bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two-fraction stereotactic MRI-guided ablative radiotherapy with simultaneous boost to dominant intraprostatic lesion: Results from the 2SMART phase 2 trial.
Authors: Ong Wee Loon , Cheung Patrick , Chung Hans T. , Chu William , Detsky Jay , Liu Stanley K. , Morton Gerard , Szumacher Ewa , Tseng Chia-Lin , Vesprini Danny , Davidson Melanie , Ravi Ananth , McGuffin Merrylee , Zhang Liying , Mamedov Alexandre , Deabreu Andrea , Poon Meghan , Loblaw Andrew 
Published: March 2023

349 Background: Prostate stereotactic ablative radiotherapy (SABR) for localised prostate cancer is commonly delivered over 5 fractions. Focal boost to the dominant intraprostatic lesion (DIL) seen on multiparametric magnetic resonance imaging (mpMRI) is an approach for dose-escalation in prostate SABR. This is the first report of the outcomes of the 2SMART trial, a phase 2 single-arm study using 2-fraction prostate SABR with DIL boost. Methods: Men with low to intermediate risk prostate cancer were enrolled in the study. Three gold fiducial markers were inserted for image guidance. The clinical target volume (CTV) included the prostate gland, and the planning target volume (PTV) was a 2mm expansion antero-posterior and laterally, and 2.5mm supero-inferiorly. The DIL was contoured on fused mpMRI. The prescribed dose was 26Gy in 2 fractions (EQD2 110Gy, α/β of 1.4) to the CTV, and up to 32Gy in 2 fractions (EQD2 164Gy) to the DIL as long as the dose constraints for the organs at risks were not exceeded. Each fraction was delivered 1 week apart. Daily image guidance with cone-beam computed tomography was used pre- and post-treatment. The primary endpoint was acute (≤3 months) changes in quality of life (QOL), assessed using the EPIC questionnaire. Minimal clinically important change (MCIC) in QOL was defined as an EPIC score decrease of >0.5 standard deviation of the baseline EPIC score for each domain. Secondary endpoints were acute and late toxicities (assessed using CTCAEv4), and biochemical failure (based on Phoenix criteria). Results: 30 men were enrolled in the study, of which 2 (7%) had low risk and 28 (93%) had intermediate risk prostate cancer. The median follow-up was 44 months (range: 39-49 months). The median PSA nadir was 0.2ng/mL, with median time to nadir of 37 months. One patient (3%) had biochemical failure at 44 months post-treatment. 1 (3%) and 17 (57%) had acute Grade 2 GU and GI toxicities, while 3 (10%) and 15 (50%) had late (>6 months) Grade 2 GU and GI toxicities. No acute or late Grade ≥3 GU or GI was reported. 10 (33%), 6 (20%), and 3 (10%) men had acute MCIC in urinary, bowel and sexual domains respectively. 15 (50%), 9 (30%) and 13 (43%) had late MCIC in urinary, bowel and sexual domain respectively. Conclusions: Two-fraction prostate SABR with DIL boost is a safe approach for dose-escalation for localised prostate cancer, with minimal impact on acute QOL, and no grade 3-4 toxicities. Clinical trial information: NCT03588819 .
Comparison of ctDNA between African American and Caucasian patients with CRPC post abiraterone and/or enzalutamide.
