tbuckley/cabot-search huggingface dataset:
Sequential chemotherapy in Her 2/neu + metastatic breast cancer (MBC): A retrospective single institution analysis
Authors: M. Rosenzweig
Journal: Journal of Clinical Oncology (2004)

8257 Background: Traztuzumab (T) shows a clear benefit when added to chemotherapy as treatment for first line Her2 (+) MBC. The usefullness of T therapy + chemotherapy after first line treatment failure is not defined, Methods: Retrospective repeated measures design of record analysis of MBC HER 2/neu + established (2 or more visits) patients from MWH/UPCI from Jan 1999 through Sept 2003. Time to progression (TTP) measured by time to treatment change, integrating clinical and radiographic patient data. Results: Of total 310 patient MBC cohort, n=92 Her 2neu+ patients were analyzed. Forty-three patients are deceased. Mean age at metastatic diagnosis was 51 yoa. First Line Chemotherapy + T Fifty-six Her 2 neu+ patients received chemotherapy as first line metastatic treatment, n=12 without H, n=44 with H. Docetaxel/Carbo (DC+T) (n=21) was the most heavily utilized chemotherapy regimen with TTP 13.5 months and minimal toxicity. Seven different first line chemo regimens + T were well tolerated with no cardiac dysfunction. Sequential Chemotherapy Following first line treatment failure with chemotherapy and T, sequential chemotherapy +/- T utilization in Her 2/neu+ patients was analyzed. Vinorelbine (V) +T was the most commonly used chemotherapy, with benefit (TTT>6 months) even in late stage treatments. Additionally there is anecdotal evidence of benefit (TTP>6 months) with docetaxel +T, capecitabine+T and gemcitabine + T in up to 8th line salvage MBC chemotherapy. Conclusions: T with chemotherapy has benefit as therapy for Her2 (+) MBC patients in this single institution retrospective cohort. There is extended TTP, even beyond first line treatment. Toxicities are manageable and cardiac toxicity is minimal. In order to maximize T's therapeutic potential. chemotherapeutic regimens + T must be analyzed. Mean TTP (months) in Sequential Chemotherapy with and without Traztuzumab. No significant financial relationships to disclose.
Examining the role of treatment complexity in survivorship care planning.
Authors: Nicole Marie Mahr, Karen Marie de Sola-Smith, Janice Bell
Journal: Journal of Clinical Oncology (2017)

242 Background: The cancer survivor population will reach 19M by 2025, increasing demand on primary care providers to manage late and long-term effects of treatment. To improve care quality, the IOM recommends survivorship care plans (SCPs) that include two components: a treatment summary (TS) detailing disease and treatment characteristics; and evidence based follow up care instructions (FCI). SCPs remain underutilized despite evidence they enhance physician communication, increase self-efficacy and improve health outcomes of cancer survivors. Little is known about treatment related and socio-demographic factors associated with receipt of SCPs and their components. The purpose of this study was to examine the relationship between care complexity, operationalized as multiple cancers or treatments, and survivor reported SCP receipt. Methods: This was a secondary analysis of data collected in the 2012 LIVESTRONG Survey for People Affected by Cancer, an online self-selection survey. Descriptive statistics and multivariate regression were used to examine relationships between survivor characteristics and SCP receipt among 3,599 respondents. Results: Half (52%) of survivors received a complete SCP. Care complexity was significantly associated with lower odds of SCP receipt. Each additional treatment modality lowered odds of receipt by 8% (95% CI 0.86-0.99). Survivors with multiple diagnoses had 19% lower odds of receipt than those with single diagnoses (CI 0.68-0.95). Other predictors of SCP receipt were being female (OR 0.56; 95% CI 0.48-0.65), having at least a bachelor’s degree (OR 0.77; CI 0.60-0.99), age over 66 years (OR 1.38; CI 1.01-1.89), and race of “other” (OR 1.56; CI 1.14-2.13). Similar results were found for receipt of TS alone. Conclusions: Only 52% of survivors received SCPs as recommended by the IOM. Increased case complexity was associated with lower odds of SCP receipt, suggesting patients at highest risk are least likely to receive coordination. Results indicate the need to identify and eliminate barriers to SCP implementation, with special focus on high risk patients. Future research should investigate these findings in diverse populations and identify specific characteristics associated with SCP receipt.
Phase I participants as a vulnerable population
Authors: E. Horstmann, C. Grady, M. McCabe, E. J. Emanuel
Journal: Journal of Clinical Oncology (2004)

