tbuckley/cabot-search huggingface dataset:
Associations of insulin-like growth factor binding proteins and adiponectin with disease progression and mortality in metastatic colorectal cancer: Results from CALGB/SWOG 80405 (Alliance).
Authors: Brendan John Guercio, Alan P. Venook, Sui Zhang, Fang-Shu Ou, Donna Niedzwiecki, Heinz-Josef Lenz, Federico Innocenti, Michael N. Pollak, Andrew B. Nixon, Michelle R. Mahoney, Bert O'Neil, James Edward Shaw, Blase N. Polite, Crystal S. Denlinger, James Norman Atkins, Richard M. Goldberg, Robert J. Mayer, Charles David Blanke, Charles S. Fuchs, Jeffrey A. Meyerhardt
Journal: Journal of Clinical Oncology (2019)

3035 Background: Energy balance-associated biomarkers such as insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) have been associated with risk and prognosis of various malignancies. Their relationship to disease progression and mortality in metastatic colorectal cancer (mCRC) requires further study. Methods: In a prospective cohort study, baseline plasma IGFBP-3, IGFBP-7, C-peptide, IGF-I, and adiponectin were measured at trial registration among 1,086 patients participating in a National Cancer Institute-sponsored clinical trial of first-line therapy for mCRC. We used Cox proportional hazards regression to adjust for confounders and examine associations of biomarkers with overall (OS) and progression-free survival (PFS). Results: Higher plasma IGFBP-3 was associated with longer OS (adjusted P trend &lt; .001) and PFS (adjusted P trend = .003). Compared to patients in the lowest IGFBP-3 quintile, patients in the highest quintile experienced an adjusted HR for all-cause mortality of 0.58 (95% CI 0.42 to 0.78) and for disease progression or mortality of 0.60 (95% CI 0.45 to 0.82). Higher plasma IGFBP-7 was associated with shorter OS (adjusted P trend &lt; .001) and PFS (adjusted P trend = .02). Compared to patients in the lowest IGFBP-7 quintile, patients in the highest quintile experienced an adjusted HR for all-cause mortality of 1.52 (95% CI 1.24 to 1.88) and for disease progression or mortality of 1.28 (95% CI 1.05 to 1.57). C-peptide and IGF-I were not significantly associated with patient outcomes (adjusted P trend = .73 and .30 for OS). Adiponectin was not associated with OS; there was a U shaped association between adiponectin and PFS, wherein low and high values were associated with shorter PFS ( P non-linear trend = .03). Conclusions: In patients with mCRC, high plasma IGFBP-3 and low IGFBP-7 were associated with reduced risk of disease progression and mortality. These data suggest that energy-balance associated biomarkers may offer prognostic and biologic insights into mCRC. Support: U10CA180821, U10CA180882, BMS, Genentech, Pfizer, Sanofi; https://acknowledgments.alliancefound.org .
BIOLUMA: A phase II trial of nivolumab in combination with ipilimumab to evaluate efficacy and safety in lung cancer and to evaluate biomarkers predictive for response—Preliminary results from the SCLC cohort.
