tbuckley/cabot-search huggingface dataset:
Retrospective analysis of complications following central venous port insertions: A single institution experience.
Authors: William Paul Skelton, Aaron J Franke, Samantha Welniak, Raphael Bosse, Fares Ayoub, Martina Cathryn Murphy, Jason Scott Starr
Journal: Journal of Clinical Oncology (2018)

e18767 Background: Central venous access devices, specifically implantable ports, play an essential role in the care of oncology patients. Despite their routine use in cancer patients complications related to insertion and management of these devices remain prevalent. This retrospective single-institutional review was performed to identify rates of complications from port placement, and potential factors associated with these events Methods: Retrospective analysis of 539 cancer patients who underwent port insertion between 3/2016 and 3/2017 at the University of Florida was conducted. Data examining 18 potentially predictive factors was collected, and multivariate analysis was conducted using logistic regression and odds ratios with standard errors to determine predictive factors Results: Out of 539 patients, 100 patients (19%) experienced a complication, and 12 patients (2%) experienced 2 or more complications. An overall lower rate of complications was seen in patients on therapeutic anticoagulation (OR 0.17, p < 0.001, 95% CI 0.06-0.49) or on antiplatelet agents (OR 0.47, p = 0.02, 95% CI 0.25-0.90). No patients on therapeutic anticoagulation developed VTE (0%). Right-sided port insertion was associated with decreased rates of infection (OR 0.44, p = 0.04, 95% CI 0.20-0.96). Insertion as inpatient was associated with increased risk for mechanical failure (OR 4.60, p < 0.01, 95% CI 1.66-12.80) Conclusions: This analysis identified multiple predictive factors that can potentially put patients at higher risk of experiencing a complication from port insertion. Intuitively our data shows lower rates of VTE complications for patients on anticoagulation or antiplatelet therapy. This emphasizes that a thorough risk assessment for VTE should be done in all patients receiving a port and an individualized approach (ie prior VTE, Khorana score > 3) should be considered for prophylactic anticoagulation. Further analysis is also necessary to determine why port insertion as an inpatient places patients at higher risk of complications. This study highlights the risks associated with port placement and prompts the clinician to have an informed discussion with the patient weighing the risks and benefits
Efficacy and tolerability of vemurafenib in BRAF-mutant acral and mucosal melanoma.
Authors: Xue Bai, Lu Si, Zhihong Chi, Xinan Sheng, Chuanliang Cui, Yan Kong, Jie Dai, Li Li Mao, Xuan Wang, Si Ming Li, Bixia Tang, Bin Lian, Li Zhou, Xieqiao Yan, Jun Guo
Journal: Journal of Clinical Oncology (2017)

e21017 Background: Vemurafenib has substantially impressive clinical efficacy in cutaneous melanoma (CM). However, compared with their cutaneous counterpart, acral melanoma (AM) and mucosal melanoma (MM) have distinct genetic patterns and worse prognosis. The efficacy and safety profiles of vemurafenib in AM and mm remain unclear. Methods: Clinical, pathological, and therapeutic data were collected and reviewed of patients (pts) with metastatic or unresectable BRAF-mutant AM and mm hospitalized and administrated vemurafenib during January 2011 and January 2017. Responses were evaluated by RECIST v1.1, survival data were analyzed by Kaplan-Meier survival curve, and adverse effects were assessed by CTCAE v4.0. Results: 24 pts were identified, 13 (54.2%) with AM, 11 (45.8%) with mm (1 patient without available radiology data). All 13 AM pts harbored BRAF V600E mutation (1 with simultaneous C-KIT E861K mutation); 10/11 (90.9%) mm pts carried BRAF V600E mutation (1 with simultaneous PDGFRA V824I mutation), 1/11 (9.1%) had BRAF D594N mutation. Median PFS were 5.4 (95%CI 3.5-8.7) and 4.5 (95%CI 1.5-15.0) months, median OS were 11.7 (95%CI 8.1-23.6) and 7.9 (95%CI 4.6-26.2) months; ORRs were 61.5% (8/13) and 40.0% (4/10), DCRs were 92.3% (12/13) and 90.0% (9/10) in AM and MM, respectively. Vemurafenib was well tolerated. The most common adverse effects (AEs) were hand-foot syndrome in AM and elevation of total cholesterol in MM, with the incidence of 23.1% (3/13) and 18.2% (2/11), respectively. Grade 3/4 AEs have not been observed. No patient discontinued vemurafenib because of treatment related toxicity. Conclusions: Vemurafenib yields substantial response in pts with AM and MM. Compared with in CM, vemurafenib has similar efficacy and safety profiles in BRAF-mutant AM and MM.
Novel treatment (Tx) use and associated outcomes among African American patients (pts) with multiple myeloma (MM): A SEER-Medicare analysis.
Authors: Kejal Parikh, Zoe Clancy, Zheng-Yi Zhou, Wenxi Tang, Claudia Cheung, Zhou Zhou, Jipan Xie, Sikander Ailawadhi
Journal: Journal of Clinical Oncology (2018)

