bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of household income on prostate cancer diagnosis, treatment, and outcomes.
Authors: Panzone John , Wu Maximillian S , Chandrasekar Thenappan , Basnet Alina , Bratslavsky Gennady , Goldberg Hanan 
Published: June 2023

5038 Background: Financial difficulties can lead to cancer patients delaying or deferring necessary care, resulting in later presentation with more advanced disease and worse clinical outcomes. Methods: A cross-sectional study was conducted assessing 488,853 prostate cancer patients from the Surveillance, Epidemiology, and End Results (SEER) Program between the years of 2010 and 2018. The association between annual household income (HHI) and diagnosis and outcomes of prostate cancer were examined using ANOVA and Chi-square analyses comparing clinical measures based on categorical HHI groupings. Results: Sociodemographic data and univariate analyses are displayed. The average age across all HHI classifications was 66.63 years. ANOVA analysis demonstrated that patients with a lower HHI had higher PSA levels upon diagnosis (12.10 vs. 10.90, 10.61, and 10.37 for <=35k, 35-55k, 55-75k, and >=75k, respectively, p<0.001). Patients with lower HHI also demonstrated lower rates of undergoing surgical treatment (31.9%, 36.9%, 37.6%, and 35.1% for <=35K, 35-55k, 55-75k, and >=75k, respectively, p<0.001) and the highest rate of disease metastasis to bone upon diagnosis (6.3%, 5.6%, 5.7%, and 5.8% for <=35k, 35-55k, 55-75k, and >=75k, respectively, p<0.001). Lastly, patients with lower HHI demonstrated progressively higher rates of cancer-specific-mortality (8.4%, 6.8%, 6.5% and 5.1% for <=35k, 35-55k, 55-75k, and >=75k, respectively, p<0.001), as well as higher overall mortality (21.2%, 18.0%, 15.0%, and 11.9% for <=35k, 35-55k, 55-75k, and >=75k, respectively, p<0.001). Conclusions: In conclusion, these data suggest that prostate cancer patients with lower household income are diagnosed with more aggressive disease, tend to undergo surgery at lower rates, develop more advanced disease, and endure worse clinical outcomes than those in higher income brackets. Healthcare providers should be made aware of the clear associations between lower income and more aggressive disease at diagnosis, lower rates of surgical treatment and worse cancer-specific and overall mortality. [Table: see text]
Evaluation of PAM50 intrinsic subtypes and risk of recurrence (ROR) scores in premenopausal women with early-stage HR+ breast cancer: A secondary analysis of the SOFT trial.
Authors: Brown Lauren Claire , Luen Stephen James , Molania Ramyar , Caramia Franco , Savas Peter , VanGeelen Courtney , Chic Nuria , Fleming Gini F. , Kammler Rosita , Colleoni Marco , Viale Giuseppe , Speed Terence Paul , Regan Meredith M. , Francis Prudence A. , Loi Sherene 
Published: June 2023

504 Background: The landmark Suppression of Ovarian Function Trial (SOFT) in premenopausal breast cancer patients revealed that the addition of ovarian function suppression (OFS) to adjuvant endocrine therapy with either tamoxifen (T+OFS) or exemestane (E+OFS) reduces the risk of recurrence compared with adjuvant tamoxifen alone. There are no biomarkers to aid decision-making about intensification of endocrine therapy with OFS. The purpose of this study is to assess the prognostic and predictive ability of PAM50 intrinsic subtypes and ROR scores in premenopausal women with HR+/HER2- breast cancer in the SOFT trial. Methods: Gene expression analyses were performed via the NanoString Breast Cancer 360 assay on RNA isolated from FFPE tumor samples from the SOFT trial that were HR+/HER2- (n=1245/3047). PAM50 subtype and ROR score were determined centrally by NanoString Technologies (Seattle, WA, USA), blinded to clinical characteristics, treatment and outcome. Median follow-up was 12 years. Primary endpoint in this study was distant recurrence-free interval (DRFI). Secondary endpoints were breast cancer-free interval (BCFI) and disease-free survival (DFS). Kaplan-Meier analysis and Cox proportional hazards regression models, stratified by prior chemotherapy and lymph node status, were used to evaluate the predictive performance of PAM50 intrinsic subtypes and ROR categories (low vs intermediate vs