bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance of a validated urine exosome gene expression test (EPI) in men within the USPSTF suggested age-group of 55 to 69 years at initial biopsy with a PSA 2-10 ng/mL.
Authors: Donovan Michael J. , Noerholm Mikkel , Torkler Phillipp , Skog Johan , Margolis Eric , Brown Gordon Andrew , McKiernan James M. 
Published: March 2019

53 Background: Prostate-specific antigen (PSA) plays a key-role in prostate cancer (PCa) risk stratification but leads to over-diagnosis of low grade PCa. Recently, the USPSTF recommended that the decision to undergo PSA-based screening for men aged 55 to 69 years should be an individual one. We have developed and validated a non-invasive diagnostic test (ExoDx Prostate(IntelliScore), EPI) as a decision aid to guide the initial prostate biopsy decision process for men in the PSA gray zone of 2-10 ng/mL. The EPI test is a urine exosome gene expression assay to discriminate high-grade (GG 2) from low-grade (GG 1) and benign disease, thereby reducing the number of unnecessary biopsies. Methods: Patient data from two clinical trials were merged and constrained by age (55-69) according to the USPSTF suggested age-group resulting in a cohort of 701 patients with PSA 2-10 ng/mL, scheduled for initial prostate needle biopsy. EPI test results as well as PCPT2.0 risk calculator, ERSPC risk calculator and PSA results are compared with biopsy outcomes. Performances are reported using the area under the receiver operating characteristic curve (AUC), Negative predictive value (NPV), Positive predictive value (PPV), Sensitivity, and Specificity for discriminating ≥GG2 from GG1 and benign disease. Results: EPI showed a superior AUC of 0.70 compared to PSA (AUC: 0.57), PCPT2.0 (AUC: 0.60) and ERSPC (AUC: 0.58) (all p-values < 0.001) for discriminating ≥GG2 PCa from benign and GG1. The previously validated EPI cut-point of 15.6 would avoid 22% of all prostate biopsies and 29% of unnecessary biopsies, with an NPV of 93% and miss only 5.4% of ≥GG2, respectively. Conclusions: EPI is a non-invasive, easy to use urine exosome RNA expression assay to discriminate high-grade (GG2) from low-grade (GG1) PCa and benign disease. EPI significantly outperformed the other standard of care parameters tested and applying the EPI test for risk stratification of patients in the USPSTF suggested age group, should reduce the number of unnecessary biopsies.
Clinical features and outcomes of secondary somatic malignancy (SSM) associated with primary mediastinal nonseminomatous germ cell tumors (PM-NSGCT).
Authors: Dean Lucas W. , Wong Nathan Colin , Dason Shawn , Isharwal Sumit , Donoghue Mark , Jia Liwei , Tap William D. , Joseph Gabriella , Funt Samuel Aaron , McHugh Deaglan Joseph , Al-Ahmadie Hikmat , Reuter Victor E. , Sheinfeld Joel , Bajorin Dean F. , Motzer Robert J. , Bosl George J. , Bains Manjit S. , Jones David Randolph , Solit David B. , Feldman Darren R. 
