tbuckley/cabot-search huggingface dataset:
Mutational landscapes and PD-L1 expression in non-small cell lung cancer.
Authors: Kang Zhang, Guanghui Wang, Chao Guo, Xinyu Chen, Shiyue Zhang, Wenjing Wang, Ming Yao, Angen Liu
Journal: Journal of Clinical Oncology (2019)

8541 Background: Programmed death-ligand 1 (PD-L1) serves as a major predictive biomarker for immune checkpoint inhibitors in non-small cell lung cancer (NSCLC). However, the relationship between PD-L1 expression and genetic features of NSCLC remains unclear. The aim of this study was to explore the correlation between genetic profiles and PD-L1 expression in NSCLC. Methods: FFPE tumor and matched blood samples from 568 NSCLC (487 adenocarcinomas (ACAs) and 81 squamous carcinomas (SCAs)) patients were collected for NGS-based targeted panel sequencing. Genomic alterations including single nucleotide variations, short and long insertions/deletions, copy number variations and gene rearrangements were assessed. Tumoral PD-L1 expression was evaluated by immunohistochemical analysis (Dako 22C3 and 28-8). Results: The prevalence of PD-L1 expression was 9.9% with a ≥50% cutoff and 27.5% with a ≥1% cutoff. High PD-L1 expression (using a ≥1% cutoff) in tumor cells was significantly associated with mutations of MET (p &lt; 0.001), RET (p = 0.036), ROS1 (p &lt; 0.001), TP53 (p = 0.0013) and 11q13 amplification (p = 0.004), and was inversely correlated with EGFR mutations (p = 0.011). SOX2 and KLHL6 mutations were more frequent in SCAs (33.3% and 28.4%, respectively) than in ACAs (0.4% and 1%, respectively) and were adversely associated with PD-L1 expression in SCAs (p = 0.01, p = 0.004). Gene set 1 (GS1) mutations included EGFR, ALK, KRAS, BRAF, MET, RET, ROS1 and ERBB2 and gene set 2 (GS2) mutations included TP53, RB1, PTEN, APC and MYC. According to the mutation status of GS1 and GS2, 18 patients were classified as type I (GS1-, GS2-), 92 as type II (GS1-, GS2+), 202 as type III (GS1+, GS2-) and 256 as type IV (GS1+, GS2+). PD-L1 expression was higher in Type IV tumors than in type III (33.2% vs. 14.4%, respectively, p &lt; 0.001). Conclusions: We highlighted the genomic heterogeneity of NSCLC according to the mutation status of different gene sets. Our results indicate that patients with GS1 and GS2 gene mutations might correlate with higher PD-L1 expression. Our results help to understand the relationship between genomic features and PD-L1 expression and may be a potential guide for immunotherapy.
Correction to: Vaccination with nanoparticles combined with micro-adjuvants protects against cancer
Authors: Mona O. Mohsen, Matthew D. Heath, Gustavo Cabral-Miranda, Cyrill Lipp, Andris Zeltins, Marcos Sande, Jens V. Stein, Carsten Riether, Elisa Roesti, Lisha Zha, Paul Engeroff, Aadil El-Turabi, Thomas M. Kundig, Monique Vogel, Murray A. Skinner, Daniel E. Speiser, Alexander Knuth, Matthias F. Kramer, Martin F. Bachmann
Journal: Journal for ImmunoTherapy of Cancer (2019)

Following publication of the original article [1], the author reported an author's family name has been misspelled. Paul Engroff should be replace Paul Engeroff.Furthermore, there are two mistake in two affiliations: 9) Department of dermatology, University of Zurich, Bern, Switzerland and 10) Department of Oncology, University of Lausanne, Bern,Switzerland should be replace with 9) Department of dermatology, University of Zurich, Zurich, Switzerland.10) Department of Oncology, University of Lausanne, Lausanne, Switzerland.
Impact of next-generation sequencing on clinical outcomes in advanced EGFR-mutant lung cancer patients after resistance to osimertinib.
Authors: Jia-Tao Cheng, Jin-Ji Yang, Yi-Long Wu
Journal: Journal of Clinical Oncology (2019)

