tbuckley/cabot-search huggingface dataset:
Retrospective analysis to compare the efficacy of oral (O) vs. intravenous (IV) etoposide given in combination with carboplatin for small cell lung cancer (SCLC), extensive disease (ED).
Authors: Anders Mellemgaard, Ditte Stampe Hersby, Farruhk Naheed Chaudhary, Seppo W. Langer
Journal: Journal of Clinical Oncology (2017)

e20020 Background: Approximately two thirds of patients diagnosed with SCLC will have ED at the time of diagnosis. Response rates to chemotherapy are high but median overall survival for patients treated with chemotherapy is only 9 to 10 months. Patients with ED SCLC considered fit for chemotherapy is normally treated with combination chemotherapy including cisplatin or carboplatin, and etoposide or irinotecan. The usual dosing scheme is 3 weeks intervals with the platin administered on day 1 and etoposide given day 1-3 or 1-5. Etoposide is available in as well intravenous as oral formulations. Concerns about the incomplete and variable bioavailability of oral etoposide have been raised. A randomized study of cisplatin with either oral or IV etoposide found no significant difference in treatment outcome but increased rate of severe or life-threatening hematologic toxicity. Methods: The two cancer hospitals serving the Copenhagen area are using carboplatin + etoposide for palliative treatment of SCLC ED. While carboplatin is used identically (AUC5, IV d1), etoposide is given IV by HUH (120mg/m 2 , IV d1-3) and orally by CUH (200mg/m 2 O, d1-3). From the hospital patient database, we identified patients with SCLC, ED treated in 2011-2013. Route of etoposide administration, dose reductions and GCSF use was noted. PFS and OS was calculated from hospital records. Results: 200 SCLC, ED patients received treatment (116 at HUH, 84 at CUH). A non-significant higher proportion of women were treated at HUH while median age was identical. PFS was longer at HUH than CUH (195 vs 140 days), but the OS was identical (235 vs 227 days). Conclusions: The two dosing schemes: O and IV yield similar OS, but longer PFS with the IV schedule. The survival seen is in line with results from randomized trials although the present study includes all patients irrespectible of PS or comorbidity. We have no information on adverse events, quality of life or rates of hospitalization.
Cardioprotective effects of nanoemulsions loaded with natural anti-inflammatory bioactives against doxorubicin-induced cardiotoxicity in rat cardiomyocytes.
Authors: Vincenzo Quagliariello, Raffaele Vecchione, Chiara Di Cicco, Alberta De Capua, Carmela Coppola, Giovanna Piscopo, Fabrizio Maurea, Rolando Paciello, Rosario Vincenz Iaffaioli, Paolo Netti, Nicola Maurea
Journal: Journal of Clinical Oncology (2018)

e24227 Background: Doxorubicin is a highly active antineoplastic agent; however, its clinical use is limited due to associated cardiotoxicity. This study was performed to evaluate the beneficial effects of bioavailable nanoemulsions loaded with lycopene or curcumin, both natural molecules with anti-inflammatory and vascular protective properties, against doxorubicin-induced cardiotoxicity in rat cardiomyocytes Methods: Nanoemulsions were produced by using a high-pressure homogenizer. H9C2 cells were incubated with lycopene or curcumin loaded nanoemulsions at different concentrations ranging from 0,05 up to 2% oil alone or in combination with Doxorubicin at 200 nM. Cell viability was evaluated by using a modified MTT method. The levels of lipid peroxidation products (MDA and 4-HNA), interleukins involved in cardiotoxicity (IL-6, IL-8, IL-1β), IL-10, tumour necrosis factor-alpha (TNF-α), nitric oxide (NO) were analyzed using ELISA method. Results: Nanoemulsions loaded with both bioactives showed a nanometric and homogeneous dimension in time with an overall hydrodynamic size of around 100 nm. A marked cell viability enhancement of around 35-40 % compared to only Doxorubicin-treated cells (p < 0,01) and significant reduction of lipid peroxidation (MDA and 4-HNA) in cardiomyocytes pretreated with both nanoemulsions in combination with doxorubicin. Moreover, both nanoemulsions ameliorated the cardiomyocytes release of IL-6, IL-8, IL-1β, TNF-α and NO of around 37 and 53 %, respectively and increased IL-10 production of 40-47 % compared to un-pretreated cells (p < 0,05 for all) indicating anti-inflammatory properties. Conclusions: This study demonstrates for the first time the cardioprotective effects of lycopene and curcumin loaded nanoemulsions against doxorubicin -induced cardiotoxicity. Collectively, these data indicate that pretreatment of cardiomyocytes with nanoemulsions alleviates doxorubicin-induced cardiotoxicity via reducing oxidative lipid damage, NO and cytokines release. This results places interesting initial biological evidences for subsequent cardioprotection studies in preclinical models.
Effect of hypoglycemic agents on survival outcomes of patients with lung cancer and diabetes mellitus: A systematic review and meta-analysis.
Authors: Ping Huang, Wenxiu Xin, Luo Fang, Haiying Ding, Xiaowei Zheng
Journal: Journal of Clinical Oncology (2017)