Authors: Jang Albert , Huang Minqi , Casado Crystal , Caputo Sydney , Sweeney Patrick L , Lanka Sree M , Gupta Kanika , Pocha Olivia , Habibian Nicholas , Hawkins Maddie , Lieberman Alexandra , Schwartz Jennifer , Jaeger Ellen B. , Miller Patrick , Layton Jodi Lyn , Barata Pedro C. , Lewis Brian E. , Ledet Elisa M. , Sartor A. Oliver 
Published: March 2023

35 Background: Genetic differences between African American and Caucasian patients with advanced prostate cancer may contribute to racial disparities in terms of treatment outcomes and survival, hence further exploration is warranted. We assessed ctDNA differences between African American and Caucasian men in the setting of CRPC post treatment with abiraterone and/or enzalutamide. Methods: From 2015 through 2022 at Tulane Cancer Center, 250 patients with CRPC including 50 African Americans and 200 Caucasian with prior abiraterone and/or enzalutamide treatment were included. All patients had ctDNA assessed via Guardant360. Data including both gene mutations and types of mutations were for between 73-80 genes. Clinical annotation including initial staging, treatment history, and genetic testing were obtained. Statistical analyses included Fisher’s exact test and Wilcoxon rank-sum test. Results: The most common pathogenic/likely pathogenic (P/LP) alterations in both African Americans and Caucasians were TP53 (44% and 46%, respectively), AR (50% and 39%), and PIK3CA (14% and 9%). CDK12 (OR= 8.955, 95% C.I. [2.156, 37.192], p=0.003) and KIT (OR= 5.710, 95% C.I. [1.235, 26.397]. p=0.031) alterations were more frequently detected in African Americans. In terms of pathologic mutation type, frameshift mutations were significantly more frequent in African Americans (OR= 2.293, 95% C.I. [1.103, 4.769], p=0.035). All patients were CRPC at the time of testing and had prior abiraterone and/or enzalutamide, but there were no significant differences between African American and Caucasian patients with regards to prior life-extending therapies. Conclusions: African Americans with CRPC post treatment with abiraterone and/or enzalutamide had a higher frequency of P/LP CDK12 and KIT mutations, which have both been shown to lead to aggressive clinical features and treatment resistance. African Americans also had a higher incidence of frameshift mutations, a finding not previously noted. [Table: see text]
Planned interim analysis of perioperative safety of fluzoparib combined with abiraterone in the neoadjuvant treatment of locoregional high-risk prostate cancer: Results from multicenter, phase 2 FAST-PC trial.
Authors: Zhu Yao , Zhang Tingwei , Wang Beihe , Li Huajun , Ye Dingwei 
Published: March 2023

356 Background: Previous studies confirmed that the combination of PARP inhibitors and abiraterone might bring survival benefits to prostate cancer (PC) patients (pts) regardless of HRR mutation status. Hence, we conducted a single-arm, multicenter, phase II trial (FAST-PC, NCT05223582) to investigate safety and efficacy of fluzoparib combined with abiraterone and androgen deprivation therapy (ADT) in the neoadjuvant treatment of locoregional high-risk PC. Herein, a planned interim analysis of safety outcome of this study was reported. Methods: FAST-PC trial enrolled pts with only pelvic lymph node metastasis or high-risk localized (cT3-4 or prostate specific antigen (PSA) >20 ng/mL or Grade Group ≥4) PC. Eligible pts received fluzoparib (150mg PO BID), abiraterone (1000mg PO QD), prednisone (5mg PO BID), and ADT for 24 weeks followed by minimally invasive radical prostatectomy (RP). Perioperative outcomes were collected and evaluated during treatment period and follow-up period which was three months after surgery. Post-surgery AEs within 90 days were classified by Clavien-Dindo. Results: As of Sep 2022, 31 pts were recruited. All the 12 pts (patient No.1 to No.12) who have completed both the 24-week neoadjuvant regimen and surgery were analyzed. Baseline characteristics were shown in table. None of them were lost to follow-up or discontinued the protocol due to adverse events (AEs). The common AEs related to medication including anemia (4, 33.3%), hypokalemia (3, 25.0%), and liver dysfunction (3, 25.0%). As for post-surgery outcomes, median days of hospitalization, surgical time, and blood loss were 8.5 days (6-12.8), 144 minutes (16.5-171.3), and 100ml (50-200), respectively. Overall, 7 (58.3%) pts experienced post-surgery AEs of any grade, in which 4 (33.3%) were grade 1 and 3 (25.0%) were grade 2. 6 (50.0%) experienced fever, and 2 (16.7%) had urinary tract infections. Of note, pulmonary thrombosis (grade 2) was diagnosed in one patient after RP. Conclusions: Our data represent the first prospective evidence supporting the perioperative safety in locoregional high-risk PC pts who received neoadjuvant fluzoparib combined with abiraterone and ADT. The combined regimen is generally safe and reliable, while special vigilance should be paid to the occurrence of anemia, hypokalemia and liver dysfunction. Clinical trial information: NCT05223582 . [Table: see text]
Effect of undetectable PSA following SRT for biochemical recurrence on BPFS, FFM, and OS.
