bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liver metastases in germ cell tumors.
Authors: Boulos Suliman , Shamash Jonathan , Wong Han Hsi , Rudman Sarah Maria , Doherty Gary , Ansell Wendy , Berney Daniel , Reinius Marika , Wilson Peter , Shephard Linda , Mazhar Danish 
Published: March 2017

403 Background: Metastatic germ cell tumour (GCT) to the liver is considered rare and usually caries adverse outcomes. We aimed to determine the outcome of patients with metastatic GCT to the liver. Methods: We identified retrospectively 36 patients with metastatic germ cell tumour to the liver between the years 2001 and 2015, from which 34 were non-seminomatous germ cell tumours (NSGCT) and two seminomas. 35 patients had other sites of metastases including lungs, bones and brain. Elevated tumour markers were seen in the vast majority of patients (97.2%). 15 patients received treatment with dose intense regime including actinomycin-D, high-dose methotrexate, etoposide and cisplatin (GAMEC) every 14 days, 20 patients received the standard protocol of bleomycin, etoposide and cisplatin (BEP) every 21 days and one patient received POMB/ACE chemotherapy. 20 patients had an induction cycle of cisplatin, vincristine and bleomycin (Baby-BOP) prior to initial treatment. Results: 12 patients had radiological complete response (CR) and 19 patients had radiological partial response (PR) in the liver, with five patients having a CR in all sites with negative markers. Five patients underwent liver resection with no viable tumour seen. Three patients that underwent liver resection also had retroperitoneal lymph node dissection (RPLND) the histology from which was viable seminoma in one case, mature teratoma in one case and necrosis in the final patient.16 patients had marker negative PR, 10 patients had marker positive PR and 5 patients had a marker negative CR. 15 patients eventually relapsed and 10 died with only one liver relapse. Median Overall survival for patients that received BEP was 35.38 months (not reached for GAMEC) (p = 0.0147). The median progression free survival (PFS) for the BEP group was 24.45 months (not reached for GAMEC) (p = 0.22) and the 2-years PFS for the GAMEC and BEP groups were 73% and 55% respectively. Conclusions: Within this cohort, liver metastasis from germ-cell tumour had a good response to chemotherapy, with progression occurring mainly in extra-hepatic sites. There was also a suggestion that dose dense GAMEC regime may offer superior efficacy compared with BEP.These results also question the role of liver metastectomy after initial response to chemotherapy.
Predictors for malignant tissue (MT) in residual masses (RM) of non-seminomatous germ cell tumors (NSGCT) treated by chemotherapy (CT) before surgery.
Authors: Stern Natacha , Bompas Emmanuelle , Bogart Emilie , Laestadius Fredrik , Mouillet Guillaume , Schlurmann Friederike , Leblanc Eric , Penel Nicolas , Lotz Jean-Pierre , Amela Eric 
Published: March 2017

405 Background: About half of the patients operated for RM after CT for a NSGCT doesn’t benefit from surgery because RM contain only necrosis. We develop and validate a predictive score for identifying MT (teratoma and/or viable cancer cells) after primary CT for disseminated NSGCT. Methods: We have conducted a retrospective study. The development cohort (cohort 1) consists in 193 pts treated with CT and surgery of RM at the Oscar Lambret Cancer Center between 1997 and 2014. The validation cohort (cohort 2) consists in 98 pts treated in 5 other French sites. Size of RM, modification in size after CT, pre- and post-CT AFP levels, pre- and post-CT HCG levels, pre- and post-CT LDH levels were collected. The predictive factors have been first identified using univariate logistic regression analysis and then selected using step-by-step (forward) logistic regression. Discrimination has been assessed using Akaike Information Criterion (AIC) and ROC curve. Results: The rates of MT in the RM were 52% and 68%, in the cohort 1 and 2, respectively. The 1-, 2- and 5-y OS in the development cohort were 99, 97 and 95%, respectively. The 1-, 2 and 5-y relapse-free survival in the development cohort were 96, 92 and 91%, respectively. In univariate analysis, the predictive factors for MT were: size of RM > 15 mm (OR=3.32 [95%-CI: 1.6-6.2], p=0.001), stable RM versus diminution in size of RM (OR=3.0 [1.5-5.9] p=0.001) or increase in size versus diminution in size of RM (OR=8.6 [1.7-41.9] p=0.008) and pre-CT AFP level > ULN (OR=2.9 [1.4-6.3], p=0.006). The multivariate analysis had retained 2 predictors for MT: size of RM and pre-CT AFP level > ULN. The ROC was 0.71 [0.61-0.80] with an AIC=143 in the development cohort, and was 0.59 [IC95% 0.46-0.72] in the validation cohort. The model showed adequate calibration with a Hosmer-Lemeshow test p=0.69. Conclusions: Surgery of RM is part of standard of care of disseminated NSGCT. However, this surgery is morbid and at the end about 50% of pts are free of MT. We have developed and validated a predictive score for identifying pts benefiting of surgery.
Nonguideline concordant treatment of testicular cancer.
Authors: Paffenholz Pia , Pfister David , Heidenreich Axel 
Published: March 2017

