tbuckley/cabot-search huggingface dataset:
Clinical, pathological and molecular characterization of long-term survivors with advanced non-small cell lung cancer in a multicenter experience in Madrid: Final results.
Authors: Juan Moreno, Santiago Ponce Aix, Rosa Maria Alvarez Alvarez, Maria Eugenia Olmedo Garcia, Sandra Falagan, Xabier Mielgo, FÃ¡tima Navarro, Patricia Cruz, Luis Cabezon-Gutierrez, Marta Muñoz Fernandez de Legaria, Ana Belen Enguita, Maria Cebollero, Amparo Benito, Isabel Alemany, Carolina Castillo Torres, Ana Ramirez de Molina, Enrique Casado, Ricardo Ramos, Gonzalo Colmenarejo, Maria Sereno Moyano
Journal: Journal of Clinical Oncology (2019)

e20621 Background: Long survivors (LS) in non-small-cell lung cancer (NSCLC), defined as an overall survival (OS) greater than 2 years, are less than 10% in most series. Classical prognosis factors include stage, weight loss and ECOG, but more information is missing in the literature. Recently, EGFR, ALK and ROS 1 population (less than 20%) reach OS longer than 2 years. Immunotherapy has demonstrated very promising results with more LS compared to chemotherapy in first and second line setting. In this study, we focused in the analysis of LS patients with advanced NSCLC EGFR wt (wild type) and ALK nt (non-translocated), defined as those with OS greater than 36 months, in 7 hospitals in Madrid. Methods: In this serie, first of all, we will try to make a clinical, histopathological characterization collecting data from clinical reports according to a previously defined information. In a second step, we will carry out a genetic analysis of these patient samples comparing to an opposite extreme short survivors (SS) samples (OS less than 9 months). Initially, we used a NGS method of RNA-seq technology to identify differentiating profiles of gene expression between the two opposite populations. And finally, we confirmed this preliminary profile by RT-PCR in the rest of samples. Results: Ninety-six patients were initially included. The majority were men, smokers or former with adenocarcinoma and ECOG 0- 1. We have obtained a differential transcriptome expression between samples from 6 LS and 6 SS, resulting 13 over-expressed and 42 down-expressed genes in LS comparing to SS transcriptome expression. Some of the genes involved in this initial profile belong to different cellular pathways: Secretin Receptor, Surfactant Protein, Trefoil Factor 1, Serpin Family, Ca-bindings Protein channel and Toll like Receptor family. Finally, we carried on by RT-PCR in 40 samples of SS and LS survivors and only four genes were significantly down-regulated in SS compared to LS in the multivariate analysis. These 4 genes were related to Surfactant Proteins: SFTPA1 (p = 0.023), SFTPA2 (p = 0.027), SFTPB (p = 0.02) and SFTPC (p = 0.047). Conclusions: We present a sequential genetic analysis of a LS population with NSCLC EGFR wt (wild type) and ALK nt (non-translocated), obtaining a differential RNA seq- and RT-PCR gene profile based on different surfactant proteins expression. A further confirmation in a larger sample is ongoing.
CA045-001: A phase III, randomized, open label study of bempegaldesleukin (NKTR-214) plus nivolumab (NIVO) versus NIVO monotherapy in patients (pts) with previously untreated, unresectable or metastatic melanoma (MEL).
Authors: Nikhil I. Khushalani, Adi Diab, Paolo Antonio Ascierto, James M.G. Larkin, Shahneen Kaur Sandhu, Mario Sznol, Henry B. Koon, Anthony Jarkowski, Ming Zhou, Rui Wang, Gaurav Bajaj, Georgina V. Long
Journal: Journal of Clinical Oncology (2019)

