bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilization of neoadjuvant chemotherapy (NAC) and pathologic outcomes in upper tract urothelial carcinoma (UTUC).
Authors: Xu Vincent Eric , Azari Sarah , Klein Matthew Nicholas , Drouaud Arthur , Chang Phat , Antar Ryan Michael , Gordon Olivia French , Smith Armine , Whalen Michael Joseph 
Published: June 2024

e16620 Background: UTUC is a rare malignancy with a poorer prognosis compared to bladder urothelial carcinoma. Radical nephroureterectomy (RNU) remains the standard treatment for high-risk UTUC. Considering the decline in renal function with RNU and promising pathologic complete response rates from the phase II trial ECOG-ACRIN 8141, NAC has emerged as a favored perioperative treatment regimen for chemo-eligible patients with high-risk UTUC. However, RCTs exploring NAC's efficacy are absent, and large-scale studies examining NAC's role and predictors for its use are scarce. Methods: This study aimed to assess trends in NAC utilization, determinants for receiving NAC, and pathologic outcomes. The National Cancer Database was queried for patients with high-grade cM0 UTUC treated with RNU from 2004-2019. Outcomes included pathologic response (pR) and pathologic complete response (pCR), defined as ≤pT1pN0/X and pT0pN0/X, respectively. Multivariate regressions were adjusted for relevant patient and tumor characteristics. Results: Of 6,436 patients treated with RNU alone and 209 with RNU and NAC, older age, greater home distance from the treatment facility, and higher comorbidity scores decreased the likelihood of receiving NAC. In contrast, higher cT stage (OR 1.72, p=0.028) and cN+ status (OR 7.40, p<0.001) predicted NAC treatment. NAC was more commonly used in academic centers (OR 2.02, p<0.001). Use of NAC peaked in 2016 at 10%, but dropped to ~2% by 2019. There was minimal nodal response to NAC (23.4% cN+ vs 22.0% pN+). NAC was associated with 34.0% pR and 5.3% pCR rates, increasing the likelihood of pCR (OR 57.5, p<0.001). In cT2-4 UTUC, 19.3% and 7.1% of patients had pR and pCR with NAC, and NAC improved odds of pR (OR 1.78, p=0.024). Conclusions: Our study demonstrated variable NAC use for UTUC, illustrating the evolving landscape of perioperative systemic therapies. We report significant response rates even in cT2-4 UTUC. Our observed poor nodal response to NAC emphasizes the crucial role of retroperitoneal lymph node dissection in staging, regardless of NAC status. We note poor NAC utilization in non-academic settings and among patients living farther from care facilities, underscoring the need for improved care quality in the context of regionalization and multi-disciplinary approaches in UTUC management. [Table: see text]
Real world data of 177 Lutetium-PSMA-617 for metastatic castration resistant prostate cancer (mCRPC): Analysis of patients treated from 2 large reference centers.
Authors: Bruzzi Helena F. , Herchenhorn Daniel , Lopes Gabriela C. K. , Bekierman Hannah , Altino de Almeida Sergio , Mosci Camila , Magalhães Chisthiane , Palazzo Isabella , Fernandes Laura , Freire Vinicius , Andrade Juliana Tarouquella da Silva 
Published: June 2024

e17050 Background: 177Lu-PSMA-617 was recently approved for the treatment of patients with mCRPC in the USA. While treatment is associated with improved survival, responses to therapy are lower in patients with visceral metastasis and with FDG avid disease. In this study, we aim to characterize response to the therapy trying to optimize patient selection for 177Lu-PSMA-617. Methods: Patients treated from 2020 to 2023 in 2 large oncology centers in Brazil were analyzed. Our primary endpoint was to investigate the PSA response rate. Secondary endpoints included overall survival (OS), time to next sequential therapies (TNST) and PSA response in patients with visceral disease. Patients were treated after being submitted to a double image consisting of PET-CT PSMA and a PET-CT FDG (as indicated by the TheraP trial, Hoffman et al.) confirming disease uptake without divergent disease. Results: A total of 32 patients with mCRPC were included in this analysis. The median age was 73 years. Median number of prior lines of therapy for mCRPC was 3 with 20 receiving more than one androgen receptor signaling inhibitor (ARSI) and 5 receiving more than one taxane. The percentage with a PSA response was 48,5% and visceral disease was present in 56,3% of patients. Response rate for pts with visceral disease versus non-visceral was 21,9% vs 43,8%. The Medians of TNST and OS were respectively 7 and 9,6 months. The characteristics of patients with and without a PSA response are detailed in the table. Conclusions: Our cohort, characterized by advanced age, extensive prior treatments, and elevated PSA values, exhibited a PSA response that aligns with patients treated in randomized trials. Notably, our patients with visceral disease demonstrated a lower PSA response. [Table: see text]
Efficacy and safety of PARP inhibitors (PARPi) with immune checkpoint inhibitors (ICI) in metastatic castration-resistant prostate cancer (mCRPC): A systematic review and single-arm meta-analysis.