6059 Background: Given the high-risk, low-benefit nature of phase I oncology trials, some assert that phase I trials exploit socially vulnerable populations. This review was undertaken because no current comprehensive data on the characteristics of phase I participants exist. Methods: Data on participants in non-pediatric phase I oncology trials opened between 1991 and 2002 and sponsored by the Cancer Therapy Evaluation Program at the NCI were reviewed. Participants in trials of only supportive care or for diseases other than cancer were eliminated from analyses. Percentages for each characteristic were calculated based on the number of participants for whom data was reported for that characteristic. Results: There were 9841 participants in the 11 year period. The median age was 57, 52% were male, 90% white and 85% had insurance (58% private, 27% public) while only 4% were self pay or had no means of payment. 93% of participants had a performance status on the ECOG scale of 0 or 1. 91% of participants had received treatment for their cancer prior to enrolling in the phase I study, the majority of whom received chemotherapy. Less than 9% of participants had received no treatment prior to enrolling on a phase I study. Conclusions: Participants in phase I oncology trials are predominantly white, have private health insurance, good performance status, and have been treated for their cancer prior to trial enrollment. These are not the characteristics of a socially vulnerable population. Phase I oncology trials should not be seen as exploiting socially vulnerable populations. This does not, however, preclude the possibility that individual phase I participants might be vulnerable for other reasons. No significant financial relationships to disclose.
Two-year follow up results of a population-based prospective case control study of 143 stage IV colorectal cancer (CRC) patients treated with 2<sup>nd</sup> line irinotecan (iri) outside of clinical trial
Authors: I. Lang, E. Hitre, Z. Horvath
Journal: Journal of Clinical Oncology (2004)

3687 Background: 2nd line iri treatment for stage for CRC has been financed by the Hungarian Natiional Insurance Company since 2001. This therapy was found to be active in clinical trials as compared to BSC and in 5-FU treated patients. Our aim was to evaluate its effect in compassionate use in the Hungarian population. Methods: All data of the patients (>70 yr, ECOG 0–2, no brain metastasis) were reported to an independent committee prior to iri treatment, after every 2nd cycle up 6 cycles and then every six months until death. First-line chemotherapy was bolus or infusional 5-FU-Leucovorin. 62 patients had rectal cancer, 79 had colon cancer. Primary tumor was resected in 124 cases. Fifty eight % received monotherapy (350 mg/m2 q3 weeks, the rest received FOLFIRI combination (180 mg/m2 iri q2 weeks). 52,6% had liver metastases, 22,4 % had lung metastases. Results: 29,8% ORR, (CR 4%, PR 25,8%), and 61,4% SD was found. TTP was 7,41 ± 6,14 months. OS: 11,67 ± 7,2 months, mOS:11,2 month. At a two years follow-up time 35 out of 143 pts were alive (24,5 %). Median OS was significantly longer if primary tumor was removed (16,77 vs 8,43 months; p=0,0002). Grade III/IV diarrhoea, vomiting and granulocytopenia were around 20 %. Conclusions: In a population-based compassionate setting the efficacy and safety of 2nd line iri therapy was comparable to those found in randomised phase III trials. No significant financial relationships to disclose.
Nucleolin-targeted Extracellular Vesicles as a Versatile Platform for Biologics Delivery to Breast Cancer
Authors: Yayu Wang, Xiaojia Chen, Baoqing Tian, Jiafan Liu, Li Yang, Lilan Zeng, Tianfen Chen, An Hong, Xiaogang Wang
Journal: Theranostics (2017)

