tbuckley/cabot-search huggingface dataset:
Phase II study of the frontline combination of ipilimumab and temozolomide in patients with metastatic melanoma.
Authors: Sapna Pradyuman Patel, Wen-Jen Hwu, Kevin B. Kim, Nicholas E. Papadopoulos, Patrick Hwu, Laszlo George Radvanyi, Sandy Mahoney, Tawania L Deburr, Ping Liu, Agop Y. Bedikian
Journal: Journal of Clinical Oncology (2012)

8514 Background: Ipilimumab (Ipi) alters the immune system balance by inhibiting the suppression of T-cell function. In two phase III trials, Ipi has shown an overall survival benefit alone and in combination with dacarbazine in previously treated and treatment-naïve patients (pts) with metastatic melanoma (MM), respectively. We performed a single-institution, phase II clinical trial of Ipi plus temozolomide (Tem) in pts with MM. Methods: Pts between the ages of 18 and 75 with previously untreated unresectable stage III or stage IV MM and an ECOG Performance Status of 0 to 1 were enrolled in a phase II trial of Ipi plus Tem. Induction phase consisted of Ipi 10mg/kg intravenous on Day 1 and oral Tem 200 mg/m 2 on Days 1 – 4 every 3 weeks for 4 doses. Maintenance consisted of Ipi 10 mg/kg intravenous on Day 1 starting week 12 and repeated every 12 weeks and oral Tem 200 mg/m 2 on Days 1 – 5 starting week 12 and repeated every 4 weeks until disease progression or unacceptable toxicity occurred. The primary endpoint was progression-free survival (PFS) rate at 6 months. Responses were evaluated using immune-related response criteria. Results: Sixty-four pts were enrolled and received at least one dose of study drug. All pts were included in the analysis. With a median follow-up of 8.5 months, the PFS rate at 6 months was 43%, exceeding the proposed rate of 30%, and the median PFS was 5.1 months. There were 10 (15.6%) confirmed complete responses and 8 (12.5%) confirmed partial responses. At the time of this analysis, median overall survival has not been reached. Immune-related adverse events (irAEs) were experienced by 88% of pts, most commonly pruritus (88%), rash (83%), diarrhea (56%), transaminitis (45%), and colitis (11%). Grade 3/4 irAEs seen in more than one patient were skin rash (11%), diarrhea (9%), pruritus (6%), and transaminitis (5%). Constipation occurred in 70% of pts and was the most common gastrointestinal (GI) toxicity. There were no GI perforations or deaths on study due to treatment. Conclusions: At a median follow-up of 8.5 months, the best overall response rate in this study is 28%. Ipi at 10 mg/kg in combination with Tem given in an induction followed by maintenance fashion is safe, well-tolerated, and efficacious in MM.
Structural indices of erythrocytes membrane in patients with vulvar cancer.
Authors: Irina Aleksandrovna Goroshinskaya, Galina Nerodo, Ludmila Anatolievna Nemashkalova, Ekaterina Igorevna Surikova, Ekaterina Alekseevna Nerodo
Journal: Journal of Clinical Oncology (2013)

e16515 Background: The analysis of membranes flow property in the zone of protein and lipid contacts, and of proteins submergence degree into lipid erythrocytes membrane bilayer in patients with vulvar cancer. Methods: 34 patients with vulvar cancer at the different stages of the disease were examined. We studied the characteristics of blood erythrocytes membranes with the use of pyrene probe: flow of protein and lipid contacts zones and lipid bilayer, submergence of proteins into lipid bilayer. Results: The analysis of the data received showed, that the most interesting results were obtained during the study of proteins submergence level. In the group with vulva primary tumor the level of proteins submergence into erythrocytes membrane lipid matrix was authentically higher than 25.9% (0.243±0.012, p &lt; 0.001) as compared with the index the healthy women have (0.193±0.006). The degree of proteins submergence into lipid matrix of the patients, being at the state of remission, was decreasing by 25.1% (0.182±0.013, p &lt; 0.01), as compared with the index in the group with primary tumor, achieving the level of the healthy women. Subsequently, during the progress of the relapse, the proteins submergence increased again (0.242±0.019, p &lt; 0.01), achieving the indices in the group with primary tumor. Also, membrane flow property in the zone of protein and lipid contacts was increasing by 25.1% (0.564±0.053, p &lt; 0.05) in the group with relapse, as compared with the group of the primary tumor (0.451±0.017). Conclusions: According to our observations, the increase of proteins submergence into erythrocytes membrane lipid matrix in patients with vulva cancer in remission preceded the clinical manifestation of the disease’s relapse, thus showing the prognostic significance of blood erythrocytes membranes studying during the progress of vulvar cancer.
Identifying targetable pathways in pancreatic cancer from endoscopic ultrasound-guided fine-needle aspirates (EUS/FNA): Providing a personalized approach to targeted therapy.
Authors: Andrea Wang-Gillam, Sachin Wani, Emma J. Langley, Feng Gao, Faris Murad, Daniel Mullady, Dayna S Early, Steven Alphonse Edmundowicz, David Linehan, Anne Kuller, Anjali Jain, Phillip Sangwook Kim, Sharat Singh, Riad Azar
Journal: Journal of Clinical Oncology (2013)

