tbuckley/cabot-search huggingface dataset:
AB0681 SCLERODERMIC HAND: SUBCLINICAL JOINT INVOLVEMENT?
Authors: Laura Belloli, Cinzia Casu, Mariaeva Romano, Elisa Verduci, Maria DI Cicco, Emanuela Schito, Valeria Campanella, Michel Chevallard, Marina Muscarà, Davide antonio Filippini, Oscar Massimiliano Epis
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disorder of not fully understood aetiology characterized by vascular and fibrotic abnormalities in the skin and internal organs. Musculoskeletal involvement, mainly affecting hands and feet, is frequent in SSc and represents a major cause of disability. Ultrasonography is a non-invasive, cost-effective imaging modality which is able to detect the presence of joint involvement in SSc. <h3>Methods</h3> 61 consecutive patients (60 women) were enrolled. Each patient has completed a dichotomous survey to evaluate the presence of joint symptoms (presence of pain, swelling, morning stiffness in the last 3 months). Subsequently a rheumatologist - blinded to clinical data and survey results - performed the ultrasound examination of hands and wrists to evaluate the presence of effusion, synovial hypertrophy, power-Doppler signal, erosions and tenosynovitis defined according to the OMERACT definitions. The ultrasound examination was performed using the Esaote MyLab70 with a multifrequency linear probe (6-18 MHz). <h3>Results</h3> Of the 61 patients analyzed, 29 showned joint involvement on the ultrasound examination (47.54%), in particular, 37.93% had tendon involvement and 72.41% joint involvement (Table 1). 31 patients did not report joint symptoms (50.82%) but 13 (41.93%) still had ultrasound alterations (Table 2). <h3>Conclusion</h3> Musculoskeletal involvement is frequent in SSc and can be asymptomatic in more than 20% of patients. The ultrasound examination can make it possible to detect articular and periarticular involvement at an early stage of the disease before the onset of disability. <h3>Disclosure of interests</h3> Laura Belloli: None declared, Cinzia Casu: None declared, Mariaeva Romano Speakers bureau: janssen, Elisa Verduci: None declared, Maria Di Cicco: None declared, Emanuela Schito: None declared, Valeria Campanella: None declared, Michel Chevallard: None declared, Marina Muscarà: None declared, Davide antonio Filippini: None declared, Oscar Massimiliano Epis Speakers bureau: BMS
The efficacy of anlotinib in squamous cell carcinoma (SCC) patients with or without hypertension in ALTER0303: Anlotinib as a third-line therapy in patients with advanced non-small cell lung cancer (NSCLC).
Authors: Jianhua Shi, Baohui Han, Kai Li, Qiming Wang, Li Zhang, Wang Zhe-Hai, Ying Cheng, Jianxing He, Yuankai Shi, Weiqiang Chen, Yi Luo, Lin Wu, Xiuwen Wang, Kejun Nan, Faguang Jin, Jian Dong, Baolan Li
Journal: Journal of Clinical Oncology (2019)

e20503 Background: As a promising multi-target tyrosine kinase inhibitor (TKI), anlotinib hydrochloride significantly improved overall survival (OS) and progression-free survival (PFS) in advanced NSCLC patients in the phase 3 trial (ALTER0303). Here, we demonstrated the efficacy of anlotinib in SCC patients with or without hypertension. Methods: Patients (n = 439) were randomized in a 2:1 ratio to receive anlotinib (12mg daily for 14 days in a 21 day cycle) or placebo. The primary endpoint was OS and second endpoints were PFS, ORR, DCR and QoL. The correlation between hypertension and efficacy (PFS and OS) was analyzed in SCC patients treated with anlotinib. Results: For different ECOG score (0 and 1) SCC patients (n = 46) in the anlotinib arm, the PFS was significantly improved in patients with hypertension in ECOG 1 group (7.00 vs 4.83 months, p = 0.043). There is no statistical difference in other subgroups. Moreover, for the SCC patients in anlotinib arm, PFS was significantly prolonged in patients with hypertension compared to the patients without hypertension (7.23 vs 3.23 months; HR = 0.36; 95% CI, 0.16–0.84; P = 0.001). However, the median OS of the patients with hypertension was numerically but not statistically longer than the patients without hypertension (13.93 vs 6.30 months; HR = 0.56; 95%CI, 0.26-1.22; P = 0.100). Conclusions: In the ALTER0303 trial, anlotinib significantly improved PFS with a potential benefit of OS for SCC patients with hypertension. And ECOG score does not affect the efficacy of anlotinib in SCC patients with or without hypertension. Clinical trial information: NCT02388919. [Table: see text]
Association of radiomic features from prostate bi-parametric MRI with Decipher risk categories to predict risk for biochemical recurrence post-prostatectomy.
Authors: Lin Li, Rakesh Shiradkar, Patrick Leo, Andrei Purysko, Ahmad Algohary, Eric A. Klein, Cristina Magi-Galluzzi, Anant Madabhushi
Journal: Journal of Clinical Oncology (2019)

