bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting biochemical recurrence after prostatectomy: Can machine learning beat CAPRA score? Results of a multicentric retrospective analysis on 4,700 patients.
Authors: Sargos Paul , Leduc Nicolas , Giraud Nicolas , Gandaglia Giorgio , Roumiguie Mathieu , Ploussard Guillaume , Niazi Tamim , Chaddad Ahmad , Beauval Jean-Baptiste 
Published: February 2020

343 Background: Recent advances in machine learning algorithms and deep learning solutions paved the way for improved accuracy in survival analysis. We aim to investigate the accuracy of conventional machine learning and deep learning methods in the prediction of 3-year biochemical recurrence (BCR) as compared to CAPRA score prediction. Methods: A total of 5043 men who underwent RP between 2000 and 2015 for clinically localized PCa iwere analyzed retrospectively. Three-year BCR was predicted using the following models: CAPRA score, Cox regression analysis, logistic regression, k-nearest neighbor, random forest and densely connected feed-forward neural network classifier. The discrimination of the models was quantified using the C-index or the area under the receiver operating characteristics curve. Results: Patients with CAPRA score 2 and 3 accounted for 64% of the population. C-index measuring performance for the prediction of the three-year BCR for CAPRA score was 0.63. C-index values for k-neighbor classifier, logistic regression, Cox regression analysis, random forest classifier and densely optimized neural network were respectively 0.55, 0.63, 0.64, 0.64 and 0.70 (pairwise, adjusted p-value < 0.01). After inclusion of available post-surgical variables, C-index value reached respectively 0.58, 0.77, 0.74, 0.75 and 0.84 (pairwise, adjusted p-value < 0.05). Conclusions: Our results show that CAPRA score performed poorly in intermediate-risk patients undergoing RP. Densely connected neural networks with simple architecture further increased predictive power with low computational cost. In order to predict 3-years BCR, adding post-surgical features to the model greatly enhanced its performance.
Trends and oncological outcome of testosterone recovery after androgen deprivation therapy in prostate cancer patients who received external beam radiotherapy.
Authors: Takei Akinori , Sakamoto Shinichi , Tamura Takaaki , Wakai Ken , Maimaiti Maihulan , Imamura Yusuke , Komiya Akira , Nakatsu Hiroomi , Akakura Koichiro , Ichikawa Tomohiko 
Published: February 2020

345 Background: Although androgen deprivation therapy (ADT) combined with external beam radiation therapy (EBRT) is standard treatment for high risk prostate cancer (PC) patients, the shift of testosterone (TST) levels after ADT and the optimal duration of ADT is unclear. TST recovery and outcome were studied in PC patients who received EBRT with ADT. Methods: Eighty-two patients who underwent EBRT with ADT for PC were retrospectively analyzed. Serum TST levels after ADT terminations were studied. Cox proportional hazard models and the Kaplan-Meier method were used for statistical analysis. Results: Median age, baseline TST, nadir TST, and duration of ADT were 73 years, 456 ng/dL, 16 ng/dL, and 26 months, respectively. ADT duration of 33 months (HR 0.13; p=0.0018), nadir TST of 20 ng/dL (HR 0.35; p=0.0112), and TST >50 ng/dL at 6 months after ADT termination (HR 0.21; p=0.0075) were significantly associated with TST recovery to normal levels (200 ng/dL) on multivariate analysis. ADT duration of 33 months (HR 0.31; p=0.0023) and nadir TST of 20 ng/dL (HR 0.38; p=0.0012) were significantly associated with TST recovery to supracastrate level (50 ng/dL) on multivariate analysis. In high risk PC patients, ADT≤ 2 year group showed shorter time to TST recovery to supracastrate levels compare to those of ADT>2 year group (HR 4.21; p=0.0022) without affecting biochemical recurrence (p=0.49) and overall survival (p=0.674). Conclusions: ADT duration of 33 months and nadir TST of 20 ng/dL predicted the TST recovery to suparacastrate levels. Less than 2 year of ADT provided better TST recovery without affecting the oncological outcome in high risk patients.[Table: see text]
Natural history of an immediately detectable PSA following radical prostatectomy: A description of a contemporary cohort.
