bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating tumor DNA for recurrence monitoring following resection for pancreas adenocarcinoma.
Authors: Amini Neda , Koti Shruti , ASCHERMAN BENJAMIN , King Daniel 
Published: July 2024

e16365 Background: Detecting early recurrence among patients with resected pancreatic cancer may facilitate earlier treatment and better outcomes for patients with resected pancreatic ductal adenocarcinoma (PDAC). Circulating tumor DNA (ctDNA) has shown promise as a tumor-specific biomarker for PDAC but has not yet entered routine clinical use. This study aims to conduct analytical and clinical validation of Signatera ctDNA profiling to predict recurrence in patients with PDAC. Methods: A retrospective IRB-approved protocol evaluating the use of Signatera ctDNA testing among patients who underwent resection at Northwell Health during 2019-2023. The utility of ctDNA status to predict PDAC recurrence during follow-up was assessed using cox regression. Results: There were 91 ctDNA tests among 24 patients. With a median follow-up of 15 months, recurrence was observed in 38% (9/24) of patients and 8 patients died. Among patients with recurrence, most of them had positive ctDNA before showing signs of recurrence on the imaging (6/9, 66.7%) with mean lead time of 116 days, while 2 of them had positive ctDNA after recurrence and one patient never had positive ctDNA. At the time of recurrence, eight patients had elevated CA19-9, while two patients with normal CA19-9 had positive ctDNA. The median recurrence-free survival (RFS) was 23 months (95% CI, 11-not reached). Patients with detectable preoperative ctDNA had significantly decreased median RFS (14 months; 7 of 10 (70%) recurred) when compared with patients negative for ctDNA [not reached; 2/14 (14.3%) recurred; P= 0.005). In multivariable Cox model after adjusting for potential risk factors, detection of ctDNA was associated with RFS. (table). Conclusions: Signatera ctDNA profiling identified relapse earlier than imaging for most patients. These results suggest the potential for a prospective trial evaluating early treatment interventions in this deadly disease to improve survival rates. [Table: see text]
Association of human interpretable features derived from pancreatic ductal adenocarcinoma pathology slides with disease-free survival.
Authors: Siddiqui Zafar , Haemmerle Robert , Carr Ryan Michael 
Published: July 2024

e16368 Background: Pancreatic ductal adenocarcinoma (PDAC) is predicted to be the second cause of cancer death in the US by 2040. For the minority of patients who are candidates for curative-intent surgical resection, a neoadjuvant approach with chemotherapy or chemotherapy followed by chemoradiotherapy (chemoRT) has become the standard of care. The tumor microenvironment (TME) has been recognized as a key factor in therapeutic resistance and disease progression. This study aims to explore the prognostic value of human-interpretable machine learning image features (HIFs) derived from whole-slide H&E images. Methods: Consecutive PDAC patients who underwent neoadjuvant therapy followed by surgical resection were studied in this single-institution retrospective study. Clinical variables collected include tumor site (head/body/tail), surgery extent, histology, sex, age at diagnosis, grade, treatment response (4-point scale), LVI, PNI, resection margin status, pathological TNM staging, number of lymph nodes removed/positive, neoadjuvant strategy (chemotherapy vs chemoRT), and number of neoadjuvant chemo cycles. These factors were analyzed with a multivariable Cox proportional hazards model for disease-free survival (DFS) after surgery. Additionally, 420 human-interpretable image features (HIFs) derived from a commercial machine learning software were analyzed with a univariable Cox model on a binary outcome of 1-yr DFS, applying a Bonferroni correction for multiple comparisons to identify significant predictors. Results: Increased neoadjuvant chemotherapy cycles (HR = 0.62, p = 0.001, [median: 8, IQR: 6-12]) and receipt of combination neoadjuvant therapy (HR = 0.15, p = 0.020, [29% chemo, 71% +chemoRT]) exhibited a protective effect in the multivariable DFS model. 3 HIFs quantifying immune cells and macrophages within the cancerous tissue and its stroma were associated with an improved probability of 1-year DFS. Conclusions: In addition to clinical factors, HIFs may offer valuable insights into the tumor microenvironment's influence on PDAC progression, paving the way for improved prognostic models and therapeutic strategies. Future work will integrate clinical predictors with HIFs in a combined model.
Longitudinal circulating tumor DNA monitoring for detection of molecular residual disease in patients with advanced germ cell tumors.
Authors: Au Cherry , Patel Mukti , Tan Alan 
Published: July 2024

