Measurement of the

^{140}Ce(n,γ) is a key reaction for slow neutron-capture (s-process) nucleosynthesis due to being a bottleneck in the reaction flow. For this reason, it was measured with high accuracy (uncertainty ≈5%) at the n_TOF facility, with an unprecedented combination of a high purity sample and low neutron-sensitivity detectors. The measured Maxwellian averaged cross section is up to 40% higher than previously accepted values. Stellar model calculations indicate a reduction around 20% of the s-process contribution to the Galactic cerium abundance and smaller sizeable differences for most of the heavier elements. No variations are found in the nucleosynthesis from massive stars.

EV-301 long-term outcomes: 24-month findings from the phase III trial of enfortumab vedotin versus chemotherapy in patients with previously treated advanced urothelial carcinoma.

INTRODUCTION: This exploratory analysis evaluated efficacy and safety data for enfortumab vedotin versus chemotherapy over a median follow-up of ∼2 years from EV-301. MATERIALS AND METHODS: Patients with locally advanced/metastatic urothelial carcinoma with prior platinum-containing chemotherapy and disease progression during/after programmed cell death protein 1/ligand 1 inhibitor treatment were randomized to enfortumab vedotin or chemotherapy (docetaxel, paclitaxel, vinflunine). Endpoints were overall survival (primary), progression-free survival (PFS), objective response, and safety. RESULTS: In total, 608 patients were included (enfortumab vedotin, n = 301; chemotherapy, n = 307). With a median follow-up of 23.75 months, 444 deaths had occurred (enfortumab vedotin, n = 207; chemotherapy, n = 237). Risk of death was reduced by 30% with enfortumab vedotin versus chemotherapy [hazard ratio (HR) 0.70 (95% confidence interval [CI] 0.58-0.85); one-sided, log-rank P = 0.00015]; PFS improved with enfortumab vedotin [HR 0.63 (95% CI 0.53-0.76); one-sided, log-rank P < 0.00001]. Treatment-related adverse event rates were 93.9% for enfortumab vedotin and 91.8% for chemotherapy; grade ≥ 3 event rates were 52.4% and 50.5%, respectively. Grade ≥ 3 treatment-related decreased neutrophil count (14.1% versus 6.1%), decreased white blood cell count (7.2% versus 1.4%), and anemia (7.9% versus 2.7%) were more common with chemotherapy versus enfortumab vedotin; maculopapular rash (7.4% versus 0%), fatigue (6.8% versus 4.5%), and peripheral sensory neuropathy (5.1% versus 2.1%) were more common with enfortumab vedotin. Of special interest adverse events, treatment-related skin reactions occurred in 47.3% of patients receiving enfortumab vedotin and 15.8% of patients receiving chemotherapy; peripheral neuropathy occurred in 48.0% versus 31.6%, respectively, and hyperglycemia in 6.8% versus 0.3%. CONCLUSIONS: After a median follow-up of ∼2 years, enfortumab vedotin maintained clinically meaningful overall survival benefit versus chemotherapy, consistent with findings from the EV-301 primary analysis; PFS and overall response benefit remained consistent. Adverse events were manageable; no new safety signals were observed.

74 Ge( n , γ ) cross section below 70 keV measured at n_TOF CERN.

Neutron capture reaction cross sections on 74 Ge are of importance to determine 74 Ge production during the astrophysical slow neutron capture process. We present new resonance data on 74 Ge( n , γ ) reactions below 70 keV neutron energy. We calculate Maxwellian averaged cross sections, combining our data below 70 keV with evaluated cross sections at higher neutron energies. Our stellar cross sections are in agreement with a previous activation measurement performed at Forschungszentrum Karlsruhe by Marganiec et al., once their data has been re-normalised to account for an update in the reference cross section used in that experiment.

