tbuckley/cabot-search huggingface dataset:
Electronic calculation of quality measures in the EMR and dependence on data capture in structured fields: The OCM quality reporting experience.
Authors: James Hamrick, Cindy Revol, Rohit Parulkar, Olaf Lemmers, James Gippetti, Nick Bauer-Levey, DJ Lee, Alison Fugaro, Robert J Green, Amy Pickar Abernethy, Michael A. Kolodziej
Journal: Journal of Clinical Oncology (2017)

e18278 Background: Reporting of quality measures is ideally achieved electronically. This is dependent on presence of data elements in structured fields. We report on the variability of quality measure reporting in the OCM for quality measures OCM 8 (adjuvant chemotherapy in stage 3 colon cancer), 9 (adjuvant chemotherapy in HR- breast cancer), 10 (adjuvant trastuzumab for Her2+ breast cancer), and 11 (adjuvant hormonal therapy for HR+ breast cancer). Methods: Quality measures were calculated for 30,524 patients across 35 practices participating in the OCM. We examined the calculation of quality metrics OCM-8, 9, 10, and 11 based on presence or absence of data elements in the medical record. Results: For quality measures OCM-8 and 9 that require documentation of date of surgery, only 1.3% and 1.6%, respectively, of patients could be included in the calculation due to absence of surgical date in a structured field. For quality measures OCM 9 and 11 that require attestation of surgical staging of breast cancer, this data element was documented in 0% of patients. For OCM 9 and 10 that require stage documentation of breast cancer, this data element was documented in 63% and 75%, respectively, of patients (range 12-100%). In cases where staging criteria were not met, 58% and 44%, respectively, of patients were removed due to total absence of staging data in structured fields. Conclusions: Quality measure calculation and reporting is highly dependent on documentation of data elements in structured fields. Lack of documentation of key elements distorts calculation of the measure. Modification of physician workflow or restructuring of measure calculation to optimize use of well documented structured elements will improve generalizability of quality measure reporting. Manual abstraction of data does not represent a feasible alternative.
Mutational landscape of myelodysplastic/myeloproliferative neoplasm–unclassifiable
Authors: Prithviraj Bose, Aziz Nazha, Rami S. Komrokji, Keyur P. Patel, Sherry A. Pierce, Najla Al-Ali, Andrew Sochacki, Aaron Shaver, Wencai Ma, Xiaoping Su, Naval G. Daver, Courtney D. DiNardo, Guillermo Garcia-Manero, Sanam Loghavi, Carlos Bueso-Ramos, Hagop M. Kantarjian, Mikkael A. Sekeres, Michael R. Savona, Jaroslaw P. Maciejewski, Srdan Verstovsek
Journal: Blood (2018)
Risk of mortality in adult cancer febrile neutropenia patients with a machine learning approach.
Authors: Chintan Shah, Xinsong Du, Rohit Bishnoi, Jiang Bian
Journal: Journal of Clinical Oncology (2018)

e13562 Background: Febrile neutropenia (FN) is a major dose-limiting toxicity of myelosuppressive therapy in cancer patients and impose substantial morbidity and mortality risks. We analyzed National Inpatient Sample (NIS) database to understand the trend in FN and predict mortality in cancer patients who experienced FN using a machine learning (ML) approach. Methods: We used the Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS) data. Cancer discharges were identified using the HCUP Clinical Classifications Software (CCS) categorizations (11-45), within which FN patients were identified with International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes (ICD-9-CM: 7806 and 288, 2841 or 1125). We examined trends in FN discharges and mortality rates using during 2003 – 2015, and then built various models on NIS 2013 data to predict mortality. Results: The percentage of discharges secondary to cancer-related FN kept increasing from 0.2% in 2003 and stabilized around 2% since 2010. However, associated cost has continued to rise (average cost of $36,853 vs $105,912 respectively, in 2003 and 2015). The unadjusted mortality rate also kept increasing from 2.2% in 2003 and has stabilized around ~ 4.2% since 2010. The logistic regression model showed significantly higher odds of mortality with advancing age (2.8%, 3.8%, 7%, 8.3% respectively, for age group 18-44, 45-64, 65-84, 85+). Presence of bacteremia compared to no bacteremia (4.5 vs, 3.3, P < 0.01), non-teaching hospitals compared to teaching hospital (4.9% vs, 4.3%, P < 0.01), and comorbidities such as hypertension, paralysis, hypothyroidism, depression showed higher risk of mortality (P < 0.05). Patients admitted over weekend and transferred from another institute had higher odds of mortality (P < 0.01). Conclusions: Even in this era of widespread use of granulocyte colony-stimulating factor for primary prophylaxis and less cytotoxic immunotherapy, mortality from FN remains significantly higher and continues to impose significant financial burden. Identification of risk factors and predicting mortality risk will help clinicians take better therapeutic decisions and thus patient survival.
Surgical outcomes of single port lapraroscopic radical hysterectomy in cervical cancer.
Authors: Ji Geun Yoo, Yoon Kyung Elena Lee, Keun Ho Lee
Journal: Journal of Clinical Oncology (2017)

