tbuckley/cabot-search huggingface dataset:
Transcriptomic and metabolomic correlates of increased colonic permeability in post-infection irritable bowel syndrome
Authors: Ana Y Caceres Lessa, Adam Edwinson, Hiroki Sato, Lu Yang, Antonio Berumen, Margaret Breen-Lyles, Anjali Byale, Michael Ryks, Ashley Keehn, Michael Camilleri, Gianrico Farrugia, Jun Chen, Marijke Decuir, Kirk Smith, Surendra Dasari, Madhusudan Grover
Journal: Clinical Gastroenterology and Hepatology (2024)
Measuring COVID-19's impact on diagnosis of cervical cancer by race/ethnicity, age, and region of the United States.
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)

e17535 Background: The COVID-19 pandemic brought to light significant access-to-care issues for patients across the country, which we hypothesized may have disrupted recent trends in incidence for certain screenable diseases. The goal of this study was to evaluate the impact of the COVID-19 pandemic on cervical cancer incidence based on age, race, stage at presentation, and regions of the US. Methods: Data on cervical cancer incidence were obtained from the United States Cancer Statistics (USCS) program from 2001-2020. We employed SEER*Stat 8.4.1.2 and Joinpoint regression program 5.0.2 to calculate estimated and actual incidence rates per 100,000 women. We compared actual cervical cancer incidence rates in the year 2020 to estimated rates based on trends from the years 2001-2019. Results: From 2001-2020, 245,618 cases of cervical cancer were identified. In 2019, prior to the pandemic, the incidence was 7.64 per 100,000 women. From 2001-2019, cervical cancer incidence decreased by 0.96% per year (p=0.023). Based on this trend, we expected the incidence to be 7.57 per 100,000 women in 2020, but the reported incidence was only 6.83 per 100,000, therefore, there were 9.8% less cervical cancer cases (1,189 cases) in 2020 than expected. This was most noticeable at the lower and upper ends of the age distribution, with 17.6% less cases than expected in the year 2020among 25-29 year-olds and 18.4% less cases than expected among 85+ year-olds. This is in comparison to the median age group for cervical cancer (50-54 year-olds) in whom there were 14.5% (193) less cases than expected in 2020. Based on stage of disease, for local, regional, and distant disease there were 16.3%, 2.8%, and 1.9%, less cases than expected in 2020, respectively. Within racial and ethnic groups, we found that Non-Hispanic Black (NHB) and Hispanic patients had 15.0% and 13.9% less cases than expected, versus 8.7% among Non-Hispanic White (NHW) and 5.8% among Non-Hispanic Asian and Pacific Islander (NHAPI) patients. Comparing U.S. regions, the Midwest, Northeast, West, and South had 14.6%, 10.2%, 10.2%, and 9.0% less cases than expected for 2020, respectively. Conclusions: Our data suggest that the reported cervical cancer cases were significantly less than predicted based on past trends during the COVID-19 pandemic.. Older age, NHB and Hispanic patients, and those residing in Midwest states had the greatest number of possible missed diagnoses of cervical cancer during this time. Mitigating strategies are needed to reinstate screening programs, particularly in these at-risk groups to prevent increased rates of advanced stage disease and mortality.
Patterns of pembrolizumab use for recurrent cervical cancer.
Authors: Yongmei Huang, Katherine Yoh, Elizabeth A. Szamreta, Xiao Xu, Dawn L. Hershman, Jason Dennis Wright
Journal: Journal of Clinical Oncology (2024)

