tbuckley/cabot-search huggingface dataset:
Feasibility and clinical value of circulating tumor DNA testing in patients with gastroesophageal adenocarcinoma.
Authors: Madiha Iqbal, Pashtoon Murtaza Kasi, Kabir Mody
Journal: Journal of Clinical Oncology (2018)

e16045 Background: Gastroesophageal (GE) adenocarcinoma is one of the leading causes for cancer and mortality worldwide. Most patients are diagnosed at an advanced stage. Liquid biopsy or circulating cell free tumor DNA (ctDNA) testing has emerged as promising prognostic and predictive biomarker patients with advanced malignancies including GE adenocarcinoma. Methods: At Mayo Clinic Florida (MCF), we did a small pilot of testing advanced and metastatic gastroesophageal (GE) adenocarcinoma. The platform used is the Guardant health’s Guardant360 panel – which reports single nucleotide variants (SNVs) in 73 genes, gene copy number amplifications in 18 genes, fusions/rearrangements in 6 genes as well as indels in 23 genes. Results: Table 1 shows the data regarding patients who were treated at MCF. All patients were tested at the time of initial consultation. Patients who continued their treatment at MCF received serial testing (Patient 3 and 5), which was done at the time of clinical progression. Clinically relevant mutations were detected with the help of liquid biopsy with some aberrations having clear therapeutic implications like the HER-2. These were compared to results from tissue based tumor testing. Conclusions: CtDNA testing is a non-invasive and feasible tool that has the potential of being integrated into the care of patients with GE adenocarcinoma by providing insights into actionable targets and mechanisms of resistance on treatment. Table 1:. Circulating tumor DNA testing and serial evaluation in patients gastroesophageal adenocarcinoma Date liquid biopsy done Level of ctDNA (%) Aberrations detected Patient 1 5/19/17 6.3% TP53,APCHER2/Neu Patient 2 6/19/17 0.1% TP53 Patient 3 5/15/17à7/13/17 1.9%à6.4% TP53,ROS1,PTEN,KRAS,CCEN1,BRCA2 Patient 4 7/18/17 2.4% GNAS,TP53,NF1 Patient 5 9/21/17à11/24/17 2.3%à7.1% CTNNB1,PIK3CA,ARID1A,TP53
Landscape of osimertinib resistant mutations between the two common subtypes of EGFR 19del or L858R in NSCLC.
Authors: Yan Zhang, Jun Zhao, Renhua Guo, Gen Lin, Li Liu, Chenchen Zhu, Naixin Liang, Huaxia Yang, Wen xian Wang, Pingping Dai, Yan-Fang Guan, Ling Yang, Xin Yi, Xuefeng Xia
Journal: Journal of Clinical Oncology (2018)

12108 Background: Acquired EGFR mutations (C797, L792, G796) co-occurring with T790M were reported to lead the resistance to osimertinib. It was reported that for advanced NSCLC patients, exon 19 deletion (19del) might be associated with longer PFS compared to L858R mutation accepted EGFR-TKIs therapy. In this study, we try to analyze the difference of the resistant mutation spectrum in patients accepted osimertinib treatment carrying these two types of mutations. Methods: Using targeted gene capture and next-generation sequencing technologies, we analyzed the somatic mutations in 110 NSCLC patients (pts) that were clinically resistant to osimertinib. Results: All of the 110 patients had an EGFR activating mutation (19del in 64 pts and L858R in 46 pts) and 104 were EGFR T790M positive. EGFR mutations which may lead to the acquired resistance of osimertinib were identified in 52.7% (58/110) patients, including C797S (43 pts), C797G (6 pts), L792H (6 pts), L792V (2 pts), G796S (3 pts), G796C (1 pts), L718V (4 pts), L718Q (7 pts), and 18 patients had multi-clonal resistant mutations. In all analyzable patients, at least one resistant mutation was identified in cis with T790M, and two of them also carrying an in trans mutation who were also co-existent with L858R. No patient had only in trans mutation in our study. The resistant mutation were more frequently detected in 19del group than in L858R (62.5% vs 39.1%, p= 0.015), with 21.9% vs 10.9% patients had mult-clones and 15.6% vs 8.7% EGFR amplification. These may due to the larger drug selection pressure from longer treatment of 19del group. Bypass or downstream co-occurring activating mutations detected were EML4-ALK rearrangement (1 pts), MET amplification (1 pts), RET-CCDC6 rearrangement (1 pts), KRAS mutations (1 pts), BRAF mutations (7 pts), PIK3CA mutations (5 pts), and PTEN deficiency (3 pts). Conclusions: In our study, acquired EGFR mutations leading to osimertinib resistance were more likely to be identified with EGFR 19del than L858R mutation NSCLC patients. Understanding these resistance mechanisms may be useful to develop more effective therapies for patients resistant to osimertinib.
