tbuckley/cabot-search huggingface dataset:
Abstract AP26: CANCER STEM CELLS: DISTINCT SEEDS FOR RECURRENT OVARIAN CANCER
Authors: Nuzhat Ahmed, Ruth Escalona, Elif Kadife, Dilys Leung, George Kannourakis
Journal: Clinical Cancer Research (2019)

Abstract PURPOSE: The treatment of ovarian cancer (OC) with chemotherapy leaves resistant cancer cells which in a short time re-grow as recurrent cancer. A diverse array of resistance mechanisms for chemotherapy has been described but none have proven as viable targets in a clinical setting. Cancer stem cells (CSCs) are increasingly accepted as the putative mediators of chemoresistance and relapse of cancer. This study aimed to understand the molecular mechanisms involved with chemoresistance and recurrence by investigating the proteomic profile of ascites-derived tumor cells obtained from OC patients prior to (chemonaive, CN) and after chemotherapy treatments (recurrent, CR). METHODS: Ascites collected from CN and CR OC patients diagnosed with advanced-stage serous OC were cultured using a novel in vitro method to obtain a distinct population of epithelial tumor cells. Flow cytometry and immunofluorescence were used to characterize the tumor population. High-resolution label-free quantitative proteomic profiling was used to define significantly differentially expressed proteins between CN and CR tumor cells. KEGG and DAVID software's were used to determine pathways associated with CR cells. The mechanisms of survival of cisplatin and paclitaxel-treated OC cancer cells were determined in vitro by mRNA analysis and in vivo mouse xenograft models by immunohistochemistry. RESULTS: Proteomic profiling of CN and CR tumor cells showed significant differences in proteins encoding for CSC, immune surveillance, DNA repair mechanisms, cytoskeleton rearrangement, cell-cell adhesion, cell cycle pathways, cellular transport, and proteins involved with glycine/proline/arginine synthesis in tumor cells isolated from CR relative to CN patients. Pathway analyses revealed enrichment of chemoresistance markers, energy metabolism, DNA repair mechanisms and immune surveillance pathways in recurrent CR tumor cells. Validation of these pathways in OC cell lines and nude mice treated with chemotherapy demonstrated increased expression of CSC and chemoresistant markers, enhancement in glycolytic pathway and oxidative phosphorylation, suppression of immune surveillance in chemotherapy treated cell lines and recurrent mice xenografts compared to untreated control. CONCLUSION: These findings unravel some of the molecular mechanisms by which chemoresistance and relapse occur in OC patients' post-chemotherapy treatment; and may be important in designing novel therapeutic options for advanced-stage OC patients. Citation Format: Nuzhat Ahmed, Ruth Escalona, Elif Kadife, Dilys Leung and George Kannourakis. CANCER STEM CELLS: DISTINCT SEEDS FOR RECURRENT OVARIAN CANCER [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr AP26.
Winship 4851-19: A pilot study of neoadjuvant and adjuvant cemiplimab for high-risk cutaneous squamous cell carcinoma.
Authors: Michael C. Lowe, Melinda Lynne Yushak, Keith A. Delman, Monica Rizzo, Caroline Claar, Allyson Schmidt, Jeffrey M. Switchenko, David H. Lawson, Ragini Reiney Kudchadkar
Journal: Journal of Clinical Oncology (2021)

