tbuckley/cabot-search huggingface dataset:
Integrated molecular analysis of Asian ovarian cancer: Gene expression and whole exome sequencing analyses from the iPocc Translational Research study (TriPocc).
Authors: Ruby Huang, Tuan Zea Tan, Jieru Ye, Christiane Kuschal, Zuan Yu Mok, Shane Ee Goh, Sili Tan, Jia Xian Tay, Mohd Feroz Mohd Omar, Sho Sato, Anand Devaprasath Jeyasekharan, Diana Lim, Richie Chuan Teck Soong, Keiichi Fujiwara, Kosei Hasegawa, David Shao Peng Tan
Journal: Journal of Clinical Oncology (2018)

5562 Background: iPocc is a randomized, multicenter international study comparing the efficacy of first line intravenous (IV) dose-dense paclitaxel and intraperitoneal (IP) carboplatin with standard IV dose-dense paclitaxel and carboplatin in women with epithelial ovarian, fallopian tube or primary peritoneal cancer. TriPocc is the translational research protocol evaluating the molecular and predictive biomarkers for differences in treatment outcome. Methods: Fresh frozen (FF) biopsies (N = 123) collected during surgeries from participating institutions in Japan and Singapore were included into TriPocc. Briefly, DNA and RNA were extracted from FF biopsies and paired germline DNA were extracted from the peripheral blood mononuclear cells (PBMC). Whole-transcriptome profiling (WTP) was done by Affymetrix Human Transcriptome Array (HTA) 2.0 (N = 120) for gene expression molecular subtypes (GEMS). Whole-exome sequencing (WES) was done by Nextera Rapid Capture Custom Enrichment Kit for library preparation followed by Illumina NextSeq 500 for paired somatic and germline sequencing (N = 116). The Broad Institute Genome Analysis Tool Kit (GATK) V3.7 was used for variant calling. Results: High grade serous carcinoma (HGSC) was the most frequent histotype (N = 72; 60%), followed by endometrioid (N = 18; 15%) and clear cell carcinoma (N = 16; 13.3%). Mes was the dominant GEMS (N = 43; 35.8%), followed by Epi-B (N = 29; 24.2%), Stem-A (N = 27; 22.5%), Stem-B (N = 17; 14.2%), and Epi-A (N = 4; 3.3%). Unique mutations were discovered in HGSC. Top significant mutations identified (q-value lower than 1xE-9) included ITGA4, UCN3, COL4A3, ACP2, SEH1L, AGL, FAM26F, OR5H15, EXO1, TEKT3, ZNF720, IFI44L, MERTK, TP53, DHX57, TTC31, which were not reported previously in the TCGA cohort. BRCA1/2 mutations (26.1% of all samples) were found in 35.2% of HGSC and 13.5% of non-HGSC, which is higher than previously reported. Conclusions: The integrated genomic analysis from TriPocc has enabled the discovery of potentially novel molecular alterations in Asian ovarian cancers. The predictive value of these molecular alterations will be assessed once the iPocc outcome data are mature.
Combined treatment of apatinib with docetaxel as post second-line therapy in advanced non-squamous non-small cell lung cancer(NSCLC): Results from a pilot, multi-center study.
