bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical outcome of patients diagnosed with testicular sex cord stromal tumors.
Authors: Bukhari Syed Abdullah Javaid , Malik Maira Iqbal , Hutton Paul , Porfiri Emilio , Jafri Mariam 
Published: May 2020

e17055 Background: Testicular Sex Cord Stromal Tumors (TSCST) are rare representing approximately 5% of testicular cancers. Leydig Cell Tumours (LCT) constitute 1-3% of testicular tumours, occur commonly in third to sixth decade and are up to 50mm in diameter. Sertoli Cell Tumours(SCT) constitute less than 1%, occur commonly in the fourth decade and have an average diameter of 35mm. High-risk histological features include; tumour size, increased mitotic activity, pleomorphic nuclei, necrosis, vascular invasion and rete testis invasion. Management is surgical with no standard chemotherapy or radiotherapy in adjuvant or metastatic setting. Methods: A retrospective review of epidemiology, radiological staging, histopathological features, relapse rate and treatment in 82 patients diagnosed with TSCST between 4/12/2001 -27/12/2018 at a tertiary referral centre. Results: 2,170 testicular cancer patients were diagnosed in this period of whom 82 patients (3.8%) had TSCST. 65 patients (2.9% ) had LCT,13 patients (0.59%) had SCT, 3 patients had Unclassified SCST and 1 patient had Mixed SCST. Median patient age for LCT was 43 years, SCT was 29 years, unclassified SCST was 46 years and for mixed SCST was 49 years (age range of TSCST was 18 - 82 years). Median size of LCT was 11mm (range 4 – 28 mm) in 43 patients and of SCT was 16mm (range 7 – 60mm) in 10 patients. 79 patients (3.6% ) presented with stage 1 disease. One patient with LCT and 4 high risk histological features on initial diagnosis had local retroperitoneal recurrence 4 years later and underwent surgical resection with 1year distant disease-free survival. On distant relapse, he was treated with mitotane. One patient presented with metastatic SCT with 4 histological high risk features. He was treated with carboplatin and etoposide. Median survival in the metastatic disease was 10.5 months. Conclusions: TSCST have an excellent prognosis with over 98% of patients are free of disease post-surgery. Our relapse rate is 1.2% which is lower than previously reported and is confined to patients with high risk features. Metastatic LCT and SCT are resistant to chemotherapy with poor survival.
The effect of primary granulocyte-colony stimulating factor prophylaxis on incidence of febrile neutropenia in patients with testicular germ cell tumors.
Authors: Hapakova Nikola , Chovanec Michal , Rejlekova Katarina , Kalavska Katarina , Obertova Jana , Palacka Patrik , De Angelis Valentina , Sycova Zuzana , Mardiak Jozef , Mego Michal 
Published: May 2020

e17056 Background: Testicular germ cell tumors (GCTs) represent only one percent of all solid tumors; however, they are the most common solid malignancy in men 15-35 years old. Febrile neutropenia (FN) is a grievous complication of chemotherapy, frequently occurring in GCT patients. The aim of this retrospective study was to assess the effect of primary granulocyte-colony stimulating factor (G-CSF) prophylaxis on the incidence of FN in GCT patients. Methods: This study was conducted using the National Cancer Institute medical records database. Patients diagnosed with germ cell tumors treated with first line/adjuvant chemotherapy at the National Cancer Institute, Bratislava, Slovakia from January 2000 to December 2017 were eligible. Starting in January 2006, patients received G-CSF prophylaxis after every cycle of chemotherapy. Results: Out of 393 patients, 265 patients received primary G-CSF prophylaxis and 128 patients did not receive prophylaxis. The majority of patients (69.97%) were treated with bleomycin, etoposide and cisplatin chemotherapy. There were 61 deaths (15.5%) in our study population. 2- and 5-year OS of the study group was 86.8% and 83.1%, respectively. During the study period, 71 patients (18.1%) suffered FN events. Out of 128 patients who did not receive primary prophylaxis, 42 (32.8%) patients suffered FN, while only 29 (10.9%) patients with primary prophylaxis suffered FN ( P = 0.0000001). On subgroup analysis, FN incidence decreased in all groups with primary prophylaxis, except for patients with stage I GCT receiving adjuvant chemotherapy. Patients receiving G-CSF prophylaxis had significantly longer overall survival when compared to patients without prophylaxis. (HR = 0.44, 95% CI 0.26-0.75; P = 0.0009). Conclusions: Primary G-CSF prophylaxis was associated with significantly decreased FN incidence and longer overall survival in patients treated with first line chemotherapy and should be consider in all patients except stage I disease.
Testicular cancer in Hispanics: Are we approaching ethnic parity?
Authors: Janania Martinez Michelle , Garza Juan , Snedden Tyler William , Surapaneni Prathibha , Fernandes Flavia , Williams Madison H , Williams Ryan , Cox Travis , Blaize Jean-Pierre , Warnecke Brian , Djoufack Djoumessi Lakene Raissa , Yoo James , Kakarla Sushanth , Pippin Kelly , Moore Christine Ann , Lathrop Kate Ida 
Published: May 2020