Authors: Lonergan Peter Eoin , Washington Samuel L. , Cowan Janet E. , Nguyen Hao , Cooperberg Matthew R. , Carroll Peter 
Published: February 2020

356 Background: Radical prostatectomy (RP) can provide good long-term oncological outcomes in patients with localized and locally advanced prostate cancer (PCa). After RP, prostate specific antigen (PSA) represents the corner stone for follow-up of patients. A persistently detectable PSA immediately following RP is an unfavourable prognostic factor. We described the natural history of the management and outcomes in men with a detectable PSA in an academic cohort. Methods: A retrospective review of prospectively collected clinical and pathologic data from consecutive patients who underwent RP for non-metastatic PCa between 2000 and 2018 was performed. A detectable PSA was defined as PSA ≥ 0.05 ng/ml between 2-6 months post-surgery. Biochemical recurrence (BCR) was defined as two consecutive PSA values ≥ 0.2 ng/ml after 6 months post-surgery or any salvage treatment for a rising PSA. Second recurrence was defined as additional treatment after post-RP salvage treatment. Outcomes were defined as time to other cause mortality (OCM) or prostate cancer specific mortality (PCSM). Results: We identified 499 men with a detectable PSA within 6 months following RP. Median PSA at diagnosis was 7.95 ng/ml (IQR 5.57-12.97). Median CAPRA-S score was 5 (IQR 2-7). Median follow-up was 41 months (IQR 20-77). 296 (59%) underwent salvage treatment for a rising PSA at a median of 5 months. 33 (23%) of these men required further treatment (10 for bone metastases) at a median of 7 months. 203 (41%) of men with an immediately detectable PSA did not undergo any further treatment after RP. Treatment-free survival after post-RP salvage (31 on ADT and 2 underwent salvage RT) in men with a detectable vs undetectable PSA was 86% vs 92% at 1 year, 78% vs 89% at 3 years, 72% vs 86% at 5 years and 70% vs 76% at 10 years (Log-rank p =0.02). Prostate cancer specific survival in men with a detectable vs undetectable PSA was 100% vs 100% at 1 year, 99% vs 100% at 3 years, 96% vs 100% at 5 years and 91% vs 99% at 10 years (Log-rank p < 0.01). Conclusions: This report describes the natural history of the management and outcomes in men with a detectable PSA following RP. We demonstrate that men with a detectable PSA after RP may have excellent long-term outcomes.
Adjuvant docetaxel after definitive radiotherapy for high-risk prostate cancer: A meta-analysis of randomized clinical trials.
Authors: Manneh Kopp Ray , Lema Mauricio , Ibatá Linda 
Published: February 2020

374 Background: In order to improve long term results for high-risk prostate cancer, several clinical trials have tested the addition of docetaxel chemotherapy. The outcomes of this trials have not led to clear conclusions. We conducted a meta-analysis of randomized phase 3 trials testing the efficacy of docetaxel after radiotherapy in high risk prostate cancer patients. Methods: A systematic review of PubMed (Medline), Embase and the Cochrane Library was conducted. We followed the PRISMA guidelines, three investigators independently selected the articles and verified inclusion criteria. We compared the overall survival and disease-free survival between the intervention group (adjuvant chemotherapy with docetaxel) and the control group (without adjuvant chemotherapy) by calculating the hazard ratio (HR) with 95% confidence intervals (CIs). Pooled effects were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies. Results: 382 publications were identified, four phase III trials (STAMPEDE, RTOG0521, SPCG-13, GETUG 12) comparing docetaxel vs standard of care after radiotherapy for high-risk prostate cancer fulfilled the inclusion criteria with data from 2034 patients (1135 in placebo group and 899 in adjuvant docetaxel group). Heterogeneity was not found between the included studies for OS (I 2 0%), but it was found between studies for disease-free survival (I2 60%). Adjuvant docetaxel chemotherapy showed overall survival benefit when compared to ADT alone (HR 0,72 95% CI 0,54-0,96). Adjuvant docetaxel also improved the disease-free survival when compared to ADT alone (HR 0,74 95% CI 0,64-0,86). No evidence of publication bias was observed. Conclusions: This meta-analysis shows that docetaxel after definitive radiotherapy in high-risk prostate cancer is likely to be more effective than standard of care in terms of overall survival and disease-free survival. Further prospective studies are needed in order to increase the sample that would lead to show a more robust data.