4051 Background: Targeted therapy trials in pancreatic cancer patients have either failed or, at most, provided only marginal benefit. Identification of activated key signaling pathways would allow the optimal selection of patients for kinase inhibitor trials. Hence, we launched a study to profile targetable pathways from EUS/FNA samples using an ultrasensitive multiplexed protein microarray platform (CEER, Prometheus). Methods: Patients who underwent routine diagnostic FNA for a suspicious lesion in the pancreas underwent two dedicated passes for CEER profiling of the following phosphorylated (activated) key molecules: HER1, HER2, HER3, c-met, IGF-IR, PI3K, AKT, MEK, ERK, and other signaling proteins. Results: Of 100 participants, final cytology results were: 73 carcinomas, 8 indeterminate, 13 negative, and 5 neuroendocrine. Pathway activation was heterogeneous in patients with carcinoma. Among 61 pancreatic cancer patients with adequate HER evaluation, a high prevalence of HER3 activation (62%) was observed, and concomitant activation of two or more HER pathways was seen in 52% of patients. In particular, activation of HER2 and HER3 was noted in 23% of carcinoma patients. High concordance of HER, PI3K and AKT activation was seen. Conclusions: Our study confirmed the feasibility of profiling targetable pathways from FNA samples. Furthermore, it illustrates highly variable and concomitant pathway activation among pancreatic cancer patients, suggesting the feasibility of a personalized approach to targeted therapy. Future trials will need to be designed to explore the clinical benefit of combinations of HER-targeted agents in defined subsets of pancreatic cancer patients, and further evaluation of the HER3 pathway is especially warranted. An analysis of pathway interactions and prognostic effects is in progress. [Table: see text]
Next-generation sequencing for genetic cancer risk assessment: Critical needs and perceptions of community clinicians.
Authors: Kathleen R. Blazer, Carin Espenschied, Benjamin Weissman, Sharon Sand, Jeffrey N. Weitzel
Journal: Journal of Clinical Oncology (2013)

1536 Background: Current standard-of-care practice for genetic cancer risk assessment (GCRA) focuses on single-gene testing for specific hereditary cancer syndromes. Next-generation sequencing (NGS) technologies recently became available for clinical applications. This study explored the perspectives and experiences of community-based clinicians regarding NGS testing for personalized GCRA. Methods: A 27-item survey was developed and administered online to 325 members of an interdisciplinary nationwide clinical cancer genetics community of practice. Results: Of 94 (29%) respondents, 25 (27%) have ordered at least one multi-gene panel and only 2 (2.1%) have ordered a whole exome or genome test from a commercial vendor for GCRA. Concerns about clinical utility, the challenge of interpreting and communicating results, lack of knowledge about and potential costs were most often cited as reasons for not pursuing NGS testing. Respondents were significantly more confident about their ability to interpret and counsel about single gene test results compared with multi-gene panels or whole exome/genome sequencing; and about multi-gene panels over whole exome/genome sequencing (p&lt;.0001 for all comparisons). Conclusions: Findings suggest that while NGS tests are entering the realm of GCRA, multidisciplinary genomics education and clinical support resources are needed to address barriers to utilization and promote successful integration of NGS testing into community-based GCRA practice settings.
International validation of an IGF-CTP scoring system for assessing hepatic reserve in hepatocellular carcinoma.
Authors: Reham Abdel-Wahab, Samir-Shehata M. Eid, Manal Hassan, Lianchun Xiao, Ju-Seog Lee, Sheree H. Cheung, Hesham M. Hassabo, Ahmed S Shalaby, Hoda H. Essa, Eman Mossad, Kanwal Pratap Singh Raghav, Asif Rashid, Robert A. Wolff, Jeffrey Morris, Hesham M. Amin, Ahmed Omar Kaseb
Journal: Journal of Clinical Oncology (2015)