e21617 Background: Although hypoglycemic agents (metformin, insulin, sulfonylureas [SUs] and thiazolidinediones [TZDs]) may influent prognosis of cancer at several sites, very little is known about their effects on clinical outcomes of lung cancer patients with diabetes mellitus (DM) and results from clinical trials are often inconsistent. Methods: To assess the association between hypoglycemic agents and clinical outcomes of lung cancer, we performed a systematic review of published studies from PubMed, EMBASE, Web of Science and The Cochrane Library up to January, 2016. Meta-analysis was performed to calculate the pooled hazard ratio (HR) and 95% confidence interval (95% CI). Results: The pooled HRs favoring metformin users was 0.77 for overall survival (OS) (n = 12, 95% CI: 0.66-0.89) and 0.59 for disease-free survival (DFS) (n = 6, 95% CI: 0.47-0.72). Only one study assessed the relation between metformin and cancer-specific survival (CSS) in lung cancer patients, reporting no statistically significant results. No significant association between insulin use and OS (n = 2, HR: 0.95, 95% CI: 0.79-1.13) or CSS (n = 2, HR: 1.03, 95% CI: 0.76-1.41) was noted. Only one study evaluated the effect of SUs in patients with lung cancer and reported no statistically clinical benefit (HR: 1.10; 95% CI: 0.87-1.40). Likewise, one study evaluated the effect of TZDs on OS in patients of lung cancer and reported no significant difference between TZDs and non-TZDs groups (HR: 1.04, 95% CI: 0.65-1.66). Conclusions: This meta-analysis demonstrated that metformin could improve survival outcomes of patients with lung cancer and DM. No association between insulin, TZDs or SUs and lung cancer outcomes was found.
Clinical outcome of patients with microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) treated with pembrolizumab.
Authors: Frank A. Sinicrope, Sakti Chakrabarti, Rachel Eiring, Jessica L Mitchelll, Heidi D. Finnes, Joleen Marie Hubbard, Robert R. McWilliams
Journal: Journal of Clinical Oncology (2018)

