tbuckley/cabot-search huggingface dataset:
Clinicopathological features and genomic profiles of prostate cancer with elevated carbohydrate antigen 19-9.
Authors: Yilin Li, Yang Liu, Ping Yang, Ruiqi Liu, Jianming Gao, Xin An, Yonghong Li, Fangjian Zhou, Liru He
Journal: Journal of Clinical Oncology (2024)

e17003 Background: The elevated carbohydrate antigen 19-9 (CA199) is commonly observed in digestive system tumors, but rarely in prostate cancer (PCa). Due to the rarity and the poor understanding of the special subtype of PCa, the clinicopathological and genomic characteristics and survival outcomes in PCa patients with elevated CA199 in our center were analyzed. Methods: Cases were collected retrospectively from 2012 to 2023 in Sun Yat-sen University Cancer Center. The tumor genomic profiles were analyzed by R (http://www.rproject.org). Kaplan-Meier survival analyses were performed to compare survival outcomes. All statistical analyses were performed using SPSS version 26.0 and GraphPad Prism version 8.0. All analyses were two‐tailed, and the significance level was set at P&lt;0.05. Results: A total of 137 PCa patients with elevated CA199 (&gt;35ng/ml) were identified, with an exclusion of 47 patients with secondary cancers and 40 patients with other diseases that may cause elevated CA199, finally 50 cases (22 with primary and 28 with secondary elevated CA199) were included. The median initial PSA and the median time from diagnosis to CRPC were 102ng/ml and 14 months. Most patients were with a high GS score (GS≥8: 82%) and an advanced stage (M1: 84%). Poorly differentiated adenocarcinoma (22%) was frequently observed. Compared with patients with primary elevated CA199, patients with secondary elevated CA199 had higher levels of CA199 (102ng/ml vs. 78ng/ml, p=0.0456), lower levels of PSA at diagnosis (65ng/ml vs. 132ng/ml, p=0.0131) and higher proportion of poorly differentiated adenocarcinoma (36% vs. 5%, p=0.0138). The level of CA199 in patients with primary elevated CA199 was correlated with the level of CEA (R 2 =0.2658, p=0.0168), but not with the level of NSE or PSA. At a median follow-up of 31 months, the median OS of the whole group, primary elevated CA199 and secondary elevated CA199 subgroups was 49 months, 31 months and not reached. Secondary elevated CA199 (p=0.0009), abiraterone treatment (p&lt;0.0001) and chemotherapy treatment (p=0.0331) were significant prognostic factors of OS. To study the genomic characteristics of PCa patients with elevated CA199, 29 PCa patients with normal CA199 were included as a control (genomic data available in 13 and 29 cases respectively). Patients with elevated CA199 were more likely to have mutations in castration resistant associated genes (AR, FOXA1, ASXL1, KMT2B, JAK2 and AKT1), malignant progression associated genes (RARA, BLM, PIK3R1) and CA199 metabolism associated gene (ERBB2). Conclusions: PCa with elevated CA199 is highly malignant and with poor prognosis. Intensive treatment with abiraterone and chemotherapy could benefit such patients. Poor pathological differentiation and the gene mutation profile may partly explain the clinical outcome.
Molecular characterization of growing teratoma syndrome in patients with testicular germ cell tumor.
