bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular characterization to delineate the clonal evolution of primary prostate cancer with synchronous lymph node metastasis.
Authors: Singhal Udit , Nallandhighal Srinivas , Tosoian Jeffrey J. , Pham Trinh , Liu Chia-Jen , Kareem Razeen , Kunder Komal Ramesh , Morgan Todd Matthew , Lucianò Roberta , Shariat Shahrokh F , Dambrosio Lucia , Doglioni Claudio , Tomlins Scott A. , Briganti Alberto , Palapattu Ganesh S. , Udager Aaron M. , Salami Simpa 
Published: February 2022

266 Background: Primary prostate cancers (PCa) harbor multiple spatially distinct tumors with significant inter-lesion molecular heterogeneity. This diversity can result in many subclones that compete for biological and clinical dominance. The defining features of primary PCa that give rise to lymph node (LN) metastases is unknown. We performed multiregional targeted DNA/RNA next generation sequencing (NGS) of primary PCa with synchronous LN metastases to identify primary PCa foci capable of metastasis. Methods: Patients who underwent radical prostatectomy and LN dissection with pathologic node positive disease were identified. Punch biopsies were performed from pre-identified regions of cancer on formalin fixed paraffin embedded (FFPE) prostate and LN specimens and DNA/RNA samples were co-isolated. Targeted NGS was performed to characterize the genomic profile of each tumor region and to evaluate gene fusion status of each sample. We compared somatic DNA mutations, copy number alterations (CNA), and gene fusion status between primary and LN disease. Phylogenetic analysis was performed using the Phylip’s dollo and parsimony, neighbor-joining method to determine the likely clonal source of LN metastasis. Results: We analyzed 88 primary tumor (1°) and 23 LN-metastases samples from 14 patients. After quality control, 11 patients (69 and 18 primary and LN tumor samples, respectively) had sufficient quality data for analyses. Seven had evidence of extraprostatic extension (EPE), with phylogenetic analysis supporting this as the source of LN-metastasis in 4 cases. One patient had concordant TP53 and TPR non-synonymous mutations and broad CNAs between all 1°and two LN-metastasis foci, with two of the 1° regions showing high-level CNAs with both LN-metastasis foci. In two patients with pT2N1 disease, sub-clonal seeding and clonal evolution was observed with metastases arising from a GG5 area. Seven had cribriform pattern in both LN and 1° foci. One patient showed CDK12 mutation within the 1° and LN foci. FOXA1 was mutated in two patients within 1° and LN foci. Conclusions: Using targeted DNA/RNA NGS to assess primary PCa and synchronous LN metastases, we demonstrate that LN metastases is related to a combination of histopathologic and genomic factors. This highlights the need to develop robust prognostic biomarkers for identification of novel therapeutic targets for LN metastasis.
Temporal changes in the screening, diagnosis and surgical treatment of genitourinary (GU) malignancies during the COVID-19 pandemic.
Authors: Labaki Chris , Schmidt Andrew Lachlan , Bakouny Ziad , Labban Muhieddine , El Zarif Talal , Chang Steven Lee , McGregor Bradley Alexander , Kibel Adam S. , Rebbeck Timothy , Trinh Quoc-Dien , Choueiri Toni K. 
Published: February 2022

281 Background: The COVID-19 pandemic has been associated with a significant disruption in healthcare services including cancer screening and diagnosis. Delays in cancer screening and treatment may lead to increased mortality. We aimed to analyze changes in screening, diagnosis and surgical treatment of common GU malignancies in relation to the COVID-19 pandemic. Methods: We evaluated screening, novel diagnoses, and surgical management modalities of prostate cancer (PCa), urothelial carcinoma (UC) and renal cell carcinoma (RCC) within Massachusetts General Brigham, the largest healthcare system in the Northeastern United States, over four 3-month time periods during the pandemic (March 2020- March 2021). The percentage change in screening, diagnoses and management modalities during pandemic periods as compared to the immediate pre-pandemic period (December 2019-March 2020) was calculated as (Nperiod – Ncontrol)/Ncontrol. The difference in “predicted” versus “observed” diagnoses in each pandemic period was compared to the average of the four preceding 3-month periods (March 2019-March 2020) to account for seasonal variation. Results: The first pandemic peak (March-June 2020) was associated with a significant decline across screening, diagnosis and treatment, ranging from -15.7 to -64.8%, followed by a progressive recovery, ranging from -5.9 to +25.1% in the latest period (December 2020-March 2021) (Table). Although 725 diagnoses were “missed“ between March and June 2020 as compared to the previous 12 months, 971 diagnoses were “recovered” between June 2020 and March 2021. Conclusions: A substantial disruption in the screening, diagnosis and treatment of GU malignancies was observed early in the pandemic, followed by a progressive rebound and recovery. The highest declines were observed for PSA screening, and the lowest for cystectomy procedures, reflecting triaging of care based on severity during the pandemic.[Table: see text]
Distribution of NCCN risk classifications using MRI-ultrasound fusion versus systematic 12 core biopsies.
Authors: Khajir Ghazal , Press Benjamin , Levi Angelique W. , Sprenkle Preston C. , Leapman Michael S. 
Published: February 2022

