tbuckley/cabot-search huggingface dataset:
Treatment-adherence beliefs and behaviors in patients with chronic myeloid leukemia (CML).
Authors: Joanne S. Buzaglo, Clare Karten, Melissa F Miller, Joseph A. Greer, Elisa S Weiss, Michael J. Mauro
Journal: Journal of Clinical Oncology (2015)

9558 Background: Tyrosine kinase inhibitors (TKIs) are effective yet chronic indefinite therapy for CML. Strong links exist between TKI adherence and optimal outcomes. Suboptimal adherence is common, affecting clinical outcomes and healthcare costs. Nonadherent patients underrecognize missed-dose impact on response. This study explored the link between belief and behavior vis-à-vis adherence. Methods: With outreach to online, national and community networks from 10/13 to 7/14, 484 CML patients enrolled in the Cancer Experience Registry: CML, an online project to advance CML knowledge and patient engagement. 393 (81%) completed a web-based survey including questions assessing accord with 2 statements (1) It is okay to miss a dose of my CML medicine every now and then, and (2) I need to take every dose of my CML medicine or it might not work; as well, participants reported missed TKI-dose frequency. Logistic regression was used to study the beliefs-behavior link among US patients taking TKIs (n = 318). Regression models were adjusted for age, gender, time since diagnosis, and TKI cost/month. Results: Responders averaged 56 y of age and 5.2 y from diagnosis; the majority was female (68%) and white (90%). 23% reported TKI spending of ≥ $100/month; 19% spent $50-100; 58% spent < $50. Regarding statement 1 and missed TKI dose, 5% strongly agreed, 28% agreed, 24% disagreed, 43% strongly disagreed. For statement 2, 6% strongly disagreed they needed to take every dose, 17% disagreed, 32% agreed, 45% strongly agreed. 19% reported missing a dose at least monthly. Compared to those who disagreed/strongly disagreed, those who agreed/strongly with statement 1 were significantly more likely to have reported missing doses monthly (OR = 7.04; 95% CI = 3.65, 13.57). Also, those who disagreed/strongly disagreed with statement 2 vs. those who agreed/strongly agreed were significantly more likely to have reported missing doses at least once monthly (OR = 5.36; 95% CI = 2.81, 10.2). Conclusions: CML patients’ medication beliefs were strongly associated with suboptimal adherence. The results suggest multifaceted patient education would impact adherence, outcome and survival. The relationship between beliefs and drug adherence merits further study.
Comparison of Antibiotic Therapy and Appendectomy for Acute Uncomplicated Appendicitis in Children
Authors: Libin Huang, Yuan Yin, Lie Yang, Cun Wang, Yuan Li, Zongguang Zhou
Journal: JAMA Pediatrics (2017)