Authors: Daiyuan Ma, Qian Jiang, Ningling Zhang, Bangxian Tan, Xin Hu, Xiangdong Fang
Journal: Journal of Clinical Oncology (2018)

e21213 Background: There is no effective treatment strategy for patients with advanced non-small cell lung cancer (NSCLC) who experienced progression with one or two lines of chemotherapy. Apatinib, a new tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 (VEGFR-2), has been shown promising antitumor activity and manageable toxicities in NSCLC. The purpose of this study was to evaluate the effectiveness and safety of apatinib combined with docetaxel in NSCLC. Methods: This multicenter, open-label, single arm study enrolled stage Ⅳa~Ⅳb NSCLC patients who failed in the metastatic setting at least 1 and at most 3 prior platinum-based chemotherapy regimens. The primary end point of this study was progression free survival (PFS). Secondary end points included objective response rate (ORR), disease control rate (DCR), 6-month overall survival rate, and toxicity. Patients received oral apatinib, at a dose of 250 mg daily, and docetaxel, at a dose of 75mg/m2 on days 1 and 22, repeat every 4 weeks. Treatment was continued until disease progression. Results: Between Nov 30, 2016 and Jun 1, 2018, 14 patients were enrolled. In 14 patients, there were 12 patients available for efficacy and safety evaluation. Followed up to Dec 28, 2017, the median time of follow-up was 9.76 months. Median PFS and 6-month overall survival rate were 2.92 months(95% CI 1.38–4.48) and 80%, respectively. According to RECIST criteria, the DCR was 66.67%, 8/12 (partial response 33.33%, 4/12 and stable disease 33.33%, 4/12). The DCR was 50% for 2 patients with brain metastases following apatinib administration. The most frequent treatment-related adverse events were leukopenia (58.33%, 7/12), hand-foot syndrome (41.67%, 5/12) and diarrhea (33.33%, 4/12). Main grade 3 toxicities were leukopenia (33.33%, 4/12), hand-foot syndrome (8.33%, 1/12). No grade 4 toxicities were observed. Conclusions: Apatinib plus Docetaxel exhibits superior activity and acceptable toxicity for the heavily pretreated patients with advanced non-small cell lung cancer, and might provide a new option for the treatment of such patients with brain metastases. Clinical trial information: NCT03416231.
Abstract 17899: Relationship Between Galectin-3 and Coronary Plaque Burden and Plaque Structure in Obstructive Sleep Apnea Syndrome
Authors: Hamdi Pusuroglu, Umut Somuncu, Huseyin Altug Cakmak, Ismail Bolat, Ozgur Akgul, Vesile Ornek, Sinem Ozbey Ozyilmaz, Hayriye Ak Yildirim, Umit Bulut, Huseyin Karakurt, Fatih Uzun, Ayfer Utkusavas
Journal: Circulation (2016)

Introduction: Obstructive sleep apnea syndrome (OSAS) has been reported to be related with hypertension, coronary artery disease and heart failure in recent studies. Galectin-3 plays an important r...
End of life spending among cancer patients in an ACO vs. non-ACO.
Authors: Miranda Lam, Jose Figueroa, Kim Reimold, E. John Orav, Ashish Jha
Journal: Journal of Clinical Oncology (2018)

6511 Background: Nearly 25% of the annual Medicare budget is devoted to care of beneficiaries who die in a given year. Therefore, there has been increased policy and provider focus on understanding the care provided to patients at the end of life. Of the many initiatives aimed at improving the value of healthcare services in the United States, Accountable Care Organizations (ACOs) are receiving substantial policy attention. Early evidence shows modest reductions in total healthcare costs for Medicare beneficiaries. However, we are unaware of any data looking specifically at the impact of ACOs on spending for cancer patients at the end of life. Methods: We analyzed a 20% sample of Medicare beneficiaries age 66 years or older. We followed CMS guidelines to attribute patients to an ACO or non-ACO practice. Using ICD-9 codes, we identified patients with cancer. We matched ACO and non-ACO practices within the same HRR and narrowed to patients who died in 2013 or 2014. We calculated mean annual standardized total costs in the 180 days prior to death and stratified by inpatient, outpatient, physician, skilled nursing facility, home health, hospice, radiation oncology, and chemotherapy spending. Spending was adjusted for patient characteristics and by chronic conditions. Results: 36% of patients were in an ACO. ACO and non-ACO patients were similar in terms of patient characteristics (age, race, sex, dual eligibility, comorbidities). ACO beneficiaries had modest but significantly higher total annual standardized costs compared to beneficiaries not in an ACO ($47,629 vs. $45,582; p = 0.02). The ACO and non-ACO patients had similar spending by categories: inpatient ($23,908 vs. $22,843; p = 0.06), outpatient ($4,939 vs. $4,403; p = 0.09), physician services ($13,412 vs. $12,975; p = 0.26), SNF ($2,164 vs. $1,952; p = 0.18), HHA ($2,009 vs. $2,027; p = 0.82), hospice ($683 vs. $793; p = 0.07), radiation oncology ($449 vs. $422; p = 0.62), and chemotherapy ($1,927 vs. $1,813; p = 0.57). Conclusions: Spending in the last 6 months of life among cancer patients treated in an ACO was slightly higher compared to those not treated in an ACO. This study suggests that ACOs have not had a meaningful impact in reducing costs at the end of life for cancer patients.
