tbuckley/cabot-search huggingface dataset:
Exploring disparities in patients’ preference for adjuvant chemotherapy in culturally and linguistically diverse (CALD) groups: One Australian centre’s experience.
Authors: Alesha Thai, Mark Tacey, Shane C White, Mandy Byrne, Jaclyn Yoong
Journal: Journal of Clinical Oncology (2016)

e18063 Background: Racial disparities have been identified in the treatment of cancer patients worldwide, often associated with differences in outcomes. International data has shown reduction in cancer-related mortality in the general population that is not paralleled in migrant populations. Differences in treatment include uptake of adjuvant chemotherapy for potentially curable cancers. Possible reasons for this are barriers such as language, health beliefs and access to healthcare. Australia has a large CALD population; however, there is little published data on these patients in oncology and in particular, for adjuvant chemotherapy use. Methods: We conducted a retrospective analysis of patients who were recommended to have adjuvant chemotherapy for stage III colorectal cancer (CRC) or early-stage breast cancer (EBC) between July 2006 and October 2014. We compared the rates of adjuvant chemotherapy participation between those who identified English as their preferred language, versus those for whom English is not their first preferred language. Results: Of 212 patients, 143 patients had EBC (median age 55.7 years, SD 12.3) and 69 patients had stage III CRC (median age 62.0 years, SD 12.3). The proportion of English speaking patients was slightly higher in the CRC group (75.4%) compared to the EBC group (72.5%). There was no statistically significant difference in adjuvant chemotherapy use between English speaking and non-English speaking groups (80.3% versus 81.8% p = 0.802). Patients who accepted chemotherapy were younger in the EBC group (Mean ± SD: 54.1 ± 11 years vs. 63.6 ± 15.3 years p = 0.004). They were also younger in the CRC group but the difference was not significant (Mean ± SD: 60.8 ± 11.9 vs. 65.8 ± 13.2 years p = 0.186). Gender was not a factor in acceptance rates in the CRC group (p = 0.710). Conclusions: There was no significant difference observed in uptake of adjuvant chemotherapy between patients who identify English as their first preferred language compared to those who identify as non-English speaking. This is the first study to assess these differences in Australia and contrasts the prevailing data from other countries.
Lethality of Civilian Active Shooter Incidents With and Without Semiautomatic Rifles in the United States
Authors: Elzerie de Jager, Eric Goralnick, Justin C. McCarty, Zain G. Hashmi, Molly P. Jarman, Adil H. Haider
Journal: JAMA (2018)

Semiautomatic rifles have been used in some of the largest active shooter incidents in US history. 1 The weapons were banned in 1994 under the federal assault weapons ban but were reintroduced to the public marketplace in 2004. 2 Currently, there are no comprehensive assessments of injuries from different types of firearms.We compared the number of persons wounded, killed, and either wounded or killed during active shooter incidents with and without semiautomatic rifles.Methods | An active shooter incident is defined by the Federal Bureau of Investigation (FBI) as a situation in which an individual is actively engaged in killing or attempting to kill people in a confined or populated area. 3 The FBI has tracked all active shooter incidents since 2000 and has the most comprehensive data set available. 3 We retrieved active shooter incident characteristics from the publicly accessible FBI database through 2017 (accessed May 18, 2018). 3 For each incident, we extracted shooter age, name, year, location (city and state), number of people wounded, killed, and wounded or killed, place of shooting (commerce, education, government, open space, residences, health care, and house of worship), and type of firearms present (rifle, shotgun, handgun).The FBI reports do not distinguish whether a rifle was semiautomatic; therefore, for each incident in which the FBI reported that a rifle was present, a media content analysis was performed to identify semiautomatic rifle presence.An a priori search hierarchy was established in which the primary data sources were court and police documents or statements (44.9%; 35 of 78), and secondary data sources were news articles.At least 3 news articles from different media outlets were required to triangulate data.No discrepancies among sources were found.All incidents with the presence of a semiautomatic rifle were classified as semiautomatic rifle incidents regardless of other firearm presence.The Las Vegas, Nevada, shooting, which represented a statistical outlier, and the San Bernardino, California, shooting, which had more than 1 shooter present, were excluded.Negative binomial regression was used to estimate the association between presence of a semiautomatic rifle and the total numbers nonfatally wounded, killed, and either wounded or killed, and the percentage of persons who died if wounded at the incident, controlling for the place and year of shooting and the presence of other firearms.Significance was set at P < .05(2-sided).Stata version 15.1 was used for analysis.Results | Of the 248 active shooter incidents, 76 involved a rifle, and we identified the type in all instances.A semiautomatic rifle
Abstract 15865: Novel, Highly Selective Direct Thrombin Inhibitors: Efficacy, Safety, and Tolerability Studies
Authors: Chengpei Xu, Subhadra Dash, Daniel Clemens, Kenneth Lin, Georg Neckermann, Simon Yau, Elaine To, Lev Igoudin, Samuel Keutzer, Nichole Sandoval, Sivan Sizikov, Angels Estiarte, Kevin Short, Timothy Shiau, David Williams, Mohan Sivaraja, Anirban Datta, David Kita
Journal: Circulation (2016)

