tbuckley/cabot-search huggingface dataset:
Phase I study of temsirolimus in combination with cetuximab in patients with advanced solid tumors.
Authors: Antoine Hollebecque, Rastislav Bahleda, Jean Christophe Thery, Laura Faivre, Marie-Cécile Le Deley, Angelo Paci, Andrea Varga, Anas Gazzah, Christophe Massard, Vianney Poinsignon, Katty Malekzadeh, Vincent Ribrag, ERIC ANGEVIN, Sophie Postel-Vinay, Carlos Alberto Gomez-Roca, Myriam Gharib, Fabienne Dufour, Jean-Charles Soria, Jean-Philippe Spano
Journal: Journal of Clinical Oncology (2015)

2599 Background: Preclinical studies suggest that temsirolimus (T), an inhibitor of mammalian target of rapamycin (mTOR) combined with cetuximab (C), an anti-EGFR monoclonal antibody, may have synergistic antitumor effects. Methods: A dose escalation study was conducted to define the MTD and to characterize the pharmacokinetics and safety profile of T (30 min infusion) given 1 hour later after C (1 hour infusion) on a weekly schedule of a 28-day cycle. Five dose-levels were evaluated with dose range of T from 15 to 25 mg weekly and C from 150 to 250 mg/m2weekly. Sequential biopsies were mandatory during the expansion cohort. Results: 39 patients (15M/24F), median age 57 years (range 38-76), previous number of lines 3 (range: 2-15) received the combination of T + C. The most common tumor types were colorectal (N = 6), breast (N = 5), uterine cervix SCC (N = 4) and NSCLC (N = 4). Three patients experienced dose limiting toxicities: grade 3 pulmonary embolism (at C 200 + T 20 level), grade 3 stomatitis (at C 250 + T 20 level) and grade 3 acneiform rash (at C 250 + T 25 level). The C 250 mg/m2and T 25mg/week dose level was selected as the recommended dose. The most common treatment-related adverse events were (All grade/grade 3-4): rash acneiform (97%/15%), mucositis oral (82%/23%), fatigue (59%/13%), nausea (41%/0%) diarrhea (36%/0%), hypomagnesaemia (79%/5%), , and hyperglycemia (66%/10%). The median progression-free survival and overall survival were respectively 2.0 months 95%CI [1.8-3.5] and 7.5 months 95%CI [5.5-11.9]. Among all patients partial responses (PR) and stable diseases were observed in 2 (5.1%) and 18 pts (46.2%). Fifteen pts (38.5%) were treated because of a molecular aberration involving the EGFR and/or PIK3 pathways. Among molecularly selected patients (N = 16), 2 PR (12.5%) were observed (cervix scc with an EGFR amplification and head and neck cancer with a PIK3CA amplification) and 7 pts (44%) had a PFS upper 5.5 months. Conclusions: Tolerance of T + C was acceptable. Clinical activity was modest among all patients. Molecular selection increased the objective response rate. Pre and post-exposure biopsies are available in 20 patients and are currently been analyzed for pathway modulation and DNA structural changes. Clinical trial information: NCT02215720.
Cellular Prion Protein PrPC and Ecto-5′-Nucleotidase Are Markers of the Cellular Stress Response to Aneuploidy
Authors: Patrícia H. Domingues, Lalitha S.Y. Nanduri, Katarzyna Seget, Sharavan V. Venkateswaran, David Agorku, Cristina Viganó, Conrad von Schubert, Erich A. Nigg, Charles Swanton, Rocío Sotillo, Andreas Bosio, Zuzana Storchová, Olaf Hardt
Journal: Cancer Research (2017)

Abstract Aneuploidy is a hallmark of most human tumors, but the molecular physiology of aneuploid cells is not well characterized. In this study, we screened cell surface biomarkers of approximately 300 proteins by multiparameter flow cytometry using multiple aneuploid model systems such as cell lines, patient samples, and mouse models. Several new biomarkers were identified with altered expression in aneuploid cells, including overexpression of the cellular prion protein CD230/PrPC and the immunosuppressive cell surface enzyme ecto-5′-nucleotidase CD73. Functional analyses associated these alterations with increased cellular stress. An increased number of CD73+ cells was observed in confluent cultures in aneuploid cells relative to their diploid counterparts. An elevated expression in CD230/PrPC was observed in serum-deprived cells in association with increased generation of reactive oxygen species. Overall, our work identified biomarkers of aneuploid karyotypes, which suggest insights into the underlying molecular physiology of aneuploid cells. Cancer Res; 77(11); 2914–26. ©2017 AACR.
Interleukin 3- receptor targeted exosomes inhibit <i>in vitro</i> and <i>in vivo</i> Chronic Myelogenous Leukemia cell growth
Authors: Daniele Bellavia, Stefania Raimondo, Giovanna Calabrese, Stefano Forte, Marta Cristaldi, Agostina Patinella, Lorenzo Memeo, Mauro Manno, Samuele Raccosta, Patrizia Diana, Girolamo Cirrincione, Gianluca Giavaresi, Francesca Monteleone, Simona Fontana, Giacomo De Leo, Riccardo Alessandro
Journal: Theranostics (2017)

