bluuebunny/crossref_metadata_2025_split huggingface dataset:
Salvage radiotherapy guided by functional imaging for macroscopic local recurrence following radical prostatectomy: A multicentric retrospective study.
Authors: Benziane-Ouaritini Nicolas , Zilli Thomas , Giraud Antoine , Ingrosso Gianluca , Di Staso Marco , Trippa Fabio , Meyer Emmanuel , Francolini Giulio , Schick Ulrike , Cosset Jean Marc , Martin Etienne , Ferrari Victoria , Achard Verane , Giraud Nicolas , Pasquier Corentin , Magné Nicolas , Pasquier David , Supiot Stephane , Latorzeff Igor , Sargos Paul 
Published: February 2022

251 Background: For prostate cancer (Pca), salvage radiotherapy (sRT) with or without androgen deprivation therapy (ADT) is currently the only curative treatment option in case of post-radical prostatectomy (RP) biochemical relapse (BR). Functional imaging techniques have shown that macroscopic recurrence (MR) in the prostate bed (PB) are frequent. In this study, we aimed to assess efficacy and safety of sRT in patients with MR inside the PB proven by functional imaging. Methods: A multicenter retrospective study was conducted in 16 European centers. Patients were included if they displayed BR after RP for Pca, with MR only in the PB proven by functional imaging. All patients had to be eligible for sRT. The overall population was divided along 4 groups according to the delivered treatment: dose escalation on MR (A), dose escalation on PB (B), double dose escalation MR+PB (C), no dose escalation (D). The primary endpoint was progression-free survival (PFS). Secondary outcomes included the metastasis-free survival (MFS), biochemical PFS (bPFS) and overall survival (OS). Grade ≥2 genito-urinary (GU) and gastro-intestinal (GI) acute and late toxicities were collected. Results: Between January 2000 and December 2019, 363 patients with isolated MR after RP for Pca were treated by sRT. The median pre-sRT PSA level was 0.63ng/mL (range, 0.2-23.6). At the time of BR, 266 (73%) patients presented MR in the PB proven by magnetic resonance imaging, and 110 (30%) by positron emission tomography. The median follow-up was 53.6 months (range, 47.52; 58.32). The 5-year PFS and MFS were 70% (95%CI [63.8-75.4]) and 83.7% (95%CI [78.4-87.8]), respectively. Grade ≥2 GU and GI late toxicities were found in 43 (12%) and 11 (3%) patients, respectively. A 5-year PFS benefit was highlighted for groups A, B and C (313 patients) when the MR dose was ≥72Gy: 72,8% (95%CI 64.6-79.4) versus 60.3% (95%CI 48,4-70,3), p = 0.03. Conclusions: In a modern series integrating functional imaging data, we confirmed that sRT is effective in the event of MR inside the PB, with an acceptable toxicity profile. Prospective data should further investigate the correlation between MR-targeted dose escalation and PFS.
High-dose external BEAM intensity-modulated radiotherapy (HD-IMRT) versus intensity-modulated radiotherapy plus HDR brachytherapy boost (LD-IMRT+HDR-B) dose escalation for intermediate- or high-risk prostate cancer
Authors: Guix Ines , Bartrina Jose Maria , Panichi Marco , Tello Jose Ignacio , Garcia Ivan , Del Campo Jose Maria , Quinzaños Luis , Lacorte Teresa Maria , Guix Teresa , Guix Benjamin , Guix Benjamin 
Published: February 2022

263 Background: To report early & late toxicity & biochemical outcome in a prospective series of 1,465 patients with intermediate- or high-risk clinically localized prostate cancer treated with either HD-IMRT or with LD-IMRT+HDR-B. Methods: Between 12/1999 and 10/2011, 1,465 patients (pts) with PSA›10, Gleason score›6 and/or T2b-T3 N0 M0 prostate cancer entered the study. Pts were prospectively assigned to one of the two treatment groups: 76 Gy HD-IMRT to the prostate in 38 fractions (group 1; 733 patients) or 46 Gy LD-IMRT followed by 16 Gy HDR-B given in 2 fractions of 8 Gy (group 2, 732 patients), limiting the maximum rectal dose to 85% of the prescribed dose. Both groups were well balanced taking into account patient’s as well as tumor’s characteristics. Toxicities were scored by the EORTC/RTOG morbidity grading scales. Special attention to local, regional or distant recurrence, survival, late effects, PSA and testosterone levels and quality of life was done. Results: All pts completed treatment. None pts included in the group 1 or 2 experienced grade 3 or more rectal toxicity. 94 pts of group 1 (12.8%) and 20 pts of group 2 (2.7%) developed grade 2 rectal toxicity (rectal bleeding or urgency). 49 pts in group 1 (6.7%) and 10 pts in group 2 (1.3%) developed grade 1 rectal bleeding (less than 2 times/week). With a mean follow-up of 112 months, the 10-year free-from-failure survival was 90.7% and 98.3% (p<0.001) in group 1 and 2 respectively; free-from-metastases survival 93.9% and 97.8% (p<0,002)for group 1 and 2 respectively; and cause-specific survival 90.1% and 98.2% (p<0.001). No complications grade 2-4 were seen in either group. Conclusions: IMRT + HDR brachytherapy boost was a safe and extremely effective method of escalating the dose to the prostate without increasing the risk of late effects. Acute as well as late rectal complications were significantly reduced. Control rates were significantly better in the HDR-boosted patients as expected by higher effective-dose. Brachytherapy boost treated patients had a significant longer survival.
