bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proposal for reclassification of upstaged T1 and T2 and pathological T3 RCC based on improved alignment of survival analyses.
Authors: Meagher Margaret , Cerrato Clara , Puri Dhruv , Liu Franklin , Shah Aastha , Ghassemzadeh Saeed , Dhanji Sohail , Wang Luke , Patil Dattatraya H , Saito Kazutaka , Yasuda Yosuke , Nasseri Ryan , Fujii Yasuhisa , Master Viraj A. , Derweesh Ithaar H 
Published: March 2023

732 Background: Patients with pathologically upstaged tumors have worse survival outcomes than their non-upstaged matched counterparts. However, we do know that original clinical tumor staging does still predict outcomes. We sought to examine if pathologic upstaging incrementally may more rationally stratify cancer specific survival outcomes. Methods: Multi-institutional (Emory, TMDU, UCSD) retrospective analysis of patients with renal cell carcinoma who underwent partial or radical nephrectomy between 1998-2020. Patients were divided into cT1 upstaged to pT3 (cT1/pT3), cT2 non-upstaged (cT2/pT2), cT2 upstaged to pT3 (cT2/pT3), and cT3 non-upstaged (cT3/pT3). Patients were analyzed for demographics, clinical parameters, and post-surgical outcomes. Primary outcome was cancer specific mortality (CSM). Secondary outcomes were all cause mortality and recurrence free survival. Cox regression was utilized to analyze factors associated with outcomes. Kaplan Meier analysis (KMA) was performed to analyze 5-year cancer specific survival. ROC analysis was utilized to compare predictive value of AJCC 8th edition TNM staging vs proposed staging. Results: 1093 patients were analyzed (283 cT1/pT3, 237 cT2/pT2, 244 cT2/pT3, and 329 cT3/pT3). Median follow-up was 25.9 months. Cox regression demonstrated that cT2/pT3 (HR 2.7, p<0.001 vs. cT1/pT3 [referent]) and cT3/pT3 (HR 2.6, p<0.001 vs. cT1/pT3 [referent]) were significantly associated with worsened cancer specific mortality, while cT1/pT3 (HR 0.4, p<0.001 vs. cT3/pT3 [referent]) and cT2/pT2 (HR 0.4, p<0.001 vs. cT3/pT3 [referent]) were associated with improved cancer specific mortality. Based on this, we proposed to realign cT1/pT3 with cT2/pT2 and cT2/pT3 with cT3/pT3. KMA revealed significant differences in 5-year cancer specific survival (cT1/pT3 82%, cT2/pT2 81%, cT2/pT3 67%, and cT3/pT3 60%, p<0.001). There were significant differences in 5-year overall survival (cT1/pT3 63%, cT2/pT2 67%, cT2/pT3 49%, and cT3/pT3 49%, p<0.001), and 5-year recurrence free survival (cT1/pT3 80%, cT2/pT2 83%, cT2/pT3 70%, and cT3/pT3 59%, p<0.001) on KMA. ROC analysis revealed an AUC of 0.529 for CSM and AUC of 0.502 for ACM using the current AJCC 8th edition TNM staging. ROC analysis revealed an AUC of 0.597 for CSM and AUC of 0.545 for our new proposal. Conclusions: Our analysis suggests that cT1 tumors pathologically upstaged to pT3 behave more similarly to pT2 tumors. Further delineation of pathologically upstaged tumors may more rationally stratify cancer specific survival outcomes to guide patient counseling and clinical decision making.
The impact of homologous recombination repair (HRR) gene mutation status on treatment (tx) patterns and clinical outcomes among patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) in the United States (US).
