tbuckley/cabot-search huggingface dataset:
Camouflaging iRGD-EGFR anchored human cytotoxic T-lymphocyte membranes to the surface of nanoparticles combined with low-dose irradiation: New approach to enhance drug-delivery targeting in gastric cancer.
Authors: Lianru Zhang, Huizi Sha, Rutian Li, Jia Wei, Baorui Liu
Journal: Journal of Clinical Oncology (2017)

e14076 Background: We report a biomimetic delivery platform based on human cytotoxic T-lymphocyte membranes. In this platform, T-lymphocyte membranes were camouflaged to the surface of poly-lactic-co-glycolic acid nanoparticles, with local low-dose irradiation (LDI) as a chemoattractant. These carriers were further anchored with the recombinant protein anti-EGFR-iRGD, improving tumor accumulation, facilitating tumor uptake. Methods: The T-lymphocyte membrane coating was verified by dynamic light scattering, transmission electron microscopy and confocal laser scanning microscopy. The particle phagocytosis study was performed using a human phagocytic cell line. In vivo NIR fluorescence imaging was performed to monitor the route of nanoparticles. EGFR expression of tumor cells was tested before and after LDI. Results: This new platform reduced phagocytosis of macrophages by 23.99% (p = 0.002). iRGD-EGFR anchored T-lymphocyte membrane-encapsulated nanoparticles accumulated in tumor site more than unfunctionalized groups, while LDI significantly enhanced the targeting ability. LDI could up-regulate EGFR expression on tumor cells, which was important in the process of localization of iRGD-EGFR anchored T-lymphocyte membrane-encapsulated nanoparticles in tumors. Conclusions: This new platform included both the long circulation time and tumor sites accumulation ability while LDI could significantly enhance the tumor accumulation ability.
Tyrosine kinase inhibitor (TKI) therapy discontinuation in patients with CML in chronic phase: A US clinical practice perspective.
Authors: Ellen K. Ritchie, Johannes E. Wolff, Dominick Latremouille-Viau, Annie Guerin, Irina Pivneva, Owanate Briggs, George J. Joseph, Ehab L. Atallah
Journal: Journal of Clinical Oncology (2017)

7052 Background: This study assessed TKI discontinuation practice in the US before the publication of new practice guidelines in November 2016 including recommendations on TKI discontinuation for patients (pts) with CML in chronic phase (CML-CP). Methods: From 10/12/2016 to 11/9/2016, 300 US oncologists/hematologists completed a survey on the reasons for TKI discontinuation in pts with CML-CP, their perspective on adequate response pts should achieve before considering TKI discontinuation (minimum response to TKI, response duration, and TKI therapy duration), and post-discontinuation CML monitoring. Results: One third of participating physicians reported having attempted TKI discontinuation (102 of 300); 66 did so outside of a clinical trial. Physicians who reported TKI discontinuation were more likely to practice in academic centers; were more experienced clinicians ( &gt; 10 years in practice); and followed a larger number of CML pts vs those who did not. Among the 66 physicians, the majority would consider TKI discontinuation for medical reasons (76% adverse events, 47% pregnancy planning), with fewer for economic reasons (35%); 12% reported they would consider it for all of their pts who achieve an adequate response. There was no consensus on the minimum response achieved (56% consider a decrease in BCR-ABL of ≥4.5 log, 21% 3 log, and 11% 1 log), the minimum response duration (29% 3 yrs, 24% 2 yrs, and 20% 1 yr), and the minimum TKI therapy duration (44% 3yrs, 20% 2 yrs, 19% 1 yr) before TKI discontinuation. There was no consensus on the frequency of CML monitoring post-discontinuation with &lt; 10% of physicians considering monthly molecular monitoring in the first year. Conclusions: TKI discontinuation in pts with CML-CP responding to TKI was attempted outside of clinical trials without clear guidelines. Conditions under which TKI therapy was discontinued differed from new recommended practice guidelines, which may have resulted in discontinuation where deep response may not be achieved and disease not adequately monitored. The recommended practice guidelines need to be communicated to physicians as TKI discontinuation is likely to be conducted in a broader population.
Extended tacrolimus release via the combination of lipid-based solid dispersion and HPMC hydrogel matrix tablets
Authors: Hui Xu, Li Liu, Xuehui Li, Junyuan Ma, Rui Liu, Shaoning Wang
Journal: Asian Journal of Pharmaceutical Sciences (2018)