Atezolizumab in locally advanced or metastatic urothelial cancer: a pooled analysis from the Spanish patients of the IMvigor 210 cohort 2 and 211 studies

Background The studies IMvigor 210 cohort 2 and IMvigor211 evaluated the efficacy of atezolizumab in patients with locally advanced or metastatic urothelial cancer (mUC) upon progression to platinum-based chemotherapy worldwide. Yet, the real impact of this drug in specific geographical regions is unknown. Materials and methods We combined individual-level data from the 131 patients recruited in Spain from IMvigor210 cohort 2 and IMvigor211 in a pooled analysis. Efficacy and safety outcomes were assessed in the overall study population and according to PD-L1 expression on tumour-infiltrating immune cells. Results Full data were available for 127 patients; 74 (58%) received atezolizumab and 53 (42%) chemotherapy. Atezolizumab patients had a numerically superior median overall survival although not reaching statistical significance (9.2 months vs 7.7 months). No statistically significant differences between arms were observed in overall response rates (20.3% vs 37.0%) or progression-free survival (2.1 months vs 5.3 months). Nonetheless, median duration of response was superior for the immunotherapy arm (non-reached vs 6.4 months; p = 0.005). Additionally, among the responders, the 12-month survival rates seemed to favour atezolizumab (66.7% vs 19.9%). When efficacy was analyzed based on PD-L1 expression status, no significant differences were found. Treatment-related adverse events of any grade occurred more frequently in the chemotherapy arm [46/57 (81%) vs 44/74 (59%)]. Conclusion Patients who achieved an objective response on atezolizumab presented a longer median duration of response and numerically superior 12 month survival rates when compared with chemotherapy responders along with a more favorable safety profile. PD-L1 expression did not discriminate patients who might benefit from atezolizumab (AU)

Atezolizumab in locally advanced or metastatic urothelial cancer: a pooled analysis from the Spanish patients of the IMvigor 210 cohort 2 and 211 studies.

BACKGROUND: The studies IMvigor 210 cohort 2 and IMvigor211 evaluated the efficacy of atezolizumab in patients with locally advanced or metastatic urothelial cancer (mUC) upon progression to platinum-based chemotherapy worldwide. Yet, the real impact of this drug in specific geographical regions is unknown. MATERIALS AND METHODS: We combined individual-level data from the 131 patients recruited in Spain from IMvigor210 cohort 2 and IMvigor211 in a pooled analysis. Efficacy and safety outcomes were assessed in the overall study population and according to PD-L1 expression on tumour-infiltrating immune cells. RESULTS: Full data were available for 127 patients; 74 (58%) received atezolizumab and 53 (42%) chemotherapy. Atezolizumab patients had a numerically superior median overall survival although not reaching statistical significance (9.2 months vs 7.7 months). No statistically significant differences between arms were observed in overall response rates (20.3% vs 37.0%) or progression-free survival (2.1 months vs 5.3 months). Nonetheless, median duration of response was superior for the immunotherapy arm (non-reached vs 6.4 months; p = 0.005). Additionally, among the responders, the 12-month survival rates seemed to favour atezolizumab (66.7% vs 19.9%). When efficacy was analyzed based on PD-L1 expression status, no significant differences were found. Treatment-related adverse events of any grade occurred more frequently in the chemotherapy arm [46/57 (81%) vs 44/74 (59%)]. CONCLUSION: Patients who achieved an objective response on atezolizumab presented a longer median duration of response and numerically superior 12 month survival rates when compared with chemotherapy responders along with a more favorable safety profile. PD-L1 expression did not discriminate patients who might benefit from atezolizumab.

Patterns of relapse and treatment outcome after active surveillance or adjuvant carboplatin for stage I seminoma: a retrospective study of the Spanish Germ Cell Cancer Group.

PURPOSE: Active surveillance (AS) and adjuvant chemotherapy (AC) with carboplatin are valid alternatives for managing stage I seminoma, and most relapses can be cured with cisplatin-based chemotherapy. However, some reports suggest that AC may modify the classical pattern of recurrences. METHODS: We analyzed all relapses observed in a series of 879 patients with stage I seminoma included in 4 consecutive studies of the Spanish Germ Cell Cancer Group. After a median follow-up of 67 months, recurrences were detected in 56/467 (12%) low-risk cases on AS and 13/412 (3%) high-risk cases after AC (p < 0.001). The objective was to describe clinical features, treatment and outcome. Univariate comparisons were performed between both groups. RESULTS: No significant differences were found between relapses on AS and those after AC in terms of time to relapse (13 vs 17 months), size (26 vs 27 mm), location (retroperitoneum in 88% vs 85%), and method of detection (computed tomography in 77% vs 69%). Treatment consisted of chemotherapy (etoposide + cisplatin ± bleomycin) in 89% and 92%, respectively. Late relapses (after > 3 years) were seen in 11% vs 7.7% (p = NS) and second or successive recurrences in 1.8 vs 23% (p < 0.05). With a median follow-up of 130 moths, two patients died of seminoma-unrelated causes (AS group) and the rest are alive and disease-free. CONCLUSION: In the setting of a risk-adapted treatment of stage I seminoma, the administration of two courses of AC in patients with tumor size > 4 cm and/or rete testis invasion is associated with a higher incidence of second recurrences but does not significantly modify the pattern of relapses or their outcome.

