bluuebunny/crossref_metadata_2025_split huggingface dataset:
Germline genetic testing of patients with penile carcinoma.
Authors: Sonpavde Guru P. , Nielsen Sarah M. , Heald Brandie , Hatchell Kathryn E. , Esplin Edward D. , Nassar Amin 
Published: March 2023

10 Background: Penile carcinoma (PeCa) is a rare malignancy with a mean age at diagnosis of 60 years. PeCa is epidemiologically associated with phimosis, HPV, HIV, tobacco, obesity, Psoralen and ultraviolet A photochemotherapy and lichen sclerosis. However, the prevalence and type of pathogenic germline variants (PGVs) associated with PeCa are unknown. Methods: A retrospective cohort of patients (pts) with PeCa who underwent germline testing (range of genes tested, 1-134) from 10/2016 to 5/2022 at a large commercial laboratory (Invitae) was evaluated. Clinician-reported clinical and demographic information from test requisition forms (TRF) were analyzed and the frequency and type of PGVs was determined. Pts were identified via keywords and/or ICD-10 codes for PeCa, but the final study cohort was limited to those whose diagnosis could be corroborated by details in the TRF and/or accompanying medical records. Pts with other pathologies were excluded. Results: Of the 29 pts who met inclusion criteria, the majority were White (65.5%), with a median age (range) of 62.5 years (36-79) at diagnosis. 44.8% of pts had documented squamous cell carcinoma (SCC) pathology, 55.2% of pts had an additional non-PeCa cancer, and 62.1% of pts had a documented family history of relevant cancers (penile, prostate, breast, ovarian, pancreatic and/or colorectal). Among 29 pts with PeCa, 3 harbored PGVs (10.3%) and 16 (55.2%) had > 1 variants of uncertain significance (VUS) in the absence of a PGV. Of the 3 positive pts, 2 harbored BRCA2 PGVs and one harbored a RAD51C PGV. One pt with a BRCA2 PGV had additional malignancies of the prostate and pancreas. Conclusions: This is the first study to our knowledge reporting PGVs in PeCa. PGVs in DNA repair genes ( BRCA2, RAD51C) were identified in 10.3% of selected high-risk PeCa pts with the majority exhibiting other malignancies or family history of malignancies. Larger cohorts of PeCa patients should be studied in pts with different ethnicities. Nonetheless, these data highlight the potential role of germline testing in selected PeCa pts as a tool to aid in clinical management, cascade testing and potential therapeutic relevance in the future.
Investigating documented reasons for withdrawal from clinical trials for patients with advanced prostate cancer (PCa).
Authors: Lloyd Jennifer , Nordblad Blake , Sahu Kamal Kant Kant , Swami Umang , Phunrab Tenzin Kunsang , Batten Julia Anne , Maxwell Lindsay , Kohli Manish , Gupta Sumati , Maughan Benjamin L. , Agarwal Neeraj 
Published: March 2023

105 Background: In clinical trials, treatment efficacy rates are based on participants who can tolerate treatment through study endpoints. Attrition from clinical trials can potentially lead to biased results (PMID: 30379822). Many oncology clinical trials censor the subject data of participants because of early trial intervention discontinuation due to adverse events (AEs), withdrawal of consent, or loss to follow-up. Despite high attrition rates reported across various oncology clinical trials (10-38%), there is inconsistency regarding investigating the reasons for withdrawal (PMID: 23132290). We aim to identify the causes of the withdrawal of participants with advanced PCa from clinical trials. Methods: In this IRB-approved single-center retrospective study (Sept 2014 to Sept 2022), the OnCore Research Database was used to capture data on the participants with advanced PCa enrolled in clinical trials. The included trials were specific to prostate cancer, and mixed solid tumor trials were excluded. Endpoint reports from all included trials were assessed. Participants who discontinued treatment for any reason were included. The primary objective was to obtain reasons for clinical trial withdrawal before primary endpoints, identify potential clinical intervention areas, and determine potential areas of adjustment to future study designs to improve retention rates. Eligibility criteria: diagnosis of metastatic prostate cancer, receipt of protocol treatment until discontinuation, and documentation of a reason for discontinuation of the protocol treatment. Results: 272 pts from the 18 clinical trials met eligibility criteria and were included in the study. The most common reasons documented for discontinuation were: the progression of disease (46.69%), other reasons (15.44%), adverse events (5.15%), personal preference (15.81%), and completion of protocol treatment (11.76%) of the total number of enrolled participants. We noted a statistically significant difference between participants who withdrew for other reasons in the castration-resistant versus castration-sensitive setting (6.08% vs. 32.38%, p value=0.03). Notably, declining performance status and symptom progression were listed under the “other reasons” category. The documentation of patient withdrawal due to clinical symptoms was reported across multiple withdrawal categories. Conclusions: In approximately one-third of participants, the reason for protocol treatment discontinuation was not apparent (documented as patient preference and other reasons with no further specifications). Further exploration of the exact reasons contributing to therapy discontinuation in these patients will be critical to improving patient retention in clinical trials.
