tbuckley/cabot-search huggingface dataset:
Development of the medical appointment planner.
Authors: Margaret Clayton, Lee Ellington, Kathi Mooney
Journal: Journal of Clinical Oncology (2017)

86 Background: Breast cancer survivors experience multiple physical and emotional symptoms. Difficulties occur when women cannot effectively present questions and concerns during surveillance visits resulting in unmet needs and unanswered questions. Methods: The Medical Appointment Planner (MAP) is a structured visit preparation approach providing communication skills to facilitate presentation of a woman’s symptoms/concerns to medical providers. MAP was developed sequentially in 4 phases: Phase 1) Focus groups explored women’s issues during surveillance visits. Phase 2) Feasibility pilot, using paper-pencil delivery. Phase 3) IPad feasibility, usability / satisfaction pilot. Phase 4) National trial pilot with Susan Love’s Army of Women comparing electronic MAP delivery to a usual care group developing question lists. Results: Focus Groups. A major theme was “difficult interactions with medical providers” especially presenting concerns. Paper-Pencil Feasibility. Eight women (age 30-79) used MAP for medical visit preparation; the average number of symptoms endorsed was 17 out of a possible 21. All women successfully used MAP to prepare for their upcoming medical visit. MAP was determined to be feasible with women asking for electronic delivery for ease of use. IPad Prototype: 26 women (age 40-80); Outcomes of symptoms, mood, uncertainty, and well-being, improved pre to post-visit. National pilot: 49 women (age 50-77); 21 in the MAP intervention group, 28 in the usual care group preparing questions pre-visit. No differences between groups in age or breast cancer stage were observed. After first use, women report MAP is helpful, and providers have reacted favorably to visit preparation with feasible electronic national delivery. The question list group also reports ease of program use. Conclusions: Across MAP pilot studies women report that MAP helps organize thinking, condense thoughts, and stay “on track”. Improving current practice that recommends preparing question lists before medical appointments; the structured MAP visit preparation approach teaches communication skills to facilitate presentation of symptoms and concerns to providers, enabling women to break into the medical “script” and get their symptoms/concerns addressed.
Soluble oligomeric amyloid-β induces calcium dyshomeostasis that precedes synapse loss in the living mouse brain
Authors: Michal Arbel-Ornath, Eloise Hudry, Josiah R. Boivin, Tadafumi Hashimoto, Shuko Takeda, Kishore V. Kuchibhotla, Steven Hou, Carli R. Lattarulo, Arianna M. Belcher, Naomi Shakerdge, Pariss B. Trujillo, Alona Muzikansky, Rebecca A. Betensky, Bradley T. Hyman, Brian J. Bacskai
Journal: Molecular Neurodegeneration (2017)

Amyloid-β oligomers (oAβ) are thought to mediate neurotoxicity in Alzheimer's disease (AD), and previous studies in AD transgenic mice suggest that calcium dysregulation may contribute to these pathological effects. Even though AD mouse models remain a valuable resource to investigate amyloid neurotoxicity, the concomitant presence of soluble Aβ species, fibrillar Aβ, and fragments of amyloid precursor protein (APP) complicate the interpretation of the phenotypes. To explore the specific contribution of soluble oligomeric Aβ (oAβ) to calcium dyshomeostasis and synaptic morphological changes, we acutely exposed the healthy mouse brain, at 3 to 6 months of age, to naturally occurring soluble oligomers and investigated their effect on calcium levels using in vivo multiphoton imaging. We observed a dramatic increase in the levels of neuronal resting calcium, which was dependent upon extracellular calcium influx and activation of NMDA receptors. Ryanodine receptors, previously implicated in AD models, did not appear to be primarily involved using this experimental setting. We used the high resolution cortical volumes acquired in-vivo to measure the effect on synaptic densities and observed that, while spine density remained stable within the first hour of oAβ exposure, a significant decrease in the number of dendritic spines was observed 24 h post treatment, despite restoration of intraneuronal calcium levels at this time point. These observations demonstrate a specific effect of oAβ on NMDA-mediated calcium influx, which triggers synaptic collapse in vivo. Moreover, this work leverages a method to quantitatively measure calcium concentration at the level of neuronal processes, cell bodies and single synaptic elements repeatedly and thus can be applicable to testing putative drugs and/or other intervention methodologies.
