tbuckley/cabot-search huggingface dataset:
A Cytokine Working Group (CWG) 3-arm phase II trial of gp100 (209–2M<u>)</u> peptide + high dose (HD) Interleukin-2 (IL-2) in HLA-A2+ (A2+) advanced melanoma patients (pts)
Authors: M. Ernstoff, C. Carrillo, W. Urba, L. Flaherty, J. Clark, J. Dutcher, K. Margolin, M. Atkins, J. A. Sosman
Journal: Journal of Clinical Oncology (2005)

7504 Background: HD IL-2 induces responses in 15% of advanced melanoma pts, of which 5–8% are durable CRs. The A2-restricted gp100 peptide (209–2M), is able to induce T cell responses in vivo, but is inactive as a single agent. The NCI combined 209–2M with HD IL-2 for a 42% (13/31) response rate (RR),(Nat Med,1998). We studied the vaccine in a randomized phase II trial, involving 3 different IL-2 schedules. The different schedules were based on the NCI experience. Methods: All patients received 209–2M, subcutaneously, weeks (wks) 1, 4, 7, 10 and HD IL-2 (0.6MU/kg/dose IVP q 8hrs x 14) on wk 1 and 3 (arm 1), wk 7 and 9 (arm 2), or wk 1, 4, 7, 10 (arm 3) starting 24 hrs post 209–2M. The treatment (Rx) was repeated up to 2x at 12 wk intervals in patients with CR, PR, or SD. Initial preferential assignment was given to arm 3 (Proc ASCO abst 1423, 2001) with subsequent randomized assignment to arms 1 and 2. Results: 131 A2+ pts (arm 1=46 arm 2=43 arm 3=42) were enrolled from 9/1998 to 11/2003. 117 are fully evaluable. Groups had similar characteristics. Overall, M:F 60%:40%, median age 50(20–76), PS 0:1 84%:16%, High LDH 27%, prior adjuvant IFN 36%, prior chemotherapy 14%. 14 pts (12%) (9 from arm 2) did not receive any IL-2 due to disease progression. Median # IL-2 doses over 1st course relative to a maximum were 20/28, 20/28, and 34/56 in arms 1, 2, and 3, respectively. 3 pts died on protocol due to disease progression. With a median f/u of 3.5 yrs, the overall RR is 14.5%, (17/117) with 19% arm 1, 12.5% arm 2, and 8.8% arm 3. Responses included 9 CR (8%) and 8 PR (7%). 20 pts (17%) remain progression-free, 12 on arm 1 (28%). 30 pts (26%) remain alive at 12–62+ mos. Conclusions: None of the schedules of 209–2M + HD IL-2 produced better activity than expected with IL-2 alone. Arm 3 with greater dose intensity and arm 2 with 6 wks of 209–2M prior to starting IL-2 were particularly disappointing. Results support the early initiation of standard HD IL-2 after the diagnosis of advanced melanoma. Lymphocytes are available pre-Rx and at 12 wks on a large # of pts. These will be analyzed for immune changes and these findings will be presented along with the clinical results. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Chiron Chiron Chiron
Rational design of polyarginine nanocapsules intended to help peptides overcoming intestinal barriers
Authors: Zhigao Niu, Erik Tedesco, Federico Benetti, Aloïse Mabondzo, Isabella Monia Montagner, Ilaria Marigo, David Gonzalez-Touceda, Sulay Tovar, Carlos Diéguez, Manuel J. Santander-Ortega, María J. Alonso
Journal: Journal of Controlled Release (2017)

The aim of this work was to rationally design and characterize nanocapsules (NCs) composed of an oily core and a polyarginine (PARG) shell, intended for oral peptide delivery. The cationic polyaminoacid, PARG, and the oily core components were selected based on their penetration enhancing properties. Insulin was adopted as a model peptide to assess the performance of the NCs. After screening numerous formulation variables, including different oils and surfactants, we defined a composition consisting of oleic acid, sodium deoxycholate (SDC) and Span 80. This selected NCs composition, produced by the solvent displacement technique, exhibited the following key features: (i) an average size of 180nm and a low polydispersity (0.1), (ii) a high insulin association efficacy (80-90% AE), (iii) a good colloidal stability upon incubation in simulated intestinal fluids (SIF, FaSSIF-V2, FeSSIF-V2), and (iv) the capacity to control the release of the associated insulin for >4h. Furthermore, using the Caco-2 model cell line, PARG nanocapsules were able to interact with the enterocytes, and reversibly modify the TEER of the monolayer. Both cell adhesion and membrane permeabilization could account for the pronounced transport of the NCs-associated insulin (3.54%). This improved interaction was also visualized by confocal fluorescent microscopy following oral administration of PARG nanocapsulesto mice. Finally, in vivo efficacy studies performed in normoglycemic rats showed a significant decrease in their plasma glucose levels after treatment. In conclusion, here we disclose key formulation elements for making possible the oral administration of peptides.
Assessment of pathologic response to neoadjuvant chemotherapy in locally advanced non-small cell lung cancer using FDG-PET/CT: SUVmax versus metabolic tumor volume.
Authors: M. Soussan, K. Chouahnia, M. Kambouchner, A. Khafagy, G. Des Guetz, L. H. Zelek, E. Martinod, J. F. Morere
Journal: Journal of Clinical Oncology (2011)

