tbuckley/cabot-search huggingface dataset:
Improving documentation of surrogate decision makers in medical oncology clinic.
Authors: Melisa L. Wong, Hala Borno, Reena Mahajan, Kara E. Bischoff, Brook Calton, Emily K. Bergsland, Won Kim, Rahul Raj Aggarwal, Katy K. Tsai, Pelin Cinar
Journal: Journal of Clinical Oncology (2017)

63 Background: Advance care planning (ACP) is an important component of high quality care for cancer patients. A measurable and early step in the ACP process is for patients to identify a surrogate decision maker and document this information in the medical record. Methods: To improve documentation of surrogate decision makers for stage IV cancer patients, we designed a hematology/oncology fellow-led multidisciplinary quality improvement (QI) initiative including: 1) ACP education for fellows, 2) ACP patient education materials and online resources, and 3) standardized note templates for surrogate documentation. We aimed to document surrogate decision makers or discussions for &gt; 50% of stage IV cancer outpatients evaluated by a fellow cumulatively over the 2016-2017 academic year. Patients seen for second opinion visits were excluded. Audit and feedback of individual fellow and group results were conducted twice a month. During each audit period, we randomly selected 2 medical oncology clinic sessions per outpatient fellow and reviewed all new patient and follow-up notes for surrogate decision maker documentation. Results: Prior to implementation, baseline surrogate decision maker documentation by fellows was 2% (1 out of 55 stage IV cancer patients seen during 2 randomly selected clinic sessions per outpatient fellow from January to March 2016). Since implementation in July 2016, 20 fellows have participated during outpatient rotations. During randomly selected clinic sessions from July to October 2016, 156 eligible stage IV cancer patients were evaluated by fellows. Surrogate decision makers or discussions were documented for 64 patients (41%). Overall, fellows felt comfortable discussing surrogate decision making with patients but often forgot to address it during the visit. Conclusions: Our fellow-led QI initiative improved surrogate decision maker documentation for stage IV cancer patients from 2% to 41%. A centralized ACP navigator (which includes a surrogate decision maker section) was recently added to our electronic medical record. As part of the ongoing efforts to achieve our cumulative goal, we will leverage this new feature to engage clinic staff in documentation of surrogate decision making as well.
Regulatory Review of New Therapeutic Agents — FDA versus EMA, 2011–2015
Authors: Nicholas S Downing, Audrey D Zhang, Joseph S Ross
Journal: New England Journal of Medicine (2017)

Between 2011 and 2015, the Food and Drug Administration (FDA) approved 170 new therapeutic agents, and the European Medicines Agency (EMA) approved 144. The times for those regulatory reviews were, on average, 60 days shorter at the FDA than at the EMA.
Expression profiling of ovarian epithelial cancers with intratumoral T cells identifies genes mediating the host immune response: Implications for survival
Authors: T. Bonome, R. Buckanovich, M. Birrer, G. Coukos
Journal: Journal of Clinical Oncology (2004)

5011 Background: The presence of intratumoral T cells has been demonstrated to be a predictor of increased progression free and overall survival in primary ovarian tumors (Zhang et al. N ENGL J MED 348;3 203–213). Understanding the molecular mechanisms underlying the biology of these tumors may help identify the critical pathway(s) facilitating the host immune response in ovarian cancer. Methods: From 174 primary ovary tumors, a subset of 57 samples with confirmed RNA integrity were randomly selected (35 T cell + / 22 T cell -) and underwent tyramide signal amplification detection on spotted cDNA microarrays (11,000 features). A total of 63 genes with ≥ 2 fold difference in expression were identified using a two group t-test with separate variance (P < .01). The gene list was independently corroborated with a Prediction Analysis of Microarray analysis (P < .01). For validation, quantitative real-time polymerase chain reaction (Q-RT-PCR) was performed on 5 genes identified in the final list. Results: Twelve of 48 genes identified as up-regulated in T cell infiltrated tumors are involved in host immune system response. HLA genes encoding the variable regions of major histocompatibility complexes I and II, as well as beta-2-microglobulin, were elevated in + T cell samples. In addition, complement genes C1r and C3 were up-regulated. Additional genes of interest were also identified in the analysis. Q-RT-PCR results confirmed the microarray expression data. Conclusions: Detection of immune related genes in + T cell samples substantiates the initial observation of a host immune response mounted against altered-self tumor cells. Furthermore, this study suggests a critical role for complement effector genes in the anti-tumor immune response not only as potential T cell chemoattractants, but as direct mediators of tumor cell killing. Besides implicating principal effectors in the cell mediated and innate branches of the immune system, this study has identified genes which may restrict tumor cell proliferation or enhance the host immune response. No significant financial relationships to disclose.
Survey of community pharmacists regarding their role and desire for managing chemotherapy related toxicities in cancer patients.
Authors: Kathy Vu, Daniella Santaera, Erin Redwood, Monika K. Krzyzanowska
Journal: Journal of Clinical Oncology (2017)