e17059 Background: Hispanics (HI) are the fastest growing ethnic group in the US, representing 52% of US population growth from 2010-2018. In the past decade, they have also experienced a rise in incidence of testicular cancer. Studies have shown that HI have a higher incidence of Non-Seminomatous Germ Cell Tumors (NSGCT), present at an earlier age, have advanced stage at diagnosis, and worse outcomes (including increased mortality) when compared to Non-Hispanics (NH). However, there is a paucity of data and a growing need to better characterize this patient population. To our knowledge, this is the largest cohort of testicular cancer patients from a single academic institution that serves primarily HI. Methods: We retrospectively reviewed 243 patients with Testicular Cancer, both Seminoma and NSGCT; all diagnosed between 2010-2018. Key variables included age, race/ethnicity, comorbidities, insurance status, diagnosis, stage, treatment received/response and vitality status in 2018. Continuously distributed outcomes were summarized with mean/standard deviation; categorical outcomes with frequencies/percentages. Significance of associations between categorical outcomes was assessed with Chi Square test of association. Results: We identified 243 patients with testicular cancer, 168 (69%) HI and 75 (31%) NH. See Table. Median duration of follow up was 18.7 months (SD 27.3). When comparing HI vs NH: 65% vs 64% achieved complete response after primary treatment (p value 0.982); 16% vs 23% had a disease relapse (p value 0.184); and 82 vs 90% were alive at end of 2018 (p value 0.257). Conclusions: Our study supports available data that HI present at an earlier age. However, we found no significant difference in insurance status, histology, stage at diagnosis and outcomes in HI compared to NH. HI predominance in our population could explain the lack of difference observed but further studies are needed. Research Sponsor: None.[Table: see text]
Clinical outcomes of checkpoint inhibitors in metastatic non-clear cell renal cell carcinoma and clear cell renal cell carcinoma with variant features.
Authors: Chang Guy vin , Ellithi Moataz , Elnair Radowan , Bleeker Jonathan 
Published: May 2020

e17065 Background: Checkpoint inhibitors (CPI) are a well-established treatment option for advanced clear cell renal cell carcinoma (ccRCC); however, there is a paucity of data on efficacy of CPI on advanced non-clear cell renal cell carcinoma (nccRCC) and ccRCC with variant (sarcomatoid or rhabdoid) features. Recently, small series have demonstrated benefit for CPI in these entities. Methods: We performed a retrospective review of patients with metastatic nccRCC or ccRCC with variant features, who received a single agent CPI (nivolumab or pembrolizumab) or combination therapy (nivolumab and ipilimumab) between Feb 2016 – Oct 2019 at our integrated community-based health system. The primary endpoint was objective response rate (ORR), and the secondary endpoints were progression-free survival (PFS) and overall survival (OS). We used Kaplan-Meier survival analysis for PFS and OS. Results: A total of 26 patients met eligibility criteria; 11 patients with nccRCC (papillary n = 6, chromophobe n = 1, unclassified n = 4), 12 patients with sarcomatoid ccRCC, 2 patients with rhabdoid ccRCC, and 1 patient with both sarcomatoid and rhabdoid features. Sixteen patients received nivolumab, 3 received pembrolizumab, and 7 received a combination of nivolumab and ipilimumab. CPI was halted in 4 patients due to adverse effects including arthralgia, hyperthyroidism, hepatitis, and colitis. Among these 26 patients, 5 patients (19.2%) achieved complete response (CR), 3 patients (11.5%) achieved partial response (PR), and 10 patients (38.5%) had stable disease (SD). All patients who achieved CR or PR had a durable response throughout the follow-up period. At the median follow-up of 16.4 months, median PFS was 14.3 months, and median OS was not reached. Conclusions: In this retrospective series, the ORR of CPI in metastatic nccRCC and ccRCC with variant features was 30.7%, and disease control rate was 69.2%. These findings suggest that CPI may provide significant clinical benefit in patients with nccRCC and ccRCC with sarcomatoid and/or rhabdoid features. Sample size may limit inference and additional studies are needed.
Minimally invasive partial nephrectomy versus percutaneous cryoablation for stage Ia renal cell carcinoma: A cost-effectiveness analysis.
Authors: Wu Xiao , Uhlig Johannes , Shuch Brian M. , Kim Kevin 
Published: May 2020