e20030 Background: MM is the most common blood cancer among African Americans (AA). The study aimed to compare clinical and economic outcomes for AA with newly diagnosed MM who received novel vs non-novel agents as first-line (1L) Tx for MM. Methods: Pts with MM in SEER-Medicare (2007-2014) were included. Continuous Medicare enrollment for 6 mos before (baseline) and after 1L initiation date (index date) was required, unless pts died. Novel agent (eg, bortezomib [V], lenalidomide [R]) and non-novel agent users were identified based on the 1L Tx pts received. Overall survival (OS), myeloma specific survival (MSS), and healthcare costs were compared between AA novel and non-novel users. Among AA novel users, outcomes were further compared between 1L R + steroid (Rd) vs V + steroid (Vd) users. Results: Among 657 included AA pts, 398 (61%) used 1L novel agents. This proportion was significantly lower compared with caucasian (66%, p = 0.02). AA novel users were significantly younger (mean: 70 vs 73 yrs, p < 0.001). Both median OS (3.1 vs 1.8 yrs, p < 0.001) and MSS (not reached vs 57.7 mos, p < 0.01) were significantly longer for AA novel users than non-novel users; after adjusting for baseline characteristics, the risk of all-cause death remained lower for AA novel users (adj hazard ratio [HR] = 0.77, p = 0.01). AA non-novel users had numerically higher monthly medical costs than AA novel users (adj mean difference: $951), which were driven by higher inpatient ($2,571) and emergency room ($38) costs (both p < 0.05). Total costs (medical + pharmacy) were comparable between the two AA cohorts. Among AA novel users, 102 (26%) and 147 (37%) used 1L Rd and Vd, respectively. Time on Tx (DOT) was longer for Rd vs Vd (median 4.6 vs 4.0 mos, adj HR = 0.72, p = 0.04). A trend of longer time to next line Tx (TTNT) initiation or death (a proxy of PFS) was observed among Rd users (median 17.6 vs. 12.1 mos, p = 0.06). Conclusions: AA pts with MM who received 1L novel agents had longer OS and MSS compared with those who did not. Among novel users, pts receiving Rd had longer DOT and trended toward longer TTNT, compared with Vd. Results suggest that increasing the novel agents use, particularly Rd, may improve outcomes among AA pts with MM.
TCT-578 Assessment of Lesion-Specific Ischemia Using Fractional Flow Reserve (FFR) Profiles Derived from Coronary Computed Tomography Angiography (FFRCT) and Invasive Measurements (FFRINV): Importance of the Site of Measurement and Implications for Patient Referral for Invasive Coronary Angiography
Authors: Elvis Cami, Robert Safian, Gilbert Raff, Travis Tagami, Brian Renard, Michael Gallagher, Kavitha Chinnaiyan, Abhay Neil Bilolikar, Austin Fan, Adam Hafeez
Journal: Journal of the American College of Cardiology (2018)
Molecular signatures of class II HLA and p-16 status as an immune-based classification of OPSCC relying on known predictors of sensitivity to PD-1 blockade.
Authors: Nabil F. Saba, Sandra Seby, Michael R. Rossi, Kelly R. Magliocca, Christopher C Griffith, Xu Wang, Dongsheng Wang, Bhakti Dwivedi, Mihir Patel, Mark El-Deiry, Conor Ernst Steuer, Dong Moon Shin, Jeanne Kowalski, Zhuo Georgia Chen
Journal: Journal of Clinical Oncology (2017)

