tbuckley/cabot-search huggingface dataset:
Indian doctors take to streets to demand better security
Authors: Prashun Mazumdar
Journal: BMJ (2017)

Kunal Patel/Hindustani Times/Getty Images

Nearly 40 000 doctors in Delhi and Mumbai have gone on strike to demand better security in government hospitals, after a spate of attacks on medical professionals. Pictured are staff from Sion Hospital, in Mumbai. If the government continues to ignore their safety concerns, doctors have threatened to call a nationwide strike.

Last week a 35 year old junior doctor, Rohan Mhamunkar, was brutally assaulted by relatives of …
Abstract 14926: Uninterrupted Novel Oral Anticoagulants vs Uninterrupted Warfarin Peri-Ablation of Atrial Fibrillation: A Meta-Analysis of Embolic and Bleeding Complications
Authors: Dan L Musat, Naga V Garikipati, Mark W Preminger, Tina Sichrovsky, Suneet Mittal, Jonathan S Steinberg
Journal: Circulation (2015)

Introduction: Novel oral anticoagulants (NOACs) like dabigatran (D), rivaroxaban (R) or apixaban (A), are being used much more commonly pre and post-atrial fibrillation (AF) ablation. Many prior reports have included patients with NOACs held for varying periods before, after or both relative to ablation. It is unclear if uninterrupted (U) NOACs increase procedural risk vs the preferred peri-ablation regimen, uninterrupted warfarin (UW). Because individual studies may be too small given low complication rates, we conducted a meta-analysis to provide more robust data to guide current practice Methods: All published papers (n=4) and abstracts (n=5) to date that compared complication rates for peri-AF ablation use of U-NOACs vs. UW were included. Bleeding complications included pericardial effusion and vascular bleeding, and embolic complications included stroke/TIA or systemic embolism. The Mantel-Haenszel fixed effect model for pooling the study results was used, with a random effects model for heterogeneous samples/results. Results: The 1404 pts on a U-NOACs (15% D, 59% R, 26% A) were similar to the 1528 pts on UW. There was no difference in composite total complication rates between the 2 groups (6.4% U-NOACs vs 7.7% UW), (OR 0.78, 95% CI 0.58 - 1.05; I2 = 0%). Composite embolic and bleeding rates were similar in both groups (0.14% in U-NOACs vs 0.20% in UW, OR 0.99, 95% CI 0.25 - 4.06; I2 = 0%; and 6.3% in U-NOACs vs 7.5% in UW, OR 0.78, 95% CI 0.58 - 1.06; I2 = 0%, respectively, Figure). Conclusions: This meta-analysis demonstrates that U-NOACs are a legitimate alternative for peri-AF ablation anticoagulation with no significant difference in bleeding or embolic events compared to UW.
Safety of pembrolizumab (pem) in patients (pts) who stopped ipilimumab (ipi) due to immune-related adverse events.
Authors: Alexander Noor Shoushtari, Michael Andrew Postow, Troy Z Horvat, Nelly G. Adel, Thu Dang, Paul B. Chapman
Journal: Journal of Clinical Oncology (2015)