Patients with atrial fibrillation and venous thromboembolism require anticoagulation prophylaxis/treatment. Direct oral anticoagulants (DOACs) offer certain advantages over warfarin and heparins, b...
Phase II trial of continuous dosing of regorafenib in patients with metastatic or recurrent gastrointestinal stromal tumors (GISTs) after failure of imatinib and sunitinib.
Authors: Yoon-Koo Kang, Jae-Joon Kim, Changhoon Yoo, Mo Youl Beck, Jungeun Ma, Min-Hee Ryu
Journal: Journal of Clinical Oncology (2018)

11537 Background: Regorafenib in the standard intermittent dosing schedule (160 mg po per day for 3 weeks followed by 1week rest) was proven effective in the GRID trial in refractory gastrointestinal stromal tumors (GISTs). However, with this dosing schedule, frequent dose reduction was needed and progression of GIST tumors or tumor-related symptoms during the off-treatment period were also noted in some patients (pts).Therefore, we conducted this phase 2 trial to evaluate the efficacy and safety of regorafenib in lower dose continuous dosing schedule (NCT02889328). Methods: Pts with measurable, metastatic or recurrent GIST who failed both imatinib and sunitinib were eligible for this study. Regorafenib 100 mg po per day was administered continuously. The primary endpoint was disease control rate [DCR] (CR + PR + SD) lasting for at least 12 weeks by the RECIST v1.1. Results: From September 2016 to August 2017, a total of 25 pts were enrolled.The median age was 60 years (range, 42-74), and male was dominant (84%). Small bowel was the most common primary site (n = 15, 60%), followed by stomach (n = 7, 28%). The median treatment duration of imatinib and sunitinib was 40.5 months (range, 7.1–100.5) and 8.3 months (range, 0.7–37.5), respectively. Primary mutation was in kit exon 11 (n = 16, 64%) and 9 (n = 5, 20%), with 3 wild type (12%). The best response was PR in 2 (8%), SD in 16 (64%), and PD in 6 (24%) pts. DCR lasting for at least 12 weeks was 64% (16 of 25). With a median followup of 8.6 months (range, 2.3–14.6), the median PFS was 7.3 months (95% CI, 5.9–8.6), and the median OS was not reached with 1-year survival rate of 64.5%. Treatment was well tolerated. Ten pts (40%) experienced grade 3-4 toxicities including hand-foot skin reaction (n = 4, 16%), and elevation of alanine aminotransferase (n = 2, 8%). Only 5 pts (20%) needed dose modification with relative dose intensity of 91.8% for 8 cycles in all pts. Conclusions: With comparable efficacy and better safety profile compared to standard intermittent dosing schedule, regorafenib in this trial with lower dose continuous schedule might be an alternative treatment in GIST pts after failure of imatinib and sunitinib. Clinical trial information: NCT02889328.
A phase II study of JS001, a humanized PD-1 mAb, in patients with advanced melanoma in China.
Authors: Zhihong Chi, Bixia Tang, Xinan Sheng, Lu Si, Chuanliang Cui, Yan Kong, Yingbo Chen, Shukui Qin, Jing Chen, Di Wu, Xin Song, Xieqiao Yan, Jiayi Yu, Jun Guo
Journal: Journal of Clinical Oncology (2018)

