bluuebunny/crossref_metadata_2025_split huggingface dataset:
Active surveillance in metastatic renal cell carcinoma: A single-center cohort.
Authors: Schwartzman William , Elias Roy , Govil Malvika , Nosair Waseem , Christie Alana , Courtney Kevin Dale , Bowman Isaac Alex , Cole Suzanne , Arafat Waddah , Hammers Hans J. , Brugarolas James 
Published: February 2022

389 Background: Emerging data suggest that active surveillance (AS) may be safely implemented in a subset of patients (pts) with metastatic renal cell carcinoma (RCC) and indolent disease to delay the initiation of systemic therapy without undermining long-term survival. However, widespread adoption of AS has been limited by a lack of data on factors portending favorable outcomes. In this study we sought to characterize pts undergoing AS at a large academic medical center to identify factors associated with time on AS. Methods: We identified pts on AS using Kidney Cancer Explorer (KCE), the data management platform of the Kidney Cancer Program at UT Southwestern Medical Center (2005-2020), as well as input from medical oncologists. The AS cohort was defined by (1) having metastatic RCC (determined by either a suspicious lesion > 1cm or a positive biopsy), and (2) the absence of prior systemic therapy. Baseline characteristics and IMDC criteria were evaluated at the outset. Outcomes of interest included progression free survival (PFS), time to systemic therapy (TST), and overall survival (OS). Survival estimates were generated using Kaplan Meier methods. Cox proportional hazard models were used in univariate and multivariate analyses to identify baseline characteristics associated with TST. Results: We identified 37 pts with metastatic RCC undergoing AS; 31 pts (83.8%) had ccRCC, 28 pts (75.7%) had a favorable IMDC prognostic group, 18 pts (48.6%) had one metastatic lesion at baseline, and the cohort had an average tumor burden of 21mm. The majority of pts had clinical or radiologic progression with a median PFS of 10.8 months (95% CI: 8.13-23.31). The median TST was 37 months (95% CI: 24.3-94.9). In total, there were 11 deaths (none of which occurred prior to the initiation of systemic therapy) and median OS after the initiation of AS was 132.5 months (95% CI: 87.3-NR). Multivariate analyses showed that higher numbers of metastatic lesions at baseline were associated with a shorter TST (HR:1.45; 95% CI: 1.03-2.03, p = 0.03). At a median follow-up of 62.5 months, 11/37 (29%) of pts had not yet started systemic therapy. Conclusions: These results expand upon previous studies and support a role for AS to delay systemic therapy in selected pts with metastatic RCC.
Impact of neoadjuvant immune checkpoint inhibitor therapy on primary tumor size and complexity: Correlation with surgical quality and short term oncological outcomes.
Authors: Saidian Ava , Hakimi Kevin , Panian Justine , Ajmera Archana , Barata Pedro C. , Berg Stephanie A. , Chang Steven Lee , Choueiri Toni K. , Dzimitrowicz Hannah Elizabeth , Emamekhoo Hamid , Gross Evan , Kilari Deepak , Lam Elaine Tat , Nonato Taylor , Psutka Sarah P. , Thapa Bicky , Weise Nicole , Zhang Tian , McKay Rana R. , Derweesh Ithaar 
Published: February 2022