e17022 Background: Germ cell malignancies, commonly manifesting as testicular cancer, is one of the most common malignancies in men 15 to 45 years of age, with the incidence doubling over the past 40 years. When identified promptly and treated with a multidisciplinary approach, germ cell tumors have an excellent prognosis with cure rate >90% and 5-year survival rate >95%. Treatment involves radical orchiectomy for diagnostic and therapeutic purposes. Further management includes active surveillance, adjuvant chemotherapy, retroperitoneal lymph node dissection (RLND), and radiation therapy. While AFP, B-HCG, and LDH are good biomarkers, they are not sensitive or specific for detecting molecular residual disease (MRD). B-HCG is detected in <30% of individuals with seminoma and B-HCG and AFP are detected in 50–60% of patients with non-seminomatous tumors. We describe the use of circulating tumor DNA (ctDNA) for detection of MRD in advanced germ cell malignancy, especially when baseline biomarkers are negative. Methods: This is a retrospective analysis of 20 patients with testicular cancer treated at Rush University Medical Center who monitored closely for MRD. Signatera (Natera Inc.), a personalized tumor-informed ctDNA assay, was utilized for detection and quantification of ctDNA in patients’ plasma samples, measured at MRD (1-12 weeks post-orchiectomy) and regular intervals thereafter, regardless of treatment modality. Event free survival (EFS) was determined, defined as the period from radical orchiectomy to date of radiographic progression of disease. Results: There was a total of 20 patients (35% seminoma, 65% non-seminoma) with 2 of the patients having extragonadal disease. The mean age was 32.2 years old with IQR (28-36). Post operatively, 20% underwent RLND, 10% were on surveillance, 53% received post-orchiectomy chemotherapy, 6.7% of patients underwent autologous stem cell transplant. The median follow up time is 1.14 years. Two patients had positive ctDNA despite negative baseline traditional biomarkers. There were 23.3% (7/30) of patients that had evidence of radiographic progression. Of the patients with progression, serial ctDNA monitoring had high rates of concordance (85%, 6/7) of ctDNA positivity with biomarker positivity and radiographic progression. Conclusions: Overall, ctDNA correlated with, and sometimes even preceded, traditional biomarkers and radiographic findings of disease progression. The ctDNA positivity of 2 patients in this cohort despite negative baseline AFP, B-HCG, and LDH, highlights the sensitivity and specificity of ctDNA for MRD compared to more traditional biomarkers. Serial monitoring of ctDNA offers valuable insights into germ cell tumor disease status, including presence of MRD, and there is a need for prospective studies to guide treatment escalation and de-escalation in germ cell tumors.
Xerostomia and ocular dryness as predictors of PSA response to Lu177-PSMA-617 in metastatic castration resistant prostate cancer.
Authors: Hassoun Rebecca , Tann Mark , Sims Justin , Auxier Ashleigh , Althouse Sandra K. , Salous Tareq , King Jennifer , Adra Nabil 
Published: July 2024

