bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical outcomes in patients with post-chemotherapy residual non-retroperitoneal (RP) disease in non-seminomatous germ-cell tumors (NSGCT).
Authors: King Jennifer , Ashkar Ryan , Kesler Kenneth , Althouse Sandra K. , Hanna Nasser H. , Einhorn Lawrence H. , Adra Nabil 
Published: June 2023

e17027 Background: In patients (pts) with metastatic NSGCT, the presence of teratoma in the primary tumor specimen or in the post-chemo RP lymph node dissection (RPLND) has previously been shown to have no impact on prognosis. We report clinical outcomes of pts based on pathology in primary tumor and from post-chemotherapy non-RP disease surgical resection. Methods: The prospectively maintained Indiana University testicular cancer database was queried for pts with metastatic NSGCT treated between 1990-2021 who completed first-line chemotherapy and had residual extra-RP disease in the absence of residual RP disease. Pts who had post-chemo non-RP surgical resection were included. Kaplan-meier methods were used to analyze progression-free survival (PFS) and overall survival (OS). Results: 131 pts met eligibility. Median age at diagnosis was 28.6 (range, 16.2-51.5). Primary site was testis in 130 pts (99%). Primary tumor predominant histology was embryonal (34.4%), mixed (26%), choriocarcinoma (14.5%), teratoma (11.5%), yolk sac (10.7%), seminoma (1.5%). Metastatic sites at diagnosis were lung (27.5%), brain (19.8%), RP (14.5%), liver (8.4%), mediastinal LN (7.6%), bone (7.6%). All pts with RP mets at diagnosis had normalization of RP nodes after chemo. All pts had surgical resection of non-RP disease. None had RPLND. IGCCCG risk was good in 56, intermediate in 23, and poor in 52 pts. Median pre-chemo AFP was 66.7 (0.9-467,000). hCG was 692 (0.5-500,000). First-line chemo was BEPX4 in 68, BEPX3 in 29, EPX4 in 10, VIPX4 in 8, and other in 16 pts. 76 pts (58%) had teratoma in the primary tumor. Median follow-up was 3.16yrs. 2-yr PFS for pts with teratoma in primary was 59% (95% CI 45-71) vs. 54% for pts without (95% CI 38-67); p = 0.42. 2-yr OS for pts with teratoma in primary was 85% (95% CI 73-92) vs. 70% for pts without (95% CI 54-81); p = 0.18. 2-yr PFS and OS based on pathology and location of non-RP site are listed in Table 1. Conclusions: The presence of teratoma in primary tumor and post-chemotherapy non-RP resections is not associated with worse PFS or OS in pts with metastatic NSGCT. [Table: see text]
Chemotherapy induced peripheral neuropathy (CIPN) and biomarkers of gut microbial translocation in long-term survivors of testicular germ cell tumors.
