bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating the association (assoc) between mental health illness (MHI) and development of prostate cancer (PC) in a nationwide matched cohort of >5,000,000 US Veterans.
Authors: Klaassen Zachary , Janes Jessica , Parrish Joshua , Sayyid Rashid K. , McIntire Sydney , De Hoedt Amanda Marie , Satkunasivam Raj , Williams Stephen B. , Wallis Christopher J.D. , Terris Martha K. , Freedland Stephen J. 
Published: June 2023

e17113 Background: Previous reports suggest that men with MHI who subsequently develop PC have worse outcomes. However, it has not been established whether a history of MHI is associated with a PC diagnosis (dx) or more aggressive PC. The objective of this study was to (i) investigate the assoc between MHI and development of PC, and (ii) in a subset of men with available Gleason Score (GS) data, assess the assoc between MHI and aggressive PC as measured by GS ≥7 PC at dx. Methods: This was a retrospective matched-cohort analysis to assess the assoc between MHI and time to PC dx in the Veterans Affairs (VA) Health Care System. Men with an ICD code for MHI dx between 2000-2020 were matched 1:1 to men with no MHI dx in the same time frame. The MHI dx date of the exposed (exp) male was assigned as the index date of the unexp male. Variables matched on included race, age at MHI exp (+/- 3 years), census region, and median household income. Uni- and multivariable competing risks models were used to test the assoc between MHI and time to PC using death from other causes as competing risk. In a subset of men with GS data available, logistic regression was used to test the assoc between MHI and GS ≥7 at PC dx. All multivariable models were adjusted for age, race, census region, income, Charlson Comorbidity Index, year of MHI index, and year of VA entry. Results: There were 2,597,810 MHI-exp men matched 1:1 to unexp men. During a median (Q1, Q3) follow up of 128 (65, 192) months, 390,977 PC diagnoses were observed (172,442 MHI-exp vs. 218,535 unexp). MHI-exp men were significantly less likely to be diagnosed with PC than unexp men in both uni- (HR: 0.798, 95% CI: 0.793-0.803) and multivariable (HR: 0.763, 95% CI: 0.758-0.768) analysis. Cumulative incidence estimates at 3, 5, 10, and 20 years were 2.1%, 3.1%, 5.2%, and 8.5%, respectively, for MHI-exp men vs 2.9%, 4.2%, 6.9%, and 11.7%, respectively, for unexp men. Among men with PC and available GS data (n = 51,404), 32,645 had GS ≥7 PC, of which 20,749 were MHI-exp vs 11,896 unexp. MHI-exp men had significantly higher odds of GS ≥7 PC in both uni- (OR: 2.38, 95% CI: 2.32-2.43) and multivariable (OR: 1.97, 95% CI: 1.92-2.02) analysis. Conclusions: Men with MHI are 20% less likely to be diagnosed with PC, however when diagnosed, are nearly 2 times more likely to have aggressive PC compared to non-MHI men. Although speculative based on the nature of the study, this may be due to poorer access to preventative health services resulting in delayed diagnoses.
Evaluating genetic screening/counseling for patients diagnosed with prostate cancer who meet hereditary risk assessment based on NCCN Guidelines.
Authors: Ruiz Vega Ruben , Abidoye Oluseyi , Adewunmi Comfort , Ghosh Aditya Kumar , Caton Andria P. , Johnson Andrew Thomas 
Published: June 2023

e17117 Background: Prostate cancer is most common cancer among men and is the second leading cause of cancer deaths in American men. Genetic predisposition to cancer is increasingly noted as a cause in many cancers including prostate cancer. Genetic testing and counseling are recommended in certain groups of men; Men with or without a personal history of prostate cancer who have a family history of prostate, breast, colon, ovarian, or pancreatic cancers, especially if any of these were diagnosed under age 50 and those with metastatic prostate cancer. A recent study of 3,600 men with prostate cancer found that 17% had inherited genetic mutations that may have contributed to their cancer. Of those men, 31% of the mutations were in the BRCA genes. Because of this, familiarity and understanding of the most current clinical guidelines for genetic risk assessment are of great importance in the survivorship care of men with prostate cancer. The National Comprehensive Cancer Network (NCCN) guidelines recommends genetic assessment/counseling for genetic/familial high-risk individuals diagnosed with prostate cancer. This retrospective study reports on adherence to genetic screening based on NCCN guidelines for newly diagnosed Prostate cancer patients who were receiving treatment at Northeast Georgia Medical Center (NGMC). Methods: We obtained data using EPIC database from NGMC electronic medical records to identify patients who were diagnosed between 1/1/20-12/31/20. Data included patients who were high risk and fit the criteria for genetic testing based on NCCN as well as identifying patients who were sent for genetic testing/counsellng. The dataset was de-identified and analyzed using appropriate descriptive statistical testing. Results: A total of 42 cases for prostate cancer were reviewed. All 42 of the cases were under the age of 60 at diagnosis. A total of 13 of the cases meet the genetic/familial high-risk assessment based on NCCN guidelines. Of the 13 of the cases, only 1 case was referred for genetic counseling which was 7.6% compliance with NCCN guidelines for genetic counseling/referral. In terms of high-penetrance prostate cancer risk screening, none of the 13 cases (0%) meeting genetic/familial high-risk were screened. Based on our findings, there was poor adherence in genetic testing/counseling in high risk patients with prostate cancer at NGMC. Conclusions: This study points out poor adherence to NCCN guideline directed genetic counseling/testing in high risk patients with prostate cancer. Based on findings, it is clear that high importance should be placed on awareness on the current guidelines in relation to gene testing for patients who are high risk as this would play an important role in identifying family members who at risk and ensure early screening.
