tbuckley/cabot-search huggingface dataset:
Assessment of sociodemographic factors in timely endometrial cancer diagnosis following an abnormal transvaginal ultrasound performed for postmenopausal bleeding.
Authors: Sage Atkins, Angela Nolin, Shakthi Unnithan, Evan R. Myers, Haley Moss, Alaattin Erkanli, Laura J. Havrilesky
Journal: Journal of Clinical Oncology (2024)

e17595 Background: Postmenopausal bleeding (PMB) is the most common initial presentation of endometrial cancer. The American College of Obstetrics and Gynecology recommends evaluation of PMB with transvaginal ultrasound (TVUS) to determine the endometrial stripe (ES) thickness, followed by tissue sampling if ES &gt;4 mm. We assessed if differences in race, ethnicity, language, or insurance status were associated with delayed endometrial sampling following an abnormal ES on TVUS, and if the timing of endometrial sampling after TVUS was associated with differences in rates of endometrial cancer diagnosis and staging. Methods: We conducted a retrospective study of consecutive patients with an intact uterus and PMB who presented to a single academic institution and underwent TVUS between January 2013-December 2022. TVUS was characterized as normal (ES ≤4 mm), abnormal (ES &gt;4 mm), or inadequate (ES not fully visualized). Prompt sampling was defined as sampling with endometrial pathology within 3 months of abnormal TVUS. Logistic regression analyses were performed to characterize associations between race, ethnicity, preferred language, insurance status and prompt endometrial sampling. We assessed rates of endometrial cancer diagnosis and stage at diagnosis, comparing sampling at ≤3 versus 3-12 months after TVUS. Results: Among 3,369 patients meeting inclusion criteria, 1,671 (50%) had abnormal ES. Out of the total cohort, patients with an abnormal ES comprised 576/1336 (43%) of Black or African American and 946/1889 (50%) of White patients. 307/1671 (18%) of patients with abnormal ES did not receive prompt sampling. Neither race (Black OR 1.03, 95% CI 0.79-1.35 vs White), ethnicity, (Hispanic OR 1.1, 95% CI 0.54-2.27 vs. non-Hispanic), non-English primary/preferred language (OR 0.9, 95% CI 0.47-1.71 vs English), nor Medicare insurance status (OR 0.96, 95% CI 0.65-1.42 vs private insurance, age-adjusted) were associated with prompt endometrial sampling after abnormal ES. Endometrial cancer was diagnosed in 147/1227 (12%) of cases who underwent sampling for abnormal ES (143/1165 (12%) with prompt sampling and 4/62 (6%) with delayed sampling). The stage distribution of endometrial cancers diagnosed after prompt sampling was 107/133 (80%) Stage I and 26/133 (20%) stage II-IV, compared to 2/4 (50%) stage IA and 2/4 (50%) stage II-IV after delayed sampling. Conclusions: One in five patients with PMB and an abnormal appearing endometrium on ultrasound did not receive appropriate sampling within 3 months. Race, ethnicity, language, and insurance status were not associated with timely receipt of endometrial sampling following an abnormal ultrasound. With prompt endometrial sampling for abnormal TVUS, 80% of endometrial cancers are diagnosed at the earliest stage.
Demographic factors of malignant endometrioid adenofibroma: An NCDB study.
