tbuckley/cabot-search huggingface dataset:
Evaluation of systemic and local immune responses in patients with endometrial cancer.
Authors: Martin Ore, Ignacio Romero, Zaida Garcia-Casado, Cristina Zorrero, Carmen Illueca, Jose Antonio Lopez-Guerrero, Andres Poveda
Journal: Journal of Clinical Oncology (2017)

5594 Background: Several studies suggest that systemic immune response (SIR) and local immune response (LIR) have independent roles in multiple types of cancer. In endometrial cancer (EC), the correlation between SIR and LIR and its prognostic value remains unclear. Methods: A total of 146 EC patients (stage I-IV) who had undergone surgery from 2009 to 2015, were identified from a prospective institutional database. Lymphocyte/monocyte ratio (LMR) to represent SIR was calculated from preoperative blood samples. The presence of intratumoral and peritumoral infiltrating lymphocytes (TILs) on hematoxylin and eosin-stained slides was considered as a surrogate of LIR. LMR and TILs were correlated to pathological findings and survival outcomes (overall survival: OS, disease free survival: DFS). Results: A LMR cutoff value of 4.4 for survival was determined based on receiver operating characteristic (ROC) curve analysis. LMR high was significantly associated with endometrioid histology (p=0.03), lower grade (G1-2; p=0.003), &lt; 50% myometrial invasion (p=0.01) and I-II stage (p=0.02). TILs were correlated with MSI-high (p&lt;0.005), but not with LMR (p=0.3). Low LMR was associated with worse 5-year OS rates (64.5% vs 93.9%; p&lt;0.01) and presence of TILs with better 5-years OS rates (72% vs 27%; p=0.04). On multivariate analysis (table 1) LMR, histology, stage and grade remained independent prognostic factors for OS (p=0.01). Using the combination of LMR and TILs, four groups with decreasing 5-years OS rates were identified: LMR-high/TILs+ (100%) &gt; LMR-high/no-TILs (87%) &gt; LMR-low/TILs+ (71%) &gt; LMR-low/no-TILs (61%). Conclusions: In our series of resected EC patients, SIR (defined by LMR) constituted an independent prognostic factor for OS and LIR for DFS. We did not find any correlation between SIR and LIR, but the combination of both higher SIR and LIR showed better OS. [Table: see text]
Nimotuzumab combined with cisplatin plus fluorouracil chemotherapy in patients with metastatic nasopharyngeal carcinoma after radical radiotherapy: A multicentre, open-label, phase II clinical trial.
Authors: Chong Zhao, Jingjing Miao, Guanzhu Shen, Jin-Gao Li, Ning Zhang, Mei Shi, Lin Wang, Guoqing Hu, Xiaozhong Chen, Xuefeng Hu, Shi Xiu Wu, Jiaxin Chen, Xunfan Shao, Conghua Xie
Journal: Journal of Clinical Oncology (2017)

6028 Background: Cisplatin plus fluorouracil (PF) is main therapy for metastatic nasopharyngeal carcinoma (NPC). However, the efficacy is not satisfactory, especially in patients with metastasis after radical radiotherapy. The purpose of this study was to investigate the efficacy and toxicity of Nimotuzumab combined with PF in patients with metastatic NPC after radical radiotherapy. Methods: Patients with untreated metastatic NPC after radical radiotherapy were recruited from 9 hospitals in China with Simon’s two-stage design. All patients received Nimotuzumab (200mg/w) and cisplatin (100mg/m 2 , day 1) plus fluorouracil (4g/m², day 1-4) every 3 weeks until progressive disease (PD) or unacceptable toxicity or a maximum of 6 cycles. If patients had still not progressed at this stage, Nimotuzumab (200mg/w) as monotherapy would be delivered until PD. This study was registered in ClinicalTrials.gov, Number NCT01616849. Results: Between Jun, 2012 and April, 2015, 35 patients were enrolled (Table). The objective response rate (ORR) and disease control rate (DCR) were 71.4% and 85.7%, and the median time of progression free survival (PFS) and overall survival (OS) were 6.97 and 11.01 months. The most common toxicities were leukopenia (94.1%), vomiting (97.1%) and nausea (97.1%); the grade 3/4 toxicities were leukopenia (62.9%) and mucositis (20.0%). There was only 1 patient have mild hypotension which related to Nimotuzumab. The ORR, DCR, median time of PFS and OS were 88.9%, 100.0%, 7.29 and 11.47 months in patients who received a total dose of Nimotuzumab ≥ 2400mg, respectively. Conclusions: Nimotuzumab combined with PF has achieved encouraging efficacy with an acceptable safety profile in metastatic NPC after radical radiotherapy. A phase III randomised study is needed. Clinical trial information: NCT01616849. [Table: see text]
Are NCI-designated cancer centers websites linguistically accessible?
Authors: Jorge Alberto Rodriguez, Roger B Davis, Ryan David Nipp, Beverly Moy, Sanja Percac-Lima
Journal: Journal of Clinical Oncology (2017)