Survival outcomes in men with unfavorable intermediate-risk and high-risk prostate cancer treated with prostate-only versus whole pelvic radiation therapy.
Authors: Andruska Neal , Fischer-Valuck Benjamin Walker , Juarez Diaz Elizabeth , Agabalogun Temitope , Brenneman Randall , Gay Hiram Alberto , Michalski Jeff M. , Baumann Brian C. 
Published: February 2022

264 Background: Men with unfavorable intermediate-risk (UIR-PCa) or high-risk prostate cancer (HR-PCa) are often treated with definitive external beam radiotherapy (EBRT) plus androgen deprivation therapy (ADT). Treatment is frequently intensified by electively treating the pelvic lymph nodes with whole pelvis radiotherapy (WPRT), but practice patterns differ and the benefits of WPRT are not clearly defined, with mixed results from clinical trials. The recent POP-RT trial showed improved biochemical control with WPRT but most patients were staged with PET/CT scan. We hypothesized that men treated with WPRT would have improved overall survival (OS) relative to men treated with prostate-only radiotherapy in patients staged using conventional imaging. Methods: Men diagnosed between 2008-2015 with UIR or high-risk prostate cancer were retrospectively reviewed from the National Cancer Database (n = 28,724). Patients with involved nodes or distant metastases were excluded. Men received EBRT to a dose of 72-86.4 Gy and either prostate-only RT ± ADT (n = 13,549) or WPRT plus prostate RT ± ADT (n = 15,175). WPRT was delivered using a dose range of 40-50.4 Gy (1.8 – 2.0 Gy/fraction). The MSKCC nomogram was used to calculate risk of lymph node involvement. Unweighted or inverse probability of treatment weighting (IPTW) was used to perform multivariable analysis (MVA) using Cox regression modeling to compare OS hazard ratios, accounting for age, race, year of diagnosis, Charlson-Deyo comorbidity score, insurance status, education, income, treatment facility type, PSA, Gleason score, clinical T-stage, use of ADT, lymph node risk score, and radiation dose. Results: 53% of men received WPRT, with national utilization of WPRT increasing from 2008 to 2015. For every 1% increase in risk of lymph node involvement, there was a 1% increased risk of death ( P<.001). WPRT trended toward improved OS in all men with UIR or high-risk (Hazard Ratio (HR): 0.95 [95% Confidence Interval: 0.90-1.006], P=.07). WPRT correlated with improved OS in men with grade group 5 (GG5) disease (HR: 0.87 [0.78-0.98]. P=.02) or risk of lymph node involvement ≥ 10% (HR: 0.93 [0.87-0.99], P=.03). Conclusions: WPRT is associated with improved OS in men with a lymph node risk score ≥ 10% or GG5 disease. These results complement the recent POP-RT randomized trial in mostly PET/CT-staged patients, demonstrating that a more heterogenous population of men staged without functional imaging appears to benefit from WPRT.
A genomic classifier for prostate cancer correlates with adverse pathologic features: Transcriptomic features of cribriform and intraductal carcinoma of the prostate.