Authors: Rieke Nila Fischer, Julie George, Andreas H. Scheel, Hans Anton Schloesser, Maria Vehreschild, Peter Brossart, Walburga Engel-Riedel, Frank Griesinger, Christian Grohé, Karl-Otto Kambartel, Jens Kern, Barbara Hermes, Kathrin Nachtkamp, Jens Peter Panse, Martin Sebastian, Markus Lehmann, Rainer Gerhard Wiewrodt, Reinhard Büttner, Roman K. Thomas, Juergen Wolf
Journal: Journal of Clinical Oncology (2019)

8563 Background: Patient selection, dosing regimens and resistance mechanisms for immune checkpoint inhibitor combination therapy remain unmet medical needs in lung cancer. We present interim data from the small-cell lung cancer (SCLC) cohort of the ongoing BIOLUMA trial which evaluates efficacy and safety of nivolumab and ipilimumab in lung cancer with a broad translational program to identify potential biomarkers predictive of response and/or resistance including whole exome sequencing (WES) of serial biopsies, functional analysis of peripheral T-cells and gut microbiome analyses. Methods: BIOLUMA is an investigator initiated, multicentre non-randomised phase II trial in 2 nd line patients with SCLC. The initial all-comer SCLC cohort was recently amended for inclusion of patients with high tumor mutation burden (TMB) only. Patients are pre-screened for TMB by WES at the time of first diagnosis. After progression on platinum-based therapy, 4 cycles of nivolumab 1 mg/kg q3w in combination with ipilimumab 3 mg/kg q3w and subsequent nivolumab 240 mg flat dose as monotherapy are given. Primary endpoint is overall response rate (ORR) of the upfront combination therapy. Analysis of sequential tumor biopsies, blood and gut microbiome is performed at different timepoints. Results: The SCLC cohort was amended to include TMB high patients only, after two treatment-related deaths had occurred and emerging data indicated treatment benefit depends on high TMB status for the combination therapy. Both patients with treatment-related death had a CT-scan documented partial response (not confirmed according to RECIST due to death). One each died of pneumonitis and encephalitis. From the all-comer cohort, efficacy data are available for 18 patients. ORR was 38.8% with 7 partial and no complete responses. Stable disease occurred in 16.7% (n = 3) resulting in a DCR of 55.5%. TMB pre-screening for the amended cohort is currently ongoing. Conclusions: In the SCLC cohort, upfront combination therapy of nivolumab and ipilimumab shows remarkable ORR but is accompanied by high toxicity rates. In order to ensure a reasonable balance of risks and treatment benefit, only TMB high patients are included after an amendment of the cohort to improve the risk/benefit ratio. Clinical trial information: NCT03083691.
SAT0575 RACIAL DIFFERENCES IN PRESCRIPTION PATTERNS OF DISEASE MODIFYING ANTI-RHEUMATIC DRUGS, NARCOTICS AND GLUCOCORTICOIDS AMONG MIDDLE-AGED PATIENTS WITH DISABILITY AND RHEUMATOID ARTHRITIS
Authors: Iris Navarro-Millan, Mangala Rajan, Geyanne Lui, Lisa Kern, Laura Pinheiro, Monika Safford, Jeffrey Curtis
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Many patients with rheumatoid arthritis (RA) become disabled. While racial/ethnic differences in RA treatment have been described in RA patients without disability, less is known about racial/ethnic differences in RA treatment among middle-aged individuals with RA receiving disability benefits. <h3>Objectives:</h3> To determine if racial/ethnic differences exist in the prescription patterns of conventional synthetic (CS) and biologic (B) disease modifying anti-rheumatic drug medications (DMARD), glucocorticoids, and opioids. <h3>Methods:</h3> We conducted cross-sectional analyses in the calendar year 2014 using Medicare and Medicaid claims data of individuals receiving Social Security Disability Income (SSDI). To be included, patients had to be continuously enrolled over one year, aged &lt;65 years, eligible for both Medicare and Medicaid, and have RA, defined as: 1) two RA diagnoses (ICD9-714.xx) by a rheumatologist between 7 to 365 days apart; OR 2) one RA diagnoses by a rheumatologist and at least 1 prescription for a DMARD. We examined the proportion of patients with CS-DMARD, B-DMARD, glucocorticoid (&gt;7.5 mg prednisone daily for &gt;30 days), or opioid (either a prescription for opioids with 3 refills or at least one 90 day supply) prescriptions in each year by race/ethnicity. Generalized estimating equation (GEE) models was used to report adjusted differences in prescription rates for Blacks, Hispanics, and Other using Whites as the reference group, adjusting for age, gender, and medical comorbidities. <h3>Results:</h3> The were 9,265 patients in 2014 out of which 60% were White, 21% were Black, 15% were Hispanic, and 5% were Other race. The proportion of female patients by race/ethnicity was &gt;75% for each group. Hispanics had a 6.6% point higher rate of B-DMARD prescriptions and a 10.7% point lower rate of opioid prescriptions compared to Whites. Blacks had a 3.4% point higher rate of glucocorticoid prescriptions, and a 3.3% point lower rate of opioids prescriptions compared to Whites. <h3>Conclusion:</h3> We observed racial differences in arthritis-related treatment patterns, among disabled RA patients, with Blacks receiving less biologic treatment and Whites receiving more opioids. Hispanics received the highest prescription rates of biologics and the Other race received lowest prescription rates of opioids among the three racial/ethnic groups. Further studies are needed to examine the reasons for such differences. <h3>Disclosure of Interests:</h3> Iris Navarro-Millan: None declared, Mangala Rajan: None declared, Geyanne Lui: None declared, Lisa Kern: None declared, Laura Pinheiro: None declared, Monika Safford Grant/research support from: Amgen, Jeffrey Curtis: None declared
Circulating tumor (ct)-DNA alterations in patients with testicular germ cell tumors.