e16561 Background: Decipher test examines expression levels of 22 metastasis-related RNA sequences and provides a risk score (DS) for assessing metastasis risk within 5 years after radical prostatectomy (RP). Our previous work has shown that radiomics or computer extracted texture features are associated with DS on multiparametric MRI (mpMRI). DS associated radiomics (R DS ) may capture signatures related to poor prognosis of prostate cancer (PCa) following RP. Thus, we sought to evaluate whether R DS were also able to predict the risk of biochemical recurrence (BCR), a surrogate clinical endpoint of metastasis, after RP. Methods: Two patient cohorts from two institutions who underwent 3T mpMRI prior to RP were used in this study - I1: 70 PCa patients who had a Decipher test following RP; I2: 120 PCa patients with at least 5-year follow-up after RP. I1 was investigated as a training set to identify R DS and develop a multivariate logistic regression model (C L ). I2 was used as a testing set to validate C L for predicting BCR. A total of 150 radiomics were extracted within each lesion from T2-weighted MRI (T2WI) and apparent diffusion coefficient (ADC) maps. Area under the receiver operating characteristic curve (AUC) and Kaplan-Meier (KM) analysis were used to evaluate performance of C L . Results: Radiomics quantifying lesion spot and ripple texture patterns on ADC maps and T2WI intensity gradient changes were able to differentiate Decipher high and low/intermediate groups in I1 (AUC = 0.92). The same model C L was then applied to I2 resulting in a significant difference in BCR-free survival time between the predicted risk groups (p &lt; 0.05, hazard ratio (HR) = 2.54) independent of Gleason Grade Group (GGG, p &lt; 0.05, HR = 7.61) and PIRADS-v2 (p &lt; 0.05, HR = 5.64) in multivariate testing. Especially, for patients with GGG &gt; 2 (n = 57), C L predicted BCR risk groups shown HR = 3.1 (p &lt; 0.05) while GGG alone was not prognostic (p &gt; 0.05, HR = 1.93). Conclusions: Our radiomic model was able to predict DS and was found to also be prognostic of BCR-free survival. Further work will involve evaluating whether these radiomic features are predictive of PCa metastasis. [Table: see text]
A phase I study of a novel MDM2-P53 antagonist APG-115 in Chinese patients with advanced soft tissue sarcomas.
Authors: Xing Zhang, Xizhi Wen, Chen Yang, Shan Zeng, Lichuang Men, Hengbang Wang, Yuxiang Ma, Yang Zhang, Ruiqing Peng, Desheng Weng, Li Zhang, Jiao Ji, Wenqin Liu, Zhiyan Liang, Yingjie Huang, Dajun Yang, Yifan Zhai
Journal: Journal of Clinical Oncology (2019)