Authors: Barata Pedro C. , Du Ella X. , Yang Hongbo , Xu Chunyi , Guo Helen , Cui Caroline , Nazari Jonathan , Niyazov Alexander 
Published: March 2023

97 Background: There is a paucity of evidence that evaluates the impact of HRR mutation status on clinical outcomes in pts with mCRPC. This study assessed the real-world (rw) progression-free survival (rwPFS) based on HRR mutation status (HRR mutated [HRRm]), HRR wild type (HRRwt) among pts with mCRPC in the US. Methods: Data from pts with mCRPC initiating first line (1L) tx between 2016 and 2019 and known HRR status based on germline or tumor testing were retrospectively abstracted from medical charts by physicians in the US from 2021–2022. Pt demographic and clinical characteristics were summarized descriptively across subgroups by HRR status (HRRm vs HRRwt). HRRm was defined as a mutation in at least 1 of 12 genes of interest ( BRCA1, BRCA2, PALB2, ATM, ATR, CHEK2, FANCA, MLH1, MRE11A, NBN, RAD51C, CDK12), regardless of test type. RwPFS on 1L mCRPC tx was compared among pts with HRRm vs HRRwt genes and BRCA1/2 HRRm vs HRRwt genes using the Kaplan–Meier method and log-rank test. Results: A total of 80 physicians contributed data from charts of 130 pts (N=51 HRRm and N=79 HRRwt). Among pts with HRRm genes, 34 (67%) were positive for BRCA1 or BRCA2 mutations. In pts with known timing of testing (n=88), 33% were tested prior to initiation of 1L therapy and 67% after initiation of 1L therapy. In the 1L setting, novel hormonal therapy (NHT) was utilized in 29% of pts with HRRm vs 58% with HRRwt genes (P<0.01). Chemotherapy was utilized in 43% of pts with HRRm vs 34% with HRRwt genes (P=0.40); docetaxel was the most common agent, utilized in 26% vs 27% of pts with HRRm vs HRRwt genes. Median rwPFS on 1L tx was 19 months (95% CI: 11–NE) vs 31 months (95% CI: 23–NE), P=0.11, for pts with HRRm vs HRRwt genes, respectively. RwPFS for pts with BRCA1/2 HRRm genes (N=34) vs HRRwt genes was 19 months (95% CI: 11–NE) vs 31 months (95% CI: 23–NE), P=0.17. Conclusions: In this rw study, genomic testing was performed frequently in later stages of metastatic disease. Pts with HRRm genes had numerically shorter rwPFS on 1L standard therapies compared with HRRwt pts. While unmet needs exist to optimize mCRPC txs and prolong disease progression irrespective of HRRm mutation status, further studies are warranted to further elucidate the prognostic role of HRRm and BRCA1/2 mutations on clinical outcomes.
Survival outcomes of metastatic castration-resistant prostate cancer in Brazil (LACOG 1818).
Authors: Maluf Fernando Cotait , Martins Suelen P. S. , Silva Neto Deusdedit Cortêz Vieira , Werutsky Gustavo , Rinck Jr Jose Augusto , Bastos Diogo Assed , Rocha Roberto Odebrecht , Fay Andre P. , Fernandes Roni de Carvalho , Girardi Daniel da Motta , Araujo Daniel Vilarim , Mota Augusto C. A. , Lara Gongora Aline Bobato , Fernandes Bruno Melo , Alves Ana Caroline Fonseca , Sampaio Cristina de Deus Anjos Tavares , de Souza Andréa Lopes Ponte , de Jesus Rafaela Gomes , Gössling Gustavo Cartaxo de Lima , Soares Andrey 
Published: March 2023

TPS272 Background: Treatment of metastatic castration-resistant prostate cancer (mCRPC) has been steadily evolving during the last decade, but access remains a significant issue in low- and middle-income countries (LMICs). As novel therapies emerge and translate into clinical practice, the gap in treatment patterns between patients who do or do not have access to these therapies is expected to increase. The resulting disparities in outcomes are likely to be more noticeable in countries with pronounced inequality, such as Brazil. In Brazil, while a minority of patients have private insurance and have access to nearly all available treatment options, approximately 75% of patients depend on the public health system, which is unable to afford most of the recent treatment innovations for mCRPC, such as novel hormonal agents (NHA) or PARP inhibitors. LACOG 1818 was developed to investigate and compare outcomes of patients with mCRPC treated at private and public hospitals in Brazil. Methods: LACOG 1818 (NCT04962919) is a retrospective multicentric study investigating disparities in cancer treatment and survival among public and private institutions in Brazil. Patients