bluuebunny/crossref_metadata_2025_split huggingface dataset:
National trends in incidence of prostate cancer by age, ethnicity, region, and rurality from 2000-2018: An analysis of US NPCR Database.
Authors: Somasundaram Eashwar , Lang Jacob , Jambunathan Sree , Hadziahmetovic Mersiha , Ukaegbu Oke Oluchi , Petros Firas G. , Ekwenna Obi 
Published: June 2022

e17054 Background: Prostate cancer (PC) is the most common cancer and second leading cause of cancer-related death among males in the United States. Screening recommendations and treatments for PC have changed considerably over the past two decades, with differential effects across sociodemographic groups. This study aims to characterize trends in incidence of PC from 2000 to 2018 by age, race, region, and rurality to better understand these effects on incidence. Methods: Data were obtained from the National Program of Cancer Registries (NPCR), which represents patients for all 50 states. Incidence rates and average annual percent change (AAPC) were calculated using SEER*Stat software. Incident rates were calculated as the number of new cancers arising in the prostate (ICD-O-3 Site Code: C619) per 100,000 males. Trends across sociodemographic groups were analyzed and visualized in R. Results: PC incidence decreased significantly for all ages 40 and above from 2000 to 2018. Ages 85+ experienced the sharpest decline with an AAPC of -5.5% (95% CI: -6.0% to -5.1%). However, for all 5-year age brackets between 60 and 85, incidence reaches a minimum in 2014 before rising again as shown by segmented regression analysis. All race/ethnicity groups experienced a significant decline in incidence from 2000 to 2018 with sharpest decline in Hispanics -3.9% (95% CI: -4.5% to -3.3%). All regions also experienced a significant decline, with the greatest decline in the West at -4.0 (95% CI: -4.7 to -3.3). Metropolitan counties experienced a greater decline than nonmetropolitan. Patients ages 65 to 79, of Black race/ethnicity, and metropolitan groups had the highest overall incidence over the study period in their respective categories with 2018 incidences of 663, 181, and 115 per 100,000 males respectively. Conclusions: Nearly all sociodemographic groups have experienced a decline in the incidence of PC from 2000 to 2018. However, PC incidence increased from 2014 to 2018 for several sociodemographic groups. Importantly, 65 to 79 year olds, Black Americans, and metropolitan groups had the highest incidence over the study period. This study demonstrates a sustained rise in incidence of PC for several sociodemographic groups, as well as identifies groups at higher risk of PC. These trends may be due to evolving PC screening guidelines and merit further investigation.
ctDNA in treatment response monitoring in patients with relapsed gynecologic malignancies.
Authors: Williams Jason Russell , Grzankowski Kassondra , Castaneda Kayla , Saldivar Jose Salvador , Diaz-Arrastia Concepcion , Azzi Georges , Sindhu Hemant , Chae Young Kwang , Kalashnikova Ekaterina , Nicosia Brittany , Tekula Shilpa , George Giby V. , Malhotra Meenakshi , ElNaggar Adam , Aleshin Alexey 
Published: June 2022

e17501 Background: The role of immunotherapy in gynecologic malignancies continues to evolve. Use of immune checkpoint blockade (ICB) agents have consistently demonstrated less than a 15% response rate in ovarian, cervical, and subsets of endometrial cancer. Given the limited number of responders, a novel approach to treatment monitoring is needed to better sequence therapies. Circulating tumor DNA (ctDNA) surveillance in patients treated with ICB is one such approach that has been shown to predict clinical benefit. We sought to evaluate this approach in patients with recurrent gynecologic malignancies managed with ICB therapy. Methods: In this retrospective analysis of real-world data, plasma samples (n = 208) from 28 patients with recurrent/metastatic ovarian (n = 8), endometrial (n = 14), and cervical (n = 6) cancers were identified as having received ICB therapy. A personalized and tumor-informed multiplex PCR assay (Signatera™ bespoke mPCR NGS assay) was used for the detection of ctDNA in plasma samples. Serial time points were collected to monitor ctDNA levels in response to immunotherapy. Results: Response assessment