tbuckley/cabot-search huggingface dataset:
Revealing the crucial roles of myxoma cells and CD206+ macrophages in cardiac myxoma progression based on single-cell sequencing.
Authors: Zedong Jiang, Qianlong Kang, Huan Tong, Guangqi Li, Xuelei Ma
Journal: Journal of Clinical Oncology (2024)

e23549 Background: Cardiac myxoma is a commonly encountered tumor within the heart that has the potential to be life-threatening. However, the cellular composition and molecular characteristics of this condition are still not well understood. Methods: We performed single-cell sequencing on cardiac myxoma tissues obtained from 5 patients, focusing on the identification and characterization of cellular subtypes, cell trajectory analysis, and intercellular communication analysis. We performed a comparative analysis of the changes in cell types and states between cardiac myxoma and normal heart tissues. Furthermore, we retrospectively collected pathological sections from 49 cardiac myxoma cases and employed the multi-color immunohistochemistry (mIHC) technology to analyze the relationship between cellular infiltration and the severity of disease. Results: In total, 75,641 cells in cardiac myxoma tissues formed 9 distinct cell populations. Myxoma cells exhibited a significant resemblance to fibroblasts, yet they were distinguished by an increased expression of phosphodiesterases and genes associated with cell proliferation, differentiation, adhesion, and migration. Myxoma cells displayed cellular heterogeneity and demonstrated two distinct evolutionary pathways. One involves the transition from stem cell-like cells to stromal cells and the other involves enhancement of blood coagulation function. Immune cells surrounding the myxoma displayed suppressive features, with the presence of CD8+ T cells expressing TOX and GZMK, as well as a decrease in the secretion of cytotoxic molecules, indicating an impaired effector function. Macrophages were found to express growth factors such as EREG and PDGFC which played a role in promoting myxoma growth. Conversely, myxoma cells were also observed to secrete ANGPTL4 and ANXA1 which in turn induced the transformation of CD206+ macrophages. Extensive mIHC experiments indicated that a higher proportion of CD206+macrophages and myxoma cells infiltrating the myxoma tissues, along with their enhanced spatial interaction, were found to significantly contribute to the increased occurrence of embolism in cardiac myxoma patients. Conclusions: In summary, this study presents a comprehensive single-cell atlas of cardiac myxoma, highlighting the heterogeneity of myxoma cells and their collaborative impact on immune cells. These findings shed light on the complex pathobiology of cardiac myxoma and present potential targets for intervention.
Treatment outcomes and prognostic factors of bowel function recovery after hyperthermic intraperitoneal chemotherapy and cytoreductive surgery for metastatic cancers of the abdomen and pelvis.
Authors: Sidra Naz, Jianliang Dai, Irene Jeong-Ah Lee, Ahmed F. Sayed, Beth A. Helmink, Mehnaz Shafi
Journal: Journal of Clinical Oncology (2024)

e23225 Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) is combined with cytoreductive surgery (CRS) to treat metastatic tumors of the abdomen and pelvis. The risk factors of GI dysmotility after HIPEC and CRS are not well known. Methods: We performed a single-center, retrospective chart review including all patients who had undergone HIPEC and CRS for metastatic cancer of the abdomen and pelvis from 2016-2023 to assess the prognostic factors of bowel function after HIPEC and CRS treatment. Patients were classified into high or low peritoneal cancer burden by a peritoneal cancer index (PCI) score. Statistics: Categorical variables were summarized by count and percentage and continuous variables. Comparisons of categorical and continuous covariables were conducted using Fisher’s exact test and the Wilcoxon rank sum test. Results: 195 patients met the study criteria. Duration of bowel recovery time in the High PCI was significantly higher than in the Low PCI group (median 11.5 days vs 9 days, p = 0.027). Persistent bowel dysfunction at day 30 was (7.47 x) associated with malnutrition (p = 0.001) and (6.95 x) a venting G Tube (p = 0.032) and history of radiation (p = 0.019) and Pre-OP Opioid Use (p = 0.01). Metoclopramide, Erythromycin and Mu Antagonists were used in 32%, 4.7% and 1.2% respectively of patients with bowel dysfunction. Conclusions: Patients with a high PCI score had a statistically significant longer duration of bowel dysfunction. Malnutrition and a history of radiation were statistically higher in patients with prolonged bowel dysfunction. Use of prokinetics and mu receptor antagonists was uncommon. [Table: see text]
Tolerability, dose intensity, and prescribing patterns of capecitabine by race.
Authors: Joshua Dower, Yana Salei, Benjamin Koethe, Alex Julian, Jake Schwartz, Brett Dumas, Jacob Matt Elkon, Rachel J. Buchsbaum, Ilana Schlam
Journal: Journal of Clinical Oncology (2024)