Authors: Brianna Eillen Ramos, Rawaan Khatib, Nikhita Tandon, Assal Sadighian, Peter T. Silberstein, Craig Heise, Beau Hsia
Journal: Journal of Clinical Oncology (2024)

e17592 Background: Malignant endometrioid adenofibroma (MEA) is a rare subtype of ovarian carcinoma characterized by squamous metaplasia and frequently linked with endometriosis and colorectal cancer. This fibrous tumor with cystic spaces is primarily diagnosed in postmenopausal females who present with abnormal vaginal bleeding. The current recommended treatment option is a laparoscopic resection; however, a hysterectomy may be indicated in more serious cases. Analyzing the trends of MEA may provide significant insights into its epidemiology. An analysis of the National Cancer Database (NCDB) was conducted to identify the demographic factors of patients diagnosed with MEA. Methods: A retrospective cohort analysis utilizing the 2004–2020 National Cancer Database (NCDB) included 193 patients with a histologically-confirmed diagnosis of CA (ICD-O-3 code 8381). Demographic factors (age, sex, race, Hispanic status, insurance status, facility type, distance from facility, and Charlson-Deyo score) were analyzed by descriptive statistics and incidence trends were interpreted in regression analysis. Results: 193 patients diagnosed with MEA were recorded in the database from 2004 to 2019, with a strong declining annual incidence rate (R²=0.7833). Women were much more likely to be diagnosed (99.5%) than men (0.5%), where the average age at diagnosis was 61.40 years (SD= 12.89, Range =30-90). The primary site of diagnosis was the endometrium (54%). Most patients were noted to be non-Hispanic (85%) and White (86%), privately insured (59%), and lived in metropolitan areas with a population greater than 1 million (54%). The majority also had a Charlson-Deyo comorbidity score of 0 (78%). In regard to treatment, patients were seen relatively equally at the comprehensive community cancer program (42%) and academic/research program (32%). 93% of patients received surgery as their primary treatment, 20% received chemotherapy, and 20% received radiation. Conclusions: To the best of our knowledge, this is the first NCDB analysis on malignant endometrioid adenofibroma and thus serves to address prior gaps in the topic’s research. Results were similar to descriptions in earlier case reports, where MEA is notably more common in females who identify as non-Hispanic and White, with a primary site diagnosis at the endometrium. This is the first time the socioeconomic factors of MEA patients have been described in the literature: patients are more likely to live in metropolitan areas, be privately insured, and be treated at similar rates at both academic/research and comprehensive community cancer programs. Further studies are essential in promoting the knowledge of this topic, specifically how demographic/socioeconomic factors influence the diagnosis and treatment options of patients with MEA.
Predictive analysis of placental site trophoblastic tumors (PSTT) and epithelioid trophoblastic tumors (ETT) using machine learning.
Authors: Abdalwahab Alenezy, Sakhr Abdulsalam Alshwayyat, Mustafa Alshwayyat, Tala Abdulsalam Alshwayyat
Journal: Journal of Clinical Oncology (2024)

e17608 Background: The characteristics and outcomes of PSTT and ETT have not been well documented. To improve personalized care, machine learning was used to assess treatment effectiveness and develop accurate prognostic models. Gestational choriocarcinoma (GCC) was used as a control to emphasize the clinical features of PSTT and ETT. Methods: The Surveillance, Epidemiology, and End Results database provided the data used for this study’s analysis (2000–2019). Patients who met any of the following criteria were excluded: diagnosis not confirmed by histology, previous history of cancer or other concurrent malignancies, or unknown data. To identify prognostic variables, we conducted Cox regression analysis and constructed prognostic models using machine learning (ML) algorithms to predict the 5-year survival. Patient records were randomly divided into training (70 %) and validation (30 %) sets. A validation method incorporating the area under the curve (AUC) of the receiver operating characteristic curve was used to validate the accuracy and reliability of the ML models. Results: The study population comprised 725 patients. Among them, 139 patients had ETT, 107 had PSTT, and 479 had GCC. The median patient age was 37 years. Most of the patients were of white race (62.3%) and more than half were married (52.7%). The most common stage of primary tumor histology was distant metastasis, which occurred in 330 patients. The average tumor size was 6.13 cm. More than two-thirds of patients underwent chemotherapy (75.9%), 57.9% underwent surgery, and 4.3% underwent radiotherapy. There were no significant differences in survival between the different tumor groups. Multivariate Cox regression analysis revealed that older age, marital status, metastasis, and radiotherapy were poor prognostic factors, while surgery was a good prognostic factor. ML models revealed that the random forest classifier (RFC) accurately predicted the outcomes. The most important characteristics that influenced the model prediction performance were tumor size, years of diagnosis, race, and age. The performance metrics for all ML algorithms are summarized in Table. Conclusions: Our research sheds light on crucial aspects of clinical decision-making, emphasizing the significance of key factors affecting patient outcomes and offering hope for personalized treatment. Further research should explore the molecular markers and validate the generalizability of our findings. [Table: see text]