283 Background: The widely-used National Comprehensive Cancer Network (NCCN) risk criteria for prostate cancer are impactful for patient and clinicians, particularly when assessing suitability for initial active surveillance. However, in the era of MRI-guided biopsy, fewer patients may meet stringent “very-low risk” criteria due to improved sampling, which may lead to over-treatment of non-lethal cancers. We evaluated the distribution of prostate cancer risk classification obtained using MRI-ultrasound fusion versus systematic 12 core biopsy. Methods: We performed a retrospective study of patients who underwent prostate MRI-ultrasound fusion biopsy at a single institution from January 2017 to July 2021. The primary study objective was to characterize the proportion of patients meeting NCCN “very-low risk” designation within a contemporary biopsy cohort. We calculated NCCN risk classifications (very low, low, favorable intermediate, unfavorable intermediate, high, and very high) based on constituent components (PSA, PSA density, number of biopsy cores positive, greatest extent of core positivity). We conducted comparisons within patients based on findings obtained through MRI-ultrasound fusion biopsy versus systematic biopsy only. Results: We identified 1,132 patients, including 1,014 (89.5%) and 118 (10.5%) who underwent first-time biopsy and surveillance biopsies. The median PSA was 7.15 (interquartile range: 5.2-10.8). Using data obtained through systematic biopsy alone, 123 (10.9%) and 242 (21.4%) were classified as very-low and low NCCN risk, respectively. Incorporating data from MRI-ultrasound fusion biopsy, 86 (7.6%) and 255 (22.5%) were classified as very-low and low NCCN risk, respectively. Among patients initially electing active surveillance as management, 7.4%, 60.2%, 26.9% met very-low, low, and favorable-intermediate risk criteria, respectively. Conclusions: A small proportion of patients undergoing MRI-ultrasound fusion biopsy will be classified as ‘very-low risk’ by the NCCN definition, and the majority of patients managed initially with active surveillance fall outside of this criteria. These findings imply a need to broaden support for active surveillance outside of “very-low risk” criteria to promote greater uptake.[Table: see text]
Survival of young black males with metastatic clear cell renal cell carcinoma.
Authors: Grigg Claud , Trufan Sally J. , Riggs Stephen Boyd , Clark Peter E , Matulay Justin T. , Kearns James T , Zhu Jason , Raghavan Derek , Burgess Earle F 
Published: February 2022

294 Background: Black men have the highest incidence of clear cell renal cell carcinoma (ccRCC) and have a worse prognosis than women or White patients in the curative setting. We previously reported that women with metastatic ccRCC have an inferior prognosis to men which is dynamic with age. The prognosis of Black patients with metastatic ccRCC is not well described. Methods: Clinicopathologic features and survival of patients diagnosed with clinical stage IV ccRCC between 2004-2016 were obtained from the National Cancer Database (NCDB). Patients were stratified according to their age at diagnosis, race, and sex. Uni- and multi-variable chi-square, logistic regression, and overall survival (OS) analyses were used for comparisons. Results: In this cohort, there were 900 Black men, 461 Black women, 13,422 White men, and 6363 White women. Black patients were less likely to have private insurance, lung metastases, or to live in high income zip codes and were more likely to have liver metastases. Compared to White race, Black race was associated with worse OS in the overall cohort (HR 1.17 [95% CI 1.10-1.24], p<0.001; multivariate HR 1.14 [95% CI 1.06-1.21], p<0.001) and in a smaller cohort limited to patients receiving systemic therapy as their initial treatment modality (n=10,869; HR 1.22 [95% CI 1.11-1.33], p<0.001). Within age groups, the highest disparity was observed among younger patients (<50yr: median OS 12.0 vs 22.1mo, p=0.004; 50-64yr: 14.6 vs 20.7mo, p=0.0001; >65yr 9.7 vs 14.5mo, p=0.002). When stratified by age and race, males had similar or superior survival compared to females in most subgroups, however Black males under 50yrs had markedly inferior OS compared with Black females (median OS 10.4mo vs 17.1mo for Black females, p=0.0083) and compared with White patients (Table). Conclusions: Young Black males with metastatic ccRCC demonstrate remarkably poor OS in this cohort; whereas males otherwise have a more favorable prognosis. Potential hypotheses to explain this disparity include differences in obesity and smoking incidence in this population as well as unmeasured factors impacting access to care.[Table: see text]
Racial differences in the natural history of small renal masses: A prospective registry study.
Authors: Cheaib Joseph G. , Patel Sunil H. , Alam Ridwan , Metcalf Meredith , Trock Bruce , Jing Yuezhuo , Ged Yasser , Allaf Mohamad , Pierorazio Phil , Singla Nirmish 
Published: February 2022