e17066 Background: Minimally invasive partial nephrectomy (PN) and percutaneous cryoablation (Cryo) are treatment strategies for renal cell carcinoma (RCC). The purpose of this study is to assess the cost-effectiveness of PN and Cryo for stage Ia RCC. Methods: A decision-analysis model was constructed over 5 years from a health care sector’s perspective using TreeAge Pro Suite 2019 (TreeAge Software LLC, Cambridge, MA). The two evaluated strategies were PN and Cryo. The model incorporated the clinical course of stage Ia RCC after either treatment, including costs and quality of life associated with major complications, imaging surveillance (based on 2014 National Comprehensive Cancer Network guidelines), local and metastatic recurrences, and cancer-specific mortality. All clinical parameters were derived from the literature. A willingness-to-pay threshold of $100,000/quality adjusted life year (QALY) was used. 1 QALY is equivalent to 1 year of life in perfect health. Outcomes were measured by incremental effectiveness ratio. Base case calculations, Monte Carlo Simulations with 10,000 iterations using bootstrapping for parameters from their distributions, and multiple sensitivity analyses were performed. Results: Five-year local recurrence-free, metastasis-free, and cancer-specific survival from recent literature were 97.7% versus 95.9% ( p = 0.18), 98.0% versus 100% ( p = 0.14), 99.3% versus 100% % ( p = 0.7) for PN and Cryo. PN and Cryo yielded similar health benefits of 3.63 QALY and 3.64 QALY. Overall costs were $26,343 and $19,346 for PN and Cryo. A total of 89.28% of the 10,000 simulations showed higher cost-effectiveness of Cryo than PN. One-way sensitivity analyses varying long-term outcomes after Cryo while keeping outcomes after PN constant, revealed that Cryo is more cost-effective than PN when its local recurrence risk is < 3.94% per year (18.2% over 5 years), metastasis risk is < 1.51% per year (7.33% over 5 years), or cancer-specific mortality risk is < 0.96% per year (4.7% over 5 years). PN is more cost-effective if Cryo local recurrence risk is 3.5% higher than PN per year, when the metastasis risk is 1.1% higher than PN per year, or when its cancer-specific mortality is more than 0.9% higher than PN per year. Cryo is more cost-effective than PN if its cost is not more than $1,000 higher than PN. Conclusions: Our study showed that Cryo is more cost-effective than PN for stage Ia RCC patients with comparable effectiveness at a lower cost, based on multiple probabilistic and deterministic sensitivity analyses.
Clinical impact of early progression among patients (Pts) with metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors (TKIs) in first-line (1L) setting: IMPACT RCC real-world study.
Authors: Hutson Thomas E. , Liu Frank Xiaoqing , Pandya Shivani , Dieyi Christopher , Kim Ruth , Krulewicz Stan , Kasturi Vijay , Bhanegaonkar Abhijeet 
Published: May 2020

