tbuckley/cabot-search huggingface dataset:
First-in-human phase I trial of anti-hepatocyte growth factor (HGF) antibody (YYB101) in refractory solid tumor patients.
Authors: Jeeyun Lee, Seung Kim, Sujin Lee, Se Hoon Park, Joon Oh Park, Jeong-Won Lee, Kyoung Mee Kim, Hukeun Lee, Sung Hong, Jung Yong Kim, Song-Jae Lee, Seong-Won Song, Jung Ju Kim, Young Suk Park, Ho Yeong Lim, Won Ki Kang, Do-Hyun Nam
Journal: Journal of Clinical Oncology (2018)

e14501 Background: The aim of this study was to determine the maximum tolerate dose (MTD), safety, pharmacokinetics (PK), and pharmacodynamics (PD) of YYB101, a hepatocyte growth factor (HGF) neutralizing humanized monoclonal antibody, in patients with refractory solid tumors. This is the first-in-human trial. Methods: YYB101 was administered intravenously at once every 2 weeks doses of 0.3, 1, 3, 5, 10, 20, 30 mg/kg, according to a 3+3 dose escalation design. Enrolled patients was planned to receive YYB101 until disease progression or intolerable toxicity. Results: Twenty-two heavily pre-treated refractory cancer patients with ECOG < 2 have been enrolled and received YYB101. No dose limiting toxicity was observed during the first 2 dose, but grade 3-4 toxicity (anorexia, ALT increase, azotemia) were observed at later dose. YYB101 demonstrated dose proportional PK up to the dose of 30 mg/kg. No patients discontinued treatment because of adverse events. Based on PK analysis and toxicity data, the recommended dose was determined as XXX. Of XXX evaluation patients, there was 1 confirmed partial response (4.5%, n = 1; sebaceous carcinoma) and 10 stable disease as best response (45.4%, n = 10; 2 (of 2) melanoma, 1 (of 1) hepatoma and 1 (of 1) basal cell carcinoma, 1 (of 1) lung cancer, 4 (of 8) colorectal cancer, and 1 (of 2) stomach cancer,). Of note, one sebaceous metastatic carcinoma patient who have failed to surgery and systemic chemotherapy, have been responding to YYB for 14 months. The MET and HGF expressions by immunohistochemistry (IHC) were evaluated in 19 and 17 tumor specimens, respectively. Neither protein expressions were significant predictors for treatment response to anti-HGF antibody. Further, genomic profiling of the available tumor specimens and serum-biomarker will be presented in the meeting. Conclusions: YYB101 has a favorable safety profile in patients with refractory solid tumors and a dose- proportional PK. Efficacy data are encouraging and the expansion phase is ongoing in a range of tumors. Clinical trial information: NCT02499224.
Unique Gadolinium Enhancement Pattern in Spinal Dural Arteriovenous Fistulas
Authors: Nicholas L. Zalewski, Alejandro A. Rabinstein, Waleed Brinjikji, Timothy J. Kaufmann, Deena Nasr, Michael W. Ruff, Eoin P. Flanagan
Journal: JAMA Neurology (2018)

Spinal dural arteriovenous fistula (sDAVF) is often misdiagnosed as an inflammatory or a neoplastic myelopathy, often because of intraparenchymal gadolinium enhancement on magnetic resonance imaging (MRI); proper early diagnosis is important because deficits are reversible and a delay in treatment is associated with permanent morbidity. Tortuous flow voids on MRI are not universally present; thus, recognition of a unique gadolinium enhancement pattern may also aid in the early recognition and treatment of sDAVF.To describe a unique pattern of spinal cord gadolinium enhancement on MRI in sDAVF.This retrospective evaluation included pretreatment MRIs from 80 patients referred to the Mayo Clinic, Rochester, Minnesota, from January 1, 1997, through December 31, 2017, with a confirmed diagnosis of sDAVF and a control group of 144 patients with alternative confirmed myelopathy diagnoses. All participants underwent a neurologic evaluation at the Mayo Clinic.Evidence of at least 1 focal geographic nonenhancing area within a long segment of intense holocord gadolinium enhancement (termed the missing-piece sign) on MRI.Of 51 patients with an sDAVF and a pretreatment MRI with gadolinium enhancement, 44 (86%) had intraparenchymal contrast enhancement, and 19 of these patients (43%) displayed the characteristic missing-piece sign. Of these 19 patients, symptom onset occurred at a median age of 67 years (range, 27-80 years); 15 patients were men. Progressive myelopathy features affecting the lower extremities occurred during a median of 33 months (range, 1-84 months). Eleven patients (58%) received an alternative diagnosis before confirmation of sDAVF. Tortuous flow voids were present on T2-weighted MRI in 13 of 19 patients. More than 1 digital subtraction angiogram was required for 5 patients to confirm the diagnosis. The missing-piece sign was not seen in any patients from the control group.This unique gadolinium enhancement pattern in sDAVF was not found in a large control group of patients with other myelopathy. Identifying the missing-piece sign on MRI could potentially result in earlier time to angiography with improved outcomes for patients with an sDAVF.
Early CT perfusion changes and the outcome of antiangiogenic therapy and chemotherapy in patients with advanced primary lung adenocarcinoma.
Authors: Meijuan Huang, Min Yu, Kai Zhang, Yangying Li, Hongmei Liu, Wanjiang Li, Lin Zhou, Jin Wang, Youling Gong, Li Ren, Feng Peng, Zhenyu Ding, Yongsheng Wang, Zhenlin Li, You Lu
Journal: Journal of Clinical Oncology (2016)