e17028 Background: Prostate specific membrane antigen (PSMA) is highly expressed in salivary and lacrimal glands. Dry eyes and/or mouth can occur with Lu177-PSMA-617 (PSMA Lu177) therapy in metastatic castration resistant prostate cancer (mCRPC) pts. We evaluated the difference between the presence of dry mouth/eyes with PSA responses in pts with mCRPC treated with PSMA Lu177. Methods: The Indiana University Prostate Cancer database was queried for pts with mCRPC who were treated with PSMA Lu177. Toxicities were documented throughout the course of treatment. Association of xerostomia and ocular dryness with PSA30 and PSA50 response was compared using the Chi Square test, or Fisher’s Exact test, if more appropriate. Results: Between 6/21/22-11/14/23, 107 pts with mCRPC were treated with PSMA Lu177 with at least 2 doses. Median age was 73 (56, 90). 86 pts had metastatic disease in bone, 65 lymph nodes, 11 lungs, 6 liver, and 2 brain. 39 pts had 1 prior ARPI, 68 pts had ≥2 prior ARPI. 17 pts had no prior taxane regimen, 45 had 1 prior taxane, 33 had 2 prior taxanes and 12 had ≥3 taxane regimens. 19 pts had prior PARP inhibitor. Median follow-up from start of PSMA Lu177 treatment was 8.3 months (1.4-18.7). 40 (37%) pts experienced dry mouth, 7 (7%) pts experienced dry eyes, and 6 (6%) pts experienced both. 65 (61%) pts achieved PSA30 response. 57 (53%) pts achieved PSA 50 response. Conclusions: The presence of dry eyes and/or dry mouth in pts with mCRPC treated with PSMA Lu177 was associated with improved PSA response. [Table: see text]
Real-world treatment landscape in advanced metastatic castration resistant prostate cancer.
Authors: Sacchi Elizabeth , Singhal Hari , Zamalloa Jose , Lopez Sanchez Beatriz , Zhang Ke , Parihar Harish , Greshock Joel , Max Steven I 
Published: July 2024

e17032 Background: Despite a rapidly evolving treatment landscape in advanced prostate cancer (aPC) marked by recent emergence of therapies such as radioconjugates and PARP inhibitors, outcomes remain poor for many patients. Future care improvements will require innovative treatments and simplifying treatment planning. The goal of this study is to understand how the evolving treatment landscape has impacted care and outcomes in patients with aPC using real world (rw) data. This study evaluates outcomes of mCRPC patients who have advanced to a 3rd line of therapy (L3) with prior exposure to both an androgen receptor signaling inhibitor (ARSI) therapy and a taxane or platinum-based chemotherapy, in any aPC disease setting. Methods: mCRPC patients in the Flatiron Database who progressed to L3 with pre-L3 exposure to both an ARSI (abiraterone, enzalutamide, apalutamide, and darolutamide) and chemotherapy (cabazitaxel and docetaxel) were eligible for inclusion. Patients whose mCRPC diagnosis occurred between Dec 2010 and Nov 2023 were included. As the objective was to study the aPC treatment landscape, patients with prior exposure to therapies approved in the mCRPC disease setting such as radioconjugates, PARP inhibitors, radiation, investigational and palliative drugs were excluded. Outcomes were reported as median real-world overall survival (rwOS) indexed to start of L3 treatment, and median rw time to next treatment (rwTTNT) from the start of L3 to the beginning of L4 treatment. Results: 660 patients met all inclusion criteria and had at least one year of treatment history in the aPC disease setting. Median follow up time (indexed to L3 start) for all patients was 7.55 months. Median rwOS for all patients was 10.8 months (95% CI 9.9 - 12.2), while median rwTTNT was 5 months (95% CI 4.6 - 5.4). The most common L3 therapy class was chemotherapy, followed by ARSIs (Table). To aid in treatment planning strategies, drug sequence patterns were also analyzed. Frontline ARSIs were followed by second line chemotherapy for most of the patients (n = 349; 53%). Conclusions: Relatively short survival times and short durations on L3 therapies for aPC demonstrate a high unmet need, with therapeutic options dominated by ARSIs and chemotherapy. Recently approved radioconjugate therapies, like Pluvicto â, have reported median OS 15.3 months (Fallah, 2023) in prostate-specific membrane antigen (PSMA)-positive patients, which is greater than the 10.8 months observed in general mCRPC population analyzed in this study. These findings underscore the need to develop effective therapies and treatment strategies that are tailored for advanced prostate cancer. [Table: see text]
Outcome of prostate cancer with CNS metastasis: An analysis of SEER database (2010-2020).
Authors: Lee Hyun , Mei Lin , Baralo Bohdan , Poklepovic Andrew Stewart , Paul Asit K. 
Published: July 2024