e17528 Background: Pembrolizumab was approved for treatment of recurrent or metastatic cervical cancer (CC) as a single agent after chemotherapy in 2018 and in combination with chemotherapy in 2021, but little is known about how it has been actually used in clinical care. We examined real-world use of pembrolizumab for recurrent CC. Methods: The Merative MarketScan Research Databases were used to identify newly diagnosed CC patients who underwent primary hysterectomy or radiation between 2017-2022. Utilization of systemic therapy was assessed at the time of primary/adjuvant therapy and at first recurrence. Primary/adjuvant chemotherapy was defined as the use of chemotherapy within 4 months of the first cancer claim. First-line (1L) systemic therapy for recurrence was defined as the introduction of a new agent after a gap of &gt; 3 months for patients who received adjuvant/primary chemotherapy or after 4 months from primary hysterectomy or radiation. Treatment for recurrence was classified as platinum alone, platinum-based combination therapy and non-platinum therapy. The use of targeted therapy (bevacizumab) and immunotherapy (pembrolizumab, nivolumab) was noted. Patterns and duration of use of each agent are described. Results: A total of 2727 patients were identified, including 1259 (46.2%) who underwent primary hysterectomy and 1468 (53.8%) treated with primary radiotherapy. Chemotherapy for recurrent CC was initiated in 339 patients (12.4%). Treatment for recurrence was noted in 9.7% of those treated initially with hysterectomy and in 14.8% of those with primary radiotherapy. Among patients treated for recurrence, 24.8% received platinum alone, 52.5% received a platinum-based combination, and 22.7% received non-platinum regimens. A total of 41 patients (12.1%) received pembrolizumab after recurrence, including 7.1% who received pembrolizumab alone, 2.1% who received pembrolizumab in combination with platinum, and 2.9% who received pembrolizumab with non-platinum therapy. Pembrolizumab was used after recurrence in 15.7% of patients who received chemotherapy during primary therapy compared to 7.1% of those who did not receive primary chemotherapy. Use of pembrolizumab was 11.4% in 2018, 17.6% in 2019, 14.0% in 2020, 8.8% in 2021, and 11.8% in 2022. The median duration of 1L chemotherapy for recurrence was 2.3 months (IQR, 1.0-5.8) overall, and 4.3 months (IQR, 2.4, 9.8) for patients treated with pembrolizumab. Patients who had not received primary/adjuvant chemotherapy had a longer duration of treatment with pembrolizumab than those who had received upfront chemotherapy, median 7.5 (IQR 3.9-9.8) versus 4.0 (IQR 2.2-11.0) months, respectively. Conclusions: Platinum-based chemotherapy remains the predominant therapy for recurrent CC. Pembrolizumab use is increasing for patients with recurrent cervical cancer. Longer follow-up is necessary to further evaluate its post-approval usage.
The efficacy of cumulative cisplatin dose on survival in patients with locally advanced cervical cancer treated with definitive chemoradiotherapy: A multicenter study by the Turkish Oncology Group (TOG).
Authors: Arif Akyildiz, Melis Gultekin, Ecem Yigit, Ecem Demir, Rashad Ismayilov, Melin Aydan Ahmed, Mustafa Buyukkor, Hasan Çağrı Yıldırım, Nilgun Yildirim, Efnan Algin, Seval Orman, Rumeysa Çolak, Esra Özen Engin, Havva Beyaz, Kamuran Ibis, Şefika Arzu Ergen, Sezin Yuce Sari, Yilmaz Tezcan, Ferah Yildiz, Zafer Arik
Journal: Journal of Clinical Oncology (2024)

e17534 Background: This multicentric study aimed to investigate the impact of cumulative cisplatin dose on clinical outcomes in locally advanced cervical cancer patients undergoing definitive chemoradiotherapy (CRT). Methods: A retrospective analysis was conducted on 654 patients with stage IB3-IVA disease treated with definitive CRT. Radiotherapy (RT) was applied as external beam pelvic with or without para-aortic RT and brachytherapy. Concomitant chemotherapy was in the form of weekly or 3-weekly cisplatin. Data on demographics, treatment protocols, cumulative cisplatin dose, adverse effects, and survival outcomes were collected. Statistical analyses, including univariate and multivariate Cox regression models, were employed to assess factors influencing progression-free survival (PFS) and overall survival (OS). Results: The median cumulative cisplatin dose was 210 mg (range, 40-320 mg), and it was ≥200 mg in 503 (76.9%) patients. Median follow-up was 35 months. The 5-year PFS and OS rates were 66.9% and 77.1%, respectively. Multivariate analysis (MVA) identified poor performance status, non-squamous cell histology, presence of lymph node metastasis and hemoglobin &lt;10 g/dl before CRT were poor prognostic factors for both PFS and OS in the whole group. When stage III cases were evaluated separately, the cumulative cisplatin dose below 200 mg was also found to be a significant poor prognostic factor in OS (HR 1.79, 95% CI, 1.1 to 3.0, p=0.031). Conclusions: The study revealed that a cumulative cisplatin dose exceeding 200 mg, particularly in patients with lymph node metastasis, significantly improved OS. Factors such as anemia, toxicity-related challenges, and comorbidities were identified as critical considerations in treatment planning. These findings emphasize the delicate balance between maximizing therapeutic efficacy and managing toxicity, guiding personalized treatment approaches for locally advanced cervical cancer. [Table: see text]
Predictive value of C reactive protein (CRP) and D-dimer in patients with advanced cervical cancer treated with sintilimab and anlotinib.
Authors: Jing Liu, Lele Chang, Li Li, Lele Zang, Fei Zhu, Huiqi Zhang, Mingxuan Zhu, Qin Xu
Journal: Journal of Clinical Oncology (2024)

