bluuebunny/crossref_metadata_2025_split huggingface dataset:
Addition of MRI or DRE to clinical data and risk prediction for clinically significant prostate cancer.
Authors: Wallis Christopher J.D. , Paproski Robert J , Hyndman M Eric , Fairey Adrian S. , Marks Leonard , Pavlovich Christian P. , Fletcher Sean , Zachoval Roman , Adamcova Vanda , Stejskal Jiri , Aprikian Armen G. , Kinnaird Adam , Pink Desmond , Vasquez Catalina , Beatty Perrin H , Lewis John D 
Published: June 2024

e17105 Background: In patients suspected of prostate cancer, the decision to perform a biopsy hinges on available clinical data. Magnetic resonance imaging (MRI) and digital rectal exam (DRE) data are informative but may not be available. We created accurate models for clinically significant prostate cancer (csPCa), flexible to MRI and DRE data availability. Methods: Optimized ensembles of calibrated random forest models predicting csPCa (Grade Group ≥2) used total PSA, free PSA, prior negative biopsy status, and age, with or without DRE and MRI data (prostate volume and PI-RADS score). Risk models were derived (training cohorts n=1257 to 2191) and validated (validation cohorts n=317 to 1257) from different clinical sites. Models were evaluated by the area under the receiver operating characteristic curve (ROC AUC), sensitivity, specificity, positive predictive value, and negative predictive value, using thresholds providing ~ 95% sensitivity. Feature importance was determined by SHAP analysis. Results: All models had an AUC of at least 0.80, showing that predicting csPCa can be accurate without MRI or DRE data. Including MRI data significantly increased the AUC in the validation cohort (ClarityDX Prostate 0.80 vs ClarityDX Prostate +MRI 0.87). DRE had moderate value for models without MRI data (ClarityDX Prostate 0.80 vs ClarityDX Prostate +DRE 0.82) and minor value with MRI data (ClarityDX Prostate +MRI vs ClarityDX Prostate +DRE+MRI; AUC 0.87 vs 0.87; specificity 45% vs 47%, Table). Mean absolute SHAP values were highest for PI-RADS and prostate volume. Conclusions: These optimized risk models provide high accuracy for predicting csPCa in various clinical settings. Including MRI data greatly increases model accuracy, while DRE has a smaller effect on model accuracy. [Table: see text]
The silent burden: A SEER-based analysis of potential years of life lost due to genitourinary cancers in the United States (1975-2017).
Authors: Gor Rajvi , Gwalani Pranav , GOR DHAIRYA , Shah Anand , Thakur Rahul Kumar , Gartrell Benjamin Adam 
Published: June 2024

e17107 Background: Genitourinary (GU) cancers significantly impact United States (US) public health, not just in mortality but also in premature deaths. We evaluated the potential years of life lost (PYLL) due to these cancers (prostate, kidney, bladder, testicular, penile, and others) from 1975 to 2017 using the SEER database and stratified it across racial groups. Methods: From 1975 to 2017, GU cancers were identified using SEER*Stat 8.4.2 using ICD-10 CM codes. We analyzed premature deaths and calculated PYLL as [Life expectancy minus (age at diagnosis + survival time)]. Due to non-homogeneity, the Kruskal-Wallis test (α = 5%) was employed for subgroup PYLL analysis. Spearman correlation coefficient (ρ) assessed the relationship between the year of diagnosis and PYLL. Analyses were conducted using SAS OnDemand. Results: Of the 1,715,763 GU cancer cases (1975-2017), 235,279 had premature deaths, totaling 2,406,551.20 PYLL. Testicular cancer showed the highest median PYLL (33.3 years) compared to other sites, followed by penile cancer with a median PYLL of 12.2 years. Non-Hispanic (NH) Blacks had higher PYLL for prostate, kidney, ureteral, and bladder cancers (p<0.05), while Hispanics had higher PYLL for penile and testicular cancers (p<0.0001). ρ value for PYLL and year of diagnosis was 0.23. Conclusions: Our study reveals a substantial impact of GU cancers on premature mortality and PYLL in the US. Despite the lower prevalence, testicular and penile cancers contribute significantly to PYLL, likely related to younger age at diagnosis. Racial disparities were evident, with NH-Blacks and Hispanics experiencing higher PYLL for specific GU cancers compared to other racial groups. These findings underscore the pressing need for targeted interventions to address disparities and enhance GU cancer management and prevention outcomes. [Table: see text]
Disparity in education and disease stage in patients with testicular germ cell tumors.
Authors: Chovanec Michal , Alzeer Rateb , Hapakova Nikola , Kalavska Katarina , Lesko Peter , Obertova Jana , Orszaghova Zuzana , Palacka Patrik , Rejlekova Katarina , Svetlovska Daniela , Sycova-Mila Zuzana , Vasilkova Lucia , Mego Michal 
Published: June 2024