e15140 Background: The Child-Turcotte-Pugh score (CTP) is the standard tool for assessment of hepatic reserve in hepatocellular carcinoma (HCC), although it has several limitations. Recently, we reported that integrating plasma insulin-like growth factor-1 (IGF-1) level into the CTP score, creating the IGF-CTP (Kaseb-Morris) score, was associated with better patient risk stratification as compared to CTP score in two independent cohorts (training and validation) from the U.S. Our current study aimed to internationally validate the IGF-CTP score in patients who have different demographics, geographical location, and HCC risk factors. Methods: We prospectively recruited 100 Egyptian patients and their blood samples for IGF-1 analysis. We calculated their IGF-CTP scores and compared them to CTP score. The log-rank test was used to detect statistical significance. Harrell's C-index was used to compare the prognostic significance of the two scoring systems. Finally, we compared our results with the previous published data from the U.S. cohorts. Results: IGF-CTP score showed statistically significant better patient stratification as compared to CTP score in the international validation cohort, similar to our previous cohorts (P = 0.003). Among CTP class A patients, the group that is usually considered for active treatment and clinical trial enrollment, 32.5% were reclassified as IGF-CTP class B; they had a statistically significantly shorter OS than did patients classified as class A using both scoring systems with hazard ratio [HR] = 6.15, 95% confidence interval [CI] = 2.18 to 17.37, and P = .001. Conclusions: The IGF-CTP scoring system showed significantly better patient stratification and survival prediction not only in the U.S. population originally tested but also in this first international validation population, who had different demographics, geographical location, and HCC risk factors.
Well patient, worrying thoracic magnetic resonance aortogram
Authors: Jack Andrews, Marc Dweck
Journal: BMJ (2017)

An asymptomatic 82 year old man attending an outpatient clinic underwent thoracic magnetic resonance (MR) aortography, which showed a striking abnormality (fig 1⇓). What is the potentially life threatening diagnosis on this image, and how should it be managed?



Fig 1  Sagittal oblique view of thoracic magnetic resonance aortogram



The aortogram shows previously repaired, chronic aortic dissection. Strict blood pressure control and imaging surveillance are indicated, but not emergency surgery to repair the dissection.

At first glance, the findings of a large dissection in the dilated descending aorta with thrombus in the false lumen would suggest that this patient requires emergency surgery. However, on closer inspection there are several findings that would argue against this management pathway. Firstly, the patient was asymptomatic, which would be highly unusual in acute aortic dissection. Secondly, he had undergone MR imaging, which is …
OlympiA: A randomized phase III trial of olaparib as adjuvant therapy in patients with high-risk HER2-negative breast cancer (BC) and a germline <i>BRCA</i>1/2 mutation (g<i>BRCA</i>m).
Authors: Andrew Nicholas James Tutt, Bella Kaufman, Richard D. Gelber, Eleanor Mc Fadden, Carsten Dietrich Goessl, Giuseppe Viale, Amal Arahmani, Debora Fumagalli, Hatem Abdel Azim, Wenting Wu, Anna Grocholewicz, Joseph P. Costantino, Priya Rastogi, Judy Ellen Garber, Charles E. Geyer
Journal: Journal of Clinical Oncology (2015)