Treatment and Outcome of Patients with Stage IS Testicular Cancer: A Retrospective Study from the Spanish Germ Cell Cancer Group.

PURPOSE: Stage IS testicular cancer is defined by the persistence of elevated serum tumor markers, including α-fetoprotein and/or ß-human chorionic gonadotropin, after orchiectomy without radiological evidence of metastatic disease. Current treatment recommendations include cisplatin based chemotherapy up front but the recommendations are based on limited single center series. MATERIALS AND METHODS: We retrospectively analyzed clinical and pathological characteristics, and long-term outcomes in 110 patients uniformly treated with primary chemotherapy between 1994 and 2016. The primary objective was to evaluate long-term disease-free survival. We also explored factors associated with the need for additional treatment. RESULTS: The elevated prechemotherapy tumor markers were α-fetoprotein in 48% of cases, ß-human chorionic gonadotropin in 14%, and α-fetoprotein and ß-human chorionic gonadotropin in 38%. Median α-fetoprotein and ß-human chorionic gonadotropin values were 71 ng/ml and 80 mIU/ml, respectively. The IGCCCG (International Germ Cell Cancer Collaborative Group) prognostic classification was good in 94% of cases. Mixed nonseminomatous germ cell tumor was found in 78% of cases. Of the patients 103 achieved a complete response to chemotherapy. In 6 patients radiological signs of progressive disease developed during chemotherapy, while 8 experienced relapse after an initial complete response. At a median followup of 108 months 108 patients were alive and disease-free. Five and 10-year disease-free survival rates were 87% and 85%, respectively. The predominance of embryonal carcinoma in the primary tumor was the only factor associated with the probability of needing additional therapy. CONCLUSIONS: Stage IS testicular cancer is more commonly associated with elevated α-fetoprotein, an IGCCCG good prognosis and mixed nonseminomatous germ cell tumor. Treatment with cisplatin based chemotherapy leads to cure in most cases. However, a proportion of patients require the integration of additional therapies, including more frequently when embryonal carcinoma is not predominant.

Active surveillance as a successful management strategy for patients with clinical stage I germ cell testicular cancer.

BACKGROUND: Cancer-specific survival for patients with clinical stage I (CSI) germ cell testicular cancer (GCTC) is outstanding after inguinal orchidectomy regardless the treatment utilized. This study evaluated whether active surveillance (AS) of such patients yielded similar health outcomes to other therapeutic strategies such as adjuvant chemotherapy, radiotherapy or primary retroperitoneal lymphadenectomy as described in the literature. PATIENTS AND METHODS: Patients with CSI GCTC were screened between January 2012 and December 2016. Patients had previously undergone inguinal orchidectomy as the primary treatment and chosen AS as their preferred management strategy after receiving information about all available strategies. RESULTS: Out of 91 patients screened, 82 patients selected AS as their preferred management strategy. Relapse rate in the overall population was 20% (95% CI 12-30) and median time to relapse was 11.5 months (range 1.0-35.0). In patients with seminomatous tumors, relapse rate decreased to 13% and median time to relapse was 13 months; whereas in patients with non-seminomatous tumors, relapse rate was 33% (IA) or 29% (IB) and median time to relapse was 12 months in stage IA and 4.5 months in stage IB patients. All relapses were rescued with three or four cycles of chemotherapy and two also required a retroperitoneal lymphadenectomy. All patients are currently alive and free of disease. CONCLUSIONS: The clinical outcomes of patients with CSI GCTC managed by AS in this series were excellent. This strategy limited the administration of active treatments specifically to the minority of patients who relapsed without compromising performance.

Steady state magnetic sensors for ITER and beyond: Development and final design (invited).