VA-ECMO for infarct-related cardiogenic shock
Authors: Zhexuan Yu, Guanhua Li
Journal: The Lancet (2024)

Uwe Zeymer and colleagues1Zeymer U Freund A Hochadel M et al.Venoarterial extracorporeal membrane oxygenation in patients with infarct-related cardiogenic shock: an individual patient data meta-analysis of randomised trials.Lancet. 2023; 402: 1338-1346Summary Full Text Full Text PDF PubMed Scopus (45) Google Scholar report that patients with infarct-related cardiogenic shock treated with venoarterial extracorporeal membrane oxygenation (VA-ECMO) had no benefits compared with medical therapy alone. However, we should carefully interpret these findings. The absence of microcirculatory data in this work is an issue of importance for prospective studies. It is well known that a loss of coherence could be seen between macrocirculation and microcirculation in states of cardiogenic shock and resuscitation.2Bruno RR Wollborn J Fengler K et al.Direct assessment of microcirculation in shock: a randomized-controlled multicenter study.Intensive Care Med. 2023; 49: 645-655Crossref PubMed Scopus (0) Google Scholar The impairment of microcirculatory function might be evident in these patients with infarct-related cardiogenic shock: the arterial pH was 7·21 and the arterial lactate was 6·5 mmol/L. Although systemic haemodynamic variables might recover on ECMO, the normalisation of microcirculatory and tissue perfusion is unclear. The inability of rapid microcirculatory recovery is associated with higher morbidity and mortality for patients on ECMO.3Chommeloux J Montero S Franchineau G et al.Microcirculation evolution in patients on venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock.Crit Care Med. 2020; 48: e9-17Crossref PubMed Scopus (27) Google Scholar, 4Montero S Chommeloux J Franchineau G Combes A Schmidt M Microcirculation in cardiogenic shock supported with extracorporeal membrane oxygenation: the need for a homogeneous population and strict evolution assessment.Crit Care. 2018; 22: 281Crossref Scopus (3) Google Scholar Evaluation methods, such as sidestream darkfield imaging for sublingual microcirculation, capillary refill time, and skin mottling might provide valuable information on microcirculation. Incorporating microcirculatory analyses might distinguish more accurately who will benefit from ECMO.5Duranteau J De Backer D Donadello K et al.The future of intensive care: the study of the microcirculation will help to guide our therapies.Crit Care. 2023; 27: 190Crossref PubMed Scopus (0) Google Scholar We believe that prospective studies with sufficient microcirculatory data could refresh these findings. We declare no competing interests. Venoarterial extracorporeal membrane oxygenation in patients with infarct-related cardiogenic shock: an individual patient data meta-analysis of randomised trialsVA-ECMO did not reduce 30-day death rate compared with medical therapy alone in patients with infarct-related cardiogenic shock, and an increase in major bleeding and vascular complications was observed. A careful review of the indication for VA-ECMO in this setting is warranted. Full-Text PDF
Magnetic resonance texture analysis for predicting histologic tumor type in endometrial cancer.
Authors: Seung-Mi Lee, Hyun-Jung Lee, Juhun Lee
Journal: Journal of Clinical Oncology (2024)

e17580 Background: The aim of the present study was to assess the feasibility of texture analysis and histogram on magnetic resonance image for predicting histologic type in patients with endometrial cancer. Methods: A total of 85 patients who underwent surgery and had pathologically confirmed endometrial cancer were included in this study. We investigated the parameters for normalized perfusion map including perfusion ratio and integrated density, defined as the product of area and mean gray value from the normalized perfusion mapping on gadolinum-enhanced T1-weigted pelvic MRI. Apparent Diffusion Coefficient map and texture analysis by gray-level co-occurrence matrix in endometrial cancer, including angular second moment, contrast, correlation, entropy and inverse difference moment. MR parameters were correlated with pathologic feature including tumor type, FIGO staging, tumor invasion and lymph node metastasis. Results: The normalize perfusion map analysis revealed noteworthy distinctions between type 1 and type 2 endometrial cancer. Specifically, we observed significant differences in tumor area (p = 0.014), perfusion ratio (p = 0.001), perimeter (p = 0.002), integrated density (p = 0.042), median (p = 0.001), and roundness (p = 0.018). Entropy form the texture analysis demonstrated associations with integrated density and linear correlation, with notable differences observed between type 1 (R 2 = 0.363) and type 2 (R 2 = 0.471) endometrial cancer subtypes, displaying statistical significance (p = 0.010). Conclusions: In conclusion, parameters obtained by texture analysis and perfusion map could be useful for predicting the histological type of endometrial cancer.
Chemotherapy plus PD-1/PD-L1 inhibitor versus chemotherapy alone in first-line treatment for recurrent or advanced endometrial cancer: A systematic review and meta-analysis of randomized controlled trials.