Clinical outcomes of abiraterone acetate (AA) or enzalutamide (E) as first-line therapy (Rx) for men aged ≥75 with metastatic castration-resistant prostate cancer (mCRPC) according to previous use of docetaxel (D) for metastatic castration-sensitive prostate cancer (mCSPC) in a multicenter international registry: A SPARTACUSS – Meet-URO 26 study.
Authors: Lee-Ying Richard M. , Saieva Calogero , Nuzzo Pier Vitale , Malgeri Andrea , Fotia Giuseppe , Zanardi Elisa , Rossetti Sabrina , Valenca Loana Bueno , Patrikidou Anna , Modesti Mikol , Martins Oliveira Thiago , Pignata Sandro , Fornarini Giuseppe , Procopio Giuseppe , Santini Daniele , Sweeney Christopher , Heng Daniel Yick Chin , De Giorgi Ugo , Russo Antonio , Francini Edoardo 
Published: March 2023

107 Background: The optimal management of mCRPC in men aged ≥75 is challenging, and there is a paucity of clinical data in the literature. Although AA and E are commonly used as 1st line Rx for mCRPC, it is unclear whether use of upfront D for mCSPC may impact their clinical efficacy or safety in this elderly population. Methods: Patients aged ≥75 who started AA or E as 1st line Rx for mCRPC within January 2015 - April 2019 were identified from the IRB approved databases of 10 institutions in Europe, South and North America. Demographic and clinicopathological data were collected from available medical records, including Gleason, prior local therapy, newly diagnosed metastatic disease, disease volume, ECOG, PSA and sites of metastases. Patients were classified by use of upfront D for mCSPC. The primary endpoints were overall survival (OS) from AA/E onset and OS from ADT start and safety of AA/E. The endpoints distributions including median (95% CI) were estimated by Kaplan-Meier method. Results: Of the 337 patients selected, 24 (7.1%) received ADT+D and 313 (92.9%) ADT alone for mCSPC. Patients with ADT+D tended to be younger (78 vs 81, p=0.022) and, albeit not statistically significant, had higher rates of Gleason score >8 (81.0% vs 62.6%, p=0.10), newly diagnosed (83.3% vs 65.6%, p=0.08) and high volume disease (45.8% vs 34.6%, p=0.28), compared to those with ADT alone. Median follow-up was 18.8 months. No significant difference of OS from ADT start or from AA/E onset was observed between the 2 cohorts (see table). Despite OS from ADT start being longer in those having ADT+D, OS from AA/E start was approximately 2 years in both cohorts. Rates of adverse events (AEs) of any grade (58.3% vs 52.1%, p=0.67) and grade ≥3 (12.5% vs 15.7%, p=1.0) did not significantly differ between the 2 cohorts. Conclusions: While limited by small sample size for ADT+D and retrospective study design, patients aged ≥75 having AA/E as 1st line mCRPC Rx showed similar survival outcomes and tolerability regardless of previous use of D for mCSPC. [Table: see text]
Disparities in germline testing by race/ethnicity and preferred language in patients with prostate cancer.