The measurements of the magnetic field in tokamaks such as ITER and DEMO will be challenging due to the long pulse duration, high neutron flux, and elevated temperatures. The long duration of the plasma pulse makes standard techniques, such as inductive coils, prone to errors. At the same time, the hostile environment, with repairs possible only on blanket exchange, if at all, requires a robust magnetic sensor. This contribution presents the final design of novel, steady-state, magnetic sensors for ITER. A poloidal array of 60 sensors mounted on the vacuum vessel outer shell contributes to the measurement of the plasma current, plasma-wall clearance, low-frequency MHD modes and will allow for crosscheck with the outer-vessel inductive coils. Each sensor hosts a pair of bismuth Hall probes, themselves an outcome of extensive R&D, including neutron irradiations (to 1023 n/m2), temperature cycling tests (73-473 K) and tests at high magnetic field (to 12 T). A significant effort has been devoted to optimize the sensor housing by design and prototyping. The production version features an indium-filled cell for in situ recalibration of the onboard thermocouple, vital for the interpretation of the Hall sensor measurement.

High magnetic field test of the ITER outer vessel steady-state magnetic field Hall sensors at ITER relevant temperature.

The ITER outer vessel steady-state magnetic field sensor diagnostics consist of sixty sensor units. Each sensor unit features a pair of ceramic-metal Hall sensors with a sensing layer made of bismuth. The sensors were tested simultaneously in the magnetic field ranging from -12 T to +12 T at the temperature range from 27 to 127 °C. The Hall coefficient and magnetoresistance of the bismuth layer related to the sensors were identified. In the sensor operating conditions, the Hall coefficient dependence on temperature was fitted with an exponential function with a relative error of less than 0.08%, and the dependence on the magnetic field was fitted with a Gaussian-like function with a relative error of less than 0.11%. An alternative expression based on the physical understanding of the free charge carrier transport in semimetals was derived to describe the dependence of the Hall coefficient on the magnetic field, and its fitting error of 1.2 mT in terms of the magnetic field measurement has met the ITER measurement accuracy requirements.

Are there effects of age, gender, height, and body fat on the functional muscle-bone unit in children and adults?

The aim was to describe the effect of age, gender, height, different stages of human life, and body fat on the functional muscle-bone unit. All these factors had a significant effect on the functional muscle-bone unit and should be addressed when assessing functional muscle-bone unit in children and adults. INTRODUCTION: For the clinical evaluation of the functional muscle-bone unit, it was proposed to evaluate the adaptation of the bone to the acting forces. A frequently used parameter for this is the total body less head bone mineral content (TBLH-BMC) determined by dual-energy X-ray absorptiometry (DXA) in relation to the lean body mass (LBM by DXA). LBM correlates highly with muscle mass. Therefore, LBM is a surrogate parameter for the muscular forces acting in everyday life. The aim of the study was to describe the effect of age and gender on the TBLH-BMC for LBM and to evaluate the impact of other factors, such as height, different stages of human life, and of body fat. METHODS: As part of the National Health and Nutrition Examination Survey (NHANES) study, between the years 1999-2006 whole-body DXA scans on randomly selected Americans from 8 years of age were carried out. From all eligible DXA scans (1999-2004), three major US ethnic groups were evaluated (non-Hispanic Whites, non-Hispanic Blacks, and Mexican Americans) for further statistical analysis. RESULTS: For the statistical analysis, the DXA scans of 8190 non-Hispanic White children and adults (3903 female), of 4931 non-Hispanic Black children and adults (2250 female) and 5421 of Mexican-American children and adults (2424 female) were eligible. Age, gender, body height, and especially body fat had a significant effect on the functional muscle-bone unit. CONCLUSIONS: When assessing TBLH-BMC for LBM in children and adults, the effects of age, gender, body fat, and body height should be addressed. These effects were analyzed for the first time in such a large cohort.

Experience with jumping mechanography in children with cerebral palsy.

OBJECTIVES: Jumping mechanography provides robust motor function indicators among healthy children. The aim of the study was to assess the reproducibility and validity of jumping mechanography conducted as single two-legged jump (S2LJ) in children with cerebral palsy (CP). METHODS: 215 S2LJ investigations from a sample of 75 children with CP were eligible for evaluation. For the estimation of the reproducibility, only the baseline set of data per patient were used. Gross motor function was evaluated by the Gross Motor Function Measure (GMFM-66). In 135 S2LJ investigations, GMFM-66 was assessed within a week in the same child. This data was used for validity assessment. RESULTS: Coefficients of variation for the main outcome parameters ranged between 6.15-9.71%, except for jump height (CV%=27.3%). The intraclass correlation coefficients for peak velocity (Vmax) and peak power relative to body weight (Pmax/mass) was 0.927 and 0.931. Vmax and Pmax/mass were also the test parameters with the strongest correlation to the GMFM-66 score (⟩0.7). CONCLUSIONS: S2LJ assessed in the present study provided reproducible outcome measures particularly for Vmax and Pmax/mass in children with CP. Further, Vmax and Pmax/mass showed the strongest correlation with the GMFM-66 score and seem to be the most relevant evaluation criteria.

