tbuckley/cabot-search huggingface dataset:
The clinical analysis of pulmonary lymphoepithelioma-like carcinoma with epithelioid granuloma: Fourteen cases and literature review.
Authors: Yinyin Qin
Journal: Journal of Clinical Oncology (2019)

e20545 Background: Pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare subtype of non-small cell lung cancer associated with Epstein-bar virus (EBV) infection. Even less reported were those with Epithelioid granuloma (EG) and were frequently misdiagnosed. Current study aimed at investigating the clinical presentation, pathological characteristics and treatments of PLELC complicated with EG to improve our understanding of this disease. Methods: Data was collected from January 2013 to December 2017. A total of 105 patients were diagnosed as PLELC, in which 14 patients were with EG. Their clinical features, pathological characteristics and treatment were analyzed. Results: The 14 patients with EG (13.3%) in our group were followed-up 15 months (10-31 months).The median age was 48.5 year-old (38-67 year-old) and 85.7% were under the age of 60, meanwhile females had a slightly higher proportion than males (1.8:1). Most patients were at early stage (71.4%) with nonspecific manifestations such as cough, expectoration and lack of rich-lewis phenomenon. EG were often located in tumor or beside the tumor (71.4%), others were located in lymph node. It was all negative in specific stain of pathology and all positive in situ hybridization of EBV-encoded RNA (EBER). In our study, two patients received palliative chemotherapy with the duration of progression-free survival in 8 and 10 months, respectively. Twelve patients underwent surgical resection including ten with adjuvant or neo-adjuvant chemotherapy. Three patients had disease relapsed in 8, 13 and 25 months after surgery, respectively. None of them had tuberculosis occurring, progression or relapse, even if anti-tuberculosis therapy were not taken. Conclusions: PLELC complicated with EG, a rare phenomenon, was lack of rich-lewis phenomenon and specific clinical characteristic compared with those without EG. The formation of EG may be caused by immunological hypersensitivity to tumor cell or EBV infection instead of tuberculosis. It was important for us to make an exact pathological diagnosis, and attention should be paid to obtain samples by biopsy and make differential diagnosis. PLELC complicated with EG could receive multimodality therapy such as chemotherapy and surgery. However, anti-tuberculosis therapy was not necessary.
Unhealthy alcohol use and toxicity of concurrent chemoradiation for head and neck cancer.
Authors: Solomon A. Graf, Chelle L. Wheat, Madeline C. Frost, Keith Sigel, Steven B. Zeliadt, Emily C. Williams
Journal: Journal of Clinical Oncology (2019)

e17559 Background: Unhealthy alcohol use (UAU) is an important risk factor for development head and neck squamous cell carcinoma (HNSCC), but any effect on treatment outcomes is not well understood. The Veterans Health Administration (VHA) annually screens outpatients for UAU with the validated Alcohol Use Disorders Identification Test Consumption (AUDIT-C). Methods: Using national VHA data we retrospectively identified patients administered upfront radiation with concurrent systemic therapy (chemo- and/or immuno- therapy) for stage III-IVb HNSCC diagnosed 2008 –2017 and included males with a prior-year AUDIT-C. Regression models were fit to assess associations between AUDIT-C risk groups [low-level use (score 1-3), moderate UAU (4-7), severe UAU (≥ 8)] and treatment toxicity. Models were adjusted for a priori defined covariates including smoking and variables related to demographics, comorbidities, and cancer diagnosis and treatment. Results: Among 3,094 patients, 46.7% screened positive for UAU: 23.9% with moderate UAU and 22.9% with severe UAU. Compared to patients with low-level alcohol use, those with severe UAU were younger (mean age 65 vs 67 years) and more frequently active smokers (63.4% vs 36.2%) and underweight (11.2% vs 3.5%) ( p for all comparisons &lt; 0.05). There was no significant difference between alcohol use groups in race/ethnicity, cancer stage, or systemic treatment agent used. In adjusted models, severe UAU was associated with lower risk of nausea [adjusted odds ratio (AOR) 0.63, 95% CI 0.47 – 0.84], ED visits (AOR 0.79, CI 0.63 – 0.99), and hospitalizations during treatment (AOR 0.78, CI 0.62 – 0.98). UAU was not associated with a composite measure of complications of infection or organ damage (AOR 0.94, CI 0.74 – 1.20), severe weight loss (AOR 0.83, CI 0.66 – 1.05), or mortality within 100 days of completing treatment (AOR 1.01, CI 0.62 – 1.66). Conclusions: In this large cohort of male patients in the VHA treated for locoregionally advanced HNSCC with concurrent chemoradiation, moderate and severe UAU is common. UAU is not associated with increased toxicity of treatment, and future research is required to define its place in treatment selection, supportive care, and counseling.
Shared-decision making in prostate cancer with clinical decision-support.
Authors: Hermano Alexandre Lima Rocha, Irene Dankwa-Mullan, Sergio Ferreira Juacaba, Van Willis, Yull Edwin Arriaga, Gretchen Purcell Jackson, Pedro Meneleu
Journal: Journal of Clinical Oncology (2019)

