tbuckley/cabot-search huggingface dataset:
Provider characteristics and their association with burnout and career satisfaction among physician assistants in oncology.
Authors: Eric Daniel Tetzlaff, Heather Marie Hylton, Karen Ruth, Yu-Ning Wong
Journal: Journal of Clinical Oncology (2016)

6521 Background: About 45% of oncologists report burnout (BO) despite high career/specialty satisfaction (CS/SS). Little is known about BO and CS/SS among Physician Assistants (PAs) in oncology (onc). With increased utilization of PAs in onc it is important to understand the onc PA workforce & its ability to meet the expected demand. Methods: Over 4 months in 2015 we conducted a national survey of PAs in onc. The sample size (855) was from the Association. of PAs in Onc (APAO). BO was assessed using the Maslach Burnout Inventory & the emotional exhaustion (EE) & depersonalization (DP) subscales. 5-point Likert scales assessed PAs’ opinions about compensation, workload, CS/SS and their relationship with their collaborating physician (CP). A composite score was created for the 3 items on CP relationship. Results: The response rate was 29.2% (n = 250). Respondents were representative of PAs in onc; female (88.8%), age 35-44 (37.6%), academic practice (55.2%), urban location (61.2%), outpatient (74.4%), medical oncology (75.2%), worked 41-50 hours/week (52.8%), 10-20 years as PA in onc (35.2%). Overall, burnout was reported in 34.8%. High scores on EE (17.2%), DP (4.4%) or both (13.2%) contributed to overall rate of BO. Increase in hours worked per week (p = 0.0017) & disagreement with fairness of compensation ( < 0.0001) were associated with higher rates of BO. Med Onc, Surg Onc, Rad Onc & “Other” onc specialties had BO rates of 38.8%, 30%, 15.4%, 15.8% (p = 0.077). BO rates did not differ by age, gender, practice setting/location, compensation method, or years as an onc PA. An increase in BO was seen for PAs who did not feel valued by their CP, encouraged to achieve professional goals or whose contributions to the practice were unacknowledged by their CP (P < 0.001 for all items). BO increased from 20% to 62% (p < 0.001) using the CP overall composite score. Overall CS & SS were high (86% & 90%). In the next 2 years, only 3.6% PAs plan to pursue a different career or specialty & 2% plan to retire. Conclusions: Despite high CS & SS, burnout is common in PAs in onc. Negligible short-term attrition of the current onc PA workforce is anticipated. Further exploration of the PA/CP relationship may provide insight on methods to decrease BO.
Phase I trial of the combination of selinexor (SEL), liposomal doxorubicin (DOX) and dexamethasone (Dex) for relapsed and refractory multiple myeloma (RRMM).
Authors: Rachid C. Baz, Kenneth H. Shain, Melissa Alsina, Jason Brayer, Tami Rashal, Jennifer L Cooksey, Joel G Turner, Jana Dawson, Daniel Sullivan
Journal: Journal of Clinical Oncology (2016)

8013 Background: SEL, an oral, first-in-class inhibitor of XPO1 showed activity in clinical trials for hematologic malignancies. SEL inhibits DNA damage repair and exhibits marked synergy with doxorubicin in preclinical myeloma models. We report here the results of a phase I trial of SEL in combination with DOX and Dex in patients with RRMM. Methods: Eligible patients had RRMM and received ≥ 2 prior therapies including lenalidomide and a proteasome inhibitor. Treatment consisted of a loading phase with SEL and Dex for 1-2 weeks; an induction phase with DOX 20 mg/m2IV D1, SEL and Dex (once weekly) and a maintenance phase of weekly SELDex. Two loading phases were evaluated: A. SELDex twice weekly for 2 weeks, B. One dose of SELDex. Primary and secondary end points: maximum tolerated dose (MTD) / recommended phase II dose (RP2D) of the combination and overall response rate (ORR) per International Myeloma Working Group (IMWG) criteria. Results: 11 patients were enrolled (median age of 59 years, median of 5 prior lines (range 2-9)). No dose limiting toxicities (DLT) were noted in dose level (DL) 1. 