tbuckley/cabot-search huggingface dataset:
Molecular and clinical characteristics of primary pulmonary lymphoepithelioma-like carcinoma.
Authors: Ying Fan, Qian Yun Shan, Jia Li Gong, Jing Qin, Hongyang Lu
Journal: Journal of Clinical Oncology (2021)

e20541 Background: Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is an extremely rare subtype of non-small cell lung cancer (NSCLC) and there are no established treatment protocols due to its rarity. At present there are only limited studies about the molecular and clinical characteristics of PPLELC and the results are often inconsistent. Methods: The study collected patients with PPLELC who were admitted to Zhejiang Cancer Hospital from 2009 to 2020 retrospectively. Next-generation sequencing (NGS) was performed to obtain a more comprehensive mutation profile of PPLELE, tumor mutation burden (TMB) level and the expression of programmed cell death 1 ligand 1(PD-L1) was detected for 7 patients. In addition, we review the studies concerning the immunotherapy of advanced PPLELC. Results: 18 patients diagnosed as PPLELC pathologically were collected. 71.4% (5/7) patients expressed PD-L1 (≥ 1%) and the median TMB was 2.5 mutations/Mb. TP53 (43%) and CYLD (43%) were the two most common mutations and other variants included LRIG1 (14%), PTPRT (14%), PPP2R2A (14%). 15 patients survived, 3 patients died and 1 patient was lost after a followed up time for 8.8 to 138 months. A total of 11 cases of advanced PPLELC patients who received immunotherapy were analyzed retrospectively and the disease control rate (DCR) was 90.9%. Conclusions: The prognosis of PPLELC is better than that of other NSCLC and immunotherapy may be a promising treatment to prolong the survival time of advanced PPLELC.Whether the immunotherapy efficacy of PPLELC can be predict by PD-L1 and TMB is worthy of further clinical research. CYLD genetic alterations may participate in Epstein-Barr virus (EBV) -mediated tumorigenesis in PPLELC and expected to provide a new therapeutic target.
HGG-36. ONC201 TARGETING IN DIPG
Authors: Alqassem Abuarqoub, Tatiana McAnulty, Eyal Amiel, James Stafford
Journal: Neuro-Oncology (2021)

Abstract Diffuse intrinsic pontine glioma (DIPG) is a group of predominantly pediatric brain tumors with an average age of diagnosis of 6–7 years old, and a poor prognosis (median survival of ~1 year). Given the location of DIPG in the brainstem, surgical approaches are limited. Furthermore, the tumors have limited responsivity to traditional chemotherapy or radiotherapy, ergo new therapeutic options are needed. Recently, the drug ONC201 has emerged as a potential therapeutic option with outcomes sometimes surpassing progression-free and expected survival outcomes. However, the selectivity of its effect and mechanism in DIPG is still unclear. Here, we pursue a better understanding of ONC201 and its mechanism of action directly in DIPG patient-derived cell lines. First, we demonstrate that a range of DIPG cell lines are highly sensitive to ONC201 and compare this sensitivity to other patient-derived brain tumor and normal controls. Next, we directly show that the mitochondrial protease, ClpP is the primary target of ONC201 in DIPG. Given recent literature implicating the activation of ClpP by ONC201 and dysregulation of the metabolome in other tumors, we are currently examining these downstream effects in DIPG. Ultimately we hope to elucidate whether ClpP targeting can be used to better diagnose and improve therapeutic options in DIPG
Modified operations to permit safe and timely delivery of essential surgical care for high-risk skin cancer during a pandemic.
Authors: Stephanie Renae Jackson Cullison, Arda Celen, Nicole Adell Doudican, Mary Stevenson, John A. Carucci
Journal: Journal of Clinical Oncology (2021)