e16576 Background: Shared decision-making is the process of deliberately interacting with patients who wish to make informed value-based choices, when there are no indicated best treatment options. Given the wide variation in prostate cancer treatment options, clinical decision-support systems (CDSS) may effectively support treatment decisions for patients with challenging risk-benefit profiles. However, limited data are available regarding CDSS in shared decision making. This study aimed to assess the alignment of CDSS therapeutic options with treatment received through a shared decision process. Methods: We identified patients with prostate cancer (Gleason Groups 1-5) who were engaged in shared treatment decision making, (from August–September 2018) at the Instituto do Câncer do Ceará, Brazil. IBM Watson for Oncology (WfO), a CDSS was used for the study. Treatment decisions were compared with WfO options (active surveillance, clinical trial, chemotherapy [CT], hormone therapy [HT], radiation [RT], brachytherapy [brachy], surgery and systemic therapy with GnRH suppression) and categorized as concordant (equivalent), partially concordant (a partial match), or discordant. Results: Concordance between WfO and shared treatment decisions was observed in 54% (26/48) of patients, partial concordance in 15% (7/48) and discordance in 31% (15/48). Most frequent treatments were RT+HT combination therapy (25%) and prostatectomy (21%). 8/15 (53%) discordant cases were due to patient preference for treatment over active surveillance. Patient preference for treatment over active surveillance was the most common reason (53%) for discordance. Conclusions: Variation in prostate cancer treatment exists. CDSS therapy options may be useful in quantifying and modifying unwarranted variations in prostate cancer treatment. Future studies are important for understanding reasons for variations. [Table: see text]
A novel predictive biomarker of immunotherapy response in metastatic renal cell carcinoma (mRCC): The lymphocyte microRNA expression profile.
Authors: Lorena Incorvaia, Daniele Fanale, Giuseppe Badalamenti, Gaetana Rinaldi, Bruno Vincenzi, Ida De Luca, Antonio Galvano, Lidia Rita Corsini, Valerio Gristina, Aurelia Guarini, Alchiede Simonato, Giuseppe Tonini, Viviana Bazan, Stefania Gori, Camillo Porta, Antonio Russo
Journal: Journal of Clinical Oncology (2019)