Androgen receptor gene status in plasma DNA associates with worse outcome on enzalutamide or abiraterone for castration-resistant prostate cancer: a multi-institution correlative biomarker study.

BACKGROUND: There is an urgent need to identify biomarkers to guide personalized therapy in castration-resistant prostate cancer (CRPC). We aimed to clinically qualify androgen receptor (AR) gene status measurement in plasma DNA using multiplex droplet digital PCR (ddPCR) in pre- and post-chemotherapy CRPC. METHODS: We optimized ddPCR assays for AR copy number and mutations and retrospectively analyzed plasma DNA from patients recruited to one of the three biomarker protocols with prospectively collected clinical data. We evaluated associations between plasma AR and overall survival (OS) and progression-free survival (PFS) in 73 chemotherapy-naïve and 98 post-docetaxel CRPC patients treated with enzalutamide or abiraterone (Primary cohort) and 94 chemotherapy-naïve patients treated with enzalutamide (Secondary cohort; PREMIERE trial). RESULTS: In the primary cohort, AR gain was observed in 10 (14%) chemotherapy-naïve and 33 (34%) post-docetaxel patients and associated with worse OS [hazard ratio (HR), 3.98; 95% CI 1.74-9.10; P < 0.001 and HR 3.81; 95% CI 2.28-6.37; P < 0.001, respectively], PFS (HR 2.18; 95% CI 1.08-4.39; P = 0.03, and HR 1.95; 95% CI 1.23-3.11; P = 0.01, respectively) and rate of PSA decline ≥50% [odds ratio (OR), 4.7; 95% CI 1.17-19.17; P = 0.035 and OR, 5.0; 95% CI 1.70-14.91; P = 0.003, respectively]. AR mutations [2105T>A (p.L702H) and 2632A>G (p.T878A)] were observed in eight (11%) post-docetaxel but no chemotherapy-naïve abiraterone-treated patients and were also associated with worse OS (HR 3.26; 95% CI 1.47-not reached; P = 0.004). There was no interaction between AR and docetaxel status (P = 0.83 for OS, P = 0.99 for PFS). In the PREMIERE trial, 11 patients (12%) with AR gain had worse PSA-PFS (sPFS) (HR 4.33; 95% CI 1.94-9.68; P < 0.001), radiographic-PFS (rPFS) (HR 8.06; 95% CI 3.26-19.93; P < 0.001) and OS (HR 11.08; 95% CI 2.16-56.95; P = 0.004). Plasma AR was an independent predictor of outcome on multivariable analyses in both cohorts. CONCLUSION: Plasma AR status assessment using ddPCR identifies CRPC with worse outcome to enzalutamide or abiraterone. Prospective evaluation of treatment decisions based on plasma AR is now required. CLINICAL TRIAL NUMBER: NCT02288936 (PREMIERE trial).

The functional muscle-bone unit in children with cerebral palsy.

Our results suggest that the prevalence of bone health deficits in children with CP was overestimated, when using only age- and height-adjusted bone mineral content (BMC) and areal bone mineral density (aBMD). When applying the functional muscle-bone unit diagnostic algorithm (FMBU-A), the prevalence of positive results decreased significantly. We recommend applying the FMBU-A when assessing bone health in children with CP. INTRODUCTION: The prevalence of bone health deficits in children with cerebral palsy (CP) might be overestimated because age- and height-adjusted reference percentiles for bone mineral content (BMC) and areal bone mineral density (aBMD) assessed by dual-energy X-ray absorptiometry (DXA) do not consider reduced muscle activity. The aim of this study was to compare the prevalence of positive DXA-based indicators for bone health deficits in children with CP to the prevalence of positive findings after applying a functional muscle-bone unit diagnostic algorithm (FMBU-A) considering reduced muscle activity. METHODS: The present study was a monocentric retrospective analysis of 297 whole body DXA scans of children with CP. The prevalence of positive results of age- and height-adjusted BMC and aBMD defined as BMC and aBMD below the P3 percentile and of the FMBU-A was calculated. RESULTS: In children with CP, the prevalence of positive results of age-adjusted BMC were 33.3% and of aBMD 50.8%. Height-adjusted results for BMC and aBMD were positive in 16.8 and 36.0% of cases. The prevalence of positive results applying the FMBU-A regarding BMC and aBMD were significantly (p < 0.001) lower than using age- and height-adjusted BMC and aBMD (8.8 and 14.8%). CONCLUSIONS: Our results suggest that the prevalence of bone health deficits in children with CP was overestimated, when using age- and height-adjusted BMC and aBMD. When applying the FMBU-A, the prevalence decreased significantly. We recommend applying the FMBU-A when assessing bone health in children with CP.

