tbuckley/cabot-search huggingface dataset:
A real world study of efficacy and safety with apatinib therapy in advanced neuroendocrine carcinoma patients.
Authors: Chao Chen, Xinlei Gong, Feng Liao, Xianwen Luo, Xiufeng Liu
Journal: Journal of Clinical Oncology (2018)

e14567 Background: There is no standard therapeutic method for advanced neuroendocrine carcinoma patients after second line systemic therapy. It’s need novel effective therapies for these patients. Apatinib (Hengrui Pharmaceutical Co.,Ltd, Shanghai, People’s Republic of China) is a novel small molecular vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitor. This study was conducted to review the efficacy and safety of apatinib in advanced neuroendocrine carcinoma patients Methods: The clinical information of advanced neuroendocrine carcinoma patients were collected in Bayi Hospital Affiliated Nanjing University of Chinese Medicine Nanjing who received apatinib therapy for second line or after second line systemic therapy form August, 2015 to January,2018. The overall survival (OS) and progression-free survival (PFS) from the first apatinb treatment were recorded. Survival data was calculated by Kaplan-Meier method. Adverse events were evaluated based on the National Cancer Institute Common Toxicity Criteria Adverse Events (NCICTC AE) version 4.0. Radiographic assessment was assessed by oncologist and radiologists according to RECIST1.1. Results: There were ten advanced neuroendocrine carcinoma patients were received apatinib treatment, who were failed second line systemic therapy. The median age was 60 years (range 46-72), the response rate (RR) and disease control rate (DCR) were 10% and 60%. Median PFS was 8.5 months and median OS was 12.1 months. The main side effects were proteinuria (30%), oral mucositis (30%), hand-foot syndrome (30%), bone marrow suppression (20%), etc. Conclusions: Above all, apatinib may provide a novel drug for the treatment of advanced neuroendocrine carcinoma patients, and also we should pay special attention to the side effect of apatinb. In the meanwhile, furthermore studies are required for the use of apatinib in neuroendocrine carcinoma in order to guild the clinical practice.
Abstract 18038: Gender Differences in Anticoagulation and Stroke Outcomes in Atrial Fibrillation
Authors: Natasha A Kassim, Dingxin Qin, Thomas Richards, George Leef, Samir Saba
Journal: Circulation (2015)

Introduction: Women with atrial fibrillation (AF) have a higher risk of ischemic stroke than men. Hypothesis: The primary hypothesis is that rates of anticoagulation differ between men and women with AF. The secondary hypothesis is that a difference in rate of anticoagulation results in difference in ischemic stroke-free survival in men and women with AF. Methods: We analyzed the records of 5,976 consecutive AF patients who were prescribed at least one antiarrhythmic drug between 2006 and 2013. Time to clinical outcome events was assessed using the survival analysis method and adjusted for covariates using Cox regression. Results: Compared to men, women (N=2,448, 41%) were older (73 vs. 67 years, p&lt;0.001) , had higher CHADS2 scores (3.4 vs. 2.3, p&lt;0.001), and less comorbidities including CHF, coronary artery disease, prior cardiac arrest, depression, and alcohol/tobacco use. Overall, women were less likely to be anticoagulated than men (77% vs. 83%, p&lt;0.001). The cohort was divided into low, intermediate, or high risk of stroke by CHADS2 score, and difference in rates of anticoagulation by gender was seen in each subgroup (77% vs. 81% low, 75% vs. 83% intermediate, and 80% vs. 87% high, p&lt;0.05). Stroke-free survival was worse in women compared to men (unadjusted p=0.05, HR 0.77), though this difference lost statistical significance when adjusted for multiple covariates (adjusted p=0.5, HR 0.93). The difference in stroke outcome between men and women was most prominent in the low risk group (Figure). Conclusions: In our cohort, women with AF were less likely than men to be anticoagulated. In the subgroup with lowest risk of stroke, women had worse stroke-free survival.