Prophylactic treatment for acneiform rash caused by EGFR inhibitors: Prospective randomized double-blind trial comparing daily topical chloramphenicol 3% plus prednisolone 0.5% vs chloramphenicol 3% vs aqua cream.
Authors: Salomon M. Stemmer, Hadas Prag-Naveh, Ayelet Ollech, Aron Popovitzer, Ofer Purim, Dov Flex, Yael Leshem, Batya Davidovici, Olga Ulitsky, Baruch Brenner, Irit Ben-Aharon, Nir Peled, Michael David, Iris Amitay Laish
Journal: Journal of Clinical Oncology (2018)

10092 Background: Epidermal growth factor receptor inhibitors (EGFR-I), which are indicated for various tumor types, are associated with acneiform rash on the face/torso in approximately 90% of patients. This rash adversely impact patients' quality-of-life and may result in dose reductions/delays and treatment discontinuation. Methods: This randomized double blind trial investigated chloramphenicol 3% + prednisolone 0.5% (Threolone) vs chloramphenicol 3% vs aqua cream as prophylactic treatment for acneiform rash caused by EGFR-I. Adult cancer patients treated with EGFR-I (cetuximab, panitumumab, erlotinib, or gefitinib) were randomized to treatment with the 3 above mentioned options and were instructed to administer the assigned topical treatment to their face daily for 3 weeks and every 2 days for another week. The severity of the rash was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0 as well as the number of facial lesions. Severe rash was defined as grade≥3 by the CTCAE criteria or ≥10 facial lesions. The rash was assessed on Days 0, 14, and 28. Results: Overall, 69 patients were randomized (21 chloramphenicol 3% + prednisolone 0.5%, 23 chloramphenicol 3%, and 25 aqua cream). The arms were similar with respect to demographics and tumor types. Number of facial lesions and CTCAE grade were highly correlated (r = 0.9). According to the number of facial lesions, chloramphenicol + prednisolone but not chloramphenicol alone was significantly more effective than aqua cream (Table). Conclusions: Topical chloramphenicol 3% + prednisolone 0.5% may be an effective prophylactic treatment for EGFR-I-associated acneiform rash. Clinical trial information: NCT01256437. Proportion of patients with protocol specified severe acneiform rash. Study arm N Day 14 Day 28 Day 14 or 28 Severity by CTCAE, % Severity by NOL, % Severity by CTCAE, % Severity by NOL, % Severity by CTCAE, % Severity by NOL, % Chloramphenicol 3% + prednisolone 0.5% 21 0 14a 0 6a 0 19a Chloramphenicol 3% 23 5 40 5 16 5 39 Aqua cream 25 20 48 5 43 20 52 aP< 0.05 vs aqua cream treatment. All other 2-way comparisons were non-significant. NOL: number of lesions
P01.054 Patterns of first tumor progression and impact on survival of salvage therapies in low-grade gliomas following initial chemotherapy with temozolomide
Authors: A Pellerino, R Rudà, A Pace, C Carapella, C Dealis, M Caroli, M Faedi, L Bello, R Soffietti
Journal: Neuro-Oncology (2018)

Initial chemotherapy with temozolomide (TMZ) has been suggested to provide some benefit in terms of response and progression-free survival (PFS) in high-risk low-grade gliomas. To date, no standard treatment has been validated at progression. The aim of the study was to investigate which is the optimal salvage therapy after the first progression and the factors that may influence the PFS and the overall survival (OS). We evaluated 49 patients with an histological diagnosis of grade II oligodendroglioma and oligoastrocytoma according to WHO 2007 included in a phase II AINO (Italian Association for Neuro-Oncology) trial, who progressed following initial chemotherapy alone with dose-dense TMZ. Fifteen patients (30.6%) had seizures at the time of progression. Molecular data were available in 48 patients: 29 patients were IDH 1/2 mutated, 23 1p/19q codeleted, and 36 MGMT methylated. Median follow up