The objective of this study is to evaluate the feasibility of obtaining extended release of tacrolimus by a novel combination of lipid-based solid dispersion and matrix-type extended release tablet techniques. Tacrolimus solid dispersion was prepared using glycerylbehenate (Compritol® ATO888) and Pluronic F127 as the carrier materials with hot-melt method, which was then blended with hydrogel matrix materials, such as HPMC and lactose, the powders were directly compressed into tablets. In vitro drug release tests were carried out to evaluate the performance of the solid dispersions and the tablets. The dissolution rate of tacrolimus was significantly improved by the lipid-based solid dispersion, and the incorporation of HPC into the solid dispersion obviously improved its stability after storage. Extended release tablets loaded with tacrolimus solid dispersion showed prolonged drug release patterns over 24 h, the release patterns of the tablets can be tailored by the compositions of the matrix materials, including the types and content of HPMCs. A modified processing method that directly mixed the melted solid dispersion with HPMC powders improved the uniformity of the solid dispersion inside the tablet matrix and release profile. The release data of the extended release tablet fitted well to the Korsmeyer-Peppas model with n value of 0.85, which suggested diffusion- and erosion-controlled release mechanism. The combination of lipid-based solid dispersion and HPMC hydrogel matrix may find wide applications in the extended release dosage forms of high potent, water-insoluble drugs.
Bias in valuation of health care benefits in metastatic prostate cancer: A contingent valuation of willingness to pay.
Authors: Nuno Sousa, Telma Costa, Matilde Monteiro-Soares, Francisco Rocha Gonçalves, Luis Filipe Azevedo
Journal: Journal of Clinical Oncology (2017)

6616 Background: Willingness to pay (WTP) studies assess societal valuation of healthcare interventions. Prostate cancer (PC) is the most common cancer diagnosis in men. We explore factors that may bias valuation of health care benefits through contingent valuation of WTP for therapeutic innovation in metastatic castration-resistant PC. Methods: Cross-sectional study of Portuguese Society (SOC) and Healthcare Providers (HCP). Monthly WTP assessed through biding and open-ended questions by standardized survey with 2 baseline scenarios: ScA 12-month median survival, ScB 30-month median survival. Respondents considered own financial resources and expenses and for each therapeutic scenario reported WTP, out-of-pocket, and expected National Healthcare System (NHCS) WTP. Impact of demographic, personal medical history and household income assessed by tweedie generalized linear model. Results: 1000 subjects on societal cohort and 100 physicians provided valid responses. Subjects reported higher WTP values when NHCS was to provide treatment compared to out-of-pocket cost. For NHCS perspective median WTP for ScA was 2,133€ for HCP vs 5,510€ for SOC and ScB 1 963€ for HCP vs 5,479€ for SOC. Overall, societal cohort’s NHCS mean WTP was 2.6 (ScA) and 2.8 (ScB) times higher (p &lt; .001) than healthcare providers, but with no difference for out-of-pocket WTP. This difference remained significant when adjusted for all other factors. Additionally, subjects with prior personal or familial history of cancer and subjects with higher household income provided higher WTP estimates. In HCP cohort, urologists reported higher WTP compared to Medical Oncologists. Conclusions: This study provides critical insight into differing valuation of cancer treatments between physicians and society and potential biases in individual valuation of healthcare benefits. Improvement of societal’s perception and understanding of cost-benefit assessments is critical to designing an equitable healthcare system.
A phase II study of induction chemotherapy with docetaxcel, cisplatin, and S-1 (DCS) for gastric cancer with peritoneal metastasis (KUGC06): Early results.
Authors: Hiroshi Okabe, Hiroaki Hata, Shugo Ueda, Hisahiro Hosogi, Shuichi Ota, Yousuke Kinjo, Nobuaki Hoshino, Shigeo Hisamori, Shigeru Tsunoda, Kazutaka Obama, Yoshiharu Sakai
Journal: Journal of Clinical Oncology (2017)