Authors: Archana Agarwal, Amin Nassar, Rebecca Nagy, Catherine Curran, Sarah Abou Alaiwi, Richard B. Lanman, AmirAli Talasaz, Christopher Sweeney, Guru Sonpavde
Journal: Journal of Clinical Oncology (2020)

415 Background: Testicular germ cell tumors (GCT) infrequently harbor somatic mutations. ctDNA assessment allows the noninvasive genomic profiling of malignancies and may assist with understanding molecular evolution of resistance. We report ctDNA profiling of patients (pts) with testicular GCTs. Methods: 40 patients (pts) with advanced testicular GCTs from multiple institutions in the USA that underwent ctDNA analysis using the Guardant (G)-360 platform were eligible and a total of 48 samples were collected. 36 pts had one sample, 3 pts had 2 samples, 1 pt had 6 samples. De-identified demographic data were collected in addition to data for ctDNA alterations. G360 employed a CLIA-certified ctDNA panel that assessed single nucleotide variant and copy number alterations in 68 to 73 genes for potentially actionable genomic alterations. Variants reported at least 3 times in the Catalogue of Somatic Mutations in Cancer (COSMIC) database or found in OncoKB were considered pathogenic. Results: Of 40 patients with testicular GCTs, 13pts (33%) were post systemic therapy. The median age was 36 years (range 20-61). 199 ctDNA alterations were detected in 35 patients (87.5%) across 41 genes. Among the 199 alterations, 102 were believed to be pathogenic and detectable in 26 samples from 25 pts (62.5) (%). The most common pathogenic somatic alterations were KRAS (n = 16/102, 16%), TP53 (n = 16/102, 16%), CCND2 (n = 9/102, 9%), CDK6 (n = 9/102, 9%), MET (n = 9/102, 9%), and RAF1 (n = 6/102, 6%). Conclusions: ctDNA alterations were frequently detected in resistant testicular GCTs and appear similar to alterations previously described in tumor tissue analyses of testicular GCTs. Given that ctDNA offers a non-invasive means of profiling tumor DNA, further development of this promising modality is warranted to study the evolution of resistance to cisplatin-based chemotherapy and new potentially actionable alterations.
Circulating tumor cell (CTC) PD-L1 and interferon regulatory factor-1 (IRF-1) expression as biomarkers of anti-PD-(L)1 response.