e17037 Background: Brain metastasis from prostate cancer is rare, with an estimated incidence of <1%, and its characteristics and outcomes are poorly understood. We report a contemporary analysis of outcomes in patients with CNS metastasis from prostate cancer in association with clinicopathological variables by utilizing the Survival, Epidemiology, and End Result (SEER) database with data from 2010 to 2020. Methods: From the SEER database, we identified histologically confirmed primary prostate cancers with any distant metastasis. Data for survival as well as multiple clinicopathological variables including age, race, prostate-specific antigen (PSA) level, Gleason score, prior radiotherapy, histology, and specific metastatic sites were extracted. Statistical analysis included chi-square. ANOVA, and Kaplan-Meier analysis for overall survival (OS) and disease-specific survival. Results: SEER database (2010-2020) identified 27,501 patients with metastatic prostate cancer, of which 27,118 (98.6%) were adenocarcinoma and 383 (1.4%) were prostate cancer with neuroendocrine features. Brain metastasis was seen in 282 (1.04%) and 15 (5.32%) patients in these histologic groups, respectively. Brain metastases were associated with worse prognosis with median OS of 14 months compared to bone-dominant and non-regional lymph node only diseases that showed median OS of 31 months and not reached, respectively (P < 0.01). Within the population with brain metastases, outcome comparison based on age (<65 vs. ≥65 years), ethnicity (Caucasian vs. African American vs. Hispanic), PSA (<98 vs. ≥98 ng/ml), and Gleason score (<9 vs. ≥9) showed no statistically significant difference (table). Presence of metastasis to other solid organs showed numerically worse outcome without statistical significance (OS: 26 months vs. 13 months, p=0.09). Significant OS difference was observed between the adenocarcinoma and neuroendocrine tumor within the brain metastasis subgroup (OS: 14 months vs. 6 months, p=0.03). Conclusions: CNS metastasis with prostate cancer carries worse prognosis in comparison to metastases to bone or distant lymph-nodes. Neuroendocrine tumor has higher risk of CNS metastasis although most of such cases are from adenocarcinoma due to its higher prevalence. OS analysis confirms worse outcome with neuroendocrine features compared to adenocarcinoma in CNS metastatic settings. [Table: see text]
Clinical–epidemiological characterization of cervical cancer in a middle-income country.
Authors: Morquecho Walter , Argüello Mario , Reyes José Luís , Pulla Fausto Emiliano , Ávila Víctor Hugo , Estrada Lorena Paola , Paulson Guillermo , Santacruz Mayra 
Published: July 2024

e17514 Background: Despite significant advances in prevention and treatment, cervical cancer remains a global public health threat, claiming the lives of hundreds of thousands of women each year. It disproportionately affects women in low- and middle-income countries, where access to vaccination, screening, and early diagnosis is often limited. The present study aims to determine this pathology's clinical and epidemiological characteristics. Methods: This is an observational, descriptive, retrospective, and cross-sectional study. Information from the digital medical records of patients with cervical cancer from SOLCA Guayaquil from January 2010 to December 2014 was used. Results: 1909 medical records of patients with cervical cancer were reviewed during the study period; 211 were excluded for not meeting eligibility criteria, leaving 1698 to be evaluated. Regarding stages (I-II-III-IV), the most frequent was stage II (A-B), 54.2% of them, squamous cell carcinoma (44.6%), and adenocarcinoma (9.6%). 32.2% correspond to resectable cancers (IA-IIA), and 67.8% to non-resectable cancers. The mean age was 55 years, the median was 54, and the mode was 45. The absence of these comorbidities was the most frequent (47.8%), then kidney (6%) and ureteral (4.7%). Conclusions: The age of presentation of cervical cancer in this health center is higher than the global average but closer to what is seen in Latin America. The clinical stages are relatively advanced at diagnosis. The most frequent histopathological types were squamous cell carcinoma and adenocarcinoma. What predominated was the absence of comorbidities. [Table: see text]
Survival in cervical cancer IIb-IVA subjected to postchemo-radiotherapy surgery in Ecuador.
Authors: Reyes José Luís , Morquecho Walter , Argüello Mario , Pulla Fausto Emiliano , Santacruz Mayra , Veliz Elizabeth Graciela , Alarcon Carlos Jose , Plaza Jenniffer Stefania , Rivadeneira Nery Abdon 
Published: July 2024