high), and secondarily ROR score as a continuous variable. We also investigated differences between very young (<40yrs) vs young (>40yrs) women. Results: Tumor samples from 1084/1245 (87%) patients successfully completed PAM50 testing and are included in this analysis. Patient characteristics in this cohort were similar to the entire SOFT trial population. Intrinsic subtype and ROR category distribution is described below. Subtype distribution significantly differed between very young vs young premenopausal women, with fewer luminal A and more luminal B and non-luminal tumors seen in the very young (p<0.001). The ROR score distribution also differed significantly: in node-negative patients there were significantly more ROR-high scores amongst very young compared to young women (36% vs 14%, p<0.001). Conclusion: Breast cancer diagnosed in very young women has aggressive disease biology. Prognostic and predictive analyses of both intrinsic subtypes and the ROR score are ongoing and will be presented at the meeting. Clinical trial information: NCT00066690 . [Table: see text]
Bone biomarkers and subsequent survival in men with bone-metastatic hormone sensitive prostate cancer (HSPC): Results from the phase III SWOG S1216 trial of androgen deprivation +/- orteronel.
Authors: Lara Primo N , Mayerson Edward , Gertz Erik , Tangen Catherine , Goldkorn Amir , Van Loan Marta , Hussain Maha H. A. , Gupta Shilpa , Zhang Jingsong , Parikh Mamta , Twardowski Przemyslaw , Quinn David I. , LeBlanc Michael Leo , Thompson Ian M , Agarwal Neeraj 
Published: June 2023

5048 Background: We previously reported that circulating serum biomarkers of bone metabolism were significantly associated with overall survival (OS) in men with advanced prostate cancer, either in the hormone sensitive (Lara, et al. ASCO 2022) or castration resistant state (Lara, et al. JNCI 2016). In S1216, we showed that elevated bone biomarkers were significantly associated with an increased risk of death in HSPC regardless of bone metastases (mets). We also identified three risk groups (low, intermediate, and poor) with differential OS outcomes (median OS: 8.2, 5.1, and 2.1 years, respectively) based on combinations of bone biomarkers in these patients. Here we report the association of bone biomarkers with OS in men with HSPC and documented skeletal mets as part of a planned analysis of S1216. Methods: Bone resorption [C-telopeptide (CTx) and Pyridinoline (PYD)] and bone formation markers [C-terminal collagen propeptide (CICP) and bone alkaline phosphatase (BAP)] were assessed from patient sera. Patients were randomly divided into training (n=238) and validation (n=475) sets. In the training set, recursive partitioning that maximizes discrimination of OS was used to identify the dichotomous cut-point for each biomarker and for a combination of biomarker split points to define prognostic groups. In the validation set, Cox proportional hazards models were used to assess the impact of biomarkers on OS, adjusted for patient and tumor characteristics. Results: Of 1,279 men in S1216, 713 had both baseline bone mets and evaluable bone biomarkers. Patient characteristics were similar between the overall population and the subset with bone mets. Elevated levels of CICP, CTX, and PYD were strongly prognostic for OS, but not for BAP. Hazard ratios (95% CI) for OS adjusted for treatment arm and baseline clinical variables were: BAP – 1.31 (0.93, 1.84), p=0.12; CICP – 1.58 (1.09, 2.29), p<0.02; CTx – 1.55 (1.12, 2.15), p=0.008; and PYD – 1.66 (1.27, 2.217), p=0.0002. There was no evidence of interaction between elevated biomarkers and treatment (all p>0.2). Recursive partitioning algorithms identified four groups of patients with differential OS outcomes based on bone biomarkers, adjusted for baseline clinical variables, with median OS ranging from 2.3 years (highest risk group) to 7.5 years (lowest risk group). Conclusions: In this subset analysis of men with HSPC and bone mets in S1216, elevated serum markers of bone metabolism were significantly associated with worse OS. Bone biomarker levels alone and in combination with patient and tumor characteristics identify unique subsets of men with differential OS outcomes. Clinical trial information: NCT01809691 .