e17003 Background: We aim to see the postoperative outcomes of single port laparoscopic radical hysterectomy in cervical cancer. Methods: Twenty five cervical cancer patients (FIGO stage 9 IA, 13 IB, and 3 IIA) were treated by single port laparoscopic radical hysterectomy in single center. Results: Six patients were performed by type A hysterectomy, 6 by type B, and 13 by type C radical hysterectomy. Median operation time was 91, 197, and 275 minutes, respectively. Median number of pelvic nodes retrieved was 20. There was no postoperative complication except a colon serosa injury in type C radical hysterectomy and which repaired by single port approach. Ten out of 25 patients got an adjuvant radiation therapy and there were 3 recurrences (1 in type A, 2 in type C). Median disease free survival was 9.5 months in type A, 14 months in type C. Conclusions: Single port radical hysterectomy is safe and comparable to conventional laparoscopic hysterectomy in cervical cancer
Association of age, race, and public health insurance with stage of cervical cancer at diagnosis in Brazil: Results of the EVITA cohort study (LACOG0215).
Authors: Angelica Nogueira Rodrigues, Andreia Cristina de Melo, Aknar Calabrich, Eduardo Cronemberger, Kátia Luz Torres, Fernanda Damian, Rachel Jorge Dino Cossetti Leal, Carla Rameri Alexandre Silva De Azevedo, Allex Jardim da Fonseca, Yeni Verónica Neron, Joao Soares Nunes, André Lopes, Felipe Thome, Renato Leal, Giuliano Santos Borges, Paulo Ricardo Santos Nunes Filho, Facundo Zaffaroni, Gustavo Werutsky, Fernando C. Maluf
Journal: Journal of Clinical Oncology (2018)

e17509 Background: Cervical cancer (CC) is the fourth most common malignancy in women worldwide and third in Brazil. It is a health problem in in low and middle-income countries (LMIC), where most screening programs have failed to achieve its potential and 85% of the global disease burden is. Therefore, studies aiming to describe the population of patients in those countries are of uttermost importance for planning public health policies. EVITA is the major prospective CC cohort study performed in Brazil. Here we present patients’ baseline characteristics and diagnostics features. Methods: Prospective, observational study, within 16 sites in Brazil. Main eligibility criteria were 18 years-old, newly diagnosed stage I to IV invasive CC and signed informed consent. Data was collected during medical visits and from medical charts. Results are expressed as mean (± SD) and relative frequencies. Chi-square and t tests were used for comparisons. Results: A total of 631 patients were included from January 2016 to November 2017. Mean age at diagnosis was 49.3y (±13.9). Most patients had £ 8 years of formal education (49.8%), personal income £ one minimum wage (88.7%) and were treated in public health system (95.2%). 52% were smokers, 59% were had used oral contraceptives and 2% were HIV+. Of note, 87% patients reported at least one previous pap test. Squamous cell carcinoma was the most frequent histology (73.9%). Regarding stage, 12.8% of the patients were stage I, 35.2% stage II, 37.9% stage III and 10.1% stage IV at diagnosis. Factors associated with advanced stage (II-IV) at diagnosis were: older age (50.0y vs 44.6y; P .001), non-white race (89.5% vs 81.7%; P .008) and public health insurance (87.2% vs 73.1%; P .038). Conclusions: Our study shows that 82% of CC patients are stage II or more at diagnosis In Brazil and that advanced stage at diagnosis is associated with sociodemographic characteristics. It is a disease with poor prognosis, high health costs and significant social impact. Awareness campaigns towards prevention and early detection focusing on this high risk population are key for CC control in LMICs.
Abstract P246: Dietary Minerals and Metabolic Syndrome: Results From the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Authors: Catherine M Bulka, Martha L Daviglus, Daniela Sotres-Alvarez, Ramon A Durazo-Arvizu, Yasmin Mossavar-Rahmani, Victoria W Persky, Maria Argos
Journal: Circulation (2018)