Small interfering RNAs (siRNA)/microRNAs (miRNA) have promising therapeutic potential, yet their clinical application has been hampered by the lack of appropriate delivery systems.Herein, we employed extracellular vesicles (EVs) as a targeted delivery system for small RNAs.EVs are cell-derived small vesicles that participate in cell-to-cell communication for protein and RNA delivery.We used the aptamer AS1411-modified EVs for targeted delivery of siRNA/microRNA to breast cancer tissues.Tumor targeting was facilitated via AS1411 binding to nucleolin, which is highly expressed on the surface membrane of breast cancer cells.This delivery vesicle targeted let-7 miRNA delivery to MDA-MB-231 cells in vitro as confirmed with fluorescent microscopic imaging and flow cytometry.Also, intravenously delivered AS1411-EVs loaded with miRNA let-7 labeled with the fluorescent marker, Cy5, selectively targeted tumor tissues in tumor-bearing mice and inhibited tumor growth.Importantly, the modified EVs were well tolerated and showed no evidence of nonspecific side effects or immune response.Thus, the RNAi nanoplatform is versatile and can deliver siRNA or miRNA to breast cancer cells both in vitro and in vivo.Our results suggest that the AS1411-EVs have a great potential as drug delivery vehicles to treat cancers.
Is Vit D serum concentration related to Italian and Tanzanian breast cancer cases?
Authors: Patrizia Serra, Laura Mercatali, Nestory Masalu, Alberto Bongiovanni, Awkilina Pangan, Rosanna Tedaldi, Emanuela Scarpi, Oriana Nanni, Federico La Manna, Chiara Spadazzi, Toni Ibrahim, Andrea Rocca, Laura Solinas, Dino Amadori
Journal: Journal of Clinical Oncology (2015)

e22248 Background: The debate on the association between Vit D deficiency and breast cancer risk is still open. Some studies indicate that ethnic differences play a role in the circulating levels of serum Vit D. Moreover, single nucleotide polymorphisms (SNPs) in the Vit D receptor (VDR) have been associated with various types of cancer.The study evaluates Vit D and Binding Protein (DBP) levels, VDR and DBP polymorphisms in Tanzanian and Italian healthy donors (HD) and breast cancer patients (BCP). Methods: The study provides 200 adult women: 100 Tanzanian and 100 Italians (for each population: 50 donors, 25 primary and 25 advanced breast cancer patients). At first, analysis on serum Vit D concentrations has been performed until now on 25 HD and 25 BCP from Italy. The analysis on the overall population is ongoing. All bio-molecular characterization are performed at IRST IRCCS in Italy. The association between Vit D serum concentration and osteoporosis risk factors was evaluated. Results: From Sept to Dec 2014, 154 women (77%) were enrolled: 75 Tanzanian and 79 Italian. These preliminary results regard 50 cases from Italian populations. In healthy Italian population Vit D suboptimal concentration seems to be related to 2 or more osteoporosis risk factors (Tab). No relationship has been observed between Vit D serum concentration and risk factors in breast cancer patients. Moreover, optimal serum Vit D concentrations were observed in only 28% of BCP versus 40% of HD. Conclusions: This is the first study comparing Vit D levels, bone turnover markers and Vit D receptor (VDR) and DBP SNPs between HD and BCP from Caucasian and African indigenous population. Preliminary data show that breast cancer is associated to the lower Vit D serum concentrations rather than to the common risk factors for osteoporosis. The data regarding the whole Italian and Tanzanian population and the biological factors determination will be reported after the final analyses. Deficiency ( ≤ 20.0 ng/ml) Suboptimal (20.1-30.0 ng/ml) Optimal (30.1-50.0 ng/ml) Upper normal ( > 50.0 ng/ml) HD BCP HD BCP HD BCP HD BCP N (%) N (%) N (%) N (%) N (%) N (%) N (%) N (%) Risk factors 0 1 (25) 0 6 (55) 4 (31) 8 (80) 1 (14) 0 1 (100) 1 1 (25) 1 (25) 4 (36) 5 (38) 2 (20) 3 (43) 0 0 ≥ 2 2 (50) 3 (75) 1 (9) 4 (31) 0 3 (43) 0 0 Total 4 4 11 13 10 7 0 1
The role of annual personal health visits (APHV) on patients' with cancer knowledge and perceptions of the harms of continued smoking.
Authors: Delaram Farzanfar, Lin Lu, Jie Su, Devon Alton, Rahul Mohan, Sophia Liu, Olivia Krys, Tom Yoannidis, M Catherine Brown, Ashlee Vennettilli, Andrew J. Hope, Doris Howell, Jennifer M. Jones, Peter Selby, Wei Xu, David Paul Goldstein, Meredith Elana Giuliani, Geoffrey Liu, Lawson Eng
Journal: Journal of Clinical Oncology (2017)