TPS9593 Background: The PD-1 inhibitor cemiplimab was approved in 2018 for treatment of locally advanced or metastatic cutaneous squamous cell carcinoma (cSCC) that is not curable with surgery or radiation. This approval was based on the results of the phase 2 EMPOWER-CSCC-1 trial, which demonstrated an objective response rate of 47% with a significant number of these patients experiencing a durable response. However, patients with high risk cSCC that are able to undergo curative intent surgery are not candidates for checkpoint inhibitor therapy but still experience high rates of recurrence and/or systemic progression even when offered adjuvant radiotherapy. In light of data using checkpoint inhibitor therapy in the neoadjuvant setting in other cutaneous malignancies, we hypothesized that cemiplimab therapy would improve surgical outcomes and reduce long-term recurrence rates in patients with high-risk resectable cSCC if used in the perioperative setting. Methods: Winship 4851-19 is a single arm pilot study of cemiplimab in the neoadjuvant and adjuvant setting for high-risk resectable cSCC (NCT04428671). In the neoadjuvant phase, patients receive three doses of cemiplimab every three weeks followed by standard of care surgery. Radiation may be offered when clinically appropriate at the discretion of the investigator. In the adjuvant phase (following surgery +/- radiation), patients receive cemiplimab every three weeks to complete one year total of treatment. Eligible patients must have surgically resectable histologically proven high risk cSCC defined as: nodal disease with extracapsular extension or one node ≥20mm; in transit metastases &gt; 2cm from primary lesion; T4 head and neck primary tumor; perineural invasion; or recurrent cSCC with concurrent ≥N2b nodal disease, size ≥4cm or bony invasion, or poorly differentiated histology. Patients cannot have received prior immunotherapy and must have a ECOG performance status of 0 or 1. Primary objective is to establish pathologic response rate. Secondary objectives include assessments of local and distant recurrence and overall survival rates. We also plan to evaluate the immune profile of fresh tumor and blood to assess the impact of neoadjuvant cemiplimab on the tumor microenvironment and circulating immune responses. To date 5 of 20 patients have been enrolled; this sample size was selected based on feasibility and ability enroll within a timely fashion. Clinical trial information: NCT04428671.
Inhibition of spontaneous tumorigenicity in transgenic mice by modified citrus pectin
Authors: Pratima Nangia-Makker, Allen Saliganan, Larry Tait, Victor Hogan, Judith Abrams, Avraham Raz
Journal: Cancer Research (2005)

3071  Citrus pectin (CP) is a complex, highly branched, plant polysaccharide, which contains a backbone consisting of polygalacturonic acid and side chains consisting of pentose and hexose sugars. We have earlier modified citrus pectin into smaller structure by pH and temperature modification and named it MCP. MCP reduced the metastatic spread of mouse melanoma cells B16 F1, prostate cancer cells Mat-LyLu , breast cancer cells MDA-MB-435 and colon cancer cells LSLiM6 in various animal models. We questioned, whether MCP has only therapeutic effects or also preventive effects on tumor formation in mice. Therefore we selected two transgenic mouse model systems, which produce spontaneous tumors. B6.129-Apc tm1Rak mice carry a chain termination mutation in amino acid 1638 (exon 15) of the Apc gene. Mice homozygous to this mutation are embryonically lethal and heterozygous mice develop multiple colonic polyps, gastrointestinal adenomas and adenocarcinomas. The second transgenic mouse model used for prostate and mammary cancer contained a recombinant gene expressing the simian virus 40 early-region transforming sequences under the regulatory control of the rat prostatic steroid binding protein [C3(1)] gene. The female mice develop mammary tumors and the male offsprings develop prostate tumors. The mice were bred in the Wayne State University animal facility and separated after weaning in groups fed on water or MCP. The mammary tumors were studied after 6 months, and prostatic or intestinal tumors were observed after 8 months. Our results indicate that MCP does not have a preventive action on the growth of spontaneous mammary or prostate cancer, but it reduces the number of tumors of the small intestine significantly.
Financial toxicity, symptom burden, illness perceptions, and communication confidence in cancer clinical trial participants.
Authors: Subha Perni, Chukwuma Azoba, Emily Gorton, Elyse R. Park, Bruce Allan Chabner, Beverly Moy, Ryan David Nipp
Journal: Journal of Clinical Oncology (2021)