Authors: Scharl Sophia , Gartner Luca , Boehmer Dirk Heinz Gerhard , Siegmann Alessandra , Zips Daniel , Thamm Reinhard , Wiegel Thomas 
Published: March 2023

367 Background: Salvage radiotherapy (SRT) alone or in combination with androgen deprivation therapy (ADT) is the only curative treatment option for patients with biochemical recurrence after radical prostatectomy (RP) for prostate cancer. An undetectable post SRT PSA in patients without ADT (<0.1 ng/ml) has been shown retrospectively to correlate significantly with long-term freedom from progression, metastasis free survival and overall survival. The aim of this study was to investigate whether the predictive power of a post SRT-nadir <0.1 ng/ml extends to all subgroups of SRT patients. Methods: Between 1998 and 2018, 698 patients (all pN0/cN0) with persisting PSA or increasing PSA out of the undetectable range (<0.1 ng/ ml) of two German university hospitals received SRT alone without ADT. Exclusion criteria were distant metastases and/or ADT in the interval between RP and/or in combination with SRT. ADT before RP was allowed. All patients received 3D-conformal or intensity-modulated SRT to a median dose of 70.2 Gy. The impact of post-SRT nadir <0.1 ng/ml on biochemical progression free survival (BPFS), freedom from metastases (FFM) and on overall survival (OS) was analyzed by Kaplan-Meier analysis and multivariate Cox regression analysis. 9 subgroups with at least 30 patients per group were analyzed separately (pT2 + R0, pT3 + R0, pT3 + R1, pT2 + Gleason Score ≤ 7, pT3 + Gleason Score ≤ 7, pT3 + Gleason Score ≥ 8, pT3 + Gleason Score ≥ 7 + R1, pT3 + Gleason Score ≥ 7 + pre-SRT-PSA-Wert ≤1,0 ng/ ml and pT2/3 + Gleason Score ≥ 8 + pre-SRT-PSA-Wert ≤1,0 ng/ ml). Results: Median follow-up was 5.6 years. Median PSA before SRT was 0.30 ng/ ml. A post SRT PSA <0.1ng/ml was achieved by 76.6% of patients. In univariate analysis of the entire cohort, post SRT PSA <0.1 ng/ ml was a significant predictor of BPFS (p<0.001), FFM (p<0.001) and OS (p=0.01). Regarding univariate analysis of the subgroups, post SRT PSA <0.1ng/ml was a significant predictor of BPFS in all subgroups (p<0.001), FFM in 6 subgroups (p<0.001 to p=0.03) and for OS in 3 subgroups (p<0.001 to p=0.02). In multivariate analysis of the entire cohort, post-SRT PSA <0.1ng/ml was an independent predictor for BPFS (HR: 7.25, 95%-CI: 5.36-9.81, p<0.001), FFM (HR: 4.21, 95%-CI: 2.00-8.84, p=0.002) and OS (HR: 2.59, 95%-CI: 1.28-5.23, p=0.008). Conclusions: Achieving an undetectable PSA after SRT is an independent predictor of BPFS, FFM and OS. This effect is present in subgroups with favorable (pT2+Gleason score ≤ 7) as well as in those with unfavorable characteristics (pT3+ Gleason score >8). Our findings indicate that ADT could be withheld in a proportion of patients that are candidates for ADT based on their risk factors but achieve an undetectable PSA after SRT. Prospective studies are needed to confirm these results.
Partial gland ablation outcomes for localized prostate cancer in patients with MRI-visible and MRI-invisible lesions.