results and longitudinal plasma samples were available for 19 patients. Pre-ICB plasma samples were available for 11 patients. Of these ctDNA was detected in 73% (8/11) of patients. All patients with progressive disease (10/10) had rising ctDNA levels that preceded radiological findings by a median of 2.8 months. One patient with rising ctDNA concentration presented with stable disease by imaging at the last follow-up. The remaining 8 patients demonstrated response to therapy that coincided with a declining or negative ctDNA level; 5 with partial response had a decline in ctDNA level prior to imaging (n = 3) or lack of ctDNA detection (n = 2), and 3 with complete response remained ctDNA negative, prior to imaging. Patients that exhibited a rise in ctDNA concentration (n = 11) (consecutive time points) while undergoing ICB therapy were associated with resistance to treatment (HR = 4.58 95%CI: 1.048-20.03, p = 0.04). TMB and MSI status (binary) were not predictive of response in univariate (p = 0.8, p = 0.9) analyses. Conclusions: ctDNA monitoring during the course of immunotherapy for relapsed gynecologic malignancies allows for accurate determination of therapeutic response and early prediction of disease progression. This enables timely assessment with imaging, and change in treatment plan. Our data suggest that patients with gynecologic malignancies may benefit from personalized, tumor-informed ctDNA testing to guide treatment decisions. Prospective studies are needed to establish the clinical utility of ctDNA monitoring in patients with gynecologic malignancies undergoing systemic therapies.
Impact of Silva classification system on the survival of HPV-related cervical adenocarcinoma patients with stage I ̃ IIIc1p.
Authors: Li Jiehui , Li Fenghu , Junyu Mu , Li Ran , Mei Fan , Hu Lili , Du Yanjun , Tian Xue , Wei Hong , Yang Feiyue , Wanli Mao , Yao Qin , Meng Li , Shuishui Yin 
Published: June 2022

e17505 Background: The incidence of cervical adenocarcinoma is increasing progressively in recent years and shows a younger trend that seriously threatens human health. However, the conventional pathological type of cervical adenocarcinoma is insufficient to predict the prognosis and therapeutic effect. Recently,the Silva classification system, a new pathological classification system was introduced and considered to have a better potential impact on the survival of HPV-related cervical adenocarcinoma patients. Methods: The clinical data of 102 patients with cervical adenocarcinoma from January 2010 to September 2021 were retrospectively included. All patients underwent radical resection of cervical cancer and were diagnosed as cervical adenocarci.noma by pathology.The HE staining sections of the patients were divided into SilvaA, SilvaB, and SilvaC types according to the Silva typing system. SPSS26.0 software was used for statistical analysis, Kaplan-Meier calculation was used for single-factor analysis, and COX stepwise regression model was used for multi-factor analysis. Results: Of the 102 patients with cervical adenocarcinoma who could be graded according to the Silva system, 14 (13.7%, 14/102) were SilvaA, 23 (22.5%, 23/102) SilvaB, and 65 (63.8%, 65/102) SilvaC. SilvaA type cervical adenocarcinoma patients were all stage I (IB1-IB3), no lymphatic or vascular invasion, and all patients were in a survival state by the end of follow-up. All patients with SilvaB cervical adenocarcinoma were stage I (IA2-IB3), without lymphatic or vascular invasion. Among 23 patients with Silva B, 2 patients died due to tumor, and the 5-year PFS and OS were 91.3%. Sixty-five patients with SilvaC type cervical adenocarcinoma (IB1-IIIC1P) and 15 patients died of tumor-related causes. FIGO stage, tumor size, lymph node invasion, and paralegal invasion were the influencing factors for survival and prognosis of SilvaC patients (P <0.05). Conclusions: In the Silva typing system, SilvaC type has the worst prognosis, SilvaA type and SilvaB type are both stages I, without lymph node invasion, and the prognosis is better. Patients with SilvaC type are at the Ib1-IIIC1P stage and may have a lymphatic and vascular invasion. Late FIGO stage, lymph node metastasis, and paralegal infiltration are the influencing factors for survival and prognosis of SilvaC type.
