tbuckley/cabot-search huggingface dataset:
A phase I study of novel multi-HLA-binding peptides and a new combination of immune adjuvants against solid tumors.
Authors: Hiroto Matsui, Shoichi Hazama, Koji Tamada, Keiko Udaka, Yasunari Koki, Toshinari Uematsu, Hideki Arima, Hiroyuki Furukawa, Tomoya Miyakawa, Shun Doi, Masahiro Kitahara, Shinsuke Kanekiyo, Yukio Tokumitsu, Yoshihiro Tokuhisa, Kazuhiko Sakamoto, Nobuaki Suzuki, Shigeru Takeda, Shigeru Yamamoto, Shigefumi Yoshino, Hiroaki Nagano
Journal: Journal of Clinical Oncology (2017)

3086 Background: Based on the exploratory analysis of our previous studies of peptide vaccine, we concluded that the combination of adjuvants hLAG-3Ig + Poly-ICLC is essential for controlling negative immune checkpoints and enhancing the induction of CTLs to overcome the traditional peptide studies. Another issue with peptide vaccines is human leukocyte antigen (HLA) restriction. Hence, we developed novel multi-HLA-binding peptides derived from the tumor antigens, HSP70 and GPC3, and confirmed the high expression in many types of cancer. Methods: For the identification of peptides, HSP70- and GPC3-derived peptides that have high binding affinity to each of HLA-A2402, 0201, and 0206 were selected as candidate peptides by a binding prediction system (NEC Corporation). We then identified priority candidate peptides by using a peptide-binding assay. Using peripheral mononuclear blood cells from cancer patients, CD8+ T lymphocytes were stimulated with the candidate peptides, and an enzyme-linked immunospot assay was performed. Finally, we identified HSP70- and GPC3-peptide. In this phase I study of a novel peptide cancer vaccine for metastatic solid cancer, primary objective was to evaluate its safety and toxicity. Secondary objective was to examine the immune and clinical response, and also to determine the recommendable dose. This study used a three-tiered dose-escalation strategy with 3 patients’ cohorts. In addition to the 3 scheduled cases, 3 more cases were added and 6 cases were enrolled at the recommended dose. Results: Twelve HLA-A*24:02-, 02:01-, and 02:06-matched patients (esophagus, 3; colon, 4; liver, 3; pancreas, 1; stomach, 1) were treated in this study. No severe adverse effects related to the treatment were encountered. Peptide-specific CTL induction with HSP70 and GPC3 was observed in 10 and 11 patients, respectively. We observed decreased tumor marker expression in 6 cases, and disease control was observed in f5 patients (4, 3, 8, 2, 2 months, respectively). Conclusions: The combination cancer vaccine therapy using multi-HLA-restricted peptides and hLAG-3Ig + Poly-ICLC was safe and effective for treating solid tumors; it therefore warrants further clinical studies. Clinical trial information: UMIN000020440.
CAPTN: A nomogram for predicting survival and guiding therapy for patients with de novo metastatic head and neck squamous cell carcinoma.
Authors: Jared R. Robbins, Michael Stadler, Monica Shukla, Selim Firat, Becky Massey, Bruce Campbell, Christopher J. Schultz, Stuart J. Wong
Journal: Journal of Clinical Oncology (2018)