e23278 Background: Capecitabine (cap) is approved for the treatment of breast and colorectal cancer and is used off-label to treat other solid malignancies. Approved dosing varies by indication and concurrent therapies, and the initial dose of cap may be modified empirically based on different patient characteristics. Race/ethnicity have been used by some providers as factors in prescribing patterns. However, the tolerability of cap among patients of different racial/ethnic backgrounds is unknown. Here, we present an updated analysis outlining the tolerability of cap among patients of different racial/ethnic groups. Methods: We performed a retrospective, multicenter study that included patients treated with cap monotherapy, concurrent with other chemotherapy, or concurrent with radiation at three sites in Massachusetts between 2017-2021. Patients were excluded if race/ethnicity data were not available. Data on cap dose, required dose reductions/treatment discontinuation, and adverse events (AE) were collected. Dose Intensity (DI) was calculated (Total administered cap dose during the treatment period (mg)/Recommended cap dose (mg/m 2 )*BSA (m 2 )). DI was compared across groups using non-parametric Kruskal-Wallis tests. The frequency of AE leading to dose reduction/discontinuation was compared across groups using chi-square tests. Results: 239 patients were included as outlined in Table 1. Median DI (IQR) for White patients was 0.95 (0.77,1.00), for Asian patients 1.00 (0.86,1.00), for Black/African American patients 0.88 (0.67,1.00), and for patients of other race 1.00 (0.79,1.00). There was no statistically significant difference across racial groups (p = 0.233). Median DI (IQR) for Hispanic/Latino patients was 0.84 (0.73,1.00) and for non-Hispanic/Latino patients 0.96 (0.77,1.00). There was no statistically significant difference between ethnicity groups (p = 0.562). The most commonly experienced AE included Hand Foot Syndrome, Fatigue, Diarrhea, and Nausea/Vomiting (Table 1). There was no statistically significant difference in AE frequency between groups. Conclusions: Our study shows no significant difference in the tolerability of cap between patients of different racial/ethnic groups, nor did we find any difference in the predominant AE. While this study is limited by the fact that it is retrospective and small, the results reinforce the importance of considering the entire clinical context when selecting a treatment dose and avoiding empiric dose reductions based on factors such as race/ethnicity. [Table: see text]
Survival trends of soft tissue sarcomas and gastrointestinal stromal tumors from 1995 to 2019: A SEER database analysis.
Authors: Nicole Janell Hardy, Hari Anant Deshpande, Kelly Olino, Philippos Apolinario Costa
Journal: Journal of Clinical Oncology (2024)

e23528 Background: In the last 25 years, new therapies have been developed for gastrointestinal stromal tumors (GISTs), while treatments for many soft tissue sarcomas (STSs) have remained relatively stagnant with 90% of phase I/II trials focusing on repurposing existing drugs. This study compares survival changes over time in patients with STSs and GISTs. Methods: Data from the Surveillance, Epidemiology, and End Results (SEER)-9 registry were analyzed for patients aged 20+ diagnosed with GISTs and STSs from 1995 to 2019. Patients were categorized into time periods: 1995-2004, 2005-2014, 2015-2019. The primary outcomes were the 5-year overall survival (OS) difference between GISTs and STSs and survival variations across the periods. Survival was calculated using the Kaplan–Meier method, and differences were assessed with log-rank tests. Results: 26,633 STS and 3,818 GIST patients were identified. The 5-year OS rate was 53.0% (95% CI: 52.4-53.7) for STSs and 68.7% (95% CI: 67.1-70.3) for GISTs (p &lt; 0.001), with a respective median OS of 72 (95% CI: 69-75) and 121 (95% CI: 113-128) months. For STS, the 5-year OS rate was 53.3% (95% CI: 52.3-54.4), 52.8% (95% CI: 51.9-53.8), and 54.2% (95% CI: 52.2-56.3) (p = 0.66) for groups 1995-2004, 2005-2014, and 2015-2019, respectively. For GIST, the 5-year OS rate was 60.7% (95% CI: 57.3-64.2), 70.6% (95% CI: 68.5-72.7), and 71.0% (64.5-78.3) (p &lt; 0.001). In the locoregional setting (L), the GIST median 5-year OS was 70.5% (95% CI: 66.9-74.3), 78.1% (95% CI: 75.9-80.3), and 79.0% (95% CI: 71.4-87.4) (p &lt; 0.001). In the metastatic setting (M) for GIST, the 5-year OS rate was 30.7% (95% CI: 24.8-37.9), 45.7% (95% CI: 41.1-50.7), and 46.3% (95% CI: 35.8-59.8) (p &lt; 0.001). However, no significant difference was seen for STSs in either setting (L1995-2004 61.6% 95% CI: 60.5–62.8, M1995-2004 11.2, 95% CI: 9.7–12.9, L2005-2014 61.5%, 95% CI: 60.5–62.5, M2005-2014 10.2, 95% CI: 8.9–11.7, L2015-2019 63.4%, 95% CI: 61.2–65.7, M2015-2019 12.1, 95% CI: 9.4–15.6, p(L) = 0.71 and p(M) = 0.74). Conclusions: While GIST survival rates significantly improved, those for other STSs remain unchanged, highlighting an urgent need for novel STS therapies. [Table: see text]
Characterization of remote symptom alerts generated from patient-reported outcome (PRO) symptom monitoring in a real-world breast cancer population.
Authors: Marisabel Hurtado Castillo, Emelly Rusli, Debra Wujcik, Aaron Galaznik, Tara L. Kaufmann
Journal: Journal of Clinical Oncology (2024)