Surveillance of postchemotherapy subcentimeter residual retroperitoneal mass (RRM) in metastatic nonseminomatous germ cell tumor (mNSGCT).
Authors: Cotner Cody , Hilton Susan , Mamtani Ronac , Guzzo Thomas J. , Vaughn David J. 
Published: February 2020

391 Background: Approximately 30 – 60% of patients with mNSGCT treated with cisplatin-based chemotherapy (CBCT) achieve a complete response (CR), defined as normalization of serum tumor markers with either no RRM or a RRM < 1 cm. While there is universal agreement that patients with a RRM ≥ 1 cm should undergo retroperitoneal lymph node dissection (RPLND), many institutions, including ours, recommend surveillance for patients who achieve a CR. However, studies have not defined which axis of the RRM should be considered when making this decision. Methods: The electronic medical records (2007 – 2017) at the Hospital of the University of Pennsylvania (HUP) were searched to identify good-risk mNSGCT patients treated with CBCT who achieved a CR and underwent surveillance. Consistent with RECIST 1.1, we define a CR as no RRM or a RRM < 1 cm in the transaxial short axis (TSA). We do not consider the transaxial long axis (TLA) or the craniocaudal axis (CCA). A post-hoc review was performed by a blinded radiologist and the RRM dimensions in the TSA, TLA, and CCA were recorded. Differences in the frequency of recurrence between groups with a RRM < 1.0 cm and ≥ 1.0 cm in the TLA and CCA were assessed using the Fischer exact test. Results: 39 patients met study criteria and were included. At a median follow-up of 50.8 months, only 2 patients (5.1%) recurred. Both were successfully treated with RPLND and salvage chemotherapy. Post-hoc review of imaging: median TSA 6 mm (range, 0-11); median TLA 8 mm (range, 0-14); median CCA 11 mm (range, 0-34). Thirteen (33%) and 27 (69%) patients had a RRM ≥ 1 cm in the TLA and CCA, respectively. There were no statistically significant differences in the risk of recurrence between patients with a RRM < 1.0 cm and ≥ 1.0 cm in the TLA (p=0.54) or CCA (p=0.53). Conclusions: Surveillance is an effective strategy in patients with mNSGCT and a post-chemotherapy RRM < 1.0 cm in the TSA. Our study suggests that referencing the TSA and not the TLA or CCA in this decision-making may avoid unnecessary post-chemotherapy RPLND.
Prognostic significance of rate of tumor marker (TM) decline during high-dose chemotherapy (HDCT) for relapsed germ cell tumors (rGCT).