e15574 Background: Although the prognosis of gastric cancer with peritoneal metastasis is extremely poor, we previously showed the significant efficacy of S-1 plus cisplatin for limited peritoneal dissemination, and favorable outcome following curative resection. We conducted a phase II study to evaluate the safety and efficacy of induction chemotherapy with docetaxel, cisplatin, and S-1 (DCS) triplet regimen for patients (pts) with gastric cancer with peritoneal metastasis. Methods: The key eligibility criteria were gastric cancer with peritoneal metastasis or positive peritoneal cytology, without any other distant metastases, age between 20 and 75 years old, PS 0 or 1, capable of oral administration, and adequate hematologic, hepatic, and renal function. Pts received three 28-day cycles of DCS (cisplatin of 60 mg/m2, docetaxel of 40mg/m2 on day 1, and S-1 of 80 mg/m2 from day 1 to 14). Following evaluation for resectability, pts received D2 gastrectomy if R0 was possible. Primary endpoint was R0 resection rate. Secondary endpoints were clinical response of peritoneal metastasis, overall response, pathological response, adverse events, progression free survival, and overall survival. Sample size was determined to have 80% power for detecting 20% improvement of R0 resection rate over 45% baseline at one-sided alpha of 0.1. Results: Between June 2011 and April 2015, 30 pts were enrolled. All pts started DCS and were included in the analysis. Three cycles of DCS (80%) were completed in 24 pts (80%). The most frequent grade 3/4 toxicity was neutropenia (60%). Complete response of peritoneal metastasis was observed in 16 pts (53%), 21 pts underwent surgery, and 14 pts achieved R0 resection (47%; 95%CI, 28-66%). When the extent of peritoneal metastasis was classified as P0CY1, P1, P2, and P3 according to the Japanese classification, R0 resection rate for each group was 63%, 60%, 46%, or 0%, respectively. Conclusions: Induction chemotherapy with DCS is safe, and could achieve R0 resection in some patients with limited peritoneal metastasis or positive peritoneal cytology. However, the efficacy seems to be similar to the conventional S-1 plus cisplatin. Clinical trial information: UMIN000004932.
Response assessment to anti-CTLA4 or/and anti-PD1 immunotherapy in mucosal melanomas.
Authors: Antoine Moya-Plana, Ruth Gabriela Herrera-Gómez, Caroline Rossoni, Laurent Dercle, Samy Ammari, Isabelle Girault, Severine Roy, Jean-Yves Scoazec, Stephan Vagner, Francois Janot, Caroline Robert
Journal: Journal of Clinical Oncology (2018)

e21517 Background: Immune-checkpoint inhibitors improved significantly the outcomes of metastatic cutaneous melanoma. For rare sub-groups such as mucosal melanomas, only few published data are available. They suggest a lower response rate than in cutaneous melanoma without taking into account the primary tumor location. Methods: A single-center, retrospective cohort analysis of prospectively collected data on all patients with locally advanced and/or metastatic mucosal melanoma who received anti-CTLA4 (ipilimumab) and/or anti-PD1 (pembrolizumab) immunotherapy. Progression-free survival (PFS) and overall survival (OS) were assessed using the Kaplan-Meier method. Objective responses were determined using RECIST version 1.1. Results: 45 patients were enrolled; median age was 63 years. The location of the primary melanoma was head and neck (43%), ano-rectal (31%) and vulvo-vaginal (26%). At inclusion, 11 patients were stage 3 and 11 stage 4. Twenty-eight patients had previous surgery, 27 previous radiotherapy and 17 had received prior systemic therapy. First-line immunotherapy was ipilimumab in 24 (55%) patients and pembrolizumab in 20 (45%). The objective response rate (ORR) was 8.2% (including 1 complete response (CR)) for ipilimumab and 35% (including 4 CR) for pembrolizumab. No significant difference was observed with regards to the primary tumor location. Median follow-up was 24 months (range 4 to 73). The median PFS in the first-line ipilimumab group and in the first-line pembrolizumab group was 3 months (CI 95%, 2.5 to 4.6) and 5 months (CI 95%, 2.6 to 33.1) respectively (p = 0.0147). PDL1 expression in tumor cells and intra-tumoral CD8 T-cell infiltration appeared to be associated with ORR. Patients who received pembrolizumab after ipilimumab failure (N = 8) had an ORR of 12.5% with a median PFS of 8 months. Conclusions: We found objective response and PFS rates comparable to those obtained in cutaneous melanoma, with no significant differences between the different types of mucosae involved. Because of the lower mutational burden in mucosal melanoma than in cutaneous melanoma, it will be of particular interest to further explore the mechanisms underlying checkpoint inhibitors efficacy in this melanoma subtype.
Response to apatinib by the number of metastatic organs in patients with advanced or metastatic gastric cancer: Subgroup analysis from a phase IV study (Ahead-G201).
Authors: Yifu He, Jin Li, Shukui Qin, Lu Wen, Junsheng Wang, Wenying Deng, Guifang Zhang, Tongfu Jia, Yi Ba, Haijun Zhong, Jianwei Yang, Xiaoyan Lin, Yu-Xian Bai, Zhong Xie, Tienan Yi, Xiangyuan Wu, Feng Ye, Yong Huang, Mei Wang, Likun Liu
Journal: Journal of Clinical Oncology (2018)