e20726 Background: Osimertinib is used to treat EGFR-mutant non–small-cell lung cancer (NSCLC) with acquired T790M mutation. Next-generation sequencing (NGS) is helpful to understand mechanisms of resistance to osimertinib. However, whether NGS after resistance to osimertinib has an impact on clinical outcomes of patients treated with subsequent treatments has been elusive. Methods: We retrospectively identified advanced, EGFR-mutant T790M positive NSCLC patients treated with the 2nd or further-line osimertinib from January 27th, 2015 to January 31th, 2019 at our institute. Genetic profiles and clinical outcomes were analyzed. These patients were divided into 2 groups based on NGS data after resistance to osimertinib. Progression-free survival1 (PFS1) was calculated from the start of osimertinib to progression or death. PFS2 was calculated from the start of subsequent-line treatment to progression or death. Objective response rate (ORR) of subsequent-line treatments was evaluated by RECIST1.1. Results: Among 187 patients treated with osimertinib, 66 had NGS data and 27 had no NGS data after progression. Maintained EGFR T790M was detected in 23 patients (34.8%), and loss of T790M was seen in 43 patients (65.2%). Mutations of EGFR C797S were detected in 12 patients (18.1% overall; 52.2% of those with retained T790M), 11 in cis with a maintained T790M, 1 in trans with a maintained T790M. There was no significant difference in median PFS1 between the maintained T790M group and the loss of T790M group (10.8 vs. 7.0 months, P = 0.085).The NGS group was treated with TKIs according to the results of NGS strictly (n = 36), the non-NGS group received chemotherapy or best supportive care (n = 11).There was a significant difference in median PFS2 between the NGS and non-NGS groups (5.4 vs. 2.9 months, P = 0.043). The ORR of the NGS group was significantly superior to that of the non-NGS group (16.2% vs 11.1%, P &lt; 0.001). Conclusions: NGS after resistance to osimertinib might favor clinical outcomes of advanced EGFR-mutant NSCLC patients. Further more investigations are warranted.
Comparison of mortality trends in geriatric and nongeriatric patients with salivary gland tumors.
Authors: muhammad Sarfraz Nawaz, Jigarkumar R. Parikh, Achuta Kumar Guddati
Journal: Journal of Clinical Oncology (2019)

e23026 Background: The treatment of salivary gland tumors has not changed significantly in the past two decades. However, its increased incidence in the geriatric population poses new challenges for their management. This study explores the incidence-based mortality (IBM) trends in the geriatric and non-geriatric population for the time period of 2000 to 2014 and compares the trends between races. Methods: Mortality data was extracted from the Surveillance, Epidemiology, and End Results (SEER) Database for the years 2000 to 2014. IBM for all stages of salivary gland tumors was queried and the results were grouped by age (geriatric vs. non-geriatric) and race (Caucasian/White, African American (AA)/Black, American Indian/Alaskan native and Asian/Pacific Islander). All stages and both genders were included in the analysis. T-test was used to determine statistically significance difference between various subgroups. Linearized trend lines were used to visualize the mortality trends between various subgroups (Geriatric vs. Non- geriatric and Caucasian vs. African American). Results: IBM for salivary gland tumors has worsened since 2000 to 2014 for both geriatric and non-geriatric patients (P &lt; 0.05), There was a statistically significant difference between these two groups in both Caucasian/White and AA/Black patients. Notably, the worst IBM rates were noted in non-geriatric AA/Black patients followed by non-geriatric Caucasian/White patients. However, there was no statistical difference in IBM between geriatric patients of Caucasian/White and AA/Black descent. Conclusions: The similarity in IBM for geriatric patients with salivary gland tumors in both Caucasian/White and AA/Black groups suggest that the effects of race may not be pronounced in the elderly population. The high rate of IBM in non-geriatric AA/Black patients may suggest environmental influence and warrants further study.
Evaluation of radiotherapeutic and immune-modulatory response to whole brain radiotherapy or stereotactic radiosurgery in patients with brain metastases from malignant melanoma treated with or without ipilimumab (ELEKTRA).
Authors: Jessica Cecile Hassel, Heiko Smetak, Martin Salzmann, Matthias Haefner, Denise Bernhardt, Ingrid Hülsmeyer, Alexander Enk, Juergen Debus, Philipp Beckhove
Journal: Journal of Clinical Oncology (2019)