<h3>Importance</h3> Antibiotic therapy for acute uncomplicated appendicitis is effective in adult patients, but its application in pediatric patients remains controversial. <h3>Objective</h3> To compare the safety and efficacy of antibiotic treatment vs appendectomy as the primary therapy for acute uncomplicated appendicitis in pediatric patients. <h3>Data Sources</h3> The PubMed, MEDLINE, EMBASE, and Cochrane Library databases and the Cochrane Controlled Trials Register for randomized clinical trials were searched through April 17, 2016. The search was limited to studies published in English. Search terms included<i>appendicitis</i>,<i>antibiotics</i>,<i>appendectomy</i>,<i>randomized controlled trial</i>,<i>controlled clinical trial</i>,<i>randomized</i>,<i>placebo</i>,<i>drug therapy</i>,<i>randomly</i>, and<i>trial</i>. <h3>Study Selection</h3> Randomized clinical trials and prospective clinical controlled trials comparing antibiotic therapy with appendectomy for acute uncomplicated appendicitis in pediatric patients (aged 5-18 years) were included in the meta-analysis. The outcomes included at least 2 of the following terms: success rate of antibiotic treatment and appendectomy, complications, readmissions, length of stay, total cost, and disability days. <h3>Data Extraction and Synthesis</h3> Data were independently extracted by 2 reviewers. The quality of the included studies was examined in accordance with the Cochrane guidelines and the Newcastle-Ottawa criteria. Data were pooled using a logistic fixed-effects model, and the subgroup pooled risk ratio with or without appendicolith was estimated. <h3>Main Outcomes and Measures</h3> The primary outcome was the success rate of treatment. The hypothesis was formulated before data collection. <h3>Results</h3> A total of 527 articles were screened. In 5 unique studies, 404 unique patients with uncomplicated appendicitis (aged 5-15 years) were enrolled. Nonoperative treatment was successful in 152 of 168 patients (90.5%), with a Mantel-Haenszel fixed-effects risk ratio of 8.92 (95% CI, 2.67-29.79; heterogeneity,<i>P</i> = .99;<i>I</i><sup>2</sup> = 0%). Subgroup analysis showed that the risk for treatment failure in patients with appendicolith increased, with a Mantel-Haenszel fixed-effects risk ratio of 10.43 (95% CI, 1.46-74.26; heterogeneity,<i>P</i> = .91;<i>I</i><sup>2</sup> = 0%). <h3>Conclusions and Relevance</h3> This meta-analysis shows that antibiotics as the initial treatment for pediatric patients with uncomplicated appendicitis may be feasible and effective without increasing the risk for complications. However, the failure rate, mainly caused by the presence of appendicolith, is higher than for appendectomy. Surgery is preferably suggested for uncomplicated appendicitis with appendicolith.
First-in-class, first-in-human phase I trial of KPT-330, a selective inhibitor of nuclear export (SINE) in patients (pts) with advanced solid tumors.
Authors: Albiruni R A Razak, Morten Mau Soerensen, Amit Mahipal, Sharon Shacham, Cindy Y. F. Yau, Ulrik Niels Lassen, Dilara McCauley, Jennifer Cooksey, David Shao Peng Tan, Jean-Richard Saint-Martin, Yossi Landesman, Gregory Pond, Amit M. Oza, Michael Kauffman, Lillian L. Siu, Mansoor Raza Mirza
Journal: Journal of Clinical Oncology (2013)

2505 Background: In cancers, the majority of tumor suppressor proteins (TSP) are transported out of the nucleus exclusively by Exportin 1 (XPO1/CRM1), rendering these TSPs non-functional. KPT-330 is a potent inhibitor of XPO1, and forces the nuclear retention and activation of &gt; 10 TSPs resulting in tumor cell death in vitro, in murine preclinical models and in dogs with spontaneous lymphomas. Methods: KPT-330 was administered orally for 10 doses in a 28-day cycle. Detailed pharmacokinetic (PK) and pharmacodynamic (PDn) analyses and serial tumor biopsies were performed. Response evaluation was done every 2 cycles (RECIST 1.1). All pts entering the study had documented progressive disease. Results: 23 pts (10 males; median age 62 yrs; ECOG PS 0/1: 5/18) received KPT-330 across 6 dose levels (3 to 30 mg/m 2 ). There has been no dose limiting toxicity. Nine drug related grade 3/4 adverse events (AEs) post cycle 1 were reported in 6 pts (neutropenia, thrombocytopenia, hyponatremia, increased ALT, fatigue, vomiting [n=2], nausea [n=2]). The most common grade 1/2 AEs were nausea (78%), fatigue (74%) and anorexia (74%). PK analysis demonstrated a fairly proportional increase in C max and AUC with increasing dose, with no accumulation and without affecting half-life or clearance of KPT-330. At 30 mg/m 2 , AUC 0-last. (4375 ng*h/mL) was comparable to the anti tumor exposure observed in mice and dogs. T max (~3 hrs) and T 1/2 (6-7 hrs) were consistent across doses. Significant increase (2-20x) in XPO1 mRNA levels (PDn marker) in circulating leukocytes was observed at all doses, with higher doses demonstrating higher levels of XPO1 mRNA induction. Analysis of tumor biopsies confirmed nuclear localization of TSPs (e.g. p53, FOXO3A, IκB) and apoptosis of cancer cells following KPT-330 administration. RECIST response was evaluable in 13 pts. Stable disease (SD) was noted in 9 pts, with 3 (colon, endocervical &amp; endometrial stromal tumors) remaining with SD at 6+ months (dose levels 3 &amp; 6 mg/m 2 ), as well as one minor response (colon). Conclusions: KPT-330 treatment is generally well tolerated, with favorable PK and PDn properties. Preliminary signals of clinical antitumor activity were observed. Clinical trial information: NCT01607905.
Does a community cancer center one-day prostate cancer multidisciplinary clinic result in a change in treatment recommendation?
Authors: Taylor Reid Cushman, Joseph W Mashni, Rachit Kumar
Journal: Journal of Clinical Oncology (2017)