with mCRPC diagnosed within January 2014 and December 2017 will be included and their data will be abstracted from medical records. Primary endpoint is cause-specific survival, comparing patients from private and public institutions. We estimate that 299 events are needed to detect a hazard ratio of 0.75 indicating a lower risk of prostate cancer-related death for patients treated at private institutions with a power of 80% and a bicaudate significance level of 10%. Considering a follow up of 24 months and a median cause-specific survival of 20 months in patients from public institutions, 590 patients are planned to be included. Secondary endpoints include describing comorbidities, sociodemographic and clinicopathological characteristics of patients with mCRPC; comparing overall survival of patients with mCRPC treated at public and private institutions; comparing treatments patterns of patients with mCRPC treated at public and private institutions; and describing skeleton-related complications, bone-directed treatments, and admission rates. From January 2020 to August 2022, 244 of planned 590 patients have been enrolled in 7 Brazilian centers. Additional 12 centers are still planned to open before 2023. Results are expected in the first semester of 2023. Clinical trial information: NCT04962919 .
A phase II trial modifying metabolic syndrome and cardiovascular risk for patients with prostate cancer on ADT using a risk factor modification program and continuous Fitbit monitoring (ProTrio).
Authors: Hahn Andrew Warren , Slack Tidwell Rebecca , Thoman Whittney , Abdulla Amer , Koutroumpakis Efstratios , Aparicio Ana , Subudhi Sumit Kumar , Siddiqui Bilal Ahmed , Pilié Patrick Glen , Zurita Amado J. , Corn Paul Gettys , Laccetti Andrew Leonard , Jana Bagi RP , Basen-Engquist Karen , Logothetis Christopher 
Published: March 2023

TPS273 Background: Prostate cancer is a disease of older age, and there is significant overlap with age-related illnesses. Androgens play a critical role in prostate cancer but also have been linked to cardiovascular (CV) disease, metabolic syndrome, bone health, and frailty. ADT is associated with an increased risk of CV events primarily due to increased rates of diabetes, dyslipidemia, and adverse changes in body composition. We assume that prostate cancer and age-related illnesses share biology with therapeutic implications in a subset of men. The ProTrio trial will test the hypothesis that a 16-week digital risk factor modification program will improve 10-year atherosclerotic cardiovascular disease (ASCVD) risk score as compared to usual care in men with potentially lethal prostate cancer receiving ADT. Methods: This single center, open-label, randomized phase II trial is evaluating a 16-week digital risk factor modification program, which includes an exercise prescription (150 minutes of titrated cardiovascular exercise and resistance exercise 2 times a week) with support via a smart phone application (Moving Analytics) and Fitbit, in patients with prostate cancer who are receiving ADT compared to usual care with Fitbit monitoring. Eligible patients are men receiving ADT +/- an androgen signaling inhibitor for at least 3 months prior to enrollment. The study will enroll to two cohorts: (1) distant metastatic disease and (2) biochemically recurrent or regional lymph node disease. Patients will be stratified according to their baseline ASCVD risk score. The primary endpoint is the difference in ASCVD risk score post-intervention. Secondary endpoints include difference in metabolic severity index z-score, PSA velocity, 6-minute walk, 5X Sit-to-Stand, body composition, physical activity measured by Fitbit, and health-related quality of life. Up to 100 patients will be enrolled in each cohort. A clinically relevant improvement in ASCVD score reduction is 2.5%. With 44 men per arm, after 12% dropout, we can detect an improvement of 2.5% vs. 0% at a 2-sided 5% significance level with 80% power assuming a standard deviation (SD) of 4.125%. A sample size adjustment is planned based on the SD of the first cohort to reach 44 patients. Each cohort will undergo futility analysis once half the men are enrolled. The study is enrolling at MD Anderson Cancer Center. Clinical trial information: NCT05054296 .
