bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment response in the intact primary renal mass (P-Rmass) and its relationship to the overall response to treatment in patients with metastatic renal cell carcinoma (mRCC).
Authors: Emamekhoo Hamid , Kawsar Hameem I , Eickhoff Jens C. , Hester Danubia , Bice Tristan , Acharya Luna , Jaeger Ellen , Barata Pedro C. , Zakharia Yousef , Kilari Deepak , Wulff-Burchfield Elizabeth Marie , Kyriakopoulos Christos 
Published: March 2021

329 Background: With the approval of more effective systemic treatments (syst Rx) such as tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI), the impact of cytoreductive nephrectomy (CN) on response to Rx and survival remains unknown. The majority of patients (pts) previously enrolled in clinical trials have had radical nephrectomy (RN) or CN prior to syst Rx. Therefore, the response of the P-Rmass to ICIs and the effect of intact P-Rmass on response to syst Rx is not well described. Methods: A retrospective review of 209 pts with mRCC who were treated with ICI in the first or second-line was conducted. Following the appropriate regulatory process, collaborators from 5 US sites collected clinical, pathological, and outcome data via chart review. The response was investigator-assessed for all pts with at least one post-treatment scan or evidence of clinical progression after treatment initiation. Overall radiographic response (ORR) includes complete response (CR) and radiographic response (Rad-resp) to treatment. Disease control rate (DCR) includes CR, Rad-resp, and stable disease. Results: Median age at diagnosis was 63 yrs and 69% were male. 102 pts (49%) had localized disease at diagnosis and underwent radical or partial nephrectomy, 3 (1%) had ablation/radiation of P-Rmass, 26 (12%) had CN, 9 (4%) had CN after an excellent response to syst Rx, 12 (6%) had a previous nephrectomy but developed a new Rmass (measurable target lesion), and 57 (27%) did not have CN and had an intact P-Rmass. 176 (84%) pts had clear cell histology. 27 (14%) and 23 (12%) had known sarcomatoid and rhabdoid features, respectively. Overall, 77 (37%) pts had a measurable Rmass while receiving syst Rx. 84 (40%), 93 (45%), and 10 (5%) pts received ICI (Ipilimumab/Nivolumab or Nivo), TKI, or Pembrolizumab/Axitinib in the first-line. 143 (68%) and 70 (33%) pts received second- and third-line treatment. 103 (72%) and 28 (19%) pts received ICI and TKI in the second-line, respectively. The best ORR and the Rad-resp in the intact P-Rmass in evaluable pts are summarized in the table below. ORR to ICI in the first or second-line were numerically higher in pts with an intact P-Rmass compared to pts who had nephrectomy, but this difference was not statistically significant (p= .38 and .35 respectively). Conclusions: The intact P-Rmass had a good response (62-70%) to the first-line syst Rx. Although the overall Rad-resp rates to ICI are numerically higher in pts with intact P-Rmass, this difference was not statistically significant. [Table: see text]
Rechallenge of nivolumab in metastatic renal cell carcinoma, an ambispective multicenter study (RENIVO).