Salvage high-intensity focused ultrasound for residual or recurrent cervical cancer after definitive chemoradiotherapy.
Authors: Tang Fei , Zhong Qin , Ni Tingting , Chen Yanping , Liu Yuncong , Wu Jing , Feng Zhiyu , Lu Xiaokai , Tan Shisheng , Zhang Yu 
Published: June 2022

e17524 Background: Approximately 30%-65% of patients have residual disease or subsequent recurrence after completion of chemoradiotherapy (CRT) treatment. The treatment of residual/recurrent cervical cancer in previously irradiated field is challenging and generally associated with a poor prognosis. Local treatments such as salvage surgery and re-irradiation are usually traumatic and have limited efficacy. High intensity focused ultrasound (HIFU) treatment can directly ablate solid tumors without damaging neighboring healthy tissue. However, the HIFU studies for these patients are limited. Over 10 years of experience gained with the management of HIFU in cervical cancer patients with residual disease or recurrence after CRT is reported here. Methods: 153 patients with residual or recurrent cervical cancer in previously irradiated field who received HIFU treatment between 2010 and 2021 were retrospectively analyzed. Adverse effects, survival benefit, and factors affecting prognosis were given particular attention. Results: A total of 36 patients (23.5%) achieved a partial response following HIFU treatment and 107 patients (69.9%) had stable disease. The objective response and disease control rates were 23.5% and 93.5%, respectively. The median progression-free survival (mPFS) and median overall survival (mOS) were 17.0 months and 24.5 months, respectively. Moreover, patients with lesions ≥ 1.40 cm before HIFU treatment and a shrinkage rate ≥ 30% after treatment had a higher mPFS and mOS, and patients with lesions ≤ 1.00 cm after HIFU treatment had a higher mPFS (P < 0.05). All of the treatment-related adverse events were limited to minor complications, which included skin burns, abdominal pain and vaginal discharge. Conclusions: Many cervical cancer patients have few efficacious treatment options following chemoradiotherapy. This study demonstrates that HIFU treatment is likely a preferred option that can safely improve the local control rate and extend survival.
Endocervical adenocarcinoma biomarkers for immunotherapy: Descriptive analysis.
Authors: Cerda Victoria , Karamzadeh Nooshin , Scott Marla , Kinne Nolan , Mayer Christopher , Taylor Kristin , Li Andrew John , Kim Kenneth H. , Medeiros Fabiola , Balzer Bonnie , Rimel Bj 
Published: June 2022

e17526 Background: Adenocarcinoma and adenosquamous carcinoma of the cervix are subtypes of HPV related cervical cancer. As virally mediated tumors, they have become an obvious choice for immunotherapy treatment approach. Currently, there is little information about the presence of immunological tumor markers among patients with endocervical adenocarcinomas. We hypothesized cervical adenocarcinomas highly express immunotherapy markers. Here we characterize the protein status of immunotherapy markers in a large single institution dataset. Methods: An IRB approved retrospective review of cervical adenocarcinoma and adenosquamous carcinoma was performed. We gathered original slides for each patient and performed immunohistochemistry (IHC) for tumor markers CD8, PDL1, TIM3 and LAG3. Demographic and pathologic data was captured. Patients were categorized by positivity percentage for each marker. Descriptive statistics and univariate analysis were used. Results: A total of 97 patients met criteria for the study and slides were available for staining in 68 patients. Demographic data showed a median age of 42 years old with majority of patients identifying as White at 66%, followed by Hispanic (13%), Asian (10%), other (7%) and Black (1%). Of the entire cohort, 75% were adenocarcinoma, 25% were adenosquamous carcinoma. Among those with recorded status, 82% were HPV positive, 14% had metastasis, and 13% had recurrence. On univariate analysis, adenocarcinoma was significantly more common in patients who were LAG3 < 1% or PDL < 1% (p = 0.002, p = 0.007). Patients who were LAG3 < 1% or PDL < 1% were also less likely to have Grade 1 tumors (p = 0.006, 0.03). When analyzing by respective immune marker percentage group there were no statistically significant differences in LVSI, depth of invasion, stage, or recurrence rate. By IHC, 68% were PDL1 > 1% positive, 63% were LAG3 > 1% positive, 100% were TIM3 > 1% positive, 100% were CD8 > 1% positive. Seven of the 68 patients had a recurrence. Of those patients with recurrence, one was treated with immunotherapy. Conclusions: A large proportion of cervical adenocarcinomas displayed immunotherapy targets by IHC suggesting that combined immunotherapy agents may be useful in this population. Further study is needed to assess whether IHC is predictive of outcome or response.[Table: see text]
Comparison of survival outcomes between dostarlimab and comparator treatments (tx) in patients (pts) with advanced/recurrent (A/R) endometrial cancer (EC) in England: Matching-adjusted indirect comparisons (MAICs).