e17525 Background: The Sintilimab plus Anlotinib in patients with advanced cervical cancer trial was a single-arm, phase II study that showed promising activity of the programmed death-1 (PD-1) inhibitor sintilimab plus the vascular endothelial growth factor receptor inhibitor Anlotinib in patients with advanced cervical cancer. We aimed to identify prognostic values of inflammation biomarkers and coagulation biomarkers in advanced cervical cancer treated with Sintilimab and Anlotinib. Methods: We conducted a post-hoc analysis of the data from the ALTER-C201 study (Clinical trial information: ChiCTR1900023015). The predictive value of coagulation variables and inflammation variables was evaluated by receiver operating characteristic (ROC) curves. Through Cox hazards regression models, prognostic factors were determined for overall survival (OS). Survival curves were visualized by Kaplan–Meier method and compared through Log-rank analysis. Results: We involved 41 patients and followed up for 38.0 (range, 0.6–44.0) months. According to the ROC curve, the predictive values of baseline CRP and D-dimer are better than other indicators, with area under the curve (AUC) values of 0.748 and 0.848, respectively. The cut-off values for D-dimer and CRP are 1.75ug/ml and 10.9mg/L, respectively. Through regression analysis, we demonstrated that CRP (HR 2.591; 95%CI 1.099–6.106; P = 0.030) and D-dimer (HR 2.669; 95%CI 1.154–6.173; P = 0.022) were independent prognostic factors. Compared to patients with CRP ≥ 10.9mg/L, those with CRP &lt; 10.9mg/L have a longer OS (28.93 months, 95% CI, 15.23 to not reached v 10.57 months, 95% CI, 6.14 to not reached; log-rank test, P = 0.007). Compared to patients with D-dimer ≥ 1.75ug/ml, those with D-dimer &lt; 1.75ug/ml have a longer OS (28.93 months, 95% CI, 17.09 to not reached v 10.73 months, 95% CI, 4.63 to not reached; log-rank test, P = 0.005). Conclusions: CRP and D-dimer predict survival in advanced cervical cancer patients undergoing combined ICI/ VEGF-TKI therapy. We advocate further work to validate utilisation of CRP and D-dimer as prognostic biomarkers for advanced cervical cancer in clinical practice.
Survival in patients with cervical cancer undergoing chemo-radiotherapy in a middle-income country.
Authors: Mario Argüello, Fausto Emiliano Pulla, Walter Morquecho, José Luís Reyes, Felipe Campoverde, Ruth Engracia, Patricia Rocío Tamayo, Guillermo Paulson, Mayra Santacruz
Journal: Journal of Clinical Oncology (2024)

e17527 Background: Cervical cancer (CC), being a high-incidence pathology in Ecuador, requires a priority multidisciplinary therapeutic approach to obtain an optimal benefit in overall survival. The objective of the present study is to describe overall survival (OS) in patients with locally advanced CC treated with chemoradiation according to histological type and clinical stage. Methods: It is an observational, analytical, retrospective, longitudinal study of patients with stage IIB-IVA CHD who received treatment with chemoradiation from January 2010 to December 2014 with a 10-year follow-up. The SPSSv29 statistical system was used. Survival analysis was performed using the Kaplan-Meier method and the Log-Rank test. Results: Of 1909 patients, 1581 were excluded because they did not meet eligibility criteria. 328 received chemoradiation. The overall survival result was 43%. According to histological type, 276 patients presented squamous cell carcinoma (SCC) and 52 adenocarcinoma (AC), presenting a survival of 44% for SCC and 35% for AC. The calculation by clinical stage, II-B shows a survival of 46%. For stage IV-A 20% up to 46 months. The Log-Rank test (p=0.04) shows a significant statistical value. Conclusions: The 10-year overall survival was 43%, showing an essential difference for the histological type, being higher for squamous cell carcinoma, and also showing a significant difference between the stages. [Table: see text]
Single-cell sequencing to elucidate the disparities in the immune microenvironment between PIK3CA mutants and wild types.
Authors: Qin Xu, Fei Zhu, Jing Liu, Lele Chang, Li Li, Mingxuan Zhu, Huiqi Zhang, Lan Luo, Lele Zang
Journal: Journal of Clinical Oncology (2024)

