tbuckley/cabot-search huggingface dataset:
Evaluating sociodemographic, behavioral and psychologic disparities in 918 head and neck cancer survivors.
Authors: Andrew T Day, Anupama Vasudevan, Erin Wynings, Sanjana Balachandra, Saad A. Khan, Baran D. Sumer, Caitlin C. Murphy
Journal: Journal of Clinical Oncology (2019)

e17541 Background: Minority race, low-income status, tobacco dependence, alcohol abuse, and depression negatively impact overall survival among head and neck cancer (HNC) survivors. Understanding the prevalence and associations of these factors will inform the development of targeted HNC survivorship interventions. Methods: We pooled cross-sectional samples of HNC patients participating in the National Health Interview Survey from 1997-2016. Descriptive statistics were used to compare: 1) HNC survivors to age- and sex-matched adults without cancer (1:4) and 2) behavioral and psychologic conditions in HNC survivors by income status. Results: Mean age of the 918 HNC survivors was 64.8 years and 65.2% were male. Most HNC survivors were non-Hispanic white (85.3%); 7.6% were non-Hispanic black, 4.9% were Hispanic, and 2.2% were of other race and ethnicity. A substantial portion reported income below the poverty threshold (13.9%) and 5.0% consumed &gt; 14 alcoholic drinks per week. Compared to adults without cancer (n = 3,612), a higher proportion (p &lt; 0.05) of HNC survivors (n = 903) exhibited: current tobacco use (21.3% vs 17.4%); serious psychological distress (Kessler-6 score of ≥13; 6.9% vs 3.9%); depressive symptoms most or all of the time (14.1% vs 8.9%). There were particularly striking differences in the prevalence of these factors among HNC survivors by income. Specifically, a higher proportion of HNC survivors with income below the poverty threshold (n = 133) were non-Hispanic black (15.5% vs 5.8%) and exhibited current tobacco use (42.9% vs 18.6%), serious psychological distress (17.4% vs 5.7%) and depressive symptoms most or all of the time (25.3% vs 12.7%) compared to those at or above the poverty threshold (n = 646; all p &lt; 0.05). Conclusions: HNC survivors experience a disproportionate burden of behavioral and psychologic health conditions compared to age- and sex-matched adults without cancer. Low-income status exacerbates these disparities. HNC survivors, especially those in low-income settings, require comprehensive survivorship care targeting these needs.
The clinical outcome of renal cell carcinoma with rhabdoid and sarcomatoid differentiation.
Authors: Arash Samiei, Pritam Tayshetye, Angela Sanguino, Ralph Miller, John Lyne, Jeffrey Cohen, Shifeng Mao
Journal: Journal of Clinical Oncology (2019)

e16083 Background: Renal cell carcinoma (RCC) with rhabdoid (RD) or sarcomatoid differentiation (SD) represents high-grade RCC with an aggressive clinical behavior. Little success has been reported in treating these patients. No standard management has been established and there is a lack of insight in these entities because of their relatively low incidences. We reviewed a cohort of RCC patients with RD and SD and correlated the pathologic features with their clinical outcomes. Methods: A retrospective study of RCC patients with RD or SD feature at a single center from 2008 to 2016 was conducted. Patient characteristics, pathology findings, clinical management, and survival data were collected. Results: A total of 36 RCC patients, with median age of 65 [47-88] years old, were included. The male-to-female ratio was 2.6:1. Among them, 24 were with pure SD and 12 with RD (7 pure and 5 mixed features). At diagnosis, 14 patients (38.9%) presented with stage IV disease. The median follow-up was 21 [2-53] months. Of the 36 patients, 24 developed metastasis, including 16/24 (67%) with SD, 4/7 patients (57%) with pure RD, and 4/5(80%) with mixed features. Mortality rate was 79% for SD, 75% for RD and 100% for those with mixed features. The overall survival was 23, 22, and 13 months for SD, pure RD and those with mixed features, respectively. 12 patients were treated with tyrosine kinase inhibitors (TKI) in first-line and 7 with immune checkpoint inhibitors (ICI) in the second or third line setting. Longer duration of treatment was seen with ICI than TKI, 12.8 [5-25] vs 5.9 [1-18] months (p = 0.03). Partial response was seen in 6/7 (86%) and stable disease in 1/7 (14%) patients treated with ICI. No survival benefit was seen in patients treated with TKI alone (p = 0.60). Patients received ICI had significantly prolonged overall survival compared to those received TKI alone, 31.4 vs 17.8 months (p &lt; 0.001). Conclusions: The presence of RD or SD portends poor outcome in RCC with conventional management, especially in those with mix of both features. However, these patients had exceptionally high response and improved survival if treated with ICI. A prospective study using ICI focusing on RCC patients with these pathologic features is warranted and could provide hope for such dismal entities.