Authors: Caio Dabbous de Liz, Melissa Maia, Ana Caroline Fonseca Alves, Isadora Mamede Mendes da Silva, João Pedro Oliveira, Audrey Cabral Ferreira de Oliveira
Journal: Journal of Clinical Oncology (2024)

e17597 Background: More recently, the standard of care for primary advanced or recurrent DNA mismatch repair deficient (MMRd)/microsatellite instability-high (MSI-H) endometrial carcinoma has become a combination of chemotherapy (CT) and PD-1/PD-L1 inhibitor. Whether this should also be applied to all-comers and MMRp/MSS population is still an open question. Methods: PubMed, Embase, and Cochrane database were searched for randomized controlled trials (RCTs) comparing first-line CT plus PD-1/PD-L1 inhibitor versus CT, with or without (w/w) placebo, for patients with primary advanced or recurrent endometrial cancer. The primary endpoints of interest were progression free survival (PFS), overall survival (OS), overall response rate (ORR), complete response rate (CRR), and adverse events (AE) grade ≥ 3. Heterogeneity was examined with I 2 statistics, and a fixed-effects model was employed for analysis. Statistical analysis was performed using Review Manager Web. Results: We included 5 RCTs with 2460 patients, of whom 1143 (46.5%) received CT plus PD-1/PD-L1 inhibitor, and 1672 (68.0%) had MMRp/MSS tumors. Mean follow-up ranged from 7.9 to 28.3 months. The combination of CT plus anti-PD-1/PD-L1 demonstrated superiority in PFS (HR 0.72; 95% CI 0.65-0.80; p &lt; 0.0001) and OS (HR 0.77; 95% CI 0.65-0.91; p=0.002), compared to CT w/w placebo in the all-comer population. In MMRd/MSI-H patients, PFS (HR 0.34; 95% CI 0.27-0.44; p &lt; 0.00001) and OS (HR 0.37; 95% CI 0.24-0.59; p &lt; 0.0001) were statistically significantly better in combination group. For patients with MMRp/MSS disease, PFS was improved (HR 0.76; 95% CI 0.68-0.86; p &lt; 0.0001), but OS was not significantly different between groups (HR 0.92; 95% CI 0.74-1.14; p=0.44). CT plus PD-1/PD-L1 inhibitor also led to a higher ORR (OR 1.50; 95% CI 1.13-2.00; p=0.006) and CRR (OR 1.56; 95% CI 1.12-2.18; p=0.009) in MMRp/MSS patients. AE grade ≥ 3 were more often when immune checkpoint inhibitor was added (HR 1.46; 95% CI 1.23-1.75; p &lt; 0.0001). Conclusions: These findings suggest that combining PD-1/PD-L1 inhibitor to CT improves PFS, but not OS, in first-line treatment for recurrent or advanced MMRp/MSS endometrial cancer, despite grater toxicity. It supports the hypothesis that the benefit seen in survival for all-comer population appears to be driven by MMRd/MSI-H patients. However, given the immaturity of OS data, it is possible that the higher rate of complete responses may translated into more cured patients in long-term follow-up.
Vulvo-vaginal cancer trends during the pandemic.
Authors: Chelsea Stewart, Joshua Elbridge Chan, Nathan Tran, Caitlin Ruth Johnson, Kathleen M. Darcy, Chunqiao Tian, Daniel Stuart Kapp, Cheng-I Liao
Journal: Journal of Clinical Oncology (2024)

e17609 Background: During the COVID-19 pandemic, many patients in the United States experienced access-to-care issues. We hypothesized this may have disrupted recent trends in incidence for diseases such as vulvar and vaginal carcinoma often identified on physical exam and biopsy. In this study, we aimed to evaluate the impact of the COVID-19 pandemic on vulvar and vaginal carcinoma incidence based on age and race. Methods: Data on cancer incidence were obtained from the United States Cancer Statistics program. We employed SEER*Stat 8.4.1.2 and Joinpoint regression program 5.0.2. We compared actual vulvar and vaginal squamous cell carcinoma incidence rates in the year 2020 to estimated rates based on trends from the years 2001-2019. Results: From 2001-2020, 69,114 cases of vulvar carcinoma and 15,419 cases of vaginal carcinoma were identified. In 2019, the incidence rate was 2.14 and 0.44 per 100,000 people for vulvar and vaginal cancer, respectively. Using data from 2001-2019, there was a 1.19% increase per year in vulvar cases per year (p&lt;0.001), while vaginal cases remained stable (average annual percent change -0.24%, p=0.179). Based on the trend noted in vulvar SCC, we expected incidence of vulvar SCC to be 2.19 per 100,000 patients in 2020, however, the reported 2020 incidence was 1.99 per 100,000. Based on these calculations, there were 9.03% fewer vulvar cases (n=246) in 2020 than expected. Assuming vaginal incidence rates remained stable, there were 9.34% fewer vaginal cases (n=70) in 2020 than expected. Based on race, non-Hispanic Asian and Pacific Islander patients experienced the largest proportional difference in actual vs expected cases of vulvar cancer, with the actual 2020 case numbers being 38% fewer (n=23) than expected based on trends. For vaginal cancer, the largest proportional difference in actual vs expected cases was among Hispanic patients, with the actual 2020 case numbers being 24% fewer than expected (n=32). Conclusions: During the 2020 COVID-19 pandemic, the incidence of vulvo-vaginal cancers was less than expected given the established trends, particularly in NHAPI and Hispanic patients. Further research is warranted to better determine if the above-described gaps were from delayed diagnosis due to access of care or other causes.