Authors: Vauchier Charles , Auclin Edouard , Barthelemy Philippe , Carril Lucia , Ryckewaert Thomas , Borchiellini Delphine , Ajgal Zahra , Bennamoun Mostefa , Campedel Luca , Thiery-Vuillemin Antoine , Coquan Elodie , Crouzet Laurence , Berdah Jean Francois , Chevreau Christine , Ratta Raffaele , Flechon Aude , Lefort Felix , Gross-Goupil Marine , Thibault Constance , Oudard Stephane 
Published: March 2021

330 Background: Immune checkpoint inhibitors (ICIs) in combination with another ICI or an antiangiogenic targeted therapy have been approved for frontline therapy in metastatic renal cell carcinoma (mRCC). However, progression disease (PD) often occurs and subsequent therapies are needed. Rechallenge of ICI may then be an option, but there is a lack of data regarding this strategy. Methods: This ambispective multicenter study included patients who received a rechallenge of Nivolumab (ICI-2) between January 2014 and September 2020, after a first-ICI therapy (ICI-1), regardless of the reason of the discontinuation. Patients could have either a non-ICI therapy or have a prolonged free-interval (≥ 12 weeks) between ICI regimens. Those with ongoing rechallenge at inclusion were followed prospectively. Primary endpoint was investigator-assessed best ORR. Results: 45 rechallenges were included from 16 centers. Median age was 60 years (range, 42-90), 64% were male. Most of them had clear cell histology (91%) and a Fuhrman or ISUP grade ≥ 3 (80%). Single-agent Nivolumab and Nivolumab-Ipilimumab association were used in 78% and 11% during ICI-1 and in 93% and 7% during ICI-2, respectively. Discontinuation for PD, toxicity or clinical decision occurred in 49%, 27% and 24% for ICI-1 and in 94%, 3% and 3% for ICI-2, respectively. The ORR were 51% (n = 23) at ICI-1 and 16% (n = 7) at ICI-2. One patient had a complete response during both ICI-1 and ICI-2 and two had a partial response at ICI-2 although they had PD as best ICI-1 response. After a median follow-up of 14.9 months (mo), median duration of response for ICI-2 was 5.1 mo (95% CI, 2.7-not reached [NR]). For ICI-1 and ICI-2: median progression-free survival (PFS) was 11.4 mo (95% CI, 9.8-23.5) and 3.5 mo (95% CI, 2.8-9.7); median overall survival was NR (95% CI, 37.8-NR) and 24 mo (95% CI, 9.9-NR). Poor prognostic factors for PFS at ICI-2 were Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥ 2, presence of liver metastases, inflammatory syndrome and PFS under ICI-1 > 6 months. Grade ≥ 3 immune-related adverse events occurred in 24% (n = 11) during ICI-1 but only in 4% (n = 2) during ICI-2. There was no treatment-related death. Conclusions: Our study suggests that resumption of ICI with Nivolumab has a moderate efficacy in mRCC and acceptable tolerance. Predictive factors of response are needed to propose this strategy to selected mRCC patients. Larger prospective cohorts are needed to confirm these results. [Table: see text]
Safety and efficacy of nivolumab in older patients (pts) with renal cell carcinoma: Results of a sub-group analysis of the GETUG-AFU 26 NIVOREN multicenter phase II study.
Authors: Mourey Loic , Dalban Cécile , Negrier Sylvie , Chevreau Christine , Gravis Gwenaelle , Thibault Constance , Laguerre Brigitte , Barthelemy Philippe , Borchiellini Delphine , Gross-Goupil Marine , Geoffrois Lionnel , Rolland Frederic , Thiery-Vuillemin Antoine , Joly Florence , Ladoire Sylvain , Tantot Florence , Escudier Bernard , Albiges Laurence 
Published: March 2021

331 Background: NIVOREN GETUG AFU 26 study, is a french multicenter prospective study to evaluate safety and efficacy of Nivolumab (N) in a broad “real world setting” in mRCC after failure of 1 or 2 tyrosine kinase inhibitors. Methods: Between February 2016 and July 2017, 729 pts were enrolled across 27 institutions. Primary objective of the trial was safety assessed by grade ≥ 3 treatment related adverse event (TRAE). We report here results of older patients above 70 years old ([70;75[; [75;80[; ≥ 80) compared with their younger counterparts. Results: Overall, 720 patients were treated (median age 64 (22;90)). Among them 205 pts were ≥ 70 (28.5%) divided as follow: [70-75[:107 (14.9%) / [75-80[: 68 (9,4%) / ≥ 80: 30 (4,2%). Patients’ characteristics (Table) were similar in younger and older patients except for IMDC risk groups (IMDC) classification with less poor prognostic in pts ≥ 75 and fewer brain metastasis in pts ≥ 70. Treatment duration was similar across age groups despite a rate of discontinuation for TRAE increasing with age. Regarding efficacy, there was a non-significant trend toward improved response rate and progression free survival and lower specific survival with increasing age. Conclusions: In this large “real world” setting study a significant number of old pts were included. Prognostic profile appears better in older pts included. There is no signal for an excess of toxicity in this population and efficacy is comparable to younger patients. Age alone should not prevent prescribing N in mRCC. Clinical trial information: NCT03013335 . [Table: see text]
Diagnostic utility of (18)f-fluciclovine positron emission tomography (FACBC) in biochemically recurrent (BCR) prostate cancer (PCa) based on prior primary treatment modality for localized disease and the impact of FACBC findings on treatment selection.
