tbuckley/cabot-search huggingface dataset:
Efficacy and tolerability of nanoparticle docetaxel lipid suspension.
Authors: Aditya Murali, Sumant Gupta, Dinesh Pendharkar
Journal: Journal of Clinical Oncology (2018)

e14542 Background: Nano particle formulations of chemotherapeutic agents have been found to have greater activity and better tolerability in certain malignancies. A novel lipid bound formulation of docetaxel not requiring additional diluent before mixing in normal saline, was introduced. The aim of this analysis was to study feasibility, overall efficacy and tolerability of this molecule across various malignancies where docetaxel is indicated. Methods: Data of patients with solid tumors, treated over 18 months, with nano particle docetaxel lipid suspension (DoceAqualipR,75 mg/m2IV over 1 hr q3week, diluted in 500 ml of saline, without premixing with any special diluent) were retrospectively analyzed. Efficacy endpoints, toxicity, as overall response rate (ORR, complete response [CR] +Partial Response [PR]), and disease control rate (DCR, CR+PR+Stable Disease [SD]) were evaluated, as per RECIST 1.1 criteria and CTC AE v4.03 Results: Overall data from 39 patients (23 male, 16 female), with mean age of 60 years was analyzed. Majority had cancer stages III (30.77%) and IV (66.67). Majority (84.62%) received the molecule as first-line therapy. Intent of treatment was palliative in 74.36% and curative in 25.64% patients. ORR of 35.9 % (range 28.57 % - 100 %) was observed across the group (Table). There was no new toxicity observed compared to standard docetaxel preparation. There were no acute allergic reactions; and no neuropathy seen over six months follow up. Conclusions: Nano particle docetaxel appears to be equally effective to standard formulation docetaxel with no different toxicity. It additionally has ease of administration. The data warrants further study in breast and prostate cancer. Table: Effectiveness of Nano Docetaxel Treatment in Solid Tumors Carcinoma/Response CR PR SD PD ORR DCR Bladder 1 1 (100%) 0 0 0 1 (100%) 1 (100%) Breast 12 4 (33.33%) 7 (58.33%) 1 (8.33%) 0 11 (91.67%) 12 (100%) Cervix 1 0 0 1 (100%) 0 0 1 (100%) Endometrium 1 0 0 1 (100%) 0 0 1 (100%) Esophagus 3 0 0 3 (100%) 0 0 3 (100%) Head and neck 7 2 (28.57%) 0 1 (14.29%) 4 (57.14%) 2 (28.57%) 3 (42.86%) NSCLC 7 5 (71.43%) 0 0 2 (28.57%) 5 (71.43%) 5 (71.43%) Prostate 6 6 (100%) 0 0 0 6 (100%) 6 (100%) Sarcoma 1 0 0 0 1 (100%) 0 0 Total 39 7 (17.95%) 7 (17.95%) 18 (46.15%) 7 (17.95%) 14 (35.90%) 32 (82.05%)
TCT-865 Temporal Trends and Outcomes of Fibrinolytic Therapy for ST Elevation Myocardial Infarction among Patients 80 Years or Older Transferred for Percutaneous Coronary Intervention
Authors: Gbolahan Ogunbayo, Naoki Misumida, Karam Ayoub, Dustin Hillerson, Ayman Elbadawi, Robert Pecha, Ahmed Abdel-Latif, Susan Smyth, Adrian Messerli
Journal: Journal of the American College of Cardiology (2018)
Evaluation of circulating neutrophils as a biomarker for outcomes in uterine carcinosarcoma.