Impact of synchronous (sync) vs metachronous (meta) metastasis at the presentation on survival in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with androgen receptor signaling inhibitors (ARSIs).
Authors: Gebrael Georges , Sayegh Nicolas , Tripathi Nishita , Goel Divyam , Brundage James , McFarland Taylor Ryan , Ebrahimi Hedyeh , Nordblad Blake , Chigarira Beverly , Mathew Thomas Vinay , Sahu Kamal Kant , Li Haoran , Chehrazi-Raffle Alexander , Maughan Benjamin L. , Kohli Manish , Swami Umang , Agarwal Neeraj 
Published: June 2023

5049 Background: Pts with sync metastatic castration-sensitive prostate cancer (mCSPC) appear to have worse survival outcomes and earlier time to developing castration resistance than pts with meta mCSPC (PMID: 33914595). However, the impact of the initial timing of metastasis on survival in the mCRPC setting is less clear. Herein, our objective was to assess the correlation between the sync/meta metastatic disease presentation and survival in real-world newly diagnosed mCRPC pts. Methods: In this IRB-approved study, patient-level data were collected retrospectively. Eligibility: confirmed diagnosis of mCRPC, treatment with ARSI (abiraterone or enzalutamide) as first-line (1L) therapy for mCRPC, and no prior exposure to ARSI in the mCSPC or localized states. The disease was considered sync if distant metastasis was diagnosed within 90 days of the initial prostate cancer diagnosis. Study endpoints: progression-free survival (PFS) was defined from the start of therapy for 1L mCRPC to progression (per PCWG-2) or death from any cause. Overall survival (OS) was defined from the start of therapy for 1L mCRPC to the date of death from any cause or censored at the last follow-up. A multivariate analysis using the Cox proportional hazards model was used, adjusting for potential confounders. Results: 323 pts (144 sync and 179 meta) were eligible and included in the analysis. Sync and meta pts had respectively similar baseline characteristics: median PSA (19.6 vs 20.8 ng/ml), liver metastasis (9 vs 12.3%), median alkaline phosphatase (97 vs 95 IU/L), and ECOG performance > 1 (9 vs 3.9%). The difference in median PFS was not statistically significant (8.2 vs. 10.7 months, HR 1.13, 95% CI 0.85-1.49, p=0.4 for sync and meta, respectively). Median OS was significantly shorter in pts with sync compared to meta (26 vs. 38.7 months, HR 1.51, 95% CI 1.11-2.08, p=0.01). In the multivariate analysis, the initial timing of metastasis remained an independent prognostic factor. Conclusions: For the first time, we report the impact of the initial timing of metastasis on mCRPC prognosis in a real-world patient population with sync disease being associated with having a poor prognosis. Initial timing of metastasis may be worth accounting for in future mCRPC clinical trials to explore its prognostic value further. These hypothesis-generating data need external validation. [Table: see text]
Talazoparib (TALA) plus enzalutamide (ENZA) in metastatic castration-resistant prostate cancer (mCRPC): Safety analyses from the randomized, placebo (PBO)-controlled, phase 3 TALAPRO-2 study.