e17079 Background: Previous research has indicated a high burden of illness among mRCC pts who progressed to second line (2L) systemic therapy, suggesting benefits to delaying 1L progression. This study examined the clinical impact of early vs delayed disease progression among mRCC pts treated with 1L TKI monotherapies followed by 2L therapy in the US Veterans Health Administration (VHA) database. Methods: Newly diagnosed mRCC pts treated with 1L TKIs followed by 2L therapy were identified between OCT2013-MAR2018 within the VHA database (1L start date = index date). Eligible pts were required to have continuous enrollment for ≥6 months post-2L therapy initiation unless the pt died. A Kaplan-Meier (KM)-derived median time to 2L therapy initiation was used as the cut-off to categorize pts into early (≤median) and delayed ( > median) progression cohorts. KM analysis and Cox proportional hazards models were used to compare and assess the impact of predictive factors on clinical outcomes including overall survival (OS), time to 2L discontinuation (index date to 2L discontinuation or death), and time to 3L treatment initiation (index date to 3L start or death) among pts in the early vs delayed progression cohorts. Results: Among 289 mRCC pts, the mean age was 67.4 years and the median time to 2L initiation was 6.1 months. Pt characteristics were similar between the early (n = 145) and delayed (n = 144) progression cohorts. During follow-up, the delayed progression cohort had better clinical outcomes than the early progression cohort did (Table below). Conclusions: Early progression is associated with worse clinical outcomes, confirming the need to delay disease progression among mRCC pts with effective 1L treatment strategies. Results indicate the need for use of more efficacious therapies, e.g. immuno-oncology-based combinations, in 1L that can delay disease progression and have potential to reduce disease burden. [Table: see text]
Decision tree model with tumor immune function genes for predicting response to anti-PD1 therapy in renal cell carcinoma.
Authors: Bi Xingang , Luo Zhiwen , Bi Xinyu 
Published: May 2020

e17084 Background: No current models can predict prognosis as well as immunotherapy benefits in renal cell carcinoma (RCC). The current study was undertaken to develop and validate a simple decision tree model to predict survival and immunotherapy benefits in patients with RCC. Methods: Analysis on RNA expression in a reported clinical trial dataset identified tumor immune function genes differentially expressed between anti-PD-1 response and non-response RCC. The analysis on these genes in different populations and platforms to develop a Bi-Luo (BL) DTM. The predictive performance of the BL DTM on the prognosis and the immunotherapy outcome in RCC was comprehensively analyzed and validated. Then, the mechanism of BL classification on the immune microenvironment in RCC was extensively analyzed. Results: Immunologic genes expression alteration resulted in the sensitivity for anti-PD-1 therapy in RCC. Twelve tumor immune function genes were enriched based on anti-PD-1 response. Survival analysis and machine learning algorithms on 12 genes established a BL classification based on 545 RCC samples to differentiate patients into low risk (BL1) and high risk of poor survival (BL2) groups ( P < 0.0001). The BL classification was a better independent prognosis indicator ( P = 0.004). TIDE algorithm predicted the response of two subgroups to immune checkpoint blockade, and BL1 was more promising to respond to anti-PD-1 therapy ( P = 0.00003268). Our BL classification was visualized in a 3 genes-DTM (F2RL1, TNFRSF and WHSC1) with a high prediction accuracy (AUC = 0.84) in an external validation cohort. Furthermore, in a small-scale immunotherapy clinical trial dataset, our BL DTM had a high specificity (0.86) to identify the non-response RCC in anti-PD-1 therapy. Gene expression of immune inhibiting factors in BL2 subtype was higher than BL1 subtype (all P < 0.01), but less in tumor mutation burden ( P = 0.009). Moreover, we found that BL2 subtype had higher fractions of Tregs ( P < 0.001), CD8+ T cells ( P = 0.037) and lower fractions of resisting memory CD4+ T cells ( P < 0.001) than BL1 subtype. And most HLA subtype genes, namely HLA-G, HLA-E, HLA-DR, HLA-DQ and HLA-DP, were significantly down-regulated in BL2 subtype (all P < 0.05). Conclusions: Our BL based DTM could predict survival and has potential for identifying RCC patients who could not benefit from anti-PD-1 immunotherapy. Non-response of RCC to anti-PD-1 immunotherapy is strongly related to the down-regulation of the immune response.
Combination therapy with nivolumab and tyrosine kinase inhibitors in patients with metastatic renal cell carcinoma.
Authors: Garmezy Benjamin , Zhang Tian , Laccetti Andrew Leonard , Economides Minas P. , Shah Amishi Yogesh , Tannir Nizar M. , Jonasch Eric , Msaouel Pavlos , Zurita Amado J. , Corn Paul Gettys , Venkatesan Aradhana M. , Brown Landon Carter , Kao Chester , Kinsey Emily Noelle , Harrison Michael Roger , Armstrong Andrew J. , George Daniel J. , Campbell Matthew T 
Published: May 2020