Clinical and dermoscopic features of cutaneous BAP1-inactivated melanocytic tumors: Results of a multicenter case-control study by the International Dermoscopy Society
Authors: Oriol Yélamos, Cristián Navarrete-Dechent, Michael A. Marchetti, Tova Rogers, Zoe Apalla, Philippe Bahadoran, Nuria Blázquez-Sánchez, Klaus Busam, Cristina Carrera, Stephen W. Dusza, Arnaud de la Fouchardière, Gerardo Ferrara, Pedram Gerami, Harald Kittler, Aimilios Lallas, Josep Malvehy, José F. Millán-Cayetano, Kelly C. Nelson, Victor Li Quan, Susana Puig, Howard Stevens, Luc Thomas, Ashfaq A. Marghoob
Journal: Journal of the American Academy of Dermatology (2018)
c-Myc expression as a key-marker in the colorectal cancer resistance to EGFR inhibitors.
Authors: Maurizio Martini, Michele Basso, Alessandra Cocomazzi, Tonia Cenci, Antonia Strippoli, Vincenzo Fiorentino, Riccardo Ricci, Alessandra Cassano, Carlo Barone, Luigi Maria Larocca
Journal: Journal of Clinical Oncology (2016)

e15034 Background: Despite the outstanding success of EGFR inhibitors in the treatment of metastatic colorectal cancer (CC), targeted therapy (TT) leads inevitably to acquired resistance stemming from various molecular mechanisms such as activation of compensatory kinases. Alterations in the transcriptional factor c-Myc, a downstream effector of several kinase pathways, could be also involved in the TT resistance of CC. Methods: The expression of c-Myc (Abcam, Milan, Italy) was assessed in 99 naïve CC samples, wild type for KRAS, NRAS and BRAF, and in 35 subsequent metastases collected during TT treatment with anti-EGFR+Folfiri therapy or in TT resistance phase. In the same cohort, we also analyzed the expression of miRNA143 and miRNA145, using real-time assay, and performed a c-Myc Targets PCR Array (Qiagen, Milan, Italy). Results were correlated with clinical and pathological features. Results: Patients with lower c-Myc nuclear expression (LME) showed a significant higher time to progression (TTP) respect to those with a higher c-Myc expression (HME) (p = 0.0026). Interestingly, metastases from LME tumors displayed significantly higher c-Myc levels than the corresponding primaries (p < 0.0001), especially in the resistance phase. As miRNA143 and miRNA145 are involved in c-Myc regulation and their levels are inhibited by EGFR activation, we analyzed the expression of these miRNAs in a subset of our cohort (56 cases). We found LME CC showed a significantly higher expression of miRNA143 and miRNA145 when compared to HME CC (p = 0.014). Conversely, all metastatic samples had lower levels of both miRNA than corresponding primary CC samples (p = 0.033). Moreover, using an array analysis, we found several significant altered genes in HME CC respect to LME CC and a similar gene pattern expression in all metastatic samples. Conclusions: A high c-Myc expression in naïve CC might discriminate patients with a lower TTP and a worse prognosis. Moreover, the significant c-Myc pathway upregulation, unrelated to miRNAs regulation, found in metastatic samples following TT suggests that a c-Myc blockade could prevent resistance.
Circulating immune-profile as predictor of outcome in advanced NSCLC patients treated with Nivolumab
Authors: M. Tiseo, F. Facchinetti, S. Buti, F. Gelsomino, M. Veneziani, A. Squadrilli, P. Bordi, M. Bersanelli, A. Cosenza, L. Ferri, E. Rapacchi, G. Mazzaschi, F. Leonardi, F. Quaini, A. Ardizzoni, G. Missale
Journal: Annals of Oncology (2017)
TCT-311 Long-Term Vascular Response to Bioresorbable Scaffolds Versus Metallic Stents in Coronary Lesions with Myocardial Bridging: A Potential Benefit of Vascular Restoration Under Dynamic Compression Force
Authors: Ryo Kameda, Kozo Okada, Hideki Kitahara, M Brooke Hollak, Paul G. Yock, Jeffrey Popma, Hajime Kusano, Wai-Fung Cheong, Krishna Sudhir, Yasuhiro Honda, Takeshi Kimura
Journal: Journal of the American College of Cardiology (2018)
Immunomonitoring in patients with stage II and III colon cancer.