407 Background: The management of testicular cancer requires a complex multimodal therapeutic approach. Despite the availability of regularly updated national and international guidelines on testicular cancer, treatment still differs between the institutions probably affecting the patients’ outcome. Our study aims to investigate frequently occurring errors regarding the diagnosis and therapy of testicular cancer in consideration of the current EAU guidelines. Methods: We performed a retrospective analysis including 129 patients diagnosed with testicular cancer that were referred to our department between 09/2015 and 10/2016. Patients’ age, histology, clinical stage, IGCCCG risk classification, treatment (surveillance, chemotherapy, radiotherapy, surgery) and follow-up were investigated and compared to the EAU guidelines’ recommendations. Results: Of the eligible 129 patients, 34 (26%) patients displayed a non-guideline concordant care. The most common error was undertreatment (47%), mostly due to missing chemotherapy cycles. Modified treatment and overtreatment occurred in 20% and 16% respectively, while inappropriate treatment (9%) and misdiagnosis (6%) were rarely seen. In secondary treated patients, non-guideline concordant therapy was observed more frequently compared to those patients receiving primary therapy (59% vs. 41 %). Almost all patients (93%) receiving a non-guideline concordant therapy suffered a relapse in contrast to 67% of patients that were treated according to the EAU guidelines. Conclusions: Non-adherence to the current EAU guidelines on testicular cancer appears to be a major problem in various testicular cancer treating institutions. In our study, the most frequent error was undertreatment, followed by modified treatment and overtreatment. Inappropriate therapy leads to a higher relapse rate and morbidity associated with a worse curative outcome.
Treatment patterns and impact of race in patients receiving first-line therapy for advanced penile squamous cell carcinoma (PSCC).
Authors: Morgan Charity , Diorio Gregory , Spiess Philippe E. , Sonpavde Guru 
Published: March 2017

413 Background: Treatment patterns and outcomes with first-line therapy for PSCC are unclear. We conducted a retrospective analysis of the NCDB to study this issue and evaluate prognostic factors in treated patients (pts). Methods: Data from the NCDB was obtained for pts diagnosed with clinical stage 4 PSCC from 1998-2011. The following variables were evaluated: age, Charlson Comorbidity Index (CCI), race, survival, socioeconomic status (SES) based on median income of area of residence and therapy. Treatment patterns were described. Multivariate analyses (MVA) were conducted to assess the impact of factors on survival of pts receiving therapy. Results: Of 14,395 pts with PSCC, 614 pts with stage 4 PSCC were evaluable with complete data. The mean age was 61.9 (range 22-90), 498 (81.1%) were white and 91 (14.8%) were black. 300 (48.7%) pts received no anti-cancer therapy, 245 (39.9%) received chemotherapy (+/- other therapy) and 69 (11.24%) received radiation (+/- non-chemotherapy agents). Pts in the chemotherapy group were significantly younger (mean age 58.8 years) than those in the radiation (63.5 years) or no therapy (64.1 years) group (p < 0.001), but there were no significant differences in other variables between the 3 groups. The median survival from date of therapy of those in the chemotherapy and radiation groups were 9.75 and 8.65 months, respectively. MVA of pts who received therapy showed that non-white race (p = 0.006) and shorter time from diagnosis to therapy (p = 0.005) were significantly associated with poor survival, while chemotherapy, SES, age and CCI did not impact survival. Additionally, non-white race showed a trend for association with poor survival (p = 0.089) in those not receiving anti-cancer therapy. Conclusions: A minority of pts (39.9%) with stage 4 PSCC received chemotherapy in this large NCDB cohort, who were younger than those who received radiation or no therapy. The association of non-white race with poor survival suggests the impact of germline factors and disparities in therapy. The absence of significant impact of chemotherapy on survival in this real world PSCC cohort highlights unmet needs in this orphan disease and the need for discovery of effective agents.
Pazopanib (PZP) in germ cell tumors (GCT) after chemotherapy (CT) failure: Final results of the open label, single-group, phase II Pazotest trial.
Authors: Necchi Andrea , Lo Vullo Salvatore , Giannatempo Patrizia , Raggi Daniele , Calareso Giuseppina , Togliardi Elena , Crippa Flavio , Pennati Marzia , Zaffaroni Nadia , Perrone Federica , Colecchia Maurizio , Nicolai Nicola , Mariani Luigi , Salvioni Roberto 
Published: March 2017