Despite Imatinib (IM), a selective inhibitor of Bcr-Abl, having led to improved prognosis in Chronic Myeloid Leukemia (CML) patients, acquired resistance and long-term adverse effects is still being encountered.There is, therefore, urgent need to develop alternative strategies to overcome drug resistance.According to the molecules expressed on their surface, exosomes can target specific cells.Exosomes can also be loaded with a variety of molecules, thereby acting as a vehicle for the delivery of therapeutic agents.In this study, we engineered HEK293T cells to express the exosomal protein Lamp2b, fused to a fragment of Interleukin 3 (IL3).The IL3 receptor (IL3-R) is overexpressed in CML blasts compared to normal hematopoietic cells and thus is able to act as a receptor target in a cancer drug delivery system.Here we show that IL3L exosomes, loaded with Imatinib or with BCR-ABL siRNA, are able to target CML cells and inhibit in vitro and in vivo cancer cell growth.
Prognostic value of Ki67LI in HER2-negative luminal (HNL) early breast cancer (EBC): A 14-year single institution experience with long follow-up.
Authors: Antonella Ferro, Lucianna Russo, Claudio Eccher, Alessia Caldara, Renza Triolo, Mattia Barbareschi, Lucia Veronica Cuorvo, MariaChiara DiPasquale, Marco Pellegrini, Daniela Bernardi, Chiara Cantaloni, Francesca Maines, Enzo Galligioni
Journal: Journal of Clinical Oncology (2013)

e11569 Background: Several studies have emphasized the biologic and prognostic value of Ki67LI and its role in routine practice, particularly to define prognostic subgroups of luminal tumors. Methods: Ki67LI was identified by immunohistochemical staining in 3760 consecutive EBC pts followed from 1995 to 2008. Median age was 61 y. The relationship with clinic-pathological parameters and the prognostic significance of KI67LI were investigated in all EBCs and in 2380 HER2 negative luminal (HNL) cases, stratified on homogeneous grading (594 G1, 1282 G2, 504 G3). Results: Median Ki67LI values were 22% in all cases, 20% in HNL and 10%, 20% and 35% in HNL- G1,G2,G3 respectively. Ki67LI &gt; 22% (1873 pts) was significantly (p&lt;0.001) associated with younger age, ductal type, greater size, positive N, poor G, absent or low ER /PR, positive HER-2, triple negative subtypes. Local and Distant Relapses were 138 (7.3%) and 355 (18.9%) in &lt; or &gt; 22% Ki67LI respectively. Median time to first event was 31.7 ms in &gt; 22% vs 50.1 ms in &lt; 22% Ki67. At a median f-up of 77 months EFS and OS were 91.9 and 92.1% in &lt; 22% vs 78.9% and 81% in &gt; 22% Ki67 respectively (p &lt;0.001). The prognosis was consistently worse for &gt; 22% Ki 67 in all clinical-pathological subsets, except in negative ER group. In multivariate analysis, KI67 maintained an independent prognostic significance for DFS and OS. In HNL, EFS and OS were 93.7 and 92% in &lt; 20% vs 81.7 and 83.3% in &gt;20% Ki67(p &lt;0.001). Using median ki67LI value for different homogenous HNL-GG as cutoffs, we stratified these populations in low and high risk. Results are summarized in the Table. Conclusions: Our study confirms the prognostic value of Ki67LI in EBC,as well as other clinical pathological characteristics such as age, tumor size, histological type, nodal and hormonal receptors status. Cutoffs are different into HNL.They could identify different biological entities in each grading group providing additional prognostic information in outcome prediction. [Table: see text]
Identifying latent factors in the Living With Cancer (LWC) patient-reported outcomes (PRO) tool for patients with advanced malignancies.
Authors: Dhakshila Paramanathan, Raya Khoury, Mikele Bunce, Sharmi Narendra Patel, Srikesh Arunajadai, Victoria DeVincenzo, Sukhi Kaur, Ruth Pe Benito, Stuart L. Goldberg, Kelly Choi
Journal: Journal of Clinical Oncology (2017)