Authors: Anne R. Van Arsdale, Rebecca Christian Arend, Courtney J. Mitchell, Allison L. Gilbert, Charles A. Leath, Gloria S. Huang
Journal: Journal of Clinical Oncology (2016)

e17121 Background: Uterine carcinosarcoma (UCS) is an aggressive malignancy that arises from the endometrium and frequently metastasizes to the lymph nodes and distant sites. Recent data suggests that neutrophils are key mediators of metastasis initiation. This study examines the relationship between circulating neutrophils, metastasis and survival in patients with UCS. Methods: Under an IRB-approved protocol, medical records were abstracted including date of diagnosis, stage, age, race/ethnicity, body mass index, adjuvant therapy, disease recurrence or progression, and date of death. Pre-treatment laboratory data including absolute neutrophil count (ANC) were recorded. Univariable and multivariable Cox proportional hazard regression models were fit to examine the relationship of demographic variables and ANC to PFS and OS. Variables with p < 0.10 in the univariable analysis were included in the multivariable model. All p-values are two-sided and a p < 0.05 considered statistically significant. All analyses were performed using Stata v13.0 (StatCorp, College Station, TX). Results: The study cohort comprised 84 patients with histologically confirmed UCS treated at a single institution. The distribution of pre-treatment ANC by quartiles was: Q1, 0-25% = 1690-2520; Q2, 25-50% = 2520-5692.5; Q3, 50-75% = 5692.5-8911.5; Q4, 75-100% = 8911.5-26590, and was similar between black and white patients. Advanced disease (FIGO Stage III/IV; i.e., presence of pelvic or distant metastasis) was associated with higher ANC (p = 0.01). High ANC significantly increased the risk of disease progression (Hazard ratio, HR Q4:Q1 = 3.32; p = 0.002) and death (HR Q4:Q1 = 3.09; p = 0.005). On multivariable analysis adjusting for stage, race, and adjuvant therapy, ANC remained a significant independent poor prognostic factor for disease progression (HR Q4:Q1 = 3.19; p = 0.01) and death (HR Q4:Q1 = 4.23; p = 0.005). Conclusions: Pre-treatment ANC is identified as an independent prognostic biomarker for metastasis, disease progression, and death in UCS. The role of neutrophils and their secretory network merits further investigation as a potential therapeutic target to disrupt metastatic capability and disease progression in UCS.
The cost-effectiveness analysis of EGFR mutation test for management of advanced non-small cell lung cancer in Thailand.
Authors: Tanavadee Siritanadeepun, Piya Hanvoravongchai, Virote Sriuranpong, Napa Parinyanitikul, Piyada Sitthideatphaiboon, Nattaya Poovorawan, Suebpong Tanasanvimon
Journal: Journal of Clinical Oncology (2016)

e20636 Background: EGFR mutation is the most important predictive factor for EGFR TKI in advanced NSCLC. Patients who EGFR mutant should received EGFR TKI either in 1st or later line of treatments. In Thailand, EGFR TKI is reimbursable only for later line of thrapy and needs pre-approval before prescription. EGFR mutation test is not required for pre-approval process. Methods: Cost-effective analysis of EGFR mutation test before 2nd line therapy in patients with advanced NSCLC after a platinum based chemotherapy (CMT) in Thailand. The model included 2 strategies, the
Barriers to palliative care (PC) utilization in hematopoietic stem cell transplantation (HCT).