414 Background: Therapeutic options for patients (pts) with chemoresistant GCT are limited and prognosis is poor. PZP is a potent and selective tyrosine kinase inhibitor (TKI) with distinct antiangiogenic activity. Methods: In Pazotest trial (NCT01743482), pts were given PZP 800 mg/day until disease progression (PD) or unacceptable toxicity. Eligibility included failure of ≥ 2 platinum-based CT, including high-dose (HD)-CT. Baseline serum tumor markers (STM), computed tomography and FDG-PET were repeated after 4 wks and q8 weeks thereafter. The primary endpoint was PFS (H0: 3-m PFS ≤ 10%, H1: ≥ 25%, α = 5%/β = 20%). PD was defined as rising STM, increasing size of nonteratomatous masses (RECIST v1.1), or the appearance of new lesions. Translational analyses included circulating IL8 levels and next generation sequencing of pre-PZP tissue from extreme responders. Results: 43 pts were enrolled from 05/2013 to 07/2016. 35 pts (81.4%) had nonseminoma, 6 (14%) primary mediastinal GCT. The number of failed CT regimen was: 2 (11.6%), 3 (51.2%), > 3 (37.2%). 53.5% had failed HDCT. 39 pts had elevated STM: 56.4% AFP, 43.6% HCG. Grade 3-4 adverse events were seen in 4 pts (increased AST/ALT). 26/39 pts (66.7%) had STM reduction (38.5% > 50% from baseline) after 4 wks. RECIST results: 1 partial response, 20 stable disease, 16 PD (6 not evaluable). 12 (27.9%) had a decreased FDG uptake. Median follow-up was 29.6 months. 3-m PFS was 12.8% (95%CI: 5.7-28.9), median PFS was 2.5 m (IQR: 1.0-3.0). 24-m OS was 14.2% (95%CI: 6.0-33.7). In pts with > 50% STM decline, 24-m OS was 24.1% (95%CI: 8.3-69.6). Univariably, STM was associated with OS (HCG vs AFP: HR: 2.73, 95%CI: 1.24-6.02, p = 0.042). Baseline and +4wks IL8 levels did not predict for PFS/OS. In 2 responding pts, new mutations were found ( FLT3, G846V and RAD50 E448Q classified as damaging; TSC2, R197M and TNF A16V classified as benign). Conclusions: PZP was well tolerated and showed predictable activity, with early but short-living STM decline. Long term survival was obtained in a significant proportion of pts. Based on the present results, PZP may be investigated in earlier disease stages as an optimal bridging therapy preceding salvage curative treatment. Clinical trial information: NCT01743482.
A new HSP90 inhibitor as therapeutic agent for bladder cancer.
Authors: Liu Weiya , Lee Eugene K. , Pirani Karim , Blagg Brian S. J. , Holzbeierlein Jeffrey M. 
Published: March 2017

416 Background: Hsp90 represents one of the most promising biological targets for the treatment of cancer, including bladder cancer. A number of Hsp90 inhibitors that target the N-terminal ATP-binding pocket have demonstrated potent antiproliferative effects. However, a major drawback is that they induce a prosurvival heat shock response (HSR). We demonstrate the effects of a novel Hsp90 beta selective inhibitor on bladder cancer cells, which shows potent antiproliferative effects without inducing HSR. Methods: Cell Titer-Glo luminescent anti-proliferative assay was used to determine the IC50 numbers in UC3 cells. Trypan Blue Cytotoxicity assay was performed for 24h treatment with increasing concentrations of the inhibitor. Effects of the cmpound on Hsp90’s client protein degradation were investigated by Western Blot. Results: This new compound exhibits potent anti-proliferative in bladder cancer cells. IC50 number is determined as 0.30 µM for UC3 cancer cells. The toxicity assay was also performed over UC3 cells at 24h.1uM KU new compound has the similar effects on UC3 cells as 10 uM 17AAG: inhibit the cancer cells growth to half, but maintain over 60% viability of the cells. The western blot were also performed over UC3 cells, and some new target proteins such as FGFR3 and PKM2 were investigated. The data showed that, this new compound would not induce the heat shock response like 17AAG (Hsp27), and did cause some Hsp90β related protein degradation (CXCR4). FGFR3, PKM2, Her2, Hsf-1and B-raf all show degradation to different extent. Conclusions: A novel Hsp90 inhibitor, exhibits potent anti-proliferative and cytotoxic activity along with client protein degradation, without induction of HSR in bladder cancer cell lines. The reduction of Hsp90 beta related client protein caused by this compound suggests the potential to develop isoform specific inhibitors of Hsp90 for better antitumor therapies.
Outcomes for patients with advanced N3 penile cancer undergoing flap reconstruction and adjuvant chemo/radiotherapy.
Authors: Muneer Asif , MacAskill Findlay , Christodoulidou Michelle , Akers Clare , Mosahebi Ash , Younis Ibby , Nigam Raj , Malone Peter 
Published: March 2017