104 Background: There is little published about the readiness and needs of community pharmacists to manage chemotherapy related toxicities in cancer patients. A survey was conducted to understand community pharmacists’ current toxicity management practices and their education and communication needs in this area. Methods: A 21 question electronic survey was sent to community pharmacists in Ontario, Canada from April 1 – June 30, 2016. The survey asked about demographics, toxicity management behaviours/preferences, communication and training needs/preferences. Results: Out of 559 responses received, 167 were excluded due to ineligibility giving a final response of 392 surveys. The majority of respondents were full time pharmacists practicing for more than 10 years in community pharmacy. While many pharmacists reported providing assessment (80%), advice (92%) and/or monitoring (70%) at least sometimes, few reported providing assessment (10%), monitoring (10%) or advice (18%) routinely. Types of toxicities encountered and their frequency are summarized in Table 1. There was a high level of interest (96%) among the respondents in being involved in assessing and managing chemotherapy toxicity, however, only 13% reported that they felt sufficiently trained to do so. Conclusions: Community pharmacists encounter chemotherapy-related toxicities in their daily work. While there is a strong interest in managing toxicity symptoms, many community pharmacists feel that they are not adequately trained to do so. Continuing education programs for this provider group may improve toxicity management in community pharmacy settings. [Table: see text]
A retrospective analysis to evaluate adjuvant chemotherapy after radical surgery on survival and disease recurrence in patients with stage I, II, IIIA non-small cell lung cancer (NSCLC)
Authors: M. Gamaz, S. Ameur, H. Chaouche, K. Bouzid
Journal: Journal of Clinical Oncology (2004)

7360 Background: Adjuvant chemotherapy has become a standard treatment in patients (pts) with NSCLC who have had carcinologic resection (Le Chevalier, ASCO 2003, abstr 6). The aim of this retrospective study was to analyze the outcome, in terms of survival and disease recurrence, of pts with NSCLC who received adjuvant chemotherapy after radical surgery. Methods: Inclusion criteria: histologically proven NSCLC stage I-IIIA treated with carcinologic surgery, PS ≤1, and adequate hematologic, hepatic, and renal function. Twenty-eight (28) pts (all males) were reviewed. Results: Data were pooled and analyzed for 28 male pts with a median age of 54.4 years (range, 47–71 years). Stage IB, IIB, and IIIA disease was noted in 7, 5, and 16 pts, respectively. Histologic types were adenocarcinoma (n=11) and squamous cell carcinoma (n=17). Pts underwent the following surgical procedures: lobectomy (n=10), bilobectomy (n=3), and pneumonectomy (n=15). The median duration between the surgery and the onset of adjuvant chemotherapy was six weeks (range, 3–7 weeks). Adjuvant chemotherapy consisted of four cycles of cisplatin (75 mg/m2 d1) combined with vinblastine (6 mg/m2 d1) in 2 pts, vindesine (4 mg/m2 d1) in 5 pts, etoposide (150 mg/m2 d1) in 7 pts, and gemcitabine (1250 mg/m2 over 30 min d1,8) in 14 pts. Eleven pts (with p N1 disease) received locoregional radiotherapy six weeks after the fourth cycle of chemotherapy. After a median follow-up time of 28 months (range, 12–44 months), the median survival was 18 months (range, 6–43+ months). The median free survival time was 16 months (range, 3–40+ months). The one-year recurrence rate was 16% while the second- and third-year rates were 5% each. The three-year survival rate was 22%. Conclusions: The results of this retrospective analysis confirm the importance of adjuvant chemotherapy in NSCLC after carcinologic resection. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Centre Pierre et Marie Curie; Hopital Centre Pierre et Marie Centre Pierre et Marie Curie
Can visible signs predict concussion diagnosis in the National Hockey League?
Authors: Ruben J Echemendia, Jared M Bruce, Willem Meeuwisse, Michael G Hutchison, Paul Comper, Mark Aubry
Journal: British Journal of Sports Medicine (2017)