e18078 Background: The digital divide has shifted from disparities in internet access to disparities in content and design. Technology overlooks limited English proficient (LEP) patients, resulting in a lack of translated online content, possibly increasing disparities in cancer prevention, treatment and clinical trial participation. We sought to determine the language accessibility for the websites of the NCI-Designated CC. Methods: In January 2017, we performed a cross-sectional review of the language accessibility of NCI-Designated CC homepages using manual review and informatics methods (i.e., web scraping). Web scraping automates data extraction from online content. The primary outcomes were presence of translated content, number of languages available and method of translation defined as no translation, Google Translate (GT) or manual translation. Manual translation was categorized as limited (few phrases), moderate (1 webpage) or full ( &gt; 1 webpage or entire site). We used logistic regression to assess the relationship between translated website content and CC county demographics: percent LEP, median income and percent of households with an internet subscription. We performed Spearman Rank Correlation by ranking translation effort: no translation, GT, limited, moderate and full translation. Results: Of 69 NCI-Designated CC websites, 54 (78.3%) were without translation, 12 (17.4%) were manually translated and 3 (4.3%) used GT. Of 12 manually translated websites, 6 had fully, 4 had moderate and 2 had limited translations. Of 16 languages offered, Spanish was the most common (100%), followed by Chinese (50%) and Arabic (33%). We found no significant increase in the odds of having a translated website as related to LEP population, median income or percent of households with internet subscription by CC county. There was no correlation between the translation effort and LEP population, internet subscription or median income by CC county. Conclusions: We found that most NCI-Designated CC offered no translations of their website content. Despite cancer health disparities and the increasing role of health technology, the NCI-Designated CC websites currently remain inaccessible to LEP patients.
Kappa Opioid Receptor Distribution and Function in Primary Afferents
Authors: Lindsey M. Snyder, Michael C. Chiang, Emanuel Loeza-Alcocer, Yu Omori, Junichi Hachisuka, Tayler D. Sheahan, Jenna R. Gale, Peter C. Adelman, Elizabeth I. Sypek, Stephanie A. Fulton, Robert L. Friedman, Margaret C. Wright, Melissa Giraldo Duque, Yeon Sun Lee, Zeyu Hu, Huizhen Huang, Xiaoyun Cai, Kimberly A. Meerschaert, Vidhya Nagarajan, Toshiro Hirai, Gregory Scherrer, Daniel H. Kaplan, Frank Porreca, Brian M. Davis, Michael S. Gold, H. Richard Koerber, Sarah E. Ross
Journal: Neuron (2018)
COTI-2, a potent orally available small molecule targeting mutant p53, with promising efficacy as monotherapy and combination treatment in preclinical tumor models.
Authors: Richard T Ho, Kowthar Y Salim, Antje Lindemann, Ameeta A Patel, Hideaki Takahashi, Li Wang, Mei Zhao, Steven J. Frank, Jeffrey Myers, Abdullah A Osman, Christian Lynam, Alison D Silva
Journal: Journal of Clinical Oncology (2018)