86 Background: Cancer clinical trial (CCT) participants are at risk for experiencing adverse effects from financial toxicity, yet these remain understudied. We sought to describe associations among CCT participant-reported financial toxicity (financial burden [FB] and trial cost concerns), symptoms, illness perceptions, communication confidence, hospitalizations, and survival. Methods: From 7/2015-7/2017, we prospectively enrolled CCT participants who expressed interest in financial assistance (n = 100) and a patient group matched by age, sex, cancer type, specific trial, and trial phase (n = 98). We assessed FB (burdened by costs of cancer care), trial cost concerns (worried about affording medical costs of a CCT), physical (Edmonton Symptom Assessment Scale [ESAS]) and psychological (Patient Health Questionnaire-4 [PHQ-4]) symptoms, illness perceptions (Brief Illness Perception Questionnaire [BIPQ]), and communication confidence (Perceived Efficacy in Patient-Physician Interactions [PEPPI]). We used regression models to explore sociodemographic associations with FB and trial cost concerns, as well as their associations with symptom burden, illness perceptions, and communication confidence, adjusting for age, sex, race, performance status, marital status, and metastatic status. We also used Kaplan-Meier and regression methods to evaluate their associations with 6-month hospitalizations and survival. Results: Of 198 patients enrolled, 112 (56.6%) reported FB and 82 (41.4%) had trial cost concerns. Patients with FB were younger (OR 0.96, 95% CI 0.94-0.98) with lower incomes (&lt; $100,000, OR 4.61, 95% CI 2.35-9.01). Patients with trial cost concerns had lower incomes (&lt; $100,000, OR 2.78, 95% CI 1.45-5.29). On adjusted analyses, patients with FB had higher ESAS (OR 1.03, 95% CI 1.02-1.05), PHQ-4 depression (OR 1.54, 95% CI 1.22-1.94), and PHQ-4 anxiety (OR 1.30, 95% CI 1.08-1.55) scores, as well as more negative illness perceptions (OR 1.04, 95% CI 1.01-1.07), but no significant difference in communication confidence (OR 0.98, 95% CI 0.93-1.05). Patients reporting trial cost concerns had higher ESAS (OR 1.03, 95% CI 1.01-1.05), PHQ-4 depression (OR 1.35, 95% CI 1.10-1.65), and PHQ-4 anxiety (OR 1.27, 95% CI 1.07-1.51) scores, as well as more negative illness perceptions (OR 1.06, 95% CI 1.03-1.10), and lower communication confidence (OR 0.93, 95% CI 0.87-0.99). Financial toxicity was not significantly associated with hospitalizations or survival. Conclusions: In this study of CCT participants, younger patients with lower incomes were most vulnerable to financial toxicity. Financial toxicity was associated with greater symptoms, more negative illness perceptions, and lower communication confidence, underscoring the importance of addressing these issues when seeking to alleviate the adverse effects of financial toxicity in CCT participants.
Effect of income on patient decision-making in localized prostate cancer.
Authors: Xinglei Shen, Ying Cao, Aaron J. Katz, Deborah Usinger, Sarah Walden, Ronald C. Chen
Journal: Journal of Clinical Oncology (2021)

6552 Background: Socioeconomic status affects goals of care and treatment choices. We investigated the impact of low household income on diagnosis, goals of care, and treatment choice in patients with localized prostate cancer. Methods: The North Carolina Prostate Cancer Comparative Effectiveness &amp; Survivorship Study (NC ProCESS) is a population-based cohort of prostate cancer patients identified at the time of diagnosis, enrolled from 2011-2013, and followed prospectively. Sociodemographic information and decision making factors including goals of care were collected by patient report. Patients were asked to rate the importance of quality of life, cure, burden to friends and family, cost, and effect on daily activity as well as which of these goals was the most important in their treatment decision making. Annual household income was stratified in to 3 levels: &lt; 40K (low), 40-90K (middle),&gt;90K (high). Results: Of 1382 patients, 539 (39%), 553 (40%), and 290 (21%) reported low, medium, and high household income. Lower income patients were less college educated, more frequently unemployed, and had higher rates of either no insurance or government sponsored insurances. Low income patients had higher PSA and worse clinical stage at diagnosis. In goals of care, low income patients more frequently rated high importance on burden (78.8% vs 76.0% vs 65.2% p&lt;0.01) and cost of cancer (61.2% vs 38.5% vs 14.5% p&lt;0.01), and factors other than cure as the most important treatment decision factor. While overall treatment rate at 1 year was similar by income group, the type of treatment differed. On multivariate analyses, adjusting for age, race, clinical risk group, employment, insurance, and treatment goal, high income was associated with increased odds of having surgery (OR 1.81, CI 1.16 – 2.81), and reduced odds of having radiation (0.60, CI 0.36-0.99). Conclusions: Poor patients with low household income have worse prostate cancer at diagnosis. These patients have different goals of care which impact their choice of treatment. These findings provide novel insight into disparities in diagnosis and outcome in prostate cancer.[Table: see text]
Abstract 16275: Cardiac Sarcoidosis: A United States National Study of In-Hospital Outcomes and 30-Day Readmissions
Authors: Mohammad-Ali Jazayeri, Nikita A Umale, Venkat Vuddanda, Moghniuddin Mohammed, Seyed Hamed Hosseini Dehkordi, Ioannis Mastoris, Siva Sagar Taduru, Seth H Sheldon, Madhu Reddy, Nicholas Haglund, Andrew J Sauer, Zubair I Shah
Journal: Circulation (2019)