Authors: Sharifi Marina Nasrin , Lovrec Petra , Eickhoff Jens C. , Kenarsary Aria , Jarrard David Frazier , Floberg John , Cho Steve Y. , Kyriakopoulos Christos , Emamekhoo Hamid 
Published: March 2021

34 Background: Management of BCR PCa requires accurate assessment of location and extent of recurrent disease. FACBC has been shown to be a sensitive modality for detection and localization of recurrent disease but treatment guidelines are based on the findings of conventional (conv) imaging, including computed tomography, magnetic resonance imaging, or bone scintigraphy, and little is known about how prior treatment impacts FACBC findings and concordance with conv scans. Methods: This single-center retrospective study included 137 patients (pts) who had FACBC for BCR at the University of Wisconsin-Madison from 10/2017-10/2019. Clinical, pathological, imaging, and treatment data were collected by chart review. Pts were classified by type of primary treatment for localized PCa, either radical prostatectomy (RP) or radiation therapy (RT). Findings of conv scans performed within 4 weeks prior or any time after FACBC were collected. Results: 105 pts had RP and 32 pts had RT as their primary PCa treatment. Gleason score and PSA at diagnosis were similar between groups. Median PSA at time of FACBC was higher in the RT compared to RP group (3.3 vs 0.7 ng/dL) and median time from initial diagnosis to FACBC was longer (70 vs 55 months). Frequency of (+) FACBC findings was higher in the RT group (66% vs 47%); only 3% of pts in the RT group had a (-) FACBC compared to 29% in the RP group. The rate of (+) lesions in the prostate/prostate bed was higher in the RT group (41% vs 22%), while the rate of (+) lesions in pelvic nodes and distant sites was similar between groups. Of 69 pts who also had conv imaging, 61% had concordant conv imaging findings. In the RT group, conv and FACBC findings were similar in 47% of pts and not similar in 28%. In the RP group, conv and FACBC findings were similar in 26% of pts and not similar in 17%. Management after FACBC is listed in table. Median time from FACBC to first (+) conv scans was 6 (range: 0-18) and 5 (range: 0-17) months for RT and RP groups, respectively. Conclusions: In this large retrospective cohort, pts treated with initial RT had a longer median time from diagnosis to FACBC and higher median PSA at the time of FACBC compared to the RP group. RT patients had a higher rate of (+) FACBC findings but were more likely to continue on observation. The median time from FACBC to first (+) conv scan was 5-6 months, supporting the role of FACBC in earlier detection of recurrent disease in both groups of patients. Further analysis of concordance between FACBC and conv imaging is in process. [Table: see text]
Illustration of temporal evolution in patients with metastatic renal cell carcinoma (mRCC) using both circulating tumor DNA (ctDNA) and tissue-based genomic data.
Authors: Zengin Zeynep Busra , Weipert Caroline , Hsu Joann , Salgia Nicholas , Hensel Chuck , Maughan Benjamin Louis , Rathi Nityam , Goel Divyam , Agarwal Neeraj , Choueiri Toni K. , Pal Sumanta K. 
Published: March 2021

347 Background: We have previously demonstrated the feasibility of ctDNA assessment in mRCC and preliminarily showed agreement between ctDNA and tissue-based genomic findings (Zengin et al ESMO 2020). Our data suggested that the degree of agreement is dependent upon the temporal separation of blood and tissue samples. We sought to further explore this temporal impact in a separate validation cohort. Methods: Patients (pts) with mRCC who underwent ctDNA genomic profiling were identified. ctDNA analysis was performed using a CLIA-certified 73-74 gene panel (Guardant360). From this cohort we identified a subset of pts who also underwent tissue-based genomic profiling using either a whole exome sequencing platform (GemExtra [TGen, Phoenix, AZ]) or a targeted next generation sequencing platform (Foundation Medicine [Cambridge, MA] or Tempus [Chicago, IL]). Only alterations covered by both assays were included for the current analysis. The difference in the proportion of alterations detected on tissue and ctDNA was compared between these cohorts and at a 6-mo landmark using the χ2 test. Results: In total, ctDNA and tissue based genomic profiling was assessed in 112 pts (M:F, 81:31); with most common histology was clear cell (85.7%). Median time between ctDNA and tissue assessments was 9.8 months (IQR 1.15-23.7). When examining paired samples in which >1 ctDNA alteration was detected, 32% (43/133) of alterations detected on tissue were also detected in ctDNA. This proportion increased to 43% (29/67) when samples collected within 6 months of each other, and was 51% (28/55) in samples collected within 3 months of each other. There was no significant difference in the frequency of shared mutations between the cohorts (P=0.09; Table). Conclusions: Our study confirms that ctDNA and tissue-based genomic profiling continue to provide consistently high levels of agreement. Notably, the percentage of samples with ≥1 ctDNA alteration detected was significantly lower in both cohorts compared to previous studies in RCC. More shared alterations were found on ctDNA when both ctDNA and tissue-based assessment were obtained at closer intervals. [Table: see text]
Prognostic biomarkers of systemic inflammation in patients on active surveillance for metastatic renal cell carcinoma (mRCC): A biobank analysis.