6040 Background: The p53 tumor suppressor is mutated in more than half of all cancers. COTI-2, an oral 3rd-generation thiosemicarbazone, restores the structure and function of mutant p53 proteins and inhibits growth of p53 mutant cancer cell lines. While few anticancer agents are effective as monotherapies in the clinic in part due to resistance, the COTI-2 mechanism of action to reactivate normal p53 function complements DNA-damaging radiation- or chemo-therapy. Our data demonstrate that COTI-2 has a promising role in combination treatments inducing synergistic anticancer responses. Methods: Cell viability was measured with crystal violet stains or indicator dye to assess IC50. Xenograft studies used cancer cell lines with specified p53 mutations. Drug synergy was determined by combination-index and isobolograms generated using CalcuSyn software. Results: COTI-2 and chemotherapy agents were tested, singly and in combination, in carcinoma cell lines: colorectal, non-small cell lung (NSCLC), and head and neck squamous cell (HNSCC). Cell lines had wild-type p53, a variety of p53 mutations, or unknown status. COTI-2 IC50 for the HNSCC lines, both established and early passaged, were 9.6-370.0 nM with most p53 mutants having lower IC50 than wild-type. In other work, single agent and combination treatment with COTI-2 and approved anticancer agents in colorectal carcinoma, NSCLC, or HNSCC cells in vitro showed strong synergism against mutant p53 cell lines. In mice bearing A2780 or PCI13 tumors with mutant p53, COTI-2 and doxorubicin or cisplatin, singly and in combination, demonstrated significant enhancement of tumor growth inhibition, and combinations were well tolerated. Lastly, COTI-2 and radiotherapy were administered singly and in combination in a PCI13 tumor model and showed strong synergy against tumor growth. Conclusions: COTI-2 is a highly potent, orally bioavailable compound active against many tumors with p53 mutations. This work highlights the potential of combination treatment using COTI-2 with other anticancer agents to provide synergistic tumor growth inhibition with good tolerability.
Application of liquid biopsies in metastatic gastrointestinal cancer to identify candidate therapeutic targets
Authors: L. Pérez, P. Saiz López, R. Sánchez-Escribano, A. Rodrigo, M. García González, M. Durán, M. Infante, A. Terradez, I. Faull, E.A. Lastra
Journal: Annals of Oncology (2018)

Background: Next-generation sequencing (NGS) of cell-free tumor DNA (ctDNA) has great potential for liquid biopsy in cancer diagnostics and to identify patients with actionable genomic alteration. This study, a prospective longitudinal study, focused in a cohort of metastatic cancer patients without standard effective active antineoplastic medical treatment options to establish the rate of patients with actionable genomic alteration and the rate of patients accessing medical treatment. The final objective was to determine the clinical performance based on non-invasive tumor sequencing. Methods: We collected plasma of 10 metastatic gastrointestinal patients with known status of the RAS genes and microsatellites instability in tumor tissue. CtDNA was extracted from plasma and genomic alterations were analyzed by Guardant 360 (Guardant Health, Biosequence, OncoDNA), a next generation sequencing panel. This panel consists of 73 cancer related genes and is able to identify different types of genomic alterations. Informed consent was obtained from all patients. Results: We were able to identify 78 somatic mutations in total resulting in a median number of eight somatic mutations per patient. The most common altered genes are well known tumor suppressor and oncogenes like TP53, APC, KRAS, MYC andEGFR. At least one actionable alteration in plasma cfDNA were detected in eight from the 10 patients (80%) but the proportion of patients for which a genomic identified recommended therapy was available to effectively initiate the treatment were only 37,5% (3/8). In these patients, the identification of alterations like c-MET amplification, FGFR1 amplification or PIK3CA c.1633G>A (p.E545K) mutation, involved in clinically actionable pathways, allowed the selection of a specific therapy. For the rest of cases the main causes of non-access to medical treatment associated with a specific mutation were, among others, the advanced pre-treated patient and clinical trial logistical access difficulties. Conclusions: Our findings confirm the percentage of cases with potentially druggable aberrations is similar to other studies using this strategy and emphasizes their clinical value to identify candidate therapeutic targets. Legal entity responsible for the study: Dr. Enrique Lastra, Hospital de Burgos. Funding: Asociacion Caballeros Purísima Concepcion. Disclosure: A. Rodrigo, A. Terradez: Employee of Biosequence-OncoDNA. I. Faull: Employee of Guardant Health. All other authors have declared no conflicts of interest.
Comparison of predictors of metastatic liver tropism between tumors of epithelial and non-epithelial origin.
Authors: Petros Tsantoulis, Wulfran Cacheux, Pratyaksha Wirapati, Marc-Henri Stern, Sergio Roman-Roman, Nathalie Cassoux, Pascale Mariani, Mauro Delorenzi, Arnaud Roth
Journal: Journal of Clinical Oncology (2016)