Ten-fold increase in genetic testing in pancreatic and metastatic prostate cancer with implementation of point of care (POC) testing.
Authors: Heather Symecko, Rebecca Mueller, Kelsey Spielman, Melissa Batson, Stacy Pundock, Jada G. Hamilton, Mark E. Robson, Susan M. Domchek
Journal: Journal of Clinical Oncology (2019)

1506 Background: Germline genetic testing (GT) for cancer susceptibility is recommended for pancreatic and advanced prostate cancer patients, due to potential implications for targeted therapies and risk assessment of family members. Traditional cancer GT programs may create barriers for certain patient populations. To more effectively integrate testing into standard oncology care POC GT was introduced in early 2018 in a joint protocol with Memorial Sloan Kettering Cancer Center. Here we report pre and post POC referral and testing numbers at the University of Pennsylvania. Methods: Patients with metastatic prostate or pancreatic cancer were ascertained through their GU/GI oncologist onto an IRB approved protocol and shown an educational video about GT by research staff who obtained informed consent and facilitated biospecimen collection. Genetic counselors returned results and provided post-test counseling by phone. To evaluate the impact of this model on the uptake of GT services, the number of patients who were referred to and proceeded with GT was compared before and after study initiation. Results: In 2017, 77 patients were referred to genetics of which 45 underwent genetic counseling and testing. Twenty-nine (38%) did not complete genetic counseling or testing, and 3 later underwent testing through the POC study. Since the study launched in 2018, 407 patients were referred and underwent testing through the study. This represents a ten-fold increase in patients who underwent GT. Conclusions: Comparing uptake of GT services before and after study initiation suggests that a POC model with abbreviated pre-test education and post-test genetic counseling by phone is a possible solution to barriers of traditional genetic counseling, increasing physician referrals and uptake of testing by patients. This approach allows for more timely access to genetic information that may impact treatment strategies and medical management of family members. Clinical trial information: pending. [Table: see text]
Comparison of biomarkers among 34,855 GI cancer samples show heterogeneity of tumor types.
Authors: Shaheenah S. Dawood
Journal: Journal of Clinical Oncology (2019)

e14287 Background: Recent data indicate that biomarker driven use of targeted therapy and I/O-therapy among patients with GI cancer is associated with improved outcome. The presence of biomarkers varies broadly between different GI tumor types, highlighting the importance of comprehensive molecular profiling.To analyze the presence of various alterations in GI cancer samples of a large database, comparing congruency between various tumor types. Methods: A retrospective data analysis of 34855 GI cancer patients profiled at CARIS Life Sciences obtained from Jan 1 st 2010 till Sep 14 th 2018 was performed. GI tumors were classified as : CRC, esophageal/gastric/GIST, small intestine, pancreatic/hepatobiliary/liver. Technologies used to analyze the biomarkers: IHC for PD-L1, MMR and Her2, and DNA-NGS for EGFR, BRAF, KRAS, NRAS, MET-CNV, TMB, MSI, POLE and BRCA1/2. Results: Median age was 61 (range 18-89 years). 51.5% was CRC (n = 18047), 15.5 % was esophageal /Gastric/GIST (n = 5470), 3% was small intestinal cancer (n = 886) and 30% was pancreatic/hepatobiliary/liver cancer (n = 10452). Information on biomarkers was available from 2931 cases for MET amplification to 28536 for RAS information. Overall, the most common finding was a pathogenic RAS-mutation (either KRAS or NRAS) in 7650 cases (26.81%), the rarest one was a mutation in EGFR in 12 cases (0.06%). Higher rate of HER2 amplification was observed among pts with esophageal/gastric/GIST tumors (6.5%) in comparison to tumors at other GI sites ( ~1.5%). High TMB was seen among patient with CRC and small intestine tumors (~7%) while it was lowest among pancreatic cancer (1.8%). Compared to other GI sites lower MSI /MMR deficiency rates were observed in pancreatic /hepatobiliary tumors, significantly higher PD-L1 positivity was observed in gastrooesophageal cancer types, increased MET-amplifications in gastrooesophageal and small intestinal cancer types and lower RAS-mutation rate in gastrooesophageal cancer. Conclusions: Molecular profiling analyzing druggable biomarkers can help identify patients with increased likelihood for benefit from immune-checkpoint-inhibitors and targeted therapies. Further investigations are needed to evaluate the different findings in various GI cancer types.