419 Background: Patients presenting with advanced penile cancer with significant inguinal disease requiring extensive resection. Reconstruction is required to cover the defect and protect underlying vascular structures when undergoingl adjuvant treatment. Often the performance status or the extent of the disease makes neoadjuvant chemo/radiotherapy difficult. Although this group of patients undoubtedly have a poor prognosis, palliative resection reduces the tumour burden and allows improved wound management and quality of life. The aim of this study was to present the techniques and report the outcomes for patients with N3 disease undergoing flap reconstruction. Methods: Medical records were reviewed for penile cancer patients with fixed inguinal nodal disease either at presentation or recurrence. Resection was performed by a team comprising urological and plastic surgeons. Cancer specific survival and the impact of adjuvant chemo/radiotherapy was recorded. Results: Seventeen patients were included; mean age 62 (range 37–85) years. Nine (53%) patients had a first presentation with penile cancer and advanced nodal disease, with 8 (47%) presenting with inguinal disease recurrence. The majority (n = 13) underwent a vertical rectus abdominis musculocutaneous (VRAM) flap. Of these, 3 required femoral vein reconstruction. Where defects were smaller, a tensor fascia latae (n = 2) or a scrotal advancement flap was used (n = 1). The average length of stay was 23 days (10-45 days) regardless of type of flap. Ten patients had adjuvant radiotherapy, 5 underwent neoadjuvant chemotherapy with a 4 undergoing adjuvant chemotherapy. The disease specific survival was 595 days (range 24-3881). Complications were related to wound healing and managed conservatively. Post operative lower limb lymphoedema occurred in the majority of patients. There were no flap failures and all but one patient was discharged home. Conclusions: Aggressive surgical management for patients with extensive nodal disease and flap reconstruction is feasible. This aids wound management and improves the quality of life for patients. Survival rates can extend to over 12 months following adjuvant treatment.
Early replacement of CT scanning by abdomino-pelvic ultrasound as a safe alternative in the follow-up of patients with germ cell tumors.
Authors: Baciarello Giulia , Hamilou Zineb , Fayard Florence , Gizzi Marco , Albiges Laurence , Loriot Yohann , Massard Christophe , Di Palma Mario , Escudier Bernard J. , Fizazi Karim 
Published: March 2017

420 Background: Late relapse in patients with germ cell tumors (GCT) are rare events. As there is no consensus for follow-up (FU) protocols, it is unclear if shorter duration of CT scanning is safe while reducing unnecessary exposure to radiation. Methods: At the completion of their treatment, all patients with Stage I, metastatic good or intermediate prognosis seminoma and non-seminoma (NSGT) underwent physical exam, serum tumor markers and imaging at regular intervals. We retrospectively identified 2 groups of patients with different FU strategies: those with regular CT scan of the chest, abdomen and pelvis for 3 years or less, then followed by abdomino-pelvic ultrasound (Group 1); and those with CT scanning continued beyond 3 years (Group 2). Results: Between December 1997 and March 2016, 203 patients were included: 80 (39.4%) in Group 1 and 123 (60.6%) in Group 2. The mean duration of FU was 6.7 ± 2.4 years in Group 1 and 8.1 ± 2.5 years in Group 2 (p < 0.001). After year 3 the median number of abdomino-pelvic ultrasound in Group 1 was 5 (4-6) and the median number of CT scanning in Group 2 was 6 (5-8). Five (2.4%) relapses were identified: 1 in Group 1 and 4 in Group 2. Relapse was revealed by symptoms in 2 patients with NSGT (1 in each group) who had been lost for FU. Three patients underwent local treatment (2 surgeries for teratoma relapses and 1 radiotherapy for seminoma relapse) and are still disease-free. International prognostic factors score was low and intermediate for the first 2 patients, very low for seminoma relapse and low for teratoma relapses. Conclusions: Patient follow-up by regular abdomino-pelvic ultrasound instead of CT scan appears a feasible alternative after the third year in patients with GCT, with no excess risk of incurable relapses. Prospective validation is required.
The impact of the Affordable Care Act on treatment of testicular cancer.
Authors: Francis John Joseph , Abouassaly Robert , Gonzalez Christopher , Meropol Neal J. , Kutikov Alexander , Smaldone Marc C. , Psutka Sarah P. , Williams Stephen Bentley , Kim Simon P. 
Published: March 2017