Published: March 2019

531 Background: The incidence of secondary somatic malignancy (SSM) arising from teratoma is increased in 2 settings; late relapse and primary mediastinal nonseminomatous germ cell tumors (PM-NSGCT). Here, we report the clinical features and outcomes of patients with SSM in the setting of PM-NSGCT. Methods: Between 1985 and 2018, 29 patients with PM-NSGCT and SSM who had sufficient clinical follow-up to evaluate outcome were identified. Clinical and pathologic parameters were reviewed. The Kaplan-Meier method was used to estimate overall survival (OS) from time of SSM diagnosis and the log rank test to compare estimates. Results: Median age was 28 years (range 18-59) and all patients were male. Most presented with local symptoms (n=24, 83%), elevated tumor markers (n=26, 90%), and disease isolated to the mediastinum (n=25, 86%). A total of 39 SSM histologies were present in the 29 cases, with 8 (28%) having 2 (n=6) or 3 (n=2) SSM histologies; 25 (86%) also had viable non-teratomatous GCT in the mediastinal mass. Sarcoma was found in all 29 cases including rhabdomyosarcoma (n=15), angiosarcoma (n=6), sarcoma NOS (n=5), spindle cell (n=4), PNET (n=3), and other (n=3). Non-sarcoma histologies (n=1 each) included AML, SCC, and neuroblastoma. Most patients received GCT-directed chemotherapy followed by an attempt at surgical resection (90%). With a median follow-up of 2 years for survivors, median OS was 1.8 years (95% CI 0-3.9 years), with 18 patients succumbing to disease. Complete surgical resection was achieved in 23 men (79%) and was associated with superior OS (3.1 vs. 0.3 years, p=0.005). At relapse or progression, 11 received SSM histology-directed and 7 GCT-directed chemotherapy with no difference in OS (1.3 vs. 1.2 years, p=0.993). 7 patients developed SSM in the form of leukemia, a finding associated with significantly inferior OS (0.3 vs. 3.0 years, p=0.009). Conclusions: Sarcoma is the predominant SSM histology associated with PM-NSGCT and portends a poor prognosis even with initially localized disease. Complete resection following chemotherapy is critical to achieving long-term survival whereas SSM in the form of leukemia portends especially poor outcome.
Clinical features and outcomes of tumor lysis syndrome in patients with genitourinary cancers.
Authors: Wang Jue , Leung Bryan 
Published: March 2019

533 Background: Genitourinary (GU) cancers account about 20% of all human cancer in the United States. Tumor lysis syndrome (TLS) is an oncologic emergency with few treatment options. While TLS has been extensively documented in patients with hematological malignancies, it is rarely described in patients with GU cancers. The objective of this study was to investigate the clinical characteristics and outcomes of TLS, a rare but life-threatening complication in GU cancers. Methods: Systematic review of the literature and pooled analysis of published cases of TLS in GU cancers. Results: A total of 180 patients with TLS in solid tumor were included in our study. The median age was 57 years (8-94). Male: female ratio was 1.7. The most common sites were gastrointestinal (29%); followed by genitourinary (22%); lung (16%); melanoma (11%), breast cancer (8.3%). Liver metastasis was documented in 70% of study subjects. TLS occurred as a consequence of cancer therapy in 68% of subjects; and spontaneously in 32% of subjects. Older age and liver metastasis predict high mortality. The clinical features, treatment and outcomes of TLS in 40 cases of GU cancers including testicular germ cell tumor (TGCT) (n=14), renal cell carcinoma (n=10), prostate cancer (n=15), penile cancer (n=1) and urothelial carcinoma (n=3) were compared. The mortality rate of TLS were 50% in TGCT, 70% in renal cell carcinoma, 64% in prostate cancer 67% in urothelial carcinoma. Conclusions: TLS in GU cancers is associated with very high mortality. TLS should be considered on the differential diagnosis, when evaluating renal failure and electrolyte derangement in patients with metastatic GU cancers with liver metastases. The clinical features and outcomes of TLS in genitourinary cancers. [Table: see text]
Survival rates after retroperitoneal lymph node dissection (RPLND) for testicular seminoma.
