0.32 - 0.91) and was similar across therapy groups. Conclusion Burden of care for older adults with AML treated with first-line AZA or VEN is high. These individuals spend nearly half (cohort mean 42%) of days following diagnosis engaged in oncology care. In randomized studies, the addition of VEN to AZA improves OS and increases remission rates though results in higher rates of neutropenic fever. Although this study may be underpowered to detect small differences, the superior remission rates with AZA+VEN did not translate to more days at home, perhaps due to increased admissions for neutropenic fever and office/infusion visits. Given the importance of time at home to older adults with AML identified in prior research, these data provide new information to support shared decision making regarding treatment options. Future prospective trials should evaluate burden of care, including time at home, as an endpoint. While awaiting these data, larger analyses of the impact of treatment regimen on burden of care would be useful. Figure 1 Figure 1. Disclosures Bryant: Carevive: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Servier Pharmaceuticals: Honoraria, Speakers Bureau. Coombs: Alexion Pharmaceuticals: Research Funding; Machaon Diagnostics: Research Funding. Foster: Macrogenics: Research Funding; Rafael Pharmaceuticals: Research Funding; Macrogenics: Consultancy; Daiichi Sankyo: Consultancy; Agios: Consultancy; Bellicum Pharmaceuticals: Research Funding.

Introduction: Recent analyses have demonstrated that race and geographic area are important factors for outcomes in acute myeloid leukemia (AML) patients under the age of 60. Older patients with AML often receive outpatient therapy aimed at prolonging survival while maintaining time at home, a critical patient-centered outcome. We aimed to describe whether overall survival and time at home were associated with race, geographic area, and other baseline factors for older AML patients in the modern era of combination outpatient therapy including hypomethylating agents and Venetoclax. Methods: We identified all older adults (≥ 60 years) diagnosed with AML from 2015 - 2020 who received first-line treatment with Azacitidine (AZA), Azacitidine + Venetoclax (AZA+VEN), or other Venetoclax-containing regimens (Other VEN) within the University of North Carolina (UNC) Health System. Clinical and sociodemographic factors were captured. The primary independent variables of interest were race, socioeconomic status (SES), rurality, and distance from UNC Cancer Center, an NCI Comprehensive Cancer Center (NCI-CCC). Race was self-reported. SES and rurality were estimated by ZIP code, as determined by Census tract information from the American Community Survey (2015-2019). Geocoding was used to estimate distance and travel time from patient's home address to the NCI-CCC. The primary outcomes were overall survival (OS) and proportion of days engaged in oncologic services (PDEOS), which was defined as the proportion of person-days admitted, in the ED, at an office visit, or in infusion/transfusion divided by the overall number of person-days survived. Linear and logistic regression analyses were performed to assess associations between independent variables and outcomes. Cox proportional hazards models were used to identify associations with OS. Multivariable analyses were performed using covariates of potential significance (p < 0.20). Results: Of 136 newly diagnosed AML patients aged ≥ 60 years identified in the study period, 113 patients had full capture of service records (83%). These patients were treated with AZA (n = 43), AZA+VEN (n = 58), or other VEN (n = 11). Baseline demographics are shown in the Table. The median distance from the NCI-CCC was 42.3 miles. The median OS for the entire cohort was 0.64 years (CI 0.32 - 0.91). Mean PDEOS was 0.42. 35% of patients achieved remission (AZA = 14%, AZA+VEN = 52%; Other VEN = 27%). Race, SES, and rurality were not significantly associated with survival, remission, PDEOS, or chemotherapy regimen received. Median OS was shorter for Black/AA patients (0.47 years, CI 0.23 - 1.25) than for White patients (0.64 years, CI 0.28 - 0.91), although this difference was not statistically significant (p = 0.80). After adjusting for log years of follow-up time, distance from the NCI-CCC was associated with increased PDEOS. Patients who lived ≥ 50 miles from the NCI-CCC spent 7% more days engaged in oncologic services, which amounts to 2.1 more days per month (p = 0.03). No significant association was observed between distance from the NCI-CCC and OS. There was also no association seen between distance from the NCI-CCC and chemotherapy regimen received. We examined the association between PDEOS and age, ELN risk, and median household income, and none of these variables were significant enough in the model to be considered for multivariable analyses. Conclusion: Overall survival in this population of older AML patients was not significantly associated with race, SES, distance to NCI-CCC or rurality. Distance to treatment center was associated with increased burden of healthcare services. Patients who lived the greatest distances from the NCI-CCC spent a greater proportion of their days engaged in oncologic services. These conclusions are limited by the relative racial and ethnic homogeneity, lack of representation from urbanized and rural areas, and limited geographic location. Given the dismal median overall survival of only 7.7 months, targeted interventions including telehealth visits or consolidation of multidisciplinary care would likely be valuable for decreasing healthcare burden among older AML patients, especially for those with long distances to travel. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Introduction:In January of 2010, North Carolina (NC) USA implemented state-wide Trauma Triage Destination Plans (TTDPs) to provide standardized guidelines for Emergency Medical Services (EMS) decision making. No study exists to evaluate whether triage behavior has changed for geriatric trauma patients.Hypothesis/Problem:The impact of the NC TTDPs was investigated on EMS triage of geriatric trauma patients meeting physiologic criteria of serious injury, primarily based on whether these patients were transported to a trauma center.Methods:This is a retrospective cohort study of geriatric trauma patients transported by EMS from March 1, 2009 through September 30, 2009 (pre-TTDP) and March 1, 2010 through September 30, 2010 (post-TTDP) meeting the following inclusion criteria: (1) age 50 years or older; (2) transported to a hospital by NC EMS; (3) experienced an injury; and (4) meeting one or more of the NC TTDP’s physiologic criteria for trauma (n = 5,345). Data were obtained from the Prehospital Medical Information System (PreMIS). Data collected included proportions of patients transported to a trauma center categorized by specific physiologic criteria, age category, and distance from a trauma center.Results:The proportion of patients transported to a trauma center pre-TTDP (24.4% [95% CI 22.7%-26.1%]; n = 604) was similar to the proportion post-TTDP (24.4% [95% CI 22.9%-26.0%]; n = 700). For patients meeting specific physiologic triage criteria, the proportions of patients transported to a trauma center were also similar pre- and post-TTDP: systolic blood pressure 29 (23.2% versus 22.6%); and Glascow Coma Scale (GCS) score Conclusions:State-wide implementation of a TTDP had no discernible effect on the proportion of patients 50 years and older transported to a trauma center. Under-triage remained common and became increasingly prevalent among the oldest adults. Research to understand the uptake of guidelines and protocols into EMS practice is critical to improving care for older adults in the prehospital environment.