e24127 Background: We examined efficacy of the anti-PD-1 antibody, pembrolizumab (PEM), in consecutive patients with MSI-H mCRC. PEM is FDA approved for treatment of MSI-H CRC after progression on standard chemotherapy. FDA approval was based on aggregate, multi-center, single-arm trial data demonstrating a 36% objective response rate (ORR) in heavily pretreated mCRC patients. Among reported data in mCRC patients, time-to response (TTR) for PEM ranged from 21 to 28 weeks. Methods: Retrospective review of 24 consecutive patients with mCRC and MSI-H status treated with PEM (200 mg/day every 3 weeks) monotherapy at Mayo Clinic (between January 2015 and December 2017) was conducted. MSI testing was performed with a PCR-based assay or by immunohistochemistry for mismatch repair proteins. Patient data were obtained by electronic chart review. Of 24 patients, 12 had Lynch syndrome, 11 were sporadics, and 1 unknown. Radiographic response data were determined by RECIST criteria and TTR, time-to-progression (TTP) and progression-free survival (PFS) were calculated. Results: Among 24 patients, 54% (13/24) received at least one prior chemotherapy regimen: 5 had two priors, 3 had four, and 3 were previously untreated. Median number of cycles of PEM administered was 14 (range 2-32); median follow-up was 13.5 months. Radiographic response data were as follows: 5 CR (21%), 9 PR, and 7 stable disease (objective response rate (ORR) = CR + PR = 58.5%) [Table]. One patient converted from PR to CR at 10 months; all CRs are maintained. Median TTR was 12 weeks (wks) [range 6-20]. At 12 wks, 3/24 patients had progressed; median TTP was 20 wks (range 8-44). At a median follow-up of 13.5 months (range 2-36), 17/24 (71%) patients are without disease progression and median PFS has not been reached. No unexpected toxicities were observed. Conclusions: Among PEM-treated MSI-H mCRC patients, we observed a 58.5% ORR with a median TTR of 12 wks. These data confirm favorable and durable responses seen for PEM. The significantly shorter TTR in our cohort compared to other data may reflect fewer prior treatment regimens. Response MSI-H CRC (N = 24) CR 5 (21%) PR 9 (37.5%) Stable* 7 (29%) PD* 3 (12.5%) ORR 57% Median TTR 12 wks *at 12 wks
A pilot study comparing circulation tumor cells (CTC) detection by AdnaTest prostate assay to CellSearch in patients (pts) with castration resistant prostate cancer (CRPC).
Authors: Aliaksandra Samoila, Diogo Assed Bastos, Amrita Herkal, Chintan Patel, Kristen Rebecca Curtis, Nicole A Schreiber, Aseem Anand, Martin Fleisher, Howard I. Scher, Daniel Costin Danila
Journal: Journal of Clinical Oncology (2013)

e16005 Background: The detection of CTC in blood is prognostic for survival in CRPC. CellSearch is an FDA cleared CTC enumeration assays that reports the number of cells meeting strict morphologic and immunohistochemical criteria. An unmet need is to increase detection rates in pts with favorable &lt; 4 cells/7.5 ml of blood. Here we studied CTC detection using AdnaTest PCR based assay in relation to CellSearch. Methods: Whole blood was collected under an IRB approved protocol from 40 pts with CRPC for the AdnaTest and CellSearch assays. The standard CellSearch platform was used for CTC detection. The AdnaTest includes immunomagnetic cell enrichment using EpCAM and Her2 antibodies followed by mRNA isolation and multiplex PCR amplification of 3 prostate associated transcripts (PSMA, PSA and EGFR). The measurement of one or more transcripts above 0.1ng/µl is considered a positive test. Results: CellSearch CTC counts and AdnaTest detection rates are presented in the Table. Overall AdnaTest detected CTC in 26 pts (65%, 95% CI 50-80%), including 6 of the 18 (33%, 95% CI 11-55%) pts with no CTC using CellSearch. Of 23 pts with ≤ 4 CTC by CellSearch, 10 pts (45%, 95% 30-61%) were positive by AdnaTest. In contrast, in 17 pts with ≥ 5 CTC by CellSearch, 16 pts (94%. 95% 87-100%) were positive by AdnaTest. Overall, 70% (28) of the 40 pts had detectable CTC by either AdnaTest or CellSearch, with positive agreement in 71%. AdnaTest positivity was based on detection of PSA, alone or in combination with PSMA or EGFR. Only 1 patient (4%) was positive for EGFR alone, and none by PSMA alone. Conclusions: AdnaTest demonstrated incremental detection of CTC in pts with no CTC identified by CellSearch. This is consistent with the difference between PCR detection vs the strict definition of CTC using CellSearch, which is known to represent only a small proportion of the EpCAM+ events in the chamber. Further studies to assess the utility of this assay as a biomarker for clinical outcome in pts with CPRP are warranted. [Table: see text]
Circulating free plasma tumor DNA in patients with advanced gastric cancer receiving systemic chemotherapy.
Authors: Savia Raquel Costa Normando, Pamela de Oliveira Delgado, Ana Katherine Soares Barbosa Rodrigues, Waldec Jorge David Filho, Fernando Luiz Affonso Fonseca, Felipe Melo Cruz, Auro Del Giglio
Journal: Journal of Clinical Oncology (2018)