Prognostic impact of immune gene expression signature and tumor infiltrating immune cells in localized clear cell renal cell carcinoma
Authors: Pooja Ghatalia, Jennifer Gordetsky, Fengshen Kuo, Essel Dulaimi, Kathy Q. Cai, Karthik Devarajan, Sejong Bae, Gurudatta Naik, Timothy A. Chan, Robert Uzzo, A. Ari Hakimi, Guru Sonpavde, Elizabeth Plimack
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> The tumor immune microenvironment has become the focus of research in clear cell renal cell carcinoma (ccRCC) due to its important role in immune surveillance post nephrectomy. This study investigates the correlation of tumor infiltrating immune cell characteristics with rates of recurrence following surgery in localized ccRCC. <h3>Methods</h3> We morphologically identified and scored tumor infiltrating lymphocytes (TILs) in hematoxylin and eosin (H&amp;E) stained slides of patients with localized ccRCC (stage ≥T1b excluding stage IV). The University of Alabama at Birmingham (UAB) dataset (<i>n</i>&nbsp;= 159) was used to discover and the Fox Chase Cancer Center (FCCC) dataset (<i>n</i>&nbsp;= 198) was used to validate the results of morphologic immune cell analysis. We then performed gene expression analysis using the Immune Profile panel by NanoString in the UAB cohort and identified immune cells and pathways associated with recurrence, followed by validation in the Cancer Genome Atlas (TCGA) ccRCC dataset. Infiltrating immune cell types were identified by gene expression deconvolution. <h3>Results</h3> The presence of TILs identified by morphology correlated with higher T cell, Th1, CD8+ T and Treg gene signatures. Recurrence was associated with lower T cells and higher neutrophils. Higher Teffector (Teff)/Treg ratio correlated with lower rate of recurrence and was validated in the TCGA dataset. Genes associated with adaptive immune response were downregulated in tumors that recurred. Unsupervised hierarchical clustering identified a subset of patients with over-expression of adaptive response genes including <i>CD8, CD3, GZMA/B, PRF1, IDO1, CTLA4, PDL1, ICOS</i> and <i>TIGIT.</i> These patients had higher morphologic lymphocyte infiltration and T cell gene expression. Higher levels of TILs identified by morphology correlated with higher rates of recurrence in our discovery dataset but not in our validation set. <h3>Conclusions</h3> Recurrence of ccRCC following surgery was associated with lower T cell infiltrate, lower adaptive immune response and higher neutrophil gene expression. Presence of higher Teff/Treg ratio correlated with lower recurrence.
Publication rate of registered clinical trials in lung cancer.
Authors: Ghassan Al-shbool, Hira Latif, Saira Farid, Anqi Yin, Jaeil Ahn, Giuseppe Giaccone, Chul Kim
Journal: Journal of Clinical Oncology (2019)

e18211 Background: Clinical trials play a crucial role in shaping oncology practice. Publishing results of clinical trials is key to reducing publication bias. Lung cancer is the leading cause of cancer-related mortality in the U.S. We assessed the publication rate of registered lung cancer clinical trials. Methods: ClinicalTrials.gov was searched to identify registered lung cancer clinical trials with study completion date between 1/1/2000 and 8/7/2016. Interventional phase II and III clinical trials involving patients ³ 18 years old with a recruitment status of completed or terminated were included. Using National Clinical Trial identifier and keywords including the clinical trial name, three databases (PubMed, Google Scholar, EMBASE) were queried to assess the publication status of each trial. We analyzed the publication rate among the identified clinical trials and predictors of publication. Results: A total of 1293 clinical trials were identified. Among 1037 completed clinical trials, 690 (66.5%; 193,587 patients) were published in peer-reviewed journal, while 347 (33.5%; 51,505 patients) were unpublished. Industry sponsored, non-randomized, and single-center studies were less likely to be published with odds ratio 0.52 (95% CI: 0.28-0.97), 0.67 (0.45-1.00), and 0.36 (0.25-0.51), respectively. Among the 347 unpublished completed trials, 75 (21.6%) trials reported the results as meeting presentation and 63 (18.2%) trials posted the results only on ClinicalTrials.gov. Among 256 terminated clinical trials, 72 (28.1%; 19,858 patients) were published in peer-reviewed journal, while 184 (71.9%; 10,259 patients) were unpublished. Among the 184 unpublished terminated trials, 19 (10.3%) trials reported the results as meeting presentation and 70 (38.0%) trials posted the study results only on ClinicalTrials.gov; reporting of primary outcome was incomplete in 50 (71.4%) of 70 studies whose results were only available on ClinicalTrials.gov. Conclusions: A significant proportion of registered lung cancer clinical trials remain unpublished, raising the concern of publication bias in the field of thoracic oncology.