Brentuximab-induced peripheral neuropathy: Risk factors and patient experiences.
Authors: Sarah Nagle, Lauren E. Strelec, Alison W. Loren, Daniel Jeffrey Landsburg, Sunita Nasta, Anthony R. Mato, Stephen J. Schuster, Jakub Svoboda
Journal: Journal of Clinical Oncology (2017)

120 Background: Brentuximab vedotin (BV) is an immunoconjugate used in Hodgkin lymphoma (HL) and other CD30+ lymphomas. The dose-limiting adverse effect is peripheral neuropathy (BIPN). Predictors of BIPN, effect on outcomes, and the biopsychosocial impact are not well defined. Methods: We conducted a single institution, mixed-methods study of lymphoma patients (pts) who received BV between 1/2010 and 5/2016. A retrospective analysis was conducted in all pts; an open-ended survey was given to pts seen in the prior year. A univariate analysis examined the association between BIPN and potential predictors. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan Meier method. Survey data were analyzed qualitatively via a framework approach. Results: Eighty-nine pts were eligible: 56% were male, 54% had HL, 71% had prior neurotoxic drugs, 93% received single agent BV. The median number of BV doses was 5. Forty-three (48%) pts developed BIPN. It resolved completely in 14 (33%) pts at a median follow-up of 12 mo. The median time to resolution was 13 wks. BV therapy was altered in 21 (24%) pts due to BIPN. There was no difference in PFS (6 vs. 12 mo., p = 0.09) or OS (NR vs. 26 mo., p = 0.11) in pts who had therapy altered due to BIPN. Table 1 lists significant risk factors for BIPN. No additional factors investigated (age, sex, prior neurotoxic agent, underlying neuropathy, diabetes mellitus or BMI) increased risk for BIPN. Fourteen of the 18 (78%) surveyed pts reported BIPN. At a median follow-up of 24 mo., 10 (71%) pts reported ongoing symptoms. BIPN affected quality of life in 50% and work in 20% of pts. Despite significant symptoms from BIPN, all pts were satisfied with their decision to receive BV regardless of disease response. Conclusions: BIPN is a significant adverse event and may fail to resolve in a large subset of pts. Surveyed pts reported that the benefits of BV outweigh the risks. Changes in therapy due to BIPN occur, but this did not affect outcomes in our cohort. Clinicians should be aware of the risk for BIPN and educate pts accordingly. [Table: see text]
Fabrication of Synthetic Mesenchymal Stem Cells for the Treatment of Acute Myocardial Infarction in Mice
Authors: Lan Luo, Junnan Tang, Kodai Nishi, Chen Yan, Phuong-Uyen Dinh, Jhon Cores, Takashi Kudo, Jinying Zhang, Tao-Sheng Li, Ke Cheng
Journal: Circulation Research (2017)

Rationale: Stem cell therapy faces several challenges. It is difficult to grow, preserve, and transport stem cells before they are administered to the patient. Synthetic analogs for stem cells represent a new approach to overcome these hurdles and hold the potential to revolutionize regenerative medicine. Objective: We aim to fabricate synthetic analogs of stem cells and test their therapeutic potential for treatment of acute myocardial infarction in mice. Methods and Results: We packaged secreted factors from human bone marrow–derived mesenchymal stem cells (MSC) into poly(lactic-co-glycolic acid) microparticles and then coated them with MSC membranes. We named these therapeutic particles synthetic MSC (or synMSC). synMSC exhibited a factor release profile and surface antigens similar to those of genuine MSC. synMSC promoted cardiomyocyte functions and displayed cryopreservation and lyophilization stability in vitro and in vivo. In a mouse model of acute myocardial infarction, direct injection of synMSC promoted angiogenesis and mitigated left ventricle remodeling. Conclusions: We successfully fabricated a synMSC therapeutic particle and demonstrated its regenerative potential in mice with acute myocardial infarction. The synMSC strategy may provide novel insight into tissue engineering for treating multiple diseases.