9539 Background: JS001, a humanized IgG4 antibody specific for human PD-1, has demonstrated favorable safety profile and promising anti-tumor activity in phase I clinical trial. Methods: This multi-center, open-label, phase II registration study is designed to evaluate safety and efficacy of JS001 in advanced melanoma patients who have failed systemic treatment. JS001 is given at 3 mg/kg IV Q2W until disease progression or intolerable toxicity. (Clinical Trial ID: NCT03013101). Results: Enrollment was completed by 9/15/2017 with 128 melanoma subjects enrolled (51 acral, 21 mucosal, 18 chronically sun-damaged (CSD), and 38 Non-CSD or origin unknown). As of 1/4/2018, among 121 evaluable subjects, all had at least two evaluations per RECIST1.1 by independent radiologic review committee. 1 CR, 24 PR and 48 SD were observed for an ORR at 20.7% and a DCR at 60.3%. ORR was lower in acral (14.3%) and mucosal (0%) subtypes when compared with CSD (35.3%) and non-CSD (33.3%). Nevertheless, significant DCRs were achieved in acral (53.1%) and mucosal (42.1%) melanoma subjects. Additional factors have been analyzed for correlation with clinical responses (Table 1). Median duration of response has not been reached, as most responses (23/25) are ongoing. There is no treatment related death in the study. The most common treatment related AEs were grade 1/2, including proteinuria (25%), ALT increase (25%), rash (22%), hyperglycemia (20%), amylase increase (18%), leukopenia (17%), anemia (16%), vitiligo (16%), AST increase (16%), pruritus (14%) and hypothyroidism (13%). Treatment related grade 3/4 AEs occurred in 18% subjects. Conclusions: This is the first reported large scale prospective anti-PD-1 clinical study in advanced melanoma subjects with an emphasis on acral and mucosal subtypes. Anti-PD-1 mAb appears more efficacious for CSD and non-CSD than acral and mucosal subgroups. Patients will be continuously monitored for safety and efficacy readouts (DOR, PFS and OS). Clinical trial information: NCT03013101.Clinical response analysis in subgroups. Group Value n ORR % ECOG 0 70 20.0 1 51 21.6 Prior lines of systemic therapy 1L 38 29.0 2L 28 25.0 3L 26 11.5 ≥4L 29 13.8 PD-L1 (≥1% cutoff with SP142) Positive 24 45.8 Negative 80 15.0 LDH (U/L) ≤ 280 104 21.2 > 280 17 17.7 Total 121 20.7
Hepatitis B and C positivity rates in solid tumors and reactivation rates due to cytotoxic chemotherapy.
Authors: Deniz Tural, Mustafa Karaca, Hakan Kocoglu, Gülsüm özet, Orhan kemal YÃ¼cel, Rumeysa Ciftci, Mustafa Benekli, Ahmet Ozet
Journal: Journal of Clinical Oncology (2016)

e23213 Background: The aims of this study are determining Hepatitis B and C positivity rates in patients with solid tumors and comparing these rates with healthy population, and also determination of hepatitis reactivation rates due to cytotoxic chemotherapy. Methods: Patients with solid cancer(8322) were retrospectively evaluated and their results were compared with control group that consisted of 96,000 subjects. Results: In control groups, HBsAg (Hepatitis B surface antigen) positivity rate was 3.3% and anti-HCV positivity rate was 0.84%.In cancer patients, HBsAg positivity rate was 3.65% and anti-HCV positivity rate was 1.2%. no difference was detected in HBsAg positivity rate and anti-HCV positivity rate between patients and controls (p = 0.12 and p = 0.09, respectively). HBsAg positivity rates of head and neck cancer (5.88%; p = 0.02), rectum (5.6%; p = 0.025) and gastric and esophagus cancer (5.88%; p = 0.025) were significantly higher than control groups. Anti-HCV positivity rate (2.5%; p = 0.0016) was significantly higher in lung cancer when compared with control group. Liver function tests of 96 of 355 patients (27%) who HBsAg, anti-HCV, or anti-HBc positivity, have increased during follow-up time. Determined causes of high liver function tests were as follows:chemotherapy regimen (49%); hepatitis reactivation (25%); liver metastasis (18%); unknown origin (7%); and sepsis (1%). We have determined hepatitis reactivation in 19 patients (18%) with HBsAg positive, in 3 patients (2%) with anti-HBc positive, and in 2 patients (5%) patients with anti-HCV positive. There was a significant relation between lymphoma and hepatitis reactivation (p = 0.032). The most frequent chemotherapy regimens that were associated with hepatitis reactivation were R-CHOP (3 patients, 12.5%), FUFA (3 patients, 12.5%), adriablastine-cyclophosphamide (AC) (2 patients, 8%). Conclusions: Hepatitis B positivity rates were significantly higher in patients with head and neck cancer, rectum cancer or gastric and esophagus cancer than normal population. Hepatitis reactivation occurred in twenty-five percent of patients who had positive hepatitis B serology and received chemotherapy.
Fine‐Tuning of Sirtuin 1 Expression Is Essential to Protect the Liver From Cholestatic Liver Disease
Authors: Britt A. Blokker, Monica Maijo, Marta Echeandia, Mikel Galduroz, Angela M. Patterson, Anna Ten, Mark Philo, Rebecca Schungel, Virginia Gutierrez‐de Juan, Emina Halilbasic, Claudia Fuchs, Gwenaelle Le Gall, Malgorzata Milkiewicz, Piotr Milkiewicz, Jesus M. Banales, Simon M. Rushbrook, José M. Mato, Michael Trauner, Michael Müller, María Luz Martínez‐Chantar, Marta Varela‐Rey, Naiara Beraza
Journal: Hepatology (2018)