2 patients experienced a DLT in DL2 (Gr4 thrombocytopenia and Gr 3 nausea). The loading phase was shortened to 1 dose of SEL (80mg) on day -7 (DL2m). 1/3 patients experienced a DLT on DL2m (Gr3 hyponatremia). The most common Grade 3/4 at least possibly related adverse events are as follows: hyponatremia 54%, anemia 38%, thrombocytopenia 38%, neutropenia 38%, diarrhea 23%, vomiting 23%, hyperglycemia 15% and fatigue 15%. 10 patients are evaluable for response: 2 VGPR, 2 PR, 2MR, 3 SD and 1 PD. Conclusions: Enrollment on the phase I trial is expected to be completed and updated by the time of the meeting. Preliminary responses in heavily pretreated patients support the continued investigation of this combination in patients with RRMM Clinical trial information: NCT02186834.Age / gender Loading phase SEL dose (PO) Dose Level # of prior lines Cycles IMWG Best response DLT 59 / F A 40 mg/m2 1 9 3 MR No 51/ F A 40 mg/m2 1 5 12 VGPR N/E 52 / M A 40 mg/m2 1 7 loading N/E N/E 49 / F A 40 mg/m2 1 7 8 PR No 76 / M A 40 mg/m2 1 5 8 MR No 56 / M A 80 mg 2 7 4 SD Gr 4 platelet 66 / M A 80 mg 2 5 2 SD Gr 3 nausea 60 / M A 80 mg 2 6 7+ VGPR N/E 73 / F B 80 mg 2m 2 2 PD No 50 / M B 80 mg 2m 2 2+ SD No 65 / M B 80 mg 2m 4 1+ PR Gr 3 Na
Role of PET/CT in prognosticating post-transplant outcomes based on a new scoring system: Results of PIPET-M TRIAL.
Authors: Uday Yanamandra, B.R. Mittal, Arun Reddy, Kanhaiya Agarwal, Alka Khadwal, Gaurav Prakash, Neelam Varma, Subhash Varma, Pankaj Malhotra
Journal: Journal of Clinical Oncology (2016)

8028 Background: Multiple myeloma (MM) is a heterogeneous disorder with varied responses to transplantation. 18F-FDG-PET/CT has role in prognosticating post-transplant outcomes, but the PET positivity has been reported in non-homogenous fashion leading to difficulty in interpretation and inter-trial comparisons. We defined a new staging system for PET/CT reporting in MM and validated it for predicting post-transplant outcomes, first in the world literature. Methods: It is a prospective systematic protocol based single centre observational study. As part of CTRI registered PIPET-M Trial, all autologous transplant MM patients underwent 18F-FDG-PET/CT during pre-transplant work up. The conditioning and treatment protocols were not modified based on PET/CT findings. PET positivity was defined as per a newly defined PIPET-M staging in lines with modified Deauville's staging based on target lesion SUVmax. This staging was further classified into two models for defining PET positivity based on background physiological FDG uptake as internal control (In model 1 - mediastenal SUVmax and in model 2 - Liver SUVmax was taken as physiological SUVmax). Progression was defined using revised IMWG criteria. Using SPSS ver.16.0, OS/PFS was assessed by Kaplan-Meier/ Cox-regression survival analysis. Results: A total of 43 patients underwent pre-transplant PET/CT evaluation. The staging was validated in this cohort. Further using model-1, PET negative patients had better PFS (88.2 vs 69.2%, p-0.65) and better OS (94.1 vs 65.4%, p-0.01). The hazard for all-cause mortality was 22.445 times higher for PET positive individuals (p-0.02). Using model-2, only statistically significant result was delayed neutrophil-engraftment in PET positive patients (11.69 vs 10.5d, p-0.02). There was good agreement between two models, but model-1 had significantly higher sensitivity, and slightly lower specificity as compared to model-2 for predicting survival. Inter-observer variability was 0.02 for PIPET staging. Conclusions: Utilizing PET stages based on this newly proposed staging model is clinically relevant to predict post-transplant OS. Clinical trial information: U1111-1177-8850, REF/2015/12/010356.
Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents
Authors: Frederick G. Hayden, Norio Sugaya, Nobuo Hirotsu, Nelson Lee, Menno D. de Jong, Aeron C. Hurt, Tadashi Ishida, Hisakuni Sekino, Kota Yamada, Simon Portsmouth, Keiko Kawaguchi, Takao Shishido, Masatsugu Arai, Kenji Tsuchiya, Takeki Uehara, Akira Watanabe
Journal: New England Journal of Medicine (2018)

Baloxavir marboxil is a selective inhibitor of influenza cap-dependent endonuclease. It has shown therapeutic activity in preclinical models of influenza A and B virus infections, including strains resistant to current antiviral agents.We conducted two randomized, double-blind, controlled trials involving otherwise healthy outpatients with acute uncomplicated influenza. After a dose-ranging (10 to 40 mg) placebo-controlled trial, we undertook a placebo- and oseltamivir-controlled trial of single, weight-based doses of baloxavir (40 or 80 mg) in patients 12 to 64 years of age during the 2016-2017 season. The dose of oseltamivir was 75 mg twice daily for 5 days. The primary efficacy end point was the time to alleviation of influenza symptoms in the intention-to-treat infected population.In the phase 2 trial, the median time to alleviation of influenza symptoms was 23.4 to 28.2 hours shorter in the baloxavir groups than in the placebo group (P<0.05). In the phase 3 trial, the intention-to-treat infected population included 1064 patients; 84.8 to 88.1% of patients in each group had influenza A(H3N2) infection. The median time to alleviation of symptoms was 53.7 hours (95% confidence interval [CI], 49.5 to 58.5) with baloxavir, as compared with 80.2 hours (95% CI, 72.6 to 87.1) with placebo (P<0.001). The time to alleviation of symptoms was similar with baloxavir and oseltamivir. Baloxavir was associated with greater reductions in viral load 1 day after initiation of the regimen than placebo or oseltamivir. Adverse events were reported in 20.7% of baloxavir recipients, 24.6% of placebo recipients, and 24.8% of oseltamivir recipients. The emergence of polymerase acidic protein variants with I38T/M/F substitutions conferring reduced susceptibility to baloxavir occurred in 2.2% and 9.7% of baloxavir recipients in the phase 2 trial and phase 3 trial, respectively.Single-dose baloxavir was without evident safety concerns, was superior to placebo in alleviating influenza symptoms, and was superior to both oseltamivir and placebo in reducing the viral load 1 day after initiation of the trial regimen in patients with uncomplicated influenza. Evidence for the development of decreased susceptibility to baloxavir after treatment was also observed. (Funded by Shionogi; JapicCTI number, 153090, and CAPSTONE-1 ClinicalTrials.gov number, NCT02954354 .).
Efficacy of preoperative chemotherapy regimens in patients with initially unresectable locally advanced gastric adenocarcinoma: Capecitabine and oxaliplatin (XELOX) or with epirubicin (EOX).