e17108 Background: Disparities may result in delayed staging and worse outcomes in cancer patients. Testicular germ cell tumors (GCTs) have excellent prognosis. However, disparities in education may have detrimental effect on early diagnosis and treatment. This study evaluated differences in staging and disease burden based on education in GCT patients treated at National Cancer Institute in Slovakia. Methods: Our institutional database was searched for GCT patients treated at National Cancer Institute in Slovakia between 1984 and 2023. Educational status was categorized as: basic/high-school and university. Educational status was correlated with disease stage, IGCCCG risk group, non-metastatic vs metastatic disease and size of retroperitoneal lymph nodes. Methods of descriptive statistics Chi-squared test and logistic regression were used for statistical analysis. Results: This retrospective study included 232 patients treated for stage I or metastatic GCT. Of the patients, 7 (3%), 114 (49%) and 111 (48%) had basic, high-school and university education, respectively. 46 patients (20%) had stage I disease and 186 patients (80%) were treated for metastatic disease. Patients who had basic/high-school education were diagnosed with metastatic disease more commonly compared to patients with university degree (p = 0.01). The Odds ratio for higher risk in patients without university education was 4.6 (95% CI 1.4-15.1). IGCCCG risk group, nodal stage or presence of non-pulmonary visceral metastases did not correlate with educational status (all p>0.05). Conclusions: GCT patients with basic- and/or high-school education are diagnosed with metastatic disease more frequently than those with university education. Our study may suffer from referral bias. Raising awareness in schools is imperative for early diagnosis of GCTs.
Clinician documentation of shared decision making for prostate cancer screening.
Authors: Le Phuong Nhi , Shungu Nicholas 
Published: June 2024

e17109 Background: Prostate cancer is the second leading cause of cancer death among US men and disproportionally impacts Black men. Black men are 2.2 times more likely to die from prostate cancer than non-Hispanic white men. Guidelines recommend that men make an informed decision about prostate cancer screening following a conversation with their clinician about risks and benefits. Despite known racial prostate cancer disparities, Black men receive PSA screening at lower rates than Non-Hispanic White men. Black men also report inadequate education to make informed decisions about prostate cancer screening. Little is known contemporarily about how often shared decision-making (SDM) conversations occur and how they affect rates of PSA tests. The purpose of this project was to determine the extent to which clinicians are documenting prostate cancer shared decision making conversations in men aged 45 to 69, to investigate whether this documentation differs based on patient race, and to examine the relationship between SDM conversations and completion of prostate cancer screening. Methods: This retrospective chart review included 300 Black men and 300 age-matched White men between the ages of 45 and 69 who had an outpatient visit at a Medical University of South Carolina (MUSC) outpatient family medicine clinic from 2019-2020. Frequency of documented SDM conversations by patient race and frequency of PSA ordering by patient race were analyzed using Pearson chi-squares. Multivariable logistic regression was run with documented shared decision-making conversation and screening PSA ordered as dependent variables and patient demographic and clinical data as independent variables. Results: 28.1% of Black men and 29.1% of White men completed PSA screening (p=0.68). 12.1% of Black men and 6.5% of White men had SDM conversations documented (p=0.13). Among 300 Black men, SDM was associated with increased likelihood of screening PSA (p<0.01). SDM was not associated with family history of cancer, colon cancer screening, or insurance. Screening PSA was associated with insurance type among Black men (p = 0.03). Among 300 non-Black men, there was no association between SDM and screening PSA. There was also no association between insurance type and screening PSA. Conclusions: Rates of PSA screening and documented SDM conversations were strikingly low regardless of race at this large academic medical center. It is imperative that primary care clinicians engage in and appropriately document prostate cancer screening SDM conversations in order to uphold the current standard of care and reduce prostate cancer mortality. The increased likelihood of prostate cancer screening in Black men who had SDM conversations stresses the importance of these conversations in the fight to eliminate racial prostate cancer disparities.
Evaluation of persistence and adherence for oral and injectable androgen deprivation therapies (ADT) in United States (US) patients with prostate cancer (PC).
Authors: Hafron Jason , Hong Agnes , DePaauw-Holt Simon , Romdhani Hela , Kinkead Frédéric , Flanders Scott C , Ryan Michael J. , McKay Rana R. 
Published: June 2024