Early identification and evaluation of concussions is critical. We examined the utility of using visible signs (VS) of concussion in predicting subsequent diagnosis of concussion in NHL players.VS of concussion were identified through video review. Coders were trained to detect and record specific visual signs while viewing videos of NHL regular season games. 2460 games were reviewed by at least two independent coders across two seasons. The reliability, sensitivity and specificity of these VS were examined.VS were reliably coded with inter-rater agreement rates ranging from 73% to 98.9%. 1215 VS were identified in 861 events that occurred in 735 games. 47% of diagnosed concussions were associated with a VS but 53% of diagnosed concussions had no VS. Of the VS, only loss of consciousness, motor incoordination, and blank/vacant look had positive likelihood ratios greater than 1, indicating a positive association with concussion diagnoses. Slow to get up and clutching of the head were observed frequently but had low positive predictive values. Sensitivity decreased and specificity increased when multiple VS occurred together.Non-medical personnel can be trained to reliably identify events in which VS occur and to reliably identify specific VS within each of those events. VS can be useful to detect concussion early but they are not enough since more than half of physician diagnosed concussions occurred without the presence of a visual sign. The results underscore the complexity of this injury and highlight the need for comprehensive approaches to injury detection.
Antagonism of B cell enhancer networks by STAT5 drives leukemia and poor patient survival
Authors: Casey D S Katerndahl, Lynn M Heltemes-Harris, Mark J L Willette, Christine M Henzler, Seth Frietze, Rendong Yang, Hilde Schjerven, Kevin A T Silverstein, Laura B Ramsey, Gregory Hubbard, Andrew D Wells, Roland P Kuiper, Blanca Scheijen, Frank N van Leeuwen, Markus Müschen, Steven M Kornblau, Michael A Farrar
Journal: Nature Immunology (2017)
Antagonism of profibrotic microRNA-21 improves outcome of murine chronic renal allograft dysfunction
Authors: Celina Schauerte, Anika Hübner, Song Rong, Shijun Wang, Nelli Shushakova, Michael Mengel, Angela Dettling, Claudia Bang, Kristian Scherf, Malte Koelling, Anette Melk, Hermann Haller, Thomas Thum, Johan M. Lorenzen
Journal: Kidney International (2017)
Different efficacy of Mycophenolate mofetil as salvage treatment for acute and chronic GVHD after allogeneic stem cell transplant
Authors: J. H. Baek, J. G. Kim, S. K. Sohn, D. H. Kim, K. B. Lee
Journal: Journal of Clinical Oncology (2004)

6631 Background: The therapeutic options currently available for treating refractory graft-versus-host disease (GVHD) are limited. Therefore, the present study evaluated the efficacy of mycophenolate mofetil (MMF) as a salvage treatment for acute and chronic GVHD in allograft patients. Methods: Twenty-six consecutive patients with refractory acute (13 patients) or chronic (13 patients) GVHD were enrolled. The first-line treatment for all patients with acute GVHD consisted of a combination of Cyclosporine A (CyA) and steroids, while the first-line treatment for chronic GVHD was steroids with or without CyA according to the risk group. MMF was added at a dose of 1.5g or 2g daily and the steroids were tapered in the refractory cases. Results: Four (30.8%) out of 13 patients with refractory acute GVHD responded to MMF. When analyzing the overall results according to the type of acute GVHD, improvement was observed in 4/13 skin cases (30.8%), 4/9 liver cases (44.4%), and 2/9 gut cases (22.9%). Ten (76.9%) out of 13 patients with refractory chronic GVHD responded to MMF. The common side effects were gastrointestinal disturbance (26.9%) or infectious complications (23.1%). The estimated 2-year survival rate for patients with acute GVHD and chronic GVHD was 33.3% and 53.9%, respectively. Conclusions: MMF would appear to be effective and safe for treating refractory chronic GVHD, yet not as effective for treating refractory acute gut GVHD. Accordingly, a prospective, randomized clinical trial is warranted to assess the impact of MMF in the treatment of refractory GVHD. No significant financial relationships to disclose.
Comorbidity, chemotherapy toxicity, and outcomes among older women receiving adjuvant chemotherapy for breast cancer (BC).
Authors: Heidi D. Klepin, Brandy Pitcher, Karla V. Ballman, Gretchen Genevieve Kimmick, Alice B. Kornblith, Harvey Jay Cohen, Arti Hurria, Eric P. Winer, Clifford Hudis, Hyman Bernard Muss
Journal: Journal of Clinical Oncology (2012)