e20023 Background: Pembrolizumab (pembro) which blocks programmed death-1 was recently FDA-approved for the treatment (tx) of patients (pts) with advanced melanoma (mel) following tx with ipilimumab (ipi). Ipi is associated with immune-mediated adverse events (irAEs) which can lead to early tx cessation. The safety of pembro following severe irAEs from ipi is unknown. Methods: We collected demographic and clinical data onpts with mel who received pembro at Memorial Sloan Kettering Cancer Center and had received < 4 doses of standard ipi monotherapy due to irAEs Grade (G) 2 or higher requiring steroids. Toxicities were graded using CTCAE v4.03. Results: 10 patients stopped ipi due to irAEs and subsequently received pembro. Median (range) age = 60 (53-65) years (yrs); 70% male, ECOG 0 (0-1). Primary sites: cutaneous (n = 7); mucosal, acral, unknown (n = 1 each). Median ipi doses given = 2 (range: 1-3). 12 irAEs contributed to ipi cessation: colitis (n = 7), median G3 (range 2-3); G2 neuropathy (n = 2); alanine aminotransferase (ALT) elevation, n = 2, G2-3; G3 rash, n = 1. All pts received systemic steroids; n = 5 required intravenous steroids, n = 3 required infliximab. Median interval from ipi end to pembro start was 2.4 months (mo) (range 1.3-27 mo). Median pembro doses given = 5 (range: 1-27), and 7/10 pts are actively receiving tx. 2/10 pts had tx interrupted for irAEs that required systemic steroids: n = 1 G3 ALT after dose #3; n = 1 G2 pneumonitis after dose #1. Neither irAE had been seen as a result of ipi. 8/10 pts have had either no irAEs related to pembro (n = 5) or G1 only (n = 3), most commonly myalgias (n = 2). Conclusions: Patients who stop ipi due to irAEs may have different irAEs emerge when receiving pembro. Nonetheless, our early experience is that experiencing a severe irAE from ipi does not preclude a pt from subsequently receving pembro.
Combination nab-paclitaxel (Nab-P) plus gemcitabine (G) as first-line treatment in advanced pancreatic cancer (APC): Our experience.
Authors: Fernando De Vita, Michele Orditura, Antonio Febbraro, Floriana Morgillo, Maria Maddalena Laterza, Alessio Fabozzi, Guido Giordano, Beatrice Savastano, Angelica Petrillo, Jole Ventriglia, Fortunato Ciardiello
Journal: Journal of Clinical Oncology (2014)

e15257 Background: APC represents an aggressive disease with an extremely poor prognosis. Recently, Nab-P, an innovative molecule, has shown superior activity and efficacy in APC first line treatment in combination with G in a randomised phase III trial comparing Nab-P+G vs G alone. Methods: From November 2011 to June 2013, a group of 34 Patients (pts) (M/F:12/22) with APC receiving combination of Nab-P 125 mg/m2 and G 1000 mg/m2 on days 1, 8 and 15 of a 28 days cycle, as a first line treatment, were included in our analysis for activity, efficacy and safety. Activity and efficacy were evaluated respectively in terms of Disease Control Rate (DCR) and Progression Free Survival (PFS) every 12 weeks. Grade 3-4 toxicities were considered for safety evaluation. Results: The median age was 67 (range 37 - 77) and ECOG Performance Status (PS) was 0 (11.7%), 1 (70.6%) and 2 (17.7%). Primitive tumor was located in the head (64.7%), corpe-tail (35.3%). 20.6% of pts had locally advanced unresectable disease and 79.4% had metastatic disease (58.8% liver metastases; 41.2% multiple metastatic sites). 8 pts (23.5%) received prior surgery and adjuvant treatment with G and the same percentage had biliary stent. Median CA19.9 level was 469 U/I (range 20.7 – 61546 U/I) and 26 pts (76.5%) referred pain at the time of diagnosis. Nab-P + G was administered for 6 median cycles (range 1 - 12) and treatment was well tolerated with no grade 4 toxicities. Grade 3 toxicities were respectively represented by neutropenia (14.7%), diarrhoea (11.7%), piastrinopenia (8.8%), nausea (5.8%) and hypertransaminasemia (2.9%) and 20% dose reduction was needed in 6 pts (17.6%). DCR (defined as Stable Disease SD + Partial Response PR + Complete Response CR)at 6 months was 63%with amedian PFS was 7 (range 2 – 14) months. Pain control was achieved in 19 of 26 pts (73%) with a PS improvement of 1 grade according to ECOG scale. Conclusions: Targeting the stroma seems to be an effective way to treat APC. Nab-P has a peculiar mechanism of action closely linked to its molecular structure and it seems to enhance G activity in combination regimens. Our experience confirms that the combination of G+Nab-P is effective both in terms of DCR and PFS, with a good safety profile.
Primary care physicians experiences of caring for cancer survivors: Toward developing a primary care-responsive cancer survivorship research agenda.
Authors: Denalee M. O'Malley, Stacy N. Davis, Benjamin F Crabtree, Shawna V. Hudson
Journal: Journal of Clinical Oncology (2017)