LuCAB: A phase I/II trial evaluating cabazitaxel in combination with [177Lu]Lu-PSMA-617 in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC)
Authors: Kostos Louise Kathleen , Buteau James Patrick , Kong Grace , Yeung Theresa , Di Iulio Juliana , Fahey Michael T , Fettke Heidi , Furic Luc , Hofman Michael S , Azad Arun 
Published: March 2023

TPS278 Background: [177Lu]Lu-PSMA-617 was recently FDA-approved for use in the post-taxane, post-antiandrogen setting in pts with mCRPC. Despite conferring a survival benefit, for many the treatment response is short, and progression is inevitable. One of the likely mechanisms limiting the durability of responses to [177Lu]Lu-PSMA-617 is heterogeneity in tumor PSMA expression. This can be screened for visually using PSMA and FDG PET/CT scans and inspecting for discordant disease, however, micrometastatic disease is unable to be evaluated in this way. In addition, [177Lu]Lu-PSMA-617 may not effectively target micrometastatic disease due to the longer path length of beta emitters. Cabazitaxel has radiosensitizing properties that may enhance the cytotoxic effect of [177Lu]Lu-PSMA-617, whilst also treating any PSMA-negative disease. We hypothesize that the combination of [177Lu]Lu-PSMA-617 and cabazitaxel will be well tolerated and lead to more durable responses. Methods: This single-centre, single-arm phase I/II trial will enrol 32-38 pts with mCRPC to evaluate the safety and preliminary efficacy of cabazitaxel and [177Lu]Lu-PSMA-617 in combination. Up to 6 doses of [177Lu]Lu-PSMA-617 (7.4 GBq) will be administered intravenously every 6 weeks. Cabazitaxel will be given concurrently (dose range 12.5mg/m2 - 20mg/m2), on Day 2 and Day 23 of each 6-week cycle. The dose of cabazitaxel will be escalated using a traditional 3+3 design. Key eligibility criteria include a diagnosis of mCRPC with PSMA-positive disease on PSMA PET/CT (SUVmax ≥15), with no evidence of diffuse marrow disease or sites of discordance on FDG PET/CT. Pts must have progressed after prior docetaxel and a second-generation antiandrogen, have adequate bone marrow and organ function and an ECOG performance status of 0-1. The primary objective is to establish the maximum tolerated dose of cabazitaxel and [177Lu]Lu-PSMA-617. Secondary objectives include measuring the frequency and severity of adverse events, assessment of efficacy through PSA 50% response rate, radiographic and PSA progression-free survival, overall survival, objective tumor response rate, and evaluation of pain and health-related quality of life over the first 12 months. Bloods will be taken at baseline, during treatment and at progression for ctDNA analysis, the results of which will be correlated with baseline pt and disease characteristics, and response outcomes, to determine biomarkers of treatment response and resistance. Pt recruitment commenced in August 2022 and will continue for 18 months. Clinical trial information: NCT05340374 .