e24067 Background: Advanced gastric cancers are usually not curable conditions for which systemic treatments are indicated. Recent studies suggest that circulating free plasma DNA of tumoral origin (tDNA) is a promising non-invasive biomarker to predict prognosis and monitor the efficacy of systemic treatments in some types of cancer. We conducted a pilot study to analyze the potential role of tDNA as a biomarker in patients with advanced gastric cancer. Methods: We included 30 patients with locally advanced unresectable or metastatic gastric cancer. We obtained samples of each patient every 3 months concomitant with CT until disease progression or death. Blood samples were drawn through peripheral venipuncture according to the GCLP guidelines. We collected 10 mL of total blood using EDTA-coated tubes and then submitted to centrifugation at 1200 rpm for 10 minutes. The separated plasma was transferred to a dry tube, followed by a centrifugation at 2400 rpm for 10 minutes. From this material, 1 mL was collected for the extraction of tDNA from the plasma. Plasma tDNA samples were measured using GeneQuant RNA/DNA Calculator-Amersham Pharmacia Biotech (Biochrom) Ltd. Total free circulating DNA was used to evaluate ALUS sequences (247 and 115). After, the ratio between the expressions was calculated. tDNA was calculated between the ratio from ALUs expression and total free DNA concentrations. We utilized the RECIST criteria 1.1 to evaluate tumor response. Results: Patients with advanced gastric cancer had significantly higher concentrations of tDNA as compared to normal controls (0.00015) allowing us to conclude that the tDNA in the patients was from tumoral origin. We did not find any significant correlation between the tDNA and OS or with tumor response. However, we observed after the first cycles of chemotherapy (at 3 months) that patients with lower tDNA levels had significantly longer DFS as compared with those with higher levels (Cox Regression p = 0.0228). Conclusions: tDNA values at three months after the beginning of chemotherapy correlate with DFS in patients with advanced gastric cancer receiving systemic chemotherapy. tDNA may be a specific, non-invasive and cost effective new biomarker for these patients.
Screening for Syphilis in Pregnant Women
Authors: Jill Jin
Journal: JAMA (2018)

US Preventive Services Task Force; Susan J. Curry, PhD; Alex H. Krist, MD, MPH; Douglas K. Owens, MD, MS; Michael J. Barry, MD; Aaron B. Caughey, MD, PhD; Karina W. Davidson, PhD, MASc; Chyke A. Doubeni, MD, MPH; John W. Epling Jr, MD, MSEd; Alex R. Kemper, MD, MPH, MS; Martha Kubik, PhD, RN; Ann E. Kurth, PhD, RN, MSN, MPH; C. Seth Landefeld, MD; Carol M. Mangione, MD, MSPH; Maureen G. Phipps, MD, MPH; Michael Silverstein, MD, MPH; Melissa A. Simon, MD, MPH; Chien-Wen Tseng, MD, MPH, MSEE; John B. Wong, MD
“Alerta Rosa”: Novel alert and navigation program in Nuevo Leon, Mexico for reducing health system interval delays.
Authors: Cynthia Mayte Villarreal-Garza, Teresa Mireles-Aguilar, Jaime Tamez-Salazar, Jose Felipe Muñoz-Lozano, Edna Anakarenn Lopez-Martinez, Cristina Romero, Alejandra Platas
Journal: Journal of Clinical Oncology (2018)

