tbuckley/cabot-search huggingface dataset:
Neoadjuvant BEP regimen in the treatment of extensively advanced yolk sac tumor: A single institutional experience.
Authors: Gong-Yi Zhang, Rong Zhang, Ling-Ying Wu, Shu-min Li, Bin Li
Journal: Journal of Clinical Oncology (2017)

5570 Background: Due to the highly aggressive biological behavior and early intra-abdominal spread potential of ovarian yolk sac tumor (YST), a considerable proportion of patients were inoperalbe at initial diagnosis. The aim of this study was to investigate the role of neoadjuvant chemotherapy (NACT) in this cohort of patients. Methods: Between July 1982 and December 2015, 58 patients diagnosed as YSTs were initially treated at Cancer Hospital of China Academy of Medical Science (CAMS), among which 18 were evaluated to be inoperable and received NACT. They were either too debilitated by the disease (ECOG ps≥2) to undergo a major surgery, or were with too extensively disseminated lesions to be optimally debulked. Massive ascites, pleural effusion, dyspnea, neoplastic fever, hypoproteinemia, or electrolyte disturbance were also common in these 18 patients. This cohort of patients was retrospectively reviewed. Results: One or 2 cycles of BEP regimens were prescribed to the majority of patients preoperatively. At the completion of NACT, all the 18 patients had ECOG ps≤1 . Seventeen of them (94.4%) exhibited clinical partial tumor regression and 1(5.6%) had clinical stable disease. Pathological complete tumor regression was observed in 2 (11.1%) patients, whereas the remaining 16(88.9%) had nearly complete pathological response. All these 18 patients were rendered operable at the completion of NACT, yielding a resection rate of 100%. Seventeen patients (94.4%) were cytoreduced to no macroscopic residual disease, 1 (5.6%) patient was cyto-reduced to macroscopic residual disease ≤2 cm. No major surgical complications occurred in our series. After a median follow-up of 83.5 months, 17 patients were free of recurrence. Five-year DFS and OS were both 94.4%. Fertility-sparing surgery was carried out in all the 17 patients with fertility desire, and 5 infants were delivered in 6 patients who attempted conception. Conclusions: One or 2 cycles of NACT followed by early cyto-reductive surgery offers a chance for cure in patients with extensively advanced YSTs. It allows for a more through and safe cyto-reductive surgery, improves survival outcomes, and helps pave the way for fertility-sparing surgery.
Abstract 11546: The Potential Beneficial Effects of Dyad Training on Medical Students’ Cardiopulmonary Resuscitation Performance
Authors: Chin-Chou Huang, Jaw-Wen Chen, Shing-Jong LIN
Journal: Circulation (2016)

Introduction: Dyad training, which entails cooperative learning in pairs, has shown to improve student learning experiences. Cardiopulmonary resuscitation (CPR) is a team effort during which team members must cooperate to perform various tasks at the same time. Whether or not dyadic training—training two teams together—is beneficial for CPR education and simulations is still unknown. Hypothesis: Dyadic training is beneficial for CPR training. Methods: We enrolled 267 medical students (164 male and 103 female) in the study. We provided these students with a 2-hour training session on CPR for simulated cardiac arrest. Student teams were split into double groups (Dyad training groups: Groups A and B) or Single Groups. All groups received two CPR simulation rounds. CPR simulation training began with peer demonstration for Group A, and peer observation for Group B. Then the two groups switched roles. Single Groups completed CPR simulation without peer observation or demonstration. Teams were then evaluated based on leadership, teamwork, and team member skills. Results: Group B had the highest first simulation round scores overall (P= 0.004) and in teamwork (P= 0.001) and team member skills (P= 0.031). Group B also had the highest second simulation round scores overall (P&lt; 0.001) and in leadership (P= 0.033), teamwork (P&lt; 0.001) and team member skills (P&lt; 0.001). In the first simulation, there were no differences between Dyad training groups with those of Single Groups in overall scores, leadership scores, teamwork scores, and team member scores. In the second simulation, Dyad training groups scored higher in overall scores (P= 0.002), leadership scores (P= 0.044), teamwork scores (P= 0.005), and team member scores (P= 0.008). Dyad training groups also displayed higher improvement in overall scores (P= 0.010) and team member scores (P= 0.022). Conclusions: Dyad training was effective for CPR training. Both peer observation and demonstration for peers in dyad training can improve student resuscitation performance.
The impact of radiotherapy, in addition to chemotherapy, on overall survival in the initial management of patients with newly diagnosed metastatic head and neck squamous cell carcinoma.
Authors: Sujith Baliga, Rafi Kabarriti, Nitin Ohri, Chandan Guha, Shalom Kalnicki, Madhur Garg
Journal: Journal of Clinical Oncology (2017)