Authors: Chovanec Michal , Kalavska Katarina , Obertova Jana , Palacka Patrik , Rejlekova Katarina , Sycova-Mila Zuzana , De Angelis Valentina , Orszaghova Zuzana , Lesko Peter , Svetlovska Daniela , Mladosievicova Beata , Mardiak Jozef , Vlkova Barbora , Pastorek Michal , Celec Peter , Mego Michal 
Published: June 2023

e17032 Background: Survivors of testicular germ cell tumors (GCT) may suffer from long-term treatment induced peripheral neuropathy. We hypothesized markers of gut microbial translocation after chemotherapy and/or radiotherapy may be contributing factors of peripheral neuropathy. Methods: GCT survivors (N = 194) from National Cancer Institute of Slovakia completed the EORTC QLQ Chemotherapy-Induced Peripheral Neuropathy (CIPN20) questionnaires during their annual follow-up visit at 10-year median (range 2-25). Biomarkers of gut microbial translocaion and dysbiosis (GMT) lipopolysaccharide (LPS), high mobility group box-1 (HMGB-1), d-lactate and sCD14 were measured from peripheral blood obtained during the same visit. Upon obtaining the scores from questionnaires per recommended guidelines, each score was correlated with biomarkers of GMT scored as as high or low (above and below median). Survivors were treated with orchiectomy only (N = 30), cisplatin-based chemotherapy (N = 135), radiotherapy to the retroperitoneum (N = 14) or both chemotherapy and radiotherapy (N = 10). Results: GCT survivors with higher vs lower plasma levels of HMGB-1 had worse overall CIPN20 score (median ± SD = 18 229.0 ± 13 644.2 vs 17 387.0 ± 5106.6 p = 0.048). Patients with higher vs lower plasma HMGB-1 also had worse motor function (9.0 ± 1.8 vs 8.0 ± 2.3, p = 0.036). Sensory and autonomy subscales of CIPN20 qestionaire did not show significant association with HMGB-1 (both P > 0.05). There was no significant difference in CIPN20 symptom burden associated with LPS, d-lactate and sCD14 (all P > 0.05). Conclusions: HMGB-1 may serve as a promising biomarker of CIPN20 in long-term cancer survivors. Proinflammatory pathways are suggested as underlying mechanism of CIPN. Furhter research and larger patient cohorts are needed to explore the pathogenesis of CIPN in GCT survivors.
Analysis of hospitalizations of patients with penile cancer: A national population-based study.
Authors: Kanemo Philip Onyekaoso , Akhiwu Ted , Olafimihan Ayobami Gbenga , Edigin Ehizogie , Ijeli Anthonia , Ibrahim Muhammad Bilal , Aihie Osaigbokan , Castillo Dan Ran , Riaz Muhammad Nauman 
Published: June 2023

e17033 Background: Penile cancer (PC) is a rare malignancy that is more common in developing countries. However, recent studies have shown rising incidence-based mortality in the United States (U.S). National population data is scarce on reasons for hospitalizations, epidemiology, and hospitalization outcomes of patients with PC. Methods: Data were abstracted from the National Inpatient Sample (NIS) 2020 Database. T≥his database is the largest collection of inpatient admission data in the U.S. It is a 20-percent stratified sample of all discharges from U.S. community hospitals, excluding rehabilitation and long-term acute care hospitals. The numbers in the databases are weighted to optimize national estimates. Hospitalizations for patients with PC were obtained by searching for hospitalizations that contained the International Classification of Diseases (ICD)-10 code “C60” as a principal or secondary diagnosis. The principal diagnosis is the main reason for the admission, while any other diagnosis other than the principal, are secondary diagnosis. The reason for hospitalization (or principal diagnosis) was recorded in descending order of frequency based on the ICD-10 code organ system category and specific principal diagnosis. The total number of PC discharges, baseline demographic characteristics, hospital length of stay (LOS), and total hospital charges were recorded. STATA 16 was used for analysis. Since NIS contains de-identified data, Institutional Review Board (IRB) review was waived. Results: There were 32 million discharges included in the 2020 NIS database. Of those, 2,785 hospitalizations were for patients aged ≥18 years, who had either a principal or secondary ICD 10 code for PC. Patients were predominantly white (65.9%), mean age of 66.5 years, inpatient mortality of 4.7%, mean LOS of 6.1 days, and mean total hospital charge of 71,447 U.S dollars. The 7 most common reasons for hospitalization by ICD 10 code categories were neoplasm and hematological (35.9%), nonspecific (17.3%), infections (12.6%), injury & poisoning (7.1%), cardiovascular (6.4%), and Genito-urinary (4.3%). The 5 most common specific principal diagnoses for hospitalizations were malignant neoplasm of the penis (29.1%), admission for chemotherapy (12.7%), sepsis (2.7%), Malignant neoplasm of the glans penis (2.2%), secondary neoplasm of inguinal and lower limb nodes (1.8%). Conclusions: Hospitalized PC patients are mostly elderly white men. Infections, chemotherapy, and PC were the most common reasons for hospitalizations. Optimal management of underlying malignancy, prevention, and prompt treatment of infections in the outpatient is important in reducing hospitalizations of these patients.