e20543 Background: The conventional criteria based on tumor size changes is insufficient for assessing antiangiogenic efficacy. We performed a prospective study to continuously evaluate the blood status within tumors by whole-tumor perfusion CT in patients with advanced lung adenocarcinoma with the treatment of chemotherapy and Recombinant Human Endostatin (Endostar). The purpose is to find potential predictors to help determine the antiangiogenic effect earlier. Methods: Chemotherapy-naïve patients with histologically or cytologically confirmed, measurable, stage IV primary lung adenocarcinoma were enrolled into the study. Patients received Endostar 7.5 mg/m2, (days 1-10), pemetrexed 500 mg/m2 (days 6), carboplatin AUC = 5 (days 6) every 21 days for 4 cycles. To monitor the perfusion changes during cycle 1 and cycle 2, whole-tumor perfusion CT was performed on cycle 1 D-1, cycle 1 D5, cycle 1 D14 and cycle 1 D20 in arm A, while on cycle 1 D20, cycle 2 D5, cycle 2 D14 and cycle 2 D20 in arm B. The value of perfusion parameters such as blood flow (BF), blood volume (BV) and blood permeability (PMB) were recorded. Response according to RECIST1.1 and progression-free survival (PFS) were evaluated. Results: 19 patients completed the planned treatment and CT perfusion. There were 8 in arm A and 11 in arm B. The variations in each parameter number within either cycle were not significant. 6(31.6%) patients achieved PR, 9(47.4%) patients were SD. No correlations were observed between perfusion variations and response . Median PFS was 6.1 months (95%CI 5.7-6.6).PFS in patients with decreased PMB after 5 days Endostar alone was significant better than those with increased figure (8.0 versus 4.9 months, p = 0.022)。 Improved PFS had also been shown in patients with reduced BV after 5 days Endostar alone as compared to those with enlarged number. (8.0 versus 6.0 months, p = 0.049). Conclusions: The early changes of whole-tumor CT perfusion during treatment of chemotherapy and angiogenetic therapy failed to show correlation with response in patients with advanced primary lung adenocarcinoma. Early decreased PMB or BV might be associated with improved PFS Clinical trial information: NCT01564329.
Tumor PD-L1 heterogeneity in non-small cell lung cancer: Does biopsy size and volume matter?
Authors: Monica Khunger, Jennifer Bordeaux, Naveen Dakappagari, Christine Vaupel, Arjun Khunger, Bo Hu, Kurt A. Schalper, David L. Rimm, Vamsidhar Velcheti
Journal: Journal of Clinical Oncology (2018)