A phase II study to examine the effectiveness of nutritional support with elemental diet for stage II/III gastric cancer patients receiving adjuvant chemotherapy with S-1 (OGSG 1108).
Authors: Junji Kawada, Hiroshi Imamura, Jin Matsuyama, Junichi Fukui, Kazuhiro Nishikawa, Tomono Kawase, Toshio Shimokawa, Yukinori Kurokawa, Taroh Satoh, Hiroshi Furukawa
Journal: Journal of Clinical Oncology (2017)

98 Background: Postoperative weight loss after gastrectomy causes deterioration in patient’s quality of life and tolerance for adjuvant chemotherapy in gastric cancer patients. Nutritional support may prevent postoperative weight loss and chemotherapy related adverse effects to improve compliance of adjuvant chemotherapy. Methods: Clinical stage II/III gastric cancer patients received R0 resection were registered in the first stage of the present study. Those patients were qualified and enrolled in the second stage who could intake more than 60% of elemental diet (Elental, 300 kcal/day for 14 days) in the postoperative period and were proven pathological stage II/III. Enrolled patients were planned to receive a total of 300 kcal/day of Elental for 24 weeks and additional courses was permitted up to 365 days. The primary endpoint was compliance of S-1: percent of patients who accomplish S-1 adjuvant for one year with more than 70% relative performance (RP). The secondary endpoints were nutritional parameters (body weight, BMI, s-albumin, s-protein, s-cholesterol), RP of 8 courses of S-1, adverse effects of S-1, RP of Elental and ratio of patients who were enrolled to the second stage. Results: From January 2012 to September 2014, 149 patients were registered in the first stage and 82 patients were enrolled in the second stage: including 50 men; 32 women; median age of 70 years (range, 42-85 years); and performance status were zero in 45 and one in 37 patients. Compliances of S-1 were 60.5% (95%CI: 49.0, 71.2) in 81 eligible patients and 69% (95%CI: 56.9, 79.5) in eligible patients without recurrence. In 81 eligible patients, RP of 8 courses of S-1 was 87.3 % (95%CI: 88.3, 85.9), and the body weight loss was 1.80kg (95%CI: -0.38, 4.48). Grade 3-4 toxicities were neutropenia 12%, anemia 4%, anorexia 4% and diarrhea 4%. Conclusions: Nutritional support for gastric cancer patients receiving adjuvant chemotherapy contributes to increase compliance of S-1 and potential effect on survival may be expected. Clinical trial information: UMIN000006872.
Comparative effectiveness of laparoscopy versus open colectomy among nonmetastatic colon cancer patients: An analysis using the National Cancer Data Base.
Authors: Zhiyuan Zheng, Ahmedin Jemal, Chun Chieh Lin, George J. Chang
Journal: Journal of Clinical Oncology (2014)

3627 Background: Laparoscopy (LAC) has gained wide acceptance as a curative treatment for non-metastatic colon cancer after the publications of several major clinical trials in the last decade. However, there is limited data regarding the comparative effectiveness of LAC vs. open colectomy (OC) in routine clinical practice. The objective of the study is to compare short-term surgical outcomes between LAC and OC using a national hospital-based cancer registry dataset. Methods: The National Cancer Data Base was used to identify stage I-III colon cancer patients aged 18-84 between 2010 and 2011. An intent-to-treat analysis was conducted where converted cases were included in the LAC group. A propensity score matching (PS) method was used to create comparable LAC and OC groups. Patients were clustered at the hospital-level for multilevel regression analysis to investigate the associations between various clinical, demographic, and contextual variables (i.e. surgeon/hospital volume measurements, insurance types, and facility types) and short-term surgical outcomes (i.e. 30-day mortality, 30-day readmission, and length of hospital stay). Sensitivity analyses were conducted to examine the robustness of our findings by excluding converted colectomies (LAC completed only vs. OC), and including patients aged 85 and above at the time of diagnoses. Results: A total of 45,876 patients undergoing colectomy were included, 18,717 (41%) LAC and 27,159 (59%) OC. After PS, all variables were balanced and there were 18,189 patients in each of LAC and OC groups. Compared to OC, LAC showed consistent benefits in the 30-day mortality rate (OR = 0.51, 95%CI: 0.43---0.60, p < 0.001) and length of hospital stay (IRR = 0.82, 95%CI: 0.80---0.83, p < 0.001), but not the 30-day readmission rate (OR =0.93, 95%CI: 0.84---1.03, p = 0.136). These findings were not affected by either exclusion of converted cases nor inclusion of patients aged 85 and above. Conclusions: Compared to open colectomy, laparoscopic colectomy has lower 30 day mortality and shorter length of hospital stay in routine clinical practice.