e23193 Background: Women with breast cancer experience debilitating symptoms, yet the patient-reported symptom burden among patients on treatment remains largely uncharacterized. This study characterized electronic PRO (ePRO) symptom monitoring data of patients with breast cancer in real-world settings to assess differences in remote symptom alerts by clinical characteristics. Methods: We conducted a retrospective descriptive study of complete case ePRO data reported by patients at twelve US sites using Carevive PROmPT, a remote symptom monitoring platform. Participants consent to share de-identified, aggregate ePRO symptom data and sociodemographic and clinical characteristics from the electronic health record. We characterized PRO-CTCAE symptom data reported by breast cancer patients on active cancer treatment enrolled between 9/2020 and 11/2023. The PRO platform generates an algorithm-based alert if the combination of symptom severity, frequency, and interference is moderate or severe. We used descriptive statistics to characterize symptom severity and number of alerts by baseline patient-report ECOG status, age, cancer stage (Stage I-III vs. IV), and breast cancer subtype. Results: Of 646 patients, 519 (80%) generated alerts during treatment. Population characteristics were: median age 56 years-old (range 26-84), 72% White, 20% Black/African American, 62% Stage I-III, 15% HER2 positive, 47% ER and/or PR positive, HER2 negative,18% triple negative. Patients reported a total of 19,425 symptoms over a median of 12 weeks with 80% compliance rate, of which 39% resulted in alerts. Participants generated a median of 1 alert per week. About 50% of alerts occurred in the first 12 weeks of ePRO completion, with a higher proportion in Week 1-4 across all subgroups (range, 15-38%). On average, ECOG 2 or greater patients generated more alerts per week than ECOG 0-1, (mean 2.1, (SD 1.3) vs. 1.7 (SD 1.0). Younger patients ( &lt; 50 years) generated more alerts compared to those older than 50 years (87% vs. 77%). Patients with early-stage disease reported more alerts than the Stage IV group (81% vs. 78%). In the metastatic setting, triple negative patients reported a median of 3 (range 1-8) moderate/severe symptoms per week; the other subtypes reported a median of 1 (range 1-8). Conclusions: Women on breast cancer treatment reported their symptom experience with high compliance rates in the real-world setting. Nearly 40% of symptom reports generated an alert, with a higher proportion in the first month of treatment. Younger, early-stage, and metastatic triple negative patients with breast cancer reported a higher symptom burden compared to other groups. Future work will investigate symptom experience by sociodemographic and clinical characteristics to further identify patients who may benefit from more intensive symptom reporting and management.
Usage pattern of anticoagulants in oncology patients receiving active anticancer therapies in Europe and Asia.
Authors: Kriti Jindal, Magdalena Ruiz, José Luis García, Caroline Anger, Sari Heitner Enschede, Ezequiel Cayetano Pérez
Journal: Journal of Clinical Oncology (2024)