was 140 months. All patients had local tumor progression and patterns on MRI were as follows: a FLAIR lesion in 25 patients (51.0%), a mild patchy enhancing lesion in 14 patients (28.6%), and a nodular enhancing lesion in the other 10 patients (20.4%). Twenty-four patients (49%) underwent a second-line chemotherapy (TMZ rechallenge or PCV schedule), 12 patients (24.5%) a salvage radiotherapy, 11 patients (22.4%) a second surgery (10 gross-total resection and 1 subtotal resection), while 2 patients (4.1%) received palliative care. The response rate (RANO criteria) following salvage radiotherapy or chemotherapy was as follows: PR in 6/38 patients (15.8%), MR in 9/38 (23.7%), SD in 10/38 (26.3%), and PD in 13/38 (34.2%). Overall, median PFS after first salvage therapy was 18 months (IC95% 11–27). Median PFS was 11 months (IC95% 8–74) after radiotherapy, 14 months after chemotherapy and 31 months after surgery (IC95% 18–51, p 0.013). Median OS from the first salvage therapy was 63 months (IC95% 4 - non reached). Median OS was 44 months (IC95% 4 - not reached) after radiotherapy, 38 months (IC95% 22–80) after chemotherapy, and 87 months after surgery (IC95% 11-not reached, p 0.09). Seizure freedom was achieved in 6/15 (40%) patients following first salvage therapy (3 patients after surgery, 2 patients after chemotherapy, and 1 patient after radiotherapy). Reoperation aiming at total or near/total resection seems to offer a probability of a longer PFS and OS compared with the other treatment options. Seizure response may be achieved in a substantial proportion of patients receiving at tumor progression the different antineoplastic options.
Copy number variation of genes in cell-free DNA in patients with lung adenocarcinoma.
Authors: Denis S. Kutilin, Igor N. Turkin, Dmitry I. Vodolazhsky, Tamara G. Ayrapetova, Sergey P. Pyltsin, Pavel A. Anistratov, Anna V. Chubaryan, Igor A. Leyman, Yuriy N. Lazutin, Oleg N. Stateshny, Oleg Ivanovich Kit
Journal: Journal of Clinical Oncology (2018)

e24060 Background: The problem of early diagnosis of lung cancer remains unsolved since currently known molecular markers for lung cancer diagnosis do not possess necessary specificity. Studying gene copy number variation (CNV) in cell-free DNA in the blood plasma can become a basis for a new effective and minimally invasive method for predictive diagnostics. The purpose of the study was comparative analysis of CNV of genes responsible for the apoptosis regulation (BAX, BCL2, C-FLAR), proliferation (MKI67, KRAS, EGFR, MAPK1, BRAF), oxidative phosphorylation (HV2) and hypoxia response (HIF1A) in cell-free DNA in patients with lung adenocarcinoma and healthy donors. Methods: The RT-qPCR method was used to study the CNV of 10 genes (reference genes – GAPDH, B2M, ACTB) in the cell-free DNA of blood plasma (collected prior to surgery) in 60 patients with a histologically confirmed diagnosis of lung adenocarcinoma (T1N0M0, G1-2), and in the cell-free DNA of the blood plasma of 30 healthy donors (without cancer). The significance of differences was assessed by the Mann-Whitney test. Results: Reduction of HV2 (hypervariable region with 33 to 160 nucleotides of the mtDNA D-loop) copy number by 16 fold (p < 0.005), as well as increasing by 1.6 fold (p < 0.05), 2.4 fold (p < 0.05), 2.0 fold (p < 0.01) and 2.0 fold (p < 0.05) copy number of the HIF1A, BCL2, MAPK1 and BRAF genes respectively, was found in the cell-free DNA of patients with lung adenocarcinoma in comparison with healthy donors. Conclusions: Copy number of HV2, HIF1A, BCL2, MAPK1 and BRAF genes in cell-free DNA of patients differs from copy number in cell-free DNA of healthy donors, and has a high potential for minimally invasive diagnosis of lung adenocarcinoma. (The reported study was supported by RFBR, research project No. 16-34-00267 mol_a).