422 Background: The passage of the Affordable Care Act (ACA) in 2010 aimed to improve access for uninsured patients to private health insurance. Yet, the impact of the ACA on the number of privately insured young patients and on the timeliness of medical care for serious medical conditions, remain unclear. Thus, we sought to ascertain changes in insurance status and evaluate timeliness of post-orchiectomy definitive therapy for young men diagnosed with testicular cancer following passage of the ACA. Methods: From the National Cancer Database, we identified all patients 18 – 50 years of age diagnosed with stages I – III testicular cancer from 2007 to 2013. Patients were divided into groups at the time of diagnosis; 2007 – 2009 (pre-ACA) and 2011 to 2013 (post-ACA). Only patients who had undergone radical orchiectomy and had a reported insurance status were included in analysis. The primary outcomes were insurance type at diagnosis and time to treatment of secondary therapy following orchiectomy (systemic chemotherapy, radiation therapy, or surgery {Retroperitoneal lymph node dissection; RPLND}). Results: Overall, 17,945 patients were included in analysis with 53.5% diagnosed with pure seminoma and 46.5% diagnosed with nonseminomatous germ cell tumor (NSGCT). In comparing pre- and post-ACA cohorts, the percentage of patients with private health insurance decreased following the passage of the ACA (74.1% vs. 71.2%; p < 0.01). Similarly, the percentage of patients without any insurance increased between the two time frames (12.7 % vs. 13.4%; p < 0.01). More patients presented with clinical stage II and III disease following the passage of the ACA (28.9% vs. 31.9%; p < 0.01). Compared to patients without health insurance, privately insured patients received more timely secondary definitively therapy with radiation therapy (49.9 vs. 60.9 days, p < 0.01) and chemotherapy (41.5 vs. 45.7 days, p < 0.01) but no difference in the time to RPLND (18.8 vs. 16.7 days, p = 0.70). Conclusions: The impact of the ACA on patients with testicular cancer shows minimal worsening in the number of privately insured young men and increasing rates of advanced testis cancer. This was not in agreement with our hypothesis and suggests the ACA is not benefiting young men with this malignancy.
Effect of alvimopan on gastrointestinal recovery and length of hospitalization after retroperitoneal lymph node dissection for testicular cancer.
Authors: Radadia Kushan Dilip , Farber Nicholas , Tabakin Alexandra , Milas Lee , Jang Thomas 
Published: March 2017

424 Background: Alvimopan use in enhanced recovery programs has reduced the hospital LOS in patients undergoing major abdominal surgeries. Retroperitoneal lymph node dissection (RPLND) for testicular cancer may be associated with delayed GI recovery prolonging hospital LOS. In this study, we evaluate whether alvimopan is associated with enhanced GI recovery and shorter hospital LOS in men undergoing RPLND for testicular cancer. Methods: From 2010 to 2016, 29 patients underwent RPLND by a single surgeon (23 post-chemotherapy). All patients underwent bilateral template dissection. Data for patients who received alvimopan was prospectively collected and compared to a historical cohort of patients who did not receive alvimopan. Primary outcomes measured were hospital LOS and recovery of GI function. Mann-Whitney Wilcoxon and Chi square tests were used to determine statistical significance between the two groups. Results: Of 29 men who underwent RPLND, 8 received alvimopan and 21 did not. There were no differences in preoperative or operative variables between the groups (Table). Median hospital LOS for men receiving alvimopan was 4 days compared to 6 days for those who did not (p=0.074). The median time to return of flatus in men receiving alvimopan was 2 days compared to 4 days for those who did not (p=0.0023). The median time to first bowel movement (BM) in men receiving alvimopan was 2.5 days compared to 4 days for those who did not (p=0.0028). Conclusions: Alvimopan significantly reduced the median time to return of flatus and to first BM after RPLND. Furthermore, there was a trend towards shorter hospital LOS in those receiving alvimopan. [Table: see text]