tbuckley/cabot-search huggingface dataset:
The impact of postoperative complications on survival outcomes in patients with cT3/4a gastric cancer.
Authors: Masanori Tokunaga, Yukinori Kurokawa, Yuichiro Doki, Ryunosuke Machida, Shuji Takiguchi, Yuya Sato, Hitoshi Katai, Norimasa Fukushima, Yasunori Nishida, Haruhiko Cho, Takanobu Yamada, Masahide Kaji, Junya Fujita, Narikazu Boku, Takaki Yoshikawa, Masanori Terashima
Journal: Journal of Clinical Oncology (2019)

4067 Background: Recently, the negative impact of postoperative complications on long-term survival outcomes has been reported in patients with gastric cancer. However, most are single center, retrospective studies with different definitions of postoperative complications. The objective of this study was to evaluate the impact of postoperative complications on long-term outcomes using the data of a multicenter randomized controlled trial (JCOG1001). Methods: This study included 1191 out of all 1204 patients enrolled in JCOG1001 which was aimed to confirm the superiority of bursectomy for patients with cT3/4a locally advanced gastric cancer. Complications were graded by Clavien-Dindo classification. The relationships between the grade (≥grade II or ≥grade III) or type (all or intraabdominal infectious (pancreatic fistula, anastomotic leakage, and intra-abdominal abscess.)) of complications and survival outcomes were evaluated. Results: The incidences of ≥grade II and ≥grade III all complications were 23.0% and 9.7%, and those of ≥grade II and ≥grade III intraabdominal infectious complications were 13.4% and 6.9%, respectively. The hazard ratios for overall survival (OS) of patients with ≥grade II and ≥grade III all complications and those of patients with ≥grade II and ≥grade III intraabdominal infectious complications were shown in Table. With whichever definition we adopted, postoperative complications were significantly associated with OS in both univariable and multivariable analysis. Conclusions: Postoperative complication was identified as an independent prognostic factor in patients with cT3/4a gastric cancer. Hazard ratios for overall survival by univariable and multivariable Cox proportional hazard model. Clinical trial information: UMIN000003688. [Table: see text]
Characteristics of colorectal patients who discontinued oxaliplatin therapy.
Authors: Alexander Buchholz, Abe E Sahmoun, Peter C. Kurniali
Journal: Journal of Clinical Oncology (2019)

e15155 Background: The 3 rd generation platinum-based drug, Oxaliplatin, is indicated for treatment of stage II-IV colorectal cancer (CRC). Oxaliplatin combination with Fluorouracil and Leucovorin (FOLFOX) yields a 5-year disease free survival rate of 78%. Oxaliplatin use is limited by dose-limiting side effects such as neurotoxicity, peripheral neuropathy, and hepatotoxicity. Between 60 and 95% of Oxaliplatin treated patients experience neurotoxicity. The incidence of neuropathy varies between 4 and 98%, and of hepatotoxicity between 10 and 50%. There are few effective treatments to prevent or modulate neurotoxicity although infusions of calcium and magnesium may be beneficial. We sought to understand the factors that influence the discontinuation of Oxaliplatin. Objectives: 1) Determine the characteristics of CRC patients who discontinued chemotherapy involving Oxaliplatin; and 2) Examine metabolic panel monitoring among CRC patients. Methods: A retrospective chart review of newly-diagnosed adult patients with CRC stages II, III, and IV at Sanford Health. We used SAS v.9.4 to analyze demographic and clinical data. All P were two-sided, and P &lt; .05 were considered significant. IRB approval was obtained from Sanford Health and the University of North Dakota. Results: Data for 197 patients who received chemotherapy involving Oxaliplatin were studied. The mean [SD] age at diagnosis was 58.4 [± 12.9]. The majority 117 (59%) were male and 188 (96%) were White. 48% of patients had stage III and 35% had stage IV disease. 167 (85%) of patients received FOLFOX therapy. 56 (30%) discontinued Oxaliplatin. The median [range] number of cycles of chemotherapy completed before discontinuing Oxaliplatin was 8 [1-16]. Relative to patients who did not discontinue, patients who discontinued were significantly more likely to have of the descending colon (46% vs. 38%; P=0.023). Discontinuers were significantly more likely to experience moderate to severe symptoms (42% vs. 25%; P=0.032). Only 25 (13%) of patients had serum magnesium measured prior to starting chemotherapy. However, the median [range] serum potassium was significantly lower among discontinuers prior to starting chemotherapy (3.9 [3.2-5.3] vs. 4.1 [2.8-8.1]; P=0.023). Among patients (92%) who developed some form of peripheral neuropathy, the mean [SD] serum calcium was significantly lower among discontinuers (9.22 ± 0.52 vs. 9.40 ± 0.49; P=0.044). Conclusions: This study showed that serum potassium and calcium were significantly lower among patients who discontinued Oxaliplatin. Magnesium was measured rarely.