Luminal and basal subtyping of circulating tumor cells and influence on outcomes in patients with metastatic castration-resistant prostate cancer.
Authors: Wang Jasmine Jiemei , Kim Minhyung , Teng Pai-Chi , Jan Yu Jen , Chen Jie-Fu , Zhu Yazhen , You Sungyong , Tseng Hsian-Rong , Posadas Edwin Melencio 
Published: June 2023

e17034 Background: Luminal and basal subtyping using PAM50 classifier and the prostate cancer classification system (PCS) have been shown to predict outcomes and treatment response in prostate cancer (PCa). However, these genomic classifiers rely on the acquisition of tumor samples, which are usually not available in patients with metastatic castration resistant PCa (mCRPC). Circulating tumor cells (CTC) are tumors cells shed into bloodstream and can serve as surrogates of tumor. In this study, we aimed to subtype circulating tumor cells with PAM50 and PCS classifiers and evaluate their prognostic performance in mCRPC patients. Methods: A CTC RNA assay was developed by combining NanoVelcro microfluidic system for enriching CTCs and Nanostring nCounter system for PAM50 and PCS profiling of CTCs. The PAM50 and PCS genes were refined through a bioinformatic pipeline to ensure the specific profiling of CTCs. The classification and prognostic performance of the refined CTC-PAM50 and CTC-PCS gene panels were validated in GenomeDx GRID database. For the clinical study, 50 blood samples from mCRPC patients before the initiation of androgen receptor signaling inhibitors (ARSI) (n = 34) or taxanes (n = 16) were analyzed with the CTC RNA assay. Kaplan-Meier analysis and log-rank test were used to evaluate the association between CTC-PAM50/PCS subtypes and survival. Results: The refined CTC-PAM50 (36 genes) and CTC-PCS (40 genes) classifiers retained their original classification and prognostic performance in the GenomeDx GRID cohort. In the clinical study, the CTC RNA assay classified the 50 mCRPC patients into luminal A (n = 14), luminal B (n = 22), and basal (n = 14) by CTC-PAM50 classifier; and PCS1 (n = 5), PCS2 (n = 24), and PCS3 (n = 21) by CTC-PCS classifier. Overall, patients assigned as PCS1 subtype had shorter overall survival than other subtypes (hazard ratio [HR] = 4.8). In addition, basal or PCS1 subtype showed worse biochemical progression free survival than other subtypes (ARSI group: Basal: HR = 2.5; PCS1: HR = 6.9. Taxanes group: Basal: HR = 5.0; PCS1: HR = 7.2). Conclusions: Luminal and basal subtyping of CTCs is prognostic and provides a noninvasive method for molecular profiling mCRPC patients.
A phase Ib/II study of intermittent talazoparib plus temozolomide in patients with metastatic castration-resistant prostate cancer (mCRPC) and no mutations in DNA damage repair (DDR).
Authors: Autio Karen A. , Kyriakopoulos Christos , Xiao Han , Emamekhoo Hamid , Danila Daniel Costin , Devitt Michael Edward , Riedel Elyn , Jan Mehrin , Scher Howard I. 
