tbuckley/cabot-search huggingface dataset:
Impact of colonoscopy on patients older than 75.
Authors: Dhauna Karam, Mohammed Al-Hamadani, Shah Pallavi, Mohamed Shanshal, Janos Molnar
Journal: Journal of Clinical Oncology (2017)

e15096 Background: Colorectal cancer is the second leading cause of cancer related deaths in the United States. As per current screening guidelines, screening should begin by age 50 and be continued till age 75. Routine screening over 75 years is not recommended. Methods: Our primary objective was to compare survival time in patients undergoing colonoscopy aged 75 years or older to those aged 50-74. The study was conducted at Captain James A. Lovell Federal Health Care Center (FHCC), North Chicago, United States between 2002 and 2012. A retrospective chart review was performed for patients who underwent colonoscopy. Mortality in terms of survival time was compared between patients equal or older than 75 versus those aged 50-74 years with similar procedural indications and life expectancy of 5 years or more. Survival analysis was performed via Kaplan Meier curve with log-rank test. Results: A total of 213 patients were included in the study . Fifty one percent of the patients (108) were 50-74 years old (young age group), while 49% (105) were 75 or older (old age group). Patients had colonoscopy done for following indications: 92 (43%) screening colonoscopy, 62 (29.1%) diagnostic colonoscopy and 59 (27.7%) surveillance colonoscopy. There was no statistical difference between the age groups based on indication of colonoscopy (P = 0.899). Overall mean survival time for all patients was 123.6 months (10.3 years). Survival time was significantly higher for young age group with a mean overall survival of 131.1 months (10.9 years). Older age group had a mean overall survival time of 106.9 months (8.9 years). P-value = 0.009. The highest overall mean survival time was observed in patients who were under 75 and had colonoscopy for screening purposes 138.9 months (11.6 years) (P = 0.019). The lowest overall mean survival time was seen in those who were &gt; 75 years and had colonoscopy due to diagnostic purposes 93.6 months(7.8 years). (P = 0.055) Conclusions: Although statistically significant higher survival time was noted in patients younger than 75, older patients also had a survival time of more than 7 years. This will impact the decision to offer screening colonoscopy to older people who will definitely benefit from the test.
Abstract IA28: The genomic landscape of SCLC and other neuroendocrine lung tumors
Authors: Julie George
Journal: Clinical Cancer Research (2018)

Abstract Small cell lung cancer (SCLC) accounts for 15% of all lung cancers and belongs to the family of pulmonary neuroendocrine tumors. This tumor subgroup additionally includes large-cell neuroendocrine carcinomas (LCNEC) and pulmonary carcinoids (PCA), which occur in 3% and 2% of all lung cancer patients, respectively. Carcinoids are usually clinically benign, whereas SCLC and LCNEC are characterized as high-grade malignant tumors. Clinical and histologic studies have suggested similarities between SCLC and LCNECs: Both lung tumor subtypes are associated with heavy smoking and reveal an aggressive tumor growth resulting in a poor overall survival. We have performed comprehensive and multilevel genomic profiling on SCLC and LCNECs, including genome, exome, and transcriptome sequencing. SCLC and LCNEC tumors reveal high mutation rates with an average of 9.5 and 8.6 mutations per megabase, respectively. Our sequencing studies have shown that SCLC tumors are characterized by bi-allelic inactivation of TP53 and RB1 in almost 100% of the cases. LCNECs, on the other hand, are composed of two mutually exclusive subgroups, which we categorized as “type I LCNECs” and “type II LCNECs.” Type I LCNECs harbor TP53 and STK11 or KEAP1 alterations. Despite sharing genomic alterations with lung adenocarcinomas and squamous cell carcinomas, type I LCNECs exhibit a high neuroendocrine profile with close similarity to SCLC tumors. Type II LCNECs harbor loss of TP53 and RB1, thus showing genetic resemblance to SCLC. However, these tumors were revealed to be different from the majority of SCLC with reduced levels of neuroendocrine markers, an upregulated immune signaling profile, and high activity of the NOTCH pathway. Conclusively, our studies show marked biologic differences between high-grade neuroendocrine lung tumors and we emphasize the precise distinction of LCNEC subgroups from SCLC. Citation Format: Julie George. The genomic landscape of SCLC and other neuroendocrine lung tumors [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr IA28.