The benefit of modern cancer therapy for older patients.
Authors: Amandeep Mahal, Laura D. Cramer, Elyn H. Wang, Shi-Yi Wang, Amy J. Davidoff, Cary Philip Gross, James B. Yu
Journal: Journal of Clinical Oncology (2016)

e18141 Background: Assessing the improvement in national cancer outcomes over the past two decades requires measurement not only of patient survival, but quality of life as well. We examined changes in health-related quality of life (HRQOL) and survival for older patients with breast, prostate, and lung cancer diagnosed in 1998-2001 versus 2006-2009. Methods: The NCI SEER MHOS database was used to define a cohort of patients with cancers diagnosed and treated 1998-2009. Eligible patients completed two surveys two years apart, with one each pre and post cancer diagnosis, regarding their HRQOL. For each survey, a measurement of overall quality of life (health utility (HU)) was calculated from SF-6D questions within each survey, as well as Physical Component Summary (PCS) and Mental Component Summary (MCS) summary scores. Patients treated in Early Era (1998-2001) vs. Late Era (2006-2009) were matched within each cancer site by propensity scores to account for sociodemographic and clinical characteristics. Survival (overall, cancer-related, and non-cancer-related) was calculated as well as change in HU, PCS or MCS scores. Results: We identified 108 patients with prostate, 154 with breast and 37 with lung cancer who were treated in the ‘Early Era’ and matched to equal numbers in the ‘Late Era’. Overall survival was similar for early and late eras (3 year OS prostate 96.3% vs 93.5%, breast 94.2% vs. 94.2%, and lung 62.2% vs. 73.0%, respectively, log-rank p > 0.3 for all comparisons). There was a trend towards improved cancer-specific survival in the later era (prostate p = 0.157, breast p = 0.096, and lung p = 0.071) with the largest improvement seen for lung cancer. There was a lower post-diagnosis decline in health utility for patients diagnosed with prostate cancer in the later era compared to early era (mean decline in HU from baseline to 24 months of 0.008 vs. 0.048, p = 0.013). There were no other statistically significant differences in declining HU for breast or lung cancer, or in MCS, or PCS for any cancer. Conclusions: Our results suggest a trend towards improvement in cancer-specific survival for patients treated in more recent years. Patients treated for prostate cancer in the later era reported superior outcomes in terms of quality of life compared to earlier.