e16028 Background: Some studies have shown that number of metastatic sites is a significant prognostic factor in metastatic gastric cancer. In this subgroup analysis, data from a large phase IV trial were collected to assess the effect of the number of metastatic organs on apatinib treatment in patients with advanced or metastatic gastric cancer. Methods: The patients were stratified by the number of metastatic organs (≤2 or > 2). The toxicities and clinical outcomes were compared. Results: There are 824 patients with ≤2 metastatic organs and 545 patients with > 2 metastatic organs (data cut-off 2017/12/21). For baseline characteristics, differences were observed in age, gender, metastatic sites and the number of focus at baseline. The mean daily medication dosage was 510.8±99.2 mg vs. 510.1±96.7 mg, and there was no difference between two groups. The toxicities in two groups were similar, whether in incidence of all grade drug related AEs (66.4% vs. 62.9%, p= 0.203) and grade ≥3 AEs (29.6% vs. 30.8%, p= 0.631). For efficacy profile, two groups achieved similar objective response rate (ORR, 9.0% vs. 11.0%, p= 0.428) and disease control rate (DCR, 69.0% vs. 69.2%, p= 0.952). Compared with patients with > 2 metastatic organs, the patients with ≤2 metastatic organs achieved longer OS (7.6 mos vs. 5.3 mos, p< 0.001). The PFS in patients with ≤2 metastatic organs seemed longer, but the difference was not statistically significant (4.6 mos vs. 3.3 mos, p= 0.453). Multivariate regression analysis confirmed that the number of metastatic organs was an independent prognostic factor for OS, patients with ≤2 metastatic organs were associated with longer OS (HR 1.71; 95%CI, 1.35-2.15). Conclusions: Apatinib treatment was safe for all patients regardless of the number of metastatic organs. For patients with advanced or metastatic gastric cancer, the number of metastatic organs ≤2 was associated with longer OS. Clinical trial information: NCT02426034.
Inpatient utilization of naloxone at a tertiary cancer center.
Authors: Shalini Dalal, Lee Cheng, Carin Hagberg, Alma Yvette DeJesus, Eduardo Bruera, Maria Alma Rodriguez
Journal: Journal of Clinical Oncology (2018)

e18830 Background: Opioids are the mainstay of pain management in cancer patients, but may be associated with respiratory depression and excessive sedation, likely a result of opioid overdose. Hospital use of naloxone to reverse these effects can be analyzed for opioid safety trends and identify areas for improvement. The objectives of this study was to quantitate naloxone use among hospitalized adult ( > 18 years) cancer patients. Methods: Inpatient admissions between January 01, 2017 and December 31, 2017 were retrospectively reviewed at the University of Texas MD Anderson Cancer Center. Data collected included: the use of any opioid and naloxone, as well as the source of inpatient admissions (via the Emergency Center (EC), outpatient operation room (OR) or others (e.g. direct admissions). Results: In 2017, there were 15,861 unique cancer patients (mean age 60 years [range 18-97 years]) that accounted for a total of 27,876 inpatient admissions, resulting in 225,997 total inpatient-days. Of 225,997 inpatient-days, the inpatient-days with opioid use was 150,775 (66.72%) and inpatient-days with both opioids and naloxone use was 549 (445 unique patients). The hospital incidence rate of naloxone administration per 1,000 inpatient opioid days was 3.64% (549/150,775). Of 27,876 admissions, admissions that occurred via the EC had higher frequency of naloxone use (1.75%, 234/13,388) as compared to admissions via the OR (1.41%, 95/6,726) and others (1.30%, 101/7,762) during their hospital stay (P < 0.05 ). Conclusions: The overall incidence of naloxone use for suspected opioid-related overdose was low among patients during their hospitalization at a tertiary cancer center. We found admissions that occurred via the EC to have a higher frequency of naloxone administration as compared to admissions via the OR and others. This information is being used to drive improvements in patient safety
A prospective, real-world study of treatment patterns in early-stage breast cancer (ESBC) patients (pts) at high risk for febrile neutropenia (FN).
Authors: Spyridon Tzivelekis, Scott Stryker, Zandra Karina Klippel, Wayne Sheldon, Yanli Li, David Chandler, Arun Nagarajan, Maureen Reiner
Journal: Journal of Clinical Oncology (2016)