6052 Background: PD-1 inhibitors are known to have significant clinical activity in head and neck squamous cell cancer (SCCHN); there is, however, no selection criterion for SCCHN patients who may benefit from PD-1 inhibition. Utilizing RNA-seq analysis we explored a set of human genes encoding leukocyte antigens (HLAs) as part of a 37-gene panel predictive of response in melanoma patients to PD-1 inhibitors (Chen et al, Cancer Discov. 2016 Aug;6(8):827-37).We investigated whether this panel could define an immune-based classification of oropharyngeal squamous cell carcinoma (OPSCC). Methods: We have applied a minimal mutation and copy number content (151 genes) using an Agilent Clearseq DNA and an extensive Illumina Truseq RNA panel providing key information on gene fusions, differential gene expression, coding mutation and metagenomics on 47 SCCHN FFPE samples including 27 OPSCC. We performed an unsupervised hierarchical clustering of the samples. Two clusters with high and low expression were noted. Fisher’s exact test was performed to determine if the samples in each clusters were associated with p16 as a surrogate marker for HPV status. The same procedure was repeated on Level 3 transcriptome data from the TCGA via GDC data portal. Results: A set of fourteen immune related HLA antigen genes were identified within the 37-gene panel predictive to response to PD-1 inhibitors in p16+ versus - OPSCC (p = 0.015).We applied the same set of immune related HLA genes on the 103 patient samples from TCGA with known p16 status. When applied on all samples, there was no correlation between the HLA gene expression and p16 status (p = 0.1366); however, when restricted to OPSCC patients there was a high correlation with p16 status (p = 0.0047). Conclusions: We have identified a set of immune related HLA type II genes that are over-expressed in p16 positive OPSCC. This opens the door for further evaluation of these genes to better understand the immune related factors affecting the biology of HPV-associated OPSCC and its response to PD-1 inhibitors. (This research was supported by a grant NCI R21 CA182661-01A1to NFS and GZC).
Bevacizumab plus chemotherapy (bev/CT) as first-line therapy for patients with potentially resectable metastatic colorectal cancer (mCRC): Final results of the French noninterventional PICASSO study.
Authors: David Malka, Jean-Philippe Metges, Dominique Elias, Jaafar Bennouna, Franck Bonnetain, Louis-Marie Dourthe, Meher Ben Abdelghani, Abderraouf Radji, Philippe Laplaige, Fabien Petit Laurent, Vanessa Barue, Sophie Gandon, Michel Rivoire
Journal: Journal of Clinical Oncology (2016)

3554 Background: Few prospective studies specifically focused on the management of potentially resectable patients with mCRC. This prospective non-interventional cohort evaluated patients (pts) with mCRC and no evidence of new metastatic disease (NED) after 1st line bev/CT followed or not by secondary metastases resection. Methods: Previously untreated mCRC pts with potentially resectable liver and/or lung metastases treated with 1st line bev/CT were included and followed for 36 months. Decisions for patient enrollment, treatment initiation, and surgery metastases, were taken by a multidisciplinary team. The primary endpoint was frequency of pts with NED with or without secondary resection after a 1st line treatment with bev/CT. Secondary endpoints included progression-free survival (PFS), overall survival (OS), relapse-free survival, safety and criteria to define pts unresectability. Results: Between September 2010 and June 2012, 218 pts were included. Out of the 205 evaluable pts (efficacy population), 64% were men, mean age was 66 years, 96% were ECOG 0-1, 86% had liver only metastases. After the 1st line bev/CT, 104 pts (51%) had liver and/or lung metastases resection. The primary endpoint, NED, was reached by 92 pts (48%) [95% CI, 40;55%] including 88 pts after surgery (85%[76;91%] of resected patients). NED also occurred in 4 pts who did not underwent metastasis resection (4%[1;11%] of unresected pts) due to a complete response before surgery. Median PFS was 11.5 months [10.4;12.4] in the efficacy population and 15.7 months [12.9;18.9] in NED pts. The OS rate at 36 months was 52% [44;56%] and 77% [66;85%] for NED pts. In the safety population (n = 210), grade ≥ 3 adverse events (AEs) occurred in 92 pts (44%), treatment related AEs occurred in 17 pts (8%). Overall, 15 pts (7%) died of an AE, of which only 1 patient (0.5%) had a treatment related AE leading to death. Conclusions: In this non-interventional study conducted in real-life setting in potentially resectable mCRC pts treated with bev/CT in 1st line, half of pts were resected and showed no detectable metastatic disease and prolonged OS. Clinical trial information: NCT01343901.
APOLLON: A phase I/II study of panitumumab combined with TAS-102 in patients (pts) with <i>RAS</i> wild-type (wt) metastatic colorectal cancer (mCRC).
Authors: Yasutoshi Kuboki, Takayuki Yoshino, Takeshi Kato, Yoshinori Kagawa, Makio Gamoh, Hirofumi Yasui, Kentaro Yamazaki, Yoshito Komatsu, Hironaga Satake, Masahiro Goto, Hiroaki Tanioka, Eiji Oki, Masahito Kotaka, Akitaka Makiyama, Tadamichi Denda, Junpei Soeda, Kazunori Shibuya, Masaru Iwata, Koji Oba, Kensei Yamaguchi
Journal: Journal of Clinical Oncology (2018)