e17110 Background: Relugolix (REL) is the only oral gonadotropin-releasing hormone (GnRH) antagonist available for patients (pts) with advanced PC. Other ADT options for these pts include the injectable GnRH antagonist degarelix (DEG) or injections or implants of GnRH agonists (i.e., leuprolide, goserelin, triptorelin, or histrelin). This study assessed persistence and adherence for REL, DEG, and GnRH agonists in US pts with PC. Methods: This retrospective study used the Merative MarketScan Research Claims Database (Commercial Claims and Medicare Supplemental; 01/2017–12/2022). Eligible pts were adult men with ≥1 claim with PC diagnosis who initiated REL, DEG, or a GnRH agonist (first claim was the index date) between 01/01/2021 and 06/30/2022. Pts were classified into these 3 mutually exclusive cohorts based on the index ADT. Kaplan–Meier (KM) analysis was used to assess persistence (i.e., time from index to treatment discontinuation defined as a gap in treatment of ≥60 days after the last day of supply, or switch to a new ADT). Treatment adherence was assessed at 6 and 12 months (mo) using proportion of days covered (PDC) defined as the sum of non-overlapping days of supply divided by the time period. Results: In total, 173 REL, 266 DEG, and 2,955 GnRH agonist pts were included. Median age was similar across cohorts and the proportion of pts with metastatic disease was slightly lower in GnRH agonist pts (Table). Median time on index ADT was 13.5 (REL), 3.1 (DEG), and 8.8 (GnRH agonist) mo. At 6 mo, persistence was 72.9% (REL), 24.2% (DEG), and 57.3% (GnRH agonist); and the proportion of pts with PDC ≥0.80 was numerically highest in REL and GnRH agonist pts and lowest in DEG. At 12 mo, persistence was 54.8% (REL), 9.9% (DEG), and 39.9% (GnRH agonist); and the proportion of pts with PDC ≥0.80 was also numerically highest in REL and GnRH agonist pts and lowest in DEG (Table). Conclusions: Despite differences in mode of administration, findings indicate that persistence and adherence are similar in pts with PC treated with REL and GnRH agonists while higher than those treated with DEG. Future research is needed to understand the factors associated with persistence and adherence. [Table: see text]
Maximal androgen blockade therapy (MAB) for prostate cancer (PC) and risk of bone fractures: A systematic literature review and meta-analysis.
Authors: Turco Fabio , Saporita Isabella , Calabrese Mariangela , Carfi Federica Maria , Mogavero Andrea , Treglia Giorgio , Gillessen Silke , Di Maio Massimo , Tucci Marcello , ButtIgliero Consuelo , Vogl Ursula 
Published: June 2024

e17111 Background: Androgen deprivation therapy (ADT) increases the risk of fractures. The addition of an androgen receptor pathway inhibitor (ARPI) to ADT (MAB) has shown to improve outcomes compared to ADT monotherapy in patients (pts) with metastatic castration-resistant PC (mCRPC), non-mCRPC (nmCRPC), metastatic hormone-sensitive PC (mHSPC), high-risk localized disease and high-risk biochemical relapse. There is no definitive evidence whether MAB increases the risk of fractures compared to ADT alone. Methods: We conducted a systematic review of all clinical trials assessing treatment with an ARPI plus ADT for pts with PC having placebo plus ADT as control arm, using the PubMed/Medline and Cochrane library databases. We also performed a meta-analysis to compare the risk of fractures of each ARPI versus placebo. Further we assessed the number of pts receiving bone protecting agents (BPA) in the studies selected. The comparison between ARPI and placebo in terms of risk of fractures was performed using odds ratio (OR) as meta-analytic outcome. Results: We identified 15 studies comprising 15183 pts (8638 treated with an ARPI and 6545 with placebo), of which 3 studies evaluated abiraterone, 3 apalutamide, 3 darolutamide and 6 enzalutamide. Each ARPI resulted in a statistically significant increase in the risk of fractures compared to placebo (see table), but without statistical differences among the different ARPIs since there is an overlap between the confidence intervals (CI) of the pooled outcome measure of different ARPIs compared to placebo. Only 7/15 studies reported the number (n°) of pts treated with a BPA of which 4 were in mCRPC, 2 in nmCRPC and one in the mHSPC setting. The highest percentage was found in studies including mCRPC pts, of which 35-50% received a BPA. In the studies in the nmCRPC setting, 10-11% of pts received a BPA while in the only mHSPC study reporting data on the use of BPA only two pts (0.4%) in the ARPI group received BPA and no patient in the placebo group. Conclusions: In our meta-analysis MAB resulted in a statistically significant increase in fracture risk compared to ADT regardless of the ARPI used. Data on the use of BPA should be properly reported in future clinical trials. Since long term MAB represents the standard of care in various settings of PC, the use of a BPA should be generally recommended. Dosing and frequency of BPA needs to be adapted according to the specific PC setting. [Table: see text]
Rate of p53 and MMR IHC assessment accordance between matched D&C and hysterectomy samples in uterine cancer.
Authors: Syrios John , Christidis Anastasios , Tziortziotis Dimitrios , Sourla Antigoni , Mazis Kourakos Dimitrios , Vlachos Dimitrios , Vlachos Georgios , Mitsakos Barbayiannis Kyriakos 
Published: June 2024