Authors: Zhu Alec , Gereta Sofia , Stangl-Kremser Judith , Margolis Daniel , Borregales Leonardo Daniel , Basourakos Spyridon P. , McClure Timothy D , Hu Jim C. 
Published: March 2023

368 Background: Partial gland ablation (PGA) for MRI-invisible prostate cancer (PCa) remains controversial, and we compared treatment failure rates, adverse events, and health-related quality-of-life outcomes (HRQoL) following PGA in subjects with MRI-visible vs. MRI-invisible lesions. Methods: Retrospective review was done of primary PGA therapy (cryoablation, irreversible electroporation, and high-intensity focused ultrasound) performed between January 2017 and 2022 at Weill Cornell Medical Center. Analysis was restricted to men with at least one post-PGA prostate biopsy. Men with PCa on systematic biopsy outside of the MRI-targeted zone were categorized as having MRI-invisible lesions. Failure of PGA was defined as persistence or recurrence of Gleason grade group (GGG) ≥2 on surveillance biopsy for subjects diagnosed with GGG ≥2 PCa. For patients treated for GGG 1 PCa, failure was defined by the detection of GGG ≥1 PCa. Adverse events were captured by the Clavien-Dindo classification and HRQoL outcomes were captured by the Expanded Prostate Cancer Index-Clinical Practice (EPIC-CP). Groups were compared using Pearson’s chi-squared test and the 2-sided Wilcoxon-Mann-Whitney test. Results: Out of 115 men were treated for primary prostate cancer, 89 men had at least one surveillance biopsy performed, and 87 men had available pre-treatment MRI data. Out 79 subjects treated with MRI-visible lesions and 34 subjects treated with MRI-invisible lesions, 59 and 28 subjects, respectively, had surveillance biopsy data. Median (IQR) follow-up was 15.5 months (7.7-25.5) in the overall cohort; median follow-up was not significantly different between the MRI-visible and MRI-invisible groups (15 vs. 15 months, p-value=0.766). Failure of PGA occurred in 43 (48.3%) of total subjects. Failure of PGA was not significantly different between the MRI-visible and MRI-invisible groups (50.9% vs. 42.9%, p-value=0.502). Mean total EPIC-CP scores were not significantly different between both groups at baseline, 3, 6, and 12 months after PGA. Additionally, rates of 30-day complications were not significantly different between both groups. Conclusions: Failure is evident in almost half of patients treated with PGA therapy. Oncologic and functional treatment outcomes after focal therapy are similar between patients with MRI-visible and MRI-invisible lesions. [Table: see text]
Short term pathologic outcomes and biochemical recurrence rates of single port transvesical retzius-sparing radical prostatectomy as compared to multiport radical prostatectomy.
Authors: Benidir Tarik , Ferguson Ethan , Lone Zaeem M , Campbell Rebecca , Weight Christopher J. , Kaouk Jihad 
Published: March 2023

369 Background: Single port radical prostatectomy with a transvesical Retzius-sparing approach (SPRP) has shown technical feasibility and early evidence of improved time to urinary continence. How this novel approach leads to differences in pathologic outcomes and biochemical recurrence rates (BCR) as compared to multiport radical prostatectomy (MPRP) has yet to be investigated. Our goal was thus to study the pathologic and short term survival outcomes of patients undergoing SPRP as compared to those undergoing MPRP. Methods: Single center, single surgeon retrospective review of prospectively collected data on 169 patients with low and intermediate risk prostate cancer, whom either underwent SPRP or MRPR (2017-2022). Preoperative clinicopathologic and radiographic characteristics were compared. Following RP, pathologic outcomes, including T stage, grade group (GG), margin status, extraprostatic extension (EPE), seminal vesical invasion (SVI), node retrieval rates, lymph node invasion (LNI) and other adverse histopathologic features were compared between both groups. Cox proportional