e14104 Background: Immune checkpoint blockers have dramatically improved the survival of patients (pts) suffering from advanced metastasized melanoma. In pts with melanoma brain metastases (MBM) a combination with radiotherapy (RT) is routinely used. Methods: We prospectively included 106 pts with MBM in a non-randomized observational trial with 7 treatment cohorts. Patients in cohort 1-4 were treated with ipilimumab (+/- nivolumab) and either stereotactic (up to 3 MBM) or whole brain RT (≥ 4 MBM) before or after the start of immunotherapy. Cohort 5 and 6 included pts who received RT with an ipilimumab-free systemic treatment and cohort 7 pts were treated with ipilimumab (+/- nivolumab) and no RT. Primary endpoints were immunological response in the peripheral blood (FACS of T cell subsets, ELISpots against melanoma antigens) and radiological response, secondary endpoints were progression free and overall survival. Results: Included pts were in median 61 years old, 72% were male. At trial inclusion, 31% of pts had an elevated LDH. 39% of ipilimumab treated pts received combination therapy with nivolumab. Clinically, ipilimumab treated pts in the early RT groups had better responses of both intra- and extracranial disease (p = 0.04 for both). Multivariate analyses showed a better PFS for pts with early RT (p = 0.02) and normal LDH (p = 0.049). Type of radiation (p = 0.6) and immune therapy (p = 0.8) had no significant influence in this small cohort of pts. Immune monitoring revealed that ipilimumab leads to an increase in activated CD4+ and CD8+ T cells in the peripheral blood which was maintained in responding pts and higher in pts receiving early RT. Treg were not depleted in general but activated by ipilimumab. However, responders displayed a temporary decrease of Treg and activated Treg under treatment. An increase in the detection of melanoma antigens could be observed after 2 cycles of ipilimumab which was higher in pts with combined radioimmunotherapy compared to ipilimumab only. Conclusions: Preliminary data from this small observational trial might lead to a preference of a treatment sequence with radiotherapy first, followed by checkpoint inhibition in pts with MBM.
Evaluation of selective outcome reporting bias in efficacy endpoints in print and television advertisements for oncology drugs.
Authors: Cole Wayant, Greg Aran, Matt Vassar
Journal: Journal of Clinical Oncology (2019)

e18179 Background: Drug advertisements marketed to consumers and healthcare providers have been the subject of recent debate, and the efficacy endpoints that underpin these advertisements may sway perceptions of drug efficacy. Methods: Using the AdPharm database we extracted data for oncology drug advertisements printed or aired between March 1, 2017 and September 1, 2018. Our primary objective was to evaluate endpoints from television and print advertisements and endpoints from the corresponding published papers. A secondary objective is to identify the frequency of drug advertisements that are aired or printed while overall survival data is immature. Results: We included 74 advertisements for 34 unique oncology drugs and 22 unique indications. Print ads were most common (n = 66) and most print ads were targeted to healthcare providers (n = 55, 83.3%). The 74 advertisements were underpinned by 48 published clinical trials. The primary endpoint of the 48 underpinning trials was most often PFS (n = 25), followed by OS (n = 11) and ORR (n = 7). Primary endpoints of underpinning trials were not reported in 8 (8/74, 10.8%) advertisements. Statistically significant endpoints were reported more often than nonsignificant endpoints (RR 1.42; 95% CI, 1.26 - 1.60). Thirty advertisements (42.3%) ran while OS data was immature. When OS and PFS were statistically significant, they were reported at a significantly higher rate than when not reported (each P &lt; .001). ORR was not preferentially reported based on its statistical significance (RR 1.33; 95% CI, .94 - 1.87). Conclusions: Oncology drug advertisements appear to preferentially report statistically significant endpoints, which is highly suggestive of selective outcome reporting bias. By reporting only endpoints that achieve statistical significance, advertisers may encourage misconceived notions about a drug’s efficacy profile.
Comparison of preoperative serum VEGF in leiomyosarcoma and uterus myomatosus patients: A proof of concept study.
Authors: Amelie De Gregorio, Inga Bekes, Nikolaus de Gregorio, Sophia Andres, Diego Hoffmeister, Tatjana Swerev, Thomas W. P. Friedl, Wolfgang Janni, Florian Ebner
Journal: Journal of Clinical Oncology (2019)