e16109 Background: Predicting which patient with metastatic renal cell carcinoma (mRCC) will benefit from immune checkpoints inhibitors (ICPIs) still remain an issue. Biological factors particular to certain individuals have a clear effect on variation in response. Emerging evidence suggests that small non-coding RNA, such as microRNAs (miRNAs), are critical modulators of numerous cellular processes, including immune surveillance. The main aim of this study was to analyze the lymphocyte miRNA expression profile in mRCC patients and dynamic changes after the treatment with ICPI, in order to investigate the molecular mechanisms and signaling pathways involved in ICPI response and their potential role as predictive biomarker. Methods: Total RNA and miRNAs were isolated from peripheral lymphocytes of 14 mRCC patients, treated with nivolumab as second line. The blood samples were collected before nivolumab treatment (T0) and at progression disease (T1). The quality and quantity of miRNAs were assessed using the miRNeasy Mini Kit, 2100 Bioanalyzer and spectrophotometer NanoDrop ND-1000. Through a TaqMan Low Density Array A human microRNA microarray analysis, the expression profile of 377 lymphocyte miRNAs was analyzed. A cut off of fold change &gt; 2 was considered for up-regulated miRNAs and &lt; 0.3 for down-regulated. The patients were divided into 2 groups: patients with PD within 6 months of treatment (G1), and patients with stable therapy response (RC, RP or SD) over 12 months (G2). Results: Microarray analysis showed a subset of 59 miRNAs involved in several cancer-related processes, including cell cycle regulation, PI3K/Akt, FOXO and HIF-1 signaling pathways, differentially expressed in peripheral lymphocytes of mRCC of G1 and G2 group of patients. Among all miRNAs analyzed, several were deregulated, such as miR-155, miR-22, miR-24, miR-484, miR-335 and miR-492, some up-regulated and others down-regulated. This deregulation of specific miRNAs was different into G1 and G2 groups, and seem to be related with the duration of response to ICPI. Conclusions: Our data, for the first time, study the expression profile of miRNAs in the peripheral lymphocytes, and show a correlation between deregulation of miRNAs and response to Nivolumab. These knowledge could help to identify potential biomarkers predictive of response to ICPIs for the personalization of treatment.
THU0047 IA-14069, A NOVEL SMALL-MOLECULE INHIBITOR DIRECT-TARGETING TUMOR NECROSIS FACTOR-α, ATTENUATES COLLAGEN INDUCED ARTHRITIS
Authors: Sung-Dong Park, Hyung Gun Maeng, Yeon-Hwa Park, Kye-Jung Shin, Tae-Hwe Heo
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Rheumatoid arthritis (RA) is systemic autoimmune disease that is characterized by autoreactive immune cells and various cytokines-mediated inflammation in multiple joints, leading to cartilage degradation, bone erosion and finally irreversible joint destruction<sup>1</sup>. The inflammatory cytokine tumor necrosis factor-α (TNF-α) is known to play a central role in several chronic immune-mediated inflammatory disorders<sup>2</sup>. <h3>Objectives:</h3> Despite the great success of anti-TNF-α biological drugs in the treatment of RA, no chemical drug targeting TNF-α is available. Here we report that IA-14069, a novel small molecule inhibitor, binds directly to TNF-α and inhibits TNF-α activities both <i>in vitro</i> and <i>in vivo</i>. <h3>Methods:</h3> IA-14069 was screened and identified by competitive binding assay using TNF-α and TNF receptor. <i>In vitro</i> neutralization activity of IA-14069 against TNF-α was determined using MTT assay. The direct binding IA-14069 to TNF-α was demonstrated by surface plasmon resonance and bead pull-down assays. The inhibition of TNF-α-TNFR interactions by direct binding of IA-14069 to TNF-α was analyzed by flow cytometry. Levels of phosphorylated IκBα (p-IκBα) and NF-κB p65 were analyzed by western blot. IA-14069 was orally administrated to TNF-α-transgenic (TNF-α-TG) RA mice at 3.3 or 33 mg/kg twice per week or at 25, 50 or 100 mg/kg 3 times per week for preventive or therapeutic effect, respectively. <i>In vivo</i> therapeutic efficacy of IA-14069 or methotrexate was evaluated in collagen-induced arthritis (CIA) mice immunized with bovine type II collagen (CII) emulsified in complete Freund's adjuvant, and boosted with CII emulsified in incomplete Freund's adjuvant. <h3>Results:</h3> IA-14069 potently inhibits both TNF-α-induced cytotoxicity (IC<sub>50</sub> &lt; 0.7 μM) which directly binds to TNF-α and TNF-α-triggered signaling (p-IκBα and NF-κB p65) activities. The therapeutic as well as preventive anti-RA effects of IA-14069 were demonstrated in TNF-α-TG and CIA models. IA-14069 and MTX had synergistic effects in the CIA therapeutic model. According to pharmacokinetic analysis, IA-14069 showed significant bioavailability. In addition, no <i>in vivo</i> toxicity was observed even under treatment of excessive amount of IA-14069. <h3>Conclusion:</h3> The data indicate that IA-14069 can be a novel and potential TNF-α inhibitor for the treatment of RA and other inflammatory diseases. <h3>References:</h3> [1] Choy EH, et al. N Engl J Med. 2001;344:907-16. [2] Wong M, et al. Clin Immunol. 2008;126:121-36. <h3>Disclosure of Interests:</h3> Sung-Dong Park Employee of: MOGAM Institute for Biomedical Research, Hyung Gun Maeng: None declared, Yeon-Hwa Park: None declared, Kye-Jung Shin: None declared, Tae-Hwe Heo: None declared
Oncotype DX score in hormone receptor-positive/HER2-positive breast cancer: A SEER analysis.
Authors: Ayman Qasrawi, Zin Myint, Yanal Mufeed Alnimer, Edward H. Romond
Journal: Journal of Clinical Oncology (2019)