Authors: Laura Kennedy, Arturo B. Ramirez, Lance U'Ren, Yao Sun, Grace Durenberger, Laura Quan Man Chow, Petros Grivas, Vijayakrishna K. Gadi
Journal: Journal of Clinical Oncology (2019)

e14032 Background: Anti-PD-(L)1 checkpoint inhibitors (CPI) are remarkable due to durable responses, tolerability, and improvements in survival across multiple solid tumors. Unfortunately, CPI produce objective responses in only a small subset of solid tumors patients (pts). We hypothesized that PD-L1 and IRF-1 expression on CTC may correlate with CPI response, and evaluate their expression in this pilot study. Methods: Pts with metastatic solid tumors initiating anti-PD(L)-1 mono- or combination therapy were eligible. Pts had 7.5 cc of blood drawn for CTC evaluation at 3 timepoints: baseline, after 1 CPI dose, and 3-6 months after starting CPI or at time of CPI discontinuation. Peripheral blood CTC were isolated with the AccuCyte kit and stained for CK/EpCAM, anti-CD45, nuclear dye, PD-L1, and IRF-1. CTCs were then identified with CyteFinder software. Results: 16 pts have enrolled to date with median age 71 years (range 28-83) and median ECOG = 1 (range 0-3). 50% were female. Diagnoses include NSCLC (50%), head and neck cancer (13%), breast cancer (13%), and others (24%). CTC were identified at baseline in 13/16 pts (# CTCs range 0-101). 12 pts with baseline CTC have had restaging scans since starting CPI. By RECIST 1.1, 3 pts had partial response (PR), 1 had stable disease (SD), and 8 had progressive disease (PD). The pts with PR more frequently had IRF-1 staining on baseline CTC (Table), and 1/3 had PD-L1 staining. 6 pts had tumor PD-L1 staining available for correlation, and 3/6 of those pts were PD-L1+ (tissue PD-L1 ≥ 1%). 1/3 pts with PD-L1+ tumor staining had CTCs that were PD-L1+. In the 3 pts with negative PD-L1 tumor staining, 1 pt had a mixed PD-L1+/PD-L1- CTC population and the others had no PD-L1 staining. Conclusions: CTC isolation and enumeration seem feasible across tumor types. Pts with PR to anti-PD-(L)1/ might have higher prevalence of IRF-1+ CTC; however, results are preliminary and more pts and samples are being evaluated. [Table: see text]
Pilot integrated biomarker study of VX15/2503 in combination with ipilimumab and/or nivolumab in patients with resectable metastatic melanoma.
Authors: Michael C. Lowe, Gregory B. Lesinski, Keith A. Delman, Melinda Lynne Yushak, Elizabeth E. Evans, Terrence Lee Fisher, Ragini Reiney Kudchadkar
Journal: Journal of Clinical Oncology (2019)

TPS9603 Background: Interrogation of the tumor microenvironment (TME) is crucial to provide insight into biological activity, resistance mechanisms and implementation of rational combination immunotherapies. Semaphorin 4D (SEMA4D, CD100) has broad immunomodulatory effects in the TME. In preclinical models, blockade of SEMA4D promoted immune infiltration and reduced recruitment of immunosuppressive myeloid cells. Preclinical combinations of anti-SEMA4D with immune checkpoint inhibitors (ICIs) enhanced T cell activity and tumor regression. VX15/2503 (pepinemab), an IgG4 humanized monoclonal antibody targeting SEMA4D, is being evaluated in an integrated biomarker trial to characterize immunomodulatory effects in melanoma (NCT03769155). Methods: Patients with biopsy-proven stage IIIB, C, and D melanoma are eligible. Prior to curative-intent surgery, patients receive pepinemab alone or in combination with nivolumab and/or ipilimumab every three weeks for two doses. A control cohort proceed directly to surgery. Resection specimens will be collected for comparison across treatment groups and with a pre-treatment biopsy. Blood will be collected for PK, PD, and correlative biomarker assessments. The primary objective is to evaluate effects on the immune profile in TME and peripheral blood. Additional objectives include safety of pepinemab (alone and in combination with ICI), and pathologic and radiographic responses. Multiplex flow cytometry panels were created to phenotype cells in the TME and periphery. A multiplex IHC assay utilizing a sequential probe and strip procedure has been qualified that allows co-localization, orientation, and quantification of multiple immune markers. Analysis of immune subsets include cytotoxic T cells, neutrophils, Tregs, DCs, monocytes, macrophages, and myeloid-derived suppressor cells. Target engagement and expression of SEMA4D and its receptors will be evaluated. As of 01 Feb 2019, 8 of 36 patients have been enrolled. This trial will provide the first biomarker-driven clinical assessment of anti-SEMA4D antibody activity to reprogram the TME. Clinical trial information: NCT03769155.