6041 Background: Determining prognosis for de novo metastatic head and neck squamous cell carcinoma (mHNSCC) is difficult with limited data to direct clinical management. Recommendations for aggressive treatment must be measured since the duration and toxicity of treatment may exceed the projected lifespan. For this reason, tools to predict survival are needed to guide decisions like the appropriateness of radiation, standard verses experimental therapy, or supportive care alone. Purpose/Objective: To develop and evaluate a model for predicting survival for patients with de novo mHNSCC. Methods: We identified 8,441 patients diagnosed with de novo mHNSCC (oral cavity, oropharynx, larynx, hypopharynx, nasopharynx, and paranasal sinuses) in the National Cancer Database from 2004-2013. Test and validation cohorts were randomly generated. Univariate and multivariate Cox regression models were used to identify factors associated with overall survival. A simple scoring system based on clinically-relevant factors was used to generate the CAPTN nomogram (see table). Results: For all patients, the median OS was 9.5 months with 1-year OS of 43%. In both the test and validation cohorts, the CAPTN accurately predicted outcomes between each group by pairwise comparison (all p < 0.001, see table). A CAPTN score of 0 correlated to the best prognosis while higher score represented step-wise worse prognosis. Conclusions: Patients with de novo mHNSCC have heterogeneous outcomes, but the CAPTN score can accurately discriminate survival. Although further validation in other cohorts is needed, the CAPTN model is usefully clinically for tailoring treatment intensity to prognosis and may be pertinent to clinical trial design as a stratification factor. Factor 0 points 1 point 2 points Score Median OS 6-m OS 1-yr OS 3-yr OS Charlson Deyo 0 1 (mild) 2 (severe ) Test 0 16.8 m 78% 60% 29% Age (yrs) < 70 70-79 ≥80 1-2 10.7 m 68% 46% 19% Primary Site Oropharynx nasopharynx Larynx All other sites 3-4 7.0 m 56% 33% 10% ≥5 4.9 m 41% 21% 6% T-stage (4) No Yes Validation Score Median OS 6-m OS 1-yr OS 3-yr OS N-Stage (3) No Yes 0 16.3 m 78% 61% 30% 1-2 10.6 m 68% 46% 18% 3-4 7.3 m 56% 34% 12% ≥5 4.8 m 42% 20% 5%
Characterization of a bone biorepository: Comparison of bone metastases from breast, prostate, renal, lung cancers, and myeloma.
Authors: Kerith Ruoyao Wang, John A. Abraham, Peter McCue, Matthew Joseph Schiewer, Karen Marie Bussard, Alessandro Fatatis, Lucia Languino, Benjamin Leiby, Raymond O'Neill, Jianhong Li, Benjamin I. Richter, William Kevin Kelly
Journal: Journal of Clinical Oncology (2018)

e24019 Background: While bone is one of the most common sites of metastasis for many cancer types, lack of access to the necessary quantity and quality of human specimens limits the understanding of the bone microenvironment. Therefore, our multidisciplinary team has developed a method of intraoperative rapid retrieval of human bone tissue and blood as well as collection of matching primary tissue and clinical data. Methods: Bone Biorepository Bank (BBB) is notified when patients (pts) with primary or metastatic cancer to the bone with standard of care surgeries are identified and consented. Biospecimens are processed within minutes and stored as FFPE blocks, preserved in RNAlater, and snap frozen. Plasma and buffy coat are extracted from whole blood. H&E sections are reviewed by Pathology for tumor burden (TB), presence of tumor necrosis (TN), osteoblastic and osteoclastic activity level (OBC), and fibrous stromal proliferation level (SP). Primary tumor slides are obtained, and clinical information is extracted from medical records. Results: From Dec 2016 to Dec 2017 BBB enrolled 55 pts with 63 bone, 47 blood, and 26 primary samples. The bank includes 16 cancer types with the largest sample amounts in breast (N = 22), prostate (18), renal (14) myeloma (13), and lung (8) out of 96 FFPE blocks. 75.3% samples had systemic treatment (tx) before surgery. Preliminary analysis of H&Es in the 5 largest cancer types revealed no differences in TB or TN. There was significant difference in OBC (p = 0.0047); in pairwise comparisons renal had significantly lower OBC compared to OBC in breast (0.039), myeloma (0.0072), and prostate (0.0089). SP also had statistical significance (0.0037); pairwise comparisons showed that SP was significantly higher in breast compared to SP in renal (0.0093) and myeloma (0.0035). Analysis of pts who were tx naïve versus pts who received tx showed no histological difference. Conclusions: Specimen analysis showed more similarities than differences in histological patterns regardless of tx status and cancer type. Continued growth of BBB will be an invaluable resource to better understand the metastatic bone microenvironment. Additional molecular and genetic tests are ongoing.
Results from a phase I study of andecaliximab in combination with FOLFIRI and bevacizumab in patients with second line metastatic colorectal cancer.
Authors: Zev A. Wainberg, Johanna C. Bendell, Heinz-Josef Lenz, Ari David Baron, Jordan Berlin, Alberto Bessudo, Daniel Bruetman, Ki Y Chung, Haeseong Park, Manish R. Patel, Adeboye H Adewoye, JieJane Liu, Ravindranath Patel, Manish A. Shah
Journal: Journal of Clinical Oncology (2018)