97 Background: Understanding of the ecology of primary care can inform efforts that aim to build primary care capacity to address cancer survivorship issues. This study describes the experiences of primary care physicians (PCPs) delivering care to cancer survivors. Methods: Semi-structured in-depth interviews were conducted with PCPs (n=30) across two NCI-funded studies of cancer survivorship in primary care. PCPs were recruited from primary care practices enrolled in a qualitative case study of cancer survivorship in patient centered medical homes (R01 CA176545; n=21) and from a sample recruited for the formative development of a primary care mHealth and health coaching interventions for cancer survivors (R01 CA176838; n=9). Interviews averaged 30 minutes, were audio-recorded and transcribed verbatim. A multi-step immersion/crystallization approach was used to identify emergent themes using Atlas.ti. Results: PCPs stated that their role in cancer survivorship care varies widely and is often shaped by patient characteristics. These characteristics include: patient expectations of the PCPs role; the patient’s ability to provide clinical details about their cancer and its treatment; and the status of patient relationship with cancer treatment team. PCPs described having incomplete information and recounted experiences of cancer survivors presenting for visits motivated by fear of disease recurrence. PCPs described the tensions around having to make decisions about further additional testing versus offering support about recurrence of fears with incomplete clinical information. PCPs also expressed a need for basic clinical information and surveillance plans to be integrated into existing systems of care (e.g. electronic medical record systems and registries), citing immunization schedules as a potential model. Conclusions: The lack of clinical information to inform cancer survivors’ care remains a critical challenge to PCPs. Survivorship care plans are a proposed strategy to rectify informational deficits; however, further evaluation of how effectively care plans integrate into primary care systems and processes are needed.
Phase 1 study of the PSMA-tubulysin small-molecule drug conjugate EC1169 in pts with metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Samuel Ejadi, Nicholas J. Vogelzang, A. Oliver Sartor, Andrew Habbe, Binh Nguyen, Anthony W. Tolcher
Journal: Journal of Clinical Oncology (2015)

e13527 Background: EC1169 is a conjugate of a prostate-specific membrane antigen (PSMA) targeting moiety linked to tubulysin B hydrazide (TubBH) that specifically binds to PSMA-expressing tumor cells to exert its anti-tumor effect through inhibition of tubulin polymerization. The PSMA "target" that binds EC1169 is overexpressed by most prostate cancer (PCa) cells. Xenograft studies have demonstrated EC1169's potent antitumor activity with complete remissions and cures observed in mice bearing PSMA-positive LNCaP and MDA PCa 2b tumors. 99mTc-EC0652 has a 99mTc chelator linked to a DUPA moiety, which binds to PSMA on the surface of target cells. Retention of 99mTc-EC0652 in PCa masses is more sustained than has been observed with any previously described PCa imaging agent. Methods: Key inclusion criteria are age ≥18 years, ECOG PS 0–1, and adequate organ function. Patients must have failed androgen-deprivation therapy, progressed on abiraterone or enzalutamide, and have been previously treated with a taxane unless contraindicated. All patients undergo a 99mTc-EC0652 scan prior to therapy. EC1169 is IV bolus administered on 1 of 2 schedules every 21 days: Days 1, 3, 5, 8, 10, 12 (TIW cohort) or Days 1, 8 (QW cohort). Dose escalation is based upon the continuous reassessment method. Study objectives include determination of EC1169's MTD and recommended phase 2 dose, safety, pharmacokinetics, antitumor activity and its correlation with PSMA expression as measured by 99mTc-EC0652. Results: To date, 3 pts have been treated on the TIW schedule (dosage [mg/m2]: 0.2, 0.3, 0.45), and 3 pts have been treated on the QW schedule (dosage [mg/m2]: 0.3, 0.45, 0.6). All patients are Caucasian. Median age is 65.5 (53-72). The median number of administered EC1169 cycles is 3 (range: 1-4). There have been no DLTs or dose omissions due to toxicity. For 1 pt (0.3 mg/m2 TIW), cycle 4 was delayed for 2 wks due to self-limited asymptomatic troponin-I elevation. Only grade 1-2 TEAE's have been observed. Four pts remain on treatment. Conclusions: Overall, initial preliminary data suggest that EC1169 is well-tolerated on both schedules. Dose escalation is ongoing. Clinical trial information: 02202447.
Effect of metastasis associated in colon cancer-1 on vasculogenic mimicry formation in patients with gastric cancer.
Authors: Lin Wang, Huanrong Ma, Na Huang, Li Sun, Wenjun Liao, Yulin Liao, Wangjun Liao
Journal: Journal of Clinical Oncology (2014)