Authors: Michal Vocka, Jan Spacek, Irena Netikova, Eva Zavadova, Kristýna Němejcová, Bohuslav Konopasek, Pavel Dundr, Carol-Immanuel Geppert, Terezie Fucikova, Arndt Hartmann, Lubos B. Petruzelka
Journal: Journal of Clinical Oncology (2017)

e23038 Background: Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. Immunoscore has been shown to be a very powerful prognositc indicator in patients with clinically localized colorectal cancer, with no detectable tumour spread to lymph nodes or distant organs. These patients are usually treated with only surgical removal of the tumour; however, approximately 25% of these patients will have recurrence of their disease, indicating that occult metastases were already present at the time of curative surgery. VEGF is the factor responsible for neoangiogenesis and it is being considered as a possible prognostic marker of disease progression. Transforming growth factor-beta (TGF-beta) is also neoangiogenic and a highly immunosuppressive factor. The purpose of this study was to monitor the immune response in patients with stage II and III CRC, with a focus on cellular as well as humoral immunity. TGF-beta and VEGF levels were followed. Methods: 25 patients with stage II and III colon cancer included in the research project received routine cancer teratment. Basic parameters - histological type and grade - were established at baseline. Patients were evaluated by a clinical immunooncolgist to exclude any immune disorders of allergic or autoimmune origin. TGF-beta and VEGF were measured using ELISA, and anti-tumour cellular immunity (CD4, CD8, T-reg, B cells ) were measured via flow cytometry. Results: In patients with stage II and III colorectal cancer, predominantly a depression in cellular immunity was seen. Plasma levels of immunglobulins were also reduced, particularly the IgG4 subtype. Most patients showed some clinical symptoms of immunodeficiency, such as frequent respiratory tract infections and/or herpetic infections. TGF-beta and VEGF plasma levels were increased. Conclusions: The correlation of these neoangiogenic and immunosuppressive factors, as well as the state of anticancer immunity with the clinical outcome of the patients, could help in the future as a prognostic marker and contribute to the selection of targeted immune therapy in patients with colorectal cancer. Dedication: Ggrant of Czech Ministery of Health, 15-28188A, League against cancer and PRVOUK-P-27/LF1/1
Utility of Neuropilin-1 in predicting survival in patients with hepatocellular carcinoma.
Authors: Yehia I. Abugabal, Manal Hassan, Reham Abdel-Wahab, Sahin Lacin, Roberto Carmagnani Pestana, Robert A. Wolff, James C. Yao, Ahmed Omar Kaseb
Journal: Journal of Clinical Oncology (2018)

e16142 Background: With only limited data about the prognostic significance of Neuropilin-1 (NRP-1) in hepatocellular carcinoma (HCC), previous studies showed that it has a role in promoting angiogenesis, tumor growth, tumor invasion, metastasis and malignant progression of many human cancers. However, its role in tumorigenesis and progression of HCC is unknown. Methods: Between 2001 and 2014, total of 766 HCC patients from MD Anderson Cancer Center were enrolled and baseline patients’ clinical characteristics were prospectively collected. The normal level of plasma Neuropilin-1 defined based on the median among control group ( = 150 mg/ml). Survival analysis included Kaplan Meier statistic and Cox regression analysis were estimated to determine the effect on HCC prognosis. Results: The median value of Neuropilin-1 was elevated in HCC cases (250 mg/ml) , P < 0.0001. Patients were categorized into two groups: group 1 (N = 43) with normal serum level ( ≤ 150) and group 2 (N = 723) with higher values ( > 150). -Median survival (months), 95% CI were 41.5 (22.6 – 60.5) and 12.4 (10.4 – 14.5 in group 1 and 2 respectively, (P < .0001). Patients in group 2 experienced poor clinical characteristics than group 1 as vascular invasion, HCV, HBV, and elevated AFP. Conclusions: High plasma level of Neuropilin-1 were associated with advanced CLIP staging, BCLC STAGING and poor survival of HCC patients. More Future studies are warranted to come to a better understanding of the pathways of Neuropilin-1 and its role in HCC initiation and progression.