hazards univariate analysis was used to evaluate the impact of SPRP on biochemical recurrence free survival as compared to MPRP with a three year follow up. Results: A total of 84 patients underwent MPRP and 85 patients underwent SPRP. The SPRP cohort had a higher proportion of clinical T stage one as compared to the MPRP cohort (99% vs 85%, p=0.04), however both groups did not differ preoperatively in terms of median total PSA (6.9 MPRP vs 6.2 SPRP, p=0.24), PI-RADS score (p=0.60) or biopsy GG (p=0.52). Following RP, both groups had similar pathologic outcomes including final grade group, T stage, EPE rates, SVI and Cribriform/intraductal rates (p>0.05). SPRP did yield a lower median number of nodes as compared to MPRP (2 (0-5) vs 6(4-9), p<0.001), but this did not translate to differences in LNI (p=0.08). At a median of approximately 12 months of follow up, there were no differences in the biochemical recurrence-free survival rates among both groups (p=0.38). Cox proportional hazards univariate analysis did not consider SPRP to be an independent predictor of biochemical recurrence (HR 0.53, 95% CI 0.13-2.23, p=0.39). Conclusions: In well selected men, SPRP yields similar short term oncologic control as MPRP with equal rates of margin status, EPE/SVI invasion rates and rates of biochemical recurrence at 1 year. In this small, early, single surgeon experience, SPRP appears to be oncologically safe for low and intermediate risk prostate cancer patients, however longer follow up is necessary, larger numbers and multi- institutional comparisons are needed.
Geographic variation of decipher genomic classifier in patients with early prostate cancer.
Authors: Keizman Daniel , Davicioni Elai , Peer Avivit , Dresler Hadas , Sella Avishay , Sarid David Leonid , Rouvinov Keren , Manaster Yoav 
Published: March 2023

376 Background: External factors such as environmental or lifestyle-related exposure may influence genomic composition of cancer, and therefore its progression and outcome. Thus geographic data is of importance. Decipher is a gene expression classifier used in risk stratification of early non metastatic prostate cancer. Currently, there are no data reporting geographic variation of the test. We aimed to analyze Decipher genomic score results among Israeli patients, in comparison to American patients. Methods: The Decioher database (Decipher Biosciences Inc) contains data from patients who have given consent for broad data-sharing. We identified and analyzed Decipher test results ordered among Israeli patients with localized prostate cancer. Matched analysis to the US population was done. Results: 144 patients (median age 69.5, range 64-74) were included in the present analysis. The clinical NCCN risk grouping was low in 42.4% (n=61), favorable intermediate in 38.9% (n=56), unfavorable intermediate in 17.4% (n=25), and high risk in 1.4% (n=2). Physicians primarily obtained Decipher for low-intermediate NCCN risk. Median Decipher score was 0.57 (Q1 0.385, Q3 0.823). Decipher risk grouping was low in 38.1% (n=61), intermediate in 16.9% (n=27), and high in 45% (n=72). Median Decipher score increased with Grade Group. 46% of NCCN low risk patients had a higher risk as per Decipher. 82% of NCCN favorable intermediate and unfavorable intermediate risk were reclassified to lower or higher risk. 9% of NCCN high risk patients had a lower risk as per Decipher. The present study cohort had a higher proportion of higher Decipher scores than observed in similar grade US population (n=43065) in the Decipher database (Median 0.43, Q1 0.27, Q3 0.66; 52%/18%/30% with low/intermediate/high risk). Conclusions: The preliminary results of the present study suggest a higher proportion of high risk Decipher among Israeli patients with early prostate cancer. These results should be interpreted cautiously. The study and further data collection are ongoing.
CDK12 pathogenic mutations in African American and White patients with prostate cancer.