e21565 Background: Many surgical practices closed at the onset of the COVID-19 pandemic raising concerns that delayed cancer care might impact patient outcomes. We implemented operational changes to safely remain open and treat tumors with potential to threaten life or function. We studied the impact of these changes on safety, access, and treatment. Methods: A single-center retrospective study was conducted in an academic office-based dermatologic surgery practice. All patients consented to research. “Pre-pandemic” (Nov. 2019 – March 21, 2020) consultations served as controls. Consultations during the “pause” (March 22 - June 8, 2020) and “reopening” (June 9 – Sept. 30, 2020) were evaluated for time to treatment, tumor area, and upstaging. One-way ANOVA or Fisher Exact analyses were performed with P &lt; 0.05 significant. Operational changes included (1) modified scheduling, staffing, and rooming; (2) COVID-19 symptom screening; (3) N95 masks and shields for patient contact; (4) triage by tumor acuity; (5) same day or video consultation; and (6) increased utilization of same day biopsy and surgery for suspicious lesions. Results: Data from 698 patients (23-103 yrs of age, avg 71 yrs) yielded 876 tumors treated by Mohs surgery (n = 776), standard excision (n = 73), staged excision (n = 14) or electrodessication and curettage (n = 13). The average time from biopsy or consultation to treatment was faster during the pause and reopening relative to pre-pandemic (Table). More frozen section diagnostic biopsies were performed in the pause (n = 6) and reopening (n = 4) compared to pre-pandemic (n = 0). Post-operative defects were similar to pre-pandemic sizes (3.2 cm 2 ) during the pause (3.9 cm 2 ) and reopening (3.2 cm 2 ) (p = 0.72). A reduction in treatment of basal cell carcinoma (BCC, Χ 2 = 0.04) and shift toward treatment of higher risk tumors such as cutaneous squamous cell carcinoma (SCC, 49% of tumors during pause vs 37% pre-pandemic) and melanoma (11% pause vs 4.7% pre-pandemic) was noted. The percentage of SCC upstaged after treatment increased during the pause (42%, Χ 2 = 0.02) vs pre-pandemic (18.5%) or reopening (17.4%). Conclusions: Time to treatment, tumor size, and SCC upstaging pre-pandemic and during the reopening fail to identify any significant access interruptions. This likely reflects practice modifications of increased same day surgery, frozen section diagnostic biopsy, and tumor triage. Lack of COVID-19 transmission attributable to maintained operations suggests that essential surgical care can be delivered safely to patients with high-risk skin cancers during a pandemic.[Table: see text]
Efficacy of venetoclax plus rituximab for relapsed CLL: 5-year follow-up of continuous or limited- duration therapy
Authors: Shuo Ma, John F. Seymour, Danielle M. Brander, Thomas J. Kipps, Michael Y. Choi, Mary Ann Anderson, Kathryn Humphrey, Abdullah Al Masud, John Pesko, Ruby Nandam, Ahmed Hamed Salem, Brenda Chyla, Jennifer Arzt, Amanda Jacobson, Su Young Kim, Andrew W. Roberts
Journal: Blood (2021)
Treatment patterns of older adults with metastatic breast cancer in community practices.
Authors: Melissa McShane, Efrat Dotan, Elias Obeid, Elizabeth A. Handorf
Journal: Journal of Clinical Oncology (2021)