Bioinformatic inspired nanoparticles engineered for enhanced delivery to the bone.
Authors: Andrew Gdowski, Amalendu Ranjan, Jana Lampe, Victor Lin, Yu-Chieh Wang, Anindita Mukerjee, Jamboor Vishwanatha
Journal: Journal of Clinical Oncology (2019)

e14637 Background: We have engineered a programmable-bioinspired nanoparticle (P-BiNP) delivery system to simultaneously target the bone and increase uptake in homotypic tumor cells by coating polymeric nanoparticles with programmed cancer cell membranes. This approach is unique in that we have incorporated relevant clinical bioinformatics data to guide the design of these nanoparticles. Methods: A gene ontology search identified potential homotypic cell-cell adhesion genes. These were cross referenced with RNAseq expression levels from patients with metastatic prostate cancer to various organ locations using the Cbioportal database. C4-2B prostate cancer cells were grown and stimulated to express membrane ɑVβ3 by treatment with recombinant human CXCL12. The cell membrane from these cancer cells were used to coat polymeric nanoparticles by an extrusion process. Physico-chemical optimization and characterization of the P-BiNPs was performed. In vitro testing was done with flow cytometry and MTT assays. A murine model was used with high resolution near infrared imaging to identify nanoparticle localization. Results: Analysis of RNAseq from mCRPC samples (n = 118) identified ITGB3 as increased in bone metastatic lesions compared to metastases from other sites (P &lt; 0.0001). ITGB3 is a subunit of integrin ɑVβ3 and was selected as a target for enhancement to improve P-BiNP homotypic targeting and bone localization. After optimization, P-BiNPs showed optimal physico-chemical characteristics for drug delivery. Both in vitro testing and in vivo testing showed the P-BiNPs to be superior in homotypic uptake and localization to the bone. Conclusions: This platform of identifying clinically relevant targets for dual homotypic and bone targeting has potential as a strategy for treatment and imaging modalities in cancers that affects the bone as well as implications for delivering nanoparticles to other organs of interest.
Ligand-inducible, prostate stem cell antigen (PSCA)-directed GoCAR-T cells in advanced solid tumors: Preliminary results with cyclophosphamide (Cy) ± fludarabine (Flu) lymphodepletion (LD).
Authors: Carlos Roberto Becerra, Gulam Abbas Manji, Dae Won Kim, Olivia Gardner, Aditya Malankar, Joanne Shaw, Devin Blass, Xiaohui Yi, Aaron E. Foster, Paul Woodard
Journal: Journal of Clinical Oncology (2019)

2536 Background: Cell-surface protein PSCA is upregulated in many solid tumors and correlates with disease stage. BPX-601, an autologous T-cell product expressing a PSCA-CD3ζ CAR and a rimiducid (Rim)-inducible MyD88/CD40 co-activation switch to augment T-cell proliferation and persistence, is designed to have enhanced efficacy in solid tumors vs traditional CARs. This ongoing first-in-human study assesses safety, biologic, and clinical activity of BPX-601+Rim in PSCA+ cancers. Updated results, including those from patients (pts) who underwent LD with Flu/Cy, are presented. Methods: BP-012 is a 2-part, open-label trial. Part 1 is a 3+3 dose escalation of BPX-601 (1.25–5.0x10 6 cells/kg; Day [D] 0) given prior to a single, fixed Rim dose (0.4 mg/kg; D7) in pts with previously treated PSCA+ metastatic pancreatic, gastric, or prostate cancers with measurable disease. Results: As of Jan-22-2019, 15 pts have received BPX-601±Rim. Two pts at the highest cell dose received Flu/Cy for LD on D−5 to D−3 before BPX-601; LD after Flu/Cy was 96.6% and 84.3%. Thirteen pts received Cy alone on D−3; in these pts, LD ranged from 0–68.6%. Rapid cell expansion by D4 was observed in all pts with peak vector copy number 8.3-fold higher with Flu/Cy (n = 2) vs Cy LD (n = 13). Serum IP-10, IL-6 and TNFα increased &gt; 2-fold from baseline in ≥1 pt in all Rim cohorts, with 3- to 20-fold Rim-dependent cell expansion in 6 pts. No CRS or DLTs were reported. After Rim, one Flu/Cy pt experienced a serious Grade 2 AE (encephalopathy) related to BPX-601+Rim that resolved with IV steroids; despite time-matched nonserious Grade 1 pyrexia, the pt had no other CRS symptoms. After BPX-601+Rim and ≥1 scan, best responses were 8 SD and 3 PD (1 non-evaluable). With a median follow-up of 9.8 wks, time to next treatment (tx) after BPX-601 ranged from 2.7–22.1 wks (n = 8) and ongoing tx-free intervals range from 9.1–30.1 wks (n = 4). Conclusions: BPX-601+Rim was well-tolerated with manageable safety and early evidence of enhanced CAR T-cell expansion and prolonged persistence after Flu/Cy vs Cy. Additional pts will undergo Flu/Cy LD prior to BPX-601 with single- and repeat-dose Rim. Clinical trial information: NCT02744287.
