tbuckley/cabot-search huggingface dataset:
Enhancing anti-tumor effect of magnetite nanoparticles using weak electromagnetic radiation of infra-low frequencies in experiment.
Authors: Galina Vitalyevna Zhukova, Oleg Ivanovich Kit, Alla Ivanovna Shikhlyarova, Tatiana Albertovna Barteneva, Irina Aleksandrovna Goroshinskaya, Marina Igorevna Bragina, Elena Alekseevna Shirnina, Polina Sergeevna Kachesova
Journal: Journal of Clinical Oncology (2016)

e23198 Background: Activating influence of weak electromagnetic radiation of infra-low frequencies (WER ILF) used in special regimes on systemic antitumor mechanisms was shown. Effectiveness of these factors was associated with development of antistress adaptational reactions (AR) of the organism (Garkavi L.Kh., Kvakina E.B., Shikhliarova A.I. et al., 1996). Magnetite nanoparticles (NPs) were demonstrated to have self-dependent antitumor effects on transplantable tumors in animals (Garkavi L.Kh. et al., 2010). The purpose of the study was to reveal combined effect of magnetite NPs and regulatory exposure to the weak WER ILF on malignant tumors and the organism of animals. Methods: The study included male outbred rats with Pliss lymphosarcoma (PLS, n = 25) and female С57Black/6 mice with B16 melanoma (n = 25). Magnetite NPs (10±2 nm) as magnetic fluid were injected peritumorally along the borders of tumors at a single dose of 17.7 mg/kg (6 injections every 2-3 days). Exposure to weak WER ILF (0.03 – 9 Hz; 3.5 mT and less; 7 min and less) in special regimens were performed to the head in rats and to the whole body in mice. Dynamics of tumor volumes and AR structures, status of immune system organs and some parameters of oxidant and antioxidant status were studied. Results: Weak WER ILF contributed to enhancement of antitumor effect of magnetite NPs which was demonstrated by an increase in the number of rats with PLS regression by 33% and the number of mice with increased life span compared to the control (by 1.3-2.2 times, p < 0.05) from 40 to 80%, as well as the increase in the maximum life span of mice by 8%. Enhancement of systemic antistress changes and increased antiproliferative activity in the thymus and spleen were observed, as well as decreased parameters of antioxidant system activity and similarity of their values to the values in intact animals. Conclusions: Antistress influence of WER ILF on regulatory structures enhances self-dependent antitumor effect of magnetite NPs. It may indicate the participation of immune processes in realization of magnetite NPs action on the tumor. The study was supported by RScF research project 14-35-00051.
P30 68Ga-DOTATATE PET IDENTIFIES MYOCARDIAL INFLAMMATION AND BONE MARROW MONOCYTE MOBILISATION AFTER MYOCARDIAL INFARCTION
Authors: J M Tarkin, E P V Le, C Calcagno, M R Dweck, N R Evans, M M Chowdhury, D E Newby, Z A Fayad, M R Bennett, J H F Rudd
Journal: Cardiovascular Research (2018)
Response to Open Peer Commentaries on ‘‘In Defense of ‘Denial’: Difficulty Knowing When Beliefs Are Unrealistic and Whether Unrealistic Beliefs Are Bad”
Authors: J. S. Blumenthal-Barby, Peter A Ubel
Journal: The American Journal of Bioethics (2018)

This article refers to:In Defense of "Denial": Difficulty Knowing When Beliefs Are Unrealistic and Whether Unrealistic Beliefs Are Bad
Single-center analysis of 109 patients (pts) with metastatic chromophobe renal cell carcinoma (ChRCC): Differences in outcomes by histologic variant.
Authors: Yasser Ged, Andrea Knezevic, Yingbei Chen, Almedina Redzematovic, Maria Isabel Carlo, Chung-Han Lee, Darren R. Feldman, Sujata Patil, Robert J. Motzer, Martin Henner Voss
Journal: Journal of Clinical Oncology (2018)