Authors: Azad Arun , Fizazi Karim , Matsubara Nobuaki , Saad Fred , De Giorgi Ugo , Joung Jae Young , Fong Peter C.C. , Jones Robert J. , Zschaebitz Stefanie , Oldenburg Jan , Shore Neal D. , Dunshee Curtis , Carles Joan , Fay Andre P. , Lin Xun , DeAnnuntis Liza L , Di Santo Nicola , Engelsberg Arne , Agarwal Neeraj 
Published: June 2023

5053 Background: The phase 3 TALAPRO-2 study demonstrated a clinically meaningful and statistically significant improvement in radiographic progression-free survival for 1st-line TALA + ENZA versus PBO + ENZA in men with mCRPC, unselected for homologous recombination repair gene alterations (all-comers population). Here, we detail the safety profile of TALA + ENZA. Methods: In this double-blind, randomized, PBO-controlled trial, men received TALA 0.5 mg or PBO, plus ENZA 160 mg once daily (QD). Patient (pts) were ≥18 yrs of age, had Eastern Cooperative Oncology Group performance status ≤1, were receiving ongoing androgen deprivation therapy, and had no prior systemic therapy for mCRPC. Treatment-emergent adverse events (TEAEs) were evaluated: type, severity, timing, and associated dose modifications/discontinuations. Results: The all-comers safety population included 398 pts in the TALA + ENZA arm. Data cutoff was August 16, 2022. The median treatment duration of TALA was 19.8 months. All-cause any-grade TEAEs were observed in 98.5% of pts. Overall, 19.1% of pts discontinued TALA due to TEAEs. The 3 most common hematologic all-cause TEAEs and associated dose modifications are reported. To ensure optimal dosing of TALA at the individual level, the protocol did not require dose modification of TALA until anemia was grade (G) ≥3. Median time to onset of first G≥3 anemia was 3.3 months. At study entry, 49.0% had G1–2 anemia. 43.2% had anemia leading to dose reduction (with or without transfusion) and 8.3% discontinued TALA due to anemia. Despite dose reduction, the relative dose intensity of talazoparib remained >80% (approx. 0.4 mg/day). The 3 most common nonhematologic TEAEs were fatigue (33.7%; 4.0% G3), back pain (22.1%; 2.5% G3), and decreased appetite (21.6%; 1.3% G3). Conclusions: TALA 0.5 mg QD + ENZA 160 mg QD was generally manageable, with dose modifications of TALA and/or standard supportive care. Anemia was the most common TEAE and led to discontinuation of TALA in 8.3% of pts. G≥3 hematologic AEs typically occurred within 6 months of starting therapy and resolved in <1 month. A detailed understanding of the onset, duration, and severity of AEs, as well as the impact of dose adjustments in the TALAPRO-2 study, will optimize the management of pts receiving TALA + ENZA for mCRPC. Clinical trial information: NCT03395197 . [Table: see text]
The impact of circulating tumor cell HOXB13 RNA detection in men with metastatic castrate-resistant prostate cancer (mCRPC) treated with abiraterone or enzalutamide.
Authors: Guo Siyuan S , Halabi Susan , Nanus David M. , George Daniel J. , Antonarakis Emmanuel S. , Danila Daniel Costin , Szmulewitz Russell Zelig , McDonnell Donald P. , Norris John D. , Lu Changxue , Luo Jun , Armstrong Andrew J. 