6015 Background: Comorbidity increases with age. We evaluated how comorbidity was associated with toxicity and clinical outcomes among older women with BC who received adjuvant chemotherapy. Methods: Cancer and Leukemia Group B (CALGB 49907) enrolled 633 women ≥65 years with early stage BC and randomized them to standard adjuvant chemotherapy (AC or CMF) or capecitabine (N Eng J Med 360:2055, 2009). 329 women on the Quality of Life companion study completed a pre-treatment health survey (Older American Resources and Services Questionnaire, physical health subscale). The survey evaluates 14 conditions and the degree to which each interferes with daily activities (rated from 1 “not at all” to 3 “a great deal”). Comorbidity was analyzed as follows: 1) total number 2) comorbidity burden score (summed conditions multiplied by interference rating); and 3) individual diseases. Primary outcomes were: 1) grade 3-5 toxicity (incident and cumulative); 2) time to relapse (TTR), and 3) overall survival (OS). Contingency table methods were used to evaluate the association between comorbidity and toxicity. Cox proportional hazards models were used to evaluate TTR and survival outcomes. Results: Among 329 women [median age 71 years (range 65-89), 86% white, 98% ECOG performance score 0-1, 75% stage 1-2] the median number of comorbidities was 2 (0-10), median comorbidity burden score was 3 (0-25), and most common conditions were arthritis (58%) and hypertension (54%). Few patients had diabetes (17%), heart disease (16%), and pulmonary disease (9%). No comorbidity measure was associated with toxicity or TTR. With a median follow-up of 5.4 years, increasing comorbidity was associated with shorter OS. For each additional comorbid condition the hazard of death increased by 18% (HR 1.18 [95% CI; 1.06-1.33]) after adjusting for age, tumor size, treatment, node status and receptor status. Comorbidity burden score was similarly associated with OS (HR 1.08 [95% CI; 1.03-1.14]), while no specific condition was independently associated. Conclusions: Among older women with good functional status, comorbidity was not associated with toxicity or BC relapse. However, comorbidity burden was associated with shorter OS.
A phase I study of the dual kinase inhibitor GW572016 in combination with paclitaxel (EGF10009)
Authors: S. F. Jones, J. D. Hainsworth, D. R. Spigel, N. W. Peacock, N. T. Willcutt, L. N. Pandite, M. J. Versola, K. M. Koch, F. Greco, H. A. Burris
Journal: Journal of Clinical Oncology (2004)

2083 Background: GW572016 is an orally active dual EFGR/ErbB2 kinase inhibitor that has demonstrated superior in-vitro antitumor activity in combination with the taxanes when compared to either agent alone. Methods: Escalating doses of paclitaxel (135–225mg/m2) were administered q 3 weeks in combination with continuous dosing of GW572016 (1250–1500mg/day). Three patients (pts) were treated at each dose level, with expansion to 6 in the event of dose-limiting toxicity. Limited pharmacokinetic samples were obtained to determine any correlation between peak concentrations and treatment-related toxicities. Once the optimally tolerated regimen was determined, 18 additional pts were to be enrolled to establish the pharmacokinetic profiles of GW572016 and paclitaxel when given alone and in combination. Patients were allowed to continue GW572016 alone after the maximum benefit was obtained with paclitaxel. Results: Twenty-six pts (13M/13F; median age 56, range 38–77 years; median Karnofsky PS 90%) were enrolled at 6 dose levels. Dose-limiting gr 3 diarrhea was reported in 1/4 pts treated with paclitaxel 225mg/m2+ GW572016 1500mg/d. Due to the cumulative neuropathy of multiple paclitaxel doses ≥ 200 mg/m2, the optimally tolerated regimen was determined to be paclitaxel 175 mg/m2 q 3 weeks + GW572016 1500mg/d. Gr 1–2 diarrhea, neuropathy, arthralgia/myalgia, rash, and fatigue are the common non-hematologic toxicities. Gr 4 neutropenia (5 pts), gr 3 diarrhea (2 pts), gr 3 neuropathy (1pt) and gr 3 arthralgia/myalgia (1pt) have been reported, but no clear relationship exists between peak plasma drug concentration and toxicity in the samples analyzed to date. Three objective responses have been observed in pts with taxane-resistant metastatic breast cancer. Seven pts have experienced stable disease for ≥ 3 months (range 3–13+ months): colon (4pts), breast (1pt), esophageal (1pt) and NSCLC (1pt). Conclusions: Paclitaxel/GW572016 can safely be given in combination at known effective single-agent doses. A phase III trial comparing paclitaxel 175mg/m2q 3 weeks + GW572016 1500mg/d to single agent paclitaxel in women with metastatic breast cancer is planned. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline Bristol-Myers Squibb; GlaxoSmithKline GlaxoSmithKline Bristol-Myers Squibb; Genentech GlaxoSmithKline
The relationships between patient volume per oncologist, social worker presence, and capacity to provide psychosocial care.
Authors: Louise Bedard, Gabrielle Steinl, Jamie Lindsay, Jennifer Yanchula, Chandler McLeod, Stacie Myers, Jennifer J. Griggs
Journal: Journal of Clinical Oncology (2017)