Intentions to pursue future cancer screening among older adults with limited life expectancy: Results from a US nationally-representative sample.
Authors: Ashwin A. Kotwal, Louise Christie Walter, Sei Lee, William Dale
Journal: Journal of Clinical Oncology (2018)

e13546 Background: Cancer screening guidelines recommend against screening individuals with less than a 10 year life expectancy because they are subjected to greater harms with little chance to benefit. This study examines whether older individuals with limited life expectancy are aware that screening is no longer recommended and if they plan to seek cancer screening in the future. Methods: We use nationally representative, cross-sectional data from the National Social life Health and Aging Project (NSHAP W3, 2015-16), which includes 3,816 community dwelling adults ages 55-95. Cancer screening behavior was assessed through: 1) Self-reported PSA test or mammography within the last 2 years; 2) Future intentions to be screened; and 3) Discussion with a doctor about screening being no longer necessary. Ten year life expectancy was estimated using the validated Lee Prognostic Index. Multiple logistic regressions examined intentions to pursue future screening adjusting for socio-demographics, life expectancy, cognition, and depression. Results: Among women 75+ with less than a 10 year life expectancy, 75% report no conversations with a doctor that mammography may no longer be necessary and 42% intend to pursue future mammography. Among men 75+ with less than a 10 year life expectancy, 78% report no discussions that PSA screening may no longer be necessary and 46% intend to pursue future PSA screening. In adjusted analysis, those reporting recent cancer screening were much more likely to want future mammograms (OR = 8.89, 95% CI: 6.72-11.76) or PSA tests (OR = 6.14, 95% CI: 4.74-7.94). Individuals reporting no conversations with a doctor that screening was not necessary were more likely to want mammography (OR = 4.94, 95% CI: 3.36-7.27) or PSA testing (OR = 4.91, 95% CI: 3.38-7.15). Conclusions: Over 40% of older adults with limited life expectancies intend to pursue PSA and mammography screening in the future, and less than one fourth of these individuals recall ever discussing with their doctor that these tests are no longer necessary. More efforts are needed to educate patients and doctors that there comes a time when a person’s health makes cancer screening more harmful than helpful.
Risk of hypertension (HTN) and malignant hypertension (mHTN) in patients treated for multiple myeloma (MM).
Authors: Ajai Chari, Sanjay Aggarwal, Khalid Mezzi, Shao Zhu, Winifred Werther, Diana Felici, Alexander R. Lyon
Journal: Journal of Clinical Oncology (2016)

8049 Background: HTN is commonly reported in patients with MM and may be associated with older age, disease-related complications, or sequelae of MM treatments. This study evaluated incidence rates (IR) of HTN and mHTN in treated MM patients in the United States and the risk of development of mHTN in MM patients with pre-existing HTN. Methods: Newly-treated adult MM patients were identified from Truven MarketScan claims database from 1/1/05 to 3/31/14 using ICD-9 codes to identify disease state, HTN, mHTN, and comorbidities. Inclusion criteria were new diagnosis of MM with start of MM treatment, ≥ 12 months continuous enrollment (CE) prior to diagnosis, prescription drug coverage, and ≥ 30 days of CE following initial diagnosis. Non-MM patients were matched on age (within +/- 5 yrs), gender, and distribution of index dates to MM patients. The risk of HTN and mHTN based on existing HTN and other CV comorbidities were evaluated over time. Results: 7895 MM patients (38% with HTN history) and 23685 non-MM patients (24% HTN history) were included in the study. The IR of HTN in MM and non-MM patients was 260 and 178 per 1000 person-years (PYRs), respectively. The IR of mHTN in patients with and without a history HTN were 10.25 and 3.29 per 1000 PYRs, respectively for MM patients; 4.25 and 1.88 per 1000 PYRs, respectively for non-MM patients. There was a 30% increase in the risk of HTN (HR: 1.30; 95% CI: 1.22, 1.37) in MM vs. non-MM patients. MM patients with (HR: 1.90; 95% CI: 1.26, 2.87) or without (HR: 1.54; 95% CI: 1.04, 2.28) a history of HTN had a higher risk of mHTN events during the observation period vs. non-MM patients. In MM patients with a history of HTN, the risk of mHTN was significantly increased with the following comorbid conditions: cardiomyopathy (HR: 2.79; 95% CI: 1.20, 6.48), renal failure (HR: 2.13; 95% CI: 1.36, 3.34), and diabetes mellitus (HR: 1.59; 95% CI: 1.05, 2.39). Conclusions: This study confirms that the incidence of HTN and mHTN is higher in newly-treated MM patients vs non-MM patients. Existing HTN is a risk factor for MM patients developing mHTN. Management of CV comorbidities in MM patients is important based on the increased risk of HTN and mHTN among patients with these comorbidities.