390 Background:The concept of primary systemic therapy has gained increasing traction in the management of metastatic and locally advanced Renal Cell Carcinoma (RCC). Most series have evaluated the use of tyrosine-kinase inhibitors, however, with the emergence of immune checkpoint inhibitor therapy as first line agents in advanced RCC, further assessment of efficacy is warranted. We examined the effects of immunotherapy (IO) combinations on the primary tumor and consequent surgical quality and short-term oncological outcomes. Methods: We conducted a multi-center, retrospective analysis of patients with advanced/metastatic RCC having received IO followed by Radical (RN) or partial nephrectomy (PN). Primary outcome was achievement of Bifecta (composite outcome of complete resection and no 30-day post-operative complications). Predictors for achievement of Bifecta were assessed with logistic regression multivariable analysis. Secondary outcomes were change in maximal tumor dimension, RENAL nephrometry score and disease progression. Kaplan-Meier analysis was used to assess progression-free survival (PFS) for Bifecta and non-Bifecta patients. Results: We identified 52 patients with advanced RCC across 9 institutions who were eligible. The median age was 63 years and 60.4% were males. Median tumor size at diagnosis was 9.3 cm. 19.6% had T4 disease and 75% had AJCC Stage IV disease. IO treatment resulted in significant reductions in median tumor size (-25.4%; 9.7 cm vs. 7.3cm p = 0.0129) and RENAL nephrometry score (9 to 8, p = 0.032). 43 (83%) of patients underwent RN and (9) 17% had PN. Median tumor size was smaller for PN (8 vs. 4.1 cm, p < 0.001), and 30 day complication rates were higher (p = 0.024). Bifecta was achieved in 39 patients [33/42 (78.6%) RN and 6/9 (67%) PN, p = 0.264). Predictors for achievement of Bifecta were younger age (OR 1.06, p = 0.01), increasing reduction in tumor size (OR 1.187, p < 0.001), and shorter time between therapy and surgery (OR 1.07, p < 0.001). Kaplan-Meier analysis demonstrated longer median time to progression in the Bifecta-positive group compared to patients who failed to achieve Bifecta (75 vs. 30 months, p = 0.04). Conclusions: Pre-surgical therapy resulted in tumor size and complexity reduction. Tumor size reduction was predictive for achievement of Bifecta, which was associated with improved short term oncological outcomes. To our knowledge, this is the first series evaluating the effect of neoadjuvant systemic therapy on the primary tumor prior to surgical intervention.
Trends of kidney cancer burden from 1990 to 2019 in European Union 15+ countries.
Authors: Abdallah Nour , Jani Chinmay , Mouchati Christian , Jani Ruchi Tusharkumar , Bhatt Padmanabh , Salciccioli Justin , Khanna Prateek , Singh Harpreet , Shalhoub Joseph , McKay Rana R. , Marshall Dominic C 
Published: February 2022

393 Background: Kidney cancer is among the most common cancers worldwide and is increasing in incidence. During 2020, around 400,000 new cases of kidney cancer were reported, with 180,000 estimated deaths. In recent decades, significant variability in the incidence and mortality of kidney cancer has been universally reported. This study aimed to compare geographical trends in incidence, mortality, and disability-adjusted life years from kidney cancer between European Union (EU) 15+ countries from 1990 to 2019. Methods: The mortality data of kidney cancer were extracted from the Global Burden of Disease Study database. Versions 10 and 9 of the International Classification of Diseases were adopted. Age-standardized incidence rates (ASIR), age-standardized death rates (ASDR), and disability-adjusted life years (DALYs) were collected, per year and per country of the EU15+ group. Mortality-to-incidence ratios (MIR) were calculated. Data was then dichotomized into males and females. Joinpoint regression was done for analysis of trends. Results: From 1990 to 2019, ASIRs increased in most of the countries except for Luxembourg for males, the United States of America (USA) for females, and Austria and Sweden for both sexes. The largest rises of ASIRs were in Denmark for males and females (+89.3% and +82.8%, respectively). ASDRs increased in 10/19 countries for males and 9/19 in females, with the highest rise in Denmark for males and females (+41.7% and +37.7% respectively), and the largest drop in Austria for males and females (-33.8% and -35.8% respectively). MIRs decreased in all countries, for both sexes, with the widest declines in Portugal for males (-29.0%) and in Ireland for females (-26.6%). Trends in DALYs were variable, with the highest rise in Denmark for males and females (+38.6% and +30.2% respectively) and the largest drop in Austria for males and females (-39.5% and -41.2%, respectively). In 2019, the highest ASIR was observed in the USA for males (16.7/100,000) and in Finland for females (8.3/100,000), the highest ASDR in the Netherlands for males (6.1/100,000) and Finland for females (3.0/100,000), highest MIR in Sweden for both genders (0.6/100,000 each), and highest DALYs in the Netherlands for males (132.3/100,000) and in Finland for females (62.6/100,000). Conclusions: The incidence and mortality from kidney cancer rose in most EU15+ countries from 1990 to 2019. Interestingly, an improvement in the outcomes is predicted by the drop in MIR in all countries.[Table: see text]
Accuracy of germ cell tumor histological subtype and stage within the Canadian cancer registry.
Authors: Holland Patrick , Karmas Tim , Merrimen Jennifer , Wood Lori 
Published: February 2022