12058 Background: Although patients with high tumor programmed death ligand-1(PD-L1) expression benefit from PD-1/PD-L1 axis inhibitors, many studies have highlighted that a fraction of patients respond to these agents despite lacking detectable PD-L1 expression. Heterogeneity of tumor PD-L1 expression within the tumor has been postulated to be contributing to the limited performance of PD-L1 as a predictive biomarker. We evaluated the PD-L1 expression heterogeneity by comparing the percentage of PD-L1 positive tumor cells as a measure of tumor PD-L1 proportion scores (TPS) using fluorescence immunohistochemistry in paired whole tissue sections (WTS) and tissue microarray (TMA) cores from surgical non-small cell lung cancer (NSCLC) specimens. Methods: WTS and two 0.6mm TMA cores localized at least 3mm apart from each other were prepared from each formalin-fixed, paraffin-embedded surgically resected tumor specimens of 451 patients with stage I-III NSCLC. Using quantitative immunofluorescence with the E1L3N anti-PD-L1 antibody, TPS were generated in TMA and corresponding WTS and classified as 0%, 1-49% and ≥50%. Results: There was a high discordance between the TPS scores of PD-L1 expression among the WTS and TMA cores (discordance rate = 40.6%, 95% CI, 35.4%-45.9%; k = 0.26). Moderate discordance was observed between the TPS of PD-L1 expression among the two TMA cores (discordance rate = 10.2%, 95% CI, 7.6%-13.5%; k = 0.609). Conclusions: Discrepancies among the PD-L1 expression between WTS and TMA core as well as between TMA cores themselves represents intratumoral heterogeneity of PD-L1. Small needle aspirations or biopsies during endobronchial or CT-guided biopsy, which can be equated to TMA core, may not be representative of the true tumor PD-L1 expression. It is imperative to obtain bigger or multiple needle biopsies to identify patients with true positive tumor PD-L1 expression and maximize the number of patients who could benefit from PD-1/PD-L1 axis inhibitors.
Clinical Significance of Upper Airway Virus Detection in Critically Ill Hematology Patients
Authors: Jérôme Legoff, Noémie Zucman, Virginie Lemiale, Djamel Mokart, Frédéric Pène, Jérôme Lambert, Achille Kouatchet, Alexandre Demoule, François Vincent, Martine Nyunga, Fabrice Bruneel, Adrien Contejean, Séverine Mercier-Delarue, Antoine Rabbat, Christine Lebert, Pierre Perez, Anne-Pascale Meert, Dominique Benoit, Carole Schwebel, Mercé Jourdain, Michael Darmon, Matthieu Resche-Rigon, Elie Azoulay
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Noninvasive diagnostic multiplex molecular tests may enable the early identification and treatment of viral infections in critically ill immunocompromised patients.To assess the association between viral detection in nasopharyngeal swabs and ICU mortality in critically ill hematology patients.This was a post hoc analysis of a prospective cohort of critically ill hematology patients admitted to 17 ICUs. Nasal swabs sampled and frozen at ICU admission were tested using a multiplex PCR assay. Predictors of ICU mortality and assay positivity were identified.Of the 747 patients (447 with acute respiratory failure [ARF]), 21.3% had a virus detected (56.4% rhinovirus/enterovirus and 30.7% influenza/parainfluenza/respiratory syncytial viruses). Overall ICU and hospital mortality rates were 26% and 37%, respectively. Assay positivity was associated with lymphoproliferative disorders, hematopoietic stem cell transplantation, treatment with steroids or other immunosuppressants, ARF (25.5% vs. 16.3%; P = 0.004), and death in the ICU (28.9% vs. 19.3%; P = 0.008). The association with ICU mortality was significant for all viruses and was strongest for influenza/parainfluenza/respiratory syncytial viruses. In patients with ARF, detection of any respiratory virus was independently associated with ICU mortality (odds ratio, 2.07; 95% confidence interval, 1.22-3.50).Respiratory virus detection in the upper airway by multiplex PCR assay is common in critically ill hematology patients. In patients with ARF, respiratory virus detection was independently associated with ICU mortality. Multiplex PCR assay may prove helpful for the risk stratification of hematology patients with ARF. Studies to understand whether respiratory tract viruses play a causal role in outcomes are warranted.
A novel technique to predict non-cancer and cancer-specific mortality in men with prostate cancer.
Authors: Anthony Joseph Paravati, Neil Panjwani, Jiayi Hou, Ronghui Xu, James Don Murphy
Journal: Journal of Clinical Oncology (2016)