11525 Background: Uveal melanoma has a striking propensity for liver metastasis that is not explained by anatomical factors. The biological features that confer this behavior could be a useful predictor of liver metastasis when applied in other tumor types, especially colorectal cancer, where the treatment of liver lesions with curative intent can be considered. Methods: We used our previously published dataset of microarray gene expression data from 76 uveal melanoma patients, a newer cohort of 80 patients that we studied with RNAseq and a publicly available microarray study of uveal melanoma with 57 patients to compile a meta-analysis. Metastasis-free survival models were fit independently for all genes, after adjustment for the status of chromosome 3. The hazard coefficients from each dataset were then combined in a mixed effects model. The top statistically significant genes were used to build a predictive model with the GLMnet algorithm, which performs optimized feature selection and cross-validation performance estimation. Results: After removal of patients and genes with incomplete information we obtained a database of 196 uveal melanoma patients and 13392 genes. The concordance of significant genes between datasets was excellent. The most predictive model for liver metastasis combined two genes: PTP4A3 and JPH1. We validated this model for the prediction of liver metastasis in data from the PETACC-3 study of adjuvant chemotherapy in colorectal cancer. Indeed, the model was predictive of liver metastasis in colorectal cancer patients (n = 446, p= 0.001, HR = 2.27), even after multivariate adjustment for stage, MSI status and treatment group. Based on public data from The Cancer Genome Atlas, the model was also predictive of liver metastasis in gastric cancer patients (n = 217, p= 0.027, HR 4.02), after adjustment for stage. Conclusions: The genes driving liver metastasis of uveal melanoma also participate in the hepatic spread of digestive tumors. Our work provides a unifying view of the biology underlying this metastatic process and will be validated prospectively in other tumor types. Defining the contribution of JPH1 is an opportunity for further biological studies.
A health system experience with an electronic medical record based application to increase lung cancer screening.
Authors: Brandon Weckbaugh, Trent West, Melissa Rosado-de-Christenson, Timothy J. Pluard, John A Spertus, Janakiraman Subramanian
Journal: Journal of Clinical Oncology (2018)

1558 Background: Screening high risk patients for lung cancer with Low Dose Computed Tomography (LDCT) reduces lung cancer-specific mortality, however its adoption in routine clinical care has been limited. We designed an Electronic Medical Record (EMR) based application to identify patients for screening in the primary care setting. Methods: A two-step screening application was created to identify patients meeting CMS criteria for LDCT screening in a visit to a primary care provider (PCP). First, the application directs medical assistants to complete a patient’s smoking history. If the patient meets eligibility for LDCT screening, step-by-step direction for PCPs to complete the screening process, including reviewing smoking history, shared decision making and ordering the LDCT scan, is initiated. We compared the number of referrals for screening LDCT in the 12-month periods before and after implementation of the screening application. Results: During the 12-month period prior to implementation of the screening application in a 18-person PCP group, there were a total of 198 referrals for LDCT screening. Of these, 162 (81.8%) were negative (CAT 1 and 2), 20 (10.1%) required follow up CT (CAT 3), 16 (8.1%) were positive (CAT 4), 3 (1.5%) required an invasive diagnostic procedure (bronchoscopy with biopsy, endobronchial ultrasound, CT guided biopsy, thoracic surgery). Cancer was diagnosed in 2 patients (1.0%), both of whom received cancer treatment. In the 12 months after implementation, referrals increased by 40% to 278. Of these, 241 (86.7%) were negative, 19 (6.8%) required follow up CT, 18 (6.5%) were positive, 4 (1.4%) required an invasive diagnostic procedure, and 3 (1.1%) were diagnosed with cancer and are receiving treatment. Major challenges include variable user compliance in completing accurate smoking history and providers ignoring alerts to initiate lung cancer screening. Conclusions: To our knowledge this is the first report on the use of an EMR based application to identify patients at risk for lung cancer. Implementation of the EMR based application correlated with an increase in referrals for LDCT screening and led to the identification of high risk lung lesions including lung cancer.
Long-term outcomes in patients after discontinuation of PD1/PDL1 inhibitors.
Authors: Zin Myint, Ruta Arays, Arun Kumar Arumugam Raajasekar, Bin Huang, Quan Chen, Peng Wang
Journal: Journal of Clinical Oncology (2018)