P04.21 Combination therapy of CAR-NK cells and anti-PD-1 antibody displays potent efficacy against late-stage Glioblastoma and induces protective antitumor immunity
Authors: F Strassheimer, C Zhang, I C Mildenberger, P N Harter, T Tonn, J P Steinbach, W S Wels, M C Burger
Journal: Neuro-Oncology (2018)

Checkpoint inhibitors as well as adoptive cell therapy hold great promise for cancer treatment and promising treatment responses have already been demonstrated in different cancer indications. Glioblastoma (GBM) is the most common and aggressive primary brain tumor. Standard therapy prolongs life expectancy only by months. Analysis of the GBM tumor microenvironment (TME) indicates elevated suppressive leukocyte infiltration. While the surrounding brain is HER2-negative, GBM tumors are frequently HER2-positive, suggesting HER2 as a promising target for adoptive immunotherapy. Indeed, previous results show efficacy of CAR-NK cells (NK-92/5.28.z) targeted to HER2 in mouse glioma models at early stages of tumor development. The murine glioma cell line GL261 was transfected with HER2. Tumor cells were implanted subcutaneously into C57BL/6 mice and treated either with HER2-specific NK-92/5.28.z, parental NK-92 cells, or in combination with anti-PD-1. Effects on tumor growth and survival were determined, and lymphocyte infiltration and immunosuppressive TME were characterized by flow cytometry. Combined treatment with NK-92/5.28.z cells and anti-PD-1 resulted in tumor regression and long-term survival of late-stage tumor bearing mice. Analysis of TME showed enhanced cytotoxic lymphocyte infiltration after treatment. These data demonstrate enhanced efficacy of a combination of NK-92/5.28.z cells with checkpoint inhibitors in advanced tumors. Checkpoint inhibition possibly induces a cytotoxic rather than immunosuppressive TME, leading to a primed immune system. Thus, combination therapy may be a promising treatment goal for a clinical phase I/II study.
Quality of life in the CRITICS study, a multicenter randomized phase III trial of neo-adjuvant chemotherapy followed by surgery and chemotherapy or by surgery and chemoradiotherapy in resectable gastric cancer.
Authors: Romy Van Amelsfoort, Iris Walraven, Edwin PM Jansen, Annemieke Cats, Nicole C.T. van Grieken, Neil K Aaronson, Henk Boot, Pehr A. Lind, Elma Meershoek – Klein Kranenbarg, Marianne Nordsmark, Hein Putter, Anouk Kirsten Trip, Johanna W. van Sandick, Karolina Sikorska, Harm van Tinteren, Cornelis J. H. Van De Velde, Marcel Verheij
Journal: Journal of Clinical Oncology (2018)

4060 Background: Patient-reported outcome is an important objective in clinical trials, as it addresses the impact of the disease and treatment on health-related quality of life (HRQOL). In the multicenter randomized phase III CRITICS study no significant difference in overall survival was found between postoperative chemotherapy and chemoradiotherapy after neo-adjuvant chemotherapy and D2 surgery (5-year OS 42% vs 40%). The CRITICS study investigated health-related quality of life in both treatment groups as one of the secondary objectives. Methods: Patient-reported outcome questionnaires were completed at baseline, after preoperative chemotherapy, after surgery, after postoperative chemotherapy (CT) or chemoradiotherapy (CRT) and during follow-up at 12 months after the end of postoperative treatment for 788 patients with adenocarcinoma of the stomach. Cancer-related quality of life was assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). A QLQ-C30 summary score at each time point was calculated as the mean of the combined 13 QLQ-C30 scale scores (max score 100; financial impact and global quality of life scale scores excluded). Linear mixed-modeling was applied to assess differences in the QLQ-C30 summary score between the CT and CRT group, accounting for missing values during follow-up. Results: 645 patients out of the 788 patients had at least one evaluable questionnaire. The number of evaluable questionnaires was comparable between the CT and CRT groups. Evolution of QLQ-C30 summary scores over time was non-linear with baseline scores of 86 vs 84, lowest scores after surgery of 77 vs 75 and recovery of the scores to 83 vs 80 after 12 months of follow-up. No significant differences in QLQ-C30 summary scores over time were observed between the CT and CRT group (p = 0.567). Conclusions: In the CRITICS study HRQOL summary scores showed no differences over time between the CT and the CRT group. Besides HRQOL, pathological T- and N-stage, resection margin status and histological type contribute to the optimal choice of treatment. Clinical trial information: NCT00407186.