TPS9601 Background: Standard of care for pts with previously untreated, unresectable or metastatic MEL includes checkpoint inhibitors. Bempegaldesleukin is a CD122-preferential IL-2 pathway agonist designed to provide sustained signaling through the IL-2 βγ receptor to activate and proliferate effector CD8+ T and NK cells over T-regulatory cells in the tumor (Hurwitz ME et al. ASCO GU 2017). In the dose-expansion phase of the phase 1/2 PIVOT-02 trial, bempegaldesleukin + NIVO was well tolerated at the recommended phase 2 dose (RP2D; bempegaldesleukin 0.006 mg/kg IV Q3W + NIVO 360 mg IV Q3W), and previously untreated pts with MEL receiving the RP2D achieved an objective response rate (ORR) of 20/38 (53%) and a complete response of 9/38 (24%) by independent radiology review (Diab A et al. SITC 2018). Presented is the design of the first phase 3 trial in the bempegaldesleukin + NIVO development program in pts with previously untreated, unresectable or metastatic MEL. Methods: This phase 3, randomized, open-label study aims to evaluate the effectiveness, safety, and tolerability of bempegaldesleukin + NIVO (NCT03635983). Eligible pts are ≥12 y with histologically confirmed stage III (unresectable) or stage IV MEL and ECOG PS ≤1 or Lansky PS ≥80% (minors 12-17 y). Pts are ineligible if they have active brain or leptomeningeal metastases, uveal MEL, or a recurrence within 6 mo of completing adjuvant treatment with any approved agent. Pts will be stratified by PD-L1 status (measured using PD-L1 IHC 28-8 pharmDx), BRAF mutation status, and lactate dehydrogenase level, and will be randomized to receive bempegaldesleukin 0.006 mg/kg IV Q3W + NIVO 360 mg IV Q3W or NIVO 360 mg IV Q3W up to 24 mo, or until progression or unacceptable toxicity (N ~ 764). Primary endpoints are ORR and progression-free survival (PFS) by blinded independent central review (BICR) and overall survival (OS). Secondary endpoints include ORR and PFS by investigator, ORR and PFS by BICR in biomarker population, OS in biomarker population, and safety. Additional endpoints include pharmacokinetics and quality-of-life assessment. Clinical trial information: NCT03635983.
Management of brain metastases in tyrosine kinase inhibitor-treated epidermal growth factor receptor-mutant non-small-cell lung cancer from the perspective of long-term radiation brain damage: A multi-institutional retrospective analysis.
Authors: Hongqing Zhuang, Xin Wang, Zhiyong Yuan, Enmin Wang, Junjie Wang
Journal: Journal of Clinical Oncology (2019)

e13587 Background: To investigate the relationship between the timing of SRS intervention and the complications of cerebral radiation necrosis(CRN) and its impact on the cognitive function and quality of life(QOL) in patients with brain metastases of lung adenocarcinoma who received TKI treatment. Methods: A total of 361 targets from 257 patients with brain oligo-metastases of lung adenocarcinoma who received Cyberknife treatment between 2010 and 2017 were collected from three Cyberknife centers. The difference in brain necrosis between patients with or without TKI application was statistically counted. Logistic regression analysis was used to analyze the effect of applying TKI on the occurrence of CRN in patients, and the effect of SRS before and after TKI resistance on CRN. The effects of CRN on the cognitive function and quality of life of surviving patients were analyzed. Results: The rate of CRN in the TKI group was significantly higher than that in the non-TKI group. The incidence of brain necrosis in patients undergoing SRS after drug resistance was significantly higher than that in patients undergoing SRS before drug resistance. Regression analysis showed that combination of TKI with SRS, and SRS after TKI resistance were important influencing factors for CRN. The follow-up results of currently surviving patients showed that the occurrence of brain necrosis seriously affected the cognitive function and QOL of patients. Conclusions: Long-term radiation-induced brain damage needs to be seriously monitored in lung adenocarcinoma patients with brain metastasis undergoing combination of radiotherapy and TKI. Clinicians need to pay attention to this problem and make reasonable recommendations for radiotherapy and TKI treatment.
Type 2 diabetes as a potential risk marker for early onset colorectal cancer.
Authors: Joanne Young, Timothy Jay Price, Jenny Hardingham, Erin Symonds, Eric Smith, Andrew Ruszkiewicz, Amanda Rose Townsend, Helen Palethorpe, Yoko Tomita, Gary Wittert, Graeme P. Young, Peter Hewett, David Roder, Paul Drew, David Jesudason, Nicola Poplawski
Journal: Journal of Clinical Oncology (2019)