3124 Background: APG-115 is a novel and orally active small-molecule MDM2 inhibitor. APG-115 alone or in combination with chemotherapeutic, targeted or IO agents have shown potent antitumor activities in multiple human xenograft tumor models and human cancer patient derived xenograft (PDX) models. Methods: The patients with advanced solid tumors were enrolled in this study in China (CTR20170975). The study objectives were to assess safety, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of APG-115. The patients received APG-115 (ranging 100–200 mg) orally QOD for first 21 days of a 28-day-cycle, until disease progression. Antitumor response assessment was performed every 8 weeks per RECIST v1.1. Archived tumor tissues were collected for analyses of MDM2 and TP53 before treatment. Results: As cut-off on Jan 4 2019, total 13 patients (9 soft tissue sarcomas (STSs), 2 adenoid cystic carcinomas (ACCs) and 2 osteosarcomas) were treated in 3 cohorts of APG-115 (100mg, 150mg, 200mg). The median number of prior systemic anticancer therapies was 2 (range 0-4). Two DLTs were observed in one patient at 200mg including thrombocytopenia and febrile neutropenia. The most common TEAEs (≥50% of pts) included: anemia, thrombocytopenia, vomiting, hypercholesterolaemia, and leukopenia. SAEs occurred in 7 patients (54%), four of which were treatment related. The most common Grade 3 or 4 TRAEs were anemia (38.5%), thrombocytopenia (38.5%), leukopenia (30.8%), and neutropenia (23.1%). One partial response was observed in a liposarcoma patient with MDM2-amplification and TP53-wild type at the 150mg cohort, 5 patients (3 STSs, 2 ACCs) had SD as the best overall response. PK analyses indicated an approximately dose proportional increase in Cmax and AUC 0-t following a single or multiple oral administration across dose levels. Preliminary PD data showed that serum MIC-1 increase was exposure dependent within the dose range tested. Conclusions: Preliminary data suggested that APG-115 had promising anti-tumor activity in treatment of patients with MDM2-amplification and TP53-WT liposarcoma. Safety profile and PD effect were consistent with other MDM2 inhibitors. Dosing regimen optimization are ongoing. Clinical trial information: CTR20170975.
A phase I study of a novel IAP inhibitor APG-1387 as a monotherapy or in combination with pembrolizumab in treatments of patients with advanced solid tumors.
Authors: Drew W. Rasco, Yufeng Li, Yuefen Tang, Lichuang Men, Hengbang Wang, Jiao Ji, Zhiyan Liang, Joan Sun, Alex Amaya, Yingjie Huang, Dajun Yang, Yifan Zhai
Journal: Journal of Clinical Oncology (2019)

3125 Background: APG-1387 is a novel, bivalent small molecule IAP (inhibitor of apoptosis proteins) inhibitor. It has shown strong antitumor activities in multiple human xenograft cancer models. APG-1387 also acts as host immune modulator, supporting the notion that APG-1387 in combination with anti-PD1 antibody for cancer therapy. Methods: This study consists of two parts (NCT03386526). Part 1 is the dose escalation study of APG-1387 including a mPC (metastatic pancreatic cancer) cohort expansion. Part 2 is the dose escalation and cohort expansion study of APG-1387 in combination with pembrolizumab. APG-1387 is administrated IV for 30 minutes once weekly in a 21-day-cycle. Pembrolizumab is administrated at 200mg IV on day1 of a 21-day-cycle. The study objectives are to assess the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy (assessed per RECIST v1.1 every 6 weeks). Results: Through Jan 4, 2019, total 23 patients had been treated in 4 cohorts of APG-1387 (20mg, 30mg, 45mg, 60mg). Two DLTs were observed at 60mg including lipase increase and Bell’s palsy, MTD was determined as 45mg. Nineteen of 23 patients experienced at least 1 TEAE. The most common TEAEs were nausea (21.7%), fatigue (17.4%), decreased appetite (13.0%), and abdominal pain (13.0%). Three grade 3 TEAEs including elevated bilirubin, lipase increase, and shortness of breath were documented at 45mg and 60mg. Three out of six mPC patients (one at 60mg, two at 45mg) achieved SD, one of them at 45mg has been treated &gt; 5 cycles with confirmed SD (-18%). Two patients, who were treated with APG-1387 at 20mg in combination with pembrolizumab, had no DLT observed during the first cycle. Preliminary PK data of APG-1387 showed a dose proportionality in exposure (C max and AUC) over the dose range of 20-60 mg. Conclusions: APG-1387 was well tolerated and had manageable adverse events. The potential effects of APG-1387 alone or in combination with pembrolizumab deserve further exploration in patients with advanced solid tumors, especially in the mPC patients. Clinical trial information: NCT03386526.
Bloodstream infections caused by carbapenem-resistant Acinetobacter baumannii: Clinical features, therapy and outcome from a multicenter study
Authors: Alessandro Russo, Matteo Bassetti, Giancarlo Ceccarelli, Novella Carannante, Angela Raffaella Losito, Michele Bartoletti, Silvia Corcione, Guido Granata, Antonella Santoro, Daniele Roberto Giacobbe, Maddalena Peghin, Antonio Vena, Francesco Amadori, Francesco Vladimiro Segala, Maddalena Giannella, Giovanni Di Caprio, Francesco Menichetti, Valerio Del Bono, Cristina Mussini, Nicola Petrosillo, Francesco Giuseppe De Rosa, Pierluigi Viale, Mario Tumbarello, Carlo Tascini, Claudio Viscoli, Mario Venditti
Journal: Journal of Infection (2019)
Is there a role for testosterone replacement therapy in reducing biochemical recurrence following radical prostatectomy?
Authors: T Edward A, Linda My Huynh, Maxwell M Towe, Kaelyn See, Farouk El Khatib, Faysal A Yafi
Journal: Journal of Clinical Oncology (2019)