e17524 Background: In patients with cervical cancer, PIK3CA exhibits the highest mutation rate, with the predominant oncogenic alteration reported to occur in 40% of cases. Recent studies in cervical cancer have indicated that the mutation status of PIK3CA is prominently associated with a diminished overall survival. Nevertheless, in our preceding study entitled 'Efficacy and Safety of Sintilimab Plus Anlotinib for PD-L1–Positive Recurrent or Metastatic Cervical Cancer: A Multicenter, Single-Arm, Prospective Phase II Trial', the prognosis for the mutant group surpassed that of the non-mutant group. Therefore, distinguishing the differences in the immune microenvironment between PIK3CA mutant and wild-type cervical cancer patients is of great significance. Methods: We used Single-cell RNA sequencing (scRNA-seq) to analyze the tissue samples of 7 cervical cancer patients with PIK3CA mutations and 9 with wild-type. Results: We partitioned cells from both the mutated and wild-type forms of cervical cancer into nine distinct clusters. To better understand the transcriptional heterogeneity of tumor-infiltrating T lymphocytes, we re-clustered 45,574 NK/T cells into 9 clusters. A specific cell cluster, designated as CD8+ ISG15, exhibited a significant enrichment in interferon-induced genes, including ISG15, IFIT3, IFIT1, RSAD2, and IFI6. To explore intergroup differences, we performed differential analysis on the proportions of mutations and non-mutations in different subgroups. We found significant differences in CD8+ ISG15 between the mutant group and the widegroup. ISG15 plays a pivotal role in antiviral responses, and as research advances, it has been identified as a potential prognostic biomarker and therapeutic target for cancer, beyond its antiviral function. A growing body of studies indicates that ISG15 is overexpressed in the majority of tumors, however, the influence of high ISG15 expression on the overall survival of cancer patients is dependent on the cancer type. In our single-cell analysis of cervical cancer, we observed that the CD8+ ISG15 subgroup specifically expresses ISG15, and the prevalence of this subgroup is significantly greater in the PIK3CA wild-type group compared to the mutant group. Consequently, the CD8+ ISG15 subgroup is perceived as a significant subset within the cervical cancer immune microenvironment for regulating anti-tumor responses. Conclusions: We defined the CD8+ ISG15 cell cluster present in the cervical cancer immune microenvironment using scRNA-seq, and found that its proportion is significantly lower in the PIK3CA mutant group than in the wild-type group. Combined with existing research, this suggests that this subgroup plays an important role in immune regulation within the cervical cancer immune microenvironment.
Evaluation of malignant potential based on infection with high-risk human papillomaviruses 16, 52, and 58 in the uterine cervix.
Authors: Seung-Mi Lee, Hyun-Jung Lee, Juhun Lee
Journal: Journal of Clinical Oncology (2024)

e17511 Background: The high-risk human papilloma virus (HR-HPV) has been known as the most important carcinogen in uterine cervical carcinoma. Generally, gynecologists recommend medical interventions for patients diagnosed with HSIL or higher. Previous studies have evaluated genotype-specific risk for carcinogenesis. However, the genotype-specific risk remains still unclear due to some limitations of those studies. This study aimed to evaluate the malignant potential of the three most prevalent HR-HPVs in Korea. Methods: Patients who underwent uterine cervical conization were included. They had received HPV test within a year before the surgery and those exhibiting concurrent multiple infections with HR-HPVs were excluded. Of single infections with HR-HPV, the three most prevalent HR-HPVs were included to analyze. To evaluate their malignant potential, CIS+, including carcinoma in situ (CIS) and invasive carcinoma, was categorized in each HR-HPV group. The ratios of pathologic diagnoses and odds ratios for malignant potential were evaluated between the three most prevalent HR-HPVs. Results: Totally 230 patients were found to have a single infection with HR-HPV16, HR-HPV52, or HR-HPV58. Of the included patients, 119 (51.7%), 60 (26.1%), and 51 (22.8%) were noted to be infected with HR-HPV genotypes 16, 52, and 58, respectively. CIS was diagnosed in 59 (49.6%), 27 (45.0%), and 25 (49.0%) patients in the HPV16, HPV52, and HPV58 single infection groups, respectively ( p = 0.839). Invasive carcinoma, regardless of histology such as squamous cell carcinoma or adenocarcinoma, was diagnosed in 8 (6.7%), 1 (1.7%), and 1 (2.0%) patient in the HPV16, HPV52, and HPV58 single infection groups, respectively ( p = 0.187). The CIS+ ratio was not significantly different among the HPV16, HPV52, and HPV58 single infection groups (67 [56.3%] vs. 28 [46.7%] vs. 26 [60.0%], [ p = 0.460]). Conclusions: Among the Korean women with single HR-HPV infection, HPV16, HPV52, and HPV58 were the three most common genotypes, in descending order. Although HPV16 was the most prevalent among the three, its malignant potential was not significantly different from those of HPV52 and HPV58 in the uterine cervix. This result supports the need for a nine-valent vaccine against HR-HPVs, covering HPV52, HPV58, and HPV16.
Transcriptomic and epigenetic characterization of mucinous adenocarcinoma of the cervix.
Authors: Susan Duyar-Ayerdi, Yasmeen Abdo, Roshan Kumar, Erin Bishop, Denise S. Uyar, Janet S. Rader, Akinyemi I. Ojesina
Journal: Journal of Clinical Oncology (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.