Authors: Yan Wang, Yiyi Yu, Rongyuan Zhuang, Shan Yu, Jun Hou, Yuan Ji, Yihong Sun, Kuntang Shen, Zhenbin Shen, Fenglin Liu, Naiqing Zhao, Tianshu Liu
Journal: Journal of Clinical Oncology (2016)

4047 Background: Preoperative chemotherapy for initially unresectable locally advanced gastric cancer is thought to downsize tumors for curative resection and there upon prolong survival, but there is no best recommended regimen. We assessed the effectiveness of EOX (capecitabine, oxaliplatin and epirubicin) compared with XELOX (capecitabine and oxaliplatin) as preoperative chemotherapy for initially unresectable locally advanced gastric cancer. Methods: This is a prospective observational study. The trial was registered on ClinicalTrials.gov (NCT02192983). Patients with unresectable locally advanced gastric cancer were performed EOX regimen or XELOX regimen at the discretion of the investigators. They were assessed for response every 2 cycles by CT (computed tomography) scan. A multidisciplinary team reassessed resectability after 4 cycles. If disease became resectable, radical surgery would be performed within 4-6 weeks after the last treatment cycle. The primary endpoint was the response rate. Secondary end points included the R0 resection rate, survival and adverse events. Results: From November 2008 to May 2015, 242 patients were enrolled; 112 of them were assigned to EOX regimen and 130 to XELOX regimen. The response rates were 33.0% and 33.8% respectively in EOX group and XELOX group (P= 0.997). After 4 cycles of chemotherapy, 63 patients (56.3%) in EOX group and 81 patients (62.3%) in XELOX group received radical operation (P= 0.408). There was no significant difference in progress-free survival (PFS, 12.0m vs. 15.4m, P= 0.925) and overall survival (OS, 25.7m vs. 29.0m, P= 0.783) in two groups. In addition, more adverse effects occurred in EOX group, such as more leucopenia (22.3% vs. 10.0%, P= 0.014), neutropenia (23.2% vs. 11.5%, P= 0.025), fatigue (11.6% vs. 3.8%, P= 0.041) and vomiting (10.7% vs. 2.3%, P= 0.015). Conclusions: For unresectable locally advanced gastric cancer patients, XELOX regimen showed similar effects in response rate, radical resection rate and survival benefits, but with less toxicity effects.
TCT-807 Post-procedural intracoronary physiology predicts final myocardial injury after STEMI. Insights from the OxAMI study
Authors: Roberto Scarsini, Giovanni De Maria, Alessandra Borlotti, Jeremy Langrish, Andrew Lucking, Keith Channon, Rajesh Kharbanda, Adrian Banning, Adrian Banning
Journal: Journal of the American College of Cardiology (2018)
Being PrEPared — Preexposure Prophylaxis and HIV Disparities
Authors: Robert H. Goldstein, Carl G. Streed, Sean R. Cahill
Journal: New England Journal of Medicine (2018)

Being PrEPared Despite its proven benefits, preexposure prophylaxis against HIV (PrEP) has been prescribed to only a fraction of the population that would benefit from it. Stigma and limited awareness are substantial barriers to improving uptake in the communities at the highest risk.
Compassionate use study of TRC105 (Endoglin Antibody) in combination with bevacizumab (Bev) in patients (pts) with refractory and metastatic choriocarcinoma.