5085 Background: Historically, the use of testosterone replacement therapy (TRT) has not been recommended in men with a history of prostate cancer (PC). However, low testosterone levels are significantly associated with metabolic complications, decreased sexual function, and (more recently) high-grade PC. In 2009, in hopes of improving sexual function outcomes in men following radical prostatectomy (RP), we began treating low-risk patients with TRT. The current study examines the impact of TRT on biochemical recurrence (BCR). Methods: Between December 2009 and June 2018, a cohort of 850 patients underwent RP by a single surgeon. 152 (18%) men were postoperatively placed on TRT for recovery of sexual function. All data was prospectively collected and retrospectively analyzed. TRT patients were proportionately matched to 419 control patients by pathologic Gleason Grade Group (GGG) and stage. Univariate and multivariate comparisons were used to compare rates and time to BCR (two consecutive PSAs ≥ 0.2 ng/dl); Cox regression modeling was used to generate a survival function at the mean of covariates. Results: There were no statistically significant differences in preoperative PSA, age, prostate weight, pathologic GGG and stage between the control versus TRT groups. Median follow-up time was 3 years in both groups. 7/152 (4.6%) and 39/419 (9.3%) patients experienced BCR in the TRT versus control groups, respectively (unadjusted, p=0.068). In adjusted time to-analysis, TRT was an independent predictor of recurrence-free survival, after controlling for GGG, p-stage, preoperative FT and PSA. A patient on TRT was approximately 53% less likely to experience a BCR (OR: 0.534, 95%CI: 0.288-0.993). Conclusions: After accounting for pathologic GGG, stage, and other significant covariates, the use of TRT independently reduced recurrence post-RP. These results suggest the need for a multi-center randomized control trial.
Lazertinib, a 3<sup>rd</sup> generation EGFR-TKI, in patients with EGFR-TKI resistant NSCLC: Updated results of phase I/II Study.
Authors: Myung-Ju Ahn, Ji-Youn Han, Sang-We Kim, Ki Hyeong Lee, Dong-Wan Kim, Yun-Gyoo Lee, Eun Kyung Cho, Gyeong-won Lee, Jong-Seok Lee, Joo-Hang Kim, Jin-Soo Kim, Young Joo Min, Sung Sook Lee, Sang Won Shin, HyeRyun Kim, Min Hee Hong, Jin Seok Ahn, Seoung Oh Lee, Sohee Kim, Byoung Chul Cho
Journal: Journal of Clinical Oncology (2019)

9037 Background: Lazertinib (YH25448) is a highly mutant-selective, irreversible 3 rd -generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that targets the activating EGFR mutations (Del19 and L858R), as well as the T790M mutation, while sparing wild type. We report the updated results from a Phase I/II study of lazertinib (NCT03046992). Methods: Patients with advanced and metastatic NSCLC who had progressed after treatment with standard EGFR-TKIs with/without asymptomatic brain metastases (BM) were enrolled in an open-label, multicenter, phase I/II study with dose-escalation and expansion cohorts. Lazertinib was administered once daily at doses between 20 to 320 mg in a 21-day cycle. Patients were assessed for safety, tolerability and efficacy. T790M mutation was required in the dose-expansion cohorts. Results: As of 26 Nov 2018, a total of 127 patients were enrolled. The dose-escalation cohort included 38 patients administered with 20 to 320 mg across 7 dose levels, and 89 patients in the dose-expansion cohort were administered with 40 to 240 mg across 5 dose levels. No dose-limiting toxicities were observed. The median duration of treatment was 9.7 months and 58 patients are still ongoing. The objective response rate (ORR) was 60% in all patients, 64% in T790M+ patients, and 37% in T790M- patients by investigators assessment. In BM patients with measurable lesion (n = 14), the intracranial ORR was 50%. The median progression-free survival (PFS) was 8.1 months in all patients, 9.5 months in T790M+ patients, and 5.4 months in T790M- patients. Subgroup analysis showed that ORR was 65% and PFS was 12.2 months in T790M+ patients with ≥ 120 mg (n = 62). The most common treatment-emergent adverse events (TEAEs) were pruritus (27%), rash (24%), constipation (20%), decreased appetite (19%) and diarrhea (14%). TEAEs leading to dose discontinuation were observed in 3% of patients. Drug related TEAEs of grade ≥ 3 was observed in 3% of the patients. Conclusions: Lazertinib was safe, well-tolerated and exhibits promising systemic and intracranial antitumor activity in EGFR T790M+ NSCLC patients. Dose extension cohorts in the 1st and 2nd line settings are underway at 240 mg dose. Clinical trial information: NCT03046992.
Pretreatment steroid use and completion of immunotherapy: A population-based study.
Authors: Grace L. Lu-Yao, Nikita Nikita, Jennifer Maria Johnson, Scott W. Keith, Kuang-Yi Wen, Ralph Zinner, Natasha Ghosh, Joshua Banks, Sarah Hegarty, Melissa Wilson
Journal: Journal of Clinical Oncology (2019)