4577 Background: ChRCC constitutes 5-10% of all RCC cases, and is generally associated with better prognosis including benefit from approved targeted agents (Armstrong, Lancet Onc, 2016). Presence of sarcomatoid features (SF) have previously been proposed as an adverse prognostic marker, but data for systemic therapy is limited. We assessed therapeutic outcomes for pts with metastatic ChRCC with and without SF. Methods: Retrospective chart reviews of pts with newly diagnosed metastatic ChRCC evaluated at Memorial Sloan Kettering Cancer Center (MSKCC) between 2002-17. MSKCC pathology reports determined presence/absence of SF to categorize pts. Evaluated endpoints included overall survival, time to treatment (TTF) for pts who initiated first line therapy at MSKCC and time to recurrence (TTR) post nephrectomy with metastatic disease. OS between the 2 groups was compared using log-rank analysis. A subset of pts had next generation sequencing (NGS) with MSK-IMPACT. Results: 109 pts with newly diagnosed metastatic ChRCC were identified (80 without SF, 29 with SF). Pts with SF were more likely to present with IMDC poor risk status (31% vs 10%) and de novo metastatic disease (48% vs 19%). 52 pts initiated first line therapy at MSKCC (35 without SF, 17 with SF). First line agents included VEGF tyrosine kinase inhibitors (60%), mTOR inhibitors (13%), cytokines (6%) and other investigational agents (21%). Outcomes are summarized in table below. NGS was performed in 22 pts, of which 64% and 45% harbored TP53 and PTEN alterations. Conclusions: Pts with metastatic ChRCC with SF had significantly worse outcomes compared to pts without SF. Median TTR < 3 months for this subgroup supports close surveillance following nephrectomy for localized tumors. The lack of benefit observed across various classes of systemic agents warrants study of underlying biology and investigating novel agents. Outcome (Median) All pts N = 109 Months (95% CI) ChRCC without SF N = 80 Months (95% CI) ChRCC with SF N = 29 Months (95% CI) Log-rank OS 25 (12, 33) 38 (26, 51) 7.5 (4.2, 10.7) HR 4.7 (95% CI: 2.7, 8.2) p < 0.001 TTF 5.1 (2.7, 8.0) 8.0 (5.1, 13.0) 1.8 (0.9, 2.7) - TTR 25.5 (23.4, 58.3) 48.8 (30.8, 80.7) 2.7 (0.7, 6.9) -
Baseline bone mineral density testing among breast cancer patients prescribed aromatase inhibitors (AIs).
Authors: John A. Charlson, Elizabeth Smith, Purushottam Laud, Alicia Smallwood, Joan Neuner
Journal: Journal of Clinical Oncology (2013)

6642 Background: Because of the adverse effects of AI’s on bone mineral density (BMD) and fracture risk, current guidelines recommend baseline BMD testing when initiating adjuvant AI’s. Methods: We used a validated breast cancer algorithm of Medicare claims to identify older US female breast cancer patients starting adjuvant AI therapy and to examine baseline BMD testing rates. The cohort included all US non-HMO Medicare D-enrolled women age ≥67 years who initiated AI therapy within one year after a 2006-2007 initial breast cancer surgery. Women receiving IV bisphosphonates consistent with metastatic breast cancer treatment (interval &lt;90 days)were excluded. We examined BMD testing between 24 months prior and 6 months after AI initiation, adjusting for demographic and fracture risk factors, and comparing to a duration-adjusted testing rate for a 5% random sample of all cancer-free women enrolled in Medicare in 2008. Results: A majority of the cancer cohort (67.7%) had baseline BMD testing. This was substantially higher than the 2008 BMD testing rate for the non-cancer sample (15.4%, which translates into a 38.5% 30-month rate). Women of higher age and co-morbidity, as well as women of black race or lower income were less likely to be tested (see Table). Empiric use of oral bisphosphonates increased slightly with age, but this did not fully account for the testing differences by age. Conclusions: Although baseline BMD testing is high among women initiating AIs, approximately one-third do not receive guideline-recommended testing. Furthermore, those with greater risk fracture risk based on age and higher co-morbidity are less likely to have appropriate bone care. [Table: see text]
Real world data in luminal like de novo metastatic breast cancer following guidelines recommendations.
Authors: Fernando Pikabea, Borja Lopez De San Vicente, Elena Galve Calvo, Juan Fernando Arango, Ane Zumarraga, Maria Lopez Santillan, Covadonga Figaredo, María Ángeles Sala, Maria Teresa Abad, Maria Teresa Perez hoyos, Laura Sande, Maitane Nuño, Patricia Novas, Jairo Legaspi, Leire Zubiri, Purificación Martinez
Journal: Journal of Clinical Oncology (2018)