e15005 Background: Colorectal cancer (CRC) is rising in incidence in young adults. Because they are not included in population screening, and are more likely to present at an advanced stage, there is a need to identify young adults at increased risk for CRC. An association has been reported between type 2 diabetes (T2D) and CRC in the general population. Though lifestyle risk factors may be involved, the early occurrence of CRC in young adults suggests that there may also be a role for inherited predispositions. We therefore investigated whether having a personal and/or first-degree family history of T2D was a potential risk marker for early onset CRC. Methods: The South Australian Young Onset (SAYO) CRC study is an unselected series of young adults with CRC up to age 55. Fifty unrelated young adults (31/50 or 62% female) diagnosed with CRC were recruited to the study. Personal history of T2D was confirmed. Detailed family history of T2D was recorded. 253 patients with clear colonoscopies and no known CRC predisposition served as controls for personal history studies of T2D. Diabetes status was recorded on admission for colonoscopy controls. Associations were explored using a chi-squared statistic. Results: CRC patients ranged in age from 23-54 years (median age 42) and controls from 18-54 (median age 45). Six patients (12%) met the WHO clinical criteria for serrated polyposis, and two (4%) carried a Lynch syndrome mutation. CRC was present in the distal colon in 15/19 males (79%) and 17/31 females (55%) (p = 0.12). A personal history of T2D was confirmed in 12/50 (24%) CRC patients compared with clear colonoscopy controls under 55 years (13/258 or 5% P &lt; 0.001; OR = 5.9; 95%CI 2.5-13.8). T2D was seen in 7/31 or 23% females and 5/19 or 26% males. Young adults with CRC frequently reported at least one first-degree relative with T2D (24/47 or 51%). All patients with personal history of T2D also had first-degree relatives with T2D. A first-degree family history of T2D was observed in 12/27 (44%) CRC patients aged under 45 yrs and 12/20 (60%) of CRC patients aged between 45 and 54 yrs having this characteristic (p = 0.29), and was present in both males and females (10/17 or 58% and 13/30 or 43% respectively; p = 0.37). Conclusions: Though the mechanism remains unclear, given the prevalence of T2D in those aged &lt; 55yrs is 5% in Australia, our observations suggest that there is a striking enrichment for personal and first-degree family history of T2D in young adults with CRC. These features could potentially identify a subset of young adults at increased risk for CRC and in whom early screening might be appropriate.
Case 30-1983
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Marvin P. Fried, Max L. Goodman
Journal: New England Journal of Medicine (1983)

Presentation of CaseA 76-year-old man was admitted to the hospital because of a question of a meningioma.He was well until one year earlier, when he began to have a chronic cough and to lose weight. Two weeks before admission he entered another hospital because of pneumonia. Evaluation showed evidence of chronic lymphocytic leukemia, with a white-cell count of 30,000 and 75 per cent lymphocytes. Repeated stool specimens gave negative tests for occult blood. The thyroxine was normal; serum immunoelectrophoresis revealed a diffuse increase in gamma globulins. An x-ray film of the chest showed bilateral pulmonary infiltrates. A culture . . .
Cervical carcinomas that overexpress human trophoblast cell-surface marker (Trop-2) are highly sensitive to the antibody-drug conjugate sacituzumab govitecan.
Authors: Burak Zeybek, Aranzazu Manzano, Anna Bianchi, Elena Bonazzoli, Natalia Buza, Salvatore Lopez, Emanuele Perrone, Paula Manara, Stefania Bellone, Luca Zammataro, Alessandro Santin
Journal: Journal of Clinical Oncology (2019)