e17587 Background: International guidelines strongly suggest assessment of POLe, MMR, p53 in patients with early stage endometrial cancer. MMR and p53 are commonly assessed with IHC after hysterectomy (+/-BSO). The fixation procedure and the high tumor cellularity of D&C specimens may permit accurate p53 and MMR evaluation. Early knowledge of p53 and MMR status in D&C samples may drive surgical treatment modalities and fertility sparing decision. Methods: In this single center study 73 matched D&C and hysterectomy samples in patients with clinically early stage endometrial cancer were collected and p53 and MMR status was assessed with IHC.Samples were obtained by gynaecologists and gynaecological oncologists and independently assessed by two expert in gynaecological oncology pathologists at REA hospital (Athens-Greece).Immunohistochemistry was performed using Ventana Benchmark Ultra. To determine MMR status, sections were scored visually for loss or intact expression of the proteins MSH6, MSH2, MLH1 and PMS2. Interpretation of immunostaining for each protein was classified as: (i) “retained,” when ≥10% of tumor cells showed a moderate to strong expression; (ii) “loss,” when no evidence of nuclear expression was seen in cancer cells; (iii) “indeterminate,” if IHC staining in tumor cells was less intense compared to the internal control or expression was retained in <10% of neoplastic cells.If, however, the presence of “indeterminate” immunostaining in one or more proteins was coupled with a convincing loss of expression in at least one protein, the tumor was interpreted as “dMMR” tumor.The study was carried out within January 1st -December 1st 2023. Results: There was a 100% accordance between p53 assessment in all 73 matched D&C and hysterectomy specimens. Discrepancy in MMR result was observed only in 1 out of the 73 cases, which stained negative for MLH1 in D&C but positive in hysterectomy, yielding an accordance of 98,96% between D&C and hysterectomy specimens. Conclusions: p53 & MMR status can be accurately assessed with IHC in D&C samples. Repeat assessment after hysterectomy may not be necessary. Early knowledge of the molecular imprint of the disease on D&C samples may drive treatment decisions regarding surgical procedures, fertility preservation and further treatment plans. [Table: see text]
Pole mutated endometrial carcinoma: Clinical and genomic characteristics from a real-world UK cohort.
Authors: Chaabouni Narda , Vroobel Katherine , Attygalle Ayoma , Proszek Paula , Johnson Liam , Smalley Michaela , Shaikh Ridwan , Lalondrelle Susan , Taylor Alexandra , George Angela Joy 
Published: June 2024