82 Background: Multi-disciplinary clinics (MDCs) offer patients the opportunity to meet with multiple providers to discuss treatment options for recently diagnosed prostate cancer. Multiple academic centers have published their experience with these clinics. However, this approach has been sparsely reported in the community setting. Herein, we assess if an MDC results in more appropriate treatment recommendations for patients based on NCCN risk category compared to incoming (non-MDC) treatment recommendations. Methods: A retrospective chart review of patients evaluated in the institutional prostate cancer MDC clinic were reviewed over a 22 month period (January 2015 through October 2016). A single urologist and radiation oncologist served as clinic consultants for all patients. Patients were asked to report the recommendation for treatment prior to evaluation in the MDC clinic, and the patient selection for treatment after evaluation in the MDC clinic. Changes in treatment recommendation were recorded based on NCCN risk category (low [LR], intermediate [IR], and high [HR] risk groups). Results: Eighty patients were evaluated in the MDC. Of the 80 patients, 64 (80%) chose to continue care with the providers in the prostate MDC. Evaluable records (i.e. initial treatment recommendations) were available for 46 of the 64 patients (72%). Median age of the evaluable patients was 67 years (range 43-83). By risk category, 15 (33%) were LR, 21 (46%) were IR, and 10 (22%) were HR. Eleven patients in the LR group (73%) had altered treatment recommendations, 82% of whom were changed from any treatment (surgery or radiation) to active surveillance. Ten patients in the IR group (48%) and four patients in the HR group (40%) had altered treatment recommendations, mostly from surgery to radiation +/- ADT (50% in the IR, and 75% in the HR group). For all patients seen in the MDC, eight (10%) enrolled on a clinical trial (prostate stereotactic radiation). Conclusions: Implementation of a community-based, one-day prostate MDC resulted in significant changes in treatment recommendations, particularly in increasing active surveillance for LR patients and reducing surgical intervention in IR and HR patients.
International collaboration in personalized medicine for the treatment of advanced and drug-refractory cancers: Clinical application of human tumor primary culture analyses.
Authors: Fabricio Colacino Silva, Fernando C. Maluf, Antonio C. Buzaid, Robert Alan Nagourney, Nise Hitomi Yamaguchi, Paulo D'Amora, Steven Evans, Paula J Bernard, Federico Francisco
Journal: Journal of Clinical Oncology (2013)

e13562 Background: Personalized oncology has advanced through genomic and proteomic platforms. BCR-abl; EGFr and ALK have provided drug-able targets and companion diagnostics in several diseases, yet many transforming events in humans are polygenic, complex and incompletely understood at a genomic level. Recognition that oncogenesis reflects changes in the cell and its micro environment has renewed interest in whole cell experimental models that capture native-state cell-cell, -stroma and -vascular signaling. Ex vivo analysis of programmed cell death (EVA/PCD) has been shown to correlate significantly with response, time to progression and survival (Nagourney, R. Curr. Treat Op Oncol, 2006).To explore EVA/PCD functional profiling in Brazil, hospital-based investigators, Centro de Genomas and Rational Therapeutics coordinated the transport of 67 surgical specimens for analyses. Methods: Dose-response curves using metabolic (ATP-content, mitochondrial) and morphologic endpoints, interpolated to LC50's and synergy by median-effect, were compared with databases to identify patient-specific profiles for cytotoxics, targeted agents and combinations. Reports provided day 7. Results: 62/67 (92%) provided adequate tumor for analysis; 39 male (58%); 28 (42%) female; 6 chemo-naive and 61 previously treated. Results provided for &lt; 8 drugs in 14/62 (22%); 8-16 drugs in 34/62 (54%) and &gt; 16 drugs in 14/62 (22%). Of 22 tumor types, breast (8); Melanoma (8); NSCLC (8); ovary (7); pancreas (7) and sarcoma (4) predominated. EVA/PCD was used to select the most active combinations. Agents selected, response rates and durations are being tabulated and will be reported. Conclusions: The transport, processing and reporting of human tumor primary culture analyses is feasible, providing results in 92% of specimens and median of 12 drugs evaluated (range 4-32). Preliminary outcomes in these drug-refractory patients reveal that novel, often unexpected drug combinations (Everolimus and Lapatinib in triple negative breast) were identified and provided objective tumor responses, supporting EVA/PCD in therapy selection (personalized therapy) and drug development.
Annexin A1 and HPV in oropharyngeal squamous cell carcinoma.
Authors: Cleberson Jean dos Santos Queiroz, Cintia Mara de Amorim Gomes Nakata, Amilcar Sabino Damazo
Journal: Journal of Clinical Oncology (2013)