3578 Background: Matrix metalloproteinase 9 is highly expressed in several malignancies, including metastatic colorectal cancer (mCRC) and is an adverse prognostic feature. In preclinical colorectal cancer models, inhibition of MMP-9 was associated with tumor growth inhibition. Andecaliximab (ADX) is a chimeric antibody directed against MMP-9 engineered to remove T cell epitopes and reduce risk of immunogenicity. In this phase I multi-cohort study, we combined ADX with standard of care chemotherapy in patients with 2nd line mCRC. (Clinicaltrials.gov NCT# 01803282) Methods: Patients were eligible if they progressed on a front line chemotherapy backbone of a fluoropyrimidine and a platinum with or without bevacizumab. All patients received ADX 800 mg IV every two weeks in combination with standard dose FOLFIRI + bevacizumab. The primary endpoints of this study were safety and tolerability. Exploratory endpoints were investigator assessed objective response rate (ORR), progression free survival (PFS) and overall survival (OS). Results: We enrolled 44 patients (25 female) with measurable disease who had received prior treatment for metastatic colorectal cancer. The median age was 58 years (range 23-81). As of September 22, 2017, the median ADX treatment duration for this study was 5.9 months. The most common adverse events (AEs) were diarrhea (57%), fatigue (57%), nausea (57%), stomatitis (34%), and vomiting (32%). Serious AEs were reported in 25% of pts. The most common serious AE was pulmonary embolism, which occurred in 2 patients. Median PFS was 9.2 months (90% CI 7.4-10.2 months) and the ORR was 21% (90% CI 11-33%). The median OS was not reached at the time. Study treatment continues in 27% of patients. Conclusions: The combination of ADX with FOLFIRI and bevacizumab was safe and effective. The activity of the combination appears encouraging in 2nd line treatment of metastatic colorectal cancer. Updated data will be presented at the time of the presentation. Clinical trial information: NCT01803282.
TCT-139 Use of Atherectomy in Chronic Total Occlusion Intervention: Insights From the PROGRESS-CTO Registry
Authors: Iosif Xenogiannis, Dimitri Karmpaliotis, Khaldoon Alaswad, Farouc Amin Jaffer, Robert Yeh, Mitul Patel, Ehtisham Mahmud, James Choi, M. Nicholas Burke, Anthony Doing, Philip Dattilo, Catalin Toma, A.J. Conrad Smith, Barry Uretsky, Oleg Krestyaninov, Dmitrii Khelimskii, Elizabeth Holper, R. Michael Wyman, David Kandzari, Santiago Garcia, Ioannis Tsiafoutis, Wissam Jaber, Habib Samady, Nicholas Lembo, Jeffrey W. Moses, Manish Parikh, Ajay Jayant Kirtane, Ziad Ali, Darshan Doshi, Imre Ungi, Peter Tajti, Bavana Rangan, Subhash Banerjee, Emmanouil Brilakis
Journal: Journal of the American College of Cardiology (2018)
TCT-157 Pathological vascular healing following complex interventions with the Absorb bioresorbable vascular scaffold
Authors: Johan Bennett, Keir McCutcheon, Maarten Vanhaverbeke, Nina Vanden Driessche, Tom Adriaenssens, Peter Sinnaeve, Walter Desmet, Christophe Dubois
Journal: Journal of the American College of Cardiology (2018)
Early adoption of digital breast tomosynthesis in the United States.
Authors: Ilana Richman, Jessica R Hoag, Susan Busch, Cary Philip Gross
Journal: Journal of Clinical Oncology (2018)

e13543 Background: Although digital breast tomosynthesis (DBT) may improve cancer detection and decrease recall rate, major guidelines do not recommend DBT for screening because of an absence of long-term outcome data. Our goal was to describe DBT use among physician practices in the US and identify factors associated with uptake. Methods: We reviewed blinded administrative claims data from anonymous insurers conducting business across the US. We identified screening mammograms for women ages 40-74 between 1/2015-6/2016 using a validated algorithm. We defined DBT as a claim for screening DBT on the same day as a screening 2D mammogram. Claims were attributed to groups of providers (practices) based on billing identifiers. Practice size was defined as number of screening mammograms performed during the study period. We evaluated associations between DBT uptake and practice characteristics using descriptive statistics. We also evaluated whether DBT use was correlated with local area competition, quantified by the Herfindahl-Hirschman Index (HHI). We calculated the HHI for each hospital referral region (HRR) in the US. Results: Our study included 3,833,061 2D screening mammograms, of which 644,631 (16.8%) were performed with DBT. Breast cancer screening exams were attributed to a total of 8,114 practices. During the study period, 26.5% of practices used DBT. DBT uptake was associated with larger practice size (mean size 969 vs 188, p < .001). Practices using DBT were more likely to be located in a metro area compared to practices not using DBT (88.0% vs 71.4%, p < .001). Among practices already using DBT at the study start, providers typically used it in a minority of patients, though use varied widely (median use 25.0%, IQR 7.1% - 62.2%). Local competition, characterized by the HHI, was not correlated with DBT use (r = 0.01). Conclusions: In the absence of national guidelines, breast cancer screening practice patterns have diverged, with some practices using DBT commonly, while others not using it at all. Data on long term health outcomes associated with DBT are needed to help inform guidelines and standardize breast cancer screening practices in the US.
Ten years of non small cell lung cancer (NSCLC) cases mapped by mailing address, stage, follow up days and treatment in the Austin Round Rock Texas metro area.
Authors: Christopher O. Ruud, Henry T Robertson, Christopher J Kim, Paul Zito, Dennis Wylie, Junfeng Jiao
Journal: Journal of Clinical Oncology (2018)