e13063 Background: The median age at diagnosis of breast cancer is 62 with 45% of patients over the age of 65. At diagnosis, up to 5% of patients will have metastatic breast cancer (MBC) and up to 30% of patients with early-stage disease will develop MBC. There are no clear guidelines on how to treat older adults with MBC (OA-MBC) due to their poor representation in clinical trials. This lack of recommendations can often lead to under treatment of OA-MBC. This study evaluated the self-reported treatment patterns of practitioners in community practices for OA-MBC and evaluated the actual treatment their OA-MBC patients received. Methods: This is a secondary analysis of a multi-phase trial which initially evaluated the gaps in practice patterns that exist in the assessment and management of OA-MBC and did a prospective comparison between the older patient’s geriatric assessment and provider’s clinical assessment. In this analysis we focused on the practice patterns in the community. Physicians completed questionnaires detailing their front-line treatment choices for each subcategory of MBC in women over the age of 65. Data was then collected on patients in these physicians’ practices including their current line of treatment, treatment regimen, comorbidities, performance status and demographics. The appropriateness of treatment choice was then evaluated based on MBC subcategory and line of treatment using the NCCN guidelines for breast cancer. Patient and physician characteristics and treatment choices were summarized using descriptive statistics. Results: 44 providers from 9 community practices located in PA, DE, NJ, MT, and WA participated. Majority of providers were Caucasian (57%) and had been in practice for &gt;11 years (53%). 100 patients were evaluated from these practices between December 2016 – April 2019. Median age 73 (65-90). In response to front-line therapy choices, 27/44 (61%) providers selected endocrine only therapy for HR+ but in practice, 29/37 (78%) of HR+ patients were treated with combination endocrine &amp; CDK 4/6 inhibitors. For HER2+, 20/44 (45%) providers selected trastuzumab + chemotherapy for front-line therapy and in practice 8/8 (100%) of patients received this combination. For TNBC, 37/44 (84%) providers agreed with sequential single agent chemotherapy over combination and in practice 6/7 (86%) patients received this. Including all lines of therapy, 84/100 patients were treated in accordance with NCCN guidelines. Conclusions: Despite the lack of older adult guidelines, our community-based practitioners are treating the majority of their OA-MBC patients appropriately and in accordance with NCCN guidelines. In our cohort of OA-MBC there was no evidence of under treatment, however, due to the lack of sufficient data in this patient population it is not clear that this approach is beneficial. Additional research is needed to refine the treatment approach of this unique patient population.
DNMT3A Is Highly Expressed in Bone Marrow Cells from Acute Myeloid Leukemia Patients
Authors: Renata Scopim Ribeiro, João Agostinho Machado-Neto, Paula De Melo Campos, Christopher A. Eide, Samantha L Savage, Irene Lorand-Metze, Cristina E. Tognon, Fernando Ferreira Costa, Brian J. Druker, Sara Teresinha Olalla Saad, Fabiola Traina
Journal: Blood (2017)
Molecular characteristics of EGFR exon 19 deletion subtypes in NSCLC patients.
Authors: Weiquan Gu, Zhongyu Lu, Shulin Shi, Juan Ma, Guanghua Lu, Wanglong Deng, Ran Ding, Fanfeng Bu
Journal: Journal of Clinical Oncology (2021)

8530 Background: EGFR exon 19 deletion mutations are well characterized, known to be activating, and are associated with responses to EGFR tyrosine kinase inhibitors (TKIs). A variety of methods have been developed to identify EGFR mutations. Deletions of EGFR exon 19 are more complex compare to the other because they consist of different subtypes. Methods: In this study, we retrospectively analyzed the different subtypes of EGFR exon 19 deletions using next-generation sequencing(NGS). From May 2019 to December 2020, 3275 patients who were diagnosed with Non-small cell lung cancer (NSCLC)were detected. Results: In this analyzed cohort, the average age of patients was 62 years (range, 24-92 years). Most of the patients were female (61.07%) and were diagnosed with lung adenocarcinoma (82.60%). It is worth noting that the deletions in exon 19 of EGFR were also detected in 35 patients (1.07%) with squamous cell carcinoma and 1 patient (0.03%) with sarcomatoid. The most frequent EGFR exon 19 deletions were delE746-A750 (63.4%), followed by delL747-P753insS (9.7%) and L747-T751 (6.9%). The characteristics of the patients in this study are presented. Significantly, three samples with compound EGFR exon 19 deletions were detected: 1) S1:E746_A750delinsFP+E746_A750del; 2) S2: E746_S752delinsV+L747_P753delinsS; 3) S3:E746_P753delinsVS + L747_P753delinsS. Conclusions: EGFR exon 19 starting at codon 729 to 761, our data showed the deletions occur throughout almost the entire exon 19 amino acid. As our integrated data results, EGFR exon 19 has many different deletions and insertion subtypes could be defined as 79 subtypes. Among those subtypes,70 were complex with an accompanying insertion. The most frequent deletions were starting at E746 and L747. Based on several clinical researches, different deletion subtypes may have significantly different clinical responses after TKI treatment. However, more clinical research is needed to support this finding.
Analyzing the effects of depression among patients with head and neck cancer.
Authors: Muhammad Usman Zafar, Zahid Tarar, Ghulam Ghous, Umer Farooq, Masood Anwar
Journal: Journal of Clinical Oncology (2021)