Authors: Neil S. Horowitz, Kevin Meyer Elias, Donald Goldstein, Stephanie Morrissey, Siobhan A Collins, Julie Childress, Michael Seckl, Ross Stuart Berkowitz
Journal: Journal of Clinical Oncology (2016)

e17033 Background: Endoglin is a receptor expressed on tumor vessels that is overexpressed in certain tumors, including choriocarcinoma. Anecdotally Bev does not appear to be an active single agent for treatment of choriocarcinoma. Endoglin is upregulated following vascular endothelial growth factor (VEGF) inhibition and may mediate resistance to Bev. TRC105 is an endoglin antibody that may be active in patients with gestational trophoblastic neoplasia (GTN), including choriocarcinoma Methods: We performed a compassionate use study of TRC105 in combination with Bev in two pts with refractory and metastatic choriocarinoma who had exhausted known surgical and chemotherapeutic options. Patients were treated with TRC105 at 10 mg/kg iv weekly with Bev 10 mg/kg iv every two weeks. Results: Pt 1 is a 38 year old woman whose metastatic choriocarinoma progressed following prior therapy with six multi-agent chemotherapy regimens including autologous stem cell transplant. She received 8 monthly cycles of TRC105 and Bev. Beta hCG normalized during the 4th cycle and has remained in within the normal range 4 months after her last treatment, indicating an ongoing complete response. Pt 2 is a 33 year old woman whose metastatic choriocarcinoma progressed following eight prior multi-agent chemotherapy regimens. She was noted to have progression with a rising beta hCG at the end of the initial month of dosing. Treatments were well tolerated by both patients. Toxicities have included grade 1 epistaxis, rash, thrombocytopenia, and hoarseness, grade 2 gingivitis, and grade 3 hypertension, headache, and fatigue. A TRC105 dose reduction to 8 mg/m2 was required with the 4th cycle secondary to gingivitis in Patient 1. Correlative studies are ongoing, including assessment of tumor endoglin expression. Conclusions: TRC105 combined with bev was well tolerated and exhibited activity, including durable complete response in choriocarcinoma, a tumor known to densely express endoglin. Further investigation of TRC105 as a single agent or in combination with Bev is warranted. Assessment of tumor endoglin expression may identify GTN patients who are most responsive to TRC105 therapy.
Is it Useful to Repeat Magnetic Resonance Imaging of the Sacroiliac Joints After Three Months or One Year in the Diagnosis of Patients With Chronic Back Pain and Suspected Axial Spondyloarthritis?
Authors: P. A. C. Bakker, S. Ramiro, Z. Ez‐Zaitouni, M. van Lunteren, I. J. Berg, R. Landewé, R. Ramonda, M. van Oosterhout, M. Reijnierse, F. A. van Gaalen, D. van der Heijde
Journal: Arthritis & Rheumatology (2018)

Objective To investigate the value of repeated magnetic resonance imaging (MRI) of the sacroiliac (SI) joints in diagnosing chronic back pain patients in whom axial spondyloarthritis (SpA) is suspected and to examine determinants of positive MRI findings in SI joints. Methods Patients with chronic back pain (duration 3 months–2 years, age ≥16 years, age at onset &lt;45 years) with ≥1 SpA feature who were included in the Spondyloarthritis Caught Early cohort underwent visits at baseline, at 3 months, and at 1 year. Visits included an evaluation of all SpA features and repeated MRI of SI joints. MRI‐detected axial SpA positivity (according to the definition from the Assessment of SpondyloArthritis international Society) was evaluated by 2 or 3 well‐trained readers who were blinded with regard to clinical information. The likelihood of a positive MRI finding at follow‐up visits (taking into consideration contributing factors) was calculated by generalized estimating equation analysis. Results Of the 188 patients, 38.3% were male, the mean ± SD age was 31.0 ± 8.2 years, and the mean ± SD symptom duration was 13.2 ± 7.1 months. Thirty‐one patients (16.5%) had positive MRI findings in the SI joints at baseline. After 3 months and after 1 year, the MRI results had changed from positive to negative in 3 of 27 patients (11.1%) and 11 of 29 patients (37.9%), respectively, which was attributable in part to the initiation of anti–tumor necrosis factor therapy. Status changes from negative to positive were seen in 5 of 116 patients (4.3%) after 3 months and in 10 of 138 patients (7.2%) after 1 year. HLA–B27 positivity and male sex were independent determinants of the likelihood of a positive MRI scan at any time point (42% in HLA–B27+ men and 6% in HLA–B27− women). If the baseline results were negative, the likelihood of a positive scan at follow‐up was very low (≤7%). Conclusion MRI‐detected status changes in the SI joints were seen in a minority of the patients, and both male sex and HLA–B27 positivity were important predictors of MRI positivity. Our findings indicate that conducting MRI scans after 3 months or after 1 year in patients with suspected early axial SpA is not diagnostically useful.
The impact of palliative care consultation on overall survival and aggressive care at the end-of-life in unresectable pancreatic cancer.