Authors: Lone Zaeem M , Benidir Tarik , Rainey Magdalena , Nair Monica , Davicioni Elai , Gibb Ewan , Williamson Sean , Nguyen Jane , Gupta Shilpa , Ornstein Moshe Chaim , Tendulkar Rahul D. , Weight Christopher , Klein Eric A. , Mian Omar Y. 
Published: February 2022

268 Background: Invasive cribriform and intraductal carcinoma (CF/IDC) portends an unfavorable prognosis for patients diagnosed with prostate cancer (CaP). Limited studies with small sample sizes have explored whether genomic classifiers are associated with IDC and/or CF status. We investigated the correlation between Decipher genomic risk score and IDC/CF status and assessed PCa transcriptomic features. Methods: We performed a retrospective review of CaP patients who had Decipher testing at a single high volume center between 2009-2020. The highest grade index lesion from radical prostatectomy specimens was identified by GU pathologists and used for Decipher testing. Genitourinary pathologists reviewed prostatectomy specimens for the presence of CF and IDC features. Patients were divided into three groups based on pathologic features, absent CF/IDC (CF-/IDC-), CF positive only (CF+/IDC-), and CF/IDC positive (CF+/IDC+). Categorical clinical, genomic, and pathologic variables were assessed using the Pearson Chi-Square test, quantitative with the Kruskal-Wallis test. Multivariable logistic regression was used to identify predictors of high-risk Decipher GC scores. The Kaplan-Meier method with log-rank was used to compare biochemical recurrence free survival. Differential gene expression and gene network analysis was used to identify genes and pathways associated with IDC/CF features. Results: 463 patients were included with a median follow-up of 25 months. Patients who were CF+/IDC+ had higher GC scores (CF+/IDC+: 0.77 vs. CF+/IDC-: 0.71 vs. CF-/IDC-: 0.61, p<0.001). Patients who were CF+/IDC+ had a higher percentage of Gleason grade group >3 (CF+/IDC+: 79% vs. CF+/IDC-: 52% vs. CF-/IDC-: 52%, p<0.001). On multivariate logistic regression, predictors of high-risk GC score were presence of CF+/IDC+ features on final pathology (OR: 3.94, p<0.001) and pathologic Gleason grade group >3 (OR: 1.58, p=0.04). Transcriptomic analysis revealed that the hallmark androgen response pathway was significantly upregulated in CF+/IDC+ patients (Log fold change: 15.7, p<0001). Conclusions: This is the largest series investigating the association of a clinically validated genomic classifier and pathologic features such as cribriform and intraductal carcinoma. These findings have implications for the use of genomic classifiers in settings where expert GU pathology is not readily available and in potentially unmasking adverse histology at the time of biopsy.[Table: see text]
Hereditary cancer risk assessment in the community urology practice setting.
Authors: Shore Neal D. , Lenz Lauren , Flake Darl D. , Meek Stephanie , Davis Thaylon , Copeland Karen , Finch Rob , Schiff William , Korman Howard , Rao Manoj , Belkoff Laurence , D'Anna Richard , Slavin Thomas , Cohen Todd 
Published: February 2022

278 Background: Professional guidelines recommend hereditary cancer risk assessment (HCRA) for men with prostate cancer to inform both risk of cancer (primary or subsequent) and treatment decisions. The objectives of the study were to evaluate the feasibility of integrating a HCRA protocol in urology practice for patients with prostate cancer and determine the response of providers and patients to the HCRA protocol. Methods: This prospective study was divided into 4 segments: process integration (4 wks.), practice (4 wks.), post-integration (8 wks.), and follow up (10 wks.). Study site staff were trained to perform HCRA for men with prostate cancer (integration). The sites then incorporated recommendations from the integration process into their normal practice workflow (practice). During the post-integration period, the HCRA process was implemented with eligible patients consented to participate. Eligible patients were ≥18 years old, had a personal history of prostate cancer, and met National Comprehensive Cancer Network guidelines for genetic testing (2.2018). Patients and providers completed surveys regarding testing ≥ 8 weeks of test delivery or 1 week of end of data collection period, respectively (follow up). Results: In the 8 weeks prior to the study, 4.2% of patients completed testing at the study sites. During the study, 8.4% of patients completed testing, about 1/2 of eligible patients screened. Of all patients who completed testing and consented for their results to be summarized (N = 182), 10.4% (N = 19) tested positive for a single pathogenic variant (PV; monoallelic MUTYH N = 4; BRCA2 N = 3; ATM, BRCA1, BRIP1, CHEK2, HOXB13 N = 2 each; RAD51C, RAD51D N = 1 each). Not all men who tested positive or a PV reported a family history of cancer and not all PVs detected were in known prostate cancer risk genes. During follow up, most providers (61.0%) felt HCRA was as important as other assessments regularly performed and 68.3% planned to continue to use the HCRA process. In contrast, only 9.8% of providers did not believe HCRA was as important and 12.2% did not plan to continue to use the process. Of the patients that responded to the survey (N = 166), most had shared (62.0%) or planned to share (25.3%) their results with family members post-testing. Conclusions: Urologists and patients responded favorably to HCRA protocol integration. Based on this study, education around and incorporation of an HCRA process in a community urology practice setting for men with prostate cancer appears effective at increasing appropriate uptake of genetic testing. Clinical trial information: NCT04015102.