Authors: Ledet Elisa M. , Mitsiades Nicholas , Jaeger Ellen B. , Chao Calvin Y. , Sartor A. Oliver 
Published: March 2023

38 Background: African American (AA) men are underrepresented in prostate cancer (PC) trials but have a greater probability of both developing and dying from prostate cancer (PC) than other populations. CDK12 mutations in PC are associated with aggressive disease, increased metastasis, and decreased overall survival. Some preliminary data has suggested that CDK12 mutations may be more common in AA men. This study reports data from next-generation sequencing (NGS) of tissue from a large population of patients with PC in the real-world setting to investigate frequency of pathogenic CDK12 mutations in AA men and White men. Methods: De-identified records from patients with primary PC who underwent NGS with Tempus xT (solid tumor, 648 genes, 500× coverage, full transcriptome RNAseq for a subset of patients) were analyzed to characterize the frequency and types of pathogenic CDK12 mutations, and co-mutation in other assessed genes. Results were compared between patients identified as AA and White. Patients were excluded if they were Microsatellite Instability high (MSI-H), Tumor Mutational Burden (TMB) ≥10, or Mismatch Repair deficient (MMR-d). Results: Genomic profiles were analyzed from tissue samples of 6121 unique patients; of 3,555 patients with known race, 646 (18%) were AA, 2657 (75%) were White, and 252 (7%) were of other races. Of these patients, 3026 were AA or White after excluding 277 patients with known MSI-H, TMB≥10, or MMR-d status. AA were younger at diagnosis than Whites (median 63 vs 66 years; p<0.001). Tissue samples from AA men were significantly more likely than those from Whites to express a pathogenic CDK12 mutation (42 [7.2%] vs 93 [3.8%], p<0.001). The majority of the variants identified were truncating mutations. There were no differences in truncating vs. non-truncating alterations between White and AA men, nor were there differences in the prevalence or distribution of co-mutations between the two populations. Conclusions: AA men with PC show a higher frequency of pathogenic CDK12 mutations than Whites in a large real-world population. Co-mutations did not vary by race, and the alterations were most likely to be truncating mutations in both races.
Germline testing for men with prostate cancer: Need to broaden the indications in Europe?
Authors: Trevisi Elena , Koster Kira-Lee , Heinimann Karl , Zuerrer Ursina , Turco Fabio , Bosetti Davide Giovanni , Colombo Ilaria , Maitz Silvia , Nerone Marta , Omlin Aurelius Gabriel , Vogl Ursula , Gillessen Silke , Graffeo Rossella 
Published: March 2023

383 Background: The clinical role of germline testing (GT) for prostate cancer (PC) is rapidly increasing due to the growing implications of precision medicine in metastatic disease, where genetic results can address eligibility for novel targeted treatments. Thus, ESMO and NCCN guidelines recommend GT for all metastatic PC individuals, whereas American testing criteria are more broad and include family history and other tumor features, such as high-risk disease, or intraductal or cribriform histology. Methods: We have retrospectively collected and analyzed clinical and genetic features of men with PC who underwent single-gene or multi-gene GT at some Swiss Institutions with expertise in hereditary cancers from July 2018 until October 2022. All patients (pts) have given written informed consent for research. Results: 109 men with PC underwent GT and received pre- and post-test counseling. Of these, 54 (50%) were metastatic, 34 (31%) had high-risk localized disease according to NCCN criteria, 7 (6%) presented cribriform or intraductal histology. A significant family history, as defined by current NCCN guidelines, was found in 79 (72%). 67 (61%) had no pathogenic (P) or likely pathogenic (LP) variants; 25 (23%) had a variant of unknown significance (VUS); 17 (16%) were found to have a P/LP variant in the following genes: BRCA2 (8), ATM (4), BRIP1 (1), FANCA (1), NBN (1), POT1 (1), TP53 (1). Among these 17 pts, the median age at diagnosis was 66 (45-80), 10 had metastatic disease, 5 had high-risk localized disease, 14 had a family history and 5 had a personal history of another cancer. Only 6 pts were <60 years old at the time of diagnosis. Cascade screening was offered to 16 families (94%). Conclusions: Our preliminary data support the increasing role of GT in PC and suggest the need to expand its indications. In this cohort, 7/17 (41%) of men with localized PC were found to carry P/LP variants and would not have met the criteria to undergo GT according to current European guidelines. GT may have treatment implications for metastatic PC pts whereas in early stage disease can inform cancer risk and screening for pts and their male and female relatives.