e15052 Background: Vasculogenic mimicry (VM) as a blood supplyment pattern is strongly associated with tumor progression. In a previous study, metastasis-associated in colon cancer-1 (MACC1) upregulation predicted a poor prognosis of gastric cancer (GC), and induced epithelial mesenchymal transition (EMT). Recent studies showed that EMT is a key step for VM. The aim of this study was to identify whether both VM and MACC1 expression predict worse clinical outcome, and to explore how MACC1 regulate VM in GC. Methods: Using immunohistochemistry, we analysed both VM and MACC1 expression with clinicopathologically characterised 88 stage IV GC patients. We studied the roles of MACC1 on VM formation in animal models of athymic mice. RNA interference and 3D culture assay were conducted to investigate the effects of Twist1 and Twist2 on MACC1-induced VM in GC cells. Using luciferase reporter gene and co-ip assay, we analysed the effects of MACC1/Twist1 complex on Twist2 promoter activity and some key downstream genes during VM formation. Results: VM positivity was more frequent with differentiation (p=0.018), metastasis (p=0.025) and MACC1 expression (p=0.048) in GC patients. Survival analysis revealed that the three-year survival rate was 8.6% in both VM and MACC1 expression group, whereas 41.7% in non-VM and without MACC1 expression group, and the median survival time was 3.3 versus 32 months. Moreover, MACC1 upregulation was closely correlated with Twist1 (p=0.016) and Twist2 (p=0.001) in GC tissues, which also caused VM formation in animal models. In vitro study demonstrated that MACC1 induced typical pipe-like structures in a 3D culture system, and increased the expression of Twist1 and Twist2 in mRNA and protein levels. RNA interference-mediated silencing of Twist1 or Twist2 inhibited VM formation. MACC1/Twist1 complex enhanced Twist2 promoter activity and transcriptional activation of multiple downstream genes that increased VM, which partially via HGF/c-MET signaling pathway. Conclusions: These findings indicated a novel function for MACC1 in VM formation, and MACC1/Twist1 complex may play a significant role in promoting tumor progression and VM in GC partially through HGF/c-MET pathway.
Onset of neutropenia as an indicator of treatment response in the phase 3 RECOURSE trial of trifluridine/tipiracil (TAS-102) versus placebo in patients with metastatic colorectal cancer.
Authors: Atsushi Ohtsu, Takayuki Yoshino, Alfredo Falcone, Rocio Garcia-Carbonero, Guillem Argiles, Alberto F. Sobrero, Marc Peeters, Lukas Makris, Fabio M. Benedetti, Alberto Zaniboni, Yasuhiro Shimada, Kentaro Yamazaki, Yoshito Komatsu, Howard S. Hochster, Heinz-Josef Lenz, Ben Tran, Kenichiro Yoshida, Eric Van Cutsem, Robert J. Mayer
Journal: Journal of Clinical Oncology (2017)

