tbuckley/cabot-search huggingface dataset:
Abstract P4-03-10: Clinical observation of lapatinib versus continued use of trastuzumab for trastuzumab-resistant HER2-positive advanced breast cancer
Authors: Y Yin, W Li, X Huang, J Wang, Z Fu, J Li
Journal: Cancer Research (2018)

Abstract Objective: To compare the efficacy, adverse effects and survival of lapatinib versus continued use of trastuzumab for trastuzumab-resistant human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer. Methods: Patients who began the regimen of lapatinib plus capecitabine (LC or LX) or trastuzumab beyond progression (TBP) between May 2013 and October 2016 were selected from the First Affiliated Hospital of Nanjing Medical University. All of their clinical data were recorded, including age, performance status, hormone receptor status, metastatic site, primary or acquired trastuzumab resistance, previous treatment and so on. They were followed up until death or April 30, 2017. The primary end point was progression-free survival (PFS). The efficacy and safety of the two regimens were evaluated according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 and Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, respectively. Data were analyzed by SPSS version 19.0. Results: In total, 95 patients were identified, including 40 treated with LX and 55 with TBP. Median follow-up time was 16.0 months. There was no difference in objective response rate (ORR) and disease control rate (DCR) between the two groups. By the end of follow-up, median PFS was 6.3 months with LX and 7.1 months with TBP (P=0.676). In patients with primary trastuzumab resisitance, longer PFS was observed in LX group compared with TBP group [median PFS: 8.0 months vs. 5.3 months, hazard ratio (HR)=0.416, 95% confidence interval (CI): 0.177-0.981, P=0.038]. The incident rate of new brain metastases during treatment was 2.5% in LX group and 10.9% in TBP group, respectively (P=0.233). Both regimens showed similar outcomes in baseline brain metastases. Grade 3-4 adverse effects included diarrhea 7.5%(3/40) and hand-foot syndrome 12.5%(5/40) in LX group, along with leukopenia 18.2%(10/55), thrombocytopenia 9.1%(5/55) and nausea/vomiting 3.6%(2/55) in TBP group. Conclusion: LX and TBP were similarly effective for patients with HER2-positive breast cancer progressing on prior trastuzumab-containing therapy. Both were well tolerated in general. Lapatinib tended to reduce the risk of disease progression in patients resistant to trastuzumab primarily. LX or TBP after local treatment appeared to show no difference in treating patients with brain metastases. Citation Format: Yin Y, Li W, Huang X, Wang J, Fu Z, Li J. Clinical observation of lapatinib versus continued use of trastuzumab for trastuzumab-resistant HER2-positive advanced breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-03-10.
AR-V7 in Asian patients with metastatic CRPC: A multinational, multicentre study.
Authors: Hui Shan Tan, Alvin Seng Cheong Wong, Kian Tai Chong, Siew Wei Wong, Marniza Bte Saad, Chi-Fai Ng, Shigeo Horie, Phichai Chansriwong, Min-Han Tan, Chee-Keong Toh, Quan Sing Ng, Kiat Hon Lim, Liang Seah Tay, Whee Sze Ong, Ravindran Kanesvaran
Journal: Journal of Clinical Oncology (2018)