Migrant charging in the NHS: how doctors can support patients when hospital care is denied
Authors: Ingrid Torjesen
Journal: BMJ (2019)

Recent rules on charging to create a “hostile environment” in the NHS for some immigrants are complex, finds Ingrid Torjesen , but doctors can ensure they are appropriately applied Since 2017 hospitals in England have been required to check patients’ entitlement to free NHS care and charge them upfront for care to which they aren’t entitled, at 150% of the national tariff. The government introduced these rules as part of a range of policies to create a “hostile environment” to deter unofficial immigration to the UK and to tackle “health tourism.” But the rules may contravene a global commitment to universal healthcare coverage, as defined by the World Health Organization and the United Nations’ sustainable development goals, and several human rights treaties to which the UK is a signatory.1 Some migrants (people not ordinarily resident in the UK) who need treatment are being turned away, campaigners say, and some avoid seeking treatment at all because they fear their information will be shared with the Home Office, which might lead to their detention or deportation.2 Pending full publication of a recent formal review of the rules’ effects, medical royal colleges, including the Royal College of Physicians, the Royal College of Paediatrics and Child Health, the Royal College of Obstetricians and Gynaecologists, the Royal College of General Practitioners, and the Faculty of Public Health, have joined charities and other organisations to call for the suspension of NHS charges to migrants.3 Individual doctors can do much to support patients who are denied treatment by ensuring that they have the right information to challenge decisions and by signposting them to support organisations and lawyers (box 1). Box 1 ### What doctors can do to help patients challenge decisions to refuse treatmentRETURN TO TEXT
Evaluating the role of race in outcome of advanced non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitor (ICI): Our institutional experience.
Authors: Bassel Nazha, Zhengjia Chen, Subir Goyal, Anne Engelhart, Jennifer Wilkinson Carlisle, Tyler Beardslee, Harpaul Gill, Levani Odikadze, Yuan Liu, Manoj K. Mishra, Madhusmita Behera, Suresh S. Ramalingam, Taofeek Kunle Owonikoko
Journal: Journal of Clinical Oncology (2019)

9042 Background: Race-based differences in ICI efficacy for advanced NSCLC have not been studied due to under-representation of patients of minority background in pivotal trials. We systematically explored real-world differences in outcome in our diverse patient population. Methods: This is a retrospective review of clinical outcome of patients with advanced NSCLC treated with single-agent ICI between 2013 and July 2018 at the Winship Cancer Institute of Emory University. We performed univariate and multivariate analyses for overall survival (OS) and progression free survival (PFS) patients according to self-reported race and of OS according to gender and PD-L1 expression levels. Results: We analyzed clinical data from 90 eligible patients: Median age of 68.5 yrs, 51% male, White (W)/Black(B)/Asians(A) made up 62.3%/30.7%/5%; 36.5% had brain metastasis at the time of ICI initiation. The majority (85.9%) had ECOG PS ≤2; ICI was 1 st line in 15 (16.9%), 2 nd line in 59 (66.3%), 3 rd line in 12 (13.5%) and nivolumab was the most commonly used agent (41.1%) followed by atezolizumab (32.2%) and pembrolizumab (26.7%). The median OS for the entire population was not reached (NR) (95%CI: 15.6, NR) while 12-month and 24-month OS rates were 63.8% (52.8%, 72.8%) and 53.1% (40.2%, 64.4%). The median OS, 12-month and 24-month OS rates for W and B respectively, were 23.6 months vs. NR; HR: 1.02 (95%CI: 0.51-2.04), p = 0.9571; 61.8% (47.7%, 73.2%) vs. 59.3% (38.6%, 75.0%) and 46.0% (27.9%, 62.4%) vs. 53.9% (32.8%, 70.9%). The overall response rate was 16.7%; 23.8% vs. 11% for B and W respectively. The median duration of response was comparable at 3.36 months vs. 2.94 months for W and B. The median PFS and 12-month PFS rate for W and B respectively were 5.5 (3.2, 14.8) vs. 3.0 (1.4, 10.7) months, p = 0.1350 and 40.0% (27.1%, 52.5%) vs. 29.6% (14.1%, 47.0%). Conclusions: Real-world analysis of our institutional experience showed no significant racial disparity in advanced NSCLC patients treated with ICI. Larger multi-institutional studies to include other US minority population would make our findings generalizable.