Authors: Areej El-Jawahri, Thomas William LeBlanc, Linda J. Burns, Ellen M. Denzen, Christa Meyer, Lih-Wen Mau, Eric Roeland, William Allen Wood, Effie W. Petersdorf
Journal: Journal of Clinical Oncology (2018)

10116 Background: Despite the benefits of PC for patients undergoing HCT, transplant recipients rarely utilize PC. We assessed transplant physicians’ attitudes about PC and perceived barriers to PC utilization. Methods: We conducted a cross-sectional survey of transplant physicians recruited from the American Society of Blood and Marrow Transplantation. We examined physicians’ attitudes about PC and their perceived barriers to PC utilization. As noted in prior literature, we used a composite score of physicians’ attitudes about PC (mean = 16.9, SD = 3.37) and a linear mixed model to explore predictors of attitudes about PC. Results: 277/1005 (28%) completed the survey. The majority (76%) stated that they trust PC clinicians to care for their patients, but 40% felt that PC clinicians do not have enough understanding to counsel their HCT patients. Nearly half (46%) perceived the service name ‘palliative care’ as a barrier for them to refer patients; 51% thought it was synonymous with hospice and end-of-life (EOL) care; and 67% endorsed that it decreased hope in patients and families. Only 8% perceived ‘supportive care’ as a barrier to refer patients, 7% thought it was synonymous with hospice and EOL care, and 11% endorsed that it decreases hope in patients and families. Physicians endorsed the following barriers to PC utilization 1) patients’ and families’ discomfort with discussing EOL care issues (80% and 83% respectively); 2) lack of knowledge about PC by transplant physicians (60%); and 3) cultural factors influencing EOL care (84%). Female sex (β = 0.85, P = 0.024), having less than 10 years of clinical practice (β = 1.39, P < 0.01), and perceived quality of PC (β = 0.60, P < 0.001) were associated with a more positive attitude towards PC. Physicians’ perception of unmet PC needs in HCT was not associated with their attitude towards PC. Higher sense of ownership over patients’ PC issues (β = -0.36, P < 0.001) was associated with a more negative attitude towards PC. Conclusions: The majority of transplant physicians trust PC, but have substantial concerns about PC clinicians’ knowledge about HCT and patients’ perception of the term ‘palliative care’. Interventions are needed to promote collaboration and enhance integration of PC in HCT.
Parental work limitations at diagnosis of advanced stage pediatric Hodgkin lymphoma—Results of caregiver work limitations questionnaire (CG WLQ).
Authors: Susan K. Parsons, Debra Lerner, Angie Mae Rodday, Rachael Curtis, Kara Kelly, Rena Conti, Sharon M. Castellino, Tara O. Henderson
Journal: Journal of Clinical Oncology (2018)

e18927 Background: Cancer cost estimates rarely include the cost of family caregiving. Beyond the physical and emotional demands of caregiving, parents' other roles and responsibilities can be disrupted, including paid work, both prior to diagnosis and during treatment. Moreover, as cancer care shifts to the outpatient setting, caregivers' work impact may be affected due to competition for daytime hours. Methods: Parent caregivers (CG) of children and adolescents, ages 5-17.9 yrs with newly diagnosed advanced HL, were invited to participate in an embedded study to assess costs of care as part of a larger Children's Oncology Group trial. Consenting parents completed the CG WLQ prior to start of therapy. The CG WLQ is a 23-item, validated questionnaire, quantifying the amount of time respondents were unable to perform work roles because of their caregiving in four areas: physical, mental-interpersonal, and output tasks; and time management. Mean scores (SD), ranging from 0-100, indicate the percentage of time the respondent was limited in that area. Scores were compared using one-sample t-tests with 2 prior samples: 710 CG (mean age, 51 yrs) of adults with schizophrenia (Sample 1) (Lerner 2017); and 755 CG (mean age, 46 yrs) of children and adults with various chronic conditions (Sample 2) (Lerner, 2015). Results: Of the 310 parent CG enrolled in the HL study, 158 (51%) identified themselves as working for pay over the past 4 weeks. The mean age was 43.8 yrs (6.8); 76.3% were mothers. Compared to the other samples (Table), parent CG were younger and reported significantly higher rates of limitation in performing almost all work-related tasks. Conclusions: Parent CG of newly diagnosed children and adolescents with advanced HL report higher levels of work impact at the time of initial diagnosis before initiation of treatment than CG of other chronic disease populations. Longitudinal data will evaluate if work impact diminishes over time. Work Area HL Sample 1 Sample 2 Physical 33.0 (35.4) 22.0 (23.2)* 13.6 (23.3)* Mental-Interpersonal 35.1 (23.4) 29.5 (20.8)* 14.2 (17.4)* Output 31.4 (27.6) 27.1 (24.6) 10.3 (16.9)* Time Management 42.9 (28.2) 29.5 (23.1)* 16.8 (19.0)* *p < 0.05
Exome analysis to reveal genomic markers associated with better efficacy of nivolumab in lung cancer patients.