Authors: Thorn Annelise , Gordon Kelly , Tong Barry , Kwon Daniel H , Dhawan Mallika Sachdev , Borno Hala , Aggarwal Rahul Raj , Small Eric Jay , Blanco Amie 
Published: March 2023

112 Background: A remote Genetic Testing Station (GTS) workflow was implemented at an academic medical institution to expand access to genetic testing for patients with prostate cancer. During a telephone appointment, a genetic counselor assistant collects family history and facilitates genetics education, research consent, and remote sample collection for multi-gene panel testing. We compared testing completion and patient loss from workflow based on race/ethnicity and preferred language to identify disparities. Methods: Metrics were collected prospectively and analyzed retrospectively for patients with metastatic or high-grade prostate cancer referred to genetics between 3/15/2020 – 6/30/2022. Self-reported race, ethnicity, and preferred language were collected by chart review. Testing completion was compared between groups using Fisher’s exact test, with White non-Hispanic (WNH) and Preferred Language English (PLE) cohorts as controls. Odds ratios and 95% confidence intervals were reported. Patient loss at workflow checkpoints (scheduling, consenting, sample collection, and results release) was summarized for each group. Results: 827 eligible patients were identified: 78 (9%) Asian /Pacific Islander (API), 51 (6%) Black non-Hispanic (BNH), 42 (5%) Hispanic, and 625 (76%) WNH. 31 patients reporting other non-Hispanic race were not included in the analysis. 30 patients (4%) self-reported Preferred Language non-English (PLNE) and 797 (96%) PLE. BNH patients were significantly less likely to complete testing compared to WNH patients (OR 0.320, 95%CI: 0.168, 0.632, p<0.001). There was no difference in testing completion in API (OR 0.918, 95%CI: 0.467, 1.944, p=0.797) or Hispanic (OR 0.743, 95%CI: 0.325, 1.918, p=0.466) compared to WNH patients. PLNE were significantly less likely to complete testing (OR 0.393, 95%CI: 0.171, 0.965, p=0.016) compared to PLE patients. Patient loss occurred primarily at consenting and sample collection. 14% of BNH, and 9% of Hispanic patients did not consent, compared to 4% of WNH. 17% of PLNE did not consent compared to 5% of PLE patients. 13% of BNH did not return a sample, compared to 3% of WNH patients. Conclusions: In remote GTS, BNH and PLNE patients were significantly less likely to complete germline testing than WNH and PLE patients respectively. Disparities in patient loss were most pronounced at consenting and sample collection. Measures to mitigate disparities include assisted consenting (with interpreter as needed) and video-assisted or in-clinic sample collection. [Table: see text]
A retrospective review of primary prophylaxis with granulocyte-colony stimulating factor (G-CSF) for patients with genitourinary malignancies receiving chemotherapy during the COVID-19 pandemic and implications for the future.
Authors: Diaz Mejia Nely Mercy , Stecca Carlos , Jiang Di Maria , Fallah-Rad Nazanin , Bedard Philippe L. , Kumar Vikaash , Abdeljalil Osama , Zahralliyali Amer , Alqaisi Husam , Al-Ezzi Esmail Mutahar , Choy Vivian , Banwait Parmvir , Atenafu Eshetu , Sridhar Srikala S. 
Published: March 2023

115 Background: To mitigate the risks of chemotherapy associated neutropenia, during the COVID-19 pandemic, all genitourinary (GU) cancer patients treated with chemotherapy at the Princess Margaret Cancer Centre (PMCC) were offered primary prophylaxis with GCSF. We hypothesize that this reduced rates of febrile neutropenia, hospitalizations, healthcare costs and improved overall outcomes, compared to GU cancer patients treated with chemotherapy without GCSF in the 2 years prior to the pandemic. Methods: We performed a retrospective review of GU cancer patients, receiving curative or palliative intent chemotherapy, with or without primary GCSF prophylaxis between January 2018 and June 2022. GCSF was given either as a single dose or as consecutive doses post chemotherapy. Main outcomes were incidence of febrile neutropenia, hospitalization, health care expenditures as well as disease specific outcomes. Results: Overall, 248 patients with prostate cancer (44%), urothelial cancers (33%) germ cell (21%), and rare GU cancers (4%) were identified. Median age was 70 (range 19-91), 92% were male, 65% were ECOG 0/1. Treatment intent was neoadjuvant (13%), adjuvant (20%), or palliative (67%). Main regimens used were docetaxel, cabazitaxel, carboplatin, cisplatin/etoposide, gemcitabine/cisplatin and BEP. Median follow-up was 10.5 months (0.23-52.3 months). A total of 206/248 received primary GCSF prophylaxis. During chemotherapy, the median white blood cell levels were higher in the GCSF group compared to the non-GCSF group (14.1*10*9/L vs 2.90*10*9/L, p<0.0001); and neutropenia rates were markedly lower (2% vs. 93%, P=<0.0001). Hospital admission rates were significantly lower in G-CSF users compared to non-users (19% vs. 69%, P<0.0001). Symptomatic disease progression 13% was the leading cause of admission in the G-CSF group. Infectious causes such as UTI, pneumonia, COVID-19, and sepsis were seen in only 12% of the G-CSF group compared to 31% in the non-users. G-CSF was generally well tolerated with just 0.97% discontinuing G-CSF. Conclusions: During the COVID-19 pandemic, primary prophylactic G-CSF use in GU cancer patients, undergoing chemotherapy significantly lowered rates of both febrile neutropenia and hospitalizations and could be a cost-effective strategy in this patient population that warrants further study.