e23297 Background: Risks and benefits associated with use of anticoagulants (ACs) in cancer patients should be carefully assessed due to an increased risk of both thrombotic recurrences and bleeding events. Vitamin K antagonists (AVK) have been the most used ACs for patients with atrial fibrillation and venous thromboembolism for many years. Low molecular weight heparins (LMWH) and direct oral anticoagulants (DOACs) are preferred over AVK for cancer associated thrombosis. To better define the current scenario for ACs in cancer patients we propose to use market research data to describe treatment patterns in Europe and Asia. Methods: This study was conducted using Oncology Dynamics, an online secondary market research survey collecting anonymized patient data, from a representative panel of physicians. Data for 11,568 drug-treated oncology patients (p) (9,178 Europe p; 2,390 Asia p) with active cancer and anticoagulant therapies, collected between Q3 2021 and Q3 2023, from 5 European (France, Spain, Germany, Italy, &amp; UK) and 3 Asian countries (China, Japan, &amp; S. Korea), were analyzed. Patients with Genitourinary (GU) tumors were 36%, Lung 19%, Gastrointestinal (GI) 18%, Hepatobiliary/pancreas 12%, Gynecologic (Gyn) 12%, and Melanoma and Brain &lt; 5%. Results: 94% p were aged &gt; 50 years and 49% &gt; 70 years. 64% p were male and 36% female. 67% p showed advanced/metastatic stage vs 33% local/locally advanced stage. Globally, DOACs use was 55%, LMWH 35%, and AVK &lt; 10%; DOACs were the preferred ACs in Europe (64% p) and LMWH in Asia (59% p). Prescription of AVKs in Asia population was higher (17% p) compared with Europe (7% p). Difference in use of ACs by tumor type in European countries in favor of DOACs vs LMWH was noticeable in GU (75% p vs 13% p), GI (61% vs 34%) and Melanoma (71% vs 22%). In Asia population, predominance of LMWH vs DOACs was observable in Gyn (86% p vs 5% p), GI (57% vs 24%) and Hepatobiliary/pancreas (56% vs 35%). AVK were administered in 53% of GU Asia p and DOACs in 31%. Overall, bleeding was more frequently associated with AVK (32% p), compared to DOACs (15% p) and LMWH (9% p). Conclusions: This research highlights the differences in ACs prescription in oncology patients between Asia and Europe, with a preference for LMWH in former and DOACs in the latter. DOACs are the most common ACs prescribed overall, while AVK, associated with higher incidence of bleeding, are used in a small population. A more comprehensive analysis of the included variables will be shared.
After stent implantation for ACS, ticagrelor monotherapy after &lt;1 mo of DAPT vs. 12 mo of DAPT improved 1-y net clinical benefit
Authors: Jia Ee Chia, Debabrata Mukherjee
Journal: Annals of Internal Medicine (2024)

Source CitationHong SJ, Lee SJ, Suh Y, et al; T-PASS (Ticagrelor Monotherapy in Patients Treated With New-Generation Drug-Eluting Stents for Acute Coronary Syndrome) Investigators. Stopping aspirin within 1 month after stenting for ticagrelor monotherapy in acute coronary syndrome: the T-PASS randomized noninferiority trial. Circulation. 2024;149:562-573. https://pubmed.ncbi.nlm.nih.gov/37878786/AbstractClinical Impact RatingsGIM/FP/GP: Cardiology: Hematology:
Attitudes and beliefs regarding sexual dysfunction among patients with advanced cancer receiving palliative care.
Authors: Patricia Bramati, Sonal Admane, Minxing Chen, Aline Rozman de moraes, Guadalupe Padilla, McKenna Erck, Marvin Omar Delgado-Guay, Eduardo Bruera
Journal: Journal of Clinical Oncology (2024)

12054 Background: Sexual dysfunction (SD) is highly prevalent among patients with advanced cancer, but it is not regularly assessed by palliative care (PC) specialists. This study aims to investigate the frequency of SD, and its impact in PC patients with cancer, as well as the barriers they face to have an open communication with PC providers. Methods: AdultPC patients with cancer seen at the outpatient Supportive Care Clinic were invited to participate in a 25-item questionnaire about SD. The survey was voluntary and anonymous. Results: A total of 100 patients (54 women and 46 men) completed the survey. The mean age was 55 (range 24-78), 90% were Caucasians, 16% Hispanics and 77% were married or lived with a partner. In the month and within six months before the survey, the patients received treatment with chemotherapy (44 and 37%), radiation (14 and 13%), or surgery (4 and 20%), respectively. Only 29 patients (29%) would like to discuss their SD with a provider -this was consistent across gender ( p= 0.827) and age groups ( p= 0.194)-, even though 81% had experienced SD in the previous year and merely 45% were satisfied with their sexual function. Only 20 (20%) reported that their clinician had ever asked them about SD. Most of the patients (79%) responded that it was appropriate for the clinician to inquire about SD but only 32% thought that clinicians should always ask. Patients "strongly agreed or agreed" that the SD worsened their depression (39%), anxiety (28%), pain (14%), fatigue (13%), and wellbeing (39%). Factors that worsened the current sexual desire included medications in 33/59 participants, treatments (chemotherapy, radiation or surgery) in 61/80, miscommunication with the partner in 31/66, urinary incontinence in 17/24, weigh loss in 18/36, body image in 45/64, tube/lines (nephrostomy, colostomy, urinary catheter, etc) in 12/18, and oxygen in 4/12. When asked why they did not discuss SD, 64% said that discussing other symptoms was more important, 35% said that they wanted to keep it private, 29% because a family member was present, and 17% because of lack of time. Conclusions: SD is very common among PC patients with cancer and it worsens their emotional and physical symptoms as well as their overall wellbeing. About only a third of the respondents said they would want to discuss it with their provider, and almost two-thirds said that talking about other symptoms was more important. Our findings do not support the notion that PC specialists should always initiate a discussion about SD with their PC patients with cancer. Future studies should try to better identify which PC patients are open to talk about SD and exploring its therapies.
Therapy-related myeloid neoplasm risk score (TMNRS): A convenient clinical score for TMN risk assessment at presentation in adult patients (pts) with cancer.
Authors: Abhay Singh, Megan Herr, Rahul Mishra, Rusina Karia, Theresa Hahn, Swapna Thota
Journal: Journal of Clinical Oncology (2024)