Three versus six months adjuvant FOLFOX or CAPOX for high risk stage II and stage III colon cancer patients: The efficacy results of Hellenic Oncology Research Group (HORG) participation to the International Duration Evaluation of Adjuvant chemotherapy (IDEA) project.
Authors: Ioannis Sougklakos, Ioannis Boukovinas, Spyros Xynogalos, Stylianos Kakolyris, Nikolaos Ziras, Michael Vaslamatzis, Athanasios Athanasiadis, Alexandros Ardavanis, Nikolaos E. M. Androulakis, Athina Christopoulou, Paris Makrantonakis, Iliada Bompolaki, Charalampos Christofyllakis, Nikolaos K. Kentepozidis, Christos E. Emmanouilides, Charalambos Kouroussis, Efthimios Prinarakis, Ageliki Kalisperi, Dimitrios Mavroudis, Vassilis Georgoulias
Journal: Journal of Clinical Oncology (2019)

3500 Background: The IDEA aimed to investigate whether a 3-month (3M) of oxaliplatin/fluoropyrimidines-based adjuvant chemotherapy (CT) is non-inferior to the 6-month (6M) in 3-year disease free survival (DFS) in stage high risk stage II and in stage III colon cancer (CC). Methods: HORG-IDEA randomized patients between 3M and 6M of CT with FOLFOX4 or CAPOX with primary end point the 3 years DFS (3yDFS). Results: In total 1121 patients, 413 with high risk stage and 708 with stage IIICC, were randomized between May 2009 and October 2015. The median follow-up was 67 (38-126) months. There were 79 DFS events (43 in 3M and 38 in 6M arm) in high risk stage II patients leading to 3yDFS rate of 82.7 and 83.4% for 3M and 6M, respectively (HR: 1.05; 95%CI: 0.68-1.63, p = 0.829). Similarly, 214 DFS events (161 in 3M and 153 in 6M arm) has been recorded in stage III patients, leading to a 3yDFS rate of 72.9% in the 3M vs. 74.1% in the 6M (HR = 1.06; 95%CI: 0.81–1.42, p = 0.622). For high risk stage II patients receiving FOLFOX4, 3yDFS rate was 76.7% in the 3M vs.79.3% in the 6M (HR = 1.21; 95%CI: 0.54–2.70 p = 0.641). For high risk stage II patients receiving CAPOX 3-year DFS rate was 85.4% in the 3M vs. 83.8% in the 6M (HR = 0.99; 95%CI: 0.59–1.67 p = 0.968). For stage III CC patients receiving mFOLFOX6, 3-year DFS rate was 71.5% in the 3M vs.77.3% in the 6M (HR = 1.18; 95%CI: 0.74–1.86 p = 0.479). For stage III CC patients receiving CAPOX 3-year DFS rate was 74.5% in the 3M vs. 74.7% in the 6M (HR = 0.99; 95%CI: 0.70–1.44 p = 0.991). Conclusions: The results of the HORG-IDEA study are in line with those of the global IDEA project, indicating that 3yDFS is depended on the administered adjuvant regimen, and the choice of regimen and duration should be personalized. Clinical trial information: NCT01308086.
A phase I dose escalation and dose expansion study of the anti-programmed cell death-1 (PD-1) antibody AK105.