Authors: Tabakin Alexandra , Kim Sinae , Polotti Charles , Shinder Brian , Rivera-Nunez Zorimar , Sterling Joshua , Farber Nicholas , Radadia Kushan Dilip , Kim Isaac Yi , Singer Eric A. , Jang Thomas 
Published: March 2019

534 Background: RPLND as first-line treatment for testicular seminoma is less well defined than for testicular nonseminomas. Furthermore, RPLND performed in the post-chemotherapy (PC) setting for seminoma patients with a PET avid residual mass > 3 cm can be technically challenging. We describe utilization of RPLND in the primary and PC settings and report on overall survival rates following surgery for these men. Methods: Using 2004-2014 data from the National Cancer Database, we identified 62,727 men with 1° testicular cancer, of which 31,068 men were diagnosed as having seminoma. After excluding men with benign, non-germ cell, and nonseminoma histologies, those who did not undergo RPLND, and those whose clinical stage (CS) or survival data were unavailable, 412 men comprised our final cohort. Men were further stratified according to whether they had 1° RPLND vs PC-RPLND, with 1° RPLND defined as RPLND performed for CS IA-IIB without prior chemotherapy, and PC-RPLND classified as RPLND performed for CS IIA-IIIC after chemotherapy. Descriptive statistics were used to summarize clinical and demographic factors. The Kaplan-Meier method was used to determine overall survival. Results: From 2004-2014, 412 men with testicular seminoma underwent RPLND, of which 89% and 11% were in the 1° and PC settings, respectively. There were no significant differences in clinical or demographic characteristics when comparing men in these 2 groups. The majority of men with testicular seminoma undergoing PC-RPLND were treated at an academic center (63.8%) or comprehensive community cancer program (21.3%). The median follow-up was 4.1 years. Of 372 patients with available survival data, five-year overall survival was 94.2% and 89.0% in the 1° RPLND and PC- RPLND groups, respectively. Conclusions: Though RPLND is rarely used as 1° therapy in testicular seminoma, overall survival rates appear to be excellent, as they do for men with testicular seminoma after PC-RPLND. Ongoing trials evaluating the use of RPLND for early metastatic, low-volume disease will clarify its role in the management of testicular seminoma.
Intraoperative and early postoperative outcomes in post-chemotherapy retroperitoneal lymphadenectomy using validated grading classifications.
Authors: Umbreit Eric , McIntosh Andrew G. , Suk-ouichai Chalariat , Segarra Luis , Holland Levi , Fellman Bryan M. , Tu Shi-Ming , Pettaway Curtis Alvin , Pisters Louis L. , Ward John Francis , Wood Christopher G. , Karam Jose A. 
Published: March 2019

535 Background: Post-chemotherapy retroperitoneal lymphadenectomy (PC-RPLND) is an integral treatment modality in the management of advanced germ cell tumors. We sought to define the complication profile of PC-RPLND using validated grading systems for intraoperative adverse events (iAE) and early postoperative complications. Methods: After IRB approval, we analyzed perioperative outcomes of 453 patients (pts) who underwent PC-RPLND between 2000 and June 2018. iAE and early postoperative complications (within 90 days) were graded using Kaafarani and Clavien-Dindo classification, respectively. Logistic regression models were conducted to assess patient and tumor factors associated with iAEs and postoperative complications. Results: Of the 453 pts, 287 (63%) were clinical stage III and had a median post-chemotherapy retroperitoneal mass size of 4.1 cm (IQR 2.4-7.4 cm). There were 132 iAE, which occurred in 115 (25%) pts. Early postoperative complications occurred in 255 (56%) pts. Major iAE (grade ≥ 3) was observed in 15 (3%) pts and major postoperative complications (grade ≥ 3) were noted in 83 (18%) pts. The most common iAE was vascular injury (112 of 132 events, 85%), which occurred in 92 (20%) pts. The most common postoperative complication was ileus, occurring in 121 (27%) pts. Residual retroperitoneal mass size (OR = 1.14; 95% CI: 1.09–1.20, p<0.001), non-pulmonary metastases (OR = 3.18; 95% CI: 1.68–6.00, p<0.001), previous laparotomy (OR = 1.92; 95% CI: 1.01–3.66, p=0.047), previous RPLND (OR = 1.14; 95% CI: 1.01–5.59, p=0.046), and adjuvant surgical procedures (OR = 13.54; 95% CI: 7.01–26.14, p<0.001) increased the risk of iAE and postoperative complications. Postoperative complications were more likely for patients that experienced an iAE (OR = 2.50; 95% CI: 1.58–3.97, p<0.001). Conclusions: This is the first analysis of PC-RPLND defining morbidity using validated classifications of severity for iAE and postoperative complications. Larger retroperitoneal mass, non-pulmonary metastases, previous surgery and adjuvant surgical procedures increased the risk of perioperative complications. iAE increased the risk of postoperative complications.