Authors: Michal Mego, Samuel Horak, Dominik Hadzega, Katarina Kalavska, Georgina Kolnikova, Peter Lesko, Zuzana Orszaghova, Jana Obertova, Patrik Palacka, Katarina Rejlekova, Zuzana Sycova-Mila, Ramadan Aziri, Daniel Pindak, Michal Chovanec, Lucia Kucerova, Zuzana Cierna
Journal: Journal of Clinical Oncology (2024)

e17017 Background: Teratomas are unique neoplastic growths that encompass a diverse array of tissue types derived from multiple germ layers, often exhibiting varying degrees of differentiation. Among the phenomena associated with teratomas, the growing teratoma syndrome (GTS) stands out as a rare yet clinically significant occurrence. GTS, characterized by the persistence or regrowth of teratomatous elements despite initial treatment, poses challenges for both diagnosis and management. In this abstract, we present the results of our expression array analysis of teratomas, aiming to uncover novel insights into their molecular composition, heterogeneity, and potential implications for clinical management. Methods: This study included 53 patients with retroperitoneal teratoma (7 chemotherapy naïve and 46 with postchemotherapy teratoma) and 20 patients with viable postchemotherapy germ cell tumor from retroperitoneum that had surgery at National Cancer Institute in Slovakia and for whom formalin-fixed paraffin-embedded (FFPE) tumor tissue was available. Study also includes samples from 5 patients with normal testis as control group. Ten patients (18.9%) in this cohort had growing teratoma syndrome. Analysis was performed by HTG EdgeSeq Oncology Biomarker panel (HTG Molecular Diagnostics, Inc., Tucson, USA). Identified candidate genes associated with GTS were further validated by immunohistochemistry on FFPE. Results: Molecular profiling indicates no differences in expression profile in retroperitoneal teratomas regardless of previous chemotherapy. Expression analysis indicates 1586 genes being differently expressed with high significance ( p &lt; 0.05) in teratomas compared to normal testis and 1571 genes differentially expressed compared postchemotherapy viable tumors. We identified 14 genes being differently expressed in growing teratoma syndrome compared to teratoma without growth (CYP4A22, IGFBP1, CXCL6, LTF, CYP2C8, CFTR, CCL20, PFKFB3, SLC2A3, LIPA, HMOX1, GPNMB, CCL18, DLK1. Pathway analysis revealed MAPK and PI3K−Akt signaling pathways are mostly dysregulated in GTS. Conclusions: This molecular profiling identify genes differentially expressed in teratomas that are potential biomarkers for prediction of teratoma element in postchemotherapy residues in testicular germ cell tumor patients. Moreover, inhibition of identified signaling pathways associated with GTS could represent potentially novel therapeutic targets in case of unresectable disease.
HERD: A multi-centre prospective cohort study to facilitate early detection of relapse in radically treated, high risk head and neck squamous cell carcinoma.
Authors: Martin Forster, Sanjena Mithra, Tony Ng, Nitzan Rosenfeld, Elinor Sawyer, Miguel Reis Ferreira, Ralph Sinkus, Karin Shmueli, Ton Coolen, Amit Roshan, Rami Mustapha, Kenrick Ng, Camila Gomes, Imran Petkar, Teresa Guerrero Urbano, Steve Connor, Asit Arora, Alastair Fry, Michelle Berin, Chris Brew-Graves
Journal: Journal of Clinical Oncology (2024)

TPS6128 Background: Head and Neck Squamous Cell Carcinoma (HNSCC) is the 7 th most common cancer worldwide with more than 660,000 cases diagnosed annually. Many patients present with locally advanced disease, which despite aggressive multi-modality treatment remains associated with poor survival. Approximately 50% of patients relapse within 2 years, mostly occurring in the first year after treatment. Biomarkers predicting relapse are lacking and there remains no consensus on surveillance, with strategies differing according to local guidelines and recurrence too often detected when not amenable to salvage surgery (estimated to improve survival outcomes in relapsed HNSCC by up to 73%). We hypothesize that risk of relapse relies on a dynamic interplay between the immune profile, tumor microenvironment (TME; elucidated by radiology and tissue-based laboratory imaging), genomic background and clinicopathological characteristics. Our primary objectives are to develop and validate a multi-analyte based risk prediction tool and risk-stratified follow up strategy to enhance detection of early relapse and improve survival. Methods: This multi-center study is prospectively collectingsamples across multiple platforms including imaging, blood, saliva, stool, urine, and tissue from patients with newly diagnosed high risk locally advanced HPV-negative HNSCC planned for radical treatment (either surgery or (chemo)radiotherapy). We aim to recruit 200 patients in 2 stages, including discovery and validation cohorts. Three mechanistic (hypothesis-driven) meta-covariates and five working platform meta-covariates will be analysed to test recurrence prediction. Each meta-covariate represents an integrated risk score from covariate subsets. The 3 hypotheses are H1) combining magnetic resonance parameters of hypoxia and stromal composition with TME changes; H2) capturing the interactions between genomic mutations, immune cells and exosomes within the TME H3) understanding the relationship between micro-organisms and TME. The technical platforms include exosomal analyses, multi-parametric MRI including novel elastography (MRE) and quantitative magnetic susceptibility mapping (QSM) techniques, comprehensive circulating tumour and cell-free DNA analyses to aid detection of minimally residual disease, tissue immune profiling, somatic mutation testing and microbiome analysis. Regression Analysis will be performed by machine-learning with advanced mathematical and Bayesian statistical modelling. Accrual began in October 2023. Clinical trial information: NCT05097625 .