411 Background: Cancer registries are the mainstay for Canadian population-based cancer statistics and research. Data is collected in provincial and territorial registries including the Nova Scotia Cancer Registry (NSCR). The goal of this study was to determine the accuracy of the NSCR data regarding the diagnosis, primary site, histological subtype, and stage of germ cell tumors (GCT) when compared to the individual pathology reports and staging investigations from the chart. Methods: This analysis included all NSCR patients diagnosed with GCT from 2006-2015. From the NSCR, the date and method of diagnosis, primary site, histology, and stage were recorded. This data was also extracted from each patient’s chart record. Any discrepancies between the two sources were reviewed and reasons behind the discrepancies were recorded. Results: 239 unique patients were identified in the NSCR during the specified time period. Ten were excluded as no chart records were available to confirm accuracy. 229 patients make up the study cohort. Using NSCR data 57.6% had seminoma, 34.5% nonseminoma (NSGCT), and 7.9% other. Discrepancies in pathology were noted in 29 patients (12.7%) for a number of reasons including no appropriate coding option in the NSCR, multiple tumors, biopsy only specimens with misinterpretation of tumor marker elevation, and true coding error. Using NSCR staging data (available in 185 cases) 71.9% had stage I, 12.4% stage II, 11.9% stage III, and 3.8% other. Discrepancies in stage were noted in 33 patients (17.9%) with NSCR data downstaging 10 patients (5.4%) and upstaging 19 patients (10.3%) predominantly due to miscoding patients as stage IS. The site of the primary GCT was discrepant in 12 patients (5.2%) due primarily to difficulty coding post chemotherapy orchiectomy specimens and burnt out primary testicular lesions. The date of diagnosis was accurate within 1 week for all patients except one which differed by several months. Conclusions: Canadian cancer registry data is population based and used for many purposes including policy decisions and research. The NSCR higher level data such as date of diagnosis and overall pathological diagnosis appears relatively accurate. However, there are inaccuracies in more detailed information like histological subtype and stage. This study raises awareness of these gaps. It also highlights key areas for improvement in educating registry personnel who interpret and enter data about the uniqueness of GCT pathology, staging and interpretation of tumor markers.
Utilization of radiation therapy and impact on outcomes in spermatic cord sarcomas in the United States.
Authors: Matani Hirsch , Schuyler Kyle , Wegner Rodney E. , Beriwal Sushil , Horne Zachary D 
Published: February 2022

419 Background: Spermatic cord sarcomas are a rare entity with management consisting of radical orchiectomy and the value of adjuvant radiation being unclear, as the literature consists of heterogeneous case series spanning multiple decades with limited numbers of patients. Methods: The National Cancer Data Base was queried for men who underwent orchiectomy for spermatic cord sarcomas between 2004 and 2018 with known surgical margin status. Kaplan-Meier with log-rank test and Cox proportional hazards tests were utilized for overall survival (OS) calculations. Associations were determined with bivariate regression analysis. Results: A total of 912 men were identified who met inclusion criteria. Six hundred seventeen (67.7%) had liposarcomas (LS) while 32.3% had non-lipsarcomatous (NLS) histologies. 5/10-year OS for men with LS was 85.1%/67.4% and 74.1%/58.4% for NLS, respectively (p < 0.001). 238 (26.1%) men were treated with adjuvant radiation therapy with similar distributions between LS and NLS. Utilization of radiation was significantly associated with moderate-poorly differentiated histology (HR 3.228 [95%CI 2.241-4.649] p < 0.001), radical orchiectomy (HR 1.477 [1.062-2.054] p = 0.020), positive surgical margins (HR 1.826 [95%CI 1.257-2.652] p = 0.002), but not histologic subtype or tumor size. There was no difference in OS for LS nor NLS with respect to the application of adjuvant radiation, but in men with moderately-poorly differentiated LS treated with adjuvant radiation, 5-year OS was 86.8% vs. 68.6% (p = 0.148). In men with well-differentiated LS, 5-year OS was 93.6% with XRT vs 89.5% (p = 0.623). Adjuvant XRT did not impact OS in men with positive surgical margins, nor did it have an impact on OS for NLS regardless of disease grade or margins. Conclusions: Adjuvant radiation therapy is utilized for approximately one quarter of men diagnosed with spermatic cord sarcomas. XRT may impact OS for men with moderately-poorly differentiated liposarcomas; further research with patient-level data is required.
Viable germ cell tumor and teratoma can be distinguished from necrosis in postchemotherapy retroperitoneal lymph node dissection specimens by a combination of microRNA-371a-3p and 375-5p.
Authors: Nestler Tim , Kremer Lara , von Brandenstein Melanie , Koeditz Barbara , Paffenholz Pia , Hellmich Martin , Pfister David , Heidenreich Axel 
Published: February 2022