Published: June 2023

e17036 Background: Poly (ADP-ribose) polymerase (PARP) inhibition exhibits an enhanced cytotoxic effect in cancers with DDR alterations, but as monotherapy has little activity for those without DDR defects. A variety of combinatorial methods utilizing PARP inhibitors are under investigation to determine if a multimodal approach could benefit patients without DDR alterations. Supported by pre-clinical models, we hypothesized that the PARP inhibitor talazoparib in combination with the chemotherapy temozolomide could induce DNA damage leading to cell death and tumor response. Methods: This is a single arm Phase 1b/2 study of escalating doses of intermittent talazoparib (Day (D) 1-6) plus temozolomide (D2-8) in 28D cycles in patients with mCRPC without DDR mutations. Patients must have failed at least one androgen receptor signaling inhibitor and may have received chemotherapy in the hormone sensitive setting. Response is determined by a composite endpoint of overall response per RECIST v1.1, PSA50% decline, and CTC conversion from >1 to 0. Pharmacokinetic samples were collected, and the mTPI-2 method was used in escalation. Results: 13 patients were enrolled across 4 dose levels in escalation. The most common adverse events were anemia (any grade (Gr) 31%, Gr3 23%), thrombocytopenia (any Gr 54%, Gr3+ 30.7%), fatigue (Gr≤2, 62%), and nausea (Gr1 46%). There was one patient with a DLT (Gr3 neutropenic fever, Gr4 thrombocytopenia). The identified RP2D was talazoparib 1 mg (D1-6) and temozolomide 75mg/m2 (D2-8). 4 (30.8%) patients met the efficacy endpoint (3 CTC responses, 1 PR, 0 PSA50% decline). While there were no PSA50 responses, 2 (15.4%) patients had a PSA30% decline. Median duration on trial was 20 weeks with 4 (30.8%) patients on trial for ≥6mos, 2 of whom also met the efficacy endpoint. Conclusions: Hematologic toxicity was dose limiting in this combination strategy using intermittent dosing of talazoparib and temozolomide in patients with mCRPC without DDR alterations. A reduction in CTCs to 0 was identified at several dose levels, and PSA30% declines were seen in 2 patients. With identification of the RP2D, enrollment in the Phase 2 study is currently underway. Clinical trial information: NCT04019327 .
Randomized placebo-controlled trial of intravenous vitamin C plus docetaxel in metastatic prostate cancer.
Authors: Paller Channing Judith , Zahurak Marianna , Heath Elisabeth I. , Kelly William Kevin , Hoimes Christopher J. , Taksey Jason David , Marshall Catherine Handy , Markowski Mark Christopher , Barata Pedro C. , Rudek Michelle A. , Nauroth Julie , Wang Lin , Durham Jennifer N. , Eisenberger Mario A. , Carducci Michael Anthony , Denmeade Samuel R. , Levine Mark 
Published: June 2023

e17050 Background: Some phase I/II trials showed that combining high dose IV vitamin C with chemotherapies decreased toxicities and improved QoL in advanced cancers, while others failed to show benefits. While grade ¾ AEs are not typically a co-primary endpoint, they are a measure of cumulative toxicity. We investigated whether high-dose IV vitamin C could improve prostate-specific antigen (PSA) response rate and mitigate docetaxel toxicities in patients with metastatic castrate-resistant prostate cancer (mCRPC) receiving docetaxel. Methods: Patients were randomized (2:1) to receive docetaxel (75mg/m2 IV every 3 weeks) plus IV vitamin C (1g/kg) or placebo twice a week. The primary endpoints were PSA50 response by24 weeks and adverse events (AEs) of fatigue, nausea, bone pain, and anorexia. Secondary endpoints included overall survival (OS) and QoL measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P). Results: 50 patients were randomized, 47 received therapy (treatment N = 32, control N = 15), 3 untreated (withdrawal, elevated creatine, low hemoglobin). The median age was 74 years (range 45-85) and ECOG 1. The median PSA was 108.3 ng/mL (range: 0.3, 2102.3). The median number of chemotherapy cycles was 6 (IQR 3-8). The study was suspended after the pre-specified interim analysis for primary endpoints showed futility. The PSA50 response was 41% for treatment and 33% for control (P = 0.44). Grade 1-2 and grade 3-4 prespecified AEs occurred in 69% and 6% of treatment group patients versus 60% and 0% of control group patients (one-sided Cochran Armitage test, P =0.90). Diarrhea (72% vs 19%) and anemia (47% vs 25%) and neutropenia (22% vs 19%) are more frequent in the Vit C group. Compared with the control group, treatment group patients showed a trend towards shorter median OS. FACT-P was not significantly different at any timepoints. Conclusions: Initial concurrent high-dose IV vitamin C with docetaxel did not improve PSA response, toxicity, or clinical outcomes. MCRPC patients receiving docetaxel should be advised against seeking concurrent high-dose IV vitamin C. Clinical trial information: NCT02516670 .