e17517 Background: Cervical cancer (CC) is one of the leading causes of cancer death in the world. The objective of the present study is to determine the overall survival (OS), survival by age group, and histological type in patients with locally advanced CC undergoing salvage surgery after chemo-radiotherapy (CTx-RTx). Methods: A retrospective observational analytical study was carried out on patients with locally advanced CC with stages IIB-IVA who received CTx-RTx treatment from January 2010 to December 2014 with follow-up until August 2023 in SOLCA-Guayaquil. The SPSSv29 statistical program was used to analyze survival curves with the Kaplan-Meier estimator and Log-Rank test. Results: Of a total of 1909 patients, 1581 were excluded because they did not meet eligibility criteria. 328 received CTx-RTx, and 23 underwent rescue surgery. The average survival result is 107 months (m). In survival by histological type, 11 patients presented squamous cell carcinoma (SCC) and 12 adenocarcinoma (AC), with the mean survival for SCC 111 months and for AC 94 months, however in the Log-Rank statistical test (p: 0.672) was not significant, which is why it is estimated that survival is similar in the two histological types (graph 2). In the calculation of survival by age in m (every ten years), in the first group of 30-39 years, it is 98.1 m, 40-49 years 118.8 m, 50-59 years 98.6 m, 60 or more years, it is 56 m; however, in the Log-Rank statistical test (p = 0.317), it is not significant by age group. Conclusions: Of the 23 patients with a mean age of 48 years and a follow-up of 168 months, 13 (56%) are alive. Regarding survival by histological type and age group, there was no significant difference in survival with these results. [Table: see text]
Transcriptomic and epigenetic characterization of mucinous adenocarcinoma of the cervix.
Authors: Duyar-Ayerdi Susan , Abdo Yasmeen , Kumar Roshan , Bishop Erin , Uyar Denise S. , Rader Janet S. , Ojesina Akinyemi I. 
Published: July 2024

e17518 Background: Mucinous adenocarcinoma of the cervix (MAC) is a rare and aggressive histologic subtype of cervical cancer with poorer prognosis than its more common counterparts, usual type endocervical adenocarcinoma (UEA) and squamous cell carcinoma (SCC). MAC is also known to be less responsive to standard chemotherapy and radiation approaches used to treat cervical cancer. In this study, we sought to identify transcriptomic and epigenetic features of MAC that distinguish MAC from UEA and SCC, and to identify features that may contribute to poorer prognosis in MAC compared to UEA and SCC. Methods: Clinical data, gene expression, miRNA expression, and methylation data for 17 MAC, 27 UEA, and 247 SCC from The Cancer Genome Atlas Cervical Cancer Project were obtained and analyzed. Clinical data were compared for the histologic groups using Fisher’s Exact, ANOVA, and Kruskal-Wallis statistics where appropriate. Kaplan-Meier curves were used for survival analyses. Gene expression data was analyzed using DESeq2 for differential expression of mRNA. Pathway enrichment analysis of gene expression data was completed using Qiagen IPA Core Analysis software. Comparative marker selection was used to determine differential expression of miRNA, and differential methylation across histologic subtypes. Analyses were completed both by histology and by disease-progression status. Data across all three platforms were integrated to evaluate for potential explanatory relationships of interest. Results: RNAseq analysis revealed a number of genes differentially expressed in MAC as compared to UEA and SCC. Several of these genes were also found to be differentially expressed in samples from patients with disease progression compared to those without known disease progression including increased expression of PPARGC1A, SLC2A1, and ZNF703 and decreased expression of NR4A3. Analysis also revealed hypomethylation at CpG probe sites mapping to SLC2A1 and decreased expression of miRNAs known to target SLC2A1 and PPARGC1A in MAC tumors . Pathways involving translation regulation, EIF2 signaling, and oxidative phosphorylation were downregulated in MAC whereas pathways involving mitochondrial dysfunction, glucose metabolism, and estrogen receptor signaling were upregulated in MAC. Downregulation of immune and inflammatory response pathways and upregulation of tumor-supporting macrophage activation was seen in MAC tumors with disease progression. Conclusions: We identified novel transcriptomic and epigenetic features and altered pathways in MAC, as well as those features and pathways associated with poorer prognosis in this population. These findings may contribute to further confirmatory research and lead to novel therapeutic strategies for this rare cancer.