e22150 Background: Annexin-A1 (ANXA1) is a protein involved in signal transduction and inflammation. Its expression is increased in some tumors (i.e. hepatocellular carcinomas, gliomas, pancreatic adenocarcinomas), but in head and neck tumors, its expression is usually reduced. Tumor suppressor p53 is frequently expressed in cancers due to mutation. HPV infection is strongly linked to oropharyngeal tumors. Methods: We analyzed 21 formalin-fixed paraffin-embedded samples of oropharyngeal carcinoma. Using immunofluorescence (IF), ANXA1 expression was quantified by measuring mean optical density (MOD). We also evaluated p53 positivity using IF. Presence of HPV DNA (serotypes 16/18 and 31/33) was analyzed through chromogenic in situ hybridization. Interaction between ANXA1, p53 and HPV was performed by Student's t test and ANOVA, with Bonferroni test, using the software Graph Pad Prism. Results: HPV DNA was found in 12 of 21 cases (57%). Serotypes 16/18 were found in all HPV + samples, whereas serotypes 31/33 were found in 2 of the 12. Among HPV+ cases, we noticed a decreased expression of ANXA1 in tumor compared to epithelium, independent of p53 status. With respect to HPV- cases, we have found a reduced expression of ANXA1 in the tumor versus epithelium, but the difference was only statistically significant in p53+ samples. In epithelia, we observed an increased expression of ANXA1 in HPV+ compared with HPV- samples. Conclusions: Our results confirm a decreased expression of ANXA1 in oropharyngeal carcinoma independently of HPV status, suggesting its involvement in the carcinogenesis. There was no difference in the expression of ANXA1 according to p53 status. In normal epithelia, we observed an increased expression of ANXA1 in HPV+ samples, which may suggest the involvement of the protein in the early stages of HPV-driven carcinogenesis. [Table: see text]
Tumor regression as a continuous variable and survival in advanced non-small cell lung cancer (NSCLC).
Authors: David J. Stewart, Charles Lu, Pierre Saintigny, Glenwood D. Goss
Journal: Journal of Clinical Oncology (2014)

8114 Background: Tumor response is generally reported categorically by RECIST criteria as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD). SD includes patients with minor tumor growth (1-19% increase in tumor diameter) and minor tumor regression (1-29% decrease in tumor diameter). Recent publications indicate that change in tumor size correlates linearly with survival in phase I studies (R Jain et al. J Clin Oncol 30:2684, 2012) and that change in tumor size as a continuous variable might be a useful endpoint in phase II trials (T Karrison et al. JNCI 99:1455, 2007). Methods: We used serial tumor measurements from 130 patients receiving platinum-based therapy for advanced NSCLC to further assess the correlation of change in tumor size with overall survival and time to progression (TTP). Results: Median survival was 10.6 months (range, 1-60 months) for the 125 patients who had died and median follow-up was 54 months (range, 45-57 months) for the 5 who remained alive. Median TTP was 4.2 months (range, 0.5-54 months). 32 patients had tumor growth by first follow-up scan (median 19% increase in tumor diameter, range 1%-49%). For the 98 with tumor regression, maximum regression over the course of therapy was 1-76% (median 27%). Maximum tumor regression correlated with overall survival (Spearman r = 0.46, p<0.0001) and with TTP (r = 0.69, p<0.0001). (For these correlations, % tumor growth at first follow-up scan was coded as “negative tumor regression”.) Median overall survival was 15 months in patients with any tumor regression at first follow-up scan vs 5.9 months with any growth (p<0.0001), and for patients with RECIST confirmed PR (23% of patients), minor tumor regression (52% of patients), minor tumor growth (13% of patients) and PD (13% of patients) was 16.9, 13.6, 9.8 and 4.0 months, respectively (P<0.0001). Conclusions: Change in tumor size as a continuous variable correlated strongly with both overall survival and TTP in patients with advanced NSCLC receiving platinum-based therapy. Within the SD RECIST category, patients with minor tumor regression do better than patients with minor growth. Response as a continuous variable (% change in tumor size) warrants further assessment.
Activity of insulin growth factor-receptor (IGF-1R) antibody cixutumumab combined with the mTOR inhibitor temsirolimus in patients with metastatic refractory adrenocortical carcinoma.
Authors: Aung Naing, Patricia LoRusso, Siqing Fu, David S. Hong, Helen Chen, L. Austin Doyle, Alexandria Phan, Mouhammed Amir Habra, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2012)