Authors: Adra Nabil , Althouse Sandra K. , Abonour Rafat , Abu Zaid Mohammad Issam , Liu Hao , Hanna Nasser H. , Einhorn Lawrence 
Published: February 2020

403 Background: Rate of serum TM decline is prognostic in patients (pts) with GCT receiving first-line chemotherapy. We investigated the prognostic value of TM decline in rGCT treated with HDCT+peripheral-blood stem-cell transplant (PBSCT). Methods: 462 consecutive pts with rGCT treated with HDCT+PBSCT at Indiana University between 1/2004-1/2019. All pts were planned for 2 consecutive HDCT courses with carboplatin+etoposide per protocol (N Engl J Med 2007;357:340-8). Pts with elevated AFP and/or hCG were included (N=347). Slope and half-life (T1/2) were calculated for weekly AFP+hCG during HDCT starting with peak value at days 1-7 to avoid interference from lysis. T1/2 AFP≤7 days and hCG≤3 days were categorized satisfactory (SAT). Progression-free (PFS) and overall survival (OS) were compared for SAT vs unsatisfactory (UNSAT) using log-rank test and analyzed using Kaplan-Meier. Uni- and multivariable analysis using Cox regression model was performed. Results: 347 pts had elevated TM: 312 had non-seminoma and 35 had seminoma. Median age was 31 (range, 17-58). Primary site: testis (292), mediastinum (26), retroperitoneum/other (29). Metastatic sites included retroperitoneum (277), lung (233), liver (83), brain (77), and bone (21). At initiation of HDCT, 77 pts had elevated AFP, 222 elevated hCG, and 48 elevated both AFP+hCG. Median AFP 9 (1-21,347) and hCG 113 (1-178,140). 314 pts (91%) completed 2 planned cycles of HDCT. Overall, 46/347 pts had SAT decline (13 for AFP; 30 for hCG; 3 for both). Pts with SAT TM decline had superior outcomes compared to UNSAT: 2-yr PFS 69% vs 45% (p=0.006) and 2-yr OS 75% vs 51% (p=0.006). When evaluating each TM separately, SAT decline in hCG had superior outcomes vs UNSAT: 2-yr PFS 74% vs 47% (p=0.002). There was statistically non-significant difference for AFP: 2-yr PFS 48% vs 42% (p=0.65). In univariable analysis, UNSAT decline of hCG, but not AFP, was an adverse prognostic factor for PFS: HR=2.51 (95% CI, 1.40-4.51); p=0.002. Multivariable analysis will be presented. Conclusions: SAT rate of TM decline, particularly in hCG, predicts superior outcomes in rGCT undergoing HDCT+PBSCT. Pts with UNSAT TM decline are at higher risk for relapse and death.
Origin of a second malignancy harboring isochromosome 12p [i(12p)] in patients with history of testicular germ cell tumor (TGCT).
Authors: Hwang Michael J. , Siddiqui Bilal A. , Merriman Kelly W. , Uthup Joma , Ward John Francis , Karam Jose A. , Wood Christopher G. , Pisters Louis L. , Zhang Miao , Tu Shi-Ming 
Published: February 2020

412 Background: The cumulative incidence of subsequent solid malignant neoplasm (SMN) after treatment of TGCT is about 10% over a 25-year period. i(12p) has been used to define tumor of germ cell origin. We evaluated the prevalence of i(12p) on various subsequent SMN in patients with a history of TGCT. Methods: From the Tumor Registry database at MD Anderson, we identified 655 TGCT patients who developed a second (third or fourth) malignancy between January 1990 and September 2018. Of those 114 SMN from the GI tract, GU system, chest, brain, sarcomas or melanomas between 2011 and 2017, 43 had tumor tissue available at our institution and of sufficient quality for fluorescence in situ hybridization (FISH) of i(12p). Results: Our cohort comprised 43 patients, excluding 2 cases (#6 and 7) whose SMN tested positive and their non-tumor controls negative for i(12p). Diagnosis of primary TGCT and SMN: age, mean 41 yrs (range 20-68 yrs) and 59 yrs (range 34-86 yrs), respectively, and interval of 18 yrs (range 0-57 yrs). Of those 43 cases (5 did not hybridize), 5 (11%) harbored i(12p), while 16 (37%) had additional copies of chromosome 12 without apparent gain of 12p. Conclusions: Prevalence of i(12p) on subsequent SMN in our patient cohort with a history of TGCT was 11%. Detection of i(12p) in those patients with TGCT in general and with nonseminomas in particular suggests somatic transformation, emphasizes importance of a complete surgical resection of residual teratomatous tumor after chemotherapy, and implicates a stem-cell origin and nature (e.g., plasticity, heterogeneity, dormancy) of cancer. *deceased; Rx – initial treatments; S – seminoma; NS – nonseminoma; BEP – bleomycin, etoposide, cisplatin; CEB – carboplatin, etoposide, bleomycin; XRT – radiation therapy. Groot HJ, Lubberts S, de Wit R, et al. Risk of solid cancer after treatment of testicular germ cell cancer in the platinum era. J Clin Oncol 2018;36:2504-13.