e16608 Background: Treatment decisions in localized prostate cancer hinge on an accurate estimation of patient survival, yet we lack robust survival prediction tools. Current cancer prediction models depend on a limited number of predefined variables, which restricts their predictive capability. Insurance claims data contains substantial information about medical diagnoses, surgery, procedures, and overall represents an indirect reflection of a patients past medical history. This study explored a novel technique to create comprehensive survival prediction models using insurance claims data from a large administrative dataset. Methods: We identified 57,011 Medicare beneficiaries with prostate cancer diagnosed from 2004 to 2009. We created separate prediction models for cancer-specific and non-cancer survival. Potential model inputs included clinical and demographic covariables, as well as 8,971 insurance claim codes. Contemporary variable selection techniques were applied due to the high-dimensional nature of these data specifically using the least absolute shrinkage and selection operator (LASSO) technique with minimal mean squared error. Models were constructed with a training dataset, and performance was tested on a validation dataset. We used a measure of explained randomness (ρ2) to estimate each model’s predictive capacity. ρ2 ranges from 0 to 1 with ρ2= 1 indicating an ideal prediction. Our predictive models were compared to the commonly used Charlson Comorbidity Index and MSKCC nomogram. Results: With non-cancer survival we created a prediction model with 143 unique covariables. Our non-cancer prediction model explained a large proportion of randomness (ρ2 = 0.70) compared to the Charlson Comorbidity Index (ρ2 = 0.26). With cancer-specific survival we created a prediction model with 9 unique covariables that explained a substantial portion of randomness (ρ2 = 0.81), though performed similarly to the MSKCC prediction model (ρ2 = 0.78). Conclusions: Survival prediction models using contemporary high-dimensional variable selection techniques applied to high-dimensional claims data shows promise compared to standard techniques, particularly with non-cancer survival prediction.
TCT-508 Tracking tissue distribution and retention of Sirolimus and analog delivered from polymer free drug coated stents
Authors: Abraham Tzafriri, Lucas Rotllant Daurella, John Keating, Xiaojian Li, Fernando Gacia-Polite, Lynn Bailey, Peter Markham, Debashis Dutta, Hans-Peter Stoll, Elazer Edelman
Journal: Journal of the American College of Cardiology (2018)
Clinicopathological features and prediction values of HDAC1, 2, 3 and 11 in classical Hodgkin lymphoma.
Authors: Xiaojian Liu
Journal: Journal of Clinical Oncology (2018)

e19518 Background: Histone deacetylases (HDACs) are involved in multiple physical and pathological processes in classical Hodgkin lymphoma (cHL). The prognostic value of HDACs in cHL patients has not been discussed. The aim of current study is to investigate the HDAC1, 2, 3 and 11 expressions, and to evaluate the correlation of HDAC1, 2, 3, 11 expressions with survival rate in cHL patients. Methods: We retrospectively analyzed clinicopathological data of 28 patients who were diagnosed with cHL between August 2002 and March 2010. Immunohistochemistry was applied to detect the expression of HDAC1, 2, 3 and 11 in these patients. Results: The results showed that HDAC1, 3 and 11 were expressed at a higher level in Hodgkin Reed-Sternberg (HRS) cells, while HDAC2 was expressed at a lower level in HRS cells. The expression of HDAC2 had a relationship with pathological type (P = 0.012). There was also a correlation between the expression of HDAC11 and Erythrocyte Sedimentation Rate (ESR) (P = 0.054). Other clinicopathological parameters had no significant correlation with the expression of HDAC1, 2, 3 and 11 in terms of survival (P > 0.05). The 10-year total survival rate by Cox multivariate analysis, after taking into account all clinical and pathologic factors, demonstrated that bulky disease retained significance (P = 0.028). Higher expression of HDAC1 predicted shorter progression-free survival (PFS) and overall survival (OS) in cHL patients (P < 0.05, in both cases), and higher expression of HDAC11 might be correlated with lower OS (P = 0.05). Conclusions: The study demonstrated that the expression of HDAC2 and HDAC11 have a particular relationship with the pathologic subtype. Increased expression of HDAC1 was negatively correlated with PFS and OS, and increased expression of HDAC11 had a borderline relationship with OS rate in patients with cHL.
Efficacy and safety results from AvaALL: An open-label, randomized phase III trial of standard of care (SOC) with or without continuous bevacizumab (Bev) treatment beyond progression (PD) in patients (pts) with advanced non-small cell lung cancer (NSCLC) progressing after first-line Bev and chemotherapy (chemo).
Authors: Jaafar Bennouna, Javier De Castro, Anne-Marie C. Dingemans, Frank Griesinger, Francesco Grossi, Corey J. Langer, Yuichiro Ohe, Konstantinos N. Syrigos, Nick Thatcher, Ashis Das-Gupta, Margarita Donica, Vlatka Smoljanovic, Cesare Gridelli
Journal: Journal of Clinical Oncology (2017)