TPS401 Background: The detection of androgen-receptor splice variant 7 (AR-V7) mRNA transcript in circulating tumor cells (CTCs) of progressive metastatic castration-resistant prostate cancer (mCRPC) patients is associated with resistance to abiraterone and enzalutamide. This finding was validated by other studies that found no association between the presence of AR-V7 transcripts and response to both docetaxel and cabazitaxel. The results suggest that AR-V7 could represent a biomarker to guide treatment selection in mCRPC. However, data in Asian population is limited. This multinational study aims to prospectively investigate the incidence and prevalence of ARV7 in Asian mCRPC patients. This is also the first study to evaluate 3 different detection platforms and help provide guidance on which will be the best platform to carry forward in terms of clinical utility. Methods: 101 Asian subjects with histologically confirmed mCRPC whom are going to be treated with AR-directed therapies (abiraterone, enzalutamide) or taxane chemotherapy (docetaxel) will be enrolled from Singapore, Malaysia, Thailand, Hong Kong and Japan. Subjects will be excluded if they plan to receive additional concurrent anticancer therapies. Peripheral-blood samples will be obtained at baseline and at the time of progression. We will use 3 methods to analyse the samples: (i) CTC enrichment platform followed by automated immunofluorescent staining for DNA, cytokeratins, CD45 (lymphocyte common antigen), and AR-V7; (ii) CTC enrichment platform followed by reverse-transcription polymerase chain reaction analysis; and (iii) the AdnaTest platform for molecular characterization of CTCs. Subjects will be followed up to 2 years. The clinical outcomes of AR-V7-positive and AR-V7-negative patients will be compared. PSA response rates will be compared using the Fisher exact test. Time-to-event outcomes (PFS, OS) will be evaluated using Kaplan-Meier analysis, and survival time differences will be compared using log-rank test. Cox regression analyses will be used to assess the effect of AR-V7 status in predicting clinical outcomes. The study is in progress; 32 of 101 planned patients have been enrolled at the end of September 2017.
Minimizing prostate cancer admissions via enhanced outpatient care: A model for savings.
Authors: Anish Parikh, Mark Sanderson, Luis M. Isola, Ronald D. Ennis
Journal: Journal of Clinical Oncology (2018)

46 Background: Hospitalization is a major contributor to cost in oncology. Minimizing avoidable admissions can lead to substantial savings. Methods: We studied Medicare claims data from 160 admissions for prostate cancer (PCa) patients from 1/2012 to 5/2015. Admissions with the lowest 50 th percentile of charges were assessed for being potentially avoidable by 2 independent chart reviews; remaining admissions were assumed to be unavoidable due to medical complexity. Common admitting diagnoses were targeted by theoretical care pathways designed to minimize avoidable admissions via expedited outpatient follow-up. We compared the cost of the avoidable admissions to that of implementing 3 such pathways then estimated the financial impact. Results: Total cost for all 160 admissions was $1,979,200. 25% of these admissions, accounting for $494,800, were deemed potentially avoidable. Our model exchanged each of these admissions for a routine clinic visit which led to an estimated $464,800 in savings, or a 23% improvement in total cost. The most common admitting diagnoses were fever (18%), pain (12%), and dehydration (8%). On review, 3/9 fever admissions in this set were deemed avoidable with 1 extra clinic visit, 3 with 3 visits, and 3 were unavoidable, yielding a 53% reduction in cost for this diagnosis. Similar analyses led to cost reductions of 75% and 66% for pain and dehydration admissions, respectively. Combining just these 3 theoretical interventions led to an estimated savings of $146,955, or a 7.4% improvement in total cost. Conclusions: A sizable portion of PCa admissions can be avoided, with ample savings, if a system is in place to provide the additional care that often exceeds the capabilities of a busy practice. [Table: see text]
Screening for cancer-associated dysphagia: The development of two rapid tools for use in observational studies and routine care.
Authors: Michael Borean, Kishan Shani, M. Catherine Brown, Judy Chen, Mindy Liang, Joel Karkada, Simranjit Kooner, Mark K. Doherty, Grainne M. O'Kane, Raymond Woo-Jun Jang, Elena Elimova, Rebecca Wong, Gail Elizabeth Darling, Wei Xu, Doris Howell, Geoffrey Liu
Journal: Journal of Clinical Oncology (2018)