Efficacy and safety of tivozanib in recurrent, platinum-resistant ovarian, fallopian tube or primary peritoneal cancer.
Authors: Wendy M Swetzig, John Robert Lurain, Emily Berry, Mario Javier Pineda, Shohreh Shahabi, LaToya Perry, Nikki Lynn Neubauer, Wilberto Nieves-Neira, Julian C. Schink, Alissa Schiller, Karen Novak, Nancy Jean Anderson, Kirsten Bell Burdett, Anna Everett Strohl, Masha Kocherginsky, Daniela Matei
Journal: Journal of Clinical Oncology (2019)

5538 Background: Tivozanib is a potent, selective pan-vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor with a long half-life. This study assessed its activity in patients with recurrent, platinum-resistant ovarian cancer (OC), fallopian tube cancer (FTC) or primary peritoneal cancer (PPC). Methods: This open-label phase II study used a Simon’s two-stage design. Eligible patients had recurrent, platinum-resistant OC, FTC or PPC; ECOG PS of 0-1; normal end organ function; and measurable or detectable disease. There was no limit on the number of prior regimens. Treatment consisted of tivozanib 1.5 mg orally once daily (3 weeks on/1 week off). The primary endpoint was response rate. Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity assessment. If 1 partial response (PR) was observed in stage I [n = 12], enrollment proceeded to stage II. The null hypothesis was rejected for ≥ 4 responses in 30 patients. Results: Thirty-one patients were enrolled, and 30 were treated. Twenty-three had OC [76.67%], 5 FTC [16.67%] and 2 PPC [6.67%]. Twenty-six had measurable [86.67%] and 4 detectable disease [13.37%]. The median age was 60, and median number of prior regimens was 4 [range 1-9]. Four PRs [13.33%] were recorded. Twelve patients had stable disease (SD) [40%]. The clinical benefit rate (PR + SD) was 53%. Seven patients [23.33%] survived progression-free for &gt; 6 mos. One patient continued treatment for &gt; 2 yrs. The median PFS was 4 mos [range 1-25] and median OS was 8 mos [range 1-39]. There were no treatment-related deaths. Grade 3-4 related toxicities were hypertension [8], fatigue [3], fistula [2], hyponatremia [2], intestinal perforation, obstruction, stroke, proteinuria, hypomagnesemia, hypoalbuminemia, portal hypertension, nausea and anemia [1 each]. Frequent grade 1-2 related toxicities included fatigue [19], hypertension [13], anorexia [12], arthralgia [11], diarrhea [11], weight loss [10], hoarseness [8], headache [8] and nausea [7]. Exploratory analyses in tumor samples are ongoing. Conclusions: Tivozanib is active in patients with recurrent OC, FTC or PPC, without substantial toxicity, supporting its further development. Clinical trial information: NCT01853644.
Early clearance of plasma EGFR mutations as a predictor of response to osimertinib and comparator EGFR-TKIs in the FLAURA trial.