e12044 Background: The recurrence score Oncotype DX (RS) predicts the need for adjuvant chemotherapy in hormone receptor positive (HR+) early stage breast cancer (BC). However, it has not been validated for HR+/HER2+ BC cases. We aim to evaluate the results of RS in HR+/HER2+ BC by using the Surveillance, Epidemiology, and End Results Program (SEER) national database. Methods: We identified patients with non-metastatic HR+/HER2+ BC with reported RS scores from the national SEER database between 2010 and 2015. Data obtained included demographics, histologic subtypes, grading, tumor size, nodal status, HR status and overall survival (OS) outcomes. RS scores were divided into low/intermediate (≤30) and high ( &gt; 30). Histologic subtypes were further categorized into favorable (lobular, tubular, mucinous, and cribriform) and unfavorable (infiltrating ductal, mixed ductal, and micropapillary). We used Kaplan-Meier &amp; Cox regression to analyze the survival outcomes. Logistic regression analysis was used to analyze the correlation between variables and different RS scores. Results: A total of 1537 patients were included. Median age was 61 (25-90). Majority of the patients presented with node negative disease (85%), low/intermediate grade (71%), tumor size &lt; 20 mm (73%), unfavorable histology (89%), and only 15% had negative progesterone receptor (PR –). High RS score ( &gt; 30) was seen in 24% of cases. After a median follow-up of 38 m (1-72), the five-year OS was 94.5%. Chemotherapy was given to 71% and 35% of those with RS &gt; 30 and ≤30, respectively. There was a strong correlation between age &gt; 60 ([hazard ratio, HR] = 4.9, p &lt; 0.0001) and RS &gt; 30 (HR = 2.4, p = 0.004) with worse outcomes on multivariate analysis. However, there were no associations between histologic subtype, tumor size, grade, nodal status and chemotherapy with survival. Tumor size &gt; 20 mm (OR = 1.5), unfavorable histology ([odds ratio, OR] = 3.5), PR – (OR = 4.3) and high grade tumors (OR = 4.5) were independent predictors of RS &gt; 30 (p &lt; 0.0001). Conclusions: Our study shows that large tumor size ( &gt; 20 mm), higher grade, PR –, and unfavorable histology were independent risk factors for higher RS in patients with localized early stage HR+/HER2+. High RS was associated with worse outcome.
Lotte Newman: second ever female president of the Royal College of GPs and advocate for women doctors
Authors: Penny Warren
Journal: BMJ (2019)

Photo credit: David Aronsohn

Among the presidential portraits at the Royal College of GPs (RCGP), there is one that immediately draws the eye. In contrast to the dark suits of her predecessors, Lotte Newman, president from 1994 to 1997, chose something very different. She asked to be painted in a vibrantly coloured, patterned dress—with a bust of her husband and a mobile phone in the background.