164 Background: Dysphagia as a cancer symptom can be associated with significant morbidity. We developed dysphagia screener tools for use in observational studies (Phase 1) and routine symptom monitoring in clinical care (Phase 2). Methods: Various dysphagia or odynophagia screening questions, selected after an expert panel reviewed content, criterion, and construct validity, were compared to either FACT-E Swallowing Index Cut-Off Values (SICV) or to questions adapted from the Patient Reported Outcomes for Common Terminology Criteria for Adverse Events (PRO-CTCAE). Sensitivity, specificity and patient acceptability were assessed. Results: In developing a tool for observational studies (Phase 1; n = 178 esophageal cancer patients), the screening question, “How are you currently eating?” had the highest sensitivities and specificities against various SICV cut-offs, with the best optimal cut-off associated with the clinical outcome of weight loss (80% sensitivity, 75% specificity). When developing a rapid screening tool for routine symptom monitoring (Phase 2; 255 head and neck, gastro-esophageal, and patients undergoing thoracic radiation), a single question screener (“Do you experience any difficulty or pain upon swallowing?”) versus a PRO-CTCAE-like gold standard generated sensitivities between 86-94% and specificities between 93-100%. The screening question (+/- follow-up questions where indicated) had a median completion time of under 2 minutes, and &gt; 90% of patients were happy to complete the survey on an electronic tablet, did not feel that survey completion made their clinic visit more difficult, and did not find the questions upsetting or distressful. Conclusions: Two screener tools (for prospective observational studies “How are you currently eating?”, and for routine clinical monitoring “Do you experience any difficulty or pain upon swallowing?”) can effectively screen dysphagia symptoms without increasing cancer outpatient clinic burden.
Outcome of children with multiply relapsed B-cell acute lymphoblastic leukemia: a therapeutic advances in childhood leukemia &amp; lymphoma study
Authors: Weili Sun, Jemily Malvar, Richard Sposto, Anupam Verma, Jennifer J. Wilkes, Robyn Dennis, Kenneth Heym, Theodore W. Laetsch, Melissa Widener, Susan R Rheingold, Javier Oesterheld, Nobuko Hijiya, Maria Luisa Sulis, Van Huynh, Andrew E. Place, Henrique Bittencourt, Raymond Hutchinson, Yoav Messinger, Bill Chang, Yousif Matloub, David S. Ziegler, Rebecca Gardner, Todd Cooper, Francesco Ceppi, Michelle Hermiston, Luciano Dalla-Pozza, Kirk R. Schultz, Paul Gaynon, Alan S. Wayne, James A. Whitlock
Journal: Leukemia (2018)

The survival of pediatric patients with multiply relapsed and/or refractory (R/R) B-cell acute lymphoblastic leukemia has historically been very poor; however, data are limited in the current era. We conducted a retrospective study to determine the outcome of multiply R/R childhood B-ALL treated at 24 TACL institutions between 2005 and 2013. Patient information, treatment, and response were collected. Prognostic factors influencing the complete remission (CR) rate and event-free survival (EFS) were analyzed. The analytic set included 578 salvage treatment attempts among 325 patients. CR rates (mean ± SE) were 51 ± 4% for patients with bone marrow R/R B-ALL who underwent a second salvage attempt, 37 ± 6% for a third attempt, and 31 ± 6% for the fourth through eighth attempts combined. For patients achieving a CR after their second, third, and fourth through eighth attempts, the 2 year EFS was 41 ± 6%, 13 ± 7%, and 27 ± 13% respectively. Our results showed slight improvement when compared to previous studies. This is the largest and most recent study to date that evaluates the outcome of this patient population. Our data will provide detailed reference for the evaluation of new agents being developed for childhood B-ALL.
Surgeon is suspended for nine months for working without insurance for 12 days
Authors: Clare Dyer
Journal: BMJ (2018)

A medical practitioners’ tribunal has suspended Anwar Abdel-Salam, a consultant orthopaedic surgeon, for nine months for knowingly seeing patients over a 12 day period while lacking professional indemnity insurance.

Abdel-Salam saw 31 private patients at the BMI Meriden Hospital in Coventry while lacking coverage between 8 and 20 July 2016, including three patients who underwent surgery.