Colonic MicroRNA Profiles, Identified by a Deep Learning Algorithm, That Predict Responses to Therapy of Patients With Acute Severe Ulcerative Colitis
Authors: Ian Morilla, Mathieu Uzzan, David Laharie, Dominique Cazals-Hatem, Quentin Denost, Fanny Daniel, Genevieve Belleannee, Yoram Bouhnik, Gilles Wainrib, Yves Panis, Eric Ogier-Denis, Xavier Treton
Journal: Clinical Gastroenterology and Hepatology (2018)
TCT-825 The right radial access for coronary angiography reduces radiation exposure compared to other approaches - the experience from a high volume center
Authors: Wojciech Zajdel, Łukasz Wiewiórka, Łukasz Niewiara, Elżbieta Paszek, Piotr Musialek, Krzysztof Bryniarski, Jacek Legutko, Krzysztof Zmudka
Journal: Journal of the American College of Cardiology (2018)
Promoter capture Hi-C-based identification of recurrent noncoding mutations in colorectal cancer
Authors: Giulia Orlando, Philip J. Law, Alex J. Cornish, Sara E. Dobbins, Daniel Chubb, Peter Broderick, Kevin Litchfield, Fadi Hariri, Tomi Pastinen, Cameron S. Osborne, Jussi Taipale, Richard S. Houlston
Journal: Nature Genetics (2018)
A phase II randomized trial of nivolumab with stereotactic body radiotherapy (SBRT) versus nivolumab alone in metastatic (M1) head and neck squamous cell carcinoma (HNSCC).
Authors: Sean Matthew McBride, Eric Jeffrey Sherman, C. Jillian Tsai, Shrujal S. Baxi, Jahan Aghalar, Juliana Eng, Wanqing Iris Zhi, Daniel Curtis McFarland, Loren S. Michel, Daniel Spielsinger, Zhigang Zhang, Jessica Flynn, Lara Dunn, Alan Loh Ho, Nadeem Riaz, David G. Pfister, Nancy Y. Lee
Journal: Journal of Clinical Oncology (2018)

6009 Background: A minority of patients with metastatic HNSCC respond to the anti-programmed death (PD-1) monoclonal antibody, Nivolumab (Nivo). We sought to determine whether targeted radiation to a single lesion combined with Nivo would enhance tumor regression in non-irradiated lesions (abscopal response) and improve outcomes. Methods: Patients with M1 HNSCC (including nasopharynx) with at least two RECIST 1.1 measurable lesions were randomized with stratification for viral status (EBV/HPV pos vs. neg) 1:1 to either Nivo alone q 2 weeks or Nivo with SBRT to a single lesion (9 Gy x 3) between the 1st and 2nd doses of Nivo. The primary end-point was objective response rate (ORR) in non-irradiated lesions using RECIST 1.1. Secondary analyses included overall survival (OS), progression free-survival (PFS), and duration-of-response (DOR). We hypothesized that SBRT added to Nivo would increase ORR from 15% to 45%. Enrolling 53 patients thus provides a one-sided alpha of 0.10 and a power of 0.80. Results: 53 patients were randomized, 26 to Nivo alone and 27 to Nivo+SBRT; the lung was the most common irradiated site (59%). There were no significant differences between arms in terms of age (p = 0.12), viral status (pos vs neg; p = 0.786), primary site (oropharynx vs. nasopharynx vs other; p = 1.0), or median lines of prior chemotherapy (1; p = 0.73). ORR in the Nivo alone arm was 26.9% (95% CI: 13.7, 46.1%) vs 22.2% (95% CI: 10.6%, 40.8%) in the Nivo+SBRT arm (p = 0.94). Median DOR with Nivo alone was not reached (NR) vs 9.3 months (95% CI: 5.52, NR) with Nivo+SBRT (p = 0.21). Median follow-up amongst surviving patients was 12.8 mos; OS at 1 year was 64% (95% CI: 47%, 88%) in the Nivo alone arm vs 53% (95% CI: 36%, 79%) in the Nivo+SBRT arm (p = 0.79); median PFS was 1.9 mos (95% CI: 1.78, NR) with Nivo vs 2.4 mos (95% CI: 1.0, 11.4) with Nivo+SBRT (p = 0.8). Treatment-related ≥ Grade 3 toxicities in the Nivo alone vs Nivo+SBRT arms occurred in 15% vs. 11% of patients (p = 0.96). Conclusions: While safe, the addition of SBRT to Nivo in M1 HNSCC failed to improve ORR, PFS, or OS. This is the first randomized evaluation of the abscopal response in any tumor histology. Biomarker analyses are near completion. Clinical trial information: 02684253.
Chemotherapy induced nausea and vomiting in breast cancer treated with antiemetic prophylaxis as recommended by the ASCO antiemesis guidelines.
Authors: Ronda Copher, Russell L. Knoth, Glenn Magee, Soamnauth Misir, Ali McBride
Journal: Journal of Clinical Oncology (2017)

10109 Background: Current ASCO Antiemesis Guidelines recommend triple antiemetic therapy (a 5HT 3 RA, an NK1, and dexamethasone) to prevent chemotherapy (CT) induced nausea and vomiting (CINV) in patients undergoing highly emetogenic chemotherapy (HEC). This study evaluated whether this regimen resulted in reduced rates of CINV in patients diagnosed with breast cancer (BC) and initiated on HEC. The primary outcomes of interest were rates of acute and delayed CINV in patients whose antiemesis prophylaxis was or was not in accordance with the ASCO guideline (i.e., Per-guideline vs. Non-Guideline). Costs of treating CINV were also calculated. Methods: Patients were identified in the Premier Healthcare database, a complete geographically diverse census of inpatients and hospital-based outpatients. Adults treated for BC with HEC during the years 2012-14 were identified and stratified based on their antiemesis prophylaxis. Rates of acute (day of CT) and delayed CINV (days 2-7 post CT) were calculated following initiation of HEC. CINV was defined by ICD9 codes for nausea and vomiting or volume depletion/dehydration or use of a rescue antiemetic. Rates of CINV and health care costs were then compared between the two cohorts. Results: A total of 8,388 patients were included in the analysis. Of these, 5,447 (65%) had treatment Per-Guideline and 2,941 (35%) were Non-Guideline. For acute CINV, Per-Guideline patients had a significantly lower rate of CINV when compared to Non-Guideline patients (1.7% vs. 3.2%, respectively, p &lt; .001). Similarly, in delayed CINV Per-Guideline patients had significantly lower rates of CINV when compared to Non-Guideline patients (15.4% vs. 19.1%, p &lt; .001). Patients who experienced CINV also had significantly greater total health care costs versus those without CINV ($32,199 vs. $20,163, respectively, p &lt; .001). Conclusions: The results showed adherence to the ASCO Antiemesis Guidelines led to lower rates of CINV and lower costs. Although defining CINV by claims may tell an incomplete story, this study suggests that following the ASCO Antiemesis Guidelines may help both patients and payers of health care costs.