295 Background: Patients with small renal masses (SRM) can be managed conservatively by active surveillance (AS) or active treatment. A subset of patients who elect for AS undergo delayed intervention, either due to progression or other factors. Using a large, prospective registry of patients with SRMs we characterize differences in SRM growth trajectories on AS and pathologic differences among resected SRMs between African Americans (AA) and Caucasians. Methods: We stratified patients enrolled in the prospective Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry by race. DISSRM includes AS, primary intervention (PI), and delayed intervention (DI). The growth rate for patients who elected for AS was compared between AA and Caucasian patients. Pathologic features among patients who underwent PI or DI were compared by race. Results: We enrolled 745 patients in DISSRM who were either AA (n = 117, 15.7%) or Caucasian (n = 628 (84.3%)), with median follow-up of 3.3 years [IQR 1.5-6.6]. 410 patients elected for AS (84% Caucasian, 16% AA) and 401 opted for PI (n = 335) or DI (n = 66) (86% Caucasian, 14% AA). Within the AS cohort, no differences were seen in age, comorbidities, or tumor size, though Caucasians were more male-predominant (60.9% vs. 38.5%, p = 0.001), and body mass index was higher among AA (p = 0.03). Median overall growth rate for AA vs Caucasian was 0.04 cm/year [-0.03-0.3] vs 0.1 cm/year [0-0.33], p = 0.2 (Figure).In the DI arm, median time to intervention was 12.5 months, with HR (AA vs Caucasian) being 0.32 (0.13-0.82), p = 0.02. There were no differences in baseline clinical characteristics or tumor size in the DI or PI arm, however AA were more likely to undergo radical nephrectomy (24.6% vs. 10.4%, p = 0.01). pT stage and grade were similar between groups, and papillary histology was more common among AA (34.1% vs 19.9%, p = 0.007). There were 31 deaths among patients undergoing intervention, which was significantly worse for AA after multivariable adjustment (HR 2.51, p = 0.025). Conclusions: Using the largest prospective registry of SRM, we found the natural history of SRM on AS to be similar between AA and Caucasians. However, histology, surgical approach, and survival differed between groups, with worse OS among AA. Further socioeconomic and molecular analyses will help elucidate biological differences and identify strategies to improve outcomes among patients with SRM.
Clinical characteristics of patients with collecting duct carcinoma.
Authors: Zhou Li , Li Siming , Yan Xieqiao , Xu Huayan , Li Juan , Wu Xiaowen , Chi Zhihong , Si Lu , Cui Chuanliang , Kong Yan , Guo Jun , Sheng Xinan 
Published: February 2022