Androgen deprivation therapy in the treatment of prostate cancer and dementia risk: A systematic review and meta-analysis.
Authors: Kevin Thomas Nead, Sumi Sinha, Paul L. Nguyen
Journal: Journal of Clinical Oncology (2017)

5044 Background: Androgen deprivation therapy (ADT) to treat prostate cancer may be associated with an increased risk of dementia, but existing studies have shown conflicting results. Here we conduct a systematic review and meta-analysis on the association of ADT in the treatment of prostate cancer with the risk of dementia. Methods: We conducted a systematic review of articles reporting the outcome of dementia among individuals with prostate cancer in those exposed to ADT versus a lesser-exposed comparison group (e.g. no ADT, intermittent ADT) using the PRISMA statement guidelines. Two authors independently carried out searches in PubMed (1966–present), Web of Science (1945–present), Embase (1966–present), and PsycINFO (1806–present). The search was undertaken December 4 th , 2016. We assessed the validity of each study per the Newcastle-Ottawa Scale criteria. We meta-analyzed studies reporting an effect estimate and controlling for confounding.Random- or fixed-effects meta-analytic models were used in the presence or absence of heterogeneity, respectively, per the I 2 statistic. Small study effects were evaluated using Egger and Begg’s tests. Results: Nine studies were included in the systematic review. Seven studies reported an adjusted effect estimate for dementia risk. A random-effects meta-analysis of studies reporting any dementia outcome, which included 50,541 individuals, showed an increased risk of dementia among ADT users (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.08–2.00; p = 0.02). We separately meta-analyzed studies reporting all-cause dementia (HR, 1.46; 95% CI, 1.05–2.02; p &lt; 0.001) and Alzheimer’s disease (HR, 1.25; 95% CI, 0.99–1.57; p = 0.06). The I 2 statistic to evaluate the proportion of heterogeneity due to study variation was 76% (95% CI, 47–89; p &lt; 0.001) for the primary analysis. There was no evidence of bias from small study effects (Egger, p = 0.19; Begg, p = 1.00). Conclusions: The currently available combined evidence suggests that ADT in the treatment of prostate cancer may be associated with an increased risk of dementia. The potential for neurocognitive deficits secondary to ADT should be discussed with patients and evaluated prospectively.
Detection of targetable fusions using FusionPlex in oncology patients.