Authors: Caicun Zhou, Fumio Imamura, Ying Cheng, Isamu Okamoto, Byoung Chul Cho, Meng Chih Lin, Margarita Majem, Oliver Gautschi, Jhanelle Elaine Gray, Michael J. Boyer, Juliann Chmielecki, Ryan Hartmaier, Krishna Bulusu, J Carl Barrett, Rachel Hodge, Matilde Saggese, Astrid McKeown, Suresh S. Ramalingam
Journal: Journal of Clinical Oncology (2019)

9020 Background: In the Phase III FLAURA trial (NCT02296125), osimertinib, a third generation EGFR-TKI, showed superior efficacy to comparator EGFR-TKIs as first line treatment for EGFR mutation-positive (EGFRm) advanced NSCLC. In an exploratory analysis, we investigated clinical outcomes associated with detection of plasma EGFRm at 3 or 6 weeks (wks) after start of treatment. Methods: Treatment-naïve patients (pts) with EGFRm (ex19del or L858R) locally advanced or metastatic NSCLC were randomized 1:1 to receive osimertinib 80 mg once daily (QD) or comparator EGFR-TKIs (gefitinib 250 mg QD or erlotinib 150 mg QD). Plasma EGFR mutation analysis was conducted at baseline (BL), wks 3 and 6 by droplet digital PCR. Clearance was defined as undetectable levels of EGFRm in ctDNA at wks 3/6, where they were detectable at BL. Progression-free survival (PFS) was investigated based on early clearance of EGFRm. Results: In total 489/556 (88%) pts (osimertinib: 244/279; comparator: 245/277) had evaluable ctDNA at BL and wks 3/6. Of these, 342/489 (70%; osimertinib: 168/244; comparator: 174/245) had detectable BL EGFRm and were included in this analysis. See table. Conclusions: Clearance of plasma EGFRm after 3/6 wks of EGFR-TKI therapy was associated with a numerical improvement in PFS. The efficacy of osimertinib was superior to comparator EGFR-TKIs regardless of clearance status. Clinical trial information: NCT02296125. [Table: see text]
THU0111 ANGIOGENIC T CELLS AS AN INDEPENDENT PREDICTOR OF VASCULAR STIFFNESS IN VERY EARLY RHEUMATOID ARTHRITIS
Authors: Javier Rodríguez-Carrio, Mercedes Alperi-López, Patricia López, Ángel Pérez-Álvarez, Lorena Benavente, Francisco Javier Ballina-García, Ana Suárez
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Angiogenic T cells (Tang) are responsible of vascular repair and homeostasis. Decreased Tang frequencies have been reported in rheumatoid arthritis (RA), in association with disease activity and previous history of cardiovascular (CV) disease. However, excess of CV risk is already present during the early stage of RA. Whether Tang cells are associated with subclinical vascular abnormalities remains unknown. <h3>Objectives</h3> To evaluate whether Tang cells could be associated with subclinical CV endpoints (subclinical atherosclerosis and vascular stiffness) in the very early stage of RA. <h3>Methods</h3> Patients were recruited upon early referral to the rheumatology department. All patients were untreated at the time of sampling. Tang (CD3+CD31+CXCR4+) frequency was assessed by flow cytometry in peripheral blood samples. Plaque occurrence, cIMT and stiffness parameters were analyzed by Doppler ultrasound in internal carotid, middle cerebral and basilar arteries. <h3>Results</h3> 53 patients were recruited, 47 fulfilling 2010 ACR/EULAR classification criteria for RA (36 women, 26 FR+ and 26 ACPA+) and 6 fulfilling criteria for Clinically Suspect Arthralgia (CSA) (6 women, 3 RF+ and 2 ACPA+). Tang frequency did not differ between RA and CSA (p=0.382) and it was negatively associated with DAS28 (r=-0.448, p&lt;0.001) and SDAI (r=-0.385, p=0.006), but not with duration of the symptoms (r=0.053, p=0.713)). Tang levels were not related to individual traditional CV risk factors, body mass index, wait circumference (all p&gt;0.050) nor with the modified SCORE (r=-0.173, p=0.244) or Framingham Risk Score (r=-0.127, p=0.399). Neither atherosclerosis plaque occurrence (r=0.631) nor the cIMT (r=0.070, p=0.652) were associated with Tang levels. Tang frequency paralleled carotid peak systolic velocity (r=0.399, p=0.008) and end diastolic velocity (r=0.332, p=0.034) in internal carotid artery. Moreover, Tang positively correlated stiffness parameters: vascular strain (VS, r=0.428, p=0.010), vascular distensibility (VD, r=0.479, p=0.004), vascular stiffness (VSf, r=-0.519, p&lt;0.001) and pressure-strain elastic modulus (PSEM, r=-0.531, p&lt;0.015) in left internal carotid artery. Finally, Tang frequency was an independent predictor of stiffness parameters after adjusting for mSCORE, body mass index, DAS28, RF and ACPA positivity: VS (β=0.451, p=0.045), VD (β=0.462, p=0.026), VSf (β=-0.422, p=0.035) and PSEM (β=-0.446, p=0.026). <h3>Conclusion</h3> Tang cells may have a very early role on vascular stiffness in RA. These results point to the Tang subset as the missing link between disease activity and vascular abnormalities during the first stage of the disease. <h3>Disclosure of Interests</h3> None declared
Gender inequality and restrictive gender norms: framing the challenges to health
Authors: Lori Heise, Margaret E Greene, Neisha Opper, Maria Stavropoulou, Caroline Harper, Marcos Nascimento, Debrework Zewdie, Gary L Darmstadt, Margaret Eleanor Greene, Sarah Hawkes, Lori Heise, Sarah Henry, Jody Heymann, Jeni Klugman, Ruth Levine, Anita Raj, Geeta Rao Gupta
Journal: The Lancet (2019)