Authors: Corentin Richard, Jean-David Fumet, Sandy Chevrier, Valentin Derangere, Fanny Ledys, Aurelie Lagrange, Laure Favier, Bruno P. Coudert, Laurent Arnould, Caroline Truntzer, Romain Boidot, FranÃ§ois Ghiringhelli
Journal: Journal of Clinical Oncology (2018)

9044 Background: Monoclonal antibodies targeting immune checkpoint inhibitors revolutionized the treatment of lung cancer. However, only one-quarter of non-small cell lung cancer patients (NSCLC) benefit from these new therapies. The assessment of PD-L1 tumor expression by IHC is used to select responder patients and is considered as the gold standard biomarker in many studies; however, this marker does not predict the absence of anti-PD-1 efficacy. Recent studies suggest that high tumor mutational burden (TMB) is associated with better efficacy of Nivolumab compared with chemotherapy. In addition, transcriptomic and exome analyses have revealed potential biomarkers needing further confirmation. It is thus of major importance to define biomarkers that efficiently predict Nivolumab efficacy. Methods: We performed somatic and constitutional exome analyses for 77 patients with NSCLC treated with Nivolumab. We studied: 1-tumor-related characteristics: aneuploidy, tumor copy number alteration clonality, mutational signatures, TMB, mutations in WNT, AKT, MAPK and DNA repair pathways, and 2-immunological characteristics: number of intratumoral TCR clones, HLA type, number of neoantigens, and Type I IFN mutation pathway; and 6 clinical parameters. Results: A high TMB per Mb, a high number of neoantigens, mutational signatures 1A and 1B, mutations in DNA repair pathways and a low number of TCR clones are associated with greater PFS. Using the least absolute shrinkage and selection operator method, we established an exome-based model with 9 parameters that could discriminate patients with good or poor PFS (p < 0.0001) and OS (p = 0.002) independently from clinical data. Moreover, this model had improved ability to predict outcomes compared with a PD-L1 clinical model with or without TMB (Area Under Curve: Clinical = 0.80, TMB = 0.81, exome-derived = 0.93). The model was externally validated on another cohort of 34 patients treated with Pembrolizumab (Rizvi et al., 2015). Conclusions: Altogether, these data provide a validated biomarker that predicts the efficacy of Nivolumab or Pembrolizumab in lung cancer patients. Our biomarker appears to be superior to PD-L1 labelling and TMB models.
Efficacy and hematologic toxicity of carboplatin and talazoparib combination therapy in BRCA mutated patients.
Authors: Mallika Sachdev Dhawan, Rahul Raj Aggarwal, Imke Bartelink, Jim Leng, Scott Thomas, Nela Pawlowska, Laurie Stevenson, Amy Jo Chien, Robin Kate Kelley, Julia Clennell, Pamela N. Munster
Journal: Journal of Clinical Oncology (2016)

2557 Background: Synergistic anti-tumor effects of PARPi and chemotherapy have been observed in preclinical models. This Phase 1 trial evaluates the tolerability, dose limiting toxicities (DLT) and efficacy of, the PARP inhibitor, talazoparib, in combination with carboplatin in patients with or without DNA repair mutations. We hypothesize that talazoparib may overcome carboplatin resistance but induce greater toxicity in patients with DNA repair defects. Methods: Talazoparib and carboplatin pharmacokinetics (PK), safety and anti-tumor activity were evaluated in a 3+3 dose escalation design. Genetic testing, PK, pharmacodynamic effects (PD), and alternate dose modeling were evaluated to better understand the interaction of carboplatin and talazoparib. Results: 24 patients were enrolled in 4 cohorts and treated with talazoparib 0.75 or 0.1 mg/day and carboplatin AUC 1 or 1.5 for 3/3 or 2/3 weeks. Tumor types included: breast, prostate, cholangiocarcinoma, ovarian, bladder and adenoid cystic carcinoma. DLTs were fatigue and thrombocytopenia; other grade 3/4 toxicities included fatigue (13%), neutropenia (33%), thrombocytopenia (33%), and anemia (58%). Post cycle 1 heme toxicities required dose delays/reductions in almost all patients. One complete response occurred in a germline BRCA1 (gBRCA1) breast cancer patient and two partial responses (PR) occurred in gBRCA2 patients (breast and bladder cancer); 11 patients (pts) had stable disease (SD) for ≥ 3 months, 5 pts are not yet evaluable. Thrombocytopenia (11.4% vs. 1.1% P < 0.001) and neutropenia (9.1% vs. 3.8% P < 0.001) were significantly more common in gBRCA carriers. PK modeling suggested that monthly carboplatin dosing in patients with DNA repair defects and every other week dosing in non-carriers may be more tolerable for PARPi and carboplatin combinations. Conclusions: Mutation carriers in BRCA or DNA repair genes responded better to the combination and responses were in prior progression on PARPi and carboplatin, but the combination caused increased heme toxicity in gBRCA or other DNA repair mutations. Less frequent carboplatin dosing may be required when given with PARPi in germ line mutation carriers. Clinical trial information: NCT02358200.