Circulating tumor (ct)-DNA alterations in patients with testicular germ cell tumors.
Authors: Agarwal Archana , Nassar Amin , Nagy Rebecca , Curran Catherine , Abou Alaiwi Sarah , Lanman Richard B. , Talasaz AmirAli , Sweeney Christopher , Sonpavde Guru 
Published: February 2020

415 Background: Testicular germ cell tumors (GCT) infrequently harbor somatic mutations. ctDNA assessment allows the noninvasive genomic profiling of malignancies and may assist with understanding molecular evolution of resistance. We report ctDNA profiling of patients (pts) with testicular GCTs. Methods: 40 patients (pts) with advanced testicular GCTs from multiple institutions in the USA that underwent ctDNA analysis using the Guardant (G)-360 platform were eligible and a total of 48 samples were collected. 36 pts had one sample, 3 pts had 2 samples, 1 pt had 6 samples. De-identified demographic data were collected in addition to data for ctDNA alterations. G360 employed a CLIA-certified ctDNA panel that assessed single nucleotide variant and copy number alterations in 68 to 73 genes for potentially actionable genomic alterations. Variants reported at least 3 times in the Catalogue of Somatic Mutations in Cancer (COSMIC) database or found in OncoKB were considered pathogenic. Results: Of 40 patients with testicular GCTs, 13pts (33%) were post systemic therapy. The median age was 36 years (range 20-61). 199 ctDNA alterations were detected in 35 patients (87.5%) across 41 genes. Among the 199 alterations, 102 were believed to be pathogenic and detectable in 26 samples from 25 pts (62.5) (%). The most common pathogenic somatic alterations were KRAS (n = 16/102, 16%), TP53 (n = 16/102, 16%), CCND2 (n = 9/102, 9%), CDK6 (n = 9/102, 9%), MET (n = 9/102, 9%), and RAF1 (n = 6/102, 6%). Conclusions: ctDNA alterations were frequently detected in resistant testicular GCTs and appear similar to alterations previously described in tumor tissue analyses of testicular GCTs. Given that ctDNA offers a non-invasive means of profiling tumor DNA, further development of this promising modality is warranted to study the evolution of resistance to cisplatin-based chemotherapy and new potentially actionable alterations.
Incidence and risk factors for contralateral testicular tumor.
Authors: Blok Joost Marijn , Groot Harmke J. , Huele Eline H. , De Wit Ronald , Gietema Jourik A. , Groenewegen Gerard , Witjes Fred , Van den Berg Hetty , Nuver Janine , Tromp Jacqueline Maria , De Brouwer Peter , Smilde Tineke Jacoba , Aarts Maureen J.B. , Vanneste Ben G.L. , Bosch Ruud J.L.H. , Horenblas Simon , Schaapveld Michael , Meijer Richard P. 