Bone health practices in metastatic prostate cancer (mPCA).
Authors: Eule Corbin Jeffrey , Hu Junxiao , Gilbert Danielle , Eskandar Joy , Lam Elaine T. 
Published: June 2023

e17119 Background: Patients (pts) with mPCA and bone metastases (BM) are at risk for skeletal-related events (SREs), which include pathologic fracture, bone irradiation or surgery, spinal cord compression, and hypercalcemia. This study examined the evaluation, prevention, and treatment of osteopenia/-porosis (OP/P) and BM in pts with mPCA at the UCCC and affiliated sites. Methods: Pts diagnosed with mPCA and BM between 2011-2021 and treated with ADT were included. Demographic, clinical, treatment, and outcomes data were retrospectively collected. The primary endpoint was time from mPCA diagnosis to first SRE. Secondary endpoints included rates of DEXA scans, rates of vitamin D and calcium supplementation, and bone agent toxicity. The log-rank test was conducted to compare the primary endpoint by use of a bone strengthening agent. The Kruskal Wallis non-parametric test was used for continuous variables and Fisher’s exact test for categorical variables. Results: Of the 369 pts with mPCA, 247 (66.9%) were treated with a bone agent. Median age at metastatic diagnosis (mDx) was 69.6 years. Pts were predominately white (315, 85.4%) with hormone-sensitive mPCA (mHSPC) (327, 88.6%) at mDx. There were no significant differences in race, ethnicity, PSA, Gleason score, or time on ADT between patients who did and did not receive a bone agent. 222 pts (60.2%) were former or current smokers, 5 (1.4%) had pre-existing low testosterone ( < 150 ng/dL), 8 (2.2%) had prolonged glucocorticoid use (equivalent > 10 mg prednisone for 30 days), and 17 (4.6%) had known OP/P prior to mDx. 130 pts (35.3%) had a DEXA scan (27 pre-ADT, 103 post-ADT). 325 pts (88.1%) and 286 pts (77.5%) were recommended vitamin D and calcium supplementation, respectively. Bone agent use and toxicity are presented in table 1. 110 of 247 pts (44.5%) treated with a bone agent were started in the mHSPC setting without OP/P. Time from mPCA diagnosis to first SRE was a median of 32.8 months (IQR 13.5 to 66.8) for pts who received a bone agent vs. 28.2 months (IQR 8.7 to 59.1) who did not (Chi-squared = 7.089, p = 0.008). Among SREs, 102 pts (27.6%) had a pathologic fracture, 1 (0.3%) severe hypercalcemia > 14 mg/dL, 23 (6.2%) bone surgery, 142 (38.5%) bone irradiation, and 4 (1.1%) spinal cord compression. Conclusions: Bone agent use was associated with an expected improvement in time to first SRE. Pts with mPCA had high rates of vitamin D and calcium supplementation for OP/P prevention. Denosumab was the most used bone agent in concordance with guidelines for mPCA. DEXA scan rates were low, and nearly half of patients received a bone agent prior to castrate resistance. [Table: see text]
Treatment trends and prognostic factors related to histology of squamous cell carcinoma of the prostate: A SEER review.