6035 Background: The role of radiation therapy (RT) in the upfront management of patients with metastatic head and neck squamous cell carcinoma (HNSCC) is not clearly defined. In this study, we used the National Cancer Database (NCDB) to assess the association between RT use and overall survival (OS) for patients with metastatic HNSCC who received chemotherapy. Methods: We analyzed the NCDB to identify patients with newly diagnosed metastatic HNSCC from 2004-2013 who were treated with upfront chemotherapy. Associations between the use of RT and OS were evaluated using the Kaplan Meier method, univariate and multivariate cox regression, propensity score matching, and sequential landmark analysis. Survival outcomes were also compared for patients receiving a biologically effective dose (BED) ≥72 Gy 10 and &lt; 72 Gy 10 . Results: We identified 3,516 patients diagnosed with metastatic HNSCC who were treated with chemotherapy, of which 2,288 (65%) were also treated with RT. The median follow up was 11.9 months. The addition of RT to chemotherapy was associated with prolonged survival (median 13.6 v 11.3 months, logrank p &lt; 0.001). On multivariate analysis, the use of RT remained associated with prolonged survival (HR = 0.71, 95% CI 0.61-0.82, p &lt; 0.001). After propensity score matching, the addition of RT was associated with improved median survival (13.5 v 11.2 months) and 5-year (17% v 7%) OS compared to chemotherapy alone (log rank, p &lt; 0·001). Landmark analyses limited to patients who survived at least 3, 6, and 12 months after diagnosis continued to demonstrate improved OS with the addition of RT. Among patients treated with RT, the use of RT schedules with a BED exceeding 72 Gy 10 was associated with prolonged survival (median 18.0 versus 11.7 months, logrank p &lt; 0.001). Conclusions: For patients with metastatic HNSCC, the addition of RT to chemotherapy was associated with improved OS in this population based study. These results provide rationale for prospective randomized trials to validate these findings and to determine the optimal radiation therapy dose/fractionation and treatment schedule for these patients.
Burnout linked to suboptimal patient care, study finds
Authors: Jacqui Wise
Journal: BMJ (2018)

Burnt out doctors are twice as likely to be involved in patient safety incidents, to deliver suboptimal care, and to receive low satisfaction ratings from patients, a systematic review and meta-analysis has shown.1 The research, published in JAMA Internal Medicine , found that trainees and doctors in their early career were at particular risk.

“This meta-analysis provides evidence that physician burnout might jeopardise patient care,” said the authors, led by Maria Panagioti, from the National Institute for Health Research School for Primary Care Research at the University of Manchester. They added, “Physician …
Safety of apatinib as third-line or beyond treatment in advanced or metastatic gastric cancer: Results from a multicenter phase IV study (Ahead-G201).
Authors: Jin Li, Lu Wen, Junsheng Wang, Wenying Deng, Guifang Zhang, Tongfu Jia, Yi Ba, Haijun Zhong, Jianwei Yang, Xiaoyan Lin, Yu-Xian Bai, Yifu He, Zhong Xie, Tienan Yi, Xiangyuan Wu, Feng Ye, Likun Liu, Yong Huang, Mei Wang, Shukui Qin
Journal: Journal of Clinical Oncology (2018)