e17528 Background: We aimed to evaluate metabolic tumor volume (MTV) in comparison to SUVmax measurement as markers of histopathological response to neoadjuvant chemotherapy in locally advanced NSCLC. Methods: Twenty-two patients (18 men; median age:64 years) with locally advanced NSCLC received neoadjuvant platinum-based chemotherapy and, if considered resectable, proceeded to surgery (14/22). Patients had FDG-PET/CT scans before and after 3 cycles of chemotherapy. SUVmax and MTV (40%-SUVmax and adaptive-threshold methods) of the primary tumor were measured (DOSIsoft Software). SUVmax was graded using EORTC criteria. Pathological response was defined as: non-responders, partial responders (>10% residual tumor cells) and pathological responders (<10% residual tumor cells). Inflammatory cell presence within the tumor was graded as low, moderate or high. Changes in SUVmax and MTV were correlated with pathological response (Wilcoxon test). Results: There were 8 partial responders, 3 pathological responders and 3 non responders. The median decrease of tumor SUVmax was higher in pathological responders than non and partial responders (79% vs 24%, p=0.086). A median percentage decrease in MTV was more significant in pathological responders (84% vs 54% for fixed threshold, p=0.035; 90% vs 47% for adaptive-threshold method, p=0.043). EORTC criteria misclassified 4/8 partial responders patients as stable or progressive disease. In these 4 patients, MTV decreased (median percentage decrease: 59% for fixed threshold method, 40% for adaptive-threshold method) and inflammatory cell accumulation was noted within the tumor: moderate (n=3) or low (n=1). Conclusions: SUVmax measurement may misclassify patients when assessing therapeutic response, probably because of post-chemotherapy inflammatory changes. MTV could be of value in the assessment of pathological response after neoadjuvant chemotherapy in NSCLC.
Global cancer mortality: The effect of health care system resources on survival from cancer.
Authors: A. Batouli, P. Jahanshahi, J. B. Yu
Journal: Journal of Clinical Oncology (2011)

1576 Background: Per capita Gross Domestic Product (GDP) has been shown to predict improved cancer survival among European countries. Experts have proposed increased spending on radiation facilities as a cost-effective tool for battling cancer globally. We aimed to investigate the relationship between cancer survival and quantifiable measures of national healthcare systems (World Health Organization (WHO) healthcare system ranking, GDP, total healthcare expenditure (THE), physician density (PD), access to radiation oncology (measured by per capita total external beam devices (TEBD)), THE per GDP and TEBD per THE). Methods: The most recent cancer incidence and mortality data (years 2005-2008) for 27 different cancers were obtained from the Globocan cancer registry for the 85 countries with reliable non-estimated data. Mortality per incidence for a given year was used as an inverse estimate of survival. Countries were split in half according to high (GDP>$15,000) or low-income (GDP<$15,000), and multivariate linear regression was run to compare the aforementioned markers with survival. The model controlled for rates of HIV, smoking, obesity, rural residence and ethanol consumption. Results: In low income countries, only WHO ranking was a significant correlate of survival, with a 21 point improvement in rank corresponding to a 1% increase in overall cancer survival. In high-income countries, GDP, TEBD, THE and THE per GDP were all significant correlates of survival. THE and THE per GDP were the strongest correlates, with a $400 increase in THE or a 0.8% increase in THE per GDP each corresponding to a 1% increase in overall cancer survival. WHO ranking, PD and TEBD per THE correlated poorly with survival in high income countries. Conclusions: These results highlight different approaches to predicting cancer survival in low vs. high income countries. In the former, only WHO ranking correlated significantly, surpassing all specific measures of healthcare resources. In the latter, healthcare spending was the most significant predictor of survival in high income countries. For high income countries, though TEBD (but not TEBD per THE) was correlated to cancer mortality, it was less significant than overall healthcare spending.
Patient-reported physical, emotional, and social functioning in advanced breast cancer: Insights from BOLERO-2.
Authors: Denise Aysel Yardley, Gabriel N. Hortobagyi, Fabienne Lebrun, J. Thaddeus Beck, Patrick Neven, José Baselga, Katarina Petrakova, Shaker R. Dakhil, Silvia Sabatini, Anna Komorowski, Edmond Emilien Chouinard, Robyn R. Young, Michael Gnant, Kathleen I. Pritchard, Jie Zhang, Ryan Ziemiecki, Ashok Panneerselvam, Tanya Taran, Tarek Sahmoud, Shinzaburo Noguchi
Journal: Journal of Clinical Oncology (2013)