e13029 Background: De novo metastatic breast cancer (dnMBC) represents approximately 6–10% of breast cancer. In luminal-like dnMBC recommendation for endocrine therapy (ET) as first-line treatment is reported by the main international guidelines. Unfortunately studies show that around 30% of these patients receive chemotherapy (CT) as first treatment, despite the higher toxicity and no proved superior efficacy. Aim of this study was to describe the use of CT and ET as first-line treatment in real world scenario. Methods: This retrospective study analyzed our serie of consecutive patients (p) with luminal like dnMBC treated at the Basurto University Hospital (Spain) between 2006 and 2015. We analyzed overall survival (OS), progression free survival (PFS), first-line treatment choice (ET vs CT), and which factors were related with this choice. Results: Of 129 p. dnMBC, 84 p. luminal-like were identified. Median age 66.2 years (SD 14.43). Ductal carcinoma 69p. (82%), luminal B like 50p. (59.5%), only bone and soft tissue disease 44p. (52%), one metastatic site 42 p. (50%), and primary tumor surgery was realized in 22p. (26%). First-line CT was chosen in 15p. (18%) and 69 p. (82%). received ET. In the whole population median overall survival (OS) was 30 months (m) 95%C.I. (24.39-35.60), while median progression free survival (PFS) was 9 m 95% C.I.(5.98-12.01).In patients treated with CT as first-line treatment, median OS was 26m 95%C.I. (0-52.31) and median PFS was 3 m 95%C.I. (1.84-4.14). Among cases treated with ET as first-line treatment, median OS was 30m 95%C.I. (24.22-35.78) months and median PFS was 11 m 95%C.I.(8.10-13.89). No statistically difference of PFS and OS were seen between treatments. On multivariate analysis factors related to use of ET in first line were: > 70 years (OR 0.18, CI 95 % (0.04-0.70); presence of bone and soft tissue metastases only (OR 0.19 CI 95% (0.05-0.77); and date of diagnosis before or after 2010 (OR 0.11 CI 95% (0.02-0.56). Conclusions: Our study showed that ET was the preferred first-line therapy in luminal-like MBC in our clinical practice according to the current guidelines. No differences in OS or PFS were seen. Old age, non-visceral metastases and date of diagnosis were related with ET chosen.
Survival and immune analysis of radium-223 in patients with metastatic prostate cancer.
Authors: Joseph W. Kim, Min Shin, Youna Kang, Insoo Kang, Daniel Peter Petrylak
Journal: Journal of Clinical Oncology (2018)

e24144 Background: Radium223 (Ra223) is a radioisotope therapy that delivers high-energy radiation to osteoblastic metastasis of prostate cancer, resulting in detrimental irreparable double-stranded DNA damage. We previously reported the immune analysis of Ra223 in patients with metastatic prostate cancer. Here, we report the survival data of these patients and immune correlates. Methods: Fifteen men with castration resistant prostate cancer with osseous metastases with clinical indication for Ra223 and without any autoimmune or immune deficiency conditions were enrolled. Patients received a course of Ra223 50kBq/kg either as a standard of care or on a clinical trial as a monotherapy. Concurrent use of prednisone ≤ 10mg a day, was allowed. Patients were followed for survival. Peripheral blood mononuclear cells (PBMCs) were llected before and 3 to 4 weeks after the first dose of Ra223 50kBq/kg. PBMCs were purified, stimulated and stained for different subsets of CD8+ T cells and expression of co-inhibitory molecules as well as the cytokines. Results: The median overall survival in our study patients were 11.6 months (Range: 3.2~30.8). The median overall survivals among patients whose PD1+ CD8+frequency increased and among those whose frequency decreased were 20.8 months and 10.1 months, respectively (p = 0.1936). In addition, there was a trend toward a positive correlation between overall survival and baseline frequency of CD8+T cells producing TNF-a (Pearson’s correlation R = 0.5076, p = 0.0921). Conclusions: A trend toward superior survival was noted among those whose frequency of PD-1 expressing CD8+ T cells increased after a Ra223 treatment. This finding warrants further investigation and validation.
Phase 1b study of panobinostat in combination with lenalidomide, bortezomib, and dexamethasone in relapsed refractory multiple myeloma.
Authors: Jacob Laubach, Sascha Alexander Tuchman, Jacalyn Rosenblatt, Robert Redd, Kathleen Colson, Ashley Motta, Kathleen Fitzpatrick, Edie Weller, Paul G. Richardson
Journal: Journal of Clinical Oncology (2016)