421 Background: Our objective was to identify a combination of microRNAs (miRNA) to differentiate between viable tumor (V) or teratoma (T) and necrosis/fibrosis (N) in pcRPLND specimens of metastatic nonseminomatous germ cell tumor (NSGCT) patients with residual masses ≥1cm after chemotherapy. Our hypothesis is that a biomarker guided therapy could reduce overtreatment with pcRPLND in patients with only N. Methods: Forty-eight patients were identified, n = 16 each with T/V/N. Representative regions of T/V/N were microdissected, subsequently total RNA was isolated and miRNA expression was analyzed for miR-371a-3p, 375-3p, and 375-5p using qPCR. ROC analysis was performed for each miRNA and for all combinations in order to determine the discriminatory capacity of V and T vs. N. Results: For the group comparisons of V vs. N miR-371a-3p achieved the highest fold change (FC) of 31.1 (p = 0.023) while for T vs. N miR-375-5p performed best (FC 64,2; p < 0.001). Likewise, the most accurate AUC for V was 0.75 using miR-371a-3p, for T 0.80 using miR-375-5p. Combining the best performing miRNAs for V and T resulted in an AUC of 0.94 with a sensitivity of 93.75, specificity of 93.75, PPV of 96.8 and NPV of 83.3. Conclusions: In pcRPLND tissue samples V and T could be distinguished from necrosis/fibrosis by combining miR-371a-3p and miR-375-5p with great accuracy. This combination of miRNAs might serve as new biomarker in the future, in order to spare miRNA-negative patients from pcRPLND. However, further studies analyzing patient’s serum are needed to confirm the clinical impact of these biomarkers.
Biomarkers of gut microbial transfer and their association with cognitive impairment in long-term survivors of testicular germ cell tumors.
Authors: Chovanec Michal , Kalavska Katarina , Obertova Jana , Palacka Patrik , Rejlekova Katarina , Sycova-Mila Zuzana , De Angelis Valentina , Orszaghova Zuzana , Lesko Peter , Svetlovska Daniela , Mladosievicova Beata , Mardiak Jozef , Pastorek Michal , Vlkova Barbora , Celec Peter , Mego Michal 
Published: February 2022

426 Background: Survivors of testicular germ cell tumors (GCT) may suffer from long-term cognitive impairment. We hypothesized that disruption of intestinal barrier during chemotherapy and/or radiotherapy may be a contributing factor of cognitive dysfunction within the gut-blood-brain axis. Methods: GCT survivors (N = 142) from National Cancer Institute of Slovakia completed the Functional Assessment of Cancer Therapy Cognitive Function questionnaires during their annual follow-up visit at 9-year median (range 4-32). Biomarkers of gut microbial transfer and dysbiosis (GMT) high mobility group box-1 (HMGB-1), lipopolysaccharide (LPS), d-lactate and sCD14 were measured from peripheral blood obtained during the same visit. Each questionnaire score was correlated with biomarkers of GMT. Survivors were treated with orchiectomy only (N = 17), cisplatin-based chemotherapy (N = 108), radiotherapy to the retroperitoneum (N = 11) or both (N = 6). Results: GCT survivors with higher sCD14 had worse cognitive function perceived by others (CogOth domain) (mean ± SEM; 14.6 ± 0.25 vs 15.4 ± 0.25, p = 0.019), lower perceived cognitive abilities (CogPCA domain) (20.0 ± 0.74 vs 23.4 ± 0.73, p = 0.025) and lower overal cognitive function score (109.2 ± 0.74 vs 116.7 ± 1.90, p = 0.021). There were no significant cognitive declines associated with HMGB-1, d-lactate and LPS. Survivors treated with ≥ 400mg/m2 of cisplatin based chemotherapy had higher LPS (567.8 ± 42.7 vs 462.9 ± 51.9, P = 0.03). Survivors treated with chemotherapy + radiotherapy vs orchiectomy only had non-significantly higher sCD14 (7279.9 ± 810.1 vs 5851.0 ± 481.7, P = 0.09). Conclusions: sCD14 may serve as a promising biomarker of cognitive impairment in long-term cancer survivors. While chemotherapy and radiotherapy-induced intestinal injury may be the underlying mechanism, further research using animal models and larger patient cohorts are needed to explore the pathogenesis of cognitive impairment in GCT survivors.
Prognostic factors associated with malignant somatic transformation (MST) of germ cell tumors (GCT) in a Mexican cohort: The experience of the Instituto Nacional de Cancerología, Mexico (NCIM).
Authors: Sobrevilla-Moreno Nora , Pérez-Montiel Delia , López-Macias Diego , Gonzalez-Rodriguez Diana , Sobrevilla-Calvo Pedro , Avitia Miguel Angel Alvarez 
Published: February 2022