553 Background: The phase 3 BOLERO-2 study at 18 months’ median follow-up showed that everolimus (EVE) + exemestane (EXE) significantly improved progression-free survival (PFS) vs EXE alone in 724 hormone-receptor–positive (HR + ) advanced breast cancer (ABC) patients with recurrence/progression during/after nonsteroidal aromatase inhibitor (NSAI) therapy. A higher rate of grade 3/4 adverse events was noted with EVE + EXE, but was not associated with deterioration in quality of life (QOL) based on the EORTC QLQ-C30 Global Health Status scale. Additional patient-reported post hoc analyses of QOL are reported herein. Methods: During BOLERO-2, QOL (EORTC QLQ-C30 and QLQ-BR23) was assessed at baseline and q 6 wk thereafter until progression or discontinuation. Physical, emotional, and social functioning subscales of QLQ-C30 were analyzed. Time to definitive deterioration (TTD) was defined based on either a 5% (protocol specified) or 10-point (more stringent) decrease from baseline for each subscale and analyzed by Kaplan-Meier methods. The difference between treatments was assessed by a log-rank test stratified by randomization factors. Results: QLQ-C30 compliance was &gt; 80% at week 48. Among the 3 protocol-specified QLQ-C30 subscales, analyses based on a 5% decrease in QOL showed a longer TTD for both physical and emotional functioning in the EVE + EXE group vs EXE alone (log-rank P = .0120 and P = .0277, respectively). The TTD for social functioning was similar in both treatment arms (log-rank P = .3374). Analyses based on a 10-point decrease indicated a longer TTD for physical functioning in the EVE + EXE group (15.2 mo) vs EXE alone (9.7 mo; log-rank P = .0211). The TTDs for emotional and social functioning were similar between EVE + EXE and EXE alone: 13.9 vs 13.8, respectively (log-rank P = .4023), and 11.5 vs 9.5, respectively (log-rank P = .2507). Conclusions: The treatment goal for ABC is to maximize clinical benefit with minimal negative effects on QOL. These additional BOLERO-2 QOL analyses confirmed that the more than doubling of PFS with EVE + EXE was accompanied by maintained physical, emotional, and social functioning compared with EXE alone in patients with HR + ABC progressing after NSAI. Clinical trial information: NCT00863655.
Association of high rates of practice-level inpatient-intensity with end-of-life outcomes, readmission rates, and weekend hospitalizations among Medicare patients with cancer.
Authors: Jeffrey D Clough, Larisa M Strawbridge, Thomas William LeBlanc, Bradley G Hammill, Arif Kamal
Journal: Journal of Clinical Oncology (2016)

5 Background: Substantial practice-level variation exists in use of acute hospital care for patients receiving anti-cancer therapy. The aim of this study was to determine whether patient outcomes were associated with greater inpatient-intensity at the treating practices. Methods: Retrospective analysis of 397,646 Medicare beneficiaries receiving anti-cancer therapy in 2012. Each beneficiary was associated with a practice and practices were ranked based on average payments for inpatient admissions (inpatient intensity). Outcomes included 30-day readmission, weekend admissions, intensive-care unit (ICU) stays in the last month of life, and hospice stay of at least 7 days. Outcomes were measured for each quartile of practice inpatient-intensity. We fit multivariable logistic regression models to calculate adjusted odds ratios for each outcome for each quartile of inpatient-intensity. Results: Total and unplanned 30-day readmissions increased from 22.8% to 31.9% (adjusted odds ratio and 95% confidence interval: 1.45 [1.39-1.50]) and 19.8% to 27.1% (1.36 [1.31-1.41]), respectively, for patients in practices in the lowest and highest quartiles of inpatient-intensity. The proportion of admissions occurring on the weekend was similar across quartiles. The proportion of decedents with an ICU stay in the last month of life increased from 18.0% to 25.5% (1.33, 1.19–1.49) while the proportion with a hospice stay of &gt; = 7 days decreased from 50.9% to 42.5% (0.79, 0.74–0.86) between those in practices in the lowest and highest quartiles of inpatient intensity. Conclusions: Participants in oncology practice delivery reform may find significant opportunity to improve quality and reduce costs by initially focusing on processes related to improving end-of-life care and reducing readmissions.
Improving quality of pediatric oncology care via ASCO’s Quality Oncology Practice Initiative (QOPI) program.
Authors: Robert Michael Cooper, Robin Abasolo
Journal: Journal of Clinical Oncology (2012)