e16019 Background: An open-label, multicenter, post-marketing Phase IV study of apatinib (Ahead-G201; ClinicalTrials.gov: NCT02426034) is being conducted in a broad range of gastric cancer patients (pts) with a target sample size of 2000+. The interim analysis was released in 2018 Gastrointestinal Cancers Symposium (Abstract #103). Herein, we reported the updated safety data in detail. Methods: Pts with advanced or metastatic adenocarcinoma of stomach or gastro-esophageal junction after at least two lines of chemotherapy were recruited to receive oral apatinib until disease progression, death or unacceptable toxicity. The primary endpoint was safety. Results: As of 12/21/2017, 1468 pts were enrolled. Median age was 60 yrs; male/female was 72.1/27.9%; ECOG PS 0/1/≥2 was 16.4/65.6/18.0%. The mean dosage was 509.9 mg/d. During the follow-up period, 482 (32.8%) pts had to interrupt administration to manage adverse events (AEs) including hand-foot-skin reaction (HFSR), proteinuria (PTN) and hypertension (HTN). 189 (12.9%) pts lowered dose at least once mainly due to PTN, platelet decrease and HFSR, whereas dose increase occurred in 116 (7.9%) pts according to the protocol mainly owing to good tolerance or improvement in AEs. In total, 6312 drug-related AEs (DRAEs) were reported by 908 (61.9%) pts. The incidence of Grade ≥3 DRAEs was 28.6% (420/1468). The most common DRAEs included HTN (253, 17.2%), PTN (239, 16.3%), leukocyte decrease (216, 14.7%), fatigue (191, 13.0%), platelet decrease (180, 12.3%), HFSR (142, 9.7%) and neutrophil decrease (137, 9.3%). The main DRAEs of Grade ≥3 were HTN (87, 5.9%), platelet decrease (36, 2.5%) and HFSR (35, 2.4%). Typical AEs associated with anti-angiogenetic drugs occurred early following apatinib therapy: HTN was frequently diagnosed in the first 4 weeks, and its incidence decreased gradually; HFSR was commonly detected during the 2nd–5th week, and PTN during the 3rd–7th week. Conclusions: Well-established and manageable safety profile of apatinib and early presence pattern of anti-angiogenesis AEs are reaffirmed in this large clinical practice setting of pts with chemo-refractory advanced or metastatic gastric cancer. Clinical trial information: NCT02426034.
Impact of age, comorbidity, and treatment on survival in elderly women with advanced epithelial ovarian cancer.
Authors: Sarah Todd, Sharon E. Robertson, Yin Xiong, Martine Extermann, Robert Michael Wenham, Hye Sook Chon
Journal: Journal of Clinical Oncology (2017)

e17072 Background: This study aimed to assess the impact of clinical factors, including age and comorbidity, and treatment on outcomes data for women 70 years and older with advanced epithelial ovarian cancer (EOC). Methods: A retrospective chart review was performed on 501 patients with advanced EOC cancer at a single institution between January 1, 2001 and April 1, 2014. Exclusion criteria included non-epithelial histology, stage less than IIIC, and incomplete medical records. Clinical data included disease characteristics, performance measures (ECOG Performance Score, Karnofsky Performance Status, Cumulative Illness Rating Scale for Geriatrics (CIRS-G) score), method of treatment and outcome (surgical debulking status, Mayo Surgical Complexity Score, use of intraperitoneal (IP) chemotherapy, total lines of therapy), and survival data. Results: One hundred twenty-six study subjects (25.15%) were &gt; 70 years old at the time of advanced EOC diagnosis. In a univariate analysis, study subjects &gt; 70 years old were significantly more likely to have a higher CIRS-G score, fewer total lines of therapy, no IP therapy, less enrollment in clinical trials, decreased platinum sensitivity, and worse progression free survival (PFS) and overall survival (OS). A multivariate logistic regression analysis, using variables significant to a level of p &lt; 0.1 in the univariate analysis, demonstrated that patients &gt; 70 years old were significantly more likely to have a higher CIRS-G score (OR1.14, p = 0.00037), worse OS (OR0.98, p = 0.00026), and less likely to have IP therapy (OR0.57, p = 0.04973). Factors independently associated with decreased OS in all study subjects in a multivariate cox proportion hazard model were fewer total lines of therapy (HR0.24, p = 0.0035), lack of IP therapy (HR0.64, p = 0.0036), suboptimal debulking status (HR1.38, p = 0.045), lack of platinum sensitivity (HR0.30, p = 0.00001), and older age (HR1.62, p = 0.0016). Conclusions: In this cohort of patients with advanced EOC, elderly patients had worsened OS. This appears to correlate with comorbidity, lack of platinum sensitivity, along with less aggressive treatment options, number of lines of therapy, IP chemotherapy, and clinical trial enrollments.
Upfront docetaxel for castration-sensitive metastatic prostate cancer in an ethnically diverse inner-city population.
Authors: Surabhi Pathak, Romy Jose Thekkekara, Ahmed T Ahmed, Udit Yadav, Michael Russell Mullane, Kumar Kunnal Batra, Thomas E. Lad, Sarah P Psutka
Journal: Journal of Clinical Oncology (2018)