8014 Background: Panobinostat (pano), a potent inhibitor of histone deacetylases (HDACs), is approved for use in combination with bortezomib (bortez) and dexamethasone (dex) in relapsed and refractory multiple myeloma (RRMM). This phase 1b study (NCT01965353) evaluated the safety and efficacy of pano plus len, bortez, and dex (RVD). Methods: The primary objective was to evaluate the MTD and safety of pano plus len, bortez, and dex in RRMM. Secondary objectives included overall response rate (ORR), progression-free survival (PFS), and time to progression (TTP). Patients (pts) had to have received > 2 prior lines of therapy. Pano was administered orally on days 1, 3, 5, 8, 10, and 12 of a 21 day cycle; len 15 mg on days 1 – 21; bortez IV/SC 1.0 mg/m2 on days 1, 4, 8, and 11; and oral dex 20 on the day of and day after bortez. A standard 3+3 dose escalation design was utilized, followed by a 10-pt dose expansion. Adverse events (AEs) were graded by NCI-CTCAE v4 and responses assessed by the modified Uniform Response Criteria. Results: This analysis includes all pts in the dose escalation phase of the study and six from the dose expansion phase (n = 16). Among 10 pts in the dose escalation phase, 6 were treated at Dose Level 1 (pano 10 mg) and 4 at Dose Level 2 (pano 15 mg). Toxicity data is available in 15 of 16 pts, and response data in 14 of 16. Median prior lines of therapy was 4 (2 – 14) and median duration of follow up 7.8 months. There were 3 DLTs: Grade (G) 3 hyperglcyemia at the MTD of pano 10 mg and both G3 neutropenia leading to C2D1 delay and G4 thrombocytopenia at pano 15 mg. G3/4 hematologic AEs included anemia (13%), thrombocytopenia (26%), and neutropenia (20%). G 3/4 non hematologic AEs included dyspnea (7%), hyperglycemia (7%), and hypophosphatemia (20%). One pt experienced a G5 event in cycle 2 due to rapid disease progression. The ORR was 35%, including 2 pts with partial response (14%), 2 pts with VGPR (14%), and 1 pt with stringent complete response (7%). The median overall survival, PFS, and TTP were 13, 5, and 7 months respectively. Conclusions: The combination of pano plus len, bortez, and dex was well tolerated at the MTD of pano 10 mg and associated with a high level of durable response in pts with heavily pre-treated RRMM. Clinical trial information: NCT01965353.
Lean thinking: Exploring the volume of overhead and supplementary tasks (OST) in cancer care (CC) in the oncology outpatient encounter (OOE) in two tertiary centres.
Authors: Geoffrey David Peters, Madiha Rasool, David D Smith, Rahul Ladwa, David Wyld, Melissa A. Eastgate, Wen Xu, Paul Nicholas Kalokerinos, Joanne Yue-Ai Tan, Jeffrey C. Goh, Michelle K. Nottage, Po-Ling Inglis, Matthew E. Burge, Haider Al-Saig, Brett Gordon Maxwell Hughes, Zarnie Lwin
Journal: Journal of Clinical Oncology (2016)

6589 Background: As CC becomes increasingly complex clinicians face the challenge of meeting patients’ holistic care needs within limited time. Moreover, inefficient information technology systems (ITS) and multiple OST can impact upon time spent on direct CC. We explored the quantity of OST in OOEs. Methods: Two separate focus groups were conducted at a tertiary institution with oncology specialists (5) and trainees (5) to explore scope of OST required in each OOE. Content analysis was performed to define: Core, Contested, and Peripheral tasks related to direct CC. Core tasks were excluded. Contested and Peripheral tasks were further grouped into 4 themes: Script, Wait, Chase, and Consent. An audit tool was devised under these 4 themes and consensus obtained for OST item list. A prospective audit was then performed over a 2 week period for OOEs at 2 tertiary institutions. Frequency data per task were captured, tabulated and dotcharts plotted. We tested for differences between groups using two sample t-tests and Fisher’s Exact tests for proportions. Results: Among 588 OOEs, 396 (67.3%) were captured. 43% patients had curative intent treatment. Overall, we documented a median of 2.8 OST per patient encounter. 28.3% needed scripts or forms completed and 15.9% prescriptions for comorbidities unrelated to cancer. Multiple repeat computer logins for different domains included; 55% pathology, 32% radiology, 29% chemotherapy (CT) prescribing software and 24% electronic notes. In 19% imaging and pathology results required chasing from other resources. 8.2% required consent for trials and others. There were statistically significant differences between hospitals in: number of OST (p < 0.001), proportion of encounters that required at least one OST in scripts (p = 0.0221), waiting ( < 0.001), chasing ( < 0.001), and overall (p < 0.001). No differences were found comparing CT alone versus chemoradiation or curative vs palliative intent. Conclusions: A significant volume of OST in the daily OOE are not related to direct CC. Quality improvements in integrated ITS and streamlining non-core tasks are vital for future CC planning in the era of integrative medicine and Big Data.
Beyond the margins: Economic costs and complication rates associated with repeated breast-conserving surgeries.
Authors: Leanne N. Metcalfe, Adam M. Zysk, Gerald Edelman, Lan Vu, Andrew J. Cittadine, Kathryn B. Hyer, Alastair Mark Thompson
Journal: Journal of Clinical Oncology (2016)