152 Background: With improvements in cancer detection and therapies, important secondary prevention measures in survivorship include smoking cessation. Primary care providers have an opportunity to discuss these measures with cancer survivors at APHV. We evaluated whether having a recent APHV is associated with cancer patients’ awareness and perceptions of the harms of continued smoking. Methods: Cancer survivors were surveyed from April 2014 to May 2016 with respect to their smoking history, knowledge and perceptions of the harms of continued smoking along with the date of their most recent APHV (term changed from annual health physical examination in 2013). Multivariable logistic regression analyses assessed the association of having an APHV with knowledge and perceptions of the harms of continued smoking. Results: Of 985 cancer patients, 23% smoked at diagnosis; 34% quit &gt; 1 year prior to diagnosis; 55% had tobacco-related cancers; 77% received curative therapy. From a knowledge viewpoint, over 52% reported being unaware that smoking negatively impacts cancer outcomes; despite this, most perceived smoking to negatively influence quality of life (75%), survival (76%), and fatigue (73%). Within the last year, 48% had an APHV, while 84% had an APHV at any time in the past; 18 (2%) reported not having a family doctor. Patients who had an APHV in the last year were more likely to be aware that continued smoking can increase risk of death (adjusted odds ratio (aOR)=1.49, 95% CI [1.13-1.96], P=0.004), and more likely to perceive smoking to negatively impact quality of life (aOR=1.37 [0.94-1.99], P=0.10), survival (aOR=1.60 [0.95-2.71], P=0.08), and fatigue (aOR=1.63 [1.11-2.39], P=0.01). Those ever having an APHV were more likely aware that smoking can increase risk of death (aOR=1.61 [1.07-2.43], P=0.02) and second primaries (aOR=1.53 [1.02-2.33], P=0.04). Conclusions: Having a recent APHV was associated with improved awareness and perceptions of the harms of continued smoking, but it is unclear whether this is related to provider counseling or a healthy bias effect. APHV may be an appropriate time for primary care providers to treat tobacco addiction in their cancer survivors.
Abstract 202: Aging Alters the Electrical and Mechanical properties of LV Myocytes
Authors: Andrea Sorrentino, Sergio Signore, Mark Sundman, Ramaswamy Kannappan, Chiara Mangiaracina, Antonio Cannata, Andrew Webster, Kazuya Isobe, Mehrdad Shafaie, Junghyun Kim, Ewa Wybieralska, Alex Matsuda, Giulia Borghetti, Polina Goichberg, Marcello Rota
Journal: Circulation Research (2013)