A secondary analysis of PSA response in NRG Oncology/RTOG 9902: A phase III trial of adjuvant chemotherapy with androgen suppression and radiation for high-risk prostate cancer (CaP).
Authors: Stephen Andrew Mihalcik, Meredith M. Regan, Seth A. Rosenthal, Glenn J. Bubley, Kenneth J. Pienta, Leonard G. Gomella, David A. Grignon, Alan C Hartford, Mark S. Morginstin, Jeff M. Michalski, Raghu Rajan, Andrew Michael McDonald, Michael M. Dominello, James Norman Atkins, Christopher U Jones, Jennifer Moughan, Howard M. Sandler, Irving D. Kaplan
Journal: Journal of Clinical Oncology (2017)

5078 Background: RTOG 9902 was a randomized controlled trial of the addition of adjuvant chemotherapy (CT; paclitaxel, oral etoposide, and estramustine x4 cycles) to 24 mo of androgen suppression (AS) and radiation (RT) for patients (pts) with high-risk CaP., beginning with an initial 4 mo of AS; RT began after 2 mo. 9902 accrued 397 pts and closed early due to excess toxicity. At a median follow-up of 9.2 years, there was no benefit to CT, but it is hypothesized that a subset analysis by post-RT PSA identifies pts that benefit from treatment intensification with CT. Methods: Post-RT PSA status was dichotomized at &gt; 0.2 ng/mL within 1 mo of RT. Landmark analysis redefined starting times for disease-free survival (DFS), time to distant metastasis (TDM) and overall survival (OS) at 16 weeks post-RT (36 weeks post-randomization) when CT was planned to complete. Pts were excluded if they did not get RT or assigned CT, or experienced DFS events/lost to follow-up &lt; 36 wks post-randomization. Hazard ratios (HR), 95% confidence intervals (CI), and PSA-by-treatment interaction were estimated by Cox or competing-risks regression. Results: 333 pts were analyzed: 190 without and 143 with CT. 37% of pts had a post-RT PSA ≤0.2, 34% &gt; 0.2, and 29% no recorded PSA in the defined interval. CT was associated with improved DFS for pts with PSA &gt; 0.2 (HR 0.59, 0.38-0.91), but not for those with PSA ≤0.2 (HR 0.94, 0.60-1.46; interaction p = 0.13). This association, for those with PSA &gt; 0.2, persisted in those pts who received the full course of CT and trended in the same direction for pts receiving 1-3 cycles. CT was associated with a trend toward improved TDM in the PSA &gt; 0.2 group (HR 0.56, 0.23-1.35) and not in the PSA≤0.2 group (HR 1.31, 0.36-4.70), based on 32 pts with metastases. OS did not show the same pattern (PSA &gt; 0.2: HR 0.98, 0.55-1.77; PSA≤0.2: HR 0.57, 0.29-1.13). Conclusions: This analysis suggests that men with high-risk CaP and suboptimal response to AS+RT, as identified by post-RT PSA &gt; 0.2, may benefit from adjuvant CT. Prospective trials using contemporary CT (e.g. docetaxel) will help optimize treatment for these men. NRG-GU002, recently activated, is addressing this issue.
Hyperacute toxicity with combination ipilimumab (ipi) and anti-PD1 immunotherapy.