427 Background: MST is a rare entity defined as the development of somatic non-germ cell malignancies within GCT, its incidence varies between 2.7% and 8.6% of GCT’s. Previously reported favorable prognostic factors include synchronous diagnosis of MST and GCT, absence of non-pulmonary visceral metastases (NPVM) and presence of rhabdomyosarcoma. Methods: Retrospective study to describe prognostic factors of MST in GCT in a Hispanic population. Patients (pts) with diagnosis of MST from 2006 to 2019 were identified from the GCT database of the NCIM. Pts’ characteristics and outcomes were collected from clinical charts and recorded. Overall survival (OS) was performed with the Kaplan Meier (KM) method in the whole cohort and in patients with advanced disease (AD) (stage II and III). Comparisons were calculated with the log-rank test for KM and Chi squared test for categorical factors. Results: Seventy-one pts with MST were included in the overall population (OP). Non-seminoma 95.8%; testicular primary 97.2%; clinical stage (CS) I 32.4%, II 16.3%, III 49.3%; S2-S3 42.3%, 39.6% poor IGCCCG prognosis, 11.3% NPVM. Type of MST: 56.3% rhabdomyosarcoma (RMS), 21.1% spindle cell sarcoma, 12.7% PNET, 9.9% adenocarcinoma. 18.3% more than 1 MST histology. Median follow-up: 43.8 months (m). For the OP, mOS 71.1m (95% CI 80.0 – 119.2). OS for CS I have not been reached (NR). Forty-seven pts with AD were included, mOS 37m (95% CI 9.69 – 64.36). Characteristics associated with prognosis for OS for the OP and the AD cohorts are summarized in table. Pts with AD and RMS had more frequently a synchronous tumor (87.5% vs 58.3%, p=0.02) and absence of surgery for MST (70.8% vs 37.5%, p=.02). Conclusions: As far as we know, this is the largest cohort of hispanic pts with MST. Prognostic factors differed between OP and AD cohorts. Pts with MST and AD have a poor prognosis. Synchronous diagnosis of MST and presence of rhabdomyosarcoma are adverse prognostic factors for AD pts. Further study with a larger population is needed to verify these findings. Univariate analysis for OS.[Table: see text]
First line avelumab in PD-L1+ve metastatic or locally advanced urothelial cancer (aUC) patients unfit for cisplatin (cis): The ARIES trial.
Authors: Iacovelli Roberto , Ciccarese Chiara , Brunelli Matteo , Battelli Nicola , Buttigliero Consuelo , Caserta Claudia , Buti Sebastiano , Santini Daniele , Naglieri Emanuele , Galli Luca , Verri Elena , Ermacora Paola , Milella Michele , Masini Cristina , Aprile Giuseppe , Milesi Laura , Spina Francesco , Rizzo Mimma , Sperduti Isabella , Fornarini Giuseppe 
Published: February 2022

439 Background: Avelumab (ave) was approved as maintenance therapy after platinum-based first line (1L) therapy for patients (pts) with aUC based on ph. 3 Javelin Bladder 100 study (NCT02603432), showing significant overall survival (OS) improvement. Here we tested the activity of ave as 1L of therapy in cis-unfit pts with aUC and PD-L1+ve expression. Methods: ARIES is a single-arm, multi-site, open-label phase II trial. Enrolled pts had aUC, were cis-unfit (at least one of: ECOG-PS = 2, CrCl < 60 mL/min, grade ≥2 peripheral neuropathy/hearing loss, progression within 6-mos before the end of neo/adj chemo), had not previously received chemo for aUC and PD-L1≥5% (SP263) centrally assessed. Pts received ave 10 mg/Kg IV Q2W until progression, unacceptable toxicity and withdrawal, whichever occurred first. The primary endpoint was the 1-year OS. Key secondary endpoints were median-OS, -PFS, ORR and safety. Results: A total of 198 eligible cis-unfit pts have been tested for PD-L1 and 71 (35.6%) have been found positive. Among enrolled patients (N = 71), median age was 75 y, 35 (49.3%) had visceral disease, and 22 (31.0%) had ECOG-PS = 2; 50 (70.4%) had CrCl < 60 mL/min and 9 (12.7%) progressed within 6-mos from the end of neo/adj chemo. At the cut-off data (Oct 7, 2021), median follow up was 9.0 mo and 13 patients are still on treatment. The median OS was 10.0 mos (95% CI, 5.7-14.3), and 40.8% of patients were alive at 1-year. The ORR for all patients was 22.5%; complete response, 1.4% (n = 1); partial response, 21.1% (n = 15). Clinical benefit was 43.6% (n = 31). Median PFS was 2.0 mos (95% CI, 1.4-2.6). Among the 56 pts who received at least 3 cycles (29 days) of therapy the median OS was 16.0 vs 1.0 mos. Five (7.0%) grade 3 ave-related adverse events, and no treatment-related death were reported. Conclusions: Ave is active and safe in pts with cis-unfit, PD-L1+ve aUC and poor baseline characteristics. Clinical trial information: NCT03891238.