e20004 Background: Multiple myeloma (MM) and immunoglobulin light chain (AL) amyloidosis are clonal plasma cell disorders (PCDs) of aging, with median ages at diagnosis of 69 and 76 years, respectively. The care of adults with these disorders is often challenging due to the higher prevalence of vulnerabilities with advancing age. We examined the prevalence of physical or cognitive impairments and associations with quality-of-life (QoL) ratings in a longitudinal cohort of adults with PCDs. Methods: Adults undergoing treatment for PCDs were recruited to a longitudinal observational study (NCT03717844) from 2018 to 2020. A modified Cancer and Aging Research Group (CARG) geriatric assessment (GA) was administered at enrollment. Patients also completed the European Organization for Research and Treatment of Cancer QoL Questionnaire Core 30 (EORTC QLQ-C30), which provided subscales of physical function, cognitive function, and global QoL (range 0-100; higher values indicate better function or QoL). Univariate linear regression was used to evaluate associations at the time of enrollment. Results: Among 121 consecutive adults, the mean age was 69 years, 65.8% were aged ≥ 65 years, and 71.9% were white. Diagnoses included MM in 73.6%, AL amyloidosis in 14.0%, and both disorders in 7.4%. The remaining 5.0% had another PCD warranting chemotherapy. Time from diagnosis at enrollment was ≤ 6 months for 25.6%, 6 to 24 months for 18.1%, and ≥ 24 months for 56.3%. In this cohort, 80.2% had a clinician-assessed Karnofsky Performance Status (KPS) score ≥ 80. GA-identified impairments (Timed Up and Go ≥ 14 seconds and dependence in ≥ 1 instrumental activity of daily living [IADL]) were seen in 29.8% and 35.6%, respectively, with 13.5% reporting ≥ 1 fall in the prior 6 months. Polypharmacy (≥ 5 medications) was identified in 80.0%. Self-reported physical and cognitive impairments on QLQ-C30 were described by 48.7% and 20.2%, respectively. Patients with functional deficits had worse EORTC QoL scores compared to those without deficits: dependence in ≥ 1 IADL (mean QoL score 66.3 vs. 79.9, p = 0.0009), ≥ 1 fall (56.7 vs. 76.8, p = 0.0009), self-reported physical impairment on QLQ-C30 (64.0 vs. 84.5, p < 0.0001), and self-reported cognitive impairment on QLQ-C30 (61.2 vs. 77.7, p = 0.0012). Conclusions: Using a modified CARG GA and the EORTC QLQ-C30, we identified physical and cognitive impairments among adults undergoing treatment for PCDs. GA-identified impairments in physical function were more prevalent than clinician-assessed KPS would suggest. Patients with physical and cognitive impairments had worse QoL scores than those without deficits. Future research involving this cohort will investigate the longitudinal trajectory of physical and cognitive functioning, evaluate trends in QoL measurements, and test the feasibility of implementing GA-guided interventions for this population.