Unique patterns of the selection and change in circulating tumor cell (CTC) phenotypes and genotypes by drug class in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Howard I. Scher, Joseph Schonhoft, Ryon P Graf, Angel E Dago, Jerry Lee, Ramsay Sutton, Nicole A. Schreiber, Melanie Hullings, Adam Jendrisak, Yipeng Wang, Mark Andrew Landers, Ryan Dittamore
Journal: Journal of Clinical Oncology (2018)

5053 Background: Biomarkers to predict outcomes for individual patients (pts) on standard of care Rx is an unmet medical need in the treatment of mCRPC. Using baseline (BL) blood draws, we previously reported a phenotypic CTC heterogeneity algorithm that predicted for differential survival times on ARSi vs. taxanes. We have also observed that certain gene alterations as well as genomic instability are linked to different CTC phenotypic subtypes. We sought to associate CTC phenotypes to response, and to characterize phenotypic and genotypic changes to populations of CTCs associated from selection pressures by specific drug classes. Methods: 456 blood samples (228 matched BL and on-therapy) from 184 unique mCRPC pts were collected and processed utilizing the Epic Sciences CTC platform. CTCs were enumerated and characterized for phenotype (n = 11,722) including CTC subtypes, from pts who received ARSi therapy (n = 131), taxanes (n = 57) or a platinum containing regimen (n = 40). 985 CTCs of various phenotypic subtypes were single cell sequenced for DNA copy number variation. Results: CTCs were detected in 88.6% (202/228) BL and in 76.3% (174/228) on therapy samples, med = 3.5mL (0 to 490) and median = 2.7mL (0 to 992) respectively. Changes in CTC phenotypic features were observed unique to specific therapy classes, including changes to nuclear size, shape and texture. Persistent CTC phenotypes in pts treated with ARSi and taxane, but not platinum, were enriched with cells having AR over-expression and genomic instability (p < 0.001) while those in pts treated with ARSi but not taxane, were enriched with PTEN, RB1 and TP53 loss (all p < 0.001). Models to predict resistance to the therapies based on specific CTC prevalence in early on-therapy draws will be presented. Conclusions: We observed broad CTC phenotypic and genotypic heterogeneity prior to Rx, and patterns of clonal selection specific to different standard of care drug classes. Models utilizing these insights have potential to predict resistance if observed pre-therapy or during therapy to enable a change in therapy prior to clinical manifestation. Further development of these models is ongoing.
TCT-461 Association between In-stent Neoatherosclerosis and Restenosis in Patients with Acute Myocardial Infarction at 5-years Follow-up Assessed by Optical Coherence Tomography
Authors: Masaru Kuroda, Masayuki Kintsu, Mutsuki Kodaira, Yukinori Kato, Kouji Sogabe, Takeshi Matsuura, Akinori Matsumoto, Yasutaka Hirayama, Kazumasa Adachi, Akira Matsuura, Masahito Kawata
Journal: Journal of the American College of Cardiology (2018)
Clinical concordance study of a 17-gene liquid biopsy NGS panel for non-small cell lung cancer (NSCLC).