Authors: Siripurapu Vaishnavi , Pasli Melisa , Bhatt Arjun , Ashley Lucas W. , Gordon Julian , Peach Matthew Sean 
Published: June 2023

e17120 Background: Excluding skin cancers, prostate cancer is the most common malignancy in males. Over 93% of prostate cancers are adenocarcinomas, and as such, an abundance of literature exists with regards to its screening, treatment, and prognosis. Often overlooked, however, data is lacking with regards to squamous cell carcinoma (SCC) of the prostate, a rare alternative form of prostatic cancer comprising fewer than 1% of malignancies. Given the rarity of SCC of the prostate there are neither accepted treatment guidelines nor consistent characterizations of the disease’s histogenesis and histopathology. This study seeks to improve existing guidelines on the treatment of prostate SCC by supplementing current literature with a novel method of longitudinal data collection in the form of the SEER database. Methods: This was a retrospective cohort study utilizing the Surveillance, Epidemiology and End Results (SEER) database sponsored by the National Cancer Institute (NCI). Investigated variables entailed patient demographics such as race and age, tumor characteristics including grade, tumor type, and histopathologic characteristics. Treatment modalities (surgical resection, radiation therapy, and systemic therapy) as well as disease characteristics were considered in generating Kaplan Meier overall survival (OS) curves compared using log rank test. Results: The most abundantly utilized treatment was surgery (58.6%), either alone or in conjunction with systemic and radiotherapy. Surgery alone was utilized for 24 patients and chemotherapy alone was utilized for 7 patients. Interestingly, only 14% of patients received multimodality treatment. Prostatic squamous cell carcinoma was the ultimate cause of death in 63.8% of cases. Kaplan Meier analysis demonstrated a median OS of 13 months. When stratifying by histopathologic characteristics, our results showed a significant difference in overall survival between patients with papillary carcinoma, with the median survival time of four years, and non-keratinizing squamous cell carcinoma, with a median survival time of one year (p = 0.005). Conclusions: Further studies are warranted regarding this exceedingly rare and understudied malignancy. The current analysis suggests subclassification of SSC of the prostate into papillary versus non-keratinizing squamous cell carcinoma may yield valuable prognostic information. Further research may emphasize this distinction as well as the role of multimodal treatment which appears to be underrepresented in SSC of the prostate when compared to other similar malignancies.
Update on the outcome of patients with metastatic prostate cancer in Kentucky: A Kentucky Cancer Registry (KCR) study.
Authors: Pandey Deepali , Chen Quan , Huang Bin , Myint Zin , Wang Peng 
Published: June 2023

e17121 Background: Overall survival (OS) of metastatic Prostate Cancer (mPC) in USA has improved by 3.6% during 2011–2016 compared to 2001–2005 (CDC, Oct 2020). Improvements in OS for mPC might reflect changes in clinical management, with approval of several new treatments. We aim to analyze if there is an improvement in OS of mPC in Kentucky between 2004-2011(T1) and 2012-2019(T2) and also analyze the impact of socioeconomic status as defined by Area Deprivation Index (ADI) on survival of mPC. Methods: All Kentucky male patients diagnosed between 2004 and 2019 who were > 20 years old at diagnosis with first primary of metastatic prostate adenocarcinoma were extracted from the Kentucky Cancer Registry (KCR) data. Basic demographics and survival outcomes were compared between two time periods - T1 vs T2 and by Appalachian status. Kaplan Meir (KM) and Multivariate Cox Regression (MCR) were used to examine OS. ADI is divided into three groups – bottom tertile (low deprivation-ADI 1-3, Gr 1), middle tertile (ADI 4-6, Gr 2), and top tertile (high deprivation-ADI 7-10, Gr 3). Results: A total of 2619 patients with mPC were included in this retrospective analysis, of which 69.3% were Non-Appalachian (Non-AP) and 30.7% were Appalachian (AP). Caucasians predominated in both time periods (89.2% vs 90%). T2 had a higher proportion of patients aged 50-74 years (72.5% vs 64.2%), and private insurance (31.4% vs 27.1%) compared to T1. T1 had more patients who were > 75 years (31.6% vs 24.8%), smokers (51.2% vs 47.4%), had medicare (59.6% vs 56.8%) and no insurance (4.2% vs 1.5%) compared to T2. KM showed improved OS in T2 (p < 0.0001). Non-AP had better OS compared to AP and improved more between T1 & T2. Median OS in months(95% CI) in T1 vs T2 for Non-AP was - 30(27-38) vs 58(53-69), p < 0.0001 & for AP was -34 (27-39) vs 44 (37-51), p = 0.0163. MCR showed that younger age, private insurance, being a nonsmoker, and receiving treatment, contributed to better OS. Gr 3 had higher proportion of African Americans (10.7% vs 6.5%), less private insurance (23.9% vs 39.7%) and more patients receiving no treatment (10.9% vs 7.5%) compared to Gr 1. AP Kentucky had more patients in Gr 3 (60.5% vs 39.5%) compared to Non-AP. KM showed OS had improved for all ADI groups in T2 vs T1. Within ADI groups, Gr 3 had significantly lower OS compared to Gr 1 & Gr 2 (p = 0.04) in T2. In T1, OS was not different within ADI groups. In MCR, race and ADI did not impact OS. Conclusions: OS has improved in mPC patients in Kentucky during 2012-2019, likely due to new treatments being available. There is improvement in OS in Appalachian Kentucky but numerically lower than Non-Appalachian, and worse OS in Gr 3 during 2012-2019 which could be partially due to differences in access to new treatments (or quality of care). Interestingly, race did not impact survival.