3523 Background: APOLLON is an open-label, single-arm phase I/II study investigating the efficacy and safety of panitumumab (Pmab) in combination with TAS-102 (trifluridine/tipiracil) in pts with RAS (KRAS/NRAS) wt mCRC refractory to standard chemotherapy. The recommended phase II dose (RP2D) of this combination was reported in ASCO-GI 2017 as Pmab at 6 mg/kg on Days 1 and 15, every 4 weeks (Q4W) and TAS-102 at 35 mg/m² BID on Days 1–5 and 8–12, Q4W, and was well tolerated without dose-limiting toxicities. Here, we present the efficacy and safety data for pts treated with Pmab with TAS-102 at the RP2D. Methods: Eligible pts were aged 20–74 years (y); ECOG PS 0–1; with RAS wt mCRC; refractory or intolerant to fluoropyrimidines, irinotecan, oxaliplatin or anti-angiogenesis therapy; and had no prior treatment with any anti-EGFR antibody, TAS-102 or regorafenib. Primary endpoint was investigator-assessed progression-free survival (PFS) at 6 months in RP2D-treated pts (including seven pts in phase I). Secondary endpoints included PFS, response rate (RR), disease control rate (DCR) and safety. Using an exact single-stage binomial design, 47 pts were required, with a 6-month PFS of 48% deemed promising and 29% unacceptable (one-sided α = 0.05; β = 0.2). Results: From 2015 to 2017, 56 pts (30 male) with a median age of 64 y (range: 38–74 y) were enrolled. Median follow-up was 10.4 months. 6-month PFS rate (n = 54) was 33.3% (90% CI: 22.8–45.3; p = 0.2414). Median PFS, RR and DCR were 5.8 months (95% CI: 4.5–6.5), 37.0% and 81.4%, respectively (n = 54). The most common grade (G) 3/4 treatment-emergent adverse events (n = 55) included neutropenia (G3: 30.9%, G4: 16.4%), febrile neutropenia (G3: 10.9%), stomatitis (G3: 9.1%), dermatitis acneiform (G3: 9.1%), fatigue (G3: 3.6%) and hypomagnesemia (G3: 3.6%). There were no treatment-related deaths or unexpected safety signals. Conclusions: The first phase II study of Pmab with TAS-102 at the RP2D showed favorable antitumor activity with an acceptable safety profile for pretreated pts with RAS wt mCRC, although the primary endpoint of PFS at 6 months did not meet the prespecified threshold. Clinical trial information: NCT02613221.
Letter by Santoro et al Regarding Articles, “Duct Stenting Versus Modified Blalock-Taussig Shunt in Neonates With Duct-Dependent Pulmonary Blood Flow: Associations With Clinical Outcomes in a Multicenter National Study” and “Comparison Between Patent Ductus Arteriosus Stent and Modified Blalock-Taussig Shunt as Palliation for Infants With Ductal-Dependent Pulmonary Blood Flow: Insights From the Congenital Catheterization Research Collaborative”
Authors: Giuseppe Santoro, Gianpiero Gaio, Maria Giovanna Russo
Journal: Circulation (2018)
Phase I clinical trial of the glutaminase inhibitor CB-839 plus capecitabine in patients with advanced solid tumors.
Authors: Jennifer Rachel Eads, Smitha S. Krishnamurthi, Joel N. Saltzman, David Lawrence Bajor, Shaveta Vinayak, Jill Barnholtz-Sloan, Neal J. Meropol, Sanford D. Markowitz, Zhenghe Wang
Journal: Journal of Clinical Oncology (2018)