e17038 Background: Upfront docetaxel (UD) in castration-sensitive metastatic prostate cancer (CSPC) has improved failure-free and overall survival in the CHAARTED, GETUG-AFU 15 and STAMPEDE trials, resulting in a paradigm shift in practice patterns. However, the impact of docetaxel-based chemotherapy in underrepresented minority patients and in real-world practice remains to be described. The objective of this study was to evaluate toxicity and oncologic outcomes association with UD in an inner-city ethnically diverse CSPC cohort. Methods: We compared retrospectively collected clinical data for CSPC patients at Cook County Hospital treated with UD and androgen deprivation (UD, n = 49, 2013-17) to that of patients receiving androgen deprivation therapy alone (ADT, n = 49, 2010-17) using descriptive statistics and Cox Proportional Hazards analysis. Results: Median age was 59 years in UD and 60 years in ADT. African Americans, Hispanics and Caucasians formed 65%, 20%, and 10% in UD and 63%, 12% and 22% in ADT. Median (IQR) PSA at diagnosis was: UD 477 (91-1176) ng/ml, ADT 474 (54-1452) ng/ml (p = 0.7). Gleason score ≥ 7 was present in 79.4% in UD and 59% in ADT. UD and ADT had similar frequency of bone (92% vs. 96%, p = 0.3), visceral (16.3% vs. 14.3%, p = 0.7) and retroperitoneal nodal metastases (55% vs. 45%, p = 0.3). UD was initiated a median of 9 weeks from diagnosis. 94% in UD received > 3 cycles of chemotherapy. CTCAE grade > 3 events included anemia (6%); neutropenia (2%); infection (2%); diarrhea (4%); peripheral neuropathy (6%), and fatigue (2%). Median PSA nadir was 3.2 (0.5-18.6) vs. 2.95 (0.2-36.4) ng/ml and time to nadir was 30 (22-45) vs. 45 (20-77) weeks in UD vs. ADT. Biochemical progression was observed in 38.8% (UD) vs. 73.5% (ADT). Median time to progression was 73 weeks in UD vs. 88 weeks in ADT (HR: 0.9; 95% CI 0.5-1.6; p = 0.8). There were 8 deaths (UD: 2; ADT: 6) during a median follow-up of 57 (45-84, UD) and 123 (72.5-187, ADT) weeks. Conclusions: In a diverse, underserved population with CSPC, UD was well tolerated but was not associated with improvement in time to progression compared to ADT. These results warrant validation and underscore the importance of ensuring accrual of minorities in clinical trials.
Estrogen receptors expression in human bladder cancer and urogenital schistosomiasis.
Authors: Carina Bernardo, Ana Tavares, Teresina Amaro, Julio Oliveira, Vera Afreixo, Nuno Vale, Jose M Costa, Júlio H Livramento, Paul J Brindley, Céu Costa, Francisco Amado, Luisa Helguero, Lúcio Lara Santos
Journal: Journal of Clinical Oncology (2017)