The insights of mutations of gynecological oncology by liquid biopsy for Chinese patients.
Authors: Huang Yan , Yin Yan , Peng Bo , Hu Bo , Chen Shifu , Zhang Meiqin 
Published: June 2023

e17501 Background: Liquid biopsy drew dramatic attention in the field of cancer research because of its attribution of nontraumatic, easy to obtain, providing overall state of tumor, allowing for real-time monitoring and so on. However, the transformation from research to application of liquid biopsy technique in clinical gynecological oncology management require more evidence and further investigation. Methods: Blood samples of 104 patients were collected, of whom 33 were diagnosed as cervical cancer, 20 were diagnosed as endometrial cancer, and 51 were diagnosed as ovarian cancer. cfDNA were extracted from blood and examined by next-generation sequencing technique with Haplox HapOnco panel. cfDNA mutations were analyzed and compared with genomic mutations in tumor tissues in publications. Results: In cfDNA, there were 120 genes mutated in cervical cancer patients, 150 genes mutated in endometrial cancer patients, and 58 genes mutated in ovarian cancer patients. Detecting by cfDNA, the average number of mutations was 6 (4.1 to 7.9, 95% CI) for each cervical cancer patient, 8.1 (2.1 to 14.1, 95% CI) for each endometrial cancer patient, and 5.1 (3.7 to 6.5, 95% CI) for each ovarian cancer patient. As the mutations in cfDNA compared with those in tumor tissues, the results revealed that there was no significant difference in mutation rate for 94.2% genes in blood and tumor tissues for cervical cancer patients, 93.3% for endometrial cancer patients, and 98.3% for ovarian cancer patients. Besides, there were no significant differences in microsatellite instability rates in blood and tumor tissues for cervical cancer patients and endometrial cancer patients. Conclusions: Most mutated genes in tumor tissues were detected in blood for gynecological oncology patients. The mutation rate for most genes and microsatellite instability rate had no significant difference in blood and tumor tissues, which suggested that liquid biopsy using cfDNA is helpful in gynecological oncology management.
AXL pathway as a target to overcome resistance to PARP inhibitors in high-grade serous ovarian (HGSOC) and triple-negative breast cancer (TNBC) cell lines.
Authors: Perez-Fidalgo Jose Alejandro , Martinez Pretel Juan Jose , Sanchez Serrano Paloma , Heredia Victoria , Hochstadt Jan , Mendiola Marta , Redondo Andres , Gonzalez Villena Lidia , Ruiz Linuesa Miriam , Pineda Begona 
Published: June 2023

e17502 Background: PARP inhibitors (PARPi) as olaparib (OLA) have become the new standard in maintenance treatment in high grade serous ovarian carcinoma (HGSOC) and triple negative breast cancer (TNBC). Thus there is an important need to identify the mechanisms for PARPi resistance and the strategies to overcome it. Our aim is to intervene in vitro AXL, a receptor tyrosine kinase, linking its function to the OLA-resistance mechanism and assess its suitability as a therapeutical target to overcome PARPi-resistance. Methods: Three cell lines, 2 from HGSOC (PEO1-S and Kuramochi-S) and 1 from TNBC (MDA-MB-231-S) were selected, isogenic resistant pairs generated in vitro by pulsed exposure to OLA (PEO1-R) or by exposure to growing concentrations of OLA (Kuramochi-R and MDA-MB-231-R) were obtained. Resistance was confirm by the comparison of IC50 of OLA in -S vs -R lines. AXL expression was assessed by western blot (WB). Cells were treated with OLA before and after the downregulation of AXL expression by a specific siRNA. Cell viability was assessed by MTT assay and DNA damage by the evaluation of markers by western blot (WB). Results: AXL expression was maintained upon OLA treatment in all 3 resistant cell lines. However, AXL expression was reduced upon OLA exposure in 3 sensible parental cell lines. AXL silencing (Si) lead to a significantly decrease of OLA IC50 in all 3 sensitive and resistant cell lines. For sensitive cell lines, IC50 of OLA was in 1) PEO1S with control (scramble) was 5.79 mM vs 2.24 