Authors: Goulden Scott , Heffernan Kiera , Sen Nikitas Fulya , Shukla Urmi , Knott Craig , Hunger Matthias , Pahwa Ankit , Schade Rene 
Published: June 2022

e17534 Background: Limited tx options exist for pts with A/R EC who progress on/after platinum-based chemotherapy (PBCT). This study compared survival outcomes of pts with A/R mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) EC receiving dostarlimab in Cohort A1 of the single-arm, Phase I GARNET trial, with an equivalent real-world (RW) cohort receiving current tx in England. The primary objective compared second-line (2L) overall survival (OS) between cohorts; a secondary objective was time to tx discontinuation (TTD; proxy for progression-free survival). Methods: An overall-2L-tx RW cohort was established using National Cancer Registration and Analysis Service data. Five tx-specific RW cohorts were identified (tx received at 2L in > 5% of pts) (Table). Clinical outcomes between GARNET and RW cohorts were compared using MAICs. Relevant prognostic variables were used to create 3 matching scenarios (SC): SC1: grade, histology, PBCT number; SC2: histology, PBCT number; SC3: race/ethnicity, stage at diagnosis, histology, prior surgery (MMR/MSI status not considered). OS was time from first dostarlimab dose (GARNET) or 2L RW tx (RW cohorts) to any-cause death; MAIC-adjusted hazard ratios (HR, 95% confidence interval [CI]) were estimated by weighted Cox proportional-hazards models. TTD after MAIC was summarized descriptively. Results: Effective sample size (ESS) assessed matching capacity; lower ESS in SC1 reduced its robustness (Table). Following matching, distributions of baseline characteristics were similar between cohorts. Across most matching scenarios, there was a lower risk of death in pts treated with dostarlimab compared to the overall RW cohort and for tx-specific RW cohorts (Table). Median TTD (months, 95% CI) was longer for pts treated with dostarlimab across all matching scenarios (SC1: 7.8 [4.1, not estimable (NE)]; SC2: 9.7 [5.5, NE]; SC3: 14.0 [6.4, 17.9]) than the overall RW cohort (3.4 [3.2, 3.4]). Conclusions: Results suggest that pts in GARNET with dMMR/MSI-H A/R EC receiving dostarlimab had better OS and longer TTD compared with pts receiving current 2L tx in England. Funding: GSK (217216; scott.r.goulden@gsk.com).[Table: see text]
Detection of early-stage ovarian cancer using a liquid biopsy test based on extracellular vesicle proteins.
Authors: Hinestrosa Juan Pablo , Lewis Jean , Schroeder Gregor , Balcer Heath , Billings Paul R. 