e16013 Background: Epidemiological and molecular findings suggest that estrogen may play a role in bladder carcinogenesis and in urogenital schistosomiasis (UGS). Methods: A comprehensive analysis of expression of estrogen receptors (ER) in urothelial carcinomas (UC), n = 80 from non-infected patients and UGS-related bladder carcinoma (BlaCa) n = 27 was undertaken. I n vitro, we evaluated the effect of estradiol (E2) and anti-estrogens on the survival of human BlaCa cells. In addition, molecular dynamics simulations are ongoing to assess the ability of estradiol-like metabolites produced by the Schistosoma haematobiumto bind ERs. Results: Tumor cell expression of ERα was found in 17.5% of the non-infected cases, and was associated with proliferative tumors (p = 0.004, ES = 0.326) and lower overall survival. Expression of ERα was also found in normal urothelium adjacent to the tumor and in tumor stromal cells, particularly in T2 and late stage tumors (p = 0.034, ES = 0.498and p = 0.037, ES = 0.357, respectively). In UGS-related BlaCa, 22% of tumor cells were ERα positive. Presence of parasite eggs was associated with higher ERα expression in cancer cells and adjacent urothelium (p = 0.038, ES = 0.399 and p = 0.020, ES = 0.600, respectively). ERβ was found in 91% of non-infected UC and 78% of the UGS-related tumors. ERβ was equally expressed across different tumor stages and grade but more intense in tumor cells than in urothelium of normal appearance and in non-infected than in UGS-related cases. In the latter group, staining intensity was increased in women and in samples with parasite eggs. Using 3 human BlaCa cell lines, HT1374, T24 and 5637, we observed that 5637 cells express ERα and can be stimulated by E2 and inhibited by the anti-estrogens (4OH-tamoxifen and ICI 182 780). T24 cells expressed ERα at very low levels and did not respond to E2, but were inhibited by anti-estrogens; HT1376 do not express ERα. ERβ mRNA was not detected in any of the cell lines. Conclusions: Our results document an association between expression of ERα and aggressive features. The potential of expression of ERs as a prognostic tool and as therapeutic target should be further investigated especially for tumors with aggressive profile and during UGS-related carcinogenesis.
Association of circulating tumor cells (CTCs) with hyperglycemia in the follow-up of Chinese non-metastatic breast cancer patients.
Authors: Yu-Mei Shi, Guochun Zhang, Chong-Yang Ren, Ling-Zhu Wen, Wen-zhen Zhu, Xiao-qing Chen, Ning Liao
Journal: Journal of Clinical Oncology (2017)