Feasibility of an electronic implementation method of an evidence-based exercise intervention among testicular cancer survivors (TCS).
Authors: Chunkit Fung, Jennifer Peckham, Michelle Porto, Po-Ju Lin, Deepak M. Sahasrabudhe, Elizabeth A. Guancial, Bonnie Ky, Eugene Storozynsky, Michelle Christine Janelsins, Charles E. Heckler, Lauren B. Bruckner, Supriya Gupta Mohile, Karen Michelle Mustian
Journal: Journal of Clinical Oncology (2017)

161 Background: Cardiovascular (CV) disease results in significant morbidity among TCS. The effects of exercise on mitigating these late effects remain unknown in this population. Exercise for Cancer Patients (EXCAP) is a self-directed, individually tailored intervention that has been shown to improve CV fitness in cancer patients. We conducted a randomized phase II feasibility study of a novel electronic implementation method (mHealth) of EXCAP. Methods: We developed mHealth-EXCAP that integrates data from a wearable digital activity tracker (DAT) into a patient’s electronic medical record (EMR), allowing providers to monitor and adjust EXCAP prescriptions via a patient-centered virtual portal. We randomized TCS ( &lt; 69 yr at diagnosis, any treatments, not in active or maintenance stage of exercise behavior) into 3 study arms: Arm 1 (mHealth-EXCAP), Arm 2 (EXCAP) and Arm 3 (usual care). Both Arm 1 and 2 completed a 12 week EXCAP program with the goal of 12,000 daily steps and daily resistance exercises and Arm 1 has integration of mHealth. Arm 3 received a TCS care plan that encourages exercises. Results: 52 TCS were screened (23 ineligible; 12 declined), 17 consented and 13 (80.9%) completed study (3 withdrew; 1 lost to follow up) as of May 31, 2016. Median age (yr) was 34 (Arm 1; n = 6), 52 (Arm 2; n = 3), and 48 (Arm 3; n = 4). In Arm 1, 83% TCS wore DAT and synced daily step data to EMR &gt; 90% of days. Further, EXCAP prescriptions were adjusted via EMR portal on average 5 times over 12 weeks for each TCS and their weekly daily step goals were met 73% of the time. The number of daily steps recorded by DAT and those synced from DAT to EMR differed by a mean of 1.5% steps (±1.8). Median baseline number of daily steps were 5,432 (Arm 1), 6,737 (Arm 2), and 5,875 (Arm 3) and increased by 6,161, 1,742, and 1,921 respective steps, with only Arm 1 (50% TCS) achieving &gt; 12,000 daily steps at study completion. On average, TCS in Arm 1 and 2 performed resistance exercises 15 minutes a day/2 times a week and 34 minutes a day/3 times a week, respectively. Conclusions: mHealth-EXCAP is feasible to implement among TCS and may decrease sedentary behavior. Ongoing research will examine its effects on CV risk factors and cardiopulmonary function.
Diamond project: Immunohistochemical screening using EGFR mutation-specific antibodies in lung adenocarcinomas.