Published: June 2022

e17558 Background: We have recently conducted a study to evaluate the predictive value of proteins associated with extracellular vesicles (EVs) isolated using an alternating current electrokinetic (ACE) system, for the detection of early stage (I & II) ovarian cancer cases. Ovarian cancer patients, typically, have few symptoms in stages I & II; the disease is often undetected until it is advanced. Currently, only 15% of cases are detected at early stages when clinical treatment outcomes are improved. Methods: We tested the feasibility of detecting the presence of early stage (I-II) ovarian cancer using protein biomarkers carried by EVs in patient blood. Using an ACE microelectrode array, EVs were purified from ovarian cancer patient plasma (N = 70; Stage I = 51, Stage II = 19) and female non-cancer donors (N = 290) and tested for the presence of cancer biomarker proteins with multiple bead-based multiplex immunoassay kits. An adaptive boosted trees machine learning algorithm with 100x cross-validation was developed to identify the most important features for differentiation between cases and controls. Results: The machine learning algorithm identified relevant biomarkers for the detection of ovarian cancer with a receiver-operator characteristic area under the curve (AUC) of 0.952 (95% CI: 0.918 – 0.985). Overall sensitivity was 72.9% at 99% specificity, rising to 84.3% at 95% specificity. When further stratified, Stage I sensitivity was 70.6% and stage II sensitivity was 78.9% at the 99% specificity level, as expected. We also separated the cases into endometroid carcinoma (N = 24) and serous carcinoma (N = 36). At the 99% specificity level, the sensitivity was 87.5% and 63.9%, respectively. Conclusions: These results suggest that it is possible to detect early-stage ovarian cancer by analyzing the EV-bound proteins isolated with the ACE technology. EVs may carry the earliest signals of cancer development and a blood-based EV-protein biomarker test can yield high sensitivity and specificity. Stable biomarker detection with small input volumes may be possible. These results require further investigation in larger datasets to validate the current observations with the potential application for general, routine screening, as well as for populations at elevated disease risk.
Impact of paclitaxel versus docetaxel on neuropathy in ovarian cancer patients with diabetes.
Authors: Kincaid Kaitlyn , Boitano Teresa KL , Leath Charles A. , Straughn J Michael 
Published: June 2022

e17616 Background: Peripheral neuropathy is a common side effect of taxanes, particularly in diabetic patients, which can significantly affect quality of life. The objective of this study was to determine whether there was a difference in the incidence of new or worsening neuropathy between diabetic patients with ovarian cancer who received paclitaxel versus docetaxel as part of their primary therapy. Methods: This retrospective cohort study included ovarian cancer patients with Type I or Type II diabetes at a large academic institution who underwent surgery from 6/2016 to 5/2020 and received neoadjuvant and/or adjuvant chemotherapy. Individual chart review was performed to assess patient characteristics including race, body mass index (BMI), performance status (PS), Charlson Comorbidity Index (CCI), baseline hemoglobin A1c, current diabetic medications. The primary outcome was incidence of new or worsening neuropathy during primary therapy including adjuvant or neoadjuvant chemotherapy. New neuropathy was defined as no neuropathy prior to chemotherapy. Worsening neuropathy was defined as baseline neuropathy that worsened after initiation of chemotherapy. Secondary outcomes included chemotherapy treatment delay, increase of diabetic medications during therapy, and a change of chemotherapy regimen from paclitaxel to docetaxel. Statistical analysis was performed using SPSS v. 26. Results: 32 patients met inclusion criteria. Patient demographics including race, PS, BMI and CCI were similar between patients who received paclitaxel and those who received docetaxel. 24 patients (75%) received paclitaxel and 8 (25%) received docetaxel. The majority (93.8%) of patients had Type II diabetes. Patients who received paclitaxel were more likely to develop new or worsening neuropathy (81% v. 50%; p = 0.028) but less likely to require an increase of diabetic medications (0% v. 50%; p = 0.003) compared with patients receiving docetaxel. During primary therapy, 17% of patients were transitioned from paclitaxel to docetaxel due to treatment-related complications (i.e. neuropathy (50%), allergic reaction (50%)). There was no difference in incidence of treatment delays between the two treatment groups (25% v. 25%; p = 1.0). Conclusions: Patients with ovarian cancer who received paclitaxel were more likely to experience new or worsening neuropathy compared to patients who received docetaxel. There was no difference in treatment delays between the groups, but nearly one-fifth of patients receiving paclitaxel had to be transitioned to docetaxel because of treatment-related complications. Because of fewer side-effects, docetaxel is a reasonable chemotherapy alternative in ovarian cancer patients with diabetes.