Published: June 2023

5060 Background: It has been shown that HOXB13 is an important androgen receptor (AR) coregulator. The primary objective of this analysis was to correlate HOXB13 expression with clinical outcomes in men with mCRPC. Methods: We conducted a retrospective analysis of the multicenter prospective PROPHECY trial of mCRPC men (n=118) treated abiraterone (abi) or enzalutamide (enza). CTC detection and specific HOXB13 cDNA detection and expression was measured using a modified Adnatest using appropriate controls. CTC HOXB13 status was categorized into 3 groups: undetectable CTCs (CTC=0 based on CTC PSMA & PSA=0); CTC+ but HOXB13 CTC negative (<4 copies) or positive (≥4 copies) where the HOXB13 cutoff point was determined by the maximally selected rank statistic for prognostic associations. The association between HOXB13 and overall survival (OS) and radiographic progression-free survival (rPFS) were explored using the proportional hazards model. We also explored the association between the two endpoints and multigroup of HOXB13 at cutoff 0 and CellSearch CTC at cutoff 1 and 5. Results: 102 men who had sufficient CTC cDNA sample for HOXB13 detection. Of those men with detectable CTCs, 19% (n=19) had no detectable HOXB13, while the majority of men at 67% (n=58) had both CTC and HOXB13 detection. The proportion of patients with CTC=0, CTC+ HOXB13-, and CTC+ HOXB13+ using the optimal HOXB13 threshold were 25%, 31% and 44%, respectively. Men with HOXB13- CTCs were more likely to have low PSA (median 3 vs 79 copies), low CTC PSMA (0 vs 99 copies), low AR-FL (47 vs. 89 copies) and CTC AR-V7 (5.9 vs. 42 copies), and more likely to have liver/lung metastases (41% vs 25%). Median OS were 25.7, 25 and 12.1 months while the median rPFS of the three groups were 9.0, 7.2 and 4.7 months, respectively. Compared to CTC=0, men with HOXB13- CTCs did not have a worse hazard rate for OS (HR: 0.9, 95% CI: 0.4-1.9), while HOXB13+ CTC patients had a worse hazard for OS (HR: 2.0, 95% CI: 1.0-3.9), adjusting for prior abi/enza treatment and Halabi clinical risk score. The positive HOXB13 had also statistically significant increased hazard for progression/death (HR: 2.31, 95% CI: 1.24-4.30). Compared to the group with both HOXB13=0 and CellSearch CTC=0, men with HOXB13>0 and CellSearch CTC≥5 had increased hazard on both OS and rPFS (OS: HR:2.39, 95% CI: 1.06-5.4; rPFS: HR: 2.78, 95% CI: 1.38-5.59). Conclusions: Higher CTC HOXB13 expression is associated with AR dependent biomarkers in CTCs and is adversely prognostic in the context of potent AR inhibition in men with mCRPC, and this assay could be useful to select for patients appropriate for AR or future HOXB13 targeted therapies. Clinical trial information: NCT02269982 .
Phase I trial of enzalutamide (Enz) plus the glucocorticoid receptor antagonist relacorilant (Rela) for patients with metastatic castration resistant prostate cancer.
Authors: Desai Kunal , Serritella Anthony V. , Stadler Walter Michael , O'Donnell Peter H. , Sweis Randy F. , Szmulewitz Russell Zelig 
Published: June 2023

5062 Background: Resistance to androgen receptor (AR) targeted therapies is common in mCRPC. Glucocorticoid receptor (GR) expression increases with AR inhibition in patients (pts) and blockade of GR signaling inhibits CRPC growth in preclinical models when combined with AR blockade. We thus conducted a phase I study of the combination of rela and enz in patients with mCRPC. Methods: The study used a 6+3 design to assess safety and pharmacokinetics (PK) of the 2-drug combination. The starting dose of rela 100mg/day was chosen based on current clinical studies indicating this dose was both safe for daily dosing and pharmacologically active and the starting dose for Enz was 120mg based on anticipated drug-drug interactions. Escalating doses of rela were combined with Enz 120 using pre-specified dose escalation rules. An additional 12 patients were to be assessed at the MTD to refine safety and PK profiles. Primary endpoint was safety of the combination and to establish safe and pharmacologically active doses of both agents. Key secondary endpoints were tumor response per RECIST 1.1 criteria and progression-free survival (PFS; defined as either PSA progression, radiographic progression or death). PSA was measured after 12 weeks or at the last time at which PSA data was available, including times <12 weeks. Results: 35 pts were enrolled. Pts had a median age of 74 (range 62-85) and baseline PSA of 89.5 (range 7.3-2391). 