e17117 Background: The preoperative differentiation of a uterine fibroid from a sarcoma is still a pending clinical problem. Currently with the suspicion of a sarcoma (LMS) the more invasive open surgical approach is recommended to minimise the risk of LMS fragmentation and distribution. In a minority of cases, a malignancy is indicated by clinical suspicion, pre-surgical imaging or routine serum blood samples (SBS). Our hypothesis postulates higher VEGF levels in LMS compared to fibroid patients in the pre-surgical SBS. To assess this hypothesis, SBS were taken from patients with the clinical suspicion of LMS after informed consent and analysed after histology confirmed the diagnosis. Methods: Case series of patients with suspected LMS over a 4year time period. Analysis was performed via SBS collected from LMS- and fibroid patients before surgery. Serum VEGF protein was measured by ELISA. The final tumor histology was obtained from the report of the institutional pathologist. VEGF-serum levels were then compared between fibroid and LMS patients using the non-parametric Mann-Whitney U test. Results: 25 patient SBS were collected prior to surgery. In 9 cases the histopathology confirmed a LMS, with heterogeneous pTNM classifications. On average, VEGF serum levels were higher in the LMS patients as compared to the fibroid patients (628,96 pg/ml vs 351,91 pg/ml; further statistics see Table 1); however, the difference was not statistically significant (Mann-Whitney-U Test, p = 0.141). Conclusions: This proof-of-concept study with a small sample size of pre-surgical SBS indicates that VEGF serum levels may be increased in patients with histologically confirmed LMS; however, larger sample sizes are needed to validate our findings. If additional studies confirm a pronounced increase in pre-surgical serum VEGF levels in LMS patients, serum VEGF levels might routinely be used to assess the risk for a LMS in patients presenting with clinical uterine fibroids. [Table: see text]
Real-world experience and molecular features of response to immune checkpoint blockade in patients with recurrent small cell lung cancer.
Authors: Wei-Chu Victoria Lai, Hira Rizvi, Jacklynn V. Egger, Andrew J. Plodkowski, Michelle S. Ginsberg, Mark G. Kris, Amanda Beras, Natasha Rekhtman, John T. Poirier, Matthew David Hellmann, Charles M. Rudin
Journal: Journal of Clinical Oncology (2019)

8556 Background: Immune checkpoint blockade (ICB) is now a routine component of treatment in recurrent small cell lung cancer (SCLC). We evaluated the response to ICB in patients (pts) with recurrent SCLC and genomic features of response using next-generation sequencing (NGS). Methods: Pts with recurrent SCLC treated with ICB were identified. The majority of pts were treated outside of a clinical trial to focus emphasis on the real-world experience. Tumor mutation burden (TMB) and the landscape of somatic variants were determined by targeted NGS using MSK-IMPACT. Objective response rate (ORR) to ICB was determined using RECIST v1.1. PFS and OS were measured from the start of ICB and analyzed using Kaplan-Meier. Results: Between December 2013 and October 2018, 108 pts with SCLC were treated with ICB (57 subjected to NGS). Pts received PD-1 monotherapy alone (n = 28) or in combination with CTLA-4 blockade (n = 80). Median line of therapy was 2 (range 1-6). ORR was 14% (15/108, 95% CI 8-22%). From the start of ICB, median PFS was 1.4 months in non-responders and 10.8 months in responders (HR 0.2; 95% CI 0.13-0.32). Median OS was 6.3 months in non-responders and undefined in responders (range 8-44 months) (HR 0.26, 95% CI 0.16-0.44). Four responders remain on ICB treatment. TMB in the ICB-treated cohort was similar to that of an unselected cohort (n = 233) of SCLC (median 8.8 Mt/MB vs 8.2 Mt/MB, p = 0.71). Clinical benefit was enriched among those with a higher TMB (upper vs middle/lower tertile PFS HR 0.48, 95% CI 0.28-0.84, p = 0.01 and ORR 26% [5/19] vs ORR 8% [3/38]). Rates of whole genome duplication and commonly altered genes in SCLC ( TP53, RB1, KMT2C/D, NOTCH1/2/4, PTPRD, APC) were similarly distributed across responders and non-responders. Completion of whole-exome sequencing and PD-L1 testing is in progress. Conclusions: In pts with recurrent SCLC receiving routine clinical care, the ORR to ICB is comparable to reports from clinical trials. A high TMB was associated with a longer median PFS and better response. Further investigation into the genomic landscape of recurrent SCLC is needed to identify biomarkers predictive of response to ICB.
Erratum: Prolonged survival and decreased abnormal movements in transgenic model of Huntington disease, with administration of the transglutaminase inhibitor cystamine (Nature Medicine (2002) 8 (143-149))
Authors: M. V. Karpuj, M. W. Becher, J. E. Springer, D. Chabas, R. Pedotti, S. Youssef, D. Mitchell, L. Steinman
Journal: Nature Medicine (2002)
Scope of practice of advanced practice providers (APP) in US community oncology.
Authors: Andrew Klink, Bela Bapat, Yolaine Smith, Chadi Nabhan, Bruce A. Feinberg
Journal: Journal of Clinical Oncology (2019)