Introduction: Minerals play an integral role in lipid and carbohydrate metabolism and defense against oxidative damage, and thus mineral-poor diets may be an important risk factor for cardiometabolic disease. Little is known about the relationship between dietary mineral intake and metabolic health in Hispanics/Latinos - the largest ethnic minority in the U.S. Hypothesis: Individuals consuming less than recommended amounts of certain minerals may have a greater burden of metabolic syndrome, independent of individual-level risk factors. Methods: We studied 15,051 Hispanic/Latino individuals, aged 18-74 years, from the Hispanic Community Health Study/Study of Latinos, a population-based epidemiologic study of adults enrolled from 4 U.S. communities in 2008-2011. Daily intakes of selected minerals (copper, manganese, selenium, and zinc) from up to two dietary recalls were averaged, and combined with self-reported supplemental intakes. Copper, selenium, and zinc intake levels were dichotomized at the estimated average requirement (EAR); for manganese, the adequate intake (AI) was used as a cutoff point as an EAR has not been established. Metabolic syndrome and its component abnormalities were defined per the harmonized American Heart Association/National Heart, Lung, and Blood Institute criteria as at least 3 of the following 5 criteria: high blood pressure, high triglycerides, low HDL cholesterol, high fasting glucose, or abdominal obesity. Associations of mineral intakes with prevalent metabolic syndrome and its individual components were evaluated using logistic regression models accounting for the complex sampling design of the study. Results: Intakes of copper, manganese, selenium, and zinc were below the EAR/AI in 15%, 29%, 4%, and 13% of individuals, respectively. Copper intake below the EAR was positively associated with metabolic syndrome (OR: 1.23, 95% CI: 1.05-1.44) after adjustment for energy intake, age, gender, and Hispanic/Latino background, and was primarily driven by an association with high blood pressure (1.24, CI: 1.04-1.47). Manganese intake below the AI was also associated with metabolic syndrome (1.16, CI: 1.01-1.32), with the strongest associations observed for high fasting glucose levels (1.20, CI: 1.04-1.38) and abdominal obesity (1.19, CI: 1.05-1.36). Conclusion: Consuming less than the recommended amounts of copper and manganese was associated with a greater prevalence of metabolic syndrome. Future prospective studies are needed to confirm the importance of achieving copper and manganese adequacy and synergistic aspects of foods containing these minerals for optimal cardiometabolic health.
A phase 2 trial of darolutamide maintenance therapy in patients with metastatic castration resistant prostate cancer (mCRPC) previously treated with AR targeting agents and non-progressive on a subsequent taxane (SAKK 08/16).
Authors: Richard Cathomas, Stefanie Hayoz, Andrea Corinne Fuhrer, Christine Biaggi Rudolf, Augusto Pedrazzini, Giuseppe Procopio, Silke Gillessen
Journal: Journal of Clinical Oncology (2018)

TPS5087 Background: Treatment with the AR targeting agents abiraterone or enzalutamide followed by a taxane is currently the most used treatment for men with mCRPC. Further treatment after response to chemotherapy is only indicated in case of disease progression, with limited treatment options available. Darolutamide is a second-generation oral androgen receptor antagonist which has demonstrated a good safety profile and antitumor activity in mCRPC. This trial evaluates whether the immediate use of darolutamide after successful chemotherapy can prolong radiographic progression-free survival (rPFS) compared to watchful waiting in patients with mCRPC. Methods: This is a multicenter, randomized, double-blind, placebo-controlled phase 2 trial (NCT02933801) conducted in approximately 19 sites in Switzerland and Italy. Patients with mCRPC are required to have been previously treated with abiraterone and/or enzalutamide and have no evidence of disease progression on subsequent docetaxel or cabazitaxel. Patients (N = 88) will be randomized 1:1 to receive 600 mg darolutamide BID or placebo BIDuntil disease progression. Patients will be stratified by country, WHO performance status (0, 1 vs 2), presence/absence of visceral metastases, enzalutamide vs abiraterone vs both prior to chemotherapy, and planned start of trial treatment after last taxane dose ( < 35 days vs ≥35 days). The primary endpoint is rPFS at 12 weeks after treatment initiation. The secondary endpoints are rPFS, time to PSA progression, time to symptomatic/clinical progression, event-free survival, overall survival, PSA response (30%, 50%, 90%, and best), duration of PSA response (50%), adverse events, and fatigue. The rPFS rate at 12 weeks after treatment initiation will be compared between the two treatment arms using a one-sided test statistic using the Kaplan–Meier method. Recruitment is ongoing, with the first patient randomized on 20.04.2017. Clinical trial information: NCT02933801.
Early trends of ctDNA levels in non-small cell lung cancer patients treated with immunotherapy (CLIP-IT): Pilot study.
Authors: Meera Yogarajah, Ebenezer Ofori Appah, Clive D. Morris, Katherine Baker Neblett, Greg Jones, Anthony Underwood, John F. Beeler, Paul R. Walker
Journal: Journal of Clinical Oncology (2018)