150 Background: End-of-Life Care (EOLC) discussions are frequently delayed past the time of usefulness, resulting in cancer patients (pts) receiving aggressive, expensive, non-desired care. The “Living with Cancer” project has developed a 7-item, 5-level Likert scale PRO tool that evaluates, from the pt perspective, their concerns regarding performance status, pain, family/financial burden, and depression during their cancer journey. The instrument was shown to correlate well with the oncologist’s opinion of appropriateness to continue treatment and might be useful as a quality metric in guiding timing of EOLC discussions (J Palliative Med 2016). Methods: The LWC PRO was administered to 1302 pts with advanced malignancies receiving care by Regional Cancer Care Associates (NJ) between Sept 2015 and Aug 2016, with confirmation of life status in Sept 2016. Exploratory factor analysis was conducted on the LWC instrument to identify latent constructs (factors) contributing to the item scores. The data set was deemed suitable for factor analysis based on standard statistical tests, including Bartlett’s test (p &lt; 0.001). Results: A 3-factor model comprised of factors (1) Global functioning (using 5/7 items), (2) Financial toxicity (1/7 items), and (3) Depression (1/7 items) was fitted to the data using maximum likelihood and promax rotation (p = 0.043). Factor scores were compared between the cohort of 133 pts who expired within 3 months of completing their final survey and the 1124 who remained alive after 3 months. The mean global functioning score was significantly greater (worse) in the expired cohort (p &lt; 0.001), suggesting the PRO description of distress correlated with survival. Financial toxicity and depression factor scores did not correlate with survival. Conclusions: The 7-item LWC PRO instrument contains 5 items defined by a global functioning factor that discriminates based on 3-month overall survival. This finding adds further evidence that the 7-item PRO tool can be used to time EOLC discussions with the aim to ensure better correlation between pts’ treatment desires and delivered care. LWC may also serve as a quality metric evaluating timing of EOLC discussions.
A retrospective analysis of the quality of care in patients with advanced malignancies who received nivolumab at an upstate NY tertiary referral center.
Authors: Adam Zayac, Aarati Poudel, Sheila M. Lemke
Journal: Journal of Clinical Oncology (2017)

233 Background: Immune checkpoint inhibitors, such as nivolumab, have rapidly gained in popularity and use since their development and subsequent FDA approval. With an ever burgeoning list of indications for its use, we evaluated its use within our tertiary care center as well as its impact on our healthcare system to investigate the quality of care these patients received as well as the extent of the benefit that they received from this novel therapy. Methods: Charts were collected of patients at SUNY Upstate Cancer Center who were started on treatment with Nivolumab between March 4, 2015 and June 1, 2016. This returned a total of 88 (eighty-eight) patients who underwent chart review process for this IRB-exempt retrospective study. Patients who were lost to follow-up or received their oncology care outside of the Upstate Regional Cancer Center were excluded from the final analysis, leaving 83 (eighty-three) patients on whom the final analyses were performed. Statistical analyses were performed using Microsoft Excel and Apple Numbers. Results: Nivolumab was predominantly used as second or third line therapy (45% and 34%) respectively; while it was used as first line therapy in 4% of patients. Performance status was only documented in 53% of patients within two weeks of Nivolumab initiation. Fifty-eight percent of our patients were admitted to the hospital after Nivolumab initiation. Only 50% of those patients received a palliative care consultation. Twenty-six percent of our patients were admitted with an adverse effect to Nivolumab. Nearly 25% of our patients had multiple hospitalizations. Nivolumab was discontinued in 67% of our patients after an average of eight cycles. Conclusions: Nivolumab has been a relatively well tolerated novel treatment for a multitude of malignancies. However, constant re-evaluation of patients for appropriateness of treatment is needed. It is unclear how much quality of life these patients are gaining, as many patients had to discontinue therapy and had numerous hospitalizations. Palliative care remains an important intervention in this patient population that is under-utilized.
Mesoporous hydroxyapatite as a carrier of olanzapine for long-acting antidepression treatment in rats with induced depression
Authors: Yan-Jye Shyong, Mao-Hsien Wang, Li-Wei Kuo, Chang-Fu Su, Wei-Ting Kuo, Kuo-Chi Chang, Feng-Huei Lin
Journal: Journal of Controlled Release (2017)
Evaluating the efficacy of an advanced practice provider symptom management telephone triage program in reducing ED visits and “avoidable” admissions of oncology patients.
Authors: Jorge Hirigoyen, Leonard A. Kalman, Jill Szymanski, Carmen Lazo, Christopher Espinosa, Amy Malespin
Journal: Journal of Clinical Oncology (2017)