4639 Background: Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancywithout an available effective systemic chemotherapy. IGF-R2 overexpression leading to the activation of the IGF1R/mTOR pathway is well described in ACC. Cixutumumab, a fully human IgG1 monoclonal antibody directed at insulin growth factor-1 receptor (IGF-1R), was combined with temsirolimus on the basis of preclinical data. Methods: Patientsreceived cixutumumab, 3-6 mg/kg IV weekly, and temsirolimus, 25 mg-37.5 mg IV weekly (4-week cycles), with restaging after 8 weeks. Results: Twenty-six patients were enrolled (13 [50%] men); median age, 47 years; median number of prior therapies, 4. Five patients previously received an IGF-1R inhibitor and one, temsirolimus. The most frequent toxicities, at least possibly drug-related, were grade 1-2 thrombocytopenia (38%), mucositis (58%), hypercholesterolemia (31%), hypertriglyceridemia (35%), and hyperglycemia (31%). Eleven of 26 patients (42%) achieved stable disease (SD) &gt; 6 months (duration range = 6 to 21 months) with 3 of the 11 having received a prior IGF-1R inhibitor. Conclusions: Cixutumumab combined with temsirolimus was well tolerated and more than 40% of patients achieved prolonged SD. This study was supported by R21CA13763301A1 (AN), U01CA62461 (RK), and U01CA62487 (PL).
Optimal debulking surgery in patients with advanced uterine carcinosarcoma: A multi-institutional retrospective study from the Japanese Gynecologic Oncology Group.
Authors: Kenichi Harano, Akihiro Hirakawa, Mayu Yunokawa, Toshiaki Nakamura, Toyomi Satoh, Tadaaki Nishikawa, Daisuke Aoki, Kimihiko Ito, Kiyoshi Ito, Toru Nakanishi, Nobuyuki Susumu, Kazuhiro Takehara, Yoh Watanabe, Hidemichi Watari, Toshiaki Saito
Journal: Journal of Clinical Oncology (2015)

5591 Background: The benefit of cytoreductive surgery for uterine carcinosarcoma (CS) is unknown. The objective of this study was to assess the impact of optimal debulking surgery on survival of advanced uterine CS patients. Methods: We performed a multi-institutional, retrospective study of women diagnosed with stage III–IV uterine CS between 2007 and 2012. Data were retrospectively obtained from medical records and included demographic, clinicopathologic, treatment, and outcome information. Optimal debulking surgery was defined as surgery resulting in a maximum residual tumor of less than 1 cm. The Kaplan-Meier method was used to calculate disease-free survival (DFS) and overall survival (OS), and the Cox regression model was used to examine the impact of selected factors on survival. Results: A total of 225 uterine CS patients (median age, 62 years) were identified including 136 (60%) patients with stage III disease and 89 (40%) patients with stage IV disease. Among them, 185 (82%) patients received the optimal debulking surgery. The median follow-up time was 19 months. The median DFS and OS for the entire cohort were 10.9 months (95% confidence interval [CI], 9.5−12.5) and 29.0 months (95% CI, 21.6−36.2), respectively. The median DFS was 11.5 months (95% CI, 10.6−13.4) for patients who received optimal debulking surgery and 8.1 months (95% CI, 5.1−9.5) for patients who received suboptimal surgery (P < 0.0001). The median OS was 37.9 months (95% CI, 28.3−not reached) for patients who received optimal debulking surgery and 18 months (95% CI, 9.6−21) for patients who received suboptimal surgery (P < 0.0001). In the multivariate analysis, optimal debulking surgery and pelvic lymph node dissection were associated with improved OS. Conclusions: Optimal debulking surgery and pelvic lymph node dissection are associated with improved OS in patients with advanced uterine CS.
Operant learning and selectionism: Risks and benefits of seeking interdisciplinary parallels
Authors: Richard W. Malott
Journal: Behavioral and Brain Sciences (2001)

Seeking parallels among disciplines can have both risks and benefits. Finding parallels may be a vacuous exercise in categorization, generating no new insights. And pointing to analogous functions may cause us to treat them as homologous. Hull et al. have provided a basis for the generation of insights in different selectionist areas, without confusing analogy with homology.