e15014 Background: Circulating tumor DNA (ctDNA) has been reported to be an independent prognostic indicator of outcome in lung cancer. The levels of ctDNA can correlate with changes in tumor burden in response to therapy. We assessed the utility of ctDNA levels as an early indicator of response to immunotherapy. Methods: Nineteen patients with advanced non-small cell lung cancer initiated on immune therapy were enrolled in this prospective trial. Blood collections were performed prior to treatment and with every cycle up to 4 cycles. Inivata's InVisionSeq, an NGS-based 36 gene panel, analyzed the ctDNA. The trends of the ctDNA allele frequency was correlated with imaging responses post 4 cycles of therapy. Results: Patients included male 26%, median age 64 years, squamous 37%, adeno 63%, median cycles 4 with anti-PD1/PDL-1 therapy either alone or in combination with platinum-based chemotherapy. Four patients only had baseline ctDNA and were not evaluable. Clinical benefit was demonstrated in 9 (47.4%) patients (complete response (CR, n = 3), partial response (PR, n = 3) or stable disease (SD, n = 3)); 5 patients had progressive disease (PD) ;1 patient died of pneumonia after 2 cycles but showed decreasing ctDNA. In patients achieving clinical benefit, 8/9 had no detectable ctDNA following treatment, with the remaining patient (SD) having persistent ctDNA likely due to severe immune dermatitis. All 5 patients with PD had detectable ctDNA at progression. Six patients with detectable baseline ctDNA went on to demonstrate clinical benefit with > 50% decreases in ctDNA allele fractions by cycle 3. Absence of ctDNA at baseline and during therapy was indicative of clinical benefit (n = 3). In contrast, PD patients presented with increases in ctDNA allele fractions or detectable new ctDNA. Conclusions: Rapid decreases and clearance of ctDNA correlated with clinical benefit to immunotherapy. Increasing or newly detectable ctDNA was indicative of progressive disease or poor overall outcome. These results are promising and suggest the potential role of ctDNA as an early biomarker of response to immunotherapy.
Human thymopoiesis is influenced by a common genetic variant within the <i>TCRA-TCRD</i> locus
Authors: Emmanuel Clave, Itauá Leston Araujo, Cécile Alanio, Etienne Patin, Jacob Bergstedt, Alejandra Urrutia, Silvia Lopez-Lastra, Yan Li, Bruno Charbit, Cameron Ross MacPherson, Milena Hasan, Breno Luiz Melo-Lima, Corinne Douay, Noémie Saut, Marine Germain, David-Alexandre Trégouët, Pierre-Emmanuel Morange, Magnus Fontes, Darragh Duffy, James P. Di Santo, Lluis Quintana-Murci, Matthew L. Albert, Antoine Toubert
Journal: Science Translational Medicine (2018)

The thymus is the primary lymphoid organ where naïve T cells are generated; however, with the exception of age, the parameters that govern its function in healthy humans remain unknown. We characterized the variability of thymic function among 1000 age- and sex-stratified healthy adults of the Milieu Intérieur cohort, using quantification of T cell receptor excision circles (TRECs) in peripheral blood T cells as a surrogate marker of thymopoiesis. Age and sex were the only nonheritable factors identified that affect thymic function. TREC amounts decreased with age and were higher in women compared to men. In addition, a genome-wide association study revealed a common variant (rs2204985) within the T cell receptor TCRA-TCRD locus, between the DD2 and DD3 gene segments, which associated with TREC amounts. Strikingly, transplantation of human hematopoietic stem cells with the rs2204985 GG genotype into immunodeficient mice led to thymopoiesis with higher TRECs, increased thymocyte counts, and a higher TCR repertoire diversity. Our population immunology approach revealed a genetic locus that influences thymopoiesis in healthy adults, with potentially broad implications in precision medicine.
Multi-arm, open-label Phase 1b study of FP-1039/GSK3052230 with chemotherapy in malignant pleural mesothelioma (MPM).
Authors: Jose Manuel Trigo Perez, Emilie Van Brummelen, Evgeny Levchenko, Manuel Domine, Pilar Garrido Lopez, Hedy L. Kindler, Daniel Morgensztern, Marjorie Glass Zauderer, Johan F. Vansteenkiste, Santiago Viteri Ramirez, Katherine Baker Neblett, Jeffrey Botbyl, Eddie Jose, Adina Zajac, Ionel Mitrica, Robert S. Sikorski, Li Yan
Journal: Journal of Clinical Oncology (2016)