Cholestasis comprises aetiologically heterogeneous conditions characterized by accumulation of bile acids in the liver that actively contribute to liver damage. Sirtuin 1 (SIRT1) regulates liver regeneration and bile acid metabolism by modulating farnesoid X receptor (FXR); we here investigate its role in cholestatic liver disease. We determined SIRT1 expression in livers from patients with cholestatic disease, in two experimental models of cholestasis, as well as in human and murine liver cells in response to bile acid loading. SIRT1‐overexpressing (SIRT oe ) and hepatocyte‐specific SIRT1‐KO (knockout) mice ( SIRThep–/– ) were subjected to bile duct ligation (BDL) and were fed with a 0.1% DDC (3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine) diet to determine the biological relevance of SIRT1 during cholestasis. The effect of NorUDCA (24‐norursodeoxycholic acid) was tested in BDL/SIRT oe mice. We found that SIRT1 was highly expressed in livers from cholestatic patients, mice after BDL, and Mdr2 knockout mice ( Mdr2–/– ) animals. The detrimental effects of SIRT1 during cholestasis were validated in vivo and in vitro . SIRT oe mice showed exacerbated parenchymal injury whereas SIRThep–/– mice evidenced a moderate improvement after BDL and 0.1% DDC feeding. Likewise, hepatocytes isolated from SIRT oe mice showed increased apoptosis in response to bile acids, whereas a significant reduction was observed in SIRThep–/– hepatocytes. Importantly, the decrease, but not complete inhibition, of SIRT1 exerted by norUDCA treatment correlated with pronounced improvement in liver parenchyma in BDL/SIRT oe mice. Interestingly, both SIRT1 overexpression and hepatocyte‐specific SIRT1 depletion correlated with inhibition of FXR, whereas modulation of SIRT1 by NorUDCA associated with restored FXR signaling. Conclusion: SIRT1 expression is increased during human and murine cholestasis. Fine‐tuning expression of SIRT1 is essential to protect the liver from cholestatic liver damage.
Neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) as predictive indicators of nivolumab efficacy in metastatic non-small cell lung cancer (mNSCLC).
Authors: Sabrina Rossi, Luca Toschi, Giovanna Finocchiaro, Armando Santoro
Journal: Journal of Clinical Oncology (2018)

e21115 Background: The use of nivolumab in mNSCLC is to date limited by the lack of a biomarker able to reliably select patients that could potentially benefit from this checkpoint inhibitor. Methods: Medical records of 65 patients affected by mNSCLC and treated with nivolumab were reviewed. NLR and LMR were calculated at baseline (t0) and at the first tumor assessment by computed tomography scan (t1). Cut-off values of NLR ( > 4.9) and LMR (≤1.38) were determined at t0 by receiver operating characteristic analysis for overall survival (OS). Kaplan-Meier method was used to estimate survival outcomes. Median OS calculated from the start of immunotherapy was 11.3 months. Median follow-up time was 14 months. Results: Low NLR (n = 24) at t0 was associated with longer OS (14.1 vs 4.2 months; HR 0.28, 95%CI 0.14-0.58; p < 0.0001) as well as high LMR values (n = 16) (13.2 vs 8.1 months; HR 0.38, 95%CI 0.15-0.92; p = 0.0033). Similarly, low NLR (n = 23) or high LMR values (n = 16) at t1 were predictive of longer OS: 15.6 vs 8.1 months (HR 0.30, 95%CI 0.14-0.66; p = 0.0005) and 13.9 vs 8.1 months (HR 0.33, 95%CI 0.13-0.88; p = 0.0018), respectively. Then, we evaluated NLR and LMR trend from t0 to t1. Patients with NLR≤4.9 at t0 and t1 and those with decreasing NLR values had a longer OS (p = 0.0005) when compared to the group with NLR > 4.9 or increasing NLR values; also patients with LMR > 1.38 at t0 and t1 or increasing LMR values had a survival benefit (p = 0.0077) when compared to those with persistent low or decreasing LMR values. At multivariate analysis, only NLR at t0 (p = 0.0005) or t1 (p = 0.002) and NLR trend from t0 to t1 (p = 0.0034) were significantly associated with OS outcomes. Conclusions: Our study suggests that NLR at baseline, at first tumor assessment or NLR trend could be used as predictive indicator of nivolumab outcome in NSCLC.
Versican proteolysis as a key regulator of CD8+ T-cell infiltration in colorectal cancer.
Authors: Dustin A. Deming, Chelsea Hope, Philip Emmerich, Adam Pagenkopf, Kristina Matkowskyj, Dana Van DeHey, Susan Payne, Linda Clipson, Natalie Scott Callander, Peiman Hematti, Shigeki Miyamoto, Michael G Johnson, Fotis Asimakopoulos
Journal: Journal of Clinical Oncology (2017)