775 Background: TAS-102 is comprised of an antineoplastic thymidine-based nucleoside analog, trifluridine (FTD), and a thymidine phosphorylase inhibitor, tipiracil. Primary results of the RECOURSE trial demonstrated a significant improvement in overall survival (OS) and progression-free survival (PFS) with TAS-102 vs placebo (pbo) in patients (pts) with metastatic colorectal cancer refractory/intolerant to standard therapies. Neutropenia is a common TAS-102–associated adverse event and it has been hypothesized to be associated with a relatively high FTD concentration in pts. Methods: RECOURSE data were analyzed post hoc for correlations between onset of neutropenia (Grade 3/4) and survival benefit. Results: Of 533 pts given TAS-102, 75 (14%) developed Grade 3/4 neutropenia in treatment cycle 1, 86 (16%) for the first time in cycle 2, and 39 (7%) for the first time in cycle ≥3. Onset of neutropenia at any cycle was associated with longer median OS and PFS compared with no neutropenia. A consistent survival benefit was observed regardless of the cycle of initial onset of neutropenia, as demonstrated by the hazard ratio (against cycle-matched pbo control groups) and corresponding median OS differences (Table). Conclusions: An association between occurrence of earliest onset of Grade 3/4 neutropenia and survival benefit was observed. The data indicate that such survival benefit occurred regardless of whether the initial onset of neutropenia occurred after cycle 1, cycle 2, or later. Further analyses are required to fully determine whether FTD pharmacokinetics correlate with TAS-102 efficacy and onset of neutropenia, and whether cycle initiation delays affect response. Clinical trial information: NCT01607957. [Table: see text]
A short-term biomarker modulation prevention study of anastrazole in women at increased risk for breast cancer
Authors: B. Arun, V. Valero, A. Brewster, A. Gutierrez, M. Green, F. Esteva, A. Buzdar, G. N. Hortobagyi, N. Sneige
Journal: Journal of Clinical Oncology (2009)

1514 Background: Selective estrogen receptor modulators (SERMs) reduce the risk of breast cancer. Acceptance of SERMs is low due to toxicities. Agents with a better toxicity profile and surrogate endpoint biomarkers to evaluate the effect of preventive agents are needed. In addition to reducing the risk of recurrence of breast cancer, the aromatase inhibitors (AI) have been shown to reduce the risk of contralateral breast cancer in large phase III adjuvant studies. Our objective in this prospective short-term prevention study was to evaluate the effect of anastrozole on surrogate endpoint biomarkers in breast tissue and serum of women with breast cancer who are at increased risk for developing a contralateral second primary breast cancer. Methods: Women with a history of stage I, II breast cancer who were scheduled to start anastrozole for standard adjuvant treatment were eligible. After signing informed consent, patients underwent baseline fine needle aspiration (FNA) of the unaffected breast and serum collection for biomarker analysis before starting anastrozole at 1 mg per oral /day. A repeat FNA and serum collection were performed after 6 months of therapy. Biomarker endpoints included changes in ER and KI-67 expression in breast tissue analyzed by immunohistochemistry and insulin-like growth factor binding protein (IGFBP-1) in serum analyzed by ELISA. The difference in biomarkers before and after treatment was assessed using a Wilcoxon signed-rank test. Results: Forty two patients were enrolled and accrual has been completed. Median age was 58.8 (range 48–75). There was no change in ER or Ki-67 expression in pre- and posttreatment FNA samples. However, there was a statistically significant difference in pre- and posttreatment serum IGFBP-1 levels (p = 0.014); with pre-and post- mean treatment levels being 9.2 ng/mL and 13.5 ng/mL, respectively. Conclusions: We found a significant modulation of IGFBP-1 levels with 6 months of anastrozole treatment in women at increased risk of developing contralateral breast cancer. Anastrozole is currently being studied as a prevention agent in a large phase III trial, and our results provide support for continued evaluation of IGFBP-1 as a surrogate endpoint biomarker in prospective breast chemoprevention studies. [Table: see text]
Neoadjuvant chemotherapy for patients with breast cancer during pregnancy (BCP).
Authors: Sibylle Loibl, Sileny Han, Kristin Mayer, Kristina MacMillan, Samuel Gyapong, Kristina Luebbe, Cornelia Weiss, Kathi Schreiber, Isabel Witzel, Volkmar Müller, Andreas Schneeweiss, Christoph Mundhenke, Christine Waldhoer, Daniela Rezek, Nadine Vogt, Stefanie Strobel, Anna Parokonnaya, Valentina Nekljudova, Frederic Amant, Gunter Von Minckwitz
Journal: Journal of Clinical Oncology (2014)