e18666 Background: In Mexico, median time between breast cancer (BC) symptom detection and treatment initiation has been reported to be 7 months. “Alerta Rosa” intents to break down medical care barriers and reduce delays. Methods: Through several media campaigns, we reached out to patients with breast symptoms or abnormal imaging studies. Patients could contact our call center or Facebook page. A navigator recorded their main complaint and scheduled a medical consultation with a breast surgeon. We stratified and prioritized patients according to clinical risk. Those diagnosed with BC were referred to their health affiliation unit for care. This project was supported by Susan G. Komen Foundation. Results: To date, 656 patients have contacted our program. Median age was 44 years (7–82). Patients reported becoming aware of “Alerta Rosa” mainly by word of mouth (40%), TV (30%), and Facebook (14%). A total of 446 medical consultations were scheduled, and 309 patients did attend their appointments. Main reasons for not showing up were opting for another physician (16%) and personal limitations (16%). A BI-RADS 4 or 5 result was reported in 13% of patients. A biopsy procedure was solicited for 39 patients and 22 BC were diagnosed. Most patients had stage II (45%) or stage III (32%) disease. Median time from alert activation to treatment initiation was 33 days (19–56) and from first medical evaluation to treatment initiation was 28 days (16–48). Conclusions: In low-middle income countries, where BC screening programs do not effectively reach the target population, it is crucial to focus efforts in identifying and prioritizing symptomatic patients or those with abnormal imaging studies, to ultimately downstage BC. “Alerta Rosa” proved to be successful in reducing health system intervals and should be replicated and adapted for other limited resource settings.
A first-in-human phase 1a trial of sintilimab (IBI308), a monoclonal antibody targeting programmed death-1 (PD-1), in Chinese patients with advanced solid tumors.
Authors: Jian-Ming Xu, Ru Jia, Yan Wang, Rongrui Liu, Chuanhua Zhao, Hui Zhou, Linxinyu Xu, Xuan Kong
Journal: Journal of Clinical Oncology (2018)

e15125 Background: Sintilimab (IBI308), a humanized IgG4 anti-PD-1 antibody, showed potent anti-tumor activity in preclinical models. This open label, first in human, dose escalation study evaluated tolerability, safety, pharmacokinetic (PK), pharmacodynamics and preliminary efficacy in patients (pts) with advanced solid tumors. Methods: "3+3" design was used in this trial during dose escalation: 1mg/kg, 3mg/kg and 200mg (1:1 randomization) and 10mg/kg. After 28 days of dose limiting toxicity (DLT) observation, pts would repeat doses every 3 weeks for 200 mg level and every 2 weeks for the other dose levels. PK and pharmacodynamics were assessed across different dose levels. Adverse events (AEs) were graded by NCI CTCAE v4.03. Tumors were assessed by RECIST 1.1 and irRECIST every 9 weeks. Cut-off date for analysis was Dec 9, 2017. Results: In total, 12 pts with advanced solid tumor (n = 3 for each dose level) received at least one dose of sintilimab (the median exposure is 13.8 weeks). No DLTs occurred, the maximum tolerated dose (MTD) was not reached. Most common treatment-related AEs were fever (3/12, all G1), thyroid dysfunction (3/12, all G1), serum bilirubin elevation (3/12, all G1) and pneumonitis (3/12, G1, 2 and 3). Four pts experienced ≥G3 treatment-related AE, including lung infection, pneumonitis, respiratory failure, lipase increased and amylase increased. All AEs resolved after management. No treatment-related death occurred. Sintilimab showed linear PK prolife (1-10mg/kg) with PD-1 receptor occupancy > 95% across 4 does levels. Eleven pts received response evaluation, 2 confirmed PR (hepatocellular carcinoma and neuroendocrine tumor) with duration of response of 9.5 and 5.7 months respectively, and 2 SD (neuroendocrine tumor). One PD (hepatocellular carcinoma) achieved irPR after 11 months. 200 mg Q3W was recommended for the further study. Conclusions: Sintilimab is well tolerated and the preliminary efficacy results are promising. Upcoming safety and efficacy data on expansion cohorts will be presented. Clinical trial information: NCT02937116.
Asian representation in clinical trials of new drugs for the treatment of cancer.
Authors: Lola A. Fashoyin-Aje, Laura L. Fernandes, Steven Lemery, Patricia Keegan, Rajeshwari Sridhara, Jonca C. Bull, Richard Pazdur
Journal: Journal of Clinical Oncology (2017)