Authors: Su Jin Lee, Kyung Kim, Kyoung-Mee Kim, So Young Kang, Seung Tae Kim, Se Hoon Park, Young Suk Park, Ho Yeong Lim, Won Ki Kang, Jeeyun Lee, Joon Oh Park
Journal: Journal of Clinical Oncology (2018)

e24238 Background: Gene fusions, resulting from chromosomal rearrangements, are a prototypical example of a pathognomonic mutation and increasing numbers of chimeric proteins serve as specific targets for treatment, leading to dramatically improved patient outcomes. For the detection of gene fusions, targeted RNA panel sequencing was applied and here we’re reporting the results. Methods: From February 2017 through December 2017, 121 patients with gastrointestinal/hepatobiliary/gynecologic/sarcoma/rare cancers consented to participate in the clinical sequencing project at Samsung Medical Center (NCT#02593578). Of these patients, 117 passed the quality control process for the NGS-based targeted sequencing assay to detect gene fusion in 17-40 cancer-implicated genes (Archer FusionPlex). Results: The median age of these patients was 58 years (range; 31-81 years) and male to female ratio was 68:53. Various cancer types were included in this study; 28 colorectal cancer, 27 biliary tract cancer, 25 gastric cancer, 17 soft tissue sarcoma, 9 pancreas cancer, 6 ovarian cancer and 9 other rare cancers. Strong fusion was detected in 24 samples (20.5%) and known targetable fusions were found in 5 sample (4.3%); two colorectal cancers with TPM1-NTRK1 fusion, one colorectal cancer with NCOA4-RET fusion, one gastric cancer and one biliary tract cancer with FGFR3-TACC3 fusion. Conclusions: Targeted RNA panel sequencing is a useful tool to detect gene fusions in GI/rare cancers. FusionPlex was a feasible panel for detecting fusion in oncology patients. Clinical trial information: 02593578.
TCT-87 Thirty-Day Readmission Rate &amp; Etiologies after Endovascular Repair of Abdominal Aortic Aneurysm: A Nationwide Analysis
Authors: Varunsiri Atti, Nikhil Nalluri, Varun Kumar, Rabih Tabet, Srikanth Yandrapalli, Sushruth Edla, Deepak Asti, Avnish Tripathi, Mihir Dave, Wilbert Aronow, Roman Royzman, Ruben Kandov, James Lafferty, Donald McCord, Srinivas Duvvuri
Journal: Journal of the American College of Cardiology (2018)
Can VEGFA and ICAM1 polymorphisms predict response to bevacizumab?
Authors: Apostolos Papachristos, Theodora Katsila, Eirini Panoilia, Effrosyni Mendrinou, Anne John, Bassam R. Ali, Charalambos P. Kalofonos, George Patrinos, Gregory Sivolapenko
Journal: Journal of Clinical Oncology (2018)

2521 Background: Most targeted treatments are associated with biomarkers, predictive of drug response. Although bevacizumab is widely used, there are still no available biomarkers. Given the need of individualized treatment approaches and the high cost of Bevacizumab, it is necessary to find biological predictors of response. The present study investigated the role of selected single nucleotide polymorphisms (SNPs) in VEGFA (Vascular Endothelial Growth Factor) and ICAM1 (Intracellular Adhesion Molecule 1) genes as response biomarkers. Methods: 46 patients with metastatic colorectal cancer (mCRC) treated with Bevacizumab and chemotherapy (fluoropyrimidines/oxaliplatin or irinotecan) as first-line treatment were enrolled. Selected VEGFA (rs2010963, 1570360, rs699947) and ICAM1 (rs5498, rs1799969) SNPs were detected using PCR-based Sanger sequencing (KAPABIOSYSTEMS, MA, USA). Statistical analysis was done using ANOVA and Kaplan-Meier Survival Analysis on SPSS software. Ethical committee of University Hospital of Patras approved study. Results: 61% of patients were males and 39% females, mean age was 64.5 years (31-86). ICAM1 genotype analysis was available in 27 patients. For rs699947 (A > C), the % genotype frequencies were 29.8% AA, 23.4% A C , and 46.8% CC, while the rs1570360 (A > G) ones were determined to be equal to 10.6% AA, 23,4% A G , and 66% GG. For rs2010963 (C > G), 12.7% CC, 27.7% CG , and 59.6% GG were obtained. In the case of ICAM1, rs5498 AA, rs5498 AG and rs5498 GG were present with % frequencies of 37%, 37% and 26% , respectively. For rs1799969 (G > A ) , 85% GG, and 15% AG. Mean Progression Free Survival (PFS) and Overall Survival (OS) were 14 and 44 months, respectively. PFS was significantly longer in rs699947 AA (27.1 months, p = 0.039) and rs5498 GG (27.8 months, p = 0.018) carriers. Moreover, OS was significantly increased in rs2010963 GC carriers (59.5 months, p = 0.03). Conclusions: Our findings suggest that rs699947, rs5498, and rs2010963 serve as candidate response biomarkers. All three might be able to stratify patients, who may gain a long-term benefit towards the optimization of Bevacizumab therapy and achieving better-informed therapeutic outcomes.