Authors: Corrado Boni, Maria Pagano, Ione Tamagnini, Alessandra Bisagni, Licia Baldi, Moira Ragazzi, Giorgio Gardini, Fausto Barbieri, Flavia Cantile, Francesca Zanelli, Davide Nicoli, Rossi Giulio
Journal: Journal of Clinical Oncology (2014)

e19035 Background: Identification in lung adenocarcinomas (LACs) of epidermal growth factor receptor (EGFR) mutations is the single most important predictor of clinical response and outcome using EGFR tyrosine kinase inhibitors (TKI). We evaluated the accuracy of EGFR mutation-specific antibodies in LACs and showing different molecular settings and detected on cytology and histologic samples. Methods: 111 LACs diagnosed on cytology (21 cell blocks), biopsy (58 cases) and surgical resections (32 cases) were selected for the study. All cases were previously investigated by Sanger sequencing and/or pyrosequencing (EGFR exons 18 to 21; KRAS exon 2) and ALK status by Immunohistochemistry (IHC)/FISH. IHC using EGFR mutation-specific antibodies (clone 6B6 for delE746-A750 and clone 43B2 for L858R; Cell Signalling Technologies, Danvers, MA) were tested using an automated immunostainer (Benchmark, Ventana Inc, Tucson, AZ). Cases were quoted as positive when at least 2+ staining was present in at least 5% of tumor cells. Results: Conventional molecular analyses showed EGFR mutations in 52 cases (47%), KRAS mutations in 44 cases (40%), ALK positivity in 5 cases (4%) and triple negative setup in 10 cases. Of note, there were 19 and 25 tumors harboring L858R and delE746-A750, respectively, while 4 cases had uncommon mutations in exon 19 (2 delS752-I759, 1 delL747-P753insS, 1 delL747-T751 plus exox 18 G719A), 2 cases harbor L861Q in exon 21, 2 T790M in exon 20, G719G and G719A in exon 18. At IHC, overall sensitivity was 76.5% and specificity was 98.3%. The sensitivity and specificity of antibodies for exon 19 was 68% and 100%, respectively; for exon 21 were 91% and 99%, respectively. Sensitivity and specificity in non-EGFR mutated tumors was absolute (100%). No significant difference in sensitivity and specificity was observed when results were statistically matched with different types of samples. Conclusions: The EGFR mutation-specific antibodies have a high specificity and fair-to-high sensitivity in identifying LACs with classic EGFR mutations, while they do not recognized uncommon EGFR mutations, but no cross-reaction with tumors harboring different molecular settings was evidenced.
Predictors for survival with cabazitaxel (CBZ) in metastatic, castration-resistant prostate cancer (mCRPC): Long term follow-up of the Spanish registry.
Authors: Iria González-Maeso, Nuria Lainez, Daniel Castellano, Iciar Garcia Carbonero, Pablo Borrega, Begona Campos Balea, Rosa Garcia Marrero, Emilio Esteban, Alejo Rodriguez Vida, Javier Munarriz, Jose Maria Garcia-Bueno, Maria L. Villalobos, Ruth Viciana, Gustavo Rubio, Begoña Perez-Valderrama, Jose Garcia Sanchez, Beatriz Pelaez Lorenzo, Jose David Cumplido Buron, Almudena Martin, Joaquim Bellmunt
Journal: Journal of Clinical Oncology (2017)

e602 Background: The clinical experience with CBZ in mCRPC patients (pts) has enriched notably since its approval for clinical use, but there is still a lack of well-defined prognostic/predictive factors to better characterize the profile of pts that could achieve the best therapeutic benefit. Analysis of the final expanded cohort and mature long-term follow-up are presented. Methods: Medical records from mCRPC pts progressing during or after docetaxel and treated with CBZ at 21 centres in Spain were reviewed retrospectively. Baseline characteristics, overall survival (OS), radiographic progression-free survival (rPFS), and toxicity were collected. Univariate and multivariate analysis of a variety of factors predicting OS were conducted. Results: 187 consecutive pts (median age 69) with intermediate-poor prognostic baseline characteristics (Table 1) received a median of 6 cycles (range 2-59) of CBZ. Median OS from first CBZ cycle was 15.3 [CI: 11.7; 18.0] months (mo) and median clinical and/or rPFS was 7.9 mo [CI: 6.8; 10.3]. Gleason score (GS) &lt; 8 (vs ≥ 8), time under first-line androgen deprivation therapy (ADT) ( &gt; 16.1 (median) vs &lt; 16.1 mo) and the number of chemotherapy lines before CBZ did not significantly influence OS. Median follow-up was 9.5 mo. Febrile neutropenia occurred in 4 pts and 1 pt had neutropenic infection. Main nonhematologic grade ≥ 3 toxicities were asthenia (2.7%) and diarrhea (1.6%). Alopecia, nails disorders and peripheral neuropathy were uncommon. Conclusions: CBZ administered in the daily clinical practice is associated with consistent OS, similar to that observed in pivotal clinical trials. GS, median time under first-line ADT and number of chemotherapy lines before CBZ did not influence clinical benefit. CBZ has an acceptable safety profile. Funding: Sanofi [Table: see text]
Final results for gemcitabine with nab-paclitaxel in neoadjuvant treatment of resectable pancreatic adenocarcinoma: GAIN-1 study.