e15082 Background: Colorectal cancer (CRC) originates within immunologically complex microenvironments. To date the benefits of immunotherapy have been modest except in neoantigen-laden mismatch repair (MMR)-deficient tumors. Approaches to enhance tumor-infiltrating lymphocytes (TILS) in the tumor bed may substantially augment clinical immunotherapy responses. Proteolysis of the tolerogenic matrix proteoglycan versican (VCAN) generates a bioactive fragment, versikine, with putative immunostimulatory activities. Methods: Matched normal and CRC tissue samples were collected from 122 patients with cancers across all stages and locations throughout the colon and rectum. These samples were stained for VCAN, αDPEAAE (neoepitope generated in cleaving VCAN to versikine), and CD8 and scored by a pathologist. Tumors were classified as VCAN proteolysis-predominant (VPP) if their staining for total VCAN staining intensity was &lt; 1+ and staining for VCAN proteolysis (αDPEAAE antibody) was &gt; 2. Conversely, tumors were classified as VCAN proteolysis-weak (VPW) if intact VCAN staining intensity was &gt; 1+ or αDPEAAE intensity was &lt; 2+. IHC for mismatch repair (MMR) proteins was also performed. Results: Overall increased VCAN staining was observed in cancer versus (vs) normal tissue. VPP tumors had a 10 fold greater infiltration of CD8+ T-cells vs VPW cancers (p &lt; 0.001). The correlation between VCAN proteolysis and CD8+ T-cell infiltration was maintained in both cancers with proficient (p) MMR and deficient (d) MMR. In both pMMR and dMMR, the VPP tumors had the greatest degree of CD8+ T-cell infiltration (Wilcoxon rank sum tests: pMMR p = 0.006; dMMR p = 0.03). Among the VPP tumors there was a greater degree of CD8+ T cell infiltration in the dMMR cancers vs pMMR cancers (35 versus 14.8 TILs per high power filed, p = 0.04). Nuclear CTNNB1, a marker for activation of WNT signaling, negatively correlated with CD8+ T cell infiltration( p = 0.014). In addition, VCAN accumulation correlated with the presence of nuclear CTNNB1 (p &lt; 0.001) Conclusions: This is the first description indicating that VCAN proteolysis may shape CRC immune contexture and provide a rationale for testing VCAN proteolysis as a predictive and/or prognostic immune biomarker.
Evaluating financial toxicity (FT) interventions.
Authors: Jonas A. De Souza, Ellie Proussaloglou, Laura Nicholson, Yichen Wang
Journal: Journal of Clinical Oncology (2017)

e21673 Background: FT has been defined as an adverse event of cancer treatments. Several patient (pt)-level interventions have been developed to mitigate FT. However, due to the lack of longitudinal studies, the impact of these interventions has not been established. Methods: Pts with cancer receiving Co-Pay Assistance (CPA) from the Patient Access Network Foundation were approached at baseline, 1 and 3 months post-CPA. We assessed the use of pt navigators, social workers, financial counselors, support groups, and transportation vouchers by pts. The outcomes were improvements in disease-specific HRQoL measures, global HRQoL measure (FACTG, lower values are worse) and improvement in FT, as measured by the COST (lower values are worse). Multivariable regression was used to identify whether these interventions were associated with the outcomes. Results: 308 pts with cancer were assessed at baseline (prior to CPA) and at 1 and 3 months after. 275 pts (89%) had an improvement in their FT over 3 months. A majority of these pts had multiple myeloma (MM, 86 pts, 28%). Navigators were used by 179 pts (42%), social workers by 106 (34%), financial counselors by 107 (35%), support groups by 94 (31%), and transportation vouchers by 50 (16%). None of these interventions increased the odds of FT or HRQoL improvement at the 0.05 significance level. Conclusions: The selected population of cancer pts who received CPA for their treatments had a significant improvement in FT over time. Yet, this improvement was not associated with additional interventions, suggesting CPA as the main intervention. The FT improvement was not clearly translated into significant HRQoL improvements, likely due to the multidimensional HRQoL construct (which includes other symptoms) versus the unidimensional aspect of a financial event. [Table: see text]