Disease progression and competing mortality for men undergoing active surveillance for low-risk prostate cancer.
Authors: Guram Kripa , Nelson Tyler J. , Deka Rishi , Sherer Michael Vincent , Rodrigues De Moraes Gustavo , Rose Brent S. 
Published: February 2022

282 Background: Active surveillance is a common management strategy for men with low-risk prostate cancer. However, there is some concern that delaying definitive therapy could lead to progressive disease and a missed opportunity to cure the cancer. We sought to study the impact of Gleason grade progression on the risk of metastases and prostate cancer-specific mortality (PCSM). We then sought to compare the risks of PCSM with the risk of competing mortality in this real-world cohort of men on active surveillance. Methods: This was a retrospective population-based cohort study using patient records from the Veterans Heath Administration Informatics and Computing Infrastructure of patients with a diagnosis of low-risk prostate cancer from January 1, 2001, to December 31, 2015, who were managed with active surveillance. Follow-up extended through March 31, 2020. Low-risk prostate cancer was defined as International Society of Urologic Pathology grade group (GG) 1, clinical tumor stage 2A or lower, PSA level of 10 ng/dL or lower. Active surveillance was defined as no definitive treatment within the first year after diagnosis with at least 1 additional re-staging biopsy after diagnostic biopsy. We identified men with pathologic upgrading to ≥GG2 and ≥GG3. We calculated the cumulative incidence of metastases, PCSM, and non-cancer mortality for men with and without pathologic upgrading. Results: The cohort included 8562 men with low-risk PC. Pathologic upgrading to ≥GG2 and ≥GG3 occurred in 3227 and 1200 men, respectively. For all patients, the 8-year cumulative incidence of metastases and PCSM was 0.8% (95% CI: 0.6-1.0%) and 0.4% (CI:0.3-0.6%), respectively. Pathologic upgrading to ≥GG2 was associated with an increased risk of metastases at 8 years (1.2% vs 0.5%, p < 0.001). Pathologic upgrading to ≥GG3 was also associated with an increased risk of metastases at 8 years (2.7% vs 0.5%, p < 0.001). In contrast, pathologic upgrading to ≥GG2 was not associated with an increased risk of PCSM at 8 years (0.5% vs 0.4%, p = 0.793). Similarly, pathologic upgrading to ≥GG3 was not associated with an increased risk of PCSM at 8 years (0.7% vs 0.4%, p = 0.82). The 8-year cumulative incidence of non-cancer mortality for all patients was 6.5% (95% CI:5.9-7.1%). Overall, the risk of non-cancer mortality was 16.25 (6.5/0.4) times higher than the risk of PCSM, regardless of upgrading status. Conclusions: For men with low-risk PC on active surveillance, pathologic upgrading was associated with a small increased risk of metastases but no increased risk of death from prostate cancer. Regardless of upgrading status, the risk of non-cancer mortality was substantially higher than the risk of PCSM. Future work is required to better tailor the intensity of follow up for surveillance protocols for men at risk of competing mortality.
Growth kinetics and progression rates of cystic renal masses on active surveillance.