Authors: Gazzoni Gabriela , Oliveira João Pedro , Reis Pedro Cotta Abrahão , Bittar Vinicius , Carvalho Bruno Murad , Vilbert Maysa , Stecca Carlos Eduardo 
Published: June 2024

e17053 Background: Recent therapeutic advances in prostate cancer have allowed patients with metastatic disease to live longer and better, especially in the castration sensitive setting. Although improvements have been observed in the castration resistant space, survival in this setting remains suboptimal. Early-phase clinical trials suggest the combination of PARP inhibitors (PARPi) and immune checkpoint inhibitors (ICI) have synergistic effect by modulating the tumor microenvironment. In this systematic review and meta-analysis, we assessed the efficacy and safety of PARPi and ICI in the metastatic castration-resistant prostate cancer (mCRCP) setting. Methods: Pubmed, Cochrane and EMBASE were systematically searched from inception through December 10, 2023. Randomized and non-randomized clinical trials evaluating PARPi + ICI in mCRPC were included. PSA response rate (PSArr), radiographic progression-free survival (rPFS), objective response rate (ORR) and overall survival (OS) were analyzed. Subgroups according to (HRR) were assessed. We also pooled the prevalence of immune-related adverse events (irAE) and their corresponding 95% confidence intervals (95% CI). Statistical analysis was performed using R software version 4.3.2 and heterogeneity was evaluated through I2 statistics. Results: We screened 1070 reports, and six trials met the inclusion criteria (one phase III RCT and 5 phase I/II non-RCT), involving 799 participants. The overall ORR was 8.48% (95% CI 6.48-10.86 I2 0%). About 19% of patients achieved an PSArr (95% CI 9.51-32.50 I2 75%). Median OS was 15.8 months (95% IC 13.9-15.8), and rFPS was 4.5 months (95% IC 4.4-4.9). In patients harboring HRR mutations, PSArr was 17.53% (95% CI 10.43-27.95 I2 75), while in HRR non-mutated it was 10.49% (95% CI 5.89-17.99 I2 0%). The frequency of any-grade irAEs was 21.12% (95% CI 12.34-33.74 I2 85%), with 6.70% of grade 3-4 irAEs (95% CI 3.09-13.91 I2 80%). Hypothyroidism rate was 8.53% (95% CI 5.86-12.27 I2 29%) and adrenal insufficiency was 2.80% (95% CI 1.81-4.30 I2 0%). Conclusions: This meta-analysis results suggest that the combination of PARPi plus ICI in patients with mCRPC is safe and may benefit mainly patients with HRR mutations. Further studies in biomarker selected patients are needed. [Table: see text]
Real-world (RW) comparison of prostate-specific antigen (PSA) response in patients with de novo metastatic castration-sensitive prostate cancer (mCSPC) treated with apalutamide (APA) versus enzalutamide (ENZ).