Authors: Helen Clare Dearden, Lewis Au, Daniel Ying Wang, Lisa Zimmer, Zeynep Eroglu, Jessica Louise Smith, Marcello Curvietto, Chloe Khoo, Victoria Atkinson, Serigne Lo, Alexander Guminski, Georgina V. Long, Shahneen Kaur Sandhu, Paolo Antonio Ascierto, Matteo S. Carlino, Douglas Buckner Johnson, James M. G. Larkin, Alexander M. Menzies
Journal: Journal of Clinical Oncology (2018)

9545 Background: Combination ipi and nivolumab is approved for advanced melanoma and is in trials across oncology. Toxicity (tox) most often occurs 6-10 wks into treatment. Whether early tox is harder to manage or influences treatment efficacy is unknown. Methods: Consecutive metastatic melanoma patients (pts) who developed hyperacute (HA) tox, defined as grade (G) 2 or higher (2+) tox within 21 d of receiving combination immunotherapy (ipi + PD1), were retrospectively identified from 9 centres. Demographics, disease characteristics, tox and outcome data were examined. Results: 80 pts developed HA tox, at a median (med) 10 d (range 1-21). Pts had med age 55y, 66% were stage IV M1c/d, 49% had elevated LDH, 14% were ECOG 2. 61 (76%) pts were treatment naïve, 9 had received prior BRAF inhibitors, 4 ipi, 2 PD1 antibodies. Most frequent HA tox was colitis (n = 23), rash (n = 17), hepatitis (n = 9), endocrine (n = 9), pneumonitis (n = 6), and neurotoxicity (n = 4). 39% were G2, 54% G3, 8% G4. 48% required treatment beyond oral steroids, including IV steroids (21%), infliximab (18%), and other immunosuppression (9%) including mycophenolate and IVIG. Pts required a med 45 days on > 10mg prednisone equivalent. 83% of HA colitis pts required treatment beyond oral steroids (22% IV steroids, 61% infliximab), with a med 75 d on > 10mg prednisone. 20% pts received further combination therapy, 48% permanently discontinued all immunotherapy. 48% pts developed additional tox (10% had 3+ further tox), and 31% with G3-4 HA tox developed another G3-4 tox without further therapy. The overall response rate (ORR) was 54%, and after a med 11.6 mo follow-up, med PFS was 8.74 mo. Patients with G2 tox had a similar ORR but greater PFS than those with G3-4 tox (65% vs 47%, p = 0.19; 10.2 vs 2.8 mo, p = 0.01). There was no difference in ORR and PFS by type or duration of immunosuppression. Conclusions: Hyperacute toxicities from combination immunotherapy are varied. Many pts require treatment beyond oral steroids and for a prolonged duration, and pts are at risk of further severe tox. Efficacy in such pts appears similar to trial populations, although severe tox may correlate with worse outcomes. The degree and duration of immunosuppression does not appear to influence the efficacy of immunotherapy.
Assessment of prognostic factors in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) treated with abiraterone acetate (AA) after docetaxel (DOC).
Authors: Carla Cavaliere, Orazio Caffo, Cinzia Ortega, Carmine D'aniello, Marilena DI Napoli, Sabrina Chiara Cecere, Chiara Della Pepa, Anna Crispo, Francesca Maines, Fiorella Ruatta, Gelsomina Iovane, Maurizio Montella, Sandro Pignata, Gaetano Facchini
Journal: Journal of Clinical Oncology (2016)

e16569 Background: Although several new agents changed the therapeutic landscape of mCRPC, it remains a lethal disease. Among the new available agents, AA demonstrated a survival improvement in pts who have previously received DOC. The aim of this retrospective analysis is to evaluate the role of prognostic factors in mCRPC treated with AA in post docetaxel setting. Methods: We retrospectively evaluated patients with mCRPC treated with AA in compassionate use in three Italian Hospitals. We retrospectively recorded the pre-AA history, the AA treatment and outcomes. We identified several variables as having a potential prognostic value: baseline ECOG performance status score, age, Gleason score, duration of previous ADT for metastatic