AlphaBet: A phase I/II trial evaluating the combination of radium-223 and [177Lu]Lu-PSMA-I&T in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Kostos Louise Kathleen , Buteau James Patrick , Yeung Theresa , Xie Sophia , Di Iulio Juliana , Cardin Anthony , Owen Katie , Fettke Heidi , Chin Kwang Y , Emmerson Brittany , Haskali Mohammad B , Parker Belinda , Furic Luc , Azad Arun , Hofman Michael S 
Published: March 2023

TPS280 Background: [177Lu]Lu-PSMA-I&T (LuPSMA) is a small molecule radioligand that delivers radiation via beta-particulate emission to cells expressing prostate-specific membrane antigen (PSMA). Despite a survival benefit in mCRPC, responses for many are not durable, with the majority of pts developing progressive osseous disease. Due to the lack of crossfire radiation in micrometastatic disease, small cancer cell clusters in the bone marrow may not receive an adequate dose of radiation from 177Lu to induce cytotoxic double-stranded DNA breaks. Alpha-emitters have a shorter path length (≤100 µm) and higher linear energy transfer, making them better suited for treating micrometastatic disease. As a calcium-mimetic, radium-223 (223Ra) is a bone-specific alpha-emitter which targets osteoblastic bone metastases. We hypothesise that the combination of LuPSMA with 223Ra will be well tolerated and lead to improved response durability. Methods: This phase I/II, single-arm, single-centre study will enrol 36 patients with mCRPC who have progressed on a prior second-generation antiandrogen. Up to 6 cycles of LuPSMA (7.4 GBq) and 223Ra (28 kBq/kg - 55 kBq/kg) will be given intravenously every 6 weeks, along with background androgen deprivation and bone protective therapy. Key eligibility criteria include a diagnosis of mCRPC with at least two untreated bone metastases visible on bone scintigraphy and PSMA-positive disease on PSMA PET/CT (SUVmax ≥20). Sites of FDG-positive disease must be either PSMA-positive or have increased uptake on bone scan. Other eligibility criteria include an ECOG status of 0-2, and adequate bone marrow and organ function. Patients treated with more than one line of chemotherapy for metastatic prostate cancer are not eligible. Blood samples and biopsies will be taken at baseline, on treatment, and at progression to develop tumor- and immune-based biomarkers that predict treatment response and associated survival benefit. A traditional 3+3 dose-escalation model will be utilized initially, escalating the dose of 223Ra. The dose of LuPSMA will remain fixed. The co-primary objectives of this study are to determine the maximum tolerated dose of 223Ra when combined with LuPSMA, and the 50% PSA response rate. Secondary objectives include measuring the frequency and severity of adverse events, assessment of efficacy through overall, radiographic and PSA progression-free survival, overall survival, objective tumor response rate, and evaluation of pain and health-related quality of life. Enrolment commenced in September 2022 and will continue for 24 months. Clinical trial information: NCT05383079 .
AtezoCab: A phase II study of cabozantinib (C) in combination with atezolizumab (A) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) with non-measurable disease (NMD).
Authors: Swami Umang , Brown Julian , Turner Alena , Haaland Benjamin , Jones Kristen , Mathew Thomas Vinay , Sahu Kamal Kant Kant , Li Haoran , Phunrab Tenzin Kunsang , Batten Julia , Maxwell Lindsay , Lloyd Jennifer , Kohli Manish , Gupta Sumati , Thorne Kelli , Maughan Benjamin L. , Agarwal Neeraj 
Published: March 2023

TPS295 Background: Preclinical studies and clinical observations suggest that C promotes an immune permissive environment, which might lead to synergistic effects from combination treatment with immune checkpoint inhibitors. In Cohort 6 of COSMIC-021 study, the combination of C and A showed encouraging clinical activity and acceptable tolerability in mCRPC pts who had radiographically progressed in soft tissue on or after novel hormonal treatment (NHT; PMID: 35690072). CONTACT-02 is a phase 3 study randomizing pts with mCRPC with measurable disease 1:1 to C+A or NHT (NCT04446117). The objective of this study is to specifically evaluate the safety and efficacy of C+A in pts with mCRPC with NMD. Methods: AtezoCab is an IRB approved, investigator-initiated, single-arm, single-center, open-label, non-randomized phase 2 study of C+A in mCRPC patients with NMD to assess disease control rate (DCR). Treatment: C 40 mg oral daily + A 1200 mg intravenously every 3 weeks. Treatment continues until progression or intolerable toxicities. Key inclusion criteria: ≥18 years age, mCRPC with histologically or cytologically confirmed adenocarcinoma without small cell histology, Eastern Cooperative Oncology Group performance status ≤ 2, adequate organ function, prior treatment with NHT, only NMD outside the pelvis (above aortic bifurcation) per RECIST 1.1 criteria. Key exclusion criteria: prior chemotherapy for mCRPC, prior treatment with C, immune checkpoint inhibitors or other systemic immunostimulatory agents, active or history of clinically significant autoimmune disease per treating physician, corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days before first dose of study treatment. Primary endpoint: Percentage of pts with disease control. DCR will be defined as the percentage of pts with confirmed response of any duration or stable disease or noncomplete response or nonprogressive disease for 24 weeks or longer per PCWG3-modified RECIST v1.1. Up to 33 pts will be enrolled for a total of 30 evaluable pts. This will ensure that DCR can be estimated via a 95% confidence interval (CI) with margin of error <0.18. The primary analysis CI on DCR will be based on Wilson’s approach. Secondary Endpoints: Progression-free survival (PSA and radiographic), PSA50% response rate, overall survival and safety. Tissue and blood samples will be collected for correlative studies. 7 patients have been enrolled. Clinical trial information: NCT05168618 .