2562 Background: Colorectal cancers (CRCs) harboring a PIK3CA mutation demonstrate glutamine dependency in both in vitro and in vivo models, including those known to be fluoropyrimidine (FP) resistant. CB-839 (CB) is an oral inhibitor of glutaminase, a key enzyme in glutamine metabolism. Preclinical studies further show that the combination of CB and a FP is superior to either as a single agent, and can overcome FP resistance. We conducted a phase I trial to assess the maximum tolerated dose and dose limiting toxicities (DLTs) of CB when given with capecitabine (C). Methods: Patients with advanced solid tumors and disease progression on standard treatment, or for whom C is an acceptable treatment option, were enrolled. A standard 3+3 design was used to assess escalating doses of CB (400-800 mg) and C (750-1000 mg/m2) in four dose levels. CB was given orally twice daily continuously and C was given orally twice daily on days 14/21 of a 21 day treatment cycle. DLT period was 21 days. Restaging CT scans were obtained every 9 weeks with response assessment per RECIST. Adverse events were assessed per CTCv4. Results: 16 patients were enrolled: 38% male, 94% white, 6% African American, median age 69.5 years (43-80), mean number of cycles 7.3 (1-11). Seven patients were treated at the final dose level (CB 800 mg and C 1000 mg/m2) and no DLTs were observed. Grade 3 adverse events included elevated ALT (n = 1), elevated AST (n = 1), anorexia (n = 1), decreased lymphocytes (n = 1), palmar-plantar erythrodysesthesia (n = 3), diarrhea (n = 1) and vomiting (n = 1). Grade 4 AEs included decreased lymphocytes (n = 1). Ten patients achieved stable disease as their best response, 9 being FP resistant. Associated median progression free survival (PFS) was 16.5 weeks among all patients (n = 16) and 29.5 weeks in PIK3CA mutant CRC patients (n = 6). At this time 2 patients remain on treatment at 31 and 3 weeks. Conclusions: CB 800 mg may be safely administered with C 1000 mg/m2 with minimal toxicity. While no RECIST response was observed, several patients with prior FP resistance experienced prolonged PFS, particularly patients with PIK3CA mutant CRC. The phase II portion of this study in patients with PIK3CA mutant CRC is pending. NCT02861300, 2P50CA150964-06A1 Clinical trial information: NCT02861300.
Development and use of a staffing model for clinical research teams at an NCI Comprehensive Cancer Center.
Authors: Erin Fenske Williams, Joan H. Schiller, Joyce D Bolluyt, David E. Gerber
Journal: Journal of Clinical Oncology (2016)

e18267 Background: As the cost and complexity of clinical cancer research increases, the determination of staffing needs based on individual protocol characteristics is critical. There are few straightforward and generalizable models to guide these considerations for academic medical centers. Methods: We developed a model for scoring individual protocol staffing requirements that accounts for frequency of visits, quantity of research-related procedures such as safety monitoring above the requirements for routine care, and data reporting requirements. The model includes four scoring categories including active patient management, active follow up, long term follow up, and data management. Model input includes protocol acuity scores entered by research managers and patient loads entered by coordinators. Model output includes individual and team workload. Results: The model has been in use for 3.5 years. Based on manager reported staff working level and weekly work hours, we determined the optimal number of points to be 140-150. Coordinators scoring ≥ 200 or ≤ 100 points were considered over- or under-worked, respectively, and prompted managerial evaluation. By report, the model was deemed to reflect accurately staff workload for all clinical research teams except hematologic malignancies. With subsequent modification reflecting disease-specific predictable elements that influenced protocol complexity, the model was deemed to represent hematologic malignancy research staff workload. More recent updates include effort related to screening and enrollment of new subjects. Conclusions: This staffing model can be used to guide redistribution of workload among teams and add team members. Coupled with the observations of institutional and team managers, the model may provide key information for organizational structure of large clinical research operations at regional cancer centers. Future enhancements include using the model to effectively budget for new studies up front and enhancing ease of use by incorporating into a clinical trials management system to facilitate more real-time reporting.
Genotype-phenotype correlation and risk stratification in a cohort of 123 hereditary stomatocytosis patients
Authors: Immacolata Andolfo, Roberta Russo, Barbara Eleni Rosato, Francesco Manna, Antonella Gambale, Carlo Brugnara, Achille Iolascon
Journal: American Journal of Hematology (2018)

Abstract Hereditary stomatocytoses (HSts) are a wide spectrum of hemolytic anemias in which the erythrocyte membrane cation permeability is increased. Dehydrated hereditary stomatocytosis is the most frequent among HSts. It is caused by missense mutations in PIEZO1 and KCNN4 genes. We described 123 patients enrolled in our Genetic Unit from 2013 to 2017. Overall HSt subjects exhibit macrocytic mild anemia. We found that PIEZO1 is the most frequent mutated gene within our families (47% of pedigrees). In 59.1% of cases the mutations localized in the nonpore protein domain, while in 40.9% of patients they localized in the central pore region. The genotype‐phenotype correlation analysis on 29 PIEZO1 ‐patients demonstrated that most of severely affected patients carried mutations in the pore domain, suggesting that the severity of this condition is related to the pore properties and intracellular domain that could be responsible of interactions with intracellular components. This is the first cohort study on a large set of hereditary stomatocytosis patients, stratified according to their causative gene useful for diagnosis, prognosis, and management of these patients.