Randomized pilot study assessing the safety and tolerability hyperthermic intraperitoneal chemotherapy (HIPEC) at completion of interval cytoreductive surgery or chemotherapy the day prior to interval cytoreductive surgery for patients with stage III/IV ovarian cancer undergoing neoadjuvant chemotherapy.
Authors: Floor Jenniskens Backes, Corinne Calo, Laura Chambers
Journal: Journal of Clinical Oncology (2024)

TPS5638 Background: A recent randomized phase III trial demonstrated an improvement in recurrence free and overall survival when heated intraperitoneal chemotherapy (HIPEC) was given at the time of interval cytoreductive surgery (iCRS) for advanced ovarian cancer. While there is rationale for HIPEC’s mechanism of effect, it remains unclear whether the observed benefit is because the chemotherapy schedule is not interrupted perioperatively (typically at least 6-8 weeks). We hypothesize that administration of the same agent and similar dose the day before surgery, will not increase toxicity and may improve feasibility for closing the gap between treatment cycles, while also limiting length of surgery and time under anesthesia. The primary objective of this study is to assess the feasibility, safety, and tolerability of IV Cisplatin the day prior to iCRS compared to HIPEC to determine if this is an acceptable alternative. Methods: This is a single institution randomized Pilot Study (NCT05415709). Patients with newly diagnosed stage III or IV epithelial (serous, mucinous, or endometrioid) ovarian, fallopian tube, or peritoneal cancer are eligible if they achieve a partial or complete response to 3-4 cycles of neoadjuvant carboplatin/paclitaxel +/- bevacizumab and are deemed to have disease amenable to a complete or optimal iCRS. Patients are scheduled for iCRS within 3-4 weeks following the third or fourth cycle and randomized 1:1 to IV Cisplatin (75 mg/m2) given the day prior to iCRS or HIPEC with Cisplatin (100 mg/m2) given intraoperatively over 90 min at 40°Celsius at the completion of surgical debulking. 15 patient per arm are planned (N=30); currently 7 patients have completed study interventions. No formal power calculation was required for this feasibility and safety study. Frequency and severity of adverse events (AEs) and tolerability of the regimens will be collected and summarized by descriptive statistics for each group. Patients who are able to receive planned treatment will be summarized as percentage for each treatment group. Accrual is anticipated to complete in June 2025. As an exploratory secondary endpoint, we plan to explore changes to the gut microbiome before and after HIPEC and examine correlative patterns with response and toxicity. Clinical trial information: NCT05415709 .
Real-world clinical outcomes and economic burden of early discontinuation of taxane therapy among patients with metastatic castration-resistant prostate cancer.
Authors: Jeetvan Patel, Jennifer Nguyen, Vamsi Bollu, Barinder Kang, Amrita Sawhney, Clare Byrne, Jackson Tang, Magdaliz Gorritz, Chi-Chang Chen, Neal D. Shore
Journal: Journal of Clinical Oncology (2024)

e17043 Background: Despite comprising an important part of the treatment paradigm for metastatic castration-resistant prostate cancer (mCRPC) for over a decade, real-world use of taxanes is hindered by adverse events (AEs). AEs may lead to early treatment discontinuation, which may adversely affect outcomes. The two goals of this study were to determine the proportion of mCRPC patients who discontinue taxanes early (defining the early discontinuation threshold relative to efficacy results associated with androgen receptor pathway inhibitors [ARPIs]) and to evaluate the impact of early discontinuation on clinical outcomes, AEs, and healthcare costs. Methods: This was a retrospective, observational study of adult men with mCRPC treated with an ARPI as their first-line (1L) therapy and who initiated second-line (2L) therapy with another ARPI or a taxane. The Flatiron Health electronic health record database (07/01/2012–06/30/2020) was used to estimate Kaplan-Meier overall