Differential gene expression analysis of a phase II randomized clinical trial of patients with endometrial cancer (EC) treated with megestrol acetate ± pterostilbene.
Authors: Thanh Hue Dellinger, Xiwei Wu, Hyejin Cho, Susan Elaine Yost, Nora H. Ruel, Marta Invernizzi, Rosemary Noel Senguttuvan, Paul Henry Frankel, Mehdi Kebria, Ernest Soyoung Han, Mihae Song, Maria De Leon, Melissa Eng, Raechelle Tinsley, Daniel Schmolze, Sue Chang, Javier Arias Stella
Journal: Journal of Clinical Oncology (2024)

e17601 Background: The oral antioxidant pterostilbene (PT) (3,5-dimethoxy-40-hydroxystilbene) has demonstrated synergistic antiproliferative effect with megestrol acetate (MA) in endometrial cancer (EC). We conducted a preoperative (window of opportunity) study enrolling endometrial cancer patients scheduled for hysterectomy, who were randomized to preoperative PT+MA vs MA alone. Methods: This prospective, randomized phase II clinical trial (NCT03671811) enrolled patients who were surgical candidates for hysterectomy. Patients were randomized 1:1 to each arm and were treated for 3 weeks with either PT+MA (arm 1) or MA alone (arm 2). Exploratory objectives included histologic response by GOG 211 criteria, and transcriptional changes using whole transcriptome analysis. For the RNA-seq analysis, differential expression analysis used the “limma” R limma package. The differentially expressed genes were selected based on the cutoff values of p-value &lt;= 0.05 and fold change &gt;= 1.5. The gene set enrichment analysis was performed using GSEA software v. 4.3.2 to identify the affected Hallmark and KEGG pathways, using the pre-ranked gene list ranked by the -log10(p-value) with a sign determined by the fold change direction. Results: This prospective, randomized phase II clinical trial (NCT03671811) enrolled patients who were surgical candidates for hysterectomy. Patients were randomized 1:1 to each arm and were treated for 3 weeks with either PT+MA (arm 1) or MA alone (arm 2). Exploratory objectives included histologic response by GOG 211 criteria, and transcriptional changes using whole transcriptome analysis. For the RNA-seq analysis, differential expression analysis used the “limma” R limma package. The differentially expressed genes were selected based on the cutoff values of p-value &lt;= 0.05 and fold change &gt;= 1.5. The gene set enrichment analysis was performed using GSEA software v. 4.3.2 to identify the affected Hallmark and KEGG pathways, using the pre-ranked gene list ranked by the -log10(p-value) with a sign determined by the fold change direction. Conclusions: In endometrial cancer, the oral antioxidant Pterostilbene increases innate immune system pathway expression, while reducing mTOR pathway expression, potentially serving as a useful adjunct to progestin hormonal therapy in EC. Clinical trial information: NCT03671811 .
Fibrin-PET Imaging Reveals Ongoing Lung Injury in Idiopathic Pulmonary Fibrosis
Authors: Julia K. Munchel, Abhinav K. Misra, Scott A. Collins, Ryan DiGregorio, Amy Palmisciano, Pedram Heidari, Richard B. Noto, Sydney B. Montesi, Peter Caravan, Barry S. Shea
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Fibrin-PET Imaging Reveals Ongoing Lung Injury in Idiopathic Pulmonary Fibrosis." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.