1071 Background: Neoadjuvant therapy (NAT) is increasingly considered the treatment of choice for patients with HER2+ and triple-negative (TNBC) breast cancer. It is recommended to treat patients with breast cancer during pregnancy as closely as possible according to patients diagnosed outside pregnancy. Data on NAT during pregnancy are scarce. We compared patients with BCP who received NAT with pregnant patients who received NAT after delivery. Methods: Patients from the registry of the German Breast Group (GBG 29/BIG 02-03) and the international Cancer in Pregnancy initiative with BCP who received NAT were analyzed. A non-pregnant control cohort was matched using the Propensity Score based on age, cT Stage (cT 1-2 vs 3-4), cN Stage (cN0 vs cN+), grading (1 vs 2 vs 3), ER/PgR, HER2, neoadjuvant trastuzumab therapy. Results: 103/130 neoadjuvant treated BCP patients were identified with complete data who received NAT during pregnancy (n=62) or after delivery (n=41). Baseline characteristics were comparable. 42% HER2+ and 34% had TNBC. Median age was 34 years. BC was diagnosed in the first or second trimester in 63% of patients with NAT during pregnancy and in 19% of patients with NAT after delivery (p<0.001). Non-taxane containing regimen received 26% of patients with NAT during pregnancy compared to 5% of patients with NAT after delivery (p<0.001), taxane sequence received 73% and 69%, taxane combination received 0 vs 27%, and neoadjuvant trastuzumab received 64% vs. 77%, respectively. pCR (ypT0 ypN0) rate was 24% vs 23% (p=1.0). There was no difference in DFS and OS for patients with NAT during pregnancy vs thereafter (log rank p=0.940 and p=0.653). Conclusions: Based on this first analysis it seems that NAT during pregnancy is as effective as after delivery in patients with BCP. Results of the comparison with a non-pregnant control-cohort treated with NAT will be presented at the meeting.
Interim FDG PET/CT to predict progression-free survival (PFS) better than clinical and baseline metabolic measurements in Hodgkin lymphoma (cHL).
Authors: Ashley Knight-Greenfield, Richard Aaron Marshall, Martin Hutchings, John Doucette, Jamie Stern, Morton Coleman, Lale Kostakoglu
Journal: Journal of Clinical Oncology (2013)

8555 Background: Previous studies in cHL have demonstrated that conventional methods to risk stratify patients into various prognostic groups and predict PFS may not be sufficient to individualize therapy. Metabolic parameters using FDG-PET may be helpful for developing a prognostic algorithm and predict PFS. Objectives: To determine the best predictor of PFS among various variables of tm metabolic measurements at baseline and at interim PET/CT compared to conventional methods in cHL patients. Methods: Retrospective evaluation of prospectively acquired data in 58 cHL pts, all stages [IIB-IV:41%, &gt;IPS-3:24%, unfavorable (UF):44%]. Eligibility: PET/CT prior to and after 1 cycle (PET1) ABVD therapy, imaging at 60min+15min, follow-up&gt;24 mo. Baseline PET parameters including metabolic tumor volume (MTV), total lesion glycolysis (TLG), SUVmax, and SULpeak were determined using gradient method (PETVCAR2, GE Healthcare, WI). Data were also evaluated at PET1 for %ΔMTV, %ΔSUVmax, %ΔTLG, PERCIST criteria and visually with Deauville 5-PS. Variables were correlated with PFS. Results: Median follow-up: 32.2 mo. Of 58 pts 14 relapsed (median PFS:6.5 mo). Results for PFS are displayed in the Table. No baseline conventional (stage, IPS, UF vs F) or PET variable was associated with PFS. The best predictor of PFS was Deauville 5-PS at PET1. PERCIST and %ΔTLG using gradient method trended toward significance. Conclusions: Deauville 5-PS best predicts PFS at PET1 in cHL. Neither baseline PET nor conventional prognostic factors correlated with PFS in this group of cHL pts. Risk-stratification of cHL using tumor metabolic volumetry and PERCIST criteria may require a larger sample size and further assessment of various methodologies. [Table: see text]