Aging results in delays in the electrical recovery of the heart, enhancing the risk of malignant ventricular arrhythmias and sudden death. But whether altered electrical properties affect myocardial mechanical performance remains unclear. The aim of this study was to establish the ionic basis for the protracted repolarization of the senescent heart, and to determine whether these electrical changes impact on myocardial contractility. For this purpose, electrophysiological analyses were conducted in vivo and in isolated LV myocyte preparations from mice ranging from 3 to 30 months of age. Electrocardiographic parameters were preserved from 3 to 12 months of age, whereas animals 2 years or older presented prolonged PR, QRS and QT intervals. These in vivo results were confirmed in the isolated organ, using Langendorff perfused hearts. Myocytes from 30 months old mice showed longer early and late repolarization phases of the action potential (AP), in comparison with cells from animals at 3 months. By voltage-clamp, the density of the transient outward K+ current (Ito) was significantly reduced in old, whereas the late Na+ current (INaL) was increased, changes consistent with the prolonged AP of old cells. Additionally, by Western blotting, the SCN1B subunit, involved in Na+ channel gating, was reduced with age. Using field stimulation, old myocytes presented slower Ca2+ transient decay and relaxation, in comparison to young. Blockade of INaL with mexiletine in old myocytes shortened the AP duration, and fastened the decay of Ca2+ transients and relaxation. To assess the functional impact of INaL on the myocardium, papillary muscles were studied in an isometric system. Using tension-length protocols, old muscles presented elevated diastolic tension with respect to young. Importantly, inhibition of INaL in old muscles reduced diastolic tension, and attenuated the active developed force. Conversely, increasing INaL in the myocardium of young mice with anemonetoxin had opposite effects. Overall, these data indicate that aging results in a prolongation of the AP mediated, at least in part, by enhanced INaL. The prolonged repolarization of the AP contributes to the slower clearance of diastolic Ca2+ from the cytoplasm, resulting in protracted relaxation phase.
Feasibility of drug delivery to the eye's posterior segment by topical instillation of PLGA nanoparticles
Authors: Kohei Tahara, Keiichi Karasawa, Risako Onodera, Hirofumi Takeuchi
Journal: Asian Journal of Pharmaceutical Sciences (2017)

We investigated the delivery of drugs to the posterior segment of the eye by non-invasive topical instillation using submicron-sized poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs). Surface-modified PLGA NPs were developed to improve the drug delivery efficiency to the retina and were administered as topical eye drops to mice. Chitosan (CS) and glycol chitosan (GCS), which are mucoadhesive polymers, and polysorbate 80 (P80) were used as surface modifiers, and have been reported to increase the association of NPs with cells. Coumarin-6 was used as a model drug and fluorescent marker, and after ocular administration of PLGA NP eye drops, the fluorescence intensity of coumarin-6 was observed in the retina. The fluorescence image analysis indicated that there are several possible routes to the retina and fates of PLGA NPs in ocular tissue, and that these pathways involved the corneal, non-corneal, or uveal routes. Delivery to the mouse retina segments after topical administration was increased by surface modification with CS, GCS, or P80. Surface-modified PLGA NPs are a promising method for retinal drug delivery via topical instillation.
Cadherin-11 (Cad11) for detection of epithelial-mesenchymal transition (EMT) in circulating prostate cancer (PCa) cells.
Authors: Amado J. Zurita, Farideh Z. Bischoff, Ivan Gorlov, Julie Ann Mayer, Tony J. Pircher, Steve Mikolajczyk, Christopher Logothetis, Sue-Hwa Lin
Journal: Journal of Clinical Oncology (2013)