Radiation therapy and irreversible electroporation for intermediate risk prostate cancer (RTIRE).
Authors: McClure Timothy D , Ballman Karla V. , Marciscano Ariel E. E. , Barbieri Christopher , Nagar Himanshu 
Published: March 2023

TPS403 Background: The objective of the RTIRE clinical trial (NCT05345444) is to demonstrate the feasibility, safety, and early oncologic efficacy of combining MRI-guided stereotactic body radiation therapy (MRgSBRT) with irreversible electroporation (IRE) for men with intermediate-risk localized prostate cancer. Methods: Inclusion criteria: 1) Men aged ≥18, 2) ECOG 0 –1, 3) Histologically confirmed intermediate risk prostate cancer per NCCN guidelines, 4) Focal grade group 2 (GG2) or 3 (GG3) cancer in multi-parametric magnetic resonance imaging (mpMRI) target, 5) Gland size < 80cc, 6) Ability to undergo IRE, 7) Ability to receive MRI-guided SBRT, 8) Ability to complete the HRQOL assessment surveys, 9) Willingness to undergo 12 month follow up biopsy. Exclusion criteria: 1) Prior TURP, 2) Prior history of focal therapy, 3) Prior history of receiving pelvic radiotherapy, 4) Patient with history of inflammatory bowel disease, 5) History of bladder neck or urethral stricture. Study Design/Endpoints: This is a feasibility and safety study assessing the ability to perform IRE followed by real-time MRgSBRT. Subjects will undergo focal IRE followed by MRgSBRT (>6 weeks after IRE) to the prostate +/- seminal vesicles prescribed to 32.5 Gy in 5 fractions. The primary endpoint of the first portion of the trial is feasibility, defined as at least 80% of subjects (8 of 10 subjects) undergoing assessment at 12-weeks post-IRE and at 6-weeks post-MRgSBRT within 1 year from enrollment of the first subject. The expansion phase will include an additional 40 subjects to assess side effect profile and early oncologic efficacy (n=50) at 12 months post RTIRE. RTIRE has enrolled 8 subjects in 3 months and will proceed to the expansion phase. Secondary endpoints include: 1) short-term safety as measured by treatment-related adverse events, 2) oncologic efficacy as measured by number of subjects with presence of ≥GG2 cancer at 12 months post-RTIRE therapy, 3) health-related quality of life (HRQOL) as measured by Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP), International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF-5) 4) post-RTIRE prostate-specific antigen (PSA) kinetics including time to PSA nadir and post-nadir PSA stability, 5) assessment of pre and post-RTIRE mpMRI changes to evaluate the area of necrosis and presence of residual tissue, 6) rates of biochemical and clinical progression and the need for secondary or adjuvant treatment following RTIRE. Clinical trial information: NCT05345444 .