Survival outcomes and toxicity in older adults with metastatic castration-resistant prostate cancer (mCRPC) treated with androgen receptor targeted (ART) therapies.
Authors: Mellgard George Slade , Chakrani Zakaria , Mccroskery Stephen , Saffran Nathaniel , Taylor Nicole , Liaw Bobby Chi-Hung , Galsky Matt D. , Oh William K. , Tsao Kai , Patel Vaibhav G. 
Published: March 2023

117 Background: Prostate cancer (PCa) and especially advanced PCa largely affects older adults with a median age of diagnosis of 67. Despite ART’s role as a mainstay of treatment (tx) in advanced PCa, little is known about its risks/benefits in older adults. We aimed to examine survival outcomes and safety in patients (pts) with mCRPC ≥75 years-old (y.o) on ART. Methods: The records of mCRPC pts treated with ART at the Mount Sinai Hospital between 2010 and 2021 were screened for demographics, medical history, ART course, tx toxicity, and survival outcomes. PSA progression free survival (PFS) between pts ≥75 y.o and pts ≤75 y.o was assessed as the primary outcome. Secondary outcomes were overall survival (os) and tx toxicity. Tx toxicity was evaluated using physician documented tx side-effects (SE)s. Fischer’s exact was used to compare baseline characteristics and tx SEs. Cox proportional hazards models were used to compare survival outcomes. Results: Of 153 pts, 97 were < 75 y.o and 56 were ≥75 y.o. Within the <75 y.o group, 17 (17.5%) were post-chemo compared to 7 (12.5%) in the ≥75 group (p = .493) Relevant baseline characteristics (ECOG ≥2, Race, Gleason 4-5, hospitalizations, and CCI) were not significantly different. Median PSA PFS was 14.2 (≥75 y.o) and 17.3 months (<75 y.o) with no significant difference on univariate or multivariate analysis (HR: 1.1 [0.69, 1.74;] p = 0.697. Median OS was 32.4 months for the ≥75 y.o cohort and 32.3 months for the <75 y.o cohort (HR: 1.38 [0.88, 2.17;] p = 0.156). The 5 most common SEs by group are reported below. Of note, adults ≥75 y.o were more likely to report edema compared to the <75 y.o pts (8.2% vs 21.4%, p-value = .026). Conclusions: Pts ≥75 on ART experienced similar survival benefits compared with pts <75. While older adults were more likely to report edema, overall tx toxicity profiles did not differ significantly. Ultimately, these findings ground evidence-based counseling and tx for older adults with mCRPC considering ART. [Table: see text]
Clinical characteristics and outcomes of trial-ineligible patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) receiving androgen receptor targeted (ART) therapy.
Authors: Mellgard George Slade , Mccroskery Stephen , Chakrani Zakaria , Saffran Nathaniel , Taylor Nicole , Liaw Bobby Chi-Hung , Galsky Matt D. , Oh William K. , Tsao Kai , Patel Vaibhav G. 