Authors: Lowentritt Benjamin H , Khilfeh Ibrahim , Pilon Dominic , Du Shawn , Rossi Carmine , Kinkead Frédéric , Diaz Lilian , Ellis Lorie , Lefebvre Patrick , Brown Gordon Andrew 
Published: June 2024

e17067 Background: Androgen receptor signaling inhibitor (ARSIs) treatment (APA or ENZ), in combination with androgen deprivation therapy (ADT) has improved the prognosis of patients with de novo mCSPC. PSA decline ≥90% (PSA90) after ARSI initiation has been associated with improved survival and delayed disease progression. The objective of this study was to compare PSA90 response at 6-months among next-generation ARSI-naïve patients with de novo mCSPC initiating APA or ENZ. Methods: Clinical data for US community urology practices from PPS Analytics was linked with claims data from Komodo Health Solutions Research Database. Included patients were assigned to exclusive cohorts based on the first APA or ENZ dispensation or pharmacy claim on or after 12/16/2019 (index date). Patients were also included if they had de novo mCSPC, identified if a metastatic diagnosis was observed ≤180 days after the initial prostate cancer (PC) diagnosis, ≥12 months of pre-index clinical activity, and ≥1 PSA measurement within 13-weeks pre-index. Follow-up spanned from index date until the earliest of index ARSI discontinuation (i.e., gap ≥90 days supply) or switch, radiopharmaceutical initiation, or end of clinical activity/data availability (9/30/2022). Pre-index characteristics (i.e., age, race, region, payer type, index year, time from metastasis, time from PC diagnosis, prior use of ADT, first-generation antiandrogen, or chemotherapy, metastasis locations, most recent PSA and testosterone level, and earliest Gleason score) were balanced between cohorts using inverse-probability of treatment weighting (IPTW). PSA90 was defined as the earliest ≥90% decline in PSA relative to most recent pre-index PSA. The proportion of patients achieving PSA90 was compared using a weighted Kaplan-Meier analysis and the time-to-PSA90 response was compared using a weighted Cox proportional hazards model. Results: Overall, 332 APA and 383 ENZ patients were identified. Patients’ pre-index characteristics were balanced using IPTW (Table). By 6 months post-index, 81.0% of APA and 75.2% of ENZ patients had ≥1 PSA test. PSA90 response at 6 months was achieved by a significantly higher proportion of APA patients, as compared to ENZ patients (62.8% vs 49.6%; p=0.004; Table). Median time to PSA90 response was 3.5 months for APA and 6.1 months for ENZ. Conclusions: This study of RW US data showed that a greater percentage of patients with de novo mCSPC treated with APA achieved a deep, early PSA response by 6 months as compared to those treated with ENZ. [Table: see text]
An NCDB demographic and socioeconomic analysis of mixed acinar ductal carcinoma.
Authors: Alban Sierra , Breytenbach Nicoline , Chang Amber , Reyes Jyztine , Silberstein Peter T. , Heise Craig , Hsia Beau 
Published: June 2024

e17097 Background: Mixed acinar ductal carcinoma (MADC) is a rare form of prostate carcinoma with both acinar carcinoma and ductal adenocarcinoma components, originating in the prostate. Despite their infrequent occurrence, mixed carcinomas have demonstrated increasing prevalence in recent years and are associated with poor prognosis. This is especially concerning since prostate malignancies are one of the most common in men across the world. Thus, understanding the demographic patterns related to this malignancy can offer insight into its epidemiology, diagnosis, and relevant risk factors. The National Cancer Database (NCDB) was used to analyze these patterns in mixed acinar ductal carcinoma. Methods: A retrospective cohort analysis using data from the NCDB was performed for patients diagnosed with mixed acinar ductal carcinoma, ICD-O-3 Code 8552, between 2018 and 2020 (N = 206). Demographic factors were analyzed using descriptive statistics, including age, sex, race, Hispanic heritage, type of facility, distance from facility, and Charles/Deyo score. Statistical regression analysis was used to evaluate incidence patterns. Results: Between 2018 and 2020, 206 patients with a MADC diagnosis were identified with a gradually increasing incidence of diagnosis (R² = 0.2276). Of this cohort, an overwhelming majority identified as male (98.5%) and of White (83%) and non-Hispanic (95.6%) origin. The majority of patients (54.4%) received coverage from Medicare and another 39.5% were under private insurance/managed care. The most common primary site was the prostate (95.1%). NCDB Analytic Staging was not applicable in most cases (82%) and most individuals had a total Charlson-Deyo comorbidity score of 0 (77.2%). The average age at diagnosis was 67.2 years (SD = 8.6, range = 43 – 90 years). Most patients (84.0%) received surgery; following resection of the primary tumor, over half of these patients (53.4%) had no residual tumor. Many of the patients (97.4%) survived at least thirty days after primary surgery, with a similar survival rate (94.9%) after ninety days. The estimated two-year survival rate was 93.9% and the mean survival after diagnosis was 43.2 months (3.6 years). Conclusions: Based on our literature searches, this is the first analysis using NCDB data for mixed acinar ductal carcinoma addressing the lack of understanding of the demographic aspects of the disease. MADC patients were mostly White and non-Hispanic males. Most of these patients held Medicare as a primary insurance, likely due to the overall older population impacted by this cancer. MADC primarily affected the prostate and the patients typically had a favorable prognosis following surgery of the primary site. Additional investigations are necessary to determine the effects of these socioeconomic and demographic factors on individuals with mixed acinar ductal carcinoma.