Introduction: Cardiac sarcoidosis (CS) is clinically manifest in 5% of sarcoidosis patients, though up to 25% have subclinical cardiac involvement. Diagnostic advances have improved detection of CS...
Novel treatment options in advanced adenoid cystic carcinoma of the breast.
Authors: Evan Wenig, Reumu E. Birhiray
Journal: Journal of Clinical Oncology (2021)

e13071 Background: Adenoid cystic carcinoma (ACC) accounts for less than 0.1% of all breast cancer cases. The disease typically remains localized and indolent, and frequently occurs with triple negative status. Methods: In patients with locally advanced or metastatic disease, chemotherapy for triple negative breast carcinoma is seldom effective. Thus new treatment paradigms are desired. Drug targeted analysis derived from next generation sequencing and identification of driver mutations may offer a bright future in treatment options in chemo-resistant malignancy. Results: A 53 year old woman presented with breast mass and mastectomy with stage pT3N0M0 triple negative ACC of the breast resulting in observation. She later relapsed with chest wall disease, resulting in resection and radiation therapy. Shortly thereafter, she relapsed with pulmonary metastatic disease. She was treated with carboplatin and doxorubicin which were discontinued due to disease progression. Liquid assay revealed an IDH2 mutation, prompting treatment with enasidenib with ongoing evidence of disease control at 4 months. Patient tolerated treatment well without grade 3 or 4 adverse reactions. A 48 year old woman presented with an increasing 9.5 cm unresectable breast mass without distant metastasis. Pathology showed triple negative ACC of the breast, resulting in chemotherapy with doxorubicin, cyclophosphamide, and paclitaxel with clinically progressive disease. She represented with necrotic and ulcerating changes of the breast. Foundational genomic testing showed an FGFR2 mutation. After four months of treatment with erdafitinib, she had resolution of pain and cessation of pain medication. Her therapy led to a grade 2 adverse event related to hyperphosphatemia. She underwent surgical resection with negative margins. Conclusions: These examples illustrate a potential treatment paradigm for a rare malignancy for which there is no standard of care. Here we present two desperate cases, one of which had a driver mutation of IDH2, and the other FGFR2 for which there are targeted therapies approved in other disease states. The use of these two agents resulted in clinical benefit. A patient with metastatic disease treated with enasidenib has ongoing disease control for over 4 months with minimal adverse reaction. A patient with advanced local disease requiring narcotics and gabapentin for pain control treated with erdafitinib had significant symptomatic control with successful cessation of pain medications and ability to undergo potentially curable mastectomy with negative margins despite progression on prior chemotherapy. In summary, ongoing research of ACC of the breast will be required. Alternative therapeutic options related to targeted treatment may offer promise to clinical outcomes in the future. For cases of locally advanced or metastatic disease, the use of targeted therapy may offer new therapeutic options.
Predicting benefit of radium 223 based on biochemical response and site of metastasis: A real life multicenter UK study.
Authors: Prantik Das, Jessica Davies, Anand Sharma, Ajith Nair, Salil Vengalil, Carla Perna, Jenny Branagan, Benjamin Masters, Chee Goh, Sophie Otter, Vineet Prakash, Sadmeet Singh
Journal: Journal of Clinical Oncology (2021)