e17028 Background: Recurrent disseminated cervical cancer is a discouraging clinical entity with 1-year survival rates between 10-15%, and development of novel, effective treatments remains an unmet medical need. We investigated the preclinical efficacy of IMMU-132 (sacituzumab govitecan), an antibody-drug conjugate (ADC) comprised of a humanized anti-trophoblast-cell-surface-antigen (Trop-2) antibody (hRS7), conjugated with a hydrolysable linker to the active metabolite of irinotecan (SN-38), against Trop-2 positive primary cervical cancer cell lines and mouse xenografts. Methods: Trop-2 expression was evaluated in 151 cervical tumors and 5 primary tumor cell lines by immunohistochemistry, real-time polymerase chain reaction (RT-PCR) and flow cytometry. Cervical cancer cell viability against IMMU-132, non-targeting control ADC, and naked antibody (hRS7 IgG) was evaluated using flow-cytometry-based assays after 48-72 hours of incubation at a concentration of 0.05, 0.5, 1, 2, 4, and 10 nM of each agent. In vivo antitumor activity was tested in xenograft models with 3+ Trop-2 expression. Results: Out of 151 cervical tumors, 123 were squamous cell carcinoma (SCC), 26 were adenosquamous/adenocarcinoma, 1 was neuroendocrine carcinoma, and 1 was clear cell carcinoma. Strong diffuse staining was seen in 61% (75/123) of SCCs, and 92% (24/26) of adenocarcinoma/adenosquamous cancers. The neuroendocrine carcinoma was also strongly positive, while there was no staining in the clear cell carcinoma. Four out of five (80%) primary cervical cancer cell lines evaluated overexpressed Trop-2 as determined by RT-PCR and flow cytometry. Trop-2 positive cell lines showed high sensitivity to IMMU-132 in vitro, with IC 50 -values in the range of 0.18 to 0.26 nM ( P= 0.02). In contrast, a Trop-2 negative cervical cell line was highly resistant to the ADC with similar IC 50 for IMMU-132 and control ADC. In xenografts, twice-weekly intravenous administration of IMMU-132 for three weeks demonstrated significant tumor growth inhibition compared to controls ( P≤0.001). Overall survival was significantly increased in mice treated with IMMU-132 ( P= 0.014) when compared to naked antibody and ADC-control groups. Conclusions: Sacituzumab govitecan may represent a novel class of active drugs for cervical cancers overexpressing Trop-2. Clinical trials are warranted.
Frequency of Prescription Filling Among Adolescents Prescribed Treatment for Sexually Transmitted Infections in the Emergency Department
Authors: Alexandra Lieberman, Gia M. Badolato, Jennifer Tran, Monika K. Goyal
Journal: JAMA Pediatrics (2019)

Nearly 5% of US adults living in a household with children are e-cigarette users; these children are potentially exposed to secondhand aerosols, an amalgam of compounds with yet unknown health consequences.In addition to risks from secondhand aerosols, children in the same household as e-cigarette users are more likely to themselves initiate e-cigarette use 6 and may be more likely to accidentally ingest refill liquid and experience burn injuries. 2Further
Improved survival following transarterial radioembolization of infiltrative-appearance hepatocellular carcinoma.
Authors: Michael J Nisiewicz, Reema Anil Patel, Adam J Dugan, Joseph W Owen
Journal: Journal of Clinical Oncology (2019)

e15591 Background: Infiltrative-appearance hepatocellular carcinoma (IHCC), also known as diffuse HCC, presents a distinct challenge to clinicians as evidence-based treatment guidelines have yet to be established. While transarterial radioembolization (TARE) has shown efficacy in HCC, many studies exclude IHCC in their analysis. The purpose of this study was to evaluate whether TARE of IHCC improves survival. Methods: With IRB approval, patients with IHCC were identified. Patient were divided into two groups: TARE versus systemic therapy/palliative care. Demographics, date of diagnosis, date of expiry, albumin, international normalized ratio (INR), sodium, alpha-fetoprotein (AFP), creatinine, Child-Pugh class, model for end-stage liver disease (MELD) score, and bilirubin were collected. Patients with bilirubin &gt;3 were excluded. Mann-Whitney U test and Fisher’s exact test assessed for differences between groups. Kaplan-Meier survival analysis and Cox proportional hazard analysis were performed. Results: Forty-one patients were identified, 10 underwent TARE while the remaining 31 served as a control. Mean age was 62, 30 patients were male. The mean overall survival of the TARE treatment group was 16.6 months (506 days) and the mean overall survival of the control group was 5.6 months (170 days) (Log-rank p &lt; 0.004), with a combined overall survival of 8.5 months (259 days). Cox proportional regression analysis revealed statistically significant associations between survival and albumin (hazard ratio 0.12, 0.032-0.41, p &lt; 0.001), Child-Pugh class B (hazard ratio 0.25, 0.064-0.941, p &lt; 0.041), and sorafenib therapy (hazard ratio 0.246, 0.071 – 0.847, p &lt; 0.026). Conclusions: Transarterial radioembolization for patients with IHCC improves life expectancy compared to treatment with comfort measures or systemic therapy.[Table: see text]
The mutational profile analysis of different response to neoadjuvant chemoradiation therapy in local advanced esophageal squamous cell cancer patients.
Authors: Xiaofeng Wang, Xinying Shi, Xu Yang, Wenqing Wang, Lei Deng, Lili Zhao, Wanning Yang, Beibei Mao, Henghui Zhang, Jun Liang
Journal: Journal of Clinical Oncology (2019)