6646 Background: Oncology practices are increasingly employing nurse practitioners (NPs) and physician assistants (PAs) known collectively as advanced practice providers (APPs) to improve practice workflow, increase efficiency, and enable physicians to focus on complex patient care. Understanding variations in scope of practice for APPs may help establish a benchmark against which future changes are measured. Methods: US community physicians responded to a web-based survey from Sep to Nov 2018. Physicians were asked how frequently their APPs performed certain tasks on a 5-point scale (i.e., never, occasionally, sometimes, frequently, and always). Responses have been summarized using descriptive statistics. Results: In this study, 163 physicians were surveyed, most (81.0%, n = 132) used APPs in their practice. Among physicians using APPs, 91.7% (n = 121) used NPs and 49.2% (n = 65) used PAs. Most physicians stated that APPs were frequently/always involved in providing patient education (84.1%), ordering imaging and laboratory studies (68.9%), and/or making supportive care decisions (62.1%). Over 85% (57.6%-59.8% occasionally/sometimes; 28.0%-28.8% frequently/always) of physicians agreed that APPs discussed imaging reports and end of life (EOL) care (57.6% occasionally/sometimes, 28.8% frequently/always) with patients. Regarding procedures: 51.9% (28.0% occasionally/sometimes; 24.1% frequently/always) responded that APPs performed bone marrow biopsies and intrathecal chemotherapy. Regarding systemic therapy: 68.2% (58.3% occasionally/ sometimes; 9.8% frequently) allowed APPs to modify existing regimen e.g., dose/schedule change; 39.4% responded that APPs made decisions about new therapy selection. Conclusions: While substantial variation in the role of APPs in community oncology practices was observed, similar themes emerged. APPs appear to be integral in patient education, ordering laboratory and imaging studies, and discussing EOL care. Fewer are involved in managing and selecting supportive care and systemic therapy. Longitudinal and longer follow up are warranted to ascertain whether the scope of these practices change over time.
Abstract 17324: Associations Between Individual Saturated Fatty Acid Intake and Risk of Coronary Heart Disease Among American Men and Women
Authors: Geng Zong, Anne Wanders, Alssema Marjan, Peter Zock, Qi Sun
Journal: Circulation (2015)

Dietary intervention studies report neutral effects of stearic acid (18:0) on blood lipids, compared with lauric acid (12:0), myristic acid (14:0) and palmitic acid (16:0). Evidence from observational studies on the associations between intakes of individual saturated fatty acids (SFAs) and risk of CHD is scarce. We prospectively followed 72,102 women in the Nurses’ Health Study (1984-2010) and 42,874 men in the Health Professionals Follow-Up Study (1986-2010) who were free of diabetes, cardiovascular disease, and cancer at baseline. Diet was assessed by validated food-frequency questionnaire and updated every 4 years. Baseline percentages of energy from total and major 4 subgroups (4:0-10:0, 12:0-14:0, 16:0, and 18:0) of even-chain SFA, were 11.8%, 0.6%, 1.3%, 6.6%, and 3.3% for women, and 10.8%, 0.5%, 1.1%, 6.1%, and 3.1% for men. Spearman correlations among baseline individual SFA intakes ranged from 0.43 (between 4:0-10:0 group and 18:0 in both cohorts) to 0.92 (between 16:0 and 18:0 in women). We generated 18:0 residual by regressing 18:0 on intakes of other SFAs. During 2.6 million person-years of follow-up, 6,843 incident CHD cases were documented. In the multivariate model, intakes of 4:0-10:0, 12:0-14:0, and 16:0, but not 18:0, were positively associated with risk of CHD (P&lt;0.05). After further adjusting for dietary factors, hazard ratios (95% confidence interval, HR[95%CI]) of CHD per 1% energy increase were 1.10 (0.98, 1.22; P=0.10) for 4:0-10:0, 1.11 (1.03, 1.18; P=0.003) for 12:0-14:0, 1.09 (1.04, 1.13; P&lt;0.001) for 16:0, and 0.98 (0.94, 1.01; P=0.22) for 18:0. The HR per 0.2 increase in the ratio of polyunsaturated fat (PUFA) to SFA was 0.93 (0.90, 0.96; P&lt;0.001). The HRs of CHD risk per 1% of energy PUFA replacing SFA were 0.92(0.85,0.99; P=0.03) for 12:0-14:0 and 0.91(0.87,0.95;P&lt;0.001) for 16:0; but PUFA replacing 4:0-10:0 or 18:0 were not associated with CHD risk: HRs were 0.98(0.86,1.11; P=0.74) and 0.97(0.93,1.01; P=0.19), respectively. Our findings indicate that while 12:0-16:0 were associated with increased CHD risk, short-to-medium-chain SFA and 18:0 were not. However, our results need to be interpreted with caution because saturated fatty acids share common food sources and are highly correlated.