6564 Background: In the US, statistics for Asians are often aggregated with other racial groups. This poses challenges in estimating the cancer burden and in defining cancer clinical trial enrollment targets in this demographic subgroup. ‘Asian‘ refers to persons with origins in the Far East, Southeast Asia, or the Indian sub-continent. Asians comprise 6% of the US population and the largest Asian subgroups in the US are of Chinese (22%), Filipino (19%), Asian Indian (19%), Vietnamese (10%), Korean (9%), and Japanese (7%) descent. The representation of Asian patients in global clinical trials may not be reflective of the Asian subgroups in the US. FDA conducted an analysis to describe patients categorized as ‘Asian’ in clinical trials supporting the approval of new drugs. Methods: We reviewed the marketing applications of 33 new molecular entities approved for the treatment of solid tumor malignancies between 2011- 2016 to identify trials that provided the primary evidence of safety and efficacy. Results: A total of 29,941 patients were enrolled; 17 % were Asian. Most Asian patients were enrolled in Korea (20%), Taiwan (20%), mainland China (20%), Japan (16%), and US (5%). Few patients were enrolled in India (3%); the Philippines (1%); Vietnam (0). In the US, Asian patients comprised 3% of the total number of patients enrolled. Conclusions: Asian patients represented a heterogeneous mix. A large proportion was enrolled in Taiwan (20%) and Korea (20%), whereas the largest proportion of US Asians have origins in mainland China (22%), the Philippines (19%), India (19%), and Vietnam (10%). Nevertheless, although Asians share a common ancestry, it is not clear whether data from global clinical trials are generalizable to Asian patients in the US. Therefore, strategies to improve the enrollment of US Asian patients in clinical trials are needed. Among patients enrolled in the US, 3% were Asians, a proportion that is below US Asian population estimates (6%). While most site-specific cancer incidence and death rates are lower in US Asians compared to Whites, the rates of some cancers (e. g., stomach and liver) are higher in this group. Therefore, studies are needed to determine adequate enrollment targets in this demographic subgroup.
P05.38 Stereotactic radiosurgery of benign brain tumors in elderly patients: Evaluation of clinical outcome and toxicity
Authors: R Daniel, V Weyer, M Hoevels, S Grau, K Jablonska, J Tutunji, M Kocher, H Treuer, M Ruge
Journal: Neuro-Oncology (2018)

Stereotactic radiosurgery (SRS) is widely accepted as a therapeutic option for benign brain tumors such as meningioma and neurinoma; however, detailed data on outcomes and toxicity especially in the elderly population have not yet been reported. In this single center retrospective analysis we consecutively included all patients aged ≥ 60 years with benign intracranial tumors (meningiomas, neurinomas) who underwent single fraction SRS by use of modified linear accelerator (LINAC) or Cyberknife® between 1991 and 2018. Patient data were analyzed in terms of tumor control (defined as no further intervention required), symptom control (stable clinical condition), co-morbidities and incidence of early and late treatment related complications (rated by using the Common Terminology Criteria for Adverse Events, CTCAE; v4.03). We identified 224 patients with either vestibular schwannoma (n=147) or meningioma (n=77). The median age was 68 yr (range, 60–84 yr), and the mean and median follow-up were 55 and 41 mo (range, 2–227 mo), respectively. Tumor margins were irradiated with a median dose of 12 Gy (range, 10–18.7 Gy), and the median tumor volume was 2.3 ml (range, 0.1–23.7 ml). Actuarial local tumor control rates at 2, 5, and 10 yr after SRS were 98%, 94%, and 90%, respectively. Mild or moderate adverse events were noted in 41 cases (18%). No severe adverse event was observed during early and late follow up. SRS provides favorable tumor control and a low risk of treatment related adverse early and/or late events. Thus, SRS should be taken into account as treatment option for benign intracranial tumors in elderly patients.