e18669 Background: A review of the North American Cancer Registries (NAACCR) found that only 66.4% of Stage I, II NSCLC patients received curative surgery. Mapping treatment would reveal the neighborhoods with undertreated patients. Central Texas is ideal for mapping with no competing causes for clustering of cases, no EPA superfund sites and radon is distributed evenly. Aim: Define the location of NSCLC cases by staging, treatment, and survival in the Austin Metro area to guide targeted interventions. Methods: Cancer Registries at Seton and St David’s Hospitals were queried for NSCLC Diagnosed 2004-2014, Age < 80, Address in 5 county metro, excluding resident of chronic care facility, homeless. A total of 2822 patients were identified (Stage I,II = 759, Stage III = 465, Stage IV = 941, and 99 = 657) . Using the registry records each case was coded for initial treatment. The hierarchy for assigning treatment was Chest Surgery, Radiation, Chemotherapy, Metastasectomy. Combined treatment cases were assigned to the higher modality. Results: There was a minor difference from reported curative surgery rate 67% (n = 511) for Stage I, II patients with 11% (n = 82) radiation. Only 16% (n = 119) Stage I, II subjects had no treatment. Forty six percent of Stage III (n = 465) were treated for cure with combined modality therapy, 25% (105) had no treatment. Registrars code 99-unstageable when there is TX, NX, or MX. This group had 46% (n = 304) no treatment patients compared to 35% (n = 329) in stage IV. Overall 30% (n = 857) patients had no treatment, cancer registry entries indicated 48 refused treatment and 70 were considered too fragile to treat. In the entire population, 2% (n = 63) were referred out for initial treatment. Maps comparing treated and untreated patients by stage and follow up days were produced. Conclusions: It is possible to map treatment, stage, and survival. This information should be useful in implementing targeted reduction of the burden of care, screening, and health literacy interventions.
Ability to Predict New-Onset Psychological Distress Using Routinely Collected Health Data: A Population-Based Cohort Study of Women Diagnosed With Breast Cancer
Authors: Ania Syrowatka, James A. Hanley, Daniala L. Weir, William G. Dixon, Ari N. Meguerditchian, Robyn Tamblyn
Journal: Journal of the National Comprehensive Cancer Network (2018)

Objectives: The primary objective of this study was to identify the predictors of new-onset psychological distress available in routinely collected administrative health databases for women diagnosed with breast cancer. The secondary objective was to explore whether the predictors vary based on the period of cancer care. Methods: A population-based cohort study followed 16,495 female patients with newly diagnosed breast cancer who did not experience psychological distress during the 14 months before breast cancer surgery. The incidence of psychological distress was reported overall and by type of mental health problem. Time-varying Cox proportional hazards models were developed to identify predictors of new-onset psychological distress during 2 key periods of cancer care: (1) hospital-based treatment during which women undergo treatment with breast surgery, chemotherapy, and/or radiation, and (2) 1-year transitional survivorship when women begin follow-up care. Results: The incidence of psychological distress was 16% within each period. Anxiety was present in 85.1% and 65.5% of new cases during hospital-based treatment and transitional survivorship, respectively. Predictors during both periods were younger age, receipt of axillary lymph node dissection, rheumatologic disease, and baseline menopausal symptoms, as well as new opioid dispensations, emergency department visits, and hospital contacts that occurred during follow-up. Other predictors varied based on the period of cancer care. More advanced breast cancer and type of treatment were associated with onset of psychological distress during hospital-based treatment. Psychological distress during transitional survivorship was predicted by diagnosis of localized breast disease, shorter duration of hospital-based treatment, receipt of additional hospital-based treatment in survivorship, and newly diagnosed comorbidities or symptoms. Conclusions: This study identified the predictors of new-onset psychological distress available in routinely collected administrative health databases, and showed how predictors change between hospital-based treatment and transitional survivorship periods. The results highlight the importance of developing predictive models tailored to the period of cancer care.
Incidence of pre-treatment and off-treatment pericardial and pleural effusions by line of therapy in patients with small cell lung cancer: An analysis of electronic health records data.
Authors: Rui Jiang, Scott Gulbranson, Mondira Bhattacharya, Fabio A Lievano, Philip Komarnitsky, Martina Koch, Ravi C. Potluri, Jerzy Edward Tyczynski
Journal: Journal of Clinical Oncology (2018)