e23020 Background: CTCs has been confirmed to associate with a poor outcome of breast cancer at primary diagnosis. To date, CTC has not been studied with sufficient details in the follow-up of non-MBC pts, especially in Chinese population. We investigated the associations of CTC with clinicopathological features and metabolic factors to gain insight into potential interactions between physiology and disease burden. Methods: We recruited 264 cases of postoperative pts with non-MBC in Guangdong General Hospital from Jan 2009 to Dec 2015. For each enrolled pts 7.5mL blood samples were drawn for CTC enumeration using the CellSearch system. CTC results were correlated with clinicopathological features, obesity related indicators and HBsAg. A multivariate logistic regression analysis was performed to further determine the independent predictors of CTC. The study defined CTC positive as CTC ≥1. Results: In 10.6 % of all pts (n = 28) a median of 1 (range, 1–108) CTC was detected. A pT1 tumor was present in 47% of pts, 11.4 % had G1 grading and 64.4 % were node-negative. The positive rate of CTCs in pts with IDC and ILC was lower than that in pts with other pathological types (9% and 11.1% vs 28.6% P=0.02). A similar trend that approached significance was noted for age (p=0.062), histological grade( p=0.087), invasion of the nipple areola (p=0.06). CTCs was positively correlated with blood glucose (p=0.015), and negatively correlated with high density lipoprotein (p=0.049). In addition, glycated hemoglobin was positively associated with CTC in correlations that neared significance (p=0.059). The result of multivariate logistic regression analysis is shown in the Table. No associations were observed in triglycerides, free fatty acid, total cholesterol, low-density lipoprotein and HBsAg. Conclusions: This study suggested pathological type and blood glucose were independent predictors of CTC, supporting the notion that high fasting glucose level in BC pts may have severe disease burden, leading to a higher frequency of CTC. [Table: see text]
Duvelisib inhibition of chemokines in patients with CLL (DUO study) and iNHL (DYNAMO study).
Authors: David T. Weaver, Kam Sprott, Jonathan Pachter, Ngocdiep T. Le, Matthew Steven Davids, Marco Montillo, Árpád Illés, Gabriel Etienne, Julio Delgado, Bryone J. Kuss, Constantine Tam, Fritz Offner, Scott D. Lunin, Francesc Bosch, Peter Hillmen, Nicole Lamanna, Stephan Stilgenbauer, Pier Luigi Zinzani, Ian Flinn, Jennifer R. Brown
Journal: Journal of Clinical Oncology (2018)

12048 Background: Duvelisib (IPI-145) (DUV) is an oral dual inhibitor of phosphoinositide 3-kinase (PI3K)-δ and PI3K-γ being developed to treat B-cell malignancies. PI3K-δ inhibition directly targets proliferation and survival of malignant leukemia and lymphoma cells, while PI3K-γ inhibition modulates the tumor microenvironment (TME) through key support cells, including tumor-associated macrophages, nurse-like stroma and T cells, and via soluble factors stimulating tumor growth, survival and migration. The Phase 3 DUO study in relapsed/refractory (RR) CLL/SLL and the Phase 2 DYNAMO study in RR iNHL both met their primary endpoints (Flinn, ASH 2017; Zinzani EHA 2017). Methods: DUO (NCT02004522) pts were randomized to DUV (n = 160) or ofatumumab (OFA) (n = 159). DYNAMO (NCT01882803) pts (n = 129) received DUV. Serum from baseline and C2D1 was used for correlative studies of 24 chemokines, cytokines and serum factors. Bonferroni-Holm adjustment for multiple comparisons was applied. Results: In DUO, CCL1, CCL17, CXCL9, CXCL10, CXCL11, and IL-10 were reduced in pts treated with DUV (median % inhibition = 43.8%) but not in those treated with OFA (p≤0.0009). Eight chemokines were reduced in both treatment arms, but the level of reduction was significantly greater for DUV pts (median % inhibition, DUV 64.6% vs OFA 26.8%; p≤0.001). Many of the chemokines inhibited following DUV treatment are associated with the TME, including TNFα, IL-10, IL2Rα, IL12P40, CCL1, CCL17, CCL19, CXCL9, CXCL10, CXCL11, and CXCL13. In DYNAMO, 13 corresponding chemokines were also inhibited (p≤0.008), including TME factors. Reductions occurred rapidly (by C2D1) in both studies. In DUO, there was a correlation between duration of response and reduction (highest quartile) of the following chemokines: CCL17 (19.4 mo. Q4 vs 10.4 mo. Q1-3), CXCL11 (14.9 mo. Q4 vs 10.9 mo. Q1-3) IL-6 (16.6 mo. Q4 vs 10.9 mo. Q1-3), TRAIL (24 mo. Q4 vs 10.3 mo. Q1-3), VEGF_D (24 mo. Q4 vs 10.9 mo. Q1-3), TPO (14.9 mo. Q4 vs 10.9 mo. Q1-3). Conclusions: Pts with CLL and iNHL treated with DUV monotherapy showed significant reduction of chemokines potentially derived from the tumor cells and TME. Further investigation of the effects of DUV on TME pharmacodynamic markers is warranted. Clinical trial information: NCT02004522; NCT01882803.