Filamentary probe on the COMPASS tokamak.

This paper describes a new filamentary probe recently introduced on the COMPASS tokamak. It allows the measurement of electrostatic and magnetic properties of the filaments and their changes in dependence on distance from the separatrix in the region between a divertor and midplane. The probe head is mounted on a manipulator moving the probe radially on a shot-to-shot basis. This configuration is suitable for the long term statistical measurement of the plasma filaments and the measurement of their evolution during their propagation from the separatrix to the wall. The basics of the filamentary probe construction, the evolution of the plasma parameters, and first conditional averages of the plasma filaments in the scrape-off layer of the COMPASS tokamak during the L-mode regime are presented.

Acute water quality criteria for polycyclic aromatic hydrocarbons, pesticides, plastic additives, and 4-Nonylphenol in seawater.

Probabilistic environmental quality criteria for Naphthalene (Nap), Phenanthrene (Phe), Fluoranthene (Flu), Pyrene (Pyr), Triclosan (TCS), Tributyltin (TBT), Chlorpyrifos (CPY), Diuron (DUR), γ-Hexaclorocyclohexane (γ-HCH), Bisphenol A (BPA) and 4-Nonylphenol (4-NP) were derived from acute toxicity data using saltwater species representative of marine ecosystems, including algae, mollusks, crustaceans, echinoderms and chordates. Preferably, data concerns sublethal endpoints and early life stages from bioassays conducted in our laboratory, but the data set was completed with a broad literature survey. The Water Quality Criteria (WQC) obtained for TBT (7.1·10-3 µg L-1) and CPY (6.6· 10-3 µg L-1) were orders of magnitude lower than those obtained for PAHs (ranging from 3.75 to 45.2 µg L-1), BPA (27.7 µg L-1), TCS (8.66 µg L-1) and 4-NP (1.52 µg L-1). Critical values for DUR and HCH were 0.1 and 0.057 µg L-1 respectively. Within this context, non-selective toxicants could be quantitatively defined as those showing a maximum variability in toxicity thresholds (TT) of 3 orders of magnitude across the whole range of marine diversity, and a cumulative distribution of the TT fitting to a single log-logistic curve, while for selective toxicants variability was consistently found to span 5 orders of magnitude and the TT distribution showed a bimodal pattern. For the latter, protective WQC must be derived taking into account the SSD of the sensitive taxa only.

Clinical and pathologic features of patients with non-epithelial ovarian cancer: retrospective analysis of a single institution 15-year experience

Purpose. Non-epithelial ovarian cancers (NEOCs) are rare diseases. Despite their overall good prognosis, the best management and current prognostic factors remain unclear. The objective of our study was to assess the clinical and pathological features of NEOC patients treated in our institution in the last 15 years and to explore risk factors for relapse and survival. Methods/patients. All patients with a pathological diagnosis of NEOC referred to the medical oncology department at Hospital Universitario Virgen del Rocio between 1999 and 2014 were included. Demographics, tumor characteristics, treatment procedures, and clinical follow-up were retrospectively collected. Risk factors for disease-free survival (DFS) and overall survival (OS) were assessed. Results. Fifty-seven patients were included, 33 (58 %) had a sex cord-stromal tumor (SCST) and 24 (42 %) had a germ-cell tumor (GCT). Median age, non-conservative surgery rates and DFS were lower in the GCT cohort; however, salvage chemotherapy led to a high proportion of complete responses in this group translating into a 90 % 3-year OS rate in both NEOC subtypes. The only identified risk factors statistically significant were stage and tumour relapse that associated, respectively, with DFS (HR = 8.84; 95 % CI 1.85-42) and OS (HR = 11.02; 95 % CI 1.76-68.7). Conclusions. Despite their rarity, NEOCs remain a highly curable group of neoplasm. In our series, a more conservative treatment approach in ovarian GCTs revealed comparable OS outcomes to SCST. No new risk factors that would help in patient stratification were identified (AU)

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Resistance to Targeted Therapies in Renal Cancer: The Importance of Changing the Mechanism of Action.