He was aware that his insurance had lapsed, the tribunal found, and had told colleagues that he hoped to be covered soon. When coverage first lapsed, on 5 June 2016, his provider quoted him a premium for renewal in excess of £40 000. This was because a negligence claim made against …
RAINFALL: A randomized, double-blind, placebo-controlled phase III study of cisplatin (Cis) plus capecitabine (Cape) or 5FU with or without ramucirumab (RAM) as first-line therapy in patients with metastatic gastric or gastroesophageal junction (G-GEJ) adenocarcinoma.
Authors: Charles S. Fuchs, Kohei Shitara, Maria Di Bartolomeo, Sara Lonardi, Salah-Eddin Al-Batran, Eric Van Cutsem, David H. Ilson, Josep Tabernero, Ian Chau, Michel Ducreux, Guillermo Ariel Mendez, Alejandro Molina Alavez, Daisuke Takahari, Wasat Mansoor, Jill Lacy, Vera Gorbunova, David Ferry, Ji Lin, Mayukh Das, Manish A. Shah
Journal: Journal of Clinical Oncology (2018)

5 Background: Ramucirumab, a VEGFR-2 IgG1 human monoclonal antibody, is the only biologic with proven efficacy as both a single-agent and in combination with paclitaxel in the second-line treatment of G-GEJ adenocarcinoma. RAINFALL (NCT02314117) is a global, double-blind, placebo-controlled randomized clinical trial addressing the hypothesis that adding ramucirumab to first-line Cis plus Cape or 5-fluorouracil (5FU) produces significant clinical benefit. Methods: Metastatic G-GEJ cancer patients eligible for first-line chemotherapy with ECOG performance status 0-1 were randomized 1:1 to receive either RAM (8 mg/kg iv D1, D8) or placebo (PL), every 21d. All patients received Cape (or 5FU)+Cis. Cis was given for up to 6 cycles. Cape+RAM/placebo was continued until progressive disease, toxicity or other discontinuation criteria. The primary endpoint was progression-free survival (PFS) for the first 508 patients; overall survival (OS) for ITT population was a powered secondary endpoint. Results: 645 patients were randomized to receive RAM+Cape/Cis (n=326) or PL+Cape/Cis (n=319). PFS was significantly prolonged in patients treated with RAM+Cape/Cis versus PL+Cape/Cis (HR, 0.75; 95% CI 0.61–0.94; p=0.011; median, 5.7 vs 5.4 mos), meeting the primary endpoint. There was no survival benefit for patients treated with RAM+Cape/Cis versus PL+Cape/Cis (HR, 0.96; 95% CI 0.80–1.16; p=0.68; median, 11.2 vs 10.7 mos). ORR in the ITT population was 41.1% in the RAM arm (95% CI 35.8–46.4) and 36.4% (95% CI 31.1–41.6) in the PL arm. Grade ≥3 adverse events in ≥10% of patients in the RAM arm were: neutropenia (26.3% RAM; 27.0% PL), anemia (12.1% RAM; 14.0% PL), and hypertension (9.9% RAM; 1.6% PL). No new safety signals were observed. Conclusions: In treatment-naïve patients with metastatic G-GEJ adenocarcinoma, the addition of ramucirumab to first-line chemotherapy conferred a significant 25% reduction in the risk of disease progression or death in the primary endpoint of PFS; however, ramucirumab was not associated with an improved OS. Clinical trial information: NCT02314117.
Efficacy of <i>nab</i>-paclitaxel plus gemcitabine (AG) vs. FOLFIRINOX as first line chemotherapy for metastatic pancreatic cancer (mPC): Real world experiences.
Authors: Inhwang Hwang, Jihoon Kang, Changhoon Yoo, Kyu-Pyo Kim, Jae Ho Jeong, Heung-Moon Chang, Baek-Yeol Ryoo
Journal: Journal of Clinical Oncology (2018)