Investigating L1CAM and β-catenin as prognostic indicators in fertility-sparing endometrial cancer treatment.
Authors: Park Jeong-Yeol , Kang Ok-Ju , Jo Uiree 
Published: June 2024

e17582 Background: Fertility-sparing progestin therapy is well-known treatment option for young women with endometrium-confined, low-grade, endometrioid type endometrial cancer (EC). The introduction of a molecular diagnostic framework by the TCGA Research Network in 2013, categorizing tumors into four prognostic groups, has significantly influenced the prognosis prediction in EC. The ProMisE system further stratifies EC based on molecular profiles, highlighting the need for refined prognostic tools, especially for those undergoing conservative treatments. Our study aims to explore the effectiveness of ProMisE and various immunohistochemical (IHC) markers in predicting outcomes for more fertility-sparing progestin therapy in endometrial cancer. Methods: We included young EC patients treated with fertility-sparing progestin therapy at a single center between January 2011 and December 2020. Patients were categorized according to the results of IHC staining to detect mismatch repair (MMR) proteins and p53 and the results of DNA polymerase epsilon (POLE) mutations which were identified through hotspot sequencing with droplet digital polymerase chain reaction like ProMisE classification. We also measured L1CAM, β-catenin, ER, and PR expression levels through IHC staining. The Complete Response (CR) rate to progestin therapy and PFS after progestin therapy were analyzed between each biomarker-driven subgroup. Results: Out of 104 patients, 60 patients (57.7%) were treated with MPA alone, while 44 patients (42.3%) received a combination of MPA and LNG-IUS. The CR was observed in 64 patients (61.5%). Among those achieving CR, 31 patients (48.4%) experienced recurrence over a median follow-up period of 54.7 months (range:10-128 months). The 5-year PFS was recorded at 67.2%, and the 5-year OS was maintained at 100%. Each one patient showed a POLE mutation, MMRd, and P53 abnormality, leaving 101 (97.1%) with NSMP. IHC revealed L1CAM expression in 12 patients (11.5%) and dual membranous and nuclear β-catenin expression in 8 patients (7.7%). This β-catenin expression significantly correlated with higher CR rates (71.4% vs. 45.6%, p=0.022), while L1CAM presence significantly reduced PFS (3yr-PFS 28.6% vs. 53.9%, p=0.033). Conclusions: Almost all endometrium-confined, low-grade, endometrioid type EC were categorized to NSMP, so that molecular classification had little role in young women who received fertility-sparing progestin therapy. Rather, β-catenin emerges as a positive predictive biomarker for CR, and L1CAM as a negative prognostic biomarker for PFS in this treatment setting. This supports incorporating these IHC markers into molecular classifiers like ProMisE for enhanced risk stratification and personalized treatment in this disease setting.
Differential gene expression analysis of a phase II randomized clinical trial of patients with endometrial cancer (EC) treated with megestrol acetate ± pterostilbene.
Authors: Dellinger Thanh Hue , Wu Xiwei , Cho Hyejin , Yost Susan Elaine , Ruel Nora H. , Invernizzi Marta , Senguttuvan Rosemary Noel , Frankel Paul Henry , Kebria Mehdi , Han Ernest Soyoung , Song Mihae , De Leon Maria , Eng Melissa , Tinsley Raechelle , Schmolze Daniel , Chang Sue , Arias Stella Javier 
Published: June 2024

e17601 Background: The oral antioxidant pterostilbene (PT) (3,5-dimethoxy-40-hydroxystilbene) has demonstrated synergistic antiproliferative effect with megestrol acetate (MA) in endometrial cancer (EC). We conducted a preoperative (window of opportunity) study enrolling endometrial cancer patients scheduled for hysterectomy, who were randomized to preoperative PT+MA vs MA alone. Methods: This prospective, randomized phase II clinical trial (NCT03671811) enrolled patients who were surgical candidates for hysterectomy. Patients were randomized 1:1 to each arm and were treated for 3 weeks with either PT+MA (arm 1) or MA alone (arm 2). Exploratory objectives included histologic response by GOG 211 criteria, and transcriptional changes using whole transcriptome analysis. For the RNA-seq analysis, differential expression analysis used the “limma” R limma package. The differentially expressed genes were selected based on the cutoff values of p-value <= 0.05 and fold change >= 1.5. The gene set enrichment analysis was performed using GSEA software v. 4.3.2 to identify the affected Hallmark and KEGG pathways, using the pre-ranked gene list ranked by the -log10(p-value) with a sign determined by the fold change direction. Results: This prospective, randomized phase II clinical trial (NCT03671811) enrolled patients who were surgical candidates for hysterectomy. Patients were randomized 1:1 to each arm and were treated for 3 weeks with either PT+MA (arm 1) or MA alone (arm 2). Exploratory objectives included histologic response by GOG 211 criteria, and transcriptional changes using whole transcriptome analysis. For the RNA-seq analysis, differential expression analysis used the “limma” R limma package. The differentially expressed genes were selected based on the cutoff values of p-value <= 0.05 and fold change >= 1.5. The gene set enrichment analysis was performed using GSEA software v. 4.3.2 to identify the affected Hallmark and KEGG pathways, using the pre-ranked gene list ranked by the -log10(p-value) with a sign determined by the fold change direction. Conclusions: In endometrial cancer, the oral antioxidant Pterostilbene increases innate immune system pathway expression, while reducing mTOR pathway expression, potentially serving as a useful adjunct to progestin hormonal therapy in EC. Clinical trial information: NCT03671811 .