Non-V600 BRAF mutations in advanced malignancies: Prevalence and survival impact.
Authors: Ed Kheder, Yan Xing, Kenneth R. Hess, Filip Janku, Kenna Rael Shaw, Le Huang, Keyur Patel, Funda Meric-Bernstam, Vivek Subbiah
Journal: Journal of Clinical Oncology (2018)

12100 Background: BRAF mutations that occur outside of codon 600, non-V600 BRAF (non-V600BRAF), have been detected in various types of tumors. Prevalence, and prognostic impact remain underestimated Methods: We conducted a retrospective study to characterize prevalence, and potential survival impact of non-V600BRAF in advanced malignancies. We pooled patients who had BRAF mutant malignancies at MD Anderson Cancer Center. We used Kaplan-Meier to estimate survival outcomes and log rank test to compare OS between groups. We used chi-squared tests to compare mutation prevalence between cancer types. We computed survival from BRAF positive biopsy date. Results: Between September/2006 and July/2017, 3337 patients were found with BRAF mutant tumors. non-V600BRAF mutations were detected in 596 (18%) patients. [238 (40%) female, 358 (60%) male; median age: 63 years, range (4, 90), 345 (58%) > 60 years; median OS, 25.0 months]. Most common cancers (%): melanoma 179 (30%); non-small cell lung (NSCLC) 83 (14%); colorectal 76 (13%), leukemia 52 (9%); myeloma 19 (3%); prostate 15 (3%); sarcoma 14 (2%); bladder, brain 11 (2%) each. Most common mutations (%): [G469A 64 (11%); D594G 58 (10%); K601E 46 (8%); D594N 37 (6%); G466E 23 (4%); G466V 22 (4%); G469V 19 (3%); E26D, G469E, G469R 18 (3%) each; S467L 15(3%); L597R, N581I, N581S 11 (2%) each]. Common mutations against common cancers are summarized in table-1. Three-year survival rate significantly changed with tumor type (P: < 0.0001): Melanoma 65%; Leukemia 62%; NSCLC 40%; other 30%; Colorectal 24%, but not with sex, age (P = 0.22); or non-V600BRAF subtypes (P = 0.4). Conclusions: Non-V600 BRAF mutations occur in 18% of advanced malignancies. Their survival impact and prevalence significantly vary among tumor types. Future studies are warranted with MAPK or ERK kinase inhibitors. Cross-tabulation of common mutations against common cancers. Tumor Number D594G (%) D594N (%) G469A (%) K601E (%) Colorectal 76 22 (29%) 4 (5%) 8 (11%) 4 (5%) Leukemia 52 3 (6%) 2 (4%) 5 (10%) 9 (17%) Lung 83 7 (8%) 4 (5%) 16 (19%) 4 (5%) Melanoma 179 8 (4%) 13 (7%) 11 (6%) 17 (9%) Other 206 24 (12%) 35 (17%) 6 (3%) 3 (1%) P-value < 0.0001 0.85 0.033 0.038
KEYNOTE-199: Pembrolizumab (pembro) for docetaxel-refractory metastatic castration-resistant prostate cancer (mCRPC).