Authors: Lee Steven Schwartzberg, Emilio Esteban González, Dolores Isla, Michaela L. Tsai, Fabrice Barlesi, Frederique Madeleine Penault-Llorca, Hidehito Horinouchi, William Johnson Irvin, Carlos Escriu, James M. Orsini, Amparo Sanchez-Gastaldo, John A. Keech, Sigolene Galland-Girodet, John Crown, Nashat Y. Gabrail, Kim Michelle Clark-Langone, Anna Bergamaschi, Margarita Lopatin, Christer Svedman, David Chan
Journal: Journal of Clinical Oncology (2018)

e21065 Background: Testing for multiple actionable genomic alterations is recommended in advanced NSCLC but many patients (pts) are difficult to biopsy and up to 30% of pts have insufficient biopsy material for analysis of relevant alterations. Presently, there is only one FDA-approved liquid biopsy mutation test for EGFR only with a clinical sensitivity of 61-77%. There is an urgent need for sensitive and specific liquid biopsy tests for multiple alterations. We present an interim analysis of a prospective concordance study in NSCLC of a new liquid biopsy assay for alterations in 17 genes (Oncotype SEQ Liquid Select v1.2). The assay has been analytically validated demonstrating high sensitivity and specificity for detecting single-nucleotide variants (SNVs), indels, fusions and copy number (CN) gains in blood. Methods: Pts with stage IV nonsquamous NSCLC who were newly diagnosed or progressing on therapy were enrolled. 20 ml of blood was drawn within 8 weeks of tissue biopsy. No new systemic antitumoral therapy was permitted between tissue and liquid biopsies. Central NGS tissue analysis was offered but local analysis was also accepted. NGS analysis of cfDNA was performed in a central CLIA laboratory (Genomic Health) blinded to tissue results. Results: 140 (97%) of 144 protocol eligible pts had evaluable liquid assay results; 117 pts had concurrent tissue results. There were no laboratory failures. Alterations were detected in liquid in 58% of pts: EGFR (29%), KRAS (16%), MET (7%), ALK (4%), ERBB2 (4%), RET (2%), ROS1 ( < 1%), BRAF (1%). The overall concordance for pre-specified clinically actionable EGFR alterations was 94.0% (95% CI 88.1-97.6%) with a positive percent agreement (PPA) of 76.7% (57.7-90.1%) and a negative percent agreement (NPA) of 100% (95.8-100%). Overall concordance for ALK fusions was 95.7% (90.1-98.6%). Conclusions: PPA, NPA for EGFR was comparable to the FDA-approved PCR liquid biopsy test. The assay also detected SNVs, indels, fusions and CN gains in other relevant genes at a rate that is representative of large-scale NSCLC tissue analysis. These results support using the assay for therapy selection, especially in patients that are difficult to biopsy or where tissue assessment has failed.
Impact of primary tumor resection in oligometastatic non-small cell lung cancer: Experience of a resource-limited cancer center in southern Brazil.
Authors: Paulo Ricardo Santos Nunes Filho, Caroline Albuquerque Moreira da Silva, Maria Teresa Ruiz Tsukazan, Andre Poisl Fay, Carlos H. Barrios, Marcio Debiasi
Journal: Journal of Clinical Oncology (2017)

e20552 Background: Stage IV non-small cell lung cancer (NSCLC) with low volume disease represents a more indolent phenotype within the biological spectrum of lung cancer. Recent data suggest that aggressive local therapy may impact clinical benefit in this subgroup of patients, with 5-year overall survival (OS) rate around 20%. Methods: We analyzed patients with oligometetastatic (≤3 metastasis) NSCLC treated with primary tumor resection at Hospital São Lucas da PUCRS. Clinico-pathological features and survival data were retrospectively collected using standard templates. The primary endpoint was OS. Survival was estimated using the Kaplan-Meier method and log-rank test was used to univariate analysis. Results: Between April 1991 and December 2015, 25 patients with oligometastatic NSCLC underwent surgery of the primary tumor. Clinico-pathological data are summarized in Table 1. Overall, median OS was 16 months (95% CI: 8.87-23.13 months) with a 5-years survival rate of 7%. Age less than 65 years old was associated with longer OS (HR 0.34 95%CI 0.13-0.92 p = 0.02). Patients with brain metastasis had a non-significant lower OS than those without (16 vs. 24 months, respectively). Conclusions: This analysis suggests that in a resource-limited center, where immunotherapies and targeted-therapies are not available, local therapy for oligometastatic NSCLC did not provide the same clinical benefit seen in the same population from high-income countries. See table. [Table: see text]