Understanding testing for and treatment of homologous recombination repair (HRR)-mutated metastatic castrate-resistant prostate cancer (mCRPC): A quality initiative by Integra Connect (IC) PrecisionQ.
Authors: Thomas Roby Antony , Gart Mike , Blanc Simon , Choksi Rushir J. 
Published: June 2023

e17052 Background: In May of 2020, the approval of two Poly (ADP-ribose) polymerase inhibitors (PARPi) changed the landscape for treatment among patients (pts) with HRR mutations (HRRm) in mCRPC. The University of Pittsburgh Medical Center (UPMC) conducted a quality initiative (QI) with IC PrecisionQ to assess the rates of HRR testing, HRR positivity, and study the rates of PARPi use in HRRm patients with mCRPC. This QI included clinical interventions to optimize testing and treatment in these patients. We aim to show the improvement in HRR testing and rates of treatment with PARPi after implementation of the QI, in patients with HRRm mCRPC at UPMC. Methods: Using the de-identified IC PrecisionQ database, 223 UPMC pts with mCRPC were selected by medical chart curation as baseline group. Patients in the baseline group had received treatment between 5/1/2020 to 9/30/2021 that were confirmed as mCRPC. The baseline data was reviewed with UPMC clinical leadership, discussed among a physician roundtable, and HRR testing rates were shared among providers. Post-baseline, we evaluated 152 mCRPC pts who started a new line of therapy between 1/1/2022 to 12/31/2022 to assess HRR testing rates and use of PARPi in eligible mCRPC pts. The presence of one or more HRR genes was used to determine testing rates. Descriptive analyses were performed and a two-proportion z-test was used for comparisons of HRR testing in patients with mCRPC and treatment with a PARPi in HRRm mCRPC pts. Results: The average age at diagnosis was 67 years, 47% of patients had a Gleason score of > = 8, and 62% were stage IV. The rate of HRR testing at baseline was 52% (116 of 223). The results post baseline and intervention showed an increase in HRR testing to 69% (105 of 152) of mCRPC patients who started a new line of therapy in 2022 (p < 0.01). At baseline, 60% (21 of 35) of HRRm pts were treated with a PARPi after prior NHA treatment compared to 68% (19 of 28) post baseline and intervention (p > 0.05). Among all HRR mCRPC tested pts, there was a 30.9% (84/272) positivity rate, of which 11.4% were BRCA1/2 positive (30/262) and 10.5% were ATM positive (26/247). Not all patients tested for HRR were tested for all genes. Conclusions: This quality initiative to improve testing and identification of HRR mutations in patients with mCRPC led to a 33% relative increase in HRR testing. Quality initiative programs are critical to transforming cancer care and moving the field closer toward individualized, precision medicine.
Real-world genetic testing patterns in metastatic prostate cancer in Latin American (LATAM) population.