e15086 Background: PD1/PDL1inhibitors have been approved for several advanced or metastatic malignancies with improvement in both progression free and overall survival. Yet, there is a paucity of data in optimal treatment duration. Both KEYNOTE-001 and 006 studies showed durable antitumor activity in approximately 90% of melanoma patients after discontinuation of two-year Pembrolizumab treatment with median follow up duration of 32 months and 33.9 months respectively. To our knowledge, there was no similar study reported in different types of solid cancers. Hence, we reported our institute experience retrospectively in regards to durable response after discontinuation of PD1/PDL1 inhibitors. Methods: Data on patients treated with immunotherapy between 2010 and 2017 were collected retrospectively. Patients with all types of cancers who had achieved disease control (including stable disease, partial and complete response) but off therapy for any reason were included. We analyzed the outcomes of these patients after discontinuation of immunotherapy. Results: We evaluated a total 282 patients who were treated with PD1/PDL1 inhibitors in various solid cancers. Twenty patients met our criteria. They were divided into two groups; melanoma (total 8), and non-melanoma (total 12; 3 renal cell, 3 bladder, 1 hepatocellular, 1 colon, and 4 non-small cell lung). As of data cutoff date, 8 out of 8 (100%) in melanoma group had disease control after a median follow-up of 9 months after the last dose of treatment whereas 8 out of 12 (67%) in non-melanoma group had disease control after a median follow-up of 10 months. The median treatment cycle in melanoma group was 11.5 cycles (3-20) versus 11 cycles (3-15) in non-melanoma group. The main reason for stopping treatment was patient preference. Conclusions: Our study shows similar efficacy of durable response in melanoma patients after stopping immunotherapy compared to KEYNOTE studies. Despite limited sample size and short duration of follow-up, our study was the first showing sustained disease control in several non-melanoma cancers after discontinuation of approximately one-year PD1/PDL1 inhibitor treatment. Future prospective malignancy specific trials for optimal duration are warranted.
Factors associated with intention to participate in a randomized yoga intervention among African American breast cancer survivors.
Authors: Sri Lakshmi Yeruva, Danyella Green, Chloe Martin, Teletia R Taylor
Journal: Journal of Clinical Oncology (2016)

e21538 Background: Physical activity improves patient outcomes in breast cancer survivors and it has been suggested that a gentler form of physical activity such as yoga may help promote regular exercise participation. As African Americans are less likely to be yoga users compared with Caucasians, there is a need to understand factors associated with intention to engage in yoga, in order to design successful interventions for this group. The aim of this study was to examine if certain psychological and functional participant characteristics were associated with intention to engage in a yoga program using Theory of Planned Behavior (TBP) constructs. Methods: Thirty-three women were randomized to a restorative yoga group or a waitlist control group. Fourteen African-American breast cancer survivors (33-64 years, at least 12 months post-treatment) participated in an 8-week restorative yoga program and were asked to complete baseline measures of TBP (attitudes (positive or negative attitude about engaging in the yoga program), subjective norms (social support one receives regarding yoga participation), perceived behavioral control (perceived ease or difficulty of engaging in the yoga program) and intention), perceived stress, depression, sleep quality and fatigue. Results: Pearson correlation coefficient assessments revealed significant relationships between: 1) attitude and fatigue (r = -.58) and attitude and sleep quality (r = .72) (participants reporting low fatigue and better sleep quality at baseline had more positive attitudes towards engaging in the yoga program); 2) depression and subjective norm (r = -.57) (women who reported lower depression scores at baseline tended to have more support from others to engage in the yoga program) and 3) sleep quality and perceived behavioral control (r = .581) (women reporting better sleep quality at baseline were likely to be more confident in their ability to engage in the yoga program) (all Ps < .05). Conclusions: Understanding factors associated with intention to engage in yoga among African American breast cancer survivors may help create successful theory based interventions and ultimately maximize adherence in future yoga programs.