212 Background: Pediatric oncologists strive to provide a high quality of care for their patients. American Society of Clinical Oncology (ASCO) developed the Quality Oncology Practice Initiative (QOPI) Program which serves to evaluate institution’s best oncology practices. The program evaluates Core Measures in Disease Modules and Domain Modules. The Disease Modules were not useful in a pediatric practice, however, the Core Measures and Domain Modules were appropriate for evaluating pediatric quality care. Methods: Kaiser Permanente Los Angeles Medical Center Pediatric Oncology participated in the QOPI Spring 2012 Collection. Thirty-five member charts were audited by a registered nurse case manager via the electronic medical record (EMR) for Symptom/Toxicity Management, Care at End of Life, and Core Measures modules over the course of six weeks. Results: Data results revealed areas that needed improvement at LAMC included oncologist’s documentation of chemotherapy treatment and consent, physician and nurse documentation of chemotherapy and disease education, documentation of oral chemotherapy adherence and documentation of fertility preservation. Only two pediatric end-of-life cases met requirements for abstraction during this round of audit. Chart audits were easily abstracted from EMR. The QOPI computer program was easy to use and concise with information and guidelines for measures to be abstracted. QOPI personnel were readily available for any problems or concerns. Conclusions: Participation in the ASCO QOPI Program can serve as a tool to help improve oncology institution’s best practices. The QOPI Program could further expand its disease modules to include more pediatric content such as acute leukemia and neuro-oncology. In addition, participation in this program offers 3-year certification for outpatient hematology-oncology practices (limited to internal medicine at this time) and could serve as your Part IV Maintenance of Certification (limited to internal medicine).
Immunotherapy of malignant melanoma using a dendritic cell-amplified tumor RNA vaccine: A phase I study
Authors: A. B. Dietz, S. Markovic, C. Greiner, M. Maas, G. Butler, P. Bulur, V. Suman, J. Allred, S. Vuk-Pavlovic
Journal: Journal of Clinical Oncology (2005)

2597 Background: We prepared a dendritic cell (DC) vaccine specific for malignant melanoma and tested its safety in a phase 1 clinical trial of immunotherapy of stage IV malignant melanoma. Methods: Immature DCs were prepared from immunomagnetically isolated patients’ CD14+ cells. Messenger RNA was isolated from fresh tumor tissue obtained at surgery and was reversely transcribed, amplified, and in vitro transcribed. Amplified RNA was tested for the presence of melanoma-associated antigens gp100, tyrosinase and Mart1 and introduced into immature DCs by electroporation. Then the DCs were matured and cryopreserved. Five million cells were injected at three-week intervals for up to four injections. Results: We studied six patients (median age 52, range 40–66) suffering from predominantly non-visceral disease (four patients). After surgery, the tumor was measurable in three patients, evaluable in two and non-evaluable (completely resected) in one patient. Prior to DC therapy, two patients were treated by radiation, one by hormonal therapy and three by interleukin-2. The mRNA isolate from one patient did not contain any gp100, tyrosinase or Mart1, one isolate contained tyrosinase and four contained all three transcripts, with the presence of these transcripts maintained after amplification. Electroporation and transfection did not affect viability and phenotype of fresh mature DCs, but post-thaw viability was lower in comparison to non-electroporated cells (69 v. 82%; p<0.03). DC injections were tolerated well. We tested the efficiency of vaccination by measuring in vitro reactivity of patients’ T cells before and after DC injections. Both pre- and post-vaccination T cells from one patient secreted IFN-γ upon DC stimulation in vitro while post-vaccination T cells from another patient proliferated upon such stimulation. Conclusions: We demonstrated the feasibility of preparation of viable clinical-grade DCs transfected with tumor-derived mRNA. The vaccine was tolerated well indicating that it can be used in future clinical trials. No significant financial relationships to disclose.
Characterization of HER2 functional profiling in fine needle aspirates (FNA) in patients with metastatic breast cancer (MBC).
Authors: P. Kim, Y. Wu, X. Liu, E. A. Vargas-Quesada, H. L. Gomez-Moreno, P. Shin, T. Lee, G. Leesman, S. Singh, J. N. Lowder
Journal: Journal of Clinical Oncology (2010)