Authors: Johann S. De Bono, Jeffrey CH Goh, Kristiina Ojamaa, Jose Maria Piulats Rodriguez, Charles G. Drake, Christopher J. Hoimes, Haiyan Wu, Christian Heinrich Poehlein, Emmanuel S. Antonarakis
Journal: Journal of Clinical Oncology (2018)

5007 Background: Efficacy of PD-1 inhibition has not been demonstrated in large-scale mCRPC trials. Pembro showed preliminary antitumor activity in PD-L1+ mCRPC in KEYNOTE-028 (n = 23). Here, we present results from cohorts 1-3 (n = 258) of the phase 2 KEYNOTE-199 study of pembro monotherapy in docetaxel-refractory mCRPC (NCT02787005). Methods: Cohorts 1 (C1) and 2 (C2) enrolled patients (pts) with RECIST-measurable PD-L1+ and PD-L1– disease, respectively. C3 enrolled pts with nonmeasurable, bone-predominant disease. All pts had ECOG PS 0-2 and received ≥1 novel endocrine therapy (eg, abiraterone, enzalutamide) and 1-2 prior chemotherapies including docetaxel. Pts received pembro 200 mg Q3W until PD or intolerable toxicity. Response was assessed Q9W in yr 1, then Q12W. Primary end point was ORR per RECIST v1.1 by central review in C1 and C2, separately and combined. Key secondary end points included DCR (CR + PR + SD) per PCWG3-modifed RECIST and safety in all 3 cohorts. Results: 131 pts enrolled in C1, 67 in C2, and 60 in C3. Median follow-up as of Oct 13, 2017, was 8.1 mo, 7.9 mo, and 11.8 mo, respectively. Antitumor activity was observed in all cohorts (Table). Across cohorts, DCR lasting ≥6 mo was 11%. In C1 and C2, 9% of pts had a ≥30% decrease in target lesions; 48% had target lesion changes between –30% and +20%. The response rate was numerically higher in pts with somatic BRCA1/2 or ATM mutations (12%). Drug-related grade 3-5 AE rates were 13% in C1, 12% in C2, and 17% in C3. Conclusions: Pembro shows antitumor activity and disease control with acceptable safety in pts with docetaxel-refractory mCRPC, regardless of PD-L1 status, in both RECIST-measurable and nonmeasurable disease. These data support further evaluation of pembro in mCRPC, including in pts wth homologous recombination defects. Clinical trial information: NCT02787005. C1 C2 C3 C1+C2 C1+C2+C3 RECIST v1.1 ORR, % (95% CI 5 (2-11) 3 ( < 1-10) NA 5 (2-8) NA DCR, % (95% CI) 22 (15-30) 24 (14-36) 37 (25-50) 23 (17-29) 26 (21-32) DCR ≥6 mo, % (95% CI) 9 (5-16) 6 (2-15) 22 (12-34) 8 (5-13) 11 (8-16) PCWG3-modified RECIST ORR, % (95% CI) 5 (2-11) 3 ( < 1-10) NA 5 (2-8) NA DCR, % (95% CI) 27 (20-36) 42 (30-54) 57 (43-69) 32 (26-39) 38 (32-44) DCR ≥6 mo, % (95% CI) 11 (6-17) 9 (3-18) 30 (19-43) 10 (6-15) 15 (11-20)
The efficacy and safety of Apatinib in Ewing sarcoma: A retrospective analysis.
Authors: Yitian Wang, Li Min, Yong Zhou, Fan Tang, Yi Luo, Wenli Zhang, Kai Yao, Chongqi Tu
Journal: Journal of Clinical Oncology (2018)

e23522 Background: Ewing’s sarcoma (ES) is a highly aggressive and metastatic tumor, mainly in children and young adults. The standard treatment of localized ES requires a multidisciplinary approach, a combination of surgery, chemotherapy, and radiotherapy. Although the 5-year survival rate for local ES has improved, the survival rate and prognosis are still very poor for ES patients with metastases or recurrence. The aim of this study was to investigate the efficacy and safety of apatinib, a specific VEGFR-2 inhibitor, in advanced ES patients. Methods: This retrospective analysis involved ES patients in our hospital from Feb 2016 to Jul 2017. For all patients the immune-histochemical examination of the tumor tissue was positive staining for VEGF and VEGFR-2. Apatinib 500 mg or 250 mg was given every day. Tumor responses were assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Survival analysis was performed by the Kaplan–Meier test. And the safety profile was also recorded. Results: Seven ES patients received apatinib for initial treatment or palliative treatment after conventional chemotherapy (vincristine, doxorubicin and cyclophosphamide). Median age was 18 years (range, 10-31). The ratio of male/female was 4/3. Two of the patients were diagonized with lung metastases. As of 2017/11/21, the median therapy duration was 6.6 months (range, 1.2-21.1). Six patients had been evaluated for tumor response, with 3 partial response (PR) and 3 stable disease (SD). The objective response rate (ORR) was 50% and the disease control rate (DCR) was 100%. The most common adverse events included hand-foot syndrome (HFS) (5, 71.4%), mucositis (2, 28.6%), and anorexia (1, 14.3%). Conclusions: Apatinib may provide as second- or first-line treatment option for advanced ES patients, particularly in cases resistant to chemotherapy. Further studies with more cases with longer follow-up times will be necessary to determine the clinical efficacy of apatinib in ES.