Authors: Chauhan Vishwani , Malik Jahangeer , Sundaramurthy Aravindhan , Symeonides Stefan N. , Stares Mark 
Published: March 2021

348 Background: A subset of patients with metastatic renal cell carcinoma (mRCC) follow an indolent disease course. Given the toxicity and non-curative nature associated with systemic anti-cancer therapy (SACT), some patients may benefit from initial active surveillance (AS). However, selecting patients suitable for this approach is challenging. Biomarkers of systemic inflammation predict survival in mRCC, both independently and as part of the International Metastatic Database Consortium (IMDC) risk score. We sought to use these biomarkers to characterise the time to initiation of SACT (tSACT) in mRCC patients on AS. Methods: 126 mRCC patients clinically assessed and commenced on AS prior to any systemic therapy were retrospectively identified from a regional mRCC clinical database. Patients who underwent metastasectomy for oligometastatic disease at any time were excluded. The primary endpoint, tSACT, was defined as the time from radiological diagnosis of mRCC until SACT initiation, or death, or censorship if continuing AS at follow-up date. Inflammatory biomarkers from routine blood tests (haemoglobin, white cell count, neutrophil count, platelets, C-reactive protein (CRP), albumin) and the IMDC score, measured at the time of diagnosis of mRCC, were recorded. The relationship between these and tSACT was examined using Kaplan-Meier and Cox-regression methods. Results: 66 (52%) patients had commenced SACT. 17 (13.5%) had died without commencing SACT (median survival of the 17 was 40.4 months, range 9.1-130.2 months, and comorbidities may have affected fitness for starting therapy or led to all-cause mortality). 43 patients remained on AS, with minimum and median follow-up of 12.6 months and 39.6 months respectively. The median tSACT was 17.2 months (IQR 8.8-34.8 months). On univariate analysis, CRP and albumin were predictive of time on AS ( p= 0.01 and p= 0.049 respectively). On multivariate analysis, only CRP was independently associated with tSACT ( p= 0.035), stratifying tSACT from 9.1 months (CRP > 10) to 20.9 months (CRP≤10) ( p= 0.009). 111 (88.1%) patients were IMDC 0-1, while 12 (9.5%) and 3 (2.4%) were IMDC 2 or 3 and may have had comorbidities that influenced the initial AS decision. In our cohort the IMDC risk score did not predict time on AS. Conclusions: These results highlight that some patients with mRCC may undergo active surveillance for a marked time period before SACT initiation. We identify routine biomarkers of the systemic inflammatory response that predict time to systemic therapy. In particular CRP, a simple measure of inflammation, stratifies the time to initiation of SACT across a clinically significant time period. This simple, widely available test may help to objectively inform clinical decisions about AS in patients in mRCC. Additional experience is necessary to further define the risks and benefits of this approach.
Impact of concurrent ACE inhibitors and ARBs on outcomes with immune-checkpoint inhibitors (ICIs) for patients (pts) with metastatic renal cell carcinoma (mRCC).