e21029 Background: The Collaborative Proximity Immunoassay (COPIA) is a multiplexed microarray platform that utilizes the formation of a unique immuno-complex requiring co-localization of two detector-antibodies. The detector-antibodies are conjugated with corresponding channeling-enzymes for proximity mediated signal generation/amplification for the expression and activation profiling of HER1, HER2, p95HER2, HER3, IGF1-R, c-MET, PI3K, Shc, VEGFR, CK, and other signal transduction proteins. Here we report HER2 expression and activation profiling in fine needle aspirate (FNA) biopsy samples from MBC patients in an ongoing investigation with this novel technology. Methods: FNA samples were collected from metastatic sites from female patients with progressive, Stage IIIB/IV breast cancer (n = 25, baseline age 42 ± 13yr). Patients with various clinical primary ER/PR/HER2 statuses by IHC staining were allowed in the study. The ER/PR/HER2 status of the primary tumor sample was obtained by the local sites. Expression and activation status for HER2 and the other signal transduction Proteins (STP) were measured using COPIA on FNA samples. Results: Data from the FNA samples of the first 10 patients showed that 5 (50%) were HER2 activated (pHER2+), 2 (20%) were HER2 over-expressed (tHER2+), pHER2+ and p95HER2 over-expressed. 7 of 10 FNA samples expressed weak to moderate levels of tHER2 with different pHER2 levels. HER2 status (expression/activation) was negative in 1 patient. The concordance between the COPIA-derived data from the FNA and the primary tumor IHC will be evaluated. In addition, over-expression and/or activation of other STP including HER1, HER3, IGF1- R, c-MET will be measured in the entire cohort using COPIA. Conclusions: COPIA assays can be used to quantitate expression and activation of STPs in FNA specimens. These results need to be further analyzed for their potential value to inform treatment decisions in relapsed breast cancer patients. No significant financial relationships to disclose.
Molecular tumor profiling ordering trends in cancer patients.
Authors: Joseph D. Ma, Winnie S Wang, Warren Yau, Chelsea Hagmann, Carolyn Revta, Janet M Armstrong, Eric Roeland
Journal: Journal of Clinical Oncology (2016)

165 Background: Molecular tumor profiling may provide information as to whether to initiate or not initiate a targeted therapy. As to the timing of when the tumor profiling is ordered relative to date of diagnosis, date of death, and palliative care (PC) consultations are unknown. The primary objective of this study was to examine molecular tumor profiling ordering trends in the course of cancer illness. Methods: A preliminary, retrospective chart review was conducted in a cohort of patients with a confirmed diagnosis of cancer at an academic, NCI-designated comprehensive cancer center. Patients were identified from a tumor registry and then matched to a next generation sequencing molecular tumor profiling database. The date of palliative care consultation was collected from the electronic medical record. Differences in the date of when tumor profiling was ordered and date of diagnosis, date of PC consultation, and/or date of death were determined. Data were compiled into a single database and descriptive statistical analyses were performed. Results: A cohort of 397 (205 women) cancer patients was included. Metastatic disease was present in 108 (27.2%) patients, with mean±SD age of 58.7 ± 13.5 yrs. One-hundred and nine (27.6%) patients received a PC consultation (n=60 inpatient, n = 49 outpatient). As of February 2016, 119 (30%) patients died, with 58 (48.7%) out of 119 receiving a PC consultation. The difference between date of cancer diagnosis and date of tumor profiling ordered was 2467.4 ± 6865.7 days (n = 376), while the difference between date of tumor profiling ordered and date of death was 229.1 ± 185.7 days (n = 111). The difference between date of cancer diagnosis and date of death was 1507.5 ± 2002.1 days (n = 119). In patients were the tumor profiling was ordered before the PC consultation (n = 29), the difference between date of PC consultation and date tumor profiling ordered was 157.3 ± 258.1 days. In contrast, in patients were the tumor profiling was ordered after the PC consultation (n = 76), the difference was 194.6 ± 168 days. Conclusions: This analysis suggests that molecular tumor profiling is ordered at the end and not at the beginning of a cancer illness. PC consultations are not routinely performed in patients who participate in tumor profiling.
MicroRNA Signatures Associated with Cytogenetics and Outcome in Acute Myeloid Leukemia.
Authors: Ramiro Garzon, Stefano Volinia, Chang G. Liu, Flavia Pichiorri, Tiziana Palumbo, Muller Fabbri, Amelia Cimmino, Hansjuerg Alder, Neal Flomenberg, Kevin R. Coombes, George A. Calin, Michael Andreeff, Carlo M. Croce
Journal: Blood (2006)