177 Background: One of the biggest challenges for oncology patients is timely access to care. The inability to provide the right care for the right patient at the right time many times result in overuse of Emergency Departments (ED) to receive oncology care. Approximately 77% of oncology patients have an ER visit, and 63.2% of visits result in hospital admission (Mayer et al., 2011). Furthermore, the average cancer patient receiving chemotherapy has at least one hospital admission and two ED visits per year (Klodziej, et al., 2011). Establishing a “triage” program that attempts to avoid “avoidable” admissions can reduce unnecessary ED visits and associated inpatient care, therefore improving health outcomes while reducing costs. Methods: A quality improvement value-based care (VBC) initiative to prevent ED visits and avoid “avoidable” admissions, via an “Express Symptom Management Hotline” (ESMH) was created. ESMH provides oncology patients with direct and rapid phone access to an oncology Advanced Practice Provider (APP) who can appropriately triage a patient that is in need of acute symptom management. A patient can be managed over the telephone, with a clinic visit, and/or with other outpatient oncology same day services. A next day follow up call for triaged ensures that there was appropriate management. Telephone triage, associated early intervention by an APP for cancer related symptoms and a next day follow-up call will reduce ED visits and avoid “avoidable” admissions. Results: Among the 294 calls that were received from oncology patients for acute symptoms during a 12 week trial period, only 14 led to patients requiring ED services. All 14 ED visits required an admission. Conclusions: Telephone triage by APP’s via an ESMH can effectively manage oncology patients’ symptoms by providing early outpatient interventions. Such an ESMH helps avoid “avoidable” admissions, leading to improved health outcomes while reducing costs. [Table: see text]
Implementing routine assessment of patient-reported outcomes in cancer care.
Authors: Kathi Mooney, Joshua Biber, Rachel Hess, Howard Weeks, John W. Sweetenham
Journal: Journal of Clinical Oncology (2017)

229 Background: Value based cancer care includes measurement of value to the patient. Patient reported outcomes (PRO) are central to assessing outcomes of cancer care but systematically measuring them creates adoption and work flow issues. We report the Huntsman Cancer Institute’s (HCI) experience implementing routine collection of PROs. Methods: Patients on a quarterly basis either prior to a scheduled visit via email or at the visit via tablet, complete 5 PROMIS measures (fatigue, pain interference, anxiety, depression and physical function) administered in computer-assisted test (CAT) format. Patients also complete a current health visual analog scale and general health question. Data are automatically and seamlessly populated to the electronic health record (EHR) for clinician review at the visit and are stored within the data warehouse. Results: Roll-out began sequentially to all HCI oncology outpatient clinics in July 2016, with a new clinic added every 2 weeks. To date PRO assessment is operational in every HCI clinic with over 9,800 assessments completed by 8,600 patients. Most assessments have been completed in the clinic as at-home completion was a recent option. Time to complete assessments average 5 minutes. Findings to date demonstrate that HCI patients are within average norms for cancer patients on the measures. Approximately 3% of depression assessments were at an elevated level and automatically routed to social work for follow-up. Initial assessments will serve as the basis for tracking quality improvement initiatives in the future. Missed assessments were common during initial startup. Completion was more likely when the clinicians valued having the data during the clinic visit and made it an expectation for collection by front end staff at visit registration. Conclusions: Technology-aided patient reported outcomes can be systematically and successfully collected during outpatient care, with triage of scores beyond acceptable thresholds for follow-up. Baseline scores will serve to evaluate improvements in care over time. Critical to success are clinical champions who value and understand the scoring and interpretation of patient reported data and make staff facilitation of data collection an expectation.
A population-based study of quality of life in women with breast cancer
Authors: N. K. Janz, M. Mujahid, P. M. Lantz, A. Fagerlin, B. O. Salem, S. J. Katz
Journal: Journal of Clinical Oncology (2004)