9004 Background: The role of treatment with Bev beyond PD is unclear in the multiline treatment strategy of advanced NSCLC.AvaALL(NCT01351415), a multinational, open-label, randomized phase III trial, assessed continuous Bev and SOC beyond first PD (PD1) in pts with NSCLC following first-line treatment with platinum-based chemo plus Bev. Here we present efficacy and safety data from AvaALL. Methods: Pts with NSCLC who received 4–6 cycles of chemo + Bev and ≥2 cycles of maintenance Bev were randomized after PD1 to second-line SOC therapy (docetaxel, pemetrexed or erlotinib) ± Bev. After second PD (PD2) and third PD (PD3), pts received third-line or fourth-line SOC ± Bev treatment, respectively. Primary endpoint was overall survival (OS). Secondary endpoints were OS rates (6, 12, and 18-months [mos]), progression-free survival (PFS) from PD1 to PD2/from PD2 to PD3, overall response rate (ORR), disease control rate (DCR), and safety. Data cut-off: 24 Jun 2016. Results: Overall, 485 pts were randomized (n = 475 treated). Pt characteristics were well balanced between the two arms. Bev plus chemo resulted in a median OS of 11.9 mos versus 10.2 mos for SOC alone (HR 0.84, 90% CI 0.71–1.00; p = 0.1016; 387 OS events). The primary endpoint was not met (416 OS events were required, at 10% two-sided significance level). OS rates were 10% higher in the Bev arm vs SOC alone at 6-, 12- and 18-mos. Median PFS2 was 4.9 mos with Bev vs 3.8 mos with SOC (HR 0.85, 90% CI 0.72–1.00; p = 0.0907). PFS3 was significantly improved (3.5 mos for Bev, 2.4 mos for SOC; HR 0.65, 90% CI 0.51–0.84; p = 0.0047). ORR and DCR were slightly higher in the Bev arm versus the SOC arm (ORR 9.7% vs 6.7%; DCR 86.2% vs 79.3%, respectively). No new safety signals were identified. Grade ≥3 adverse events were reported in 78.2% of Bev pts and 61.6% of SOC pts. Conclusions: Although the primary endpoint was not met, efficacy data suggest a positive trend for continued Bev plus SOC after PD1 compared with SOC alone. No cumulative safety signals were identified. Clinical trial information: NCT01351415.
Appendiceal adenocarcinoma: Analysis of SEER database.
Authors: Sreenivasa Rao Chandana, Chintan Shah
Journal: Journal of Clinical Oncology (2017)

e18097 Background: Appediceal cancers (AC) are rare, and often found on appendectomies. Adenocarcinomas represents approximately two-thirds of all AC. We performed the analysis of SEER database to understand the overall incidence and survival trends. Methods: We analyzed SEER database: Incidence - SEER 18 RegsResearch Data + Hurricane Katrina Impacted Louisiana Cases, Nov 2015 Sub (1973-2013 varying). Cases diagnosed of AC between 1988 and 2013 were identified. Trend of incidence rate was calculated. Relative survival rates (RSR) were calculated stratified by age, gender, race, stage, histological subtypes which were divided into mucinous, non-mucinous and signet ring cell carcinoma (SRCC). We calculated survival difference for patient diagnosed before and after 2000. Results: Age adjusted incidence rate of appendiceal adenocarcinoma was 0.4 cases per 100,000 person years. Overall incidence rate increased on average 3.7% per 100,000 person years (P &lt; 0.05). The highest increase was seen in SRCC (4.8% per 100,000 person years). Survival was worst in SRCC (5 years RSR-28.40%) compared to other types (5 year RSR- 61.0% and 52.90% for mucinous and non-mucinous carcinoma (P &lt; 0.01). Survival significantly improved for patients diagnosed after 2000 for mucinous (5 years RSR -51.90% and 64.30%) and SRCC (5 year RSR-18.0% and 31.0%), respectively before and after 2000 in each category. No improvement in survival was found in non-mucinous carcinomas since 2000. While survival among different histological types was not different for localized disease, it was significantly better for regional or distant stages in mucinous cancers when compared to non-mucinous cancers (P &lt; 0.01). Elderly patient ( &gt; 65 years) showed significantly poor survival for mucinous and non-mucinous carcinomas, while there was no variation in survival based on age for SRCC. Moreover, females showed significantly poor survival (P &lt; 0.05) compared to males for SRCC, while no variation in survival based on gender for other types. Survival was not different among different races. Conclusions: Incidence of appendiceal adenocarcinomas is increasing. The highest increase is seen in SRCC which has the worst survival. Survival from mucinous adenocarcinomas has improved significantly in last decade.
Medicare Spending after 3 Years of the Medicare Shared Savings Program
Authors: J. Michael McWilliams, Laura A. Hatfield, Bruce E. Landon, Pasha Hamed, Michael E. Chernew
Journal: New England Journal of Medicine (2018)

Health care providers who participate as an accountable care organization (ACO) in the voluntary Medicare Shared Savings Program (MSSP) have incentives to lower spending for Medicare patients while achieving high performance on a set of quality measures. Little is known about the extent to which early savings achieved by ACOs in the program have grown and been replicated by ACOs that entered the program in later years. ACOs that are physician groups have stronger incentives to lower spending than hospital-integrated ACOs.