Newman was described by a colleague from the royal college as “a breath of fresh air.” An emigrant from Nazi Germany, she was the second ever female president of the college. According to a colleague, she was “very caring and stood for high quality practice at a time when it wasn’t a given.” She brought in a creche for events and a weekly phone-in for members, and was known for championing the interests of younger colleagues and women in general.

Newman was born Lotte Therese Neumann to …
Potential interaction of radiation therapy, antibiotic, and steroid use in non-small cell lung cancer patients treated with checkpoint inhibitors: A retrospective analysis.
Authors: Fen Wang, Kevin D'Rummo, Mohammed Al-Jumayli, Lei Pei, Chao Hui Huang
Journal: Journal of Clinical Oncology (2019)

e20724 Background: The activity of Checkpoint inhibitors (CPI) can be predicted by PD-L1 expression. Recent studies showed that other factors can also have an impact including radiation which is beneficial but the use of antibiotics and steroids can have a deleterious effect. We performed a retrospective analysis of stage IV lung cancer patients treated with CPI at our institution and the impact of radiation treatment as well as the use of antibiotics or steroids in their outcome. Methods: We reviewed the data of 121 patients with stage IV non-small cell lung that were treated with CPI from 2015 to 2017 and analyzed the impact of PD-L1 expression, radiation treatment, steroid and antibiotic use on their progression-free survival (PFS) and overall survival (OS). We determined the use of antibiotics and steroids during any time within 30 days of initiation of treatment with CPI. Results: The median age was 66; there were 57 females and 64 males;23 current smokers, 11 non-smokers and 87 previous smokers; 87 adenocarcinomas, 24 squamous cell histology, and 10 others; 38 patients had low PD-L1 ( &lt; 50%), 46 had high PD-L1 (≥50%) and 37 was unknown. The PFS and OS of patients treated with CPI who had radiation (RT) were not different from patients that did not have RT by Gehan-Breslow Wilcoxon test nor there was a difference based on the PD-L1 expression. The use of steroids (S) had a beneficial impact on PFS but it was numerically better but not significant on OS. Antibiotic (AB) use also had a beneficial impact on PFS and OS. Patients that had CPI as first-line therapy had shorter PFS than patients that had CPI as second-line therapy. There was no difference whether RT was used or not in patients that had antibiotics or steroids. Conclusions: Our analysis showed that several factors can potentially impact the PFS and OS of patients treated with CPI. Contrary to the previous report, the use of Ab or S did not affect adversely the PFS and OS. We did not observe a beneficial effect of RT. The sequence of use of CPI could potentially affect the PFS. This data should be taken with caution as it is a retrospective analysis with a small sample number but it reflects the real-life practice of patients treated outside of a clinical trial setting. [Table: see text]
An evaluation of RAS testing and survival among mCRC patients in the United States.
Authors: Enko Kiprilov, Laura Sangaré, Kimberly Lowe, Alexandra Christodoulopoulou
Journal: Journal of Clinical Oncology (2019)