e20569 Background: Pericardial (Pc) and pleural (Pl) effusions can occur as complications of lung cancer and chemotherapy. Population-based data on the risk of pre- and off-chemotherapy Pc/Pl effusions in small cell lung cancer (SCLC) are scarce. Methods: We estimated the incidence of pre-treatment and off-treatment emergent Pc/Pl effusions by line of therapy (LOT) in SCLC using Optum’s de-identified Electronic Health Record dataset. Of 8,291 patients with newly diagnosed SCLC between 01/01/2008 and 09/30/2016, 3,622, 1,211, 428 patients received 1st-, 2nd-, 3rd_LOT, respectively. Pc/Pl effusions were identified by a combination of ICD-9/ICD-10, procedures, or natural language processing (NLP) terms. Each patient contributed to follow-up time from date of diagnosis (pre-) or 30 days after end of LOT (off-) to start of next LOT, or earlier of (loss to follow-up date or 365 days from date of diagnosis (pre-) or 30 days after end of LOT (off-)) if there was no subsequent LOT, or first occurrence for those with an outcome event. Results: At diagnosis, median age was 69, 46% were male, 84% had extensive disease. The pre-treatment and off-treatment incidence rate following completion of 1st-, 2nd-, 3rd- LOT in SCLC was 0.75, 0.62, 0.85, 0.90 per 1,000 person-days for Pc effusion and was 3.96, 2.43, 2.63, 3.61 per 1,000 person-days for Pl effusion, respectively (Table 1). Conclusions: This analysis showed a ‘V’ shape pattern in Pc/Pl effusion risk during pre- and off-treatment period suggesting a possible initial treatment effect followed by increasing risk due to disease progression or chemotherapy exposure accumulation. Table 1. Incidence of pre- and off-treatment Pc and Pl effusion Pc effusion Pl effusion Index–LOT1 LOT1-2 LOT2-3 LOT3-4 Index–LOT1 LOT1-2 LOT2-3 LOT3-4 No. patients with a pre- or off-treatment event 669 243 72 20 2,792 788 196 67 Pre- or off-treatment time across all patients, days 892,206 390,640 84,715 22,100 705,661 324,464 74,496 18,550 Incidence rate per 1000 person-days (95% CI) 0.75 (0.69-0.81) 0.62 (0.55-0.71) 0.85 (0.67-1.07) 0.90 (0.55-1.40) 3.96 (3.81-4.11) 2.43 (2.26-2.60) 2.63 (2.28-3.03) 3.61 (2.80-4.59)
Transcriptional expression patterns of patient-derived tumorspheres predict outcomes in high-grade serous ovarian carcinoma.
Authors: Jonathan David Boone, Bobbi E Johnston, Sara J Cooper, John Michael Straughn, Donald J. Buchsbaum, Rebecca Christian Arend
Journal: Journal of Clinical Oncology (2016)

e23125 Background: To evaluate the molecular profile by RNA sequencing of Stage III or IV high-grade serous ovarian carcinoma (HGSC) tumor cells isolated from the ascites of platinum sensitive compared to platinum resistant/refractory patients. Methods: Under IRB approval, ascites was collected and tumor cells isolated from 19 patients with HGSC prior to receiving chemotherapy. After plating tumor cells in stem-cell media on low-attachment plates, tumorspheres formed within 24 hrs. They were confirmed by a board certified pathologist to be 95-100% malignant epithelial cells free of fibroblasts, white blood cells, and red blood cells. Ten patients were platinum sensitive (disease free interval ³ 6 months after adjuvant therapy) and 9 were platinum resistant/refractory (progressed on primary therapy or recurred within 6 months). 50M RNA-seq reads was acquired from each of the 19 ascites samples. Differential expression was determined by DESeq2. Results: We identified 923 transcripts with differential expression between platinum sensitive and resistant patient ascites. We used the DAVID Pathway analysis tool to identify 18 statistically enriched pathways (adjusted p-value < 0.05). Six of these are linked to immune response, inflammation or wound healing. Two are related to migration and three involve cell adhesion. To explore further the role of the immune system, we showed that previously described immune regulators and effectors such as CiiTA, CD274 and CTSH also have differential expression in platinum sensitive patients compared to resistant. Conclusions: Our analysis shows that expression of immune genes is critical in patient response. We hypothesize that tumor cells expressing transcription factors that enable them to act as antigen presenting cells have a better response to treatment independent of tumor infiltrating lymphocytes or other immune cells. Identifying drugs that could upregulate these genes could help reverse platinum resistance in ovarian cancer patients.