Authors: Tse Justin , Shen Luyao , Yoon Luke , Kamaya Aya 
Published: February 2022

298 Background: The Bosniak classification is used to risk stratify the probability of cancer among cystic renal masses using CT or MRI and assigns a class ranging from I-IV. Bosniak III and IV masses have the highest probabilities of cancer and are treated similarly to solid renal masses per 2021 American Urological Association (AUA) Guidelines. The purpose of this study was to determine the growth kinetics and progression rates of unresected Bosniak III and IV masses defined by Bosniak Classification, version 2019 (v2019). Methods: In this retrospective and IRB-approved study, CT and MRI images of 107 cystic renal masses from 100 patients (34 women, 66 men; range 28-92 years) with unresected Bosniak III and IV masses from 2005-2021 were reviewed. Cystic renal masses on baseline imaging were assigned a category based on v2019 by two abdominal radiologists, with discrepancies resolved by a third, such that each mass had a single Bosniak class assignment. Mass dimensions over serial imaging were measured using orthogonal planes by a radiologist with 3D laboratory training. Linear growth rate (mm/year) and volumetric growth rate (mL/year) were calculated. “Progression” off of active surveillance was defined as any of the following: linear growth rate > 5 mm a year, volume doubling rate ≤ 1 year, or increased stage based on TNM. Results: 107 cystic renal masses were categorized as 51 Bosniak III and 56 Bosniak IV masses on baseline exam. Median follow-up time was 406 days. Linear growth rate for Bosniak III masses was 0.4 ± 4.3 mm/year while linear growth rate for Bosniak IV masses was 2.3 ± 4.9 mm/year (p = 0.036; Student’s t-test). 12/51 (24%) Bosniak III masses progressed based on above definitions while 26/56 (46%) Bosniak IV masses progressed (p = 0.016; Fisher’s exact test). 13 masses upgraded from a Bosniak III to IV during surveillance, but category upgrades were not associated with progression (p = 0.131; Fisher’s exact test). 2 patients developed lung metastases; both masses were Bosniak IV and were biopsy proven papillary and clear cell renal cell carcinomas. Conclusions: Although currently treated similarly by AUA Guidelines, unresected Bosniak IV masses grow faster than Bosniak III masses and are more likely to progress off of active surveillance.
Association of cabozantinib dose reductions for toxicity with clinical effectiveness in metastatic renal cell carcinoma (mRCC): Results from the Canadian Kidney Cancer Information System (CKCis).
Authors: Graham Jeffrey , Basappa Naveen S. , Ghosh Sunita , Zhang Hanbo , Hansen Aaron Richard , Lalani Aly-Khan A. , Heng Daniel Yick Chin , Soulieres Denis , Castonguay Vincent , Kollmannsberger Christian K. , Pavic Michel , Wood Lori , Kapoor Anil , Bjarnason Georg A. 
Published: February 2022

316 Background: Cabozantinib (cabo) is an oral multi-targeted tyrosine kinase inhibitor (TKI) with activity in mRCC. TKI toxicity, an indicator of adequate drug exposure, has been associated with clinical effectiveness for sunitinib, pazopanib, and axitinib. We explored whether cabo dose reductions (a surrogate for toxicity) were associated with improved clinical outcomes in mRCC. Methods: Using the CKCis database, we performed an analysis of patients treated with cabo in the second-line or later between 2011-2021. We divided the cohort into those needing a dose reduction (DR, defined as less than the starting dose at time of treatment discontinuation) and those who did not (no-DR). We compared outcomes by dose reduction status, including objective response rate (ORR), time to treatment failure (TTF), and overall survival (OS). Results: We identified 260 patients who received cabo, of which 103 (41.0%) needed a DR. Across all lines, the ORR was similar between the DR and non-DR groups: 19.6% vs. 18.9% (p = 0.903) respectively. The median TTF was 12.75 months (95% CI 10.38 – 17.64) in the DR group vs. 6.44 months (95% CI 5.49 – 8.67) in the no-DR group. After adjusting for IMDC risk, the hazard ratio (HR) for TTF comparing DR vs. no-DR was 0.69 (95% CI 0.50 - 0.97, p-value = 0.03). The median OS was 29.6 months (95% CI 19.58 – 42.64) in the DR group vs. 15.28 (95% CI 11.04 – 22.64) in the no-DR group. After adjusting for IMDC risk, the HR for OS comparing DR vs. no-DR was 0.65 (95% CI 0.43 - 0.98, p = 0.04). Conclusions: Cabozantinib dose reductions, a surrogate for toxicity and adequate drug exposure, appear to be associated with improved TTF and OS in mRCC. Toxicity driven/individualized dosing strategies for cabo alone and in combination with immunotherapy, warrant further investigation.[Table: see text]