survival (OS) curves for the taxane cohort by the number of cycles received; these were compared with patients who received ARPI at 2L. Cox regression modeling and median PFS and OS values were used to identify the number of taxane cycles needed to achieve comparable OS to ARPI. The number of taxane cycles with similar OS outcomes to ARPI was then considered the threshold for early discontinuation. In addition, the IQVIA PharMetrics Plus claims database (01/01/2013–08/31/2021) was used to estimate taxane-related AEs (based on product information) and associated healthcare costs among patients who did and did not discontinue taxanes early. Results: From Flatiron, 473 2L ARPI patients and 214 2L taxane patients were included. Similar clinical characteristics – e.g., prostate-specific antigen level, ECOG performance status, and Gleason score – were observed between the two cohorts. Overall, 2L ARPI was associated with longer median OS (15.4 vs. 13.6 months) than 2L taxane. The number of taxane cycles needed to reach comparable OS to ARPI was determined to be 8. Patients receiving &gt;8 cycles (n=48; 22%) compared to those receiving ≤8 cycles (n=166; 78%) had longer median OS (18.4 vs. 11.9 months, respectively) and PFS (9.0 vs. 4.3 months, respectively). From PharMetrics, 158 2L taxane patients were included. Patients receiving &gt;8 cycles (n=20; 13%) were more likely to experience an AE (95% vs. 88%) than those receiving ≤8 cycles (n=138; 87%) but had lower mean AE-related total healthcare costs per patient per month ($3,429 vs. $6,334). Conclusions: These results suggest that mCRPC patients need to receive &gt;8 cycles of taxane at 2L to receive more clinical benefit than 2L ARPI. However, the vast majority of patients in the study discontinued taxane early, resulting in shorter survival outcomes compared to ARPI.
Metastatic testicular cancer (TC) presentations and outcomes: A contemporary analysis based on the National Cancer Database (NCDB).
Authors: Eun-mi Yu, Hongkun Wang, Min Woo Hwang, Jeanny B. Aragon-Ching
Journal: Journal of Clinical Oncology (2024)

e17016 Background: While most cases of testicular cancers are cured, patients with metastatic or refractory disease continue to have a poor prognosis in recent years (Shah et al; Urology 2023). We sought to determine sites of metastases and survival based on the National Cancer Database (NCDB). Methods: We extracted patient-level data from the NCDB during 2004 to 2020, and identified incidence, demographics, regional differences, treatment, metastatic sites and outcomes in men who had testicular cancer diagnoses (non-seminoma, NS; seminoma, S) with differences in metastatic presentation and outcomes. Results: There were 89550 pts in all, 51623 S pts and 37927 NS pts. Median age for S pts was 37 years and NS was 29 years. 81571 pts were White, 2860 pts were Black. 5396 S pts identified as Hispanic (H) and 5609 NS pts H with other races/unknown for the rest. More S patients were treated at comprehensive community cancer programs (17%) compared to NS pts (6.1%). The majority of patients had a Charlson-Deyo Score of 0 (92.7% of S pts and 93.7% of NS pts), had private insurance (74.1% S pts, 69.1% NS pts). Most were diagnosed with Stage I (29.6%) and Stage II and III (16.3%) though it was unknown/missing for 54%. Overall survival (OS) was better for S compared to NS in all pts (p&lt;0.0001), and in stages II &amp; III (p&lt;0.001). OS was similar for S compared to NS for brain metastasis presentation (p=0.6776), lung (p=0.8967), liver (p=0.1688), but better for S compared to NS for bone metastases (p=0.0002) and distant lymph nodes (p=0.0.0392). Conclusions: Our analysis reveals some differences in survival trends with better survival in seminoma compared to non-seminoma in bone and distant lymph node metastases though not for brain, lung and liver metastases, highlighting the need for better therapies for the poorest prognostic groups of TC patients.
Real world data of leuprorelin castration efficacy in patients with prostate cancer: A comprehensive assessment of 1,744 tests.