The rapid diagnosis of an infection is essential for the outbreak management, risk containment, and patient care. We have previously shown a method for the rapid bedside inactivation of the Ebola virus during blood sampling for safe nucleic acid (NA) tests by adding a commercial lysis/ binding buffer directly into the vacuum blood collection tubes. Using this bedside inactivation approach, we have developed a safe, rapid, and simplified bedside NA extraction method for the subsequent detection of a virus in lysis/binding buffer-inactivated whole blood. The NA extraction is directly performed in the blood collection tubes and requires no equipment or electricity. After the blood is collected into the lysis/binding buffer, the contents are mixed by flipping the tube by hand, and the mixture is incubated for 20 min at room temperature. Magnetic glass particles (MGPs) are added to the tube, and the contents are mixed by flipping the collection tube by hand. The MGPs are then collected on the side of the blood collection tube using a magnetic holder or a magnet and a rubber band. The MGPs are washed three times, and after the addition of elution buffer directly into the collection tube, the NAs are ready for NA tests, such as qPCR or isothermal loop amplification (LAMP), without the removal of the MGPs from the reaction. The NA extraction method is not dependent on any laboratory facilities and can easily be used anywhere (e.g., in field hospitals and hospital isolation wards). When this NA extraction method is combined with LAMP and a portable instrument, a diagnosis can be obtained within 40 min of the blood collection.

Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths worldwide, and advanced HCC generally caries a poor prognosis. The treatment of advanced disease is limited to sorafenib, which provides only a limited improvement in survival, and novel therapies are, thus, sorely needed. Among emerging alternative approaches, immune checkpoint inhibitors are a particularly promising treatment modality. In this review, we summarize current knowledge of the mechanisms for the two primary targets of immune checkpoint inhibitors and discuss the relevance of these pathways to the immunology of HCC. We also review the state of ongoing and forthcoming trials of immune checkpoint blockade in HCC.

622 Background: Recent reports have demonstrated inferior outcomes for patients with right-sided colorectal cancer (CRC) compared to patients with left-sided disease (Schrag et al 2016, JCO 34 (suppl; abstr 3505)) as well as differences in treatment response based on disease sidedness (Venook et al 2016, JCO 34 (suppl; abstr 3504)). However, the biological and genetic underpinnings of these clinical differences are incompletely understood. Methods: We compared mutation rates among 38 genes in a retrospective review of next-generation sequencing data of CRC samples obtained in routine clinical practice at a single academic medical center. Primary location was identified via chart review. Right = cecum to transverse colon; Left = descending colon to rectum. Results: Among 293 samples (167 left-sided, 103 right, 23 synchronous or without clear primary), BRAF and CTNNB1 mutations were more prevalent in right-sided CRC. BRAF was mutated in 15.5% of right-sided CRC (95% CI: 8.5-22.5%) compared to 4.8% (CI: 1.6-8.0%) (p=0.003). CTNNB1 was mutated in 3.9% of right-sided CRC (CI: 0.2-7.6%) compared to no instances of CTNNB1 mutations in left-sided disease (p=0.01). Among right-sided CRC, there was a trend toward more KRAS mutations at 57.3% (CI: 47.7-66.8%) versus 44.9% (CI: 37.4-52.5%) and more PIK3CA mutations at 26.2% (CI:17.7-34.7%) versus 17.4% (CI: 11.6-23.1%), though these differences did not rise to the level of statistical significance. The overall rate of BRAF mutations in our sample (8.9%, CI: 5.5-12.3%) was consistent with the rate of BRAF mutations among large intestine adenocarcinomas in the COSMIC database (10.6%, CI: 10.4-10.8%), lending support to the external validity of these data. Conclusions: These differing mutation rates may implicate these genetic pathways in the mechanisms underlying the discrepant outcomes and treatment responses between right and left-sided disease described in prior studies. Further work is needed to more clearly elucidate genetic difference between right and left-sided CRC, as well as the mechanistic relationship between these mutations and prognosis.