11164 Background: tMNs are rare, albeit serious complication in cancer survivors. A tMN risk prediction model is currently not available, therefore we leveraged clinical information and history in a large population-claims database to devise the first tMN risk prediction model in adult cancer survivors. Methods: SEER-Medicare was used to analyze 970,390 adults aged 66-84 diagnosed with first primary cancer (FPC) from 2000-2011 (with follow-up through 2015), who survived ≥1 year. Medicare claims data classified individuals with a priori identified conditions. We focused on prostate, GI, breast, lung, and bladder (n=830,468) FPCs to develop a tMN risk prediction model. The population was divided into training and validation cohorts. Χ 2 test identified risk factors associated with tMN. The tMN risk score (TMNRS) was created as a simple arithmetic sum of independent predictors of tMN weighted according to the adjusted odds ratio from logistic regression analysis. Pts were categorized into risk groups (Table) based on their TMNRS, which were tested in the validation cohort. Model performance was evaluated using ROC and c-statistics. Results: 87-96% of tMN developed within the first 10 years of FPC. Predictors of tMN included history of autoimmunity, infections, cardiovascular disease, granulocyte-colony stimulating factor, FPC stage, chemoradiotherapy exposure, age at FPC diagnosis, and sex. Training analysis distinguished survivors into distinct risk groups (table) with 10-year incidence of tMN ranging from 0.3% to 1.5% (prostate), 0.04% to 1.1% (GI), 0.2% to 1.4% (breast), 0.1% to 1.2% (lung) and 0.1% to 1.4% (bladder). The table summarizes the incidence of tMN and by risk category for each of the FPCs. After validation, the c-statistic ranged from 0.62-0.68. Conclusions: We utilized the largest SEER-Medicare cohort to date to develop a tMN risk model. The TMNRS captures several novel predictors and can be readily used in the clinic. This easy-to-use tool distinguishes cancer survivors into clinically relevant groups at risk of tMN development. This study lays the framework for screening and monitoring of pts at high risk of tMN. In future, we will leverage increasingly available molecular data to improve prediction performance of the model. Web-based calculator to be published with the manuscript/available at time of presentation. [Table: see text]
A novel endoscopic approach for the treatment of hiatal hernia combined with refractory gastroesophageal reflux disease
Authors: Yushang Yang, Xinyi Zhang, Kaihan Wu, Chencong Zhou, Xuan Huang
Journal: Endoscopy (2024)

Hiatal hernia (HH) is an important cause of refractory gastroesophageal reflux disease (GERD) [1]. Repair of hiatal hernias primarily relies on surgical intervention, with a lack of robust options for endoscopic treatments [2]. Here, we report a case in which a hiatal hernia combined with refractory GERD was successfully treated by gastric fundal and esophageal mucosal ligation combined with titanium clips (GEML-C).
Associations between BMI and hospital resource use in patients hospitalised for COVID-19 in England: a community-based cohort study
Authors: James Altunkaya, Carmen Piernas, Koen B Pouwels, Susan A Jebb, Philip Clarke, Nerys M Astbury, Jose Leal
Journal: The Lancet Diabetes & Endocrinology (2024)

Excess weight is a major risk factor for severe disease after infection with SARS-CoV-2. However, the effect of BMI on COVID-19 hospital resource use has not been fully quantified. This study aimed to identify the association between BMI and hospital resource use for COVID-19 admissions with the intention of informing future national hospital resource allocation.