e22047 Background: CTC are believed to require EMT to metastasize. Cells undergoing EMT may lack or express low levels of epithelial markers such as EpCAM and cytokeratins (CK) and experience a cadherin switch from epithelial to mesenchymal. However, most current detection methods only rely on epithelial markers for enrichment, resulting in failure to recognize other CTC phenotypes. We previously showed that PCa cells expressing the mesenchymal (osteoblast-lineage) marker Cad11 are more likely to home to and colonize bone (Cancer Res 2010). Whether Cad11 + PCa CTC lose CK expression is uncertain. Since Cad11 is an EMT marker relevant to the bone tropism of PCa, we characterized its expression in CTC from patients (pts) with bone metastasis. Methods: Blood from PCa pts (n=86) with different extents of bone involvement was analyzed employing Biocept’s microfluidic CTC technology. For cell capture, we used a PCa CTC-optimized cocktail of antibodies that included epithelial, mesenchymal and putative stem cell markers. Captured cells were scored based on standard stain criteria (CK + /CD45 − /DAPI + ) and Cad11 expression. To ascertain malignant identity of CK − /CD45 − /DAPI + cells, we used FISH to characterize androgen receptor [AR], Myc and PTEN status. Results: Among 69 pts with detectable CK + CTC, 39% had at least 1 cell co-expressing Cad11. Very rare CK − Cad11 − CTC displaying different degrees of aneuploidy were also observed, but only in 4 pts. No single CK − Cad11 + FISH “abnormal” cell was seen. FISH profiling of individual CK + CTC revealed an association between Myc gain and PTEN loss (P=0.00004). We also found positive correlations between AR and PTEN amplification (r=0.55) as well as AR amplification and Myc loss (r=0.56; both P&lt;10 -6 ). Interestingly, CK − Cad11 + cells (range, 1-910) were observed in 45 pts, all with a “normal” pattern of AR, Myc and PTEN expression. Conclusions: Complete loss of epithelial marker expression in CTC (identified by concurrent gene alterations) is a very infrequent event in PCa pts with established bone metastasis. Simultaneous individual CTC profiling of gene gains/losses may provide insights into PCa biology. Evaluation of the identity of CK − Cad11 + cells is ongoing.
Castrate-resistant prostate cancer (CRPC): Prognostic and predictive value of testosterone levels in patients receiving chemotherapy.
Authors: Alfonso Gomez De Liano Lista, Óscar Reig, Begoña Mellado, Cristina Martin Lorente, Elena Cillan, Ismael Macias, Gemma Sancho, Joan Palou, Pablo Maroto-Rey
Journal: Journal of Clinical Oncology (2013)

e16049 Background: Recent development of new second line therapies in patients with CRPC upon progression to docetaxel has raised the question of who benefit most of either a salvage hormonal treatment (HT) or chemotherapy. Objectives: To analyze the prognostic value for survival of the absolute levels of serum testosterone (TL) in patients under definition of CRPC (PSA and/or clinical progression with a TL &lt;50 ng/dL). To analyze the probability of response to salvage HT upon failure to docetaxel. Methods: 101 patients with metastatic CRPC were included in 9 different non-hormonal first line phase II-III trials in two single institutions from August 2006 until September 2012. Inclusion criteria of those trials required castrate levels of testosterone. TL was determined by automated immunoassay. Survival was calculated since the date of entrance in the trial to death. Results: Median age was 70 years (41-89). 22% of the patients had visceral metastases. Median PSA was 51 U/L (0.04-1284). Median Hemoglobin was 13 g/dL (9.3-15.6). Median TL was 11.53 ng/dL (range undetectable to 48.9). First line chemotherapy was Docetaxel (alone or in combination) in 71/101 patients (70%). Median overall survival (OS) was 24.51 months. Patients with TL under median value (N=49) had an OS of 22.4 months, compared to 32.7 months in those whose TL was higher (N=52) (p=0.0162 , HR 0.52). Anemia (Yes vs NO) was an adverse prognostic factor (OS 20.6 vs 28.4 months, p=0.0025, HR 2.4). Patients presenting both factors (anemia and lower TL) had a worse outcome compared to those who had only one or none of them (OS: 17.9 vs 22.4 vs 38.1 m; p=0.0024). 41 patients (40.6%) were treated with salvage hormone therapy after chemotherapy failure. Baseline TL was associated with PSA response to salvage HT. Only 5/23 patients (21.74%) with TL below median value showed PSA response, vs 10/18 (55.6%) if TL was over median value. Conclusions: Testosterone even under castration level (&lt; 50 ng/dL) was a prognostic factor for survival in patients with metastatic CRPC. PSA response to salvage hormonotherapy differed depending on testosterone levels. TL could help us in treatment decision after first line chemotherapy failure.