e15560 Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant diseases in the world and especially in China. The combined modality therapy neoadjuvant chemoradiation therapy (nCRT) has become the new standard of care. This study was aimed to investigate the molecular features in cell-free DNA (cfDNA) that is related with the response to nCRT in the local advanced ESCC. Methods: 24 eligible ESCC patients with received nCRT were included and baseline blood were collected from Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. 14 patients had response and the other 10 patients had no response to nCRT, respectively. Both cfDNA fragments and fragmented genomic DNA were extracted for enrichment of a 0.96M size panel covering exon regions of 1,408 genes. Gene alterations were analyzed to explore the relationship between genetic characterizations of cfDNA and response to nCRT. Results: The most common mutated genes were NOTCH1, IRS1, TP53. The somatic alternation of NOTCH1, IRS1, ZFHX4 occurred more frequently in response group than in non-response group. On the contrary, patients with response to nCRT had significantly less mutations of PDE11A, STK11. Moreover, the tumor mutation burden (TMB) of cfDNA in response group was significantly higher than non-response group(p = 0.024). Conclusions: The molecular features in cfDNA of patients with response to nCRT were different from those without response. Five genes’ mutational profile could identify the response and non-response patients with local advanced ESCC. However, prospective studies are needed to validate our findings.
Association of the ratio of CD8+ and CD163+ lymphocytes with clinical outcome in hepatocellular carcinoma.
Authors: Huan Chen, Haibei Xin, Lihong Wu, Yanhui Chen, Hongli Luo, Nan Li, Henghui Zhang
Journal: Journal of Clinical Oncology (2019)

e15613 Background: Within the tumor microenvironment (TME), infiltrating lymphocytes and myeloid cells including tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs) are key players involved in liver cancer progression. The purpose of the study was to explorer whether distinct infiltrated immune cell features differentially affect clinical outcome in hepatocellular carcinoma (HCC). Methods: We obtained respectable stage II HCC specimens, along with adjacent para-tumor tissues from 221 patients who underwent surgical resection at Eastern Hepatobiliary Surgery Hospital, (in Shanghai, China) from 2015 through April 2018. CD8+, CD163+ and CD66B+ tumor-infiltrating lymphocytes (TILs) in the cancer area (CA) and stroma area (SA), as well paratumor stroma area, were analyzed by multiple immunohistochemistry. Results: Hierarchical clustering analysis of immune cell densities revealed that all HCC samples can be classified into three distinct groups. The three immune oncology types (IO-types) were characterized by a strong CD8 T cell density in CA and SA region (IO-1), an intermediate state of CD8 and CD163+ (IO-2), and a strong CD163+ macrophage density in IO-3. Remarkably increasing risks of mortality and recurrence, as well as elevated AST, ALP, GGT and AFP levels, were identified in IO-3 group, when compared with IO-1 group. We then identified that percentages of CA-CD8+ TILs in the tumor sample and SA-CD163+ macrophages in the para-tumor region showed opposite distribution pattern among the three IO types, suggesting a predictive role for CD8/TAM ratio in HCC cohort. Therefore, we next classified all HCC samples into two subgroups, according to the levels of tumor-CA-CD8/paratumor-SA-CD163 ratio. Expectedly, higher rate of CD8/CD163 represented significantly improved overall survival (OS) and progression free survival (PFS), verses lower rate of CD8/CD163. Further association studies suggested that the two subgroups correlated with HBV DNA, tumor size, and microvascular invasion (MVI). Of note, a prognostic signature combining portal vein tumor thrombus (PVTT) and CD8/CD163 ratio discriminated HCC patients into four subtypes with increasing risk of mortality and recurrence. Conclusions: The current results indicated that the CD8/CD163 is a novel, independent prognostic factor for a lower rate of disease recurrence and favorable OS in patients with resectable HCC.