e18038 Background: Patients with head and neck cancer carry the prospect of facial disfigurement in addition to the effects on speech, smell, sight, and taste. As such they are at a higher risk of acquiring emotional distress. Despite this, depression is underreported in this population. We review the National Inpatient Sample (NIS) to understand the effects of depression in patients admitted with any diagnosis of head and neck cancer. Methods: We designed a retrospective study and utilized NIS data for the year 2018. We identified patients with any history of Head and Neck cancer using their specific ICD-10 codes. We also identified codes for depressive disorders. Primary outcome was effect of depression on comorbidities. Secondary outcome was hospital length of stay. Utilizing STATA MP 16.1 we performed multivariate logistic regression analysis. Various comorbidities including previous history of coronary artery disease, congestive heart failure, stroke, smoking, hyperlipidemia, and chemotherapy were incorporated into the analysis. Results: The study population included 15,689 patients that were 18 years or older. Mean age was 64 years. Only 28% of the population was females. The mean hospital length of stay was approximately 7 days. In this group of patients, 12% had a history of depression. Among the different types of head and neck cancers oropharyngeal cancers had the highest percentage of depression rates (14%). In multivariable analysis, patients with depression had a higher comorbidity index but this result did not reach statistical significance (Odds Ratio (OR) 1.02, p = 0.054, 95% Confidence Intervals (CI) 0.999 – 1.045). Patients had higher odds of having depression if they also had a history of stroke (OR 1.4, 95% CI 1.13 – 1.73), prior history of chemotherapy (OR 1.25, 95% CI 1.09 – 1.43), history of hyperlipidemia (OR 1.31, 95% CI 1.16 – 1.48) or were admitted over the weekend (OR 1.21, 95% CI 1.07 – 1.38). Younger age was associated with lower odds of depression (OR 0.98, 95% CI 0.98 – 0.99). Women had higher odds of having depression (OR 1.68, 95% CI 1.51 – 1.88). When compared with white people, people from the following demographics had lower odds of depression – Black (OR 0.56, 95% CI 0.47 – 0.68), Hispanic (OR 0.64, 95% CI 0.49 – 0.83), Asian (OR 0.26, 95% CI 0.17 – 0.43), and others (OR 0.53, 95% CI 0.35 – 0.79). Hospital length of stay was higher among patients with depression (OR 0.7, 95% CI 0.2 – 1.15). Conclusions: Among patients with head and neck cancer, odds of having depression are higher in the white population, older patients, females and patients with prior history of chemotherapy. Depression is associated with higher hospital length of stay. These findings help understand the effect of depression on this susceptible population and identify at risk patients for appropriate screening.
Abstract 14268: Whole Genome Sequencing Provides Insight Into the Genetic Composition Underlying CHD Severity
Authors: Gillian M Blue, Eddie Ip, Gary F Sholler, Richard P Harvey, Eleni Giannoulatou, Sally L Dunwoodie, David S Winlaw
Journal: Circulation (2019)

Introduction: Following improvements in cardiac surgery, adult congenital heart disease (CHD) now outnumbers paediatric CHD. As this growing patient group approaches reproductive age, ‘causal’ gene...
Racial and ethnic representation trends in United States oncology training programs.
Authors: Conner Lombardi, Jacob Lang, Rochell Issa, Oluchi Ukaegbu Oke, Krishna Reddy, Obi Ekwenna
Journal: Journal of Clinical Oncology (2021)