Published: March 2023

118 Background: mCRPC pts with significant comorbidities or poor performance status (PS) are often excluded from clinical trials for ART. These cohorts may not be representative of or comparable to real-world pts. We aimed to determine whether (1) baseline characteristics or (2) survival outcomes differed in pts with mCRPC categorized as eligible or ineligible for ART clinical trials. Methods: We screened for pts with mCRPC treated with abiraterone (abi-) or enzalutamide (enza-) at our institution between 2010 and 2021. Baseline characteristics were reviewed at treatment start and ART course recorded. We applied the inclusion/exclusion criteria from clinical trials, COU-AA-301, COU-AA-302, PREVAIL, and AFFIRM, to categorize pts as ineligible or eligible. Fischer’s exact was used to evaluate pt characteristics. Cox proportional hazards model was used to compare survival outcomes. Results: We identified 150 pts with mCRPC who initiated abi- or enza-. 54.7% of pts were deemed trial ineligible. Among pts on abi-, 48 of 86 (55.8%) pts were ineligible. Among those on enza-, 34 of 64 (53.1%) were ineligible. Common reasons for ineligibility included poor PS, radiation during treatment, and trial specific comorbidities. Among ineligible pts, 11% were post-chemotherapy compared to 20.6% of eligible pts (p = .162). Notably, trial ineligible pts were more likely to be non-Hispanic black when compared to trial eligible pts (29.3% vs. 17.6%, p = 0.036). Median OS was 30.2 for ineligible pts and 37.1 for eligible pts p = 0.46). for the ineligible pts and eligible pts respectively and there was no significant difference on univariate or multivariate analyses (HR: 0.84 [0.54, 1.32;]. Conclusions: Pts classified as trial ineligible had comparable survival outcomes when compared to trial eligible pts. Consistent with prior research on systemic racism in clinical trials, ineligible pts were more likely to identify as Black compared to eligible pts. Further research is warranted to confirm safety of ART in ineligible pts and identify strategies for reducing racial disparity gaps in cancer clinical trials.
Patient characteristics and safety of radium-223 dichloride in Taiwan: Analysis of real-world clinical practice.
Authors: Pang See-Tong , Huang Chao-Yuan , Huang Chi-Ping , Huang Yu-Yi , Huang Steven Kuan-Hua , Lu Kevin , Huang William J. , Meng En , Huang Shu-Pin , Lee Ming-Yang 
Published: March 2023

119 Background: Bone metastases commonly develop in patients with metastatic castration-resistant prostate cancer (mCRPC), leading to poor clinical outcomes. Radium-223 (Ra-223) is a bone-targeting radiopharmaceutical that has been shown to improve the overall survival of these patients. Here, we present data on the safety and effectiveness of Ra-223 in patients with mCRPC and symptomatic bone metastases under routine clinical practice in Taiwan. Methods: This prospective, multicenter, single-arm, non-interventional observational study enrolled patients with mCRPC and symptomatic bone metastases. A total of 224 patients were included from July 2020 to January 2022. The patients received Ra-223 (55 kBq/kg of body weight) once every 4 weeks for a maximum of 6 intravenous injections. An exploratory subgroup analysis was conducted in patients who received Ra-223 either as a first-line, second-line or third-line. This first interim analysis of the study assessed the clinical outcomes observed during 6 months of Ra-223 treatment and 1 month after the final or last tolerated injection. Results: The dataset up until September 2021 (n = 104) was available for analysis. Of the 104 patients, 69 (66.3%) received 5–6 injections of Ra-223 while 35 (33.7%) received 1–4 injections. Sixty percent of enrolled patients were chemotherapy-naive. Furthermore, 22 (21.2%), 43 (41.3%) and 39 (37.5%) patients received Ra-223 as a first-, second- or third-line therapy, respectively; 16 (72.7%), 27 (62.8%) and 26 (66.7%) patients in these subgroups received 5–6 injections of Ra-223, respectively. The incidence of any study drug-related treatment-emergent adverse events (TEAEs), hematologic TEAEs and all fracture events were 10.6%, 9.6% and 1.9%, respectively. When compared with the other subgroups, patients on first-line Ra-223 therapy had lower incidences of any drug-related AEs and discontinuation of therapy owing to AEs. In addition, there was a trend observed that better PSA control occurred in patient population using Ra-223 as mCRPC first-line treatment. Conclusions: The study data showed that under routine clinical practice in Taiwan, the rate of Ra-223-associated AEs were low and no new safety concerns were identified with this therapy. First-line Ra-223 therapy was more likely associated with fewer TEAEs and higher rates of completion with the 6-injection course of therapy. A follow-up observation of up to 2 years after the initial injection is on-going. Clinical trial information: NCT04232761 .