354 Background: AG and FOLFIRINOX have been established as standard first-line treatment in mPC patients based on the improved efficacy compared to gemcitabine monotherapy. Because there was no head-to-head comparison between these regimens, however, there is lack of data which regimen is preferable in patients with mPC. Therefore, we performed retrospective analysis comparing the efficacy of AG and FOLFIRINOX in daily practice setting. Methods: We analyzed a total of 308 patients with confirmed mPC who received AG (n = 149) or FOLFIRINOX (n = 159) as first-line treatment between 2013 and 2016 at Asan Medical Center, Seoul, Korea. Primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival (PFS) and overall response rates (ORR). Results: Median age was slightly older in AG group than FOLFIRINOX group (62 vs. 60 years, p = 0.02). Except this, there was no significant difference between the two groups in terms of baseline characteristics including sex (male, AG/FOLFIRNOX): 56%/67%, ECOG performance status (0-1): 97%/99%, pancreatic head location: 32%/40%, and baseline CA19-9 level ( &gt; UNL): 77%/82%. ORR (28% vs. 31%) and disease control rate (74% vs. 74%) did not differ between two groups (p = 0.45, and p = 0.96, respectively). Although there was no significant difference in PFS between the two groups (AG: median 6.8 months [95% CI: 5.8-7.8] vs. FOLFIRINOX: 5.1 months [95% CI: 4.2-5.9]; p = 0.15), OS was significantly better in AG group compared to FOLFIRINOX group (median 12.3 months [95% CI: 11.0-13.7] vs. 9.7 months [95% CI, 8.1-11.4]; p = 0.001). Among the patients who showed progression, 81% (180/223) received second-line chemotherapy and there was no difference between the two groups (AG vs. FOLFIRINOX: 76% vs. 85%, p = 0.09). 5-FU monotherapy or combination with oxaliplatin were given in 97% (73/75) of patients in AG group and gemcitabine-based regimens (including 2 cases of AG) were given in 97% (102/105) of patients in FOLFIRINOX group. Conclusions: Both AG and FOLFIRINOX are feasible and active as first-line treatment for patients with mPC. In daily practice setting, AG showed comparable efficacy outcomes with FOLFIRINOX.
Are We There Yet? Finding Ways to Work Together on T1D
Authors: Chantal Mathieu
Journal: Diabetes Care (2018)

All parents know the question “Are we there yet?” when on a long drive with kids in the back of the car: an expression of impatience and not understanding why it takes “forever.” Reality is often different than the perception of those in the back seat: we are driving as fast as speed limits allow, and we only left home a couple of hours ago.

The same feeling is present when clinicians speak with people with type 1 diabetes (T1D) and their families. Why does it take so long? Why haven’t you cured this disease? It becomes worse when other health care professionals come into the picture, in particular health care professionals who know of “success stories” close to biblical proportions, as in rheumatoid arthritis or inflammatory bowel disease. We find many answers in the article by Bingley et al. (1) in this issue of Diabetes Care . Dr. Bingley, one of the clinicians leading the long-term battle against T1D, has described together with her TrialNet colleagues what this initiative has achieved in the past decades. Importantly, they also give us glimpses of where they feel the field should go.