e17034 Background: Studies have shown an improvement in overall survival (OS) and symptom control in metastatic castration-resistant prostate cancer (mCRPC) with Radium-223 treatment. However, there is little information about predicting outcomes using either PSA or Alkaline Phosphatase (ALP) response or comparing bone only disease to bone and lymph node (LN) involvement. Methods: 335 patients receiving Radium 223 at 6 UK centres between March 2014 and June 2020 were included. The primary endpoint was overall survival, secondary endpoints were toxicity, symptomatic benefit and skeletal-related events(SRE) Results: The median age was 75, with 71% having bone only metastases and 29% also having lymph node involvement. Those with PSA response (30%) had a statistically significant improvement in OS, compared to non-responders (18.2 vs 13.8 months, p = 0.026). They also showed highest rate of imaging response/stable disease (54% vs 34%). ALP response was seen in 82%. This did not translate to significantly improved OS, but did correlate with better symptomatic benefit (40% vs 29%). Those with bone only disease showed a survival benefit compared to those with LN involvement (19.4 vs 11.4 months, p = 0.046). Other than anaemia (23.5%), Grade 2 or above toxicities were uncommon including thrombocytopenia and neutropenia(5.5 and 6.2% respectively ) . 14% patients required at-least one blood transfusion. SRE were seen in 24% overall, but lower of in PSA responders(18%). Conclusions: Real life multicentre data suggests that PSA response and bone only disease could be predictors for better survival following Radium-223, whereas ALP response correlates better with symptomatic benefit.
Robots Induce Parkinson Disease Hallucinations
Authors: Jennifer Abbasi
Journal: JAMA (2021)

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Health-related quality of life (HRQoL) and patient-reported outcomes at final analysis of the TITAN study of apalutamide (APA) versus placebo (PBO) in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) receiving androgen deprivation therapy (ADT).
Authors: Neeraj Agarwal, Simon Chowdhury, Anders Bjartell, Byung Ha Chung, Andrea Juliana Pereira de Santana Gomes, Robert Given, Álvaro Juárez, Axel Stuart Merseburger, Mustafa Ozguroglu, Hirotsugu Uemura, Dingwei Ye, Sabine Doris Brookman-May, Suneel Mundle, Sharon Anne McCarthy, Florence Lefresne, Shiva Dibaj, Katherine B. Bevans, Kim N. Chi
Journal: Journal of Clinical Oncology (2021)

5068 Background: The phase 3 TITAN study evaluated APA vs PBO in pts with mCSPC receiving ADT. At primary analysis with 22.7 mo median follow-up, APA significantly improved overall survival (OS) and radiographic progression-free survival vs PBO (Chi NEJM 2019) while preserving HRQoL (Agarwal Lancet Oncol 2019). The study was unblinded; pts on PBO were allowed to cross over to APA. At final analysis with 44 mo median follow-up, APA significantly improved OS vs PBO, reducing risk of death by 35% despite crossover (Chi ASCO GU 2021). We evaluated HRQoL and treatment bother at final analysis. Methods: mCSPC pts (N = 1052) were randomized 1:1 to APA (240 mg QD; n = 525) or PBO (n = 527). All pts received ADT. Patient-reported outcomes were assessed using Brief Pain Inventory-Short Form (BPI-SF) and Functional Assessment of Cancer Therapy-Prostate (FACT-P). BPI was completed for 7d consecutively (Days -6 to 1 of each 28-d cycle [C]) through end of treatment (EOT). FACT-P was completed at baseline (BL), C2-C7, then every other C through EOT. Mean scores were reported by treatment group and over time. Time to deterioration on BPI and FACT-P scores was calculated by Kaplan-Meier methods and compared between groups by fitting proportional hazards regression models. Results: Of eligible pts per C, &gt; 62% completed BPI through C32 and &gt; 50% completed FACT-P through C31. Pts were relatively asymptomatic with good BL HRQoL: on 0-10 worst pain severity scale (BPI), median scores were 1.1 (APA) and 1.0 (PBO); on 0-156 HRQoL scale (FACT-P total; higher score = better HRQoL), median scores were 113.0 (APA) and 113.3 (PBO). Low BL BPI scores remained stable over time in both groups. On average, favorable BL FACT-P scores did not notably worsen over time in APA or PBO groups. There were no significant differences between groups in median time to deterioration in any BPI or FACT-P scores (Table). At each C at least 86% (APA) and 85% (PBO) of pts were either “not at all” or “a little bit” bothered by side effects. At BL, 76% (APA) and 72% (PBO) had favorable energy levels (reporting lack of energy “not at all” or “a little bit”). Energy levels remained stable or improved at each C for &gt; 78% (APA) and &gt; 71% (PBO) of pts. Conclusions: In the final analysis of TITAN, survival benefit with addition of APA to ADT was achieved without significant patient-reported side effect burden or reduced HRQoL compared with PBO in pts with mCSPC. Clinical trial information: NCT02489318. [Table: see text]