297 Background: Collecting duct carcinoma (CDC) is traditionally classified as a rare renal cell carcinoma. It comprised less than 2% of all renal cell carcinoma but presented a highly aggressive clinical course1. The natural history of CDC was merely described in small-sample retrospective studies because of its low incidence. Methods: We retrospectively collected clinicopathological data of patients (pts) diagnosed with CDC in our center from 2006 to the present. Histological diagnoses of all patients with CDC were confirmed by two senior urologic pathologists. Results: CDC was found in 58 pts (60% males and 22% over 65 years old). Most started with hematuria, low back pain, or systemic symptoms; 7 pts (12%) had no clinical symptoms. 67% pts underwent partial or radical resection of the kidney. 39.7% pts had distant metastases at diagnosis. Among the 35 pts with no distant metastasis at diagnosis, 18 (51%) had positive regional lymph nodes, 22 (63%) had locally advanced T stage (T3 or T4), and 18 (51%) were G3/4 by Fuhrman or WHO/ISUP. For pts undergoing radical nephrectomy, the median disease-free survival (DFS) was 6.3 mos (95%CI: 0.2, 12.4), and the median OS was 22.5 mos (95%CI: 16.6, 28.4), which were significantly related to T stage (P = 0.033 and 0.001). For pts after metastasis (56 cases), the most common sites of recurrence and metastasis were lymph nodes (55%), lung (46%), bone (36%), liver (16%), adrenal glands (7%), and local recurrence (20%). The median OS after metastasis was 11.3 mos (95%CI: 9.5, 13.0). Among the locally advanced or metastatic pts, 33 received gemcitabine + cisplatin combined with sorafenib as the first-line therapy. There were 8 PR and 17 SD. The ORR was 24.2%, DCR was 75.8%, and median PFS was 6.1 mos (95% CI: 4.7, 7.5). The median OS was 12.1 mos (95% CI: 8.6, 15.5). In 2 pts receiving anti-PD-1 monoclonal antibody combined with axitinib, 1 case had PR and 1 obtained SD with tumor shrinking. They are still under follow-up. Conclusions: CDC is prone to be diagnosed at a late stage and develop metastases. There is currently no standard treatment for metastatic patients; gemcitabine + cisplatin combined with sorafenib can be tried in the first-line setting. Anti-PD-1 plus axitinib showed promising efficacy in cases of CDC, and a larger sample is needed for verification.
Health-related quality of life (HRQoL) in previously untreated patients with advanced renal cell carcinoma (aRCC): CheckMate 9ER updated results.
Authors: Cella David , Motzer Robert J. , Blum Steven I. , Ejzykowicz Flavia , Hamilton Melissa , Wallace Joel , Zhang Joshua , Simsek Burcin , Ivanescu Cristina , Choueiri Toni K. 
Published: February 2022

323 Background: In CheckMate 9ER, patients (pts) with aRCC were randomized 1:1 to nivolumab 240 mg IV Q2W + cabozantinib 40 mg PO QD (N+C; n = 323) or sunitinib (S) 50 mg PO (4 weeks of 6-week cycles; n = 328). As reported previously, at a median follow-up of 18.1 months, N+C led to superior progression-free and overall survival and more favorable HRQoL than S. We report results of HRQoL analyses for 32.9-months follow-up. Methods: Disease-related symptoms (DRS) were evaluated using the FKSI-19 instrument and HRQoL with the EQ-5D-3L visual analogue scale (VAS). Change from baseline (BL) was assessed using mixed-model repeated measures (MMRM), adjusting for baseline scores and stratification factors, and included all common timepoints (at BL and every 6 wks) through week 151. Time to deterioration analysis was conducted for first (TFD), confirmed (TCD) and definitive (TDD) deterioration events using Kaplan-Meier estimates and Cox proportional hazards models. Bother with treatment side effects (item GP5 in FKSI-19) was assessed using a generalized estimating equations model with response dichotomized as minimal bother (not at all or a little bit) vs notable bother (somewhat, quite a bit, and very much). HRQoL endpoints were exploratory and P-values are nominal and descriptive. Results: Group mean scores over time show that HRQoL was maintained or improved from BL with N+C while reductions were observed with S. Overall changes from BL though week 151 favored N+C with nominal significant differences between treatments observed for all scores except functional well-being (FWB; Table). Similarly, decreased risk of deterioration was observed with N+C vs S for all scores except FWB, irrespective of the deterioration definition used (TFD, TCD, TDD). Pts in N+C arm were 48% (odds ratio: 0.52 [95% CI, 0.35-0.77]) less likely to be notably bothered by side effects than pts in S arm. Conclusions: Pts continued to report improved HRQoL with N+C compared to S. Treatment with N+C reduced the risk of meaningful deterioration in HRQoL scores, regardless of the definition of deterioration and showed a decreased risk of being bothered by treatment side effects in contrast to S. These results suggest that the superior efficacy of N+C over S with the additional benefit of improved HRQoL is maintained with longer follow-up. Clinical trial information: NCT03141177. [Table: see text]
Early primary tumor response in metastatic RCC patients treated with immune checkpoint inhibitors-based combinations.
Authors: Ciccarese Chiara , Bimbatti Davide , Atzori Francesco , Bonato Adele , Scagliarini Sarah , Pellegrini Ilaria , Bracarda Sergio , De Giorgi Ugo , Masini Cristina , Santoni Matteo , Massari Francesco , Buti Sebastiano , Damassi Alessandra , Zampiva Ilaria , Strusi Alessandro , Sparagna Ileana , Rebuzzi Sara Elena , Tortora Giampaolo , Iacovelli Roberto 
Published: February 2022