Authors: Caitlin Lees, Swarna Weerasinghe, Tallal Younis, Nathan William Dana Lamond, Ravi Ramjeesingh
Journal: Journal of Clinical Oncology (2018)

e18729 Background: Early Palliative Care consultation has been associated with improved overall survival (OS) and lower aggressiveness of end-of-life care (AEOLC) in a number of malignancies. For patients with unresectable pancreatic cancer (UPC), aggressive and resource-intensive treatment at the end-of-life can be costly, but not necessarily of better quality. This study examined the potential impact of Palliative Care consultation on AEOLC score and OS in patients diagnosed with UPC. Methods: All patients diagnosed with UPC in Nova Scotia between January 1, 2010 and December 31, 2015 were identified through the cancer registry. A retrospective chart review was conducted to extract relevant demographics, clinical-pathologic characteristics, tumor characteristics and timing of consultations. An AEOLC score, previously described in the literature was calculated for each patient. Statistical analysis included ordinal logistic regression, univariable and multivariable Cox proportional hazard models. Results: In total, 365 patients were identified. Mean AEOLC score was 0.91 (SD 0.95). On average, patients seen by Palliative Care had lower AEOLC scores than those never seen by Palliative Care (0.82 vs 1.34, p < 0.001). Early ( < 8 weeks) or late ( > 8 weeks) Palliative Care consultation reduced odds of having a higher AEOLC score by 61% (95% CI 35%-77%) and 35% (95% CI 14%-76%), respectively, when adjusted for demographic and clinical characteristics. Compared to no Palliative Care consultation, late consultation was significantly (p < 0.001) associated with improved OS but early consultation was not. In addition, receipt of chemotherapy (p < 0.001) and metastatic disease at diagnosis (p = 0.011) were significantly associated with improved OS. Conclusions: In patients diagnosed with UPC, Palliative Care consultation appears to be associated with a lower AEOLC score and improved survival. Prospective studies are needed to confirm the observed results.
Pediatric oncologists' experiences with compassionate use.
Authors: Scott Moerdler, Lindy Zhang, Elena Gerasimov, Chong Zhu, Tamar Wolinsky, Michael Roth, Nancy Goodman, Daniel Weiser
Journal: Journal of Clinical Oncology (2018)

e18627 Background: Targeted cancer treatments are almost always first studied in adults even when there is a biologically plausible potential for efficacy in children. Through compassionate use (CU) programs, children who are not eligible for a clinical trial and for whom there are no known effective therapies may obtain investigational agents. Patients can access CU drugs only if a physician initiates an application. However, there is a lack of data on pediatric oncologists’ knowledge of and experiences with applying for investigational drugs on a CU basis, and the factors affecting their ability to obtain CU drugs. Methods: An electronic questionnaire was used to survey 132 pediatric oncologists to assess their awareness and utilization of CU programs, to identify barriers to its use, and to evaluate available institutional support and resources for CU applications. Results: We found that the process of applying for access to drugs in development is poorly understood, presenting a potential barrier to obtaining investigational drugs. Forty eight percent of the pediatric oncologists surveyed completed an application for CU. Of those who did not complete applications, 18% were unfamiliar with CU programs and 29% could not identify a potentially effective drug. More experienced providers and those at larger centers were more likely to obtain the desired drug. Fifty eight percent of those who completed an application needed assistance, and 78% of all respondents’ institutions lack support resources for CU applications. Finally, 83% of respondents believe that a service facilitating the application process would be helpful. Conclusions: We identified the lack of knowledge and paucity of support in the application process as immediate actionable barriers to wider utilization of CU in pediatric oncology. Our study suggests a possible healthcare disparity based on the experience of the provider and size of institution, with seasoned oncologists and major academic centers being more likely to successfully access investigational agents. In order to provide pediatric oncology patients equal opportunity to access investigational agents, pediatric oncologists may benefit from educational resources and assistance to support them through the CU request process.