e17090 Background: Two immunotherapy (IO) and tyrosine kinase inhibitor (TKI) combinations are FDA-approved for patients (pts) with metastatic renal cell carcinoma (mRCC). Here we present a multicenter off-protocol experience with IO/TKI combinations after progression on monotherapy. Methods: We performed a retrospective analysis of pts with mRCC who received combination non-FDA approved off-protocol IO/TKI combination therapy from 11/2015 – 1/2019 at MD Anderson Cancer Center and Duke Cancer Institute. Results: 48 pts met criteria for study inclusion. At therapy start: median (med) age 65 years; 75% clear cell histology; 68.8% IMDC intermediate risk (20.8% favorable, 10.4% poor); 81.3% prior nephrectomy; med metastatic sites: 2; med prior systemic treatments: 2; most common metastatic sites: lung (58.3%), lymph node (52.1%), and bone (43.8%). Pts received nivolumab (nivo) in combination with the following: cabozantinib (n = 24, 50%), pazopanib (13, 27.1%), axitinib (6, 12.5%), lenvatinib (2, 4.2%), ipilimumab/cabozantinib (3, 6.3%). Med PFS was 13.7 months and med OS was not reached. The two largest cohorts received nivo + cabozantinib (N+C; med dose 40 mg daily) or nivo + pazopanib (N+P; med dose 400 mg daily). The N+C cohort had higher med metastatic sites (3 vs 2) and was more pretreated with agents unique to their IO/TKI combination (med 2 vs 0). In the N+P group, more pts had started on TKI prior to addition of nivo at progression (69.2% vs 45.8%), and fewer had IO monotherapy with TKI addition (30.8% vs 50%). With a med follow up of 14.0 months after combination start, the N+C cohort had a med PFS of 7.3 months (initiated TKI first: 4.8, IO first: 8.2) and med OS of 18.2 months (TKI first: 11.8, IO first: 24.3). The N+P cohort had med follow up of 20.5 months after combination, med PFS of 21.3 months (TKI first: 16.5, IO first: 21.8), and med OS was not reached. In the N+C group, 87.5% experienced any grade adverse event (AE), most common included fatigue (79.2%), diarrhea (42.7%), nausea (29.2%), hypertension (29.2%), and weight loss (25.0%). In the N+P group, 92.3% experienced any grade AE, including fatigue (76.9%), hypertension (38.5%), diarrhea (30.8%), nausea (30.8%), and weight loss (30.8%). There were no grade ≥3 AEs. Conclusions: Slow disease progression on nivo or TKI may be safely controlled with addition of IO/TKI therapy. Med PFS after addition of nivo to TKI appears similar (N+C) and improved (N+P) compared to nivo monotherapy (Checkmate-025). Med PFS after addition of TKI to IO was also similar (N+C) and improved (N+P) compared to historical controls.
The impact of the metastasis region on patients with metastatic renal cell cancer in the intermediate-risk group.
Authors: Karacin Cengiz , Basal Fatma Bugdaycı , Bilgetekin Irem , Oksuzoglu Omur Berna 
Published: May 2020

e17091 Background: The majority of patients with metastatic renal cell carcinoma (mRCC) are in the intermediate-risk group, according to International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). Some patients in the intermediate-risk group have similar overall survival (OS) with those in the good-risk group, while others with those in the poor-risk group. In our study, we aimed to evaluate the prognostic significance of the region of the metastasis and to classify the intermediate-risk group into two as favorable or unfavorable according to the metastasis region. Methods: We retrospectively analyzed the clinical data of patients with mRCC those in the intermediate-risk group seen at our Oncology Training and Research Hospital from 2010 to 2018. Patients who received at least one line of tyrosine kinase inhibitor (TKI) were included in the study. Overall survival was calculated. The log-rank test was used to check the statistical significance for OS. Results: Of 113 patients, median age 58 (range 34-78) years, 99 (88%) had more than one site of metastasis: 61 (54%) lung, 41 (36%) bone, 21 (18%) lymph node, and 19 (17%) brain metastasis. Nine patients received one, 86 patients received two, and 18 patients received three lines of systemic therapy. Median follow up was 14 (range 4 – 54) months. Median OS for patients with bone and/or brain metastasis was 10 (95% CI = 6.1 – 13.9) months compared to 16 (95% CI = 10.1 – 22.2) months for patients with lung and/or lymph node metastasis (HR = 1.675, p-value = 0.012). Conclusions: Our data suggest that the bone and/or brain metastasis in the intermediate-risk group mRCC patients treated with TKI are unfavorable prognostic factors.