8557 Background: FGF ligand-dependent signaling plays an important role in cancer development and promotion through secretion of FGF ligands or amplification of FGF receptors (FGFRs). MPM, a disease with significant unmet needs, overexpresses FGF2 ligand, which binds FGFR1 and promotes tumor cell growth. FP-1039/GSK3052230 is a soluble fusion protein consisting of the extracellular domain of human FGFR1c linked to the Fc portion of human IgG1, and acts as a ligand trap for FGFs. Methods: This multi-arm, open-label phase 1b study evaluated GSK3052230 (IV weekly) in combination with 1st-line paclitaxel+carboplatin (Arm A) or > 2nd-line docetaxel (Arm B) in FGFR1 gene-amplified metastatic squamous NSCLC and with 1st-line pemetrexed+cisplatin in untreated, unresectable MPM (Arm C). Each arm involved dose escalation until MTD/MFD followed by a cohort expansion phase. Endpoints include safety, response rates, PFS, duration of response, and translational measures. Preliminary data from Arms A and B have been presented previously. Herein, only preliminary results from Arm C are reported. Results: As of 10 Dec 2015, 24 patients (pts) were dosed in Arm C at 10, 15 and 20 mg/kg doses of GSK3052230. Three DLTs were observed at 20 mg/kg GSK3052230: Gr 5 bowel perforation/ischemia, Gr 3 elevated creatinine levels and Gr 3 infusion reaction. There were no DLTs at 15 mg/kg GSK3052230, and therefore MTD was declared at this dose. Most common adverse events (AEs; all grades) were: nausea (54%) decreased appetite (50%), fatigue (46%), and infusion reaction (33%). Preliminary objective response rate (ORR) is 57%, with disease control rate (DCR) of 100% (n = 14 evaluable pts, 10 and 15 mg/kg GSK3052230, confirmed/unconfirmed per mRECIST 1.1). The majority of patients are still on trial (duration on trial > 7.2 months); PFS data will be presented. Conclusions: The MTD of GSK3052230 in combination with pemetrexed+cisplatin in MPM is 15 mg/kg and the most frequent AEs are nausea and decreased appetite. Toxicities associated with small-molecule FGFR inhibitors (i.e hyperphosphatemia and retinal, nail, and skin changes) were not observed. The preliminary efficacy data are encouraging. Study sponsored by GSK. Clinical trial information: NCT01868022.
Performance comparison of the Vysis automated versus manual ALK gene rearrangement assays on archived FFPE and cytology specimens.
Authors: Miriana Moran, Anna Israyelyan, Alexander Bennet, Jack Hsiang, Stephanie H. Astrow
Journal: Journal of Clinical Oncology (2016)

e20056 Background: The Vysis ALK Break Apart FISH Probe assay (ALK FISH) detects ALK gene chromosome 2p23 rearrangements in NSCLC FFPE tissue by fluorescence in situ hybridization (FISH) and involves a number of manual steps. Recently, an automated ALK FISH protocol has been developed which employs slide processing on the VP2000 instrument, in conjunction with automated slide imaging and enumeration. This study assesses the automated ALK FISH assay performance versus the manual ALK FISH and both in comparison to the validated laboratory developed test as the known test of record (TOR). Methods: Automated and manual ALK FISH probe assay performance was evaluated on proximal tissue sections obtained from 31 archived NSCLC specimens consisting of 15 FFPE core biopsy, 8 formalin fixed FNA cell pellets, and 8 resections. Concordance of the manual and automated ALK FISH assays were compared and evaluated against the known LDT TOR results. In addition, a workflow analysis of automated versus manual ALK FISH assays was performed at three distinct batch sizes (N = 3, N = 12, and N = 24). Results: Evaluable results were obtained from 23 of 31 specimens (8 positive and 15 negative for ALK rearrangement). Eight results were non-evaluable by one or more study arms, due to low cellularity and high number of non-classifiable cells, and were excluded from the analysis. The automated assay achieved 95.65% concordance against the manual assay (FDA-approved, NCCN standard), with only a single discordant result. The automated study arm achieved 100% concordance with the LDT TOR; whereas the manual arm achieved 95.65% concordance with the LDT TOR. Workflow analysis demonstrated that although the total time to results increased for the automated assay due to slide imaging time, the hands-on time was reduced for all batch sizes. Conclusions: The Vysis ALK Automated FISH assay performance is equivalent to the manual assay format. Automated slide processing streamlines workflow by decreasing hands-on processing time, and reduces subjectivity imparted by manual slide enumeration and scoring.