Role of robot assisted retroperitoneal lymph node dissection in metastatic malignant mesothelioma of the tunica vaginalis: Case series.
Authors: Faraj Kassem , Abdul-Muhsin Haidar , Navaratnam Anojan , Rose Kyle , Ho Thai Huu , Bryce Alan Haruo , Singh Parminder , Cheney Scott , Tyson Mark D. , Castle Erik P. 
Published: March 2019

536 Background: The management of malignant mesothelioma of the tunica vaginalis of the testes (MMTVT) is not clearly defined, though retroperitoneal lymph node dissection has been reported as a diagnostic and potentially therapeutic option. Herein we present our experience with robot assisted retroperitoneal lymph node dissection (RARPLND) in a series of patients with MMTVT. Methods: The Mayo Clinic cancer registry was queried from 1972-present for all patients who had a diagnosis of MMTVT. Six patients were identified, five of whom were treated with RPLND, where four underwent RARPLND. Data was collected on pertinent demographic, preoperative, perioperative, postoperative outcomes and follow-up oncological data. Results: In five patients who underwent RPLND, the median age was 50 years (IQR 34-51), median BMI was 26.9 (IQR 26.4-30.6). Four patients originally presented with right sided symptomatic hydroceles, while one presented with right sided chronic epididymitis. Orchiectomy (one simple, two inguinal radical) was performed in three patients and hydrocelectomy in the other two patients prior to presentation. Preoperative cross-sectional imaging, including PET-CT scan in three patients, was negative for lymphadenopathy or metastasis. RARPLND was performed in 4/5 (80%) cases and concomitant hemiscrotectomy in 4/5 (80%) cases. Full bilateral template was performed in three patients and right modified template was performed in the remaining two. Median lymph node yield was 29 (IQR 22-32) and median blood loss was 275 cc (IQR 200-300). Positive retroperitoneal lymph nodes were found in 3/5 (60%) cases. Final margins of hemiscrotectomy were negative in all four cases. All patients who underwent RARPLND were discharged home on postoperative day one. One patient received four cycles of adjuvant Cisplatin and Pemetrexed. Mean follow-up was 27 months (range 2-47). No patients recurred. Conclusions: MMTVT is a very rare malignancy with high potential for retroperitoneal lymph node dissemination. Regardless of the approach, RPLND may provide both a diagnostic and therapeutic benefit, with the robotic approach affording a potentially expedited recovery.
Programmed death-ligand 1 (PD-L1) expression in pheochromocytoma.