Authors: Sarunas Sliesoraitis, Neelam Vijay Desai, Jose Gilberto Trevino, Steven J. Hughes, Robert Zlotecki, Judith L. Lightsey, Alison Marguerite Ivey, Carmen Joseph Allegra, Long H. Dang, Karen Colleen Daily, Kevin Behrns, Chen Liu, Shailendra Chauhan, Amy L. Collinsworth, Xiaomin Lu, Thomas J. George
Journal: Journal of Clinical Oncology (2014)

e15201 Background: Survival after pancreatic adenocarcinoma (PCa) resection is only 20% despite adjuvant therapy. Neoadjuvant treatment (NAT) is cost effective, may improve R0 resection rates and may improve overall survival through earlier systemic therapy. Methods: Pts in this prospective pII study were assigned to low-risk (Grp 1) or high-risk/borderline-resectable (Grp 2) groups (as published by NCCN consensus). Cycles consisted of G 1,000mg/m2 and A 100mg/m2 on D1, 8, 15 q28d. Grp 1 = 3 cycles of G+A followed by resection. Grp 2 = 2 cycles of G+A followed by 2 weeks of IMRT (50.4Gy in 10 fx) concurrent with G 400mg/m2weekly followed by resection. Historic controls (non-NAT) were matched for age, sex, race, smoking, tumor site, and tumor size without NAT. Primary endpoints were R0 resection rate, biochemical, pathologic and radiologic RR. Secondary endpoints were PFS, OS, (30d) post-op mortality, toxicity, QOL and translational analyses. Clinicaltrials.gov NCT01470417. Results: 32 pts were enrolled, 10 NAT and 22 matched non-NAT controls (Table). 6 NAT and 17 non-NAT pts had R0 resections. 2 NAT pts had R1 resection and 2 others had medical inoperability or progressed with liver mets. Only BMI was different b/w the two groups. All NAT cases had CA 19-9 reductions (mean baseline 343 vs. pre-op 184 U/mL;p=0.198) and treatment effect. 5 pts (50%) had g3 AEs, 1 g4 (10%;VTE) and no g5. Most common g3 AEs included LFT elevation (40%) and neutropenia (20%). No 30d post-op mortality noted with NAT. 4 NAT pts remain disease free at 438 (mean) days of follow-up. No differences noted in mean survival between NAT and non-NAT. Conclusions: NAT with G+A is well tolerated with a significant number completing R0 resection. Correlative studies including DPC4 and SPARC expression are ongoing. Further randomized studies are warranted to investigate G+A NAT efficacy. Clinical trial information: NCT01470417. NAT (n=10) Non-NAT (n=22) p-value Age 68 (55-78) 67.1 (64-70) 0.52 BMI 26.3 (22.17-30.43) 23.79 (21.9-25.67) 0.011 Tumor location Head n=6; Uncinate n=3; Body/tail n=1 Head n=19; Uncinate n=3 n/a Risk group Low (Grp 1) n=3; High (Grp 2) n=7 n/a n/a R0 resection 6 (60%) 17 (77%) 0.68 Mean survival 506d (95% CI 357-656) 647d (95% CI 448-846) 0.89