e17600 Background: Pathogenic mutations within the DNA polymerase epsilon (POLE) exonuclease domain characterise the POLE/ultra-mutated molecular subgroup as defined by the Cancer Genome Atlas (TCGA) Research Network. Our study aimed to evaluate clinical and genomic characteristics of POLE mutated endometrial carcinoma (EC) from a real-world cohort. Methods: 246 tumour samples from patients diagnosed with primary endometrial cancer (EC) between September 2007 and June 2022 were sequenced using the Royal Marsden RMH200 Solid panel which includes 233 genes and evaluates microsatellite instability (MSI) and tumour mutational burden (TMB). Droplet Digital PCR (ddPCR) was used for MLH1 promoter methylation status in each case. Mismatch repair proteins (MMR) and P53 were tested by immunohistochemistry (IHC). Patients’ characteristics were documented from our electronic records. Results: POLE mutations were identified in 21 patients (8.5%). Mean age at diagnosis was 63 years old (52-92). Mean BMI was 28.5 (21.1-48) and 38.1% of patients had hypertension (n=8). 20 cases were stage I (95%) and 1 case was stage III (5%). Predominant histological subtype was endometrioid in 17 cases (81%). The other histological subtypes comprised clear cell (n=1), mixed (n=1) and carcinosarcoma (n=2). All patients had surgery and 15 (71.4%) received adjuvant therapy which included chemotherapy in 4 (19%) cases. Mean TMB was 125.11 mut/Mb (25.77-345.82). 8 (38%) cases demonstrated MMR deficiency with MLH1 promoter hypermethylation detected in 7/8 cases. P53 was wild type (WT) in 17 (81%) and subclonal mutant in 4 (19%) of cases. 13 (61.9%) cases were microsatellite stable and 8 (38.1%) MSI-high. Recognised pathogenic POLE variants were identified in 16 (76.2%) cases: V411L* c.1231G (n=7), P286R c.857C>G (n=4), A456P c.1366G>C (n=2), A465V c.1394C>T (n=1), P436R c.1307C>G (n=1), M444K c.1331T>A (n=1).After a median follow-up of 21 months, one patient developed distant recurrence and died of progressive brain metastases following surgery for stage IA grade 1 endometrioid carcinoma, however recurrence was not biopsied. Conclusions: In this real-world cohort, POLE mutated EC cases were associated with a favourable prognosis. One distant recurrence was observed in initially uterine-confined case but was not histologically proven. Further research is needed to prognosticate POLE mutated EC and define appropriate adjuvant treatment recommendation.
Recurrent vulvar squamous cell carcinoma: Outcomes across the treatment spectrum—Are we making progress?
Authors: Meloche Claudia , Dinh Trish , Spaans Johanna , Zhang Tinghua , Weberpals Johanne I 
Published: June 2024

e17603 Background: No standard treatment exists for recurrent vulvar squamous cell carcinoma (VSCC) and the prognosis is poor. This retrospective study reports on outcomes of recurrent and progressive VSCC patients (pts) across various treatments. Methods: This was a single-center retrospective cohort study conducted at the Ottawa Hospital (Ottawa, Canada). Pts with histologically proven VSCC treated between 2000-2023 were identified, and the study population comprised pts who either recurred or progressed after/during first-line therapy. Clinicopathologic data were collected, and descriptive statistics were performed according to pt demographics, tumor characteristics and treatment modality. Median progression free survival (PFS) and overall survival (OS) were determined by treatment type. The outcomes of unique cases treated with novel therapies are also highlighted. Results: There were 311 pts with a diagnosis of VSCC. Ninety-five pts with recurrent/progressive disease formed the study population with a median age of 72 years and 52% having at least stage III disease at initial diagnosis according to FIGO 2021 staging. The prevailing treatment at time of diagnosis was surgery (74%), with 40% of pts also undergoing radiation, chemotherapy, or a combination of both. Location of disease progression or recurrence was regional 53 (56%), inguinal 31 (33%) and distant 11(12%). There were 60 pts (63)% who had one recurrence, as well as 18 pts (19%) and 3 pts (3%) with two and three recurrences, respectively. Of all patients, 14/95 (15%) showed evidence of early progression following treatment. Treatment for first recurrence included: radiation (18.9%), surgery (16.8%), no treatment (16.8%), chemotherapy (11.6%), chemoradiation (9.4%), surgery with radiation (7.3%) surgery and chemoradiation (2.1%), surgery and chemotherapy (1.1%), and investigational therapy (1.1%). The most common chemotherapy regimen used was cisplatin, while the predominant surgical procedure performed was radical vulvectomy. Two pts received Pembrolizumab for treatment of recurrent disease. One pt received a combination of carboplatinum, paclitaxel and bevacizumab followed by maintenance pembrolizumab for 55 cycles (PFS 27.1 months, mo). A second pt was treated for a second recurrence with carbo-taxol followed by single agent pembrolizumab for 27 cycles with stable disease (PFS 15.7 mo). The mPFS after treatment of first recurrence was 11.6 mo for surgery, 8.7 mo for radiation, 8 mo for chemotherapy, 3.2 mo for chemoradiation, and 2.2 mo for no treatment. Among VSCC pts with recurrent or progressive disease, the median OS from all causes was 21 mo. Conclusions: Pts with recurrent/progressive VSCC who underwent surgery had the most favorable outcomes. Significant promise was shown with pembrolizumab and highlights the need for immunotherapy clinical trials for this rare and fatal woman’s cancer.