Authors: Hashimoto Yasuhiro , Yamamoto Hayato , Hatakeyama Shingo , Yoneyama Takahiro , Ohyama Chikara 
Published: March 2019

537 Background: Programmed cell death ligand-1 (PD-L1) is a key target molecule of immunotherapy that is frequently overexpressed in several neoplasms. But there were few reports about PD-L1 expression of pheochromocytoma. In the present study, we examined PD-L1 expression in pheochromocytoma. Methods: PD-L1 mRNA expression was compared across 184 pheochromocytoma, 492 prostate cancer cases and 404 bladder cancer cases based on The Cancer Genome Atlas (TCGA). Furthermore, we enrolled 32 pheochromocytoma patients treated with surgery at our hospital between June 2005 and February 2016. We conducted an immunohistochemistry (IHC) of PD-L1 using the SP142 assay. PD-L1 expression was scored at three diagnostic levels (0/1/2). Results: Comparison of PD-L1 mRNA expression based on the TCGA revealed that PD-L1 expression was significantly higher in pheochromocytoma than in bladder cancer and in prostate cancer (p < 0.001). In the SP 142 assay of our 32 pheochromocytoma, the prevalence of positive PD-L1 expression (IHC score 1 or 2 (1/2)) in tumor-infiltrating immune cells (TICs) was 8 patients (25%). The prevalence of positive PD-L1 expression in tumor cells (TCs) was 9 patients (28.1%). Tumor diameter of PD-L1 (+) in TICs patients was 3.36±0.35 cm and that of PD-L1 (-) in TCs patients was 5.37±0.50cm, there was statistically significance between two groups. (unpaired t test: p=0.044) In our cohort, there were two malignant pheochromocytoma. But there were not PD-L1 positive cases in malignant pheochromocytoma. Conclusions: PD-L1 expression is relatively high in pheochromocytoma compared to bladder cancer and prostate cancer based on TCGA. In the SP142 assay of our 32 pheochromocytoma cases, tumor diameter of PD-L1 (-) in TICs cases was larger than that of PD-L1 (+) cases. In our cohort, there were not PD-L1 (+) cases in malignant pheochromocytoma. These findings suggest that PD-L1 expression of pheochromocytoma was comparatively common and PD-L1 positive expression of pheochromocytoma may not be associated with tumor aggressiveness.
Pembrolizumab (pembro) plus axitinib (axi) versus sunitinib as first-line therapy for locally advanced or metastatic renal cell carcinoma (mRCC): phase III KEYNOTE-426 study.
Authors: Powles Thomas , Plimack Elizabeth R. , Stus Viktor , Gafanov Rustem Airatovich , Hawkins Robert E. , Nosov Dmitry , Pouliot Frederic , Alekseev Boris Yakovlevich , Soulieres Denis , Melichar Bohuslav , Vynnychenko Ihor , Kryzhanivska Anna , Bondarenko Igor , Azevedo Sergio Jobim , Borchiellini Delphine , Shou Qiong , Perini Rodolfo F. , Chen Mei , Atkins Michael B. , Rini Brian I. 
Published: March 2019

543 Background: A phase 1b study of pembro (anti–PD-1) plus axi (VEGFR-TKI) showed promising antitumor activity and manageable safety in patients (pts) with previously untreated mRCC. The global, open-label, phase 3 KEYNOTE-426 study assessed the efficacy and safety of pembro + axi vs sunitinib as first-line therapy for mRCC (NCT02853331). Methods: Eligible pts with clear-cell mRCC, no previous systemic therapy for mRCC, and KPS ≥70% were randomized 1:1 to pembro 200 mg IV Q3W for a maximum of 35 cycles plus axi 5 mg orally BID or sunitinib 50 mg orally QD (4-wk on/2-wk off schedule). Treatment was given until PD, intolerable toxicity, or pt/investigator decision. Randomization was stratified by IMDC risk group and geographic region. Primary endpoints were OS and PFS (RECIST v1.1 by blinded, independent central review [BICR]). ORR was the key secondary endpoint. At the protocol-specified first interim analysis, the superiority thresholds were P = 0.0001 for OS, 0.0013 for PFS, and 0.025 for ORR (if OS and PFS were significant). Results: 861 pts were randomized: 432 to pembro + axi, 429 to sunitinib. After a 12.8-mo median follow-up, 59.0% of pts in the pembro + axi arm and 43.1% in the sunitinib arm remained on treatment. Pembro + axi significantly improved OS (HR 0.53 [95% CI 0.38-0.74]; P < 0.0001; 12-mo rate 89.9% vs 78.3%), PFS (HR 0.69 [95% CI 0.57-0.84]; P = 0.0001; median 15.1 vs 11.1 mo), and ORR (59.3% vs 35.7%; P < 0.0001). Duration of response was prolonged with pembro + axi (median not reached vs 15.2 mo). The pembro + axi benefit was observed in all subgroups tested, including all IMDC risk and PD-L1 expression subgroups. Treatment-related AEs were grade 3-5 in 62.9% of pts in the pembro + axi arm vs 58.1% in the sunitinib arm and led to regimen discontinuation in 6.3% vs 10.1%. Conclusions: Pembrolizumab + axitinib provided superior OS, PFS, and ORR compared with sunitinib and had manageable safety in pts with previously untreated, advanced or metastatic clear-cell RCC. These data suggest that pembrolizumab + axitinib should be a new standard of care for this population. Clinical trial information: NCT02853331.