156 Background: The purpose of this study was to investigate the relationships between new patient volume per oncologist, the availability of a social worker, and the capacity to provide psychosocial care. Methods: Community practices within Michigan Oncology Quality Consortium (MOQC), a statewide quality collaborative, completed NCI’s 10-item Cancer Psychosocial Care Matrix (CPCM). The CPCM speaks to communication, assessment, coordination, training, and outcomes and quality, each on a separate Likert scale. Analyses describe the ability to meet psychosocial care and the availability of a social worker, new patients/full time oncologist, payer mix, and percent minorities. Results: To date,15 of 47 practices (32%) completed the CPCM. We report on 4 measures with sizeable variation between practices. Scores were the highest on the ability to communicate the importance of psychosocial care and implementing a plan (scale of 1 – 3; mean of 2.36, standard deviation, SD 0.72; mean of 1.79, SD 0.89). The lowest scores were related to linking patients with services and offering provider education (scale of 1 – 5: mean of 2.18, SD 1.08; mean of 2.20, SD 0.94). Linear regression showed an association with number of patients/oncologist and the ability to provide staff training of effective patient/provider communication and monitoring this activity’s impact. For every 100-person increase in the number of patients/oncologist, there was a -0.16 (p = 0.046) rating difference in staff training and a -0.25 (p = 0.006) rating difference to monitor the communication’s effect. A dedicated social worker was present in 3 practices. Regression analysis showed a relationship between a social worker and recognizing (p=0.02) and addressing psychosocial care (p&lt;0.001). There was wide variation in payer mix and percent minorities but no association between the dependent variables and these characteristics. Conclusions: Community practices with a larger volume of new patients/oncologist/year are less likely to provide staff training and monitoring on psychosocial communication. In this sample, payer mix and racial composition are not associated with a practice’s ability to deliver psychosocial care.
Development and validation of an immuno-PET tracer for patient stratification and therapy monitoring of antibody-drug conjugate therapy.
Authors: Ohad Ilovich, Arutselvan Natarajan, Ataya Sathirachinda, Richard Kimura, Ananth Srinivasan, Mathias Gebauer, Jochen Kruip, Chantal Carrez, Ingrid Sassoon, Veronique Blanc, Susanta K. Sarkar, Sanjiv Sam Gambhir
Journal: Journal of Clinical Oncology (2013)

11006 Background: SAR566658 is an antibody-drug immunoconjugate consisting of a humanized monoclonal antibody (huDS6) against the tumor-associated MUC1-sialoglycotope, CA6, conjugated to a cytotoxic maytansinoid (DM4). SAR566658 is currently undergoing phase I clinical trials in patients with CA6-positive solid tumors. A companion diagnostic based on huDS6 may facilitate patient stratification and early evaluation of therapeutic efficacy. The present study describes the development and preclinical evaluation of three novel Copper-64 (t ½ = 12.7h) labeled antibody fragments (two Fabs and a diabody) derived from the huDS6 antibody. One fragment was chosen based on imaging figures of merit for further specificity evaluations. Methods: The affinity of all fragments and their DOTA conjugates to CA6 was validated using flow cytometry. The DOTA conjugates were labeled with Copper-64 and evaluated in human serum stability studies, in vivo small animal PET imaging and 24-hour biodistribution studies in nude mice bearing either CA6 positive (WISH) or CA6 negative (A2780) subcutaneous tumors. The specificity of the lead tracer was evaluated in vivo via blocking studies and isotype controls. Results: All fragments and their DOTA conjugates had high affinity (K d = 4-20 nM) for WISH cells. 64 Cu-DOTA-B-Fab gave superior results in radio-synthesis (RCY - 60%, SA - 55 GBq/µmole, &gt;99% purity), serum stability (94±5%, n=3) and biodistribution profile. Its two isotype controls gave statistically significant (P&lt;0.05) uptake values in WISH but not A2780 tumors (see table). Blocking with B-Fab or huDS6 prior to tracer administration afforded a 23% (p&lt;0.05, n=8) and 26% (p&lt;0.05, n=7) decrease in WISH tumor uptake, respectively. Conclusions: These preclinical studies suggest that 64 Cu-DOTA-B-Fab may be a suitable companion diagnostic for SAR566658 in cancer patients and requires further investigation.[Table: see text]