Association of Staphylococcus aureus colonization with food allergy occurs independently of eczema severity
Authors: Olympia Tsilochristou, George du Toit, Peter H. Sayre, Graham Roberts, Kaitie Lawson, Michelle L. Sever, Henry T. Bahnson, Suzana Radulovic, Monica Basting, Marshall Plaut, Gideon Lack, Susan Chan, Adam Fox, Helen Fisher, Mable Abraham, Muhsinah Adam, Louise Coverdale, Claire Duncan, Amy Nixon, Una O'Dwyer-Leeson, Victoria Offord, Aine Sheridan, Fiona Watson, Natalie Witham, Kathryn Cockerell, Gail Harland, Tiffany Miller, Charlotte Stedman, Catherine Clarke, Richard Cleaver, Gemma Deutsch, Alicia Parr, Natalia Becares, Matthew Crossley, Natalia do Couto Francisco, Kerry Richards, Ewa Pietraszewicz, Alick Stephens, Asha Sudra, Rianne Wester, Alastair Wilson, Celine Wu, Jenna Heath, Kathryn Hersee, Devi Patkunam, Adam Asare, Eduard Chani, Judith Evind, Noha Lim, Audrey Plough, Judith Evind, Don Whitehouse, Margarita Gomez Lorenzo, Joy Laurienzo Panza, Stephanie Lussier, Jack Hu, Travis Mason
Journal: Journal of Allergy and Clinical Immunology (2019)
Impact of chemotherapy sequence on the efficacy of scalp cooling devices for alopecia prevention.
Authors: Omar Peña-Curiel, María Alejandra Garza-Ledezma, Héctor Díaz-Pérez, Bertha Alejandra Martinez-Cannon, Mauricio Canavati-Marcos, Servando Cardona-Huerta, Cynthia Villarreal-Garza
Journal: Journal of Clinical Oncology (2019)

e12034 Background: The use of scalp cooling devices (SCD) has been widely adopted for prevention against chemotherapy-induced alopecia (CIA). However, efficacy of SCD varies between different chemotherapy (CT) regimens. The aim of this study was to evaluate the effectiveness of SCD in breast cancer patients with different CT regimens treated in a tertiary cancer center in Monterrey, Mexico. Methods: All consecutive patients who used SCD were included. Data regarding treatment regimens and efficacy outcomes were prospectively collected. A descriptive analysis was performed to compare the effectiveness among the different CT regimens and sequences used. Results: We included a total of 49 patients with SCD usage from July 2016-January 2019. Table summarizes SCD efficacy, toxicities and CT regimens. In our study, 76% of patients had grade ≤1 CIA using SCD. 35% withdrew SCD use, with hair loss being the most common reason. 58% of patients who received upfront anthracycline-cyclophosphamide (AC) experienced grade 2 CIA. In contrast, no patients receiving taxane-only treatment had grade 2 CIA. Notably, only 3 of 16 patients (19%) who received upfront paclitaxel followed by anthracyclines developed grade 2 CIA. Conclusions: SCD proved to be highly effective in preventing grade 2 CIA with different CT regimens, including patients that received anthracycline-based regimens who started treatment with taxanes upfront. Accordingly, our results suggest that CT sequence, rather than type of CT agent may have a significant impact on the efficacy of SCD in CIA prevention. The results of larger studies are required to confirm our findings.[Table: see text]
Efficacy and safety profile of lurbinectedin in second-line SCLC patients: Results from a phase II single-agent trial.