e15144 Background: The status of mutations in the rat sarcoma viral oncogene homolog ( RAS) family of genes, which includes Kirsten RAS ( KRAS) and Neuroblastoma RAS ( NRAS) predicts response to anti-EGFR therapies in metastatic colorectal cancer (mCRC) patients. Current treatment guidelines recommend all mCRC patients to receive RAS testing prior to initiating treatment with an anti-EGFR agent. This study sought to establish estimates of RAS testing among mCRC patients in the US prior to initiation of first and third lines of treatment, and to describe median survival by treatment groups. Methods: Data from the Oncology Services Comprehensive Electronic Records (OSCER) 2.0 dataset were utilized. Patients diagnosed with mCRC between January 1, 2011 and July 31, 2017 were eligible. Patients were followed for up to 1 year, or until death, following their mCRC diagnosis. Results: A total of 17,387 mCRC patients were included in the analysis, among which 69% were RAS tested and 31% were never tested. Among the RAS tested patients, 23% were tested prior to their mCRC diagnosis 60% received RAS testing following mCRC diagnosis but prior to first line of treatment, 3% were tested following first line treatment but prior to third line, and the remaining 14% were tested following third line. Demographic variables did not differ between tested and untested groups, overall and by line of treatment. The overall median survival of RAS WT patients was 31.1 months (95% CI: 30.0, 32.4). MCRC patients who were not RAS tested had a lower median survival of 20.7 months (95% CI: 19.1, 22.5). Conclusions: The timing of when patients are being tested varies greatly. While nearly 70% of patients had a RAS test, approximately 30% failed to be tested, identifying a large gap in testing practices. Universal RAS testing provides patients and their physicians with knowledge of their anti-EGFR treatment options and may result in improved survival.
A phase I multiple-dose escalation study to assess the safety, tolerability, and pharmacokinetics of VEGF-receptor inhibitor telatinib (EOC315) in Chinese patients with advanced solid tumors.
Authors: Hongming Pan, Tianshu Liu, Jason Tsai, Yapeng Zhao
Journal: Journal of Clinical Oncology (2019)

3061 Background: Telatinib (EOC315) is a highly selective inhibitor of VEGFR/PDGFR (VEGFR 1-3, PDGFR-β, and c-Kit tyrosine kinases). This phase I study was to assess the safety, tolerability, and pharmacokinetics (PK) of Telatinib in Chinese patients with advanced solid tumors. Methods: Telatinib was administered to Chinese patients with advanced refractory solid tumors as a single agent in 3+3 dose escalation design, starting from 600mg and escalated to 900mg and 1200mg, given orally twice daily. The PK profile, safety, and tolerability were evaluated per protocol. Efficacy was evaluated with RECIST 1.1 criteria every 6 weeks. Results: A total of 15 subjects (6 colorectal cancer, 4 lung cancer, 1 head and neck cancer, 1 melanoma, 1 thymic carcinoma, 1 esophageal carcinoma,1 peritoneal carcinoma) were enrolled per protocol between July 2017 and August 2018, and 13 subjects received at least second line therapies before enrollment. Telatinib was well tolerated in the three dose arms. No dose limiting toxicities (DLTs) occurred during the dose escalation phase. CTC grade 3 AEs observed include hypertension (46.7%, 7/15), fatigue (6.7%, 1/15), transaminase elevation (6.7%, 1/15), hand-foot syndrome (6.7%, 1/15), oral mucositis (6.7%, 1/15), neutropenia (6.7%, 1/15), urobilinogen elevation (6.7%, 1/15), left ventricular systolic dysfunction/decreased ejection fraction (6.7%, 1/15). No CTC grade 4 AE were observed. There were 2 drug related SAEs (hospitalization due to high blood pressure. The PK profile of Telatinib (EOC315) at 600, 900, 1200 mg in Chinese patient cohorts is summarized in Table. For 12 evaluable patients, DCR was 58.3%. For all patients, mPFS was 15 weeks (3.3-34.3w). Conclusions: This study demonstrated the safety and tolerability of Telatinib (EOC315) in a multiple dose escalation design at 600, 900, and 1200 mg PO bid in Chinese patients with advanced refractory solid tumor. Telatinib AUC increased dose-proportionally from 600 mg to 900 mg bid, where 900 mg Telatinib bid is the maximum feasible and recommended dose for future studies in Chinese patients with advanced tumors. Clinical trial information: NCT03175497. [Table: see text]