The long list of interventions tested in TrialNet confirms that we have not failed in preventing or arresting T1D for lack of trying but indicates that T1D has several specific hurdles that prevent us from reaching success (2). Hurdles include the lack of accessibility of the target organ (the insulin-producing β-cell buried in the islets of Langerhans in the pancreas), making direct histological observations or staging of the immune attack or level of β-cell destruction impossible in individual patients. What we did learn is that T1D is probably not the result of a single path to β-cell destruction (3). Heterogeneity exists, in the speed of onset, in the progression of …
P024 Comparison of CCP2 and CCP3 assays in a large cohort of established rheumatoid arthritis and controls
Authors: M Malher, C Bentow, R Albesa, L Cesana, L Martinez-Prat, P Roux-Lombard, MJ Nissen, C Lamacchia, C Gabay
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> Rheumatoid Factor (RF) and anti-citrullinated protein antibodies (ACPA) are important serological marker in the diagnosis of rheumatoid arthritis (RA) and are part of the classification criteria. ACPA are generally detected using anti-cyclic citrullinated peptide (CCP) antibody assays. The first generation of the CCP test uses a peptide derived from the filaggrin protein as the antigen, whereas, the second and third generation CCP (CCP2, CCP3) are based on peptides specifically designed and optimised (mimotypes) to detect ACPA, thereby enhancing the immunoreactivity of the citrulline-containing epitope. <h3>Objectives</h3> The goal was to compare the performance of CCP2 and CCP3 assays. <h3>Methods</h3> 1655 samples including 968 RA patients and 687 controls (450 ankylosing spondylitis (AS) and 237 psoriatic arthritis (PsA) patients), all derived from the Swiss Clinical Quality Management in Rheumatic Diseases Foundation (SCQM) were included. ACPA were determined by CCP2 ELISA (Eurodiagnostica, Sweden), CCP3 ELISA (QUANTA Lite CCP3 IgG) and CCP3 CIA (QUANTA Flash CCP3 IgG) (both Inova Diagnostics, US). RF IgM was measured by ELISA (QUANTA Lite RF IgM, Inova Diagnostics, US). <h3>Results</h3> The CCP2 ELISA showed a high sensitivity (71.1%) and a moderately high specificity (86.9%) with a corresponding Odds ratio (OR) of 16.3 (95% CI: 12.5 to 21.1). The two CCP3 assays showed lower sensitivities (61.8% for the ELISA and 61.4% for the CIA), but significantly higher specificities (98.4% and 98.5% respectively), resulting in much higher predictive values, with OR of 99.3 (95% CI: 54.4 to 181.2) and 107.5 (95% CI: 57.4 to 201.5), respectively. When compared at the same specificity (95%), the sensitivities were 61.3% for the CCP2 ELISA, 68.1% for the CCP3 ELISA and 66.1% for the CCP3 CIA. When multi-parametric analyses were performed by combining ACPA with RF IgM, combining different markers resulted in higher OR than the individual markers. The combination of CCP3 and RF IgM resulted in a higher OR (OR=187.0, 510/1655) than the combination of CCP2 with RF IgM (OR=36.7, 565/1655). The addition of CCP2 to the combination of CCP3 and RF IgM resulted in a lower OR (OR=175.0, 494/1655). <h3>Conclusions</h3> CCP3 showed a better overall performance than CCP2 in this cohort of RA and controls, when analysed individually as well as in combination with RF IgM. <h3>Disclosure of interest</h3> None declared
Can you advise me on preparing for exams while working as a senior house officer?
Authors: Rahul Rao
Journal: BMJ (2004)

<i>Got a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone (www.bmjcareers.com/advicezone) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.</i>
Immunogenicity of type 2 monovalent oral and inactivated poliovirus vaccines for type 2 poliovirus outbreak response: an open-label, randomised controlled trial
Authors: Khalequ Zaman, Concepción F Estívariz, Michelle Morales, Mohammad Yunus, Cynthia J Snider, Howard E Gary, William C Weldon, M Steven Oberste, Steven G Wassilak, Mark A Pallansch, Abhijeet Anand
Journal: The Lancet Infectious Diseases (2018)
UNDETERMINED CAUSE OF DEATH: A POOLED ANALYSIS OF 9,307 DEATHS ACROSS 9 CARDIOVASCULAR TRIALS
Authors: Alexander C. Fanaroff, Robert Clare, Karen Pieper, Kenneth Mahaffey, Chiara Melloni, Jennifer Green, John Alexander, William Jones, Robert Harrison, Rajendra Mehta, Thomas Povsic, Humberto Moreira, Sana Al-Khatib, Matthew Roe, David Kong, Robin Mathews, Pierluigi Tricoci, Rury Holman, Lars Wallentin, Claes Held, Karen Alexander, Renato Lopes
Journal: Journal of the American College of Cardiology (2018)