Authors: Angel Martin , Freile Berenice , Rodriguez Andres , Cayol Federico , Manneh Kopp Ray , Rioja Patricia , Losco Federico , Bernal Vaca Laura , Penaloza Jose Mauricio , Zapata Muñoz Maycos Leandro , Neciosup Silvia P. , Sade Juan Pablo 
Published: June 2023

e17055 Background: Prostate cancer (PC) clinical course is variable. It was thought that BRCA1 and BRCA2 mutations were associated with only a small proportion of PC cases. However, recent genomic analysis has revealed that germline or somatic inactivating mutations in genes involved in the homologous recombination (HR) pathway of DNA repair collectively occur in as much as 20%-25% of advanced PC. Referring to the metastatic castration resistant PC (mCRPC) the somatic mutations were recently reported to be up to 12,7% for BRCA2 and 2% for BRCA1. PC is the most frequent tumor among LATAM men. The incidence of de novo metastatic PC is higher in LATAM than other parts of the world, and demographic changes in the region have increased disease burden. However, region-specific information about genomic profiling of this tumor is scant. This study aims to describe the genomic profile patterns of PC, either presenting as metastatic hormone treatment–naive prostate cancers, or locoregional tumors that later evolve to metastatic disease in LATAM pts. Methods: A retrospective observational cohort design was used. The study sample included patients with a confirmed PC diagnosis with adenocarcinoma histology, from 8 academic centers in 3 countries between 1st January 2020 and 30th November 2022 whom had been molecularly tested. Results: Of 185 pts tested, 183 had metastatic PC. Somatic evaluation was done in 49.5% of the pts, while 66.48% have germline test, 13% pts were tested by both methods. Forty-two (22.7%) pts were tested in the metastatic sensitive castration scenario, instead 141 (76.2%) were mCRPC. Actionable mutations were detected in 21 pts (11.35%), being the most frequents PTEN and BRCA2. The median tumor mutational burden was 5 (IQR 0-2.52). No mutation in the following clinically relevant genes were found in our pts: BRCA1, RAD51C, RAD51D, RAD54, PALB2 and BRIP1 (Table1). Between pts with actionable mutations, 27.3% had high volume disease, with a median Gleason score of 9 (IQR 8-9) and de novo metastatic setting in 40.9%. Despite that 25.9% of our pts have a VUS (Variant of unknown significance), only 7 pts (3.8%) access to oncology genomic counseling. Conclusions: In our region, the percentage of actionable mutations found in this population appears to be lower than that reported in studies from other regions of the world, but remarkably the mutations detected are different. This data shows the importance to have mutational data of the population of each region what is heterogeneous among themselves and with respect to other regions of the world. [Table: see text]
Efficacy of PARP inhibitors in patients with metastatic castration resistant prostate carcinoma: A meta-analysis of phase III randomized controlled trials.
Authors: Patel Rushin , Oyenuga Mosunmoluwa , Onyechi Afoma , Chitkara Akshit , Sartaj Sara , Mohamed Mohamed G , Patel Zalak , Patel Mrunal 
Published: June 2023

e17060 Background: PARP inhibitors effectively treat several solid tumors, regardless of the presence of BRCA mutations. Patients with castration-resistant metastatic prostate cancer become refractory to androgen deprivation therapy. PARP inhibitors were recently approved for use in prostate cancer, and have opened new avenues in prostate cancer treatment research. Methods: We systematically searched multiple databases using pre-specified search terms. We included only phase III RCTs comparing PARP inhibitors versus standard of care in patients with castration-resistant biopsy-proven metastatic prostate cancer. The outcomes studied were radiologically guided progression-free survival (PFS) and overall survival (OS). We used a random effects model via RevMan 5.4 software for statistical analysis. Results: 3 phase III RCTs met the inclusion criteria with a total of 1606 patients (PARP inhibitors = 867 patients, standard of care = 739 patients). Compared to the standard of care, PARP inhibitors showed significantly higher PFS [HR = 0.62( 95% CI, 0.49-0.78) P < 0.0001]. There was no statistically significant difference in OS [HR = 0.85( 95% CI, 0.69-0.1.04) P = 0.11] between the two groups. Conclusions: The use of PARP inhibitors in patients with castration-resistant metastatic prostate cancer is associated with improved progression-free survival. No significant difference was observed in overall survival between the two groups. There is a need to study the cost-benefit analysis of using PARP inhibitors as they do not show any improvement in overall survival. [Table: see text]