Emollients and topical glucocorticoids in adolescents with eczema
Authors: S. Lundin, C.F. Wahlgren, A. Bergström, E.K. Johansson, E. Dahlén, N. Andersson, I. Kull
Journal: British Journal of Dermatology (2018)

Eczema, also called atopic eczema, is a common skin disease among children. When you have eczema you usually have dry skin often with itchy rashes. The disease affects about 10‐30 % of all children worldwide. In Sweden, 20% of all children have had or have eczema before the age of 5 years. The disease is less common with age and affects 2‐10 % of all adults. Eczema should be treated with emollients (moisturisers) for the dry skin and cortisone cream on the itchy rash. The knowledge about adolescents with eczema is sparse. This study from Sweden, aimed to find out how adolescents with eczema treat themselves with emollient and cortisone cream, if boys and girls treat themselves differently, if the severity of eczema affects treatment behavior and how much cortisone cream they had dispensed from the pharmacy during the last year. The author used data from 16‐year‐old adolescents who answered questions about eczema and its treatment and who attended a clinical examination. The main finding shows that almost all adolescents used emollients, but only half used cortisone cream, and there were no differences between how boys and girls treated themselves. Symptoms of more severe eczema did not increase the likelihood of using cortisone. Only one out of four with moderate to very severe eczema had a potent cortisone cream dispensed from the pharmacy the preceding year. The authors therefore concluded that many adolescents with eczema are undertreated or completely untreated.
Phase III MAGIC trial of APF530 v ondansetron (Ond) with fosaprepitant (Fos) + dexamethasone (Dex) for highly emetogenic chemotherapy (HEC)-induced nausea and vomiting: analysis by age and gender.
Authors: Lee Steven Schwartzberg, Nashat Y. Gabrail, John S. Hrom, Nicholas J. Vogelzang, Michael Mosier, Robert B. Geller, Ian Schnadig
Journal: Journal of Clinical Oncology (2016)

e21700 Background: In a large (N = 902) phase III trial (MAGIC), APF530 (granisetron, extended release), showed superior complete response (CR; no emesis + no rescue medication use) in delayed ( > 24-120 h) chemotherapy-induced nausea and vomiting (CINV) with HEC v Ond (65% v 57%, P = .014), each with Fos + Dex (Schnadig et al. ASCO Breast 2015). MAGIC enrolled a high proportion of young and female patients (pts), a high-risk group for CINV. We performed an exploratory efficacy and safety analysis of APF530 on these subgroups. Methods: This double-blind, placebo-controlled multicenter trial (NCT02106494) randomized pts on single-day HEC 1:1 to APF530 500 mg SC (10 mg granisetron) or Ond 0.15 mg/kg IV ( ≤ 16 mg), stratified by cisplatin ( ≥ 50 mg/m2, yes/no). Pts had concomitant Dex 12 mg IV + Fos 150 mg IV d 1 + Dex 8 mg PO d 2, bid d 3-4. Primary end point was delayed-phase CR. Secondary end points were acute and overall CR, and safety. Adverse events (AEs) and injection-site reactions (ISRs) were assessed. Formal statistical analysis of the exploratory analysis was not done. Results: Pts were 731 female (APF530 358, Ond 373) and 171 male (APF530 92, Ond 79); 667 were < 65 y (APF530 333, Ond 334) and 235 were ≥ 65 y (APF530 117, Ond 118). Baseline characteristics were balanced between treatment arms. More pts in the APF530 v Ond arm had delayed CR in both subgroups, with CR differences favoring APF530: 8% for both male and female pts and 7% and 12% for pts < 65 and ≥ 65 y, respectively (Table). Older pts had