Published: February 2020

419 Background: Patients with testicular germ cell tumor (TGCT) are at increased risk of developing a metachronous contralateral testicular tumor (CLTT). It is unclear whether the histology of the primary tumor and treatment with platinum-based chemotherapy are associated with the risk of CLTT. The primary aim of this study was to analyze the association between number of chemotherapy cycles and risk of CLTT. Methods: We evaluated the incidence of metachronous CLTT (≥2 months after diagnosis of primary TGCT) in a nationwide cohort consisting of patients diagnosed with TGCT between 1989 and 2007. Standardized incidence ratios (SIRs) were computed to compare CLTT incidence with TGCT in the general population and the cumulative incidence of CLTT was estimated. We analyzed the association between treatment with chemotherapy and risk of CLTT in a multivariate Cox-model. Results: The entire cohort consisted of 4,755 patients (seminoma: n=2,612; 54.9%, nonseminomatous germ cell tumor [NSGCT]: n=2,143; 45.1%). The median age at diagnosis was 33 years (IQR 26-40). A total of 1,047 patients (22.0%) were treated with platinum-based chemotherapy for their primary TGCT (seminoma: n=189, NSGCT: n=858). Median follow-up was 17.0 years (IQR 12.7-22.0). A CLTT was diagnosed in 136 patients. The median interval to CLTT diagnosis was 6.1 years (range 0.8-19.7). The overall 20-year cumulative incidence was 3.4% (95% CI 2.8-4.0) and was higher after seminoma (4.0%; 95% CI 3.3-4.9), compared to NSGCT (2.6%; 95% CI 1.9-3.4). The SIRs were for seminoma: 22.1 (95% CI 17.8-27.1), for NSGCT: 8.6 (95% CI 6.3-11.6) and for the entire cohort: 14.6 (95% CI 12.2-17.2). In multivariate analysis, the risk of developing a CLTT decreased with age (HR 0.93; 95% CI 0.90-0.96), was lower after NSGCT (HR 0.58; 95% CI 0.35-0.96), and decreased with every additional cycle of chemotherapy (HR 0.74; 0.64-0.85). This corresponds to a 26% lower risk of CLTT per extra chemotherapy cycle. Conclusions: TGCT patients have an almost 15 times higher risk of developing a CLTT, compared to the general population. The risk is 2 times higher after a seminoma, compared to NSGCT, and decreases with every additional cycle of chemotherapy. Especially in high risk patients, lifelong self-examination is advised.
Outcomes of adult urogenital sarcomas: Analysis of surveillance, epidemiology, and end results (SEER) database 2004 to 2015.
Authors: Nutalapati Snigdha , Chen Quan , Huang Bin , Patel Reema Anil , Bilen Mehmet Asim , Myint Zin 
Published: February 2020

423 Background: Urogenital sarcomas are rare type of soft tissue sarcomas and represent only 1-2% of all genitourinary cancers. Given the paucity of literature, we aimed to study the clinical characteristics and factors impact outcomes of adult urological sarcomas. Methods: Adult males aged ≥ 20 years with sarcomas primarily originating from urogenital sites were identified from national SEER database between 2004-2015. Descriptive analysis was performed for all cases. Survival analysis, including Kaplan Meier estimates and Cox regression were performed. Results: A total of 1177 genitourinary sarcomas were identified. Urinary bladder (20.56%) was the most common primary site followed by spermatic cord (20.31%) and kidney (17.33%). The most common histological subtype was liposarcoma (32.9%) followed by leiomyosarcoma (32.0%). 10-year survival rate was highest for liposarcoma 58.3% (95% CI 50.3-65.5) followed by leiomyosarcoma 40.2% (95% CI 32.0-48.2), rhabdomyosarcoma 37.3% (95% CI 22.6-52.1), synovial sarcoma 22.7% (95% CI 5.6-46.6), carcinosarcoma 8.9% (95% CI 4.3-15.4) and 0% for angiosarcoma. Median follow up was 23 months and overall median survival was 54 months. There was a significant overall survival difference by age, race, primary sites, histological subtypes, grade, stage, insurance status, geographic, socioeconomic status and treatment in both univariate and multivariate analysis. On multivariate analysis, factors associated with unfavorable prognosis include age > 75 years (HR 3.9, 95% CI 2.9-5.2), distant metastasis (HR 2.0, 95% CI 1.5-2.7), ureteral sarcomas (HR 6.2, 95% CI 2.3-17.1) and having Medicaid insurance (HR 1.7, 95% CI 1.2-2.3).Surgery alone (HR 0.5, 95% CI 0.4-0.7) or in combination with chemotherapy (HR 0.4, 95% CI 0.3-0.6) or radiation (HR 0.4, 95% CI 0.3-0.6) had favorable prognosis compared to non-surgical approach. Conclusions: Urinary bladder is the most common primary sites of all urological sarcomas. Our study showed age > 75, poorly differentiated histology, angiosarcoma subtype, ureteral primary site, distant metastasis, poor socioeconomic status, Appalachian area and radiation alone were associated with less favorable outcomes.