Abstract 21234: Patient and Lesion Predictors of Stenting and Atherectomy for Peripheral Arterial Disease
Authors: Niveditta Ramkumar, Bjoern D Suckow, Jeremiah R Brown, Philip P Goodney
Journal: Circulation (2017)

Introduction: Endovascular management of peripheral arterial disease (PAD) has become popular in the past two decades. But little is understood about the practice patterns of different endovascular treatment modalities and the factors that influence their use. Objective: Identify predictors for stenting and atherectomy treatment, compared to angioplasty (PTA) for PAD. Methods: We abstracted data from all endovascular procedures for PAD during January 2010- October 2016 in the Vascular Quality Initiative clinical registry. Adjusted logistic regression models built using backward elimination with a random-effects component for patient clustering were used to identify factors predictive of stenting or atherectomy compared to PTA at the artery level. Results: Eligible patients (n=58,231) had 106,039 arteries treated (median=2, IQR=1 to 3). The majority (50%) of these arteries were treated with stents, 39% with PTA and 11% with atherectomy. Compared to PTA, those receiving stents are more likely to smoke and have iliac treatment. In atherectomy, we see more distal treatment (SFA and tibial) compared to PTA. Artery location was a significant (p&lt;0.05) effect modifier. In multivariable models, there were no significant predictors for atherectomy; TASC C trended to significance in femoropopliteal (OR 6.6 [p=0.08]) and tibial arteries (OR 11.1 [p=0.06]). TASC C and D predicted stenting in all arteries (Figure 1). Current smoking (OR 1.49 [1.32-1.68]), obesity (OR 1.30 [1.17-1.44]), and age 70-79 (OR 1.36 [1.07-1.17]) predicted stenting in femoropopliteal arteries. These factors also predicted stenting in tibial arteries: current smoking (OR 1.40 [1.04-1.88]), obesity (OR 1.50 [1.15-1.44]), and age 80-89 (OR 1.56 [1.14-2.17]). Conclusion: TASC C and D trended toward significance as predictors of atherectomy in tibial and femoropopliteal arteries. TASC C and D, artery type, smoking status, age, and obesity are significant predictors of stenting in all arteries.
Association of Legal Intervention Injuries With Race and Ethnicity Among Patients Treated in Emergency Departments in California
Authors: Alyssa C. Mooney, Shannon McConville, Aaron J. Rappaport, Renee Y. Hsia
Journal: JAMA Network Open (2018)

Increased public concern regarding police use of force has coincided with a dearth of available data to uncover the magnitude and trends in injuries, particularly across race or ethnicity.To examine trends in injury rates, severity, and disparities across black individuals, white individuals, Hispanic individuals, and Asian/Pacific Islander individuals.In this retrospective, cross-sectional study, data collected on every hospital visit in California from January 1, 2005, to September 30, 2015, were used to model trends in rates of legal intervention injuries (n = 92 386) per capita and per arrest for men aged 14 to 64 years, by race or ethnicity. The study also examined descriptive statistics on injury dispositions to assess changes in severity. Analyses were conducted between December 2017 and June 2018.All visits with an external cause of injury code of E970 to E977 were classified as legal intervention injuries. This range of codes includes injuries inflicted by the police or other law-enforcing agents in the course of arresting or attempting to arrest lawbreakers, suppressing disturbances, maintaining order, and other legal action.The study identified a total of 92 386 hospital visits that were the result of legal intervention among males aged 14 to 64 years. Black individuals were at the highest risk of legal intervention injury per capita in 2005 (for black vs white individuals, rate ratio, 2.90; 95% CI, 2.74-3.06), and remained so across the study period. Although rates among Asian/Pacific Islander individuals remained stable, rates in all other groups increased from 2005 to 2009 and then declined from 2009 to 2015, nearly returning to 2005 levels. During the period of increasing rates, the black to white disparity widened by 3% annually (rate ratio, 1.03; 95% CI, 1.01-1.05), then narrowed as rates declined. In contrast, rates of injury per arrest have increased over the past decade, although rates were broadly similar across race or ethnicity. The proportion of injuries involving firearms (ie, shootings by police) declined from 7.0% in 2005 and 2006 to 3.7% in 2014 and 2015.States with central repositories for hospital visits offer data sources to illuminate the public health problem of legal intervention injuries, and warrant greater attention to ensure consistent coding for complete capture.