TPS1109 Background: In a Phase II proof-of-concept study (NCT00494234), treatment with the PARP inhibitor olaparib (Lynparza; 400 mg twice daily [bid]; capsules) resulted in antitumor activity in patients (pts) with advanced BC harboring a gBRCAm (objective response rate: 41%; Tutt et al Lancet 2010). An AstraZeneca-sponsored Phase III trial (OlympiA; NCT02032823; coordinated by BIG, NRG Oncology, Frontier Science and AstraZeneca) of olaparib as adjuvant monotherapy has been initiated in pts with gBRCAm-associated triple negative BC (TNBC) who have completed local treatment and neoadjuvant or adjuvant chemotherapy (CT). Methods: OlympiA is a double-blind trial in which pts with TNBC at high risk of recurrence are currently randomized (1:1) to receive treatment with olaparib (300 mg tablets bid [2 x 150 mg]) or placebo for a maximum of 12 months. Eligible pts must have completed definitive local treatment and at least 6 cycles of either neoadjuvant CT (without a pathological complete response) or adjuvant CT. Pts must also have a known or suspected deleterious gBRCAm, which will be retrospectively confirmed by Integrated BRACAnalysis (Myriad Genetic Laboratories) before entering the trial. Stratification factors include prior neoadjuvant versus adjuvant CT, and whether pts have received prior platinum therapy for current BC. The primary objective is invasive disease-free survival (IDFS). Efficacy assessments will be made by mammograms/breast MRI scans annually for 10 years, beginning 6 months from randomization, and by medical history/physical examination from randomization every 3 months for 2 years, then every 6 months for a further 3 years and annually thereafter. Secondary objectives include overall survival, distant DFS, incidence of new cancers, HRQoL, safety and tolerability. The primary IDFS analysis will be performed after 330 IDFS events (25% maturity) using a stratified log-rank test. Patient enrollment began in April 2014. The target number for randomization is ~1320 patients across ~550 sites and ~25 countries worldwide. Support: U10CA12027,-69651,-37377,-69974,-180868,-180822,-189867; AstraZeneca Clinical trial information: NCT02032823.
Erratum to: Circulating presepsin (soluble CD14 subtype) as a marker of host response in patients with severe sepsis or septic shock: data from the multicenter, randomized ALBIOS trial
Authors: Serge Masson, Pietro Caironi, Caterina Fanizza, Ralf Thomae, Roberto Bernasconi, Andrea Noto, Roberto Oggioni, Giovanni Stefano Pasetti, Marilena Romero, Gianni Tognoni, Roberto Latini, Luciano Gattinoni
Journal: Intensive Care Medicine (2015)
111: A single-arm trial evaluating one cycle of BEP as adjuvant chemotherapy in high-risk, stage 1 non-seminomatous or combined germ cell tumors of the testis (NSGCTT).
Authors: Robert Anthony Huddart, Johnathan K. Joffe, Jeff D. White, Paul Hutton, Rebecca Lewis, Danish Mazhar, Colin Osborne, Deborah Piercy, Laura Wiley, Stephanie Witts, Lauren Maynard, Emma Hall, Michael H. Cullen
Journal: Journal of Clinical Oncology (2017)

400 Background: The standard post-orchiectomy treatment for UK patients (pts.) presenting with high-risk stage 1 NSGCTT is 2 cycles of bleomycin, etoposide (360mg/m 2 ) &amp; cisplatin (BE 360 P) chemotherapy or surveillance with BEPx3 at recurrence. 111 (CRUK/09/011) investigates whether BE 500 P x1 would achieve recurrence rates similar to BE 360 P x2. Methods: Pts aged ≥16 yrs post-orchiectomy for vascular invasion positive stage 1 NSGCTT or combined seminoma + NSGCT, with normalised tumour markers, received 1 cycle of bleomycin30000IU day 1, 8 &amp; 15, etoposide165mg/m 2 day 1, 2 &amp; 3, &amp;cisplatin50mg/m 2 day 1 &amp; 2. All pts received a prophylactic antibacterial &amp; GCSF. Pts were assessed for tumour markers q2m, q3m, q4m in years (yrs) 1, 2, 3, respectively and q6m in yrs 4 &amp; 5. CT scan of chest, abdo and pelvis was performed at 6, 12, 24 &amp; 60months (m) with chest x-ray at other visits. Toxicity was assessed using NCI CTCAE v3. Recurrences were independently reviewed. A sample size of 236 pts excludes a 2-yr recurrence rate of ≥5% if ≤6 recurrences were observed (80% power, 5% α). Results: Between 18/2/2010 and 31/7/2014 246 pts. were recruited at 33 UK centres; 54% with NSGCTT, 46% with combined GCT. Median follow-up was 39.1m (IQR 30.0-50.8). Four patients had malignant recurrences at 5, 8, 12 and 27m. 2 yr recurrence rate in 236 treated pts = 1.3% (95% CI: 0.4 to 4.0%). All 4 pts with recurrences were treated with 2 nd line chemotherapy +/- surgery, 3 are alive and free from disease, 1 died at 9m with refractory disease. In addition there were 3 non-malignant recurrences at 7, 10 and 13m with teratoma differentiated in retroperitoneal nodes (3, 4 and 4.4cm). All these pts are disease-free post RPLND surgery. 41% pts had grade 3-4 CTCAE at end of treatment (neutropenia: 31% and febrile neutropenia: 7%). The 2 yr overall survival is 99.2% (95% CI: 96.7, 99.8%). Conclusions: BE 500 P is safely deliverable &amp; 2 yr recurrence rate is similar to that seen with 2 cycles BE 360 P. The adoption of BE 500 P x1 as standard would reduce overall exposure to chemotherapy in this young pt population. 111 is the biggest formal, prospective trial to date investigating adjuvant BEPx1 in high-risk stage 1 NSGCTT. Clinical trial information: ISRCTN37875250.
U.S. Nutrition Assistance, 2018 — Modifying SNAP to Promote Population Health
Authors: Sara N. Bleich, Eric B. Rimm, Kelly D. Brownell
Journal: New England Journal of Medicine (2017)