Authors: Dusan Kotasek, Jermaine Coward, Paul L. de Souza, Craig Underhill, Xiaoping Jin, Baiyong Li, Yu Xia, Amy Prawira
Journal: Journal of Clinical Oncology (2019)

e14006 Background: AK105 is a humanized IgG1 mAb that blocks PD-1 binding to PD-L1 allowing T-cells to recognize and kill tumor cells. Key attributes of AK105 include antibody engineering to eliminate Fc mediated effector function, and a slower off-rate on antigen binding resulting in improved receptor occupancy (RO). These features offer more robust biological effect and enhance anti-tumor activity of AK105. Methods: A multicenter, Phase I, open-label dose escalation and expansion study in solid tumors (NCT03352531) began in Dec 2017, evaluating the safety and efficacy of AK105 administered IV q2w till confirmed progression (RECIST v1.1). For dose escalation, pts were enrolled at dose cohorts of 1, 3, and 10 mg/kg. Expansion of AK105 at the RP2D of 200 mg q2w is ongoing in pts with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma; esophageal squamous-cell carcinoma; hepatocellular carcinoma (HCC); microsatellite instability-high (MSI-H) colorectal cancer. Results: As of 1 Feb, 2019, 34 pts (median age 66.5 years [30–79], female 44%, ECOG 0/1 ([68%/32%]) in cohorts of 1 mg/kg (n = 3), 3 mg/kg (n = 6), 10 mg/kg (n = 7), and 200 mg q2w (n = 18), received a median of 5 (1–29) doses of AK105. No DLTs were reported. Treatment-related adverse events (TRAEs) occurred in 41% of pts (G3 in 12% [4/34], no G4, treatment interruption in 9% [3/34]). Most frequent TRAEs ( &gt; 5%) were hyperthyroidism (9%), hypothyroidism (6%), fatigue (6%), and rash (6%). PD-1 RO analysis showed that pts maintained full occupancy ( &gt; 80%) for all dose levels. Of 25 evaluable heavily pretreated pts, ORR was 24% (6/25; 29% [4/14] in dose escalation and 18% [2/11] in expansion phase) and disease control rate (DCR) was 56% (14/25). Five responses are confirmed and ongoing (HCC, pancreatic carcinoma, cholangiocarcinoma, GBM, gastric adenocarcinoma), one is pending confirmatory scan (GEJ). Conclusions: The RP2D obtained from the dose escalation phase, reported safety profile and encouraging antitumor activity of AK105 supports continued clinical development, which include: pivotal studies in classic Hodgkin lymphoma and nasopharyngeal carcinoma, phase 2/3 combination studies with chemotherapy in NSCLC and combination study with anlotinib, a multi-targeting tyrosine kinase inhibitor in HCC. PD analysis is ongoing and expansion is ongoing at the RP2D. Clinical trial information: NCT03352531.
High spatiotemporal heterogeneity, clonal selection and neoantigen evolution in acquired sorafenib-resistant patient-derived xenograft models of hepatocellular carcinoma.
Authors: Xin-Rong Yang, Bo Hu, Jian Zhou, Jia Fan
Journal: Journal of Clinical Oncology (2019)

e15641 Background: Patient-derived xenograft (PDX) models have been regarded as valuable preclinical models for oncology drug development and exploring underlying mechanism of drug resistance. As the standard treatment option for advanced hepatocellular carcinoma (HCC), the survival benefit of sorafenib is modest. Even among those who initially responded well to sorafenib treatment, most patients ultimately develop progressive disease owing to acquired drug resistance. Understanding how selective pressure from sorafenib directs the evolution of HCC and shapes its clonal architecture is a central biological question with important clinical implications to combat acquired drug resistance. Methods: Three sorafenib-resistant PDX models were generated by continuous sorafenib treament for more than six months. Whole exome sequencing (WES) and RNA sequencing were performed. The subclone of mutation, fusion genes, and the evolving landscape of tumor neoantigens were further explored. Finally, the antitumor efficacy of recombinant mouse PD-1 antibody was evaluated in sorafenib resistance syngeneic tumors model by immune-competent C57BL/6J mice with Hepa 1-6. Results: High spatiotemporal heterogeneity was observed in engraftment among pre- and post- sorafenib resistance in established acquired-resistance PDX models. Clonal selection on engraftment was observed in established acquired-resistance PDX models. There are many high expressed genes, which showed subclone expansion with the emergence of sorafenib resistance. There is vary difference of neoantigens between pre- and post-resistance engraftment as well as sampling points in same tissues. It was presented that a high burden of clonal neoantigens in sorafenib resistant tissues (P &lt; 0.05), while there has no difference in tumor mutation burden. Moreover, the intra-tumor heterogeneity upon the neoantigen landscape was much bigger than that upon tumor mutation burden. We found that fusion subclone sizes were increased significantly after sorafenib resistance (P &lt; 0.05). Finally, the antitumor efficacy of recombinant mouse PD-1 antibody was confirmed in sorafenib resistance syngeneic tumors mice model (P &lt; 0.001). Conclusions: High spatiotemporal heterogeneity, clonal selection and neoantigen evolution was observed in acquired sorafenib-resistant PDX model of HCC. Immunotherapy such as immune checkpoint inhibitors might be a promising strategy for HCC patients with acquired sorafenib resistance. .