349 Background: 25-30% of renal cell carcinoma presents with metastases (mRCC) at diagnosis. The activity of immune checkpoint inhibitor (ICI)-combinations on the primary tumor (PT) is debated. Patients and Methods: mRCC patients (pts) with PT who received first-line nivolumab plus ipilimumab (N/I) or pembrolizumab plus axitinib (P/A) were included. We investigated the early primary tumor response (EPTR) at the first radiological assessment. Results: 73 pts were included. The median early reduction of the PT longest diameter was 12.4% with P/A versus 6.2% with N/I (p = 0.42). We evaluated if the type of EPTR could affect the metastases response. Among pts with PT stable disease (SD), 8.3% had metastatic disease progression (PD) with P/A and 34.8% with N/I. Early PT partial response (PR) was associated with no metastatic PD with both N/I and P/A. The 2 pts with PT PD had also metastatic PD to P/A. Of the 3 PT with PD to N/I, 1 had metastatic SD and 2 PD. In the overall population, of the 94.1% without PT progression (PR+SD), 47.5% had metastatic PR, 35.6% SD, 16.9% PD. Conclusions: ICIs-combinations achieved an early PT PR in about 10-20%, without any complete responses. Only a small percentage of PT had an early PD, mainly associated with metastatic PD. However, among those PT without an early progression, metastatic PR can be achieved in approximately 50% of cases.[Table: see text]
A systematic review of immune checkpoint inhibitors (ICI) in non-clear cell renal cell cancer (nccRCC) subtypes.
Authors: Reis Ana Filipa , Odeny Thomas A , Simão Diana , Fontes-Sousa Mario , Rodrigues Ysel Chiara Vina , Paller Channing Judith , Barata Pedro C. 
Published: February 2022

353 Background: ICI were approved for advanced RCC treatment either alone or combined with another ICI or a tyrosine kinase inhibitor. While most trial data derive from clear cell (cc) histology, the differential activity of ICI in nccRCC subtypes is not entirely known. The aim of this analysis is to summarize the reported activity of ICI-based therapies in ncc-subtypes or in tumors with sarcomatoid/rhabdoid features. Methods: A systematic literature search following PRISMA guidelines was performed. PubMed, GoogleScholars and ASCO Database were searched for the key-words “renal cell cancer” and “immune check point inhibitors” and equivalents. Publications between July 2016 - July 2021 were considered. All original articles reporting outcomes of ICI in at least 5 patients with an advanced nccRCC were eligible. Case reports, reviews, out of scope publications and articles with no full text available were excluded. Results: This study included a total of 14 publications, mostly case series except one phase II and one phase IIIb/IV trial. The table below summarizes the different histological subtypes included in these studies, more frequently papillary (10-88%), chromophobe (0-34%) and unclassified (4-27.5%) RCC. As for first line (L), ICI monotherapy elicited an overall response ratio (ORR) of 5-26.7%, a median progression free survival (mPFS) of 2.2-4.2 months (m) and a median overall survival (mOS) of 16.3-28.9m. ICI combination therapy associated with a higher ORR of 14.2-33%, a mPFS of 2.4-8.3m and a mOS not reached (NR). In ≥2ndL, ICI alone elicited an ORR of 9.4-22.6%, a mPFS of 3.5-7.1m and a mOS of 11.6m-NR. ICI combination therapy was superior, with a reported ORR of 31-44.4%, a mPFS of 4.3-5.6m and a mOS NR. Overall, ICI therapy elicited a higher ORR in papillary tumors (5-50%). Unclassified RCC response was more variable (0-66.7%). Chromophobe tumors had a lower ORR of 0-20%. ICI therapy outcomes among nccRCC with sarcomatoid/rhabdoid features were of an ORR of 0-42.1%, a mPFS of 2.3-6.9m and a mOS of 25.5m–NR. Nonetheless, outcomes were inferior in ncc comparing to cc tumors. Conclusions: The observed activity of ICI-based therapies was heterogenous among nccRCC subtypes. Combination regimens, papillary subtype and sarcomatoid/rhabdoid features were associated with higher responses. These findings might help treatment decisions and require further validation.[Table: see text]