e21653 Background: ESBC is commonly treated with myelosuppressive chemotherapy, and maintaining high relative dose intensity (RDI) is associated with improved survival. However, FN can result in reduced RDI. Primary prophylaxis (PP) with colony-stimulating factors (CSFs) has been shown to reduce FN incidence, but real-world evidence on the use and patterns of chemotherapy and supportive care with CSFs is limited. Here we describe current, real-world use of chemotherapy and CSFs, RDI, and FN among ESBC pts. Methods: This was a prospective cohort study of adult pts who received their first myelosuppressive chemotherapy course for ESBC and had a high FN risk based on a combination of chemotherapy regimen and individual FN risk factors (eg, age, comorbidities, pre-existing neutropenia, infection). PP was defined as receiving CSF prior to a serious neutropenia or FN event in the first and all subsequent cycles of the chemotherapy course. RDI was defined as delivered dose intensity relative to planned dose intensity. FN was defined as having an absolute neutrophil count (ANC) < 1.0 x 109/L and a temperature > 38.0°C within 24 hours; or ANC < 1.0 x 109/L and documented sepsis, infection, and/or FN-related hospitalization. A logistic regression model was used to estimate the odds ratio (OR) and 95% CI of achieving RDI ≥ 85% with PP vs no CSF or other use of CSF. Results: 797 pts from 105 community oncology sites across the continental US and Puerto Rico were included. 99% were female, 81% white, and mean (SD) age was 55 (11) years. 50% were diagnosed with luminal A and 23% with triple-negative breast cancer. 39% received dose-dense AC, 22% TC, 18% TCH, 8% TAC, 8% AC Q3W, and 5% other regimens. 82% of pts received PP with CSF. Mean (SD) RDI across all pts was 91% (19%), and 81% of pts achieved an RDI ≥ 85%. Pts were significantly more likely to achieve an RDI ≥ 85% if they received PP with CSF (OR: 3.1, 95% CI 2.0, 4.8). FN incidences were 7% across all cycles and 3% in cycle 1. Conclusions: These data provide a large-scale description of current, real-world US treatment patterns in ESBC. Dose-dense and taxane-based chemotherapy regimens were the most commonly used. PP with CSF helped optimize chemotherapy RDI.
The cost-effectiveness of alectinib in anaplastic lymphoma kinase-positive (ALK+) advanced NSCLC previously treated with crizotinib.
Authors: Josh John Carlson, William Bruce Wong, William Canestaro
Journal: Journal of Clinical Oncology (2016)

6610 Background: Two phase II studies (NP28761 & NP28673) demonstrated the efficacy and safety of alectinib in anaplastic lymphoma kinase (ALK) positive advanced non-small cell lung cancer patients who have progressed on crizotinib. We estimated the cost-utility of alectinib vs. ceritinib from a US payer perspective. Methods: We developed a cost-utility model using partition survival methods and three health states: progression free (PF), post-progression (PP), and death. Survival data were derived from the key clinical trials (alectinib: NP28761 & NP28673, ceritinib: ASCEND I and II). We used the Kaplan Meier curves until the end of study and extrapolated using a weibull parametric function. Costs included drugs, adverse events and supportive care. Utilities in the PF state (alectinib: 0.79; ceritinib: 0.73) and PP state (0.46) were based on trial data and the literature, respectively. One way and probabilistic sensitivity analyses (PSA) were performed to assess parameter uncertainty. Results: Treatment with alectinib vs. ceritinib resulted in increases of 2.55 months in the PF state, 0.44 quality adjusted life-years (QALYs), and $22,400, yielding a mean cost/QALY of $50,300. In the PSA, alectinib had an 89% probability of being cost-effective at a willingness to pay of $100,000/QALY. Drivers of model results were drug costs and utilities in the PF health state. Comparable results were estimated in a subgroup analysis that limited the alectinib survival data to patients with both prior chemotherapy and crizotinib treatment vs. ASCEND II data. Conclusions: Treatment with alectinib in ALK+ crizotinib-treated patients increased time progression free and QALYs vs. ceritinib. The marginal cost increase was driven by longer treatment durations with alectinib. This model demonstrates that alectinib may be considered a cost-effective treatment after progression on crizotinib according to commonly used thresholds ($100,000/QALY). Results Total cost Life Years QALYs Alectinib $255,657 2.39 1.42 Ceritinib $233,274 1.67 0.976 Difference $22,383 0.72 0.44 Incremental cost-effectiveness ratio $31,172/LY $50,326/QALY