9567 Background: The relationship between immunosuppressants and immunotherapy (IO) is an active area of research. Here we study the impact of pre-treatment steroid use on the completion of ipilimumab (ipi) therapy. Methods: This population-based study identified patients diagnosed with melanoma and treated with ipi (brand name Yervoy) in 2010-2014 from the linked Surveillance, Epidemiology and End Result-Medicare files. “Completion of IO on time” was defined as receiving 4 cycles of IO within 90 days. Otherwise, the patients were considered to have delayed or incomplete IO. The frequencies of patients completing each dose, up to 4 doses were tabulated. Exact Clopper-Pearson 95% confidence intervals (CI) were computed for prevalence estimates. A crude relative risk (RR) for completing IO was calculated. Results: We identified 1,205 melanoma patients treated with ipi with a median age of 71 years. Among 709 patients with no pre-treatment steroids, 35.7% had completed 4 th dose of IO, compared to 20.3% of patients who received pre-treatment steroids within 1 month of IO (Table). In these patients, having no exposure to steroids in the year prior to initiating IO was associated with a 28% increased probability of completing the IO regimen (RR=1.28, 95% CI: 1.07-1.53). Conclusions: This large scale real-world study demonstrated both the overall completion rate of ipi in melanoma patients as well as the negative impact of pre-treatment steroids on rate of treatment completion. Further studies on treatment outcomes associated with pre-IO steroids use are warranted. [Table: see text]
Approach to Evaluation of Multiple Liver Lesions
Authors: James H. Ellis
Journal: JAMA (2019)

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Efficacy of anti-EGFR-based treatment (tx) in second-line and beyond according to tumor location (TL) in RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC) patients (pts): A mono-institutional retrospective analysis.
Authors: Raffaella Vivolo, Maria Alessandra Calegari, Michele Basso, Ina Valeria Zurlo, Brunella Di Stefano, Maria Bensi, Floriana Camarda, Maurizio Martini, Alessandra Cocomazzi, Carmelo Pozzo, Emilio Bria, Lisa Salvatore, Giampaolo Tortora
Journal: Journal of Clinical Oncology (2019)

e15038 Background: Right- (R) and left-sided (L) mCRCs exhibit different clinical and molecular features. Several retrospective analyses showed that the survival benefit of anti-EGFR-based tx is limited to RAS/BRAF wt L-sided mCRC pts, with a larger effect in the first-line setting. Few data are available concerning the anti-EGFR efficacy according to TL in 2nd and following lines. Methods: Pts affected by RAS/BRAF wt mCRC treated at our Institution with anti-EGFR-based tx in 2nd and following lines were retrospectively collected. The objective of the analysis was to compare tx activity and efficacy according to TL. Primary endpoint was overall survival (OS); secondary endpoints were progression free survival (PFS) and response rate (RR). Results: A total of 47 RAS/BRAF wt mCRC pts treated with an anti-EGFR-based tx in 2nd and following lines were identified. Of those, 32 (68%) were L-sided and 15 (32%) R-sided, respectively. Pts (age, gender, PS ECOG) and tumor (number of metastatic sites) characteristics and number of tx lines were well balanced between the two 21 pts received anti-EGFR alone, 26 pts anti-EGFR plus CT. mOS was 22.3 in L-sided and 7.3 months in R-sided group (HR 2.3, 95%CI 1.02-5.14, p = 0.04). At multivariate analysis TL and PS ECOG independently correlated with OS ( p = 0.02 and p =0.0089). mPFS was 8.4 and 3.9 months in pts with L-sided and R-sided tumor, respectively (HR 1.3; 95%CI 0.64-2.80, p =0.43). RR was higher in L-sided compared to R-sided tumor (37.5 vs 13.3) ( p= 0.09). Conclusions: Our analysis, although limited by the small sample and by its retrospective nature, indicates a better OS in L-sided compared to R-sided tumors treated with anti-EGFR-based tx in 2nd and following lines. A prospective validation is warranted.