6519 Background: Utilizing race and ethnicity data from the Accreditation Council for Graduate Medical Education (ACGME), this study aims to assess representation trends across American Society of Clinical Oncology (ASCO) participant specialties from the past five academic years in order to characterize current needs and effectively address these needs moving forward. Methods: Self-reported ethnicity/race data from the ACGME database books were collected from academic years 2015-16 to 2019-2020 for the following oncologic training programs: hematology and medical oncology, medical oncology, gynecologic oncology, pediatric hematology and oncology, radiation oncology, complex general surgical oncology. Summary statistics and chi-square analysis were conducted to compare underrepresented minority (URM) trends across programs. URM groups were cross-referenced with definitions provided by the AAMC and included those who identify as Hispanic, Latino or of Spanish origin, Black or African American, and Native American or Alaskan. Results: Over the study period, only 1,250 (9.0%) of 13,853 oncology trainees identified as URM. Chi-square analysis demonstrated no significant change in URM representation in all oncology specialties combined between 2015-16 and 2019-20 (8.9% [95% CI, 7.8%-10.0%] vs. 9.7% [95% CI, 8.7%-10.8%]; P=.31). Between 2015-16 and 2019-20, Hematology and oncology (+1.3%), pediatric hematology and oncology (+0.3%) all demonstrated insignificant increasing trends in representation while radiation oncology (-0.3%), complex general surgical oncology (-4.0%) had statistically insignificant decreasing trends in representation. Gynecologic oncology (+6.0%) demonstrated a significant increasing trend in representation. Conclusions: This is the first study to characterize the vast disparities in representation in oncologic training programs in the United States. There is a demonstrated lack of representation across all oncology training programs and a lack of significant improvement over the study period. A multiprong approach is needed to improve diversity and representation across the spectrum of the oncology workforce in the United States.
Metabolic regulation in the immune response to cancer
Authors: Qi Wu, Xin Yu, Juanjuan Li, Shengrong Sun, Yi Tu
Journal: Cancer Communications (2021)

Abstract Metabolic reprogramming in tumor‐immune interactions is emerging as a key factor affecting pro‐inflammatory carcinogenic effects and anticancer immune responses. Therefore, dysregulated metabolites and their regulators affect both cancer progression and therapeutic response. Here, we describe the molecular mechanisms through which microenvironmental, systemic, and microbial metabolites potentially influence the host immune response to mediate malignant progression and therapeutic intervention. We summarized the primary interplaying factors that constitute metabolism, immunological reactions, and cancer with a focus on mechanistic aspects. Finally, we discussed the possibility of metabolic interventions at multiple levels to enhance the efficacy of immunotherapeutic and conventional approaches for future anticancer treatments.
Abstract 15844: WWOX Contributes to the Cancer-Like Microenvironment in Pulmonary Hypertension
Authors: Marta T Gomes, Jiwang Chen, Shahzaib G Haider, Yang Bai, Jacob Saliba, Patricia Smith, Sunit Singla, Roberto F Machado
Journal: Circulation (2019)

Background: Pulmonary vascular remodeling is a hallmark of pulmonary arterial hypertension (PAH), involving exaggerated proliferation and resistance to apoptosis of pulmonary artery smooth muscle c...
Mn<sup>3+</sup>-rich oxide/persistent luminescence nanoparticles achieve light-free generation of singlet oxygen and hydroxyl radicals for responsive imaging and tumor treatment
Authors: Dandan Ding, Yushuo Feng, Ruixue Qin, Shi Li, Lei Chen, Jinpeng Jing, Chutong Zhang, Wenjing Sun, Yimin Li, Xiaoyuan Chen, Hongmin Chen
Journal: Theranostics (2021)

X-ray excited persistent luminescence (XEPL) imaging has attracted increasing attention in biomedical imaging due to elimination of autofluorescence, high signal-to-noise ratio and repeatable activation with high penetration. However, optical imaging still suffers from limited for high spatial resolution. Methods: Herein, we report Mn3+-rich manganese oxide (MnOx)-coated chromium-doped zinc gallogermanate (ZGGO) nanoparticles (Mn-ZGGOs). Enhanced XEPL and magnetic resonance (MR) imaging were investigated by the decomposition of MnOx shell in the environment of tumors. We also evaluated the tumor cell-killing mechanism by detection of reactive oxygen (ROS), lipid peroxidation and mitochondrial membrane potential changes in vitro. Furthermore, the in vivo biodistribution, imaging and therapy were studied by U87MG tumor-bearing mice. Results: In the tumor region, the MnOx shell is quickly decomposed to produce Mn3+ and oxygen (O2) to directly generate singlet oxygen (1O2). The resulting Mn2+ transforms endogenous H2O2 into highly toxic hydroxyl radical (·OH) via a Fenton-like reaction. The Mn2+ ions and ZGGOs also exhibit excellent T1-weighted magnetic resonance (MR) imaging and ultrasensitive XEPL imaging in tumors. Conclusion: Both the responsive dual-mode imaging and simultaneous self-supplied O2 for the production of 1O2 and oxygen-independent ·OH in tumors allow for more accurate diagnosis of deep tumors and more efficient inhibition of tumor growth without external activation energy.