mM after silencing with siRNA, p < 0.0001; 2) Kuramochi-S scramble OLA IC50 was 481.8 mM vs 199.7 mM with siRNA, p < 0.0001 and 3) MDA-MB-231-S with control of scramble the OLA IC50 was 61.62 mM vs 26.21 mM with siRNA, p = 0.001. For resistant cell lines, 4) PEO1R control with scramble 91.49 mM vs siRNA 45.72 mM, p < 0.0001; 5) Kuramochi-R scramble OLA IC50 579.8 mM vs 219.8 mM with siRNA, p = 0.0008 and 6) 231-R scramble OLA IC50 68.22 mM vs 9.247 mM with siRNA, p < 0.0001. These results suggest that AXL downregulation increases sensitivity to OLA in both sensitive and resistant cell lines. Histone γ-H2AX was analysed pre and post silencing and both increased when treating with OLA, especially when AXL was downregulated in alll three resistant cell lines. Conclusions: This in vitro study suggest a potential role of AXL in OLA resistance and AXL downregulation migh represent a potential mechanism to overcome resistance to OLA in ovarian and TNBC cell lines.
Incidence of low volume metastases after retrospective ultrastaging of patients with early stage, node negative cervical cancer and receipt of post-operative adjuvant therapy.
Authors: Welp Annalyn , Crawford Michael , O'Brien Rachel , Sullivan Stephanie , Duska Linda R. 
Published: June 2023

e17506 Background: Nodal positivity directs receipt of adjuvant post-operative therapy in early stage cervical cancer; the significance of low-volume metastases (LVM) is unclear. We hypothesized patients with early stage cervical cancer with high risk factors on pathology and negative nodes would have a higher incidence of LVM on retrospective ultrastaging. Methods: This retrospective cohort study collected clinicopathologic data via chart review on early stage cervical cancer patients treated at our institution from January 2011 - June 2021. The study was approved by the IRB. Inclusion criteria included patients >18 years old who underwent a radical hysterectomy/trachelectomy with pathology-proven negative nodes who went on to be recommended for post-operative adjuvant therapy, due to factors defined under Sedlis or Peters criteria. Patients were excluded for rare histology or prior pelvic radiation. Resected nodes were ultrastaged, performed by 4 re-cuts at 20 microns on each lymph node staging, stained with H&E and one level with CK AE1/AE3 to identify presence of any LVM. Analysis was performed via descriptive statistics with Microsoft Excel. Results: 199 patients were treated with radical hysterectomy between 2011-2021; 20 met study criteria. The average age at diagnosis was 51 years: 65% Caucasian, 25% Black, 10% Latino. 75% had Squamous cell carcinoma, 85% (n=17) of the cohort were a 2009 FIGO pathologic Stage 1B. 35% of the cohort underwent a minimally invasive hysterectomy. Tumor size varied: 25% (n=5) of tumors were less than 2 cm, 35% (n=7) of tumors measured greater than or equal to 2 cm, 30% (n=6) measured greater than or equal to 3 cm, and 10% (n=2) measured greater than or equal to 4 cm. Lymphovascular space invasion was noted in 75% (n=15) of samples. Superficial stromal invasion was noted in 5% (n=1), deep stromal invasion was noted in 65% (n=13). 5% (n=1) of patients had parametrial invasion, and 5% (n=1) had positive margins. A full bilateral pelvic lymphadenectomy was performed on every patient, with 245 nodal blocks ultrastaged. 80% (n=16) received adjuvant therapy: 3 chemoradiation, 13 radiation, 4 declined. LVM was identified in 5% (n=1) patients; a macrometastases was identified as missed in the initial pathologic evaluation of another. 10% (n=2) patients developed recurrence, one at the pelvic brim and one distant (lung). The patient with the newly identified LVM received adjuvant radiation, and developed recurrence at the pelvic brim. Conclusions: The results of this small study suggest traditional “high risk” factors in surgically managed cervical cancer is associated with positive ultrastaged nodes in 5% of cases. This finding suggests that utilization of sentinel node identification with associated ultrastaging will accurately identify patients who will benefit from adjuvant therapy.