100% had prior potent AR signaling inhibitor (abi or enz) with 89% receiving prior enz, 94% prior abi, 83% prior both. 69% of pts received prior docetaxel. Median PSA change was 0.1%. Enz 120mg + Rela 100mg and Enz 120+Rela 150 were found to be safe and tolerable and achieved desirable Enz PK. DLTs were noted in 3 pts at the 200mg Rela dose, which was deemed to have exceeded the MTD, which was thus defined as 150mg Rela+120mg Enz. Most common ≥ grade 3 treatment related adverse events (TRAEs) were fatigue (11% of pts), anemia (9%), abdominal pain (6%) and pericardial effusion (6%). Median PFS was 2.5 months for 21 of 35 evaluable pts. Best response per RECIST 1.1 were Not Evaluable (40%), SD (34%) & PD (26%). No CR or PR were noted. Most common reasons for discontinuation from trial included progressive disease/hospice (82%), AEs (12%), physician discretion (3%) & death (3%). 2 pts remain on trial as of data cutoff (12/31/22). Conclusions: The combination of enzalutamide and relacorilant was safe & largely well tolerated. The majority of pts were discontinued from trial due to progressive disease or hospice. Further analyses of secondary & correlative endpoints such as translational/endocrine biomarkers, GR target gene expression and circulating tumor cells are ongoing. Clinical trial information: NCT03674814 .
Enzalutamide vs abiraterone in patients with prostate cancer with and without type 2 diabetes mellitus.
Authors: Shaver Amy L , Nikita Nikita , Gandhi Krupa , Sharma Swapnil , Keith Scott W. , Yang Christopher C. , Lu-Yao Grace L. 
Published: June 2023

5066 Background: Estimations are that 8-18% of newly diagnosed cancer patients have Type 2 Diabetes Mellitus (T2DM). Current guidelines offer no clarification on the choice of therapy for prostate cancer (PCa) patients with T2DM. Since the comorbid PCa—T2DM population is increasing and these patients face unique challenges from adverse events requiring acute care utilization (ACU) it is important to ascertain which medication poses less of a threat of adverse events. The objective of this study was to describe the SEER-Medicare T2DM-PCa population in terms of those with and without complications and determine if T2DM influences ACU and PCa medication choice. Methods: We identified men with primary PCa treated with abiraterone (ABI, 2011) or enzalutamide (ENZ, 2012) with comorbid T2DM using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database (1999-2019). Patients with a missing date of diagnosis, those diagnosed at death, having HMO or no continuous A and B coverage 12 months before diagnosis and 6 months continuous part D coverage before starting treatment as well as 6 months following treatment or until death were excluded. T2DM was identified using ICD-9 and ICD-10 codes. ACU was calculated utilizing the CMS Research Data Assistance Center definition focusing on emergency room visits resulting in in-patent hospitalization during the 6 months following treatment initiation. Differences in emergency room in-patient visits were evaluated using negative binomial models adjusted for age, race, SEER region, marital status, state-buyin, education, income, and modified Charlson Comorbidity Index (excluding T2DM). Results: The sample of 11,163 men included 61.8% treated with ABI and 38.2% with ENZ. We identified 3,044 (27.3%) men with T2DM, of which, 59.1% were treated with ABI and 40.8% with ENZ. Compared to those without T2DM those with T2DM had more ACU, regardless of medication, with a higher rate in the ABI than ENZ group, see table. Among diabetics, those with complications related to T2DM compared to those without also experienced a higher rate of ACU. The rate of ACU was 43% higher among those treated with ABI compared to ENZ (IRR 1.43; 95% CI 1.28, 1.61). Overall mortality (15.7% vs 10.1%, p<0.01) and PCa-specific mortality (8.2% vs 5.3%, p<0.01) were worse in those with T2DM treated with ABI compared to ENZ. Conclusions: Outcomes for PCA patients with T2DM are worse than for those without. ACU is higher in men treated with ABI compared to ENZ regardless of T2DM status. Given the worse outcomes for comorbid T2DM patients, further study to evaluate comorbidity management in this population is warranted. [Table: see text]