8126 Background: Few studies on QOL after breast cancer and its treatment have been population-based and focused on differential impact dependent on stage, treatment course, and sociodemographics characteristics. Methods: A population-based sample of women with breast cancer in Detroit and Los Angeles (N=1,489) derived from SEER registry data completed mailed surveys (mean time from primary surgery = 6.4 months). Functional status, fatigue, body image, future perspective, and sexual enjoyment were measured using the EORTC QLQ-C30/QLQ BR-23. Regression models calculated mean QOL scores across primary surgical treatment (BCS, mastectomy only (MO)), mastectomy w/reconstruction (MR)), chemo (yes/no), and breast cancer stage (stage 0, I, II), controlling for age, health status at diagnosis, and co-morbidities. Clinically significant differences in QOL were defined as ≥ 10 point difference (out of 100) between groups. Results: Few clinically important differences in QOL were reported comparing stage at diagnosis, with the exception of women with Stage 2 reporting lower physical functioning than those with earlier stage (p<.001). Two important differences between surgical treatments were observed: body image with BCS having higher scores than either MO or MR (86.5 versus 75.2 versus 74.5 respectively, P<.001) and; role functioning with BCS reporting higher scores than MR (79.9 vs. 70.4). No clinically important differences in any QOL measure were reported between women with MO versus MR. Women who completed chemo generally reported lower QOL than those who did not receive chemo, important differences were limited to body image (75.4 vs. 85.2, P<.001), and future perspective (48.3 vs. 61.1, P<.001). African American women who received chemo (compared to those who did not) experienced a greater reduction in role functioning (drop of 15.0 vs. 4.3) and fatigue (drop of 23.3 vs. 5.3) than did their white counterparts. Conclusions: Women should be reassured that relatively few QOL differences exist dependent on surgical treatment, and informed which QOL dimensions vary by treatment course. Clinicians need to be aware of the differential impact of treatment across various subpopulations. No significant financial relationships to disclose.
Correlation of increased tumor expression of estrogen receptor alpha mRNA and low aromatase protein ratio with prognosis in resected non-small cell lung cancer (NSCLC).
Authors: Unai Aresti, Sergio Carrera, Itziar Rubio, Aintzane Sancho, Ines Marrodan, Alberto Muñoz, Mireia Martinez, Begoña Calvo, Aitziber Buque, Eider Azkona, Abigail Ruiz de Lobera, Guillermo Lopez-Vivanco
Journal: Journal of Clinical Oncology (2012)

e21009 Background: Although several studies have shown the presence of estrogen receptors (ERs) in lung tumors, published reports show inconsistent conclusions. Biological role of ER-α, ER-β and aromatase in the development of NSCLC is unclear. Aim of this study was to investigate the prognostic value of ERs and aromatase mRNA-protein concentration in resected NSCLC. Methods: Lung tumor and normal lung were analyzed for expression of ER-α, ER-β and aromatase using a 7900HT Applied Biosystem Fast PCR System. Reverse transcription-polymerase chain reaction (RT-PCR) analysis was performed for the detection of ER and aromatase expression using RNA from lung cancer tissues immediately submerged in RNA Later (Qiagen) after surgery. Aromatase protein was detected with an enzyme-linked immunosorbent assay kit for human aromatase (USCN Life Science). Results: We included 96 patients (80 male/16 female) with resected NSCLC; 51% adenocarcinoma, 43% squamous, 6% others. Pathological stages: 43% I, 33% II, 22% III and 2% IV. Mean expression of ER-α in normal lung was significantly higher than in lung tumor (0.1554 vs. 0.1182, p &lt; 0.0001). Tumoral expression of ER-β inversely correlated with cigarette consumption in current smokers (p=0.046). Patients with the highest values of tumoral ER-α mRNA had better overall survival than those with the lowest values (&lt; p50 =107 weeks &gt;p50 = 139 weeks; p= 0.037). Aromatase protein mean concentration in tumor lung was significantly higher than in normal lung (10.411 vs. 2.125, p&lt;0.0001). Aromatase protein ratio, tumoral concentration/normal tissue concentration, was significantly linked to overall survival (p=0.024; Exp (B) =1.010; 95% CI Exp (B) = 1.001-1.020), showing that a lower aromatase protein ratio is associated with better overall survival. Conclusions: We report a significant association between quantitative expression of mRNA ER-α and overall survival in tumor of resected NSCLC. We define the relationship between tumoral/ normal tissue aromatase protein ratio and overall survival. A better understanding of estrogen action in lung cancer could provide the basis for future targeted therapies.