disease, number of previous chemotherapy regimens, extent of disease, previous cumulative docetaxel dose, time course of PSA response, baseline levels of hemoglobin (Hb), lactate dehydrogenase (LDH) and alkaline phosphatase(ALP). The Cox proportional hazards model was used to test the effect of several variables on survival outcomes in multivariate analyses. Hazard ratios (HRs) and 95% CIs were estimated, adjusting for age and centre. A p-value of <0.05 was considered significant. Statistical analysis was performed using SPSS (version 21; SPSS, Inc., Chicago, IL). Results: We collected data of a consecutive series of 87 pts treated between Sep 2011 and Sep 2014. The median OS was 17,1 months (8,8-25,2) and 75/87 patients were evaluable for correlation analysis. Of the eleven variables analyzed, four have shown a positive correlation with overall survival (OS): early PSA response ( ≥ 50% from baseline at 15 days), HR 0.21 95% CI 0.06-0.72, p = 0.01; LDH level ≤ 220 IU/L, HR = 0.28 95% CI 0.09-0.81; Hb level > 10 g/dl, HR = 0.45 95% CI 0.18-1.14; ALP level ≤ 115 UI/L, HR = 0.53 95% CI 0.24-1.10. Conclusions: From our data early PSA response ( ≥ 50% at 15 days after start of AA), lower baseline level of ALP and LDH have a prognostic value
A phase II study of pembrolizumab in combination with mFOLFOX6 for patients with advanced colorectal cancer.
Authors: Safi Shahda, Anne M. Noonan, Tanios S. Bekaii-Saab, Bert H. O'Neil, Amikar Sehdev, Walid Labib Shaib, Paul R. Helft, Patrick J. Loehrer, Yan Tong, Ziyue Liu, Bassel F. El-Rayes
Journal: Journal of Clinical Oncology (2017)

3541 Background: Pembrolizumab (PEM) has activity in patients with deficient mismatch repair (dMMR) colorectal cancer (CRC). Oxaliplatin (OX) and 5FU lead to immunogenic cell death and increased antigen presentation. We hypothesized that combining mFOLFOX6 and PEM may enhance immunogenic cell death and improve outcome in patients with CRC irrespective of MMR status. Methods: Subjects ≥18 years old with untreated, unresectable CRC were assigned to a single arm study. The study had a safety run in cohort of six patients (OX 85 mg/m 2 , leucovorin 400 mg/m 2 , 5FU 400 mg/m 2 , 5FU infusion 2400 mg/m 2 over 46 hours) and PEM 200 mg Q 3 weeks, followed by a phase II cohort. The primary objective was median progression free survival (mPFS), with secondary objectives: safety and toxicity per CTCAE V4.03, median overall survival, response rate, immune related response, disease control rate, and molecular correlates. Results: Between 4/2015 and 9/2016, 30 subjects were enrolled with following characteristics: 11 female, 26 Caucasian, median age: 45 years (25-75), 3 with dMMR, 22 MMR-proficient, and 5 with no available data. During the safety run in, 2 patients had G3 febrile neutropenia (FN) and 1 G4 neutropenia. The data safety monitoring committee recommended dose reduction of mFOLFOX6 to OX 68 mg/m 2 , leucovorin 400 mg/m 2 , 5FU of 320 mg/m 2 , 5FU infusion of 1920 mg/m 2 over 46 hours and PEM 200 mg Q 3 weeks. At the data cut off (12/29/16), median follow up was 24 weeks (10-66) and 27 patients remained on study. Rate of G3/4 toxicity associated with FOLFOX/PEM and PEM alone was 36.7% and 13.2%, respectively. No further FN was observed. No grade 5 toxicity was seen on study. Best response was recorded as: 1 complete response, 15 partial response (CR +PR = 53%), and 14 stable disease, with 100% DCR at 8 weeks. One patient with dMMR had resection after 2 months of therapy with complete pathologic response. MPFS has not been reached (95% CI: 5.5 months, NR). Conclusions: Based on these preliminary results, PEM/mFOLFOX6 has acceptable toxicity though demonstrated a suggestion of increased neutropenia in the initial cohort. Clinical activity was seen in patients with untreated advanced CRC including those with proficient MMR. Clinical trial information: NCT02375672.