Authors: Luis G. Paz-Ares, Jose Manuel Trigo Perez, Benjamin Besse, Victor Moreno, Rafael Lopez, Maria Angeles Sala, Santiago Ponce Aix, Cristian Marcelo Fernandez, Mariano Siguero, Carmen Maria Kahatt, Ali Hassan Zeaiter, Khalil Zaman, Valentina Boni, Jennifer Arrondeau, Maite Martinez Aguillo, Jean-Pierre Delord, Ahmad Awada, Rebecca Sophie Kristeleit, Maria Eugenia Olmedo Garcia, Vivek Subbiah
Journal: Journal of Clinical Oncology (2019)

8506 Background: Lurbinectedin (L) is a novel anticancer drug that inhibits activated transcription and induces DNA double-strand breaks, leading to apoptosis. Methods: A multicenter phase 2 basket trial assessed the efficacy and safety of L in several cancer types, including small cell lung cancer (SCLC). Primary endpoint was confirmed overall response rate (ORR) by RECIST v.1.1. In the SCLC cohort, a target ORR ≥30% was set. One-hundred and five patients (pts) with ECOG PS 0-2 who had received one prior chemotherapy line were treated with L 3.2 mg/m 2 as a 1-hour i.v. infusion on Day 1 q3wk. Results: Median age was 60 years (range, 40-83), 60% were male, ECOG PS 0/1/2 (32%/62%/6%), liver metastasis 41%, history of CNS involvement 3.8%, prior platinum 100%, median chemotherapy-free interval (CTFI): 3.5 (0-16.1) months; prior immunotherapy (IO): 7.6%. Pts received a median of 4 cycles (range, 1-24). Conclusions: L monotherapy is active in second-line SCLC in both resistant and sensitive disease. The acceptable and manageable safety profile is also associated to a convenient treatment administration (Day 1 q3wk). L as second-line treatment in SCLC emerges as a new promising drug for this unmet clinical need. Clinical trial information: NCT02454972. [Table: see text]
Case 48-1984
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Stephen W. Parker, Edward P. Richardson, Georges F. McCormick
Journal: New England Journal of Medicine (1984)

Presentation of CaseA 43-year-old right-handed man was admitted to the hospital because of headache and visual disturbances.He was well until three days earlier, when he experienced the sudden onset of a "flashing" light in the left visual field, followed by a severe, throbbing right-sided headache and pain in the right eye; his left visual field was "cloudy." The visual symptoms soon cleared, the headache subsided after 16 hours, and he returned to his work as a dishwasher. On the following day his symptoms recurred in a milder form for four hours. One day before entry another bout of . . .
ROMAN: Reduction in oral mucositis with avasopasem manganese (GC4419)–Phase III trial in patients receiving chemoradiotherapy for locally advanced, nonmetastatic head and neck cancer.
Authors: Jon Holmlund, Jeffrey Mark Brill, Robert Fairbanks, Deborah Saunders, Stephen T. Sonis, Matt Downs, Carryn M. Anderson
Journal: Journal of Clinical Oncology (2020)

TPS6596 Background: Approximately 70% of patients receiving intensity-modulated radiotherapy (IMRT) plus cisplatin for locally advanced head and neck cancer (HNC) develop SOM, defined as WHO Grade 3 or 4, which limits patients' ability to eat solids (Gr 3) or liquids (Gr 4, requiring enteral nutrition). An RT-induced burst of superoxide initiates oral mucositis (OM) development. GC4419, a superoxide dismutase mimetic, interrupts this process by converting superoxide to H2O2. It showed promising reduction of SOM in a published open-label Phase 1b/2a trial (IJROBP 1 Feb 2018). In a subsequent randomized, double-blind placebo-controlled trial in 223 patients receiving IMRT/cisplatin for HNC (ASCO 2018), 90 mg of GC4419 administered M-F prior to IMRT demonstrated statistically significant reduction in SOM duration (p=0.024, median 1.5 days @ 90 mg vs. 19 days placebo) and meaningful reductions @ 90 mg in SOM incidence (43% vs. 65%) and severity (incidence of Grade 4, 16% vs. 30%). The safety results were acceptable and consistent with the known toxicities of IMRT/cisplatin. Methods: 335 patients at multiple centers in the U.S. and Canada with locally-advanced, nonmetastatic head and neck cancer (oral cavity/oropharyngeal) receiving 70 Gy IMRT (&gt;50 Gy to &gt; 2 oral sites) plus cisplatin (40 mg/m2 qwk x 6-7, or 100 mg/m2 q3wk x 3) are being randomized (double-blinded) 3:2 to 90 mg of GC4419 or placebo, M-F before each RT fraction. Enrollment is stratified by cisplatin schedule and treatment setting (definitive vs. post-op). OM by the WHO scale will be assessed twice weekly during RT &amp; weekly for 2 weeks post RT. The primary efficacy endpoint is incidence of SOM through the end of IMRT. Secondary efficacy endpoints include severity (incidence of Grade 4 OM through the end of IMRT), &amp; days of SOM (days from first to last SOM for all patients, with patients never developing SOM having 0 days of SOM by definition). Days of SOM for the subset developing SOM will be analyzed descriptively. Patients will be followed for one year post IMRT for tumor progression/recurrence and for two years for survival. Clinical trial information: NCT03689712 .