1050 Background: Considerable attention has been paid to the problem of repeated breast-conserving surgery (BCS; i.e., lumpectomy), but the costs and complications due to these additional operations are not well-characterized. To address this issue, a retrospective review of insurance claims data for BCS patients was performed to assess complications and economic outcomes. Methods: Private claims from a single insurer were analyzed for 9,457 women undergoing BCS for breast carcinoma between January 2010 and September 2013 in either Illinois, New Mexico, Oklahoma, or Texas. Patients undergoing a second open breast surgery (i.e., mastectomy or BCS) within 90 days of the initial BCS were classified as having a repeated surgery. Complications were identified via a set of 8 CPT and 25 ICD9 diagnosis and procedure codes related to breast cancer treatment. The analysis included these complications and the total cost of all allowed healthcare claims within two years following diagnosis. Results: 7,287/9,457 patients (77% ±0.9%, 95% confidence interval) had one BCS operation and 2,170 patients (23% ±0.9%) had at least one repeated surgery (Table). The mean patient age was 53 years. The mean two-year cost for patients undergoing a single BCS was $88,733 (±$1,884) and the cost for patients undergoing a repeated breast surgery was $104,482 (±$3,719), $99,554 for a second BCS and $117,967 for subsequent mastectomy. The mean added cost due to a repeated surgery was $16,352. The percentage of patients experiencing at least one complication was 23.7% (±1.0) for those undergoing one BCS only and 35.2% (±2.0) for those undergoing a repeated surgery. Conclusions: For the 23% of women undergoing a second operation after BCS, complications were 49% more common and the mean total cost of surgery increased more than $16,000, demonstrating a patient-centered and fiscal imperative to reduce reoperations in BCS for breast cancer. BCS, No Repeat Repeated Breast Surgery Repeated BCS Convert to Mastectomy Patients 7,287 1511 659 Percentage 77% 16% 7% Patients with Complication(s) 1,729 497 267 Percentage 24% 33% 41% Mean Two-Year Cost Per Patient $88,733 $99,554 $117,967
Evaluating the reversible control of an engineered CAR T cell ON-switch.
Authors: Amy Gilbert, Stephen Santoro, Tiffany Tse, Tara Candelario-Chopra, Tina Gomes, Jose Campos, Michael Spelman, Stephaine Seacrest, Scott Coyle, Levi Rupp, Peter Emtage
Journal: Journal of Clinical Oncology (2017)

e14550 Background: CAR T cell therapy holds enormous promise for many cancer types but its application may be limited by serious toxicities. To lower this hurdle, our aim is to engineer tunable cell therapies. One of our approaches includes a “ON-switch” chimeric antigen receptor (Wu et al., Science 2015) that requires the administration of a small molecule acting as a dimerizing agent between one polypeptide chain containing the antigen recognition domain and half of an inducible heterodimerization system and another polypeptide chain containing the second half of the inducible heterodimerization motif, the CD3ζ chain and a costimulatory motif. Using an FDA approved small molecule drug, we evaluate the reversibility of ON-switch CAR T cells in preclinical models. Methods: First, we evaluated the proliferation, cytotoxicity and cytokine production of several ON-switch constructs in human primary T cells. Next, to address the reversibility of the ON-switch (ON→OFF→ON), we performed a series of co-culture experiments where the small molecule drug was added to tumor cells and ON-switch CAR T cells, then washed out, and then re-introduced back into the co-cultures. We compared CAR T cell mediated killing and cytokine production from the On-switch CAR T cells relative to a canonical CAR T control. Results: Our On-switch CAR T cells were shown to proliferate, secrete cytokines as well as mediate dose dependent cytotoxicity in the presence of the small molecule drug. Importantly, in the presence of antigen but in absence of the small molecule drug we did not measure any significant functional activity in our ON-switch CARs. Additonally, following the removal of the small molecule drug over a period several days we did not observe any significant CAR mediated cytotoxicity. Following the subsequent re-addition of the small molecule, we observed further CAR T cell mediated cytotoxicity against tumor cells. Conclusions: These results show that the small molecule inducible On-switch CARs maintain functional activity as well as reversibility allowing for the tunable control of a CAR T cell.