Genomic profiling of Chinese patients with endometrial adenocarcinoma (EA).
Authors: Huiming Guo , Yuni Jin , Liangdi Su , Yuan Liu , Chan Bao , Tian Li , Juan Zhang , Zhang Bei 
Published: June 2024

e17606 Background: Incidences of endometrial adenocarcinoma are increasing in the Chinese with poor prognosis. Our aim was to explore the genomic profiling of Chinese endometrial adenocarcinoma and whether they could provide potential prognostic and therapeutic implications. Methods: Between January 2019 and August 2023, a total of 204 samples, were obtained from Chinese EA patients at the 3DMed Biobank (Shanghai, China) and The First Affiliated Hospital of Kunming Medical University. Genomic alterations were determined using NGS 733 cancer-related genes panel. TMB-H was defined as above 10 mutation/Mb. Positive PD-L1 expression was defined as ≥1 of CPS. Statistical analyses were performed using R version 3.4.4. Results: A total of 204 patients with EA were included in this study. The median age at diagnosis was 56 (range, 27-92) years old. Among these 204 tissue samples, 178 (87%) were collected from primary lesions. 9.0 %( 12/133) patients exhibited positive PD-L1 CPS status. 19.6% of patients in our cohort exhibited MSI. Median TMB was 6.15 mutation/Mb [0, 473], and 33.8% patients had TMB-H status. In this cohort, a total of 9404 somatic alterations were detected in 96.1% of the patients (196/204), with an average of 46 alterations per patient. The most commonly alternated genes were PTEN (68%), ARID1A (50%), PIK3CA (47%), PIK3R1 (32%), TP53 (31%), ZFHX3 (30%), CTCF (25%), KMT2C (23%), KRAS (22%), CTNNB1 (22%), CHD4 (18%), FAT4 (18%), FAT1 (18%), NCOR2 (17%), ARID1B (17%), AR (16%), BCOR1 (16%), MYC (16%), and NF1 (16%). The hotspot mutations (prevalence higher than 2%) in Chinese EA included PTEN p. R130G, PIK3CA p.R88Q, RNF43 p.G659Vfs*41, PIK3CA p.H1047R, KMT2C p.K2797Rfs*26, CTCF p.T204Nfs*26, KRAS p.G12D, and TEAD2 p.H295Mfs*12. In terms of structural-rearrangements, ten fusions were detected in six genes, with NOTCH2 (n = 4) and RAF1 (n = 2) having the highest number of events. In terms of CNVs, frequently affected genes in Chinese EA included PTEN (249), ARID1A (172), PIK3CA (137), ZFHX3 (110), LRP1B (96), and FAT4 (93). The frequently affected pathways were PI3K (88%), RTK-RAS (72%), and WNT (54%) Furthermore, pathogenic or likely pathogenic germline variants were observed in 33 patients (16.2%). The affected genes included MSH6 (6), MLH1 (4), MSH2 (4), ATM (3), FANCA (3), BRCA2 (3), BRCA1 (2), PMS2 (2), APC (1), BARD1 (1), BLM (1), CDH1 (1), FANCD2 (1), FANCG (1), PALB2 (1), RAD50 (1), RAD54L (1), and RECQL4 (1). Conclusions: In summary, we presented the large-scale genomic profiling of EA in the Chinese population and demonstrated emphasizes the importance of molecular characterization in facilitating clinical decision-making and improving patient outcomes in EA.