First-line pembrolizumab (pembro) monotherapy for advanced non-clear cell renal cell carcinoma (nccRCC): Results from KEYNOTE-427 cohort B.
Authors: McDermott David F. , Lee Jae-Lyun , Ziobro Marek , Gafanov Rustem Airatovich , Matveev Vsevolod Borisovich , Suárez Cristina , Donskov Frede , Pouliot Frederic , Alekseev Boris Y. , Wiechno Pawel , Tomczak Piotr , Climent Duran Miguel Angel , Shin Sang Joon , Silverman Rachel Kloss , Perini Rodolfo F. , Schloss Charles , Atkins Michael B. 
Published: March 2019

546 Background: PD-1/L1 pathway inhibitors are effective in clear cell (cc)RCC, but efficacy of PD-1 inhibitors (or any therapy) in nccRCC has not been established. KEYNOTE-427 is a single-arm, open-label, phase 2 study of pembro monotherapy in patients (pts) with advanced ccRCC (cohort A) and nccRCC (cohort B). Cohort B results are presented. Methods: 165 pts with histologically confirmed nccRCC, no prior systemic therapy, measurable disease (RECIST v1.1), and KPS ≥70% enrolled. Pts received pembro 200 mg IV Q3W for 35 cycles (~2 y) or until progressive disease (PD), unacceptable toxicity, or withdrawal. Pts were followed after PD for overall survival. Primary end point: objective response rate (ORR) per RECIST v1.1 by blinded independent central review. Secondary end points included duration of response (DOR) and population description by International Metastatic RCC Database Consortium (IMDC) risk. Exploratory end points: ORR by histology and PD-L1 expression (combined positive score [CPS] ≥1 for PD-L1+). Results: Histology was confirmed by a central pathologist: papillary 72% (n=118), chromophobe 13% (n=21), unclassified 16% (n=26). 68% of patients were at intermediate/poor IMDC risk, and 62% were PD-L1+. At analysis, 49 pts had died and 3 had withdrawn. At a median follow-up duration of 11.1 mo (range, 0.9-21.3), 56% of pts discontinued pembro due to PD or clinical progression. Overall ORR was 24.8% (95% CI, 18.5-32.2; 8 [4.8%] CRs, 33 [20%] PRs); median DOR was not reached. ORR (95% CI) was 25.4% (17.9-34.3) with papillary, 9.5% (1.2-30.4) with chromophobe, and 34.6% (17.2-55.7) with unclassified nccRCC. ORR (95% CI) was 28.3% (16.8-42.3) with favorable and 23.2% (15.8-32.1) with intermediate/poor IMDC risk and 33.3% (24.3-43.4) and 10.3% (3.9-21.2) with CPS≥1 and CPS<1, respectively. Grade 3-5 treatment-related adverse events (TRAEs) occurred in 11% of pts; 6% discontinued due to TRAEs. 6 pts died due to AEs, 2 of which were TRAEs (pneumonia and cardiac arrest). Conclusions: Single-agent pembro showed encouraging antitumor activity in nccRCC, especially with papillary or unclassified histology. Safety profile of pembro was generally as expected. Clinical trial information: NCT02853344.