significantly higher CR rates (P = .002). APF530 was well tolerated in each subgroup. The most common AEs were ISRs, mostly mild or moderate and no more common in pts ≥ 65 y (APF530 56.4%, Ond 50.0%) v < 65 y (APF530 63.7%, Ond 62.8%). Conclusions: Concordant with significant benefit in the overall population, younger and female subgroups benefit from APF530 v standard of care Ond regimen in HEC. Clinical trial information: NCT02106494.CR, n (%) APF530 Ond Delayed Gender M 64 (70) 49 (62) F 227 (63) 207 (55) Age < 65 203 (61) 182 (54) ≥ 65 88 (75) 74 (63) Acute Gender M 78 (85) 68 (86) F 259 (72) 262 (70) Age < 65 231 (69) 230 (69) ≥ 65 106 (91) 100 (85) Overall Gender M 60 (65) 47 (59) F 203 (57) 192 (51) Age < 65 177 (53) 165 (49) ≥ 65 86 (74) 74 (63)
P01.008 Feasibility of a structured tumor related epilepsy education intervention in adult gliomas
Authors: A Wasilewski, J Serventi, C Ibegbu, J Burke, T Wychowski, N Mohile
Journal: Neuro-Oncology (2018)

Tumor related epilepsy (TRE) occurs in over 50% of glioma patients and is the most common cause of emergency room visits and hospitalizations. TRE can lead to increased cost and health care utilization, higher distress and decreased quality of life. We designed a structured TRE-specific education intervention aimed at patients and caregivers. In this study, we sought to determine the feasibility of incorporating this into clinical practice while assessing distress and effect of the intervention on baseline TRE knowledge. We prospectively enrolled glioma patients (with or without TRE) and caregivers on an IRB approved study. Subjects underwent a pre-test to assess baseline knowledge regarding seizure management. A neuro-oncology provider guided patients and caregivers through a short presentation focused on home care and interventions in the event of an acute symptomatic seizure. Distress due to seizures was measured before and after the educational intervention using a distress thermometer. A post-test was also completed. At two and six months, distress was re-assessed and post-tests were repeated. Patient and caregiver satisfaction with the intervention was rated at the initial visit using Likert scales and with qualitative feedback. 52 subjects (24 patients, 28 caregivers) were enrolled. Median age was 59. TRE was present in 57% of patients. Patient tumors were glioblastoma (58.3%), anaplastic astrocytoma (25%) and anaplastic oligodendroglioma (16.7%). Median time to completion of distress assessments, pre-test, intervention and post-test was 21.5 minutes. Median baseline distress scores were 2/10 for patients and 5/10 for caregivers. Distress scores decreased by a mean of 1.5 points for all subjects between the initial and two-month follow-up visit. Median pre-test and post-test scores regarding TRE knowledge for all subjects were 7/9 and 9/9, respectively. All subjects considered the education understandable and stated they would recommend the intervention. 98% of subjects strongly agreed that the education was helpful and informative. Caregivers reported more distress despite better baseline seizure knowledge than patients and retained more knowledge at the two and six-month follow-up visits. A structured TRE education intervention is feasible in glioma patients and their caregivers. Our data suggests that it may be effective in reducing distress and improving awareness regarding seizure management. Structured TRE education should be considered in all glioma patients and caregivers. Further prospective studies are warranted to assess efficacy and the effect on acute care utilization, cost and distress.