The Supplemental Nutrition Assistance Program helps 45 million low-income Americans pay for food each month. Expanding the program's health emphasis would allow it to better address diet-related diseases and reduce government spending on health care.
Impact of center case volume on cardiotoxicity during adjuvant trastuzumab in breast cancer.
Authors: Nicolas J. Chin-Yee, Andrew Yan, George A. Tomlinson, Craig Earle, Maureen E. Trudeau, Murray Krahn, Dennis Ko, Monika Krzyzanowska, Raveen Pal, Christine B. Brezden, Kelvin K. Chan
Journal: Journal of Clinical Oncology (2013)

6625 Background: A recent study suggested that cardiotoxicity from trastuzumab (T) was associated with regional variation and insufficient cardiac monitoring (Ng et al.SABCS 2012). Few studies have examined the impact of centre or physician (MD) case volume (vol) on outcomes in systemic therapy. Methods: All breast cancer patients who were diagnosed in 2003-2009 in Ontario and treated with adjuvant T were identified through a provincial drug funding program, and linked to administrative databases to ascertain patient demographics, hospitalizations, cardiac risk factors, cardiac imaging, comorbidities, and treating centre and MD. For each year, we calculated case vol as the number of patients treated with adjuvant T by each MD and by each centre. Cardiotoxicity was defined as receiving less than 16 out of 18 doses of T because of heart failure (HF) admission, HF diagnosis by physician claims, or discontinuation after cardiac imaging. Insufficient cardiac monitoring was defined as per recent guideline and per Ng et al. Logistic regression and mixed models were constructed to examine factors associated with cardiotoxicity. Results: Our cohort consisted of 3,777 patients, 214 MDs and 68 centres. For patients, 16.5% were over age 65; 30.3%, 9.4%, and 1.2% had previous diagnoses of hypertension, diabetes, and HF, respectively; 16.9% had cardiotoxicity. Univariate analyses found that high centre vol, but not MD vol, was associated with lower cardiotoxicity. Cardiotoxicity rates by centre vol quintiles (Q) were 23.4% (Q1-3), 18.2% (Q4), and 15.2% (Q5). Multivariable analyses found that lower cardiotoxicity was associated with higher centre vol (OR=0.85 per Q, p=0.02) and diagnosis in recent years (2008-2009 vs. before 2008; OR=0.50, p&lt;0.001), after adjusting for age, previous HF, comorbidities, regional variation, and cardiac monitoring. Accounting for clustering within centres, there remained a strong trend of lower cardiotoxicity with higher centre vol (OR=0.77 per Q, p=0.06) and recent diagnosis (OR=0.50, p&lt;0.001). Conclusions: Our findings suggest a reduction in cardiotoxicity with experience and over time, and support the notion of centralization of systemic therapy in high vol centres to optimize outcomes.
Predictors of obstructive sleep apnoea in patients admitted for acute coronary syndrome
Authors: Jordi de Batlle, Cecilia Turino, Alicia Sánchez-de-la-Torre, Jorge Abad, Joaquín Duran-Cantolla, R. Douglas McEvoy, Nick A. Antic, Olga Mediano, Valentín Cabriada, Maria José Masdeu, Joaquín Teran, Joan Valls, Ferran Barbé, Manuel Sánchez-de-la-Torre
Journal: European Respiratory Journal (2017)

Identifying undiagnosed obstructive sleep apnoea (OSA) patients in cardiovascular clinics could improve their management. Aiming to build an OSA predictive model, a broad analysis of clinical variables was performed in a cohort of acute coronary syndrome (ACS) patients. Sociodemographic, anthropometric, life-style and pharmacological variables were recorded. Clinical measures included blood pressure, electrocardiography, echocardiography, blood count, troponin levels and a metabolic panel. OSA was diagnosed using respiratory polygraphy. Logistic regression models and classification and regression trees were used to create predictive models. A total of 978 patients were included (298 subjects with apnoea–hypopnoea index (AHI) &lt;15 events·h −1 and 680 with AHI ≥15 events·h −1 ). Age, BMI, Epworth sleepiness scale, peak troponin levels and use of calcium antagonists were the main determinants of AHI ≥15 events·h −1 (C statistic 0.71; sensitivity 94%; specificity 24%). Age, BMI, blood triglycerides, peak troponin levels and Killip class ≥II were determinants of AHI ≥30 events·h −1 (C statistic of 0.67; sensitivity 31%; specificity 86%). Although a set of variables associated with OSA was identified, no model could successfully predict OSA in patients admitted for ACS. Given the high prevalence of OSA, the authors propose respiratory polygraphy as a to-be-explored strategy to identify OSA in ACS patients.