Authors: Dr. Paulo Sergio Lages, Guilherme Augusto Zulli, Paulo Gustavo Bergerot, Michelle Barbosa, Flavio Mavignier Carcano, Luciana Lages, Anita Chavez Azevedo, Daniel Vargas Pivato de Almeida
Journal: Journal of Clinical Oncology (2024)

e17000 Background: Androgen deprivation therapy (ADT) has been standing the cornerstone of systemic prostate cancer (PCa) treatment, since Huggins’ findings.Gonadotropin-releasing hormone (GnRH) agonists or antagonists has been used broadly as ADT. However, the majority of studies has focused on Gosserelin, leading to a lack of dedicated investigations into the efficacy of leuprorelin, despite its large use on practice. In this real-world study, we thoroughly analyzed data of testosterone tests in order to comprehensively assess the leuprorelin castration efficacy on the PCa management. Methods: We gathered data from patients diagnosed with PCa who were undergoing treatment with leuprorelin alone or in combination with a novel hormonal agent (NHA) in a single cancer center. The tests spanned a nine-year period from 2014 to 2023 and we assessed the testosterone levels in baseline and after leuprorelin administration, as well as their distribution according to clinicopathologic variables. Results: A total of 1,754 test reports were retrieved from 240 individual pts. The median baseline testosterone level was 317 ng/mL (range: 37-1,136) prior to leuprorelin initiation and the distribution across Gleason grades was: 20 pts had grade 1, 30 pts had grade 2, 61 pts had grade 3, 51 pts had grade 4, and 40 pts had grade 5. Testosterone levels &lt; 50 ng/mL were achieved in 1,730 tests (98.7%) and testosterone levels &lt; 20 ng/mL were found in 1,485 tests (84.7%). A total of 80 pts received combined treatment with leuprorelin + NHA, of which the majority received abiraterone/prednisone (n=52; 65%) or apalutamide (n=11; 13.8%). Following ADT discontinuation, 91 pts presented testosterone levels ≥ 50 ng/mL after a median interval of 258.5 days (range:82-710). Conclusions: In this comprehensive real world database analysis, leuprorelin is able to achieve suitable testosterone suppression levels in nearly the whole study population, such as are seen in others GnRH agonists pivotal trials. Deeper and maintained testosterone suppression levels is predictive of longer time to castration-resistant PCa and real life use of leuprorelin seems to meet this need.
The demographics of Sertoli cell carcinoma: A National Cancer Database analysis.
Authors: Yanick Tade, Peter T. Silberstein, Craig Heise, Beau Hsia
Journal: Journal of Clinical Oncology (2024)

e17012 Background: Sertoli cell tumors (SCTs) are an extremely rare and lethal diagnosis responsible for roughly 1% of all testicular and ovarian carcinomas. No uniform treatment regimen with sufficient results has been established. Current combination of retroperitoneal lymph node dissection, chemotherapy, and radiation therapy provides the best known outcome. Analyzing trends in diagnosis may provide valuable information about its epidemiology. The National Cancer Database (NCDB) was analyzed to establish the demographic factors in diagnosed patients. Methods: A retrospective cohort study from 2004 to 2020 was conducted using the NCDB. 159 patients were found with a histologically confirmed diagnosis of SCTs (ICD-8640-3). Race, gender, Hispanic origin, type of treatment facility, insurance coverage, and distance from patient residence to treatment facility were analyzed via descriptive statistics, and trends in incidence were interpreted using regression analysis. Results: The number of patients diagnosed with SCTs has remained relatively consistent since 2004 (R^2 = 0.07), with approximately 9 diagnoses per year. Of the 159 patients found, the average age of diagnosis was 44.6 years (SD = 19.1, range = 2 – 89 years). A majority of patients were male (67%), while the remaining third were female (33%). Most of the patients were White (73%). Patient Hispanic status could not be reliably determined due to limited data. More patients were in the top income quartile (31%) than the second (24%), third (18%), or fourth (14%) quartiles, with 13% having unknown income status. Most patients were privately insured (59%), followed by coverage under Medicare/Medicaid (28%). More patients lived in metropolitan counties with a population of 250,000 or more (76%) compared to less-populated urban or rural regions (24%). The majority received treatment at comprehensive community cancer programs or academic/research programs (43%). Patients traveled an average of 30.2 miles (SD = 64.0, range = 0.5 – 474.9) to reach the treatment facility. Conclusions: SCTs remains a rare diagnosis. This study pursues a significant gap in existing knowledge on patient characteristics that may present with SCTs. Most patients were White, privately insured, in the top income quartile, and lived in metropolitan areas. This novel study may contribute data towards understanding the relationship between patient socioeconomic status and access to diagnosis. Further research is required to uncover the role of socioeconomic status in SCTs.