Authors: Nuzzo Pier Vitale , Curran Catherine , Adib Elio , Freeman Dory , Nassar Amin , Alaiwi Sarah Abou , Bakouny Ziad , McGregor Bradley Alexander , Choueiri Toni K. , Jain Rakesh K. , McKay Rana R. , Sonpavde Guru 
Published: March 2021

354 Background: The renin-angiotensin system (RAS) is involved in regulation of angiogenesis and cell proliferation and may improve drug delivery by enhancing tumor perfusion partly by downregulating transforming growth factor (TGF)-β. Since (TGF)-β appears to be associated with resistance in patients receiving immune checkpoint inhibitors (ICIs), we investigated whether angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs) may enhance the outcomes of mRCC pts receiving ICI. Methods: Data from mRCC pts who received ICIs at the Dana-Farber Cancer Institute (DFCI) was obtained. Data for ACEI and ARB administration was collected with concurrent administration defined as ongoing therapy from the time of starting ICI . The Kaplan-Meier method and Cox were used to evaluate the impact of concurrent ACEI/ARB on overall survival (OS). Results: Data was available for 134 pts. The mean age was 63 years (Range 37-85)). 94 (70%) pts were male. The therapies included Nivolumab+/-Other (104), Atezolizumab+/-Other (21), Pembrolizumab+/-Other (8) and Durvalumab +Tremelimumab (1). 35 (25%) pts received ICI as first line treatment, 52 (39%) received as second line treatment, and 48 (36%) received as third line or higher. Out of the 134 pts, 39 (29%) had been treated with an ACEI or ARB during ICI treatment. Out of the 39 pts who had ACEI or ARB, 2 (5%) had complete response (CR) as best response, 11 (28%) had partial response (PR), 17 (46%) had stable disease (SD) and 9 (23%) had progressive disease (PD). Out of the 95 pts who did not receive ACEI or ARB, 3 pts (3%) had CR as their best response to ICI, 19 (21%) had PR, 39 (43%) had SD, and 29 (32%) had PD, (5 patients’ best response were unevaluable). The median OS for those who had ACEI/ARBs and did not have ACEI/ARBs was 32 months and 20 months respectively. Univariable analysis revealed that patients who received ACEI/ARBs had improved OS (Logrank p-value = 0.002; HR = 2.5 [95%CI: 1.4 - 4.5]). Conclusions: In this hypothesis-generating study, concurrent ACEI/ARBs are associated with better outcomes for mRCC pts receiving ICIs. Given the availability of ACEI/ARBs, it is important to validate this result in a larger dataset and after controlling for known prognostic factors.
Quantifying publication rates and time to publication for urologic oncology podium presentations.
Authors: Mikhail Mark , Chua Kevin , Patel Hiren V. , Tabakin Alexandra L. , Doppalapudi Sai Krishnaraya , Ghodoussipour Saum , Kim Isaac Yi , Jang Thomas L , Srivastava Arnav , Singer Eric A. 
Published: March 2021

357 Background: The American Urological Association (AUA) annual meetings serve as a large platform for unpublished research. Among the selected abstracts, podium presentations represent the most impactful submissions. Furthermore, between large meeting attendance and social media promotion, authors can disseminate their findings to a potentially large audience prior to final manuscript publication. While all AUA abstracts do undergo peer review, it is not with the same level of scrutiny that full-length manuscripts receive. Thus, we investigated the publication rates, impact factors, and time to publication of urologic oncology podium presentations at the AUA. Methods: Of 875 podium presentation abstracts from the 2017 AUA Annual meeting, 394 (45.0%) were classified as urologic oncology. We chose 2017 to allow for a three-year window for publication. Abstracts were assessed for subsequent publication between January 1, 2015 and May 31, 2020 with a pre-determined PubMed search protocol. Abstract authors were searched for individually, with key terms being added sequentially until <30 results were generated in PubMed. Each search result was then reviewed until a matching publication was found. Abstracts were deemed published if at least one author of the presented abstract was a manuscript author and/or at least one conclusion in the presented abstract was included in the conclusions of the publication. Publication rates, time to publication, and 2019 journal impact factors were collected. Results: Of 394 urologic oncology podium presentations at the 2017 AUA, 228 (57.9%) focused on prostate cancer, while 81 (20.6%) and 58 (14.7%) presentations focused on kidney and bladder cancer, respectively (table). Overall, 211 (53.6%) podium presentations were published. Median time from presentation to publication was 13.6 months (IQR: 7.5-21.5). There were 9 (2.3%) publications that were published prior to the submission deadline and 57 (14.5%) podium presentations that were published prior to the 2017 AUA meeting. The number of articles published at one, two and three years after the meeting was 90, 170 and 202, respectively. The median journal impact factor of all published works was 3.4 (IQR: 2.7-5.9). Conclusions: While AUA podium presentations disseminate valuable data, approximately half of these presentations were not published in peer-reviewed journals within three years. Therefore, care must be taken when promoting data or adopting new practices based on these presentations alone. [Table: see text]