Renal cell carcinoma (RCC) is a complex disease characterized by mutations in several genes. Loss of function of the von Hippel-Lindau (VHL) tumour suppressor gene is a very common finding in RCC and leads to up-regulation of hypoxia-inducible factor (HIF)-responsive genes accountable for angiogenesis and cell growth, such as platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). Binding of these proteins to their cognate tyrosine kinase receptors on endothelial cells promotes angiogenesis. Promotion of angiogenesis is in part due to the activation of the phosphatidylinositol-3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) pathway. Inhibition of this pathway decreases protein translation and inhibits both angiogenesis and tumour cell proliferation. Although tyrosine kinase inhibitors (TKIs) stand as the main first-line treatment option for advanced RCC, eventually all patients will become resistant to TKIs. Resistance can be overcome by using second-line treatments with different mechanisms of action, such as inhibitors of mTOR, c-MET, programmed death 1 (PD-1) receptor, or the combination of an mTOR inhibitor (mTORi) with a TKI. In this article, we briefly review current evidence regarding mechanisms of resistance in RCC and treatment strategies to overcome resistance with a special focus on the PI3K/AKT/mTOR pathway.

Health resource utilisation associated with skeletal-related events in patients with bone metastases secondary to solid tumours: regional comparisons in an observational study.

Skeletal-related events (SREs) including spinal cord compression, pathologic fracture, and radiation or surgery to bone, occur frequently due to bone metastases in advanced cancer. This analysis of a multicentre, observational study was designed to describe cross-regional differences in health resource utilisation (HRU) of SREs in Western Europe and the US. Patients with bone metastases due to breast, lung or prostate cancer, or multiple myeloma who had experienced a SRE within the past 97 days were enrolled. Investigators recorded HRU associated with SREs, including hospitalisation and length of stay (LOS), outpatient visits, procedures and bisphosphonate use. This subanalysis includes 668 patients with solid tumours (US, n = 190 with 354 SREs; EU, n = 478 with 893 SREs). The rate of SREs associated with hospitalisation(s) was higher in the EU vs. the US (30% vs. 15%, P < 0.001) and LOS was longer in the EU [mean (SD) days/SRE: 19.87 (17.31) vs. 10.61 (9.39)]. However, the US was associated with higher rate of SREs with outpatient visits than the EU (88% vs. 74%, P < 0.0001) and more procedures [mean (SD)/SRE: 11.26 (7.94) vs. 6.91 (6.48)]. Bisphosphonates were less often used in the EU (65% vs. 76% of US, P = 0.0033). In patients experiencing SREs due to bone metastases, HRU patterns reflect regional diversity with a substantial burden in both regions.

Clinical and pathologic features of patients with non-epithelial ovarian cancer: retrospective analysis of a single institution 15-year experience.

PURPOSE: Non-epithelial ovarian cancers (NEOCs) are rare diseases. Despite their overall good prognosis, the best management and current prognostic factors remain unclear. The objective of our study was to assess the clinical and pathological features of NEOC patients treated in our institution in the last 15 years and to explore risk factors for relapse and survival. METHODS/PATIENTS: All patients with a pathological diagnosis of NEOC referred to the medical oncology department at Hospital Universitario Virgen del Rocio between 1999 and 2014 were included. Demographics, tumor characteristics, treatment procedures, and clinical follow-up were retrospectively collected. Risk factors for disease-free survival (DFS) and overall survival (OS) were assessed. RESULTS: Fifty-seven patients were included, 33 (58 %) had a sex cord-stromal tumor (SCST) and 24 (42 %) had a germ-cell tumor (GCT). Median age, non-conservative surgery rates and DFS were lower in the GCT cohort; however, salvage chemotherapy led to a high proportion of complete responses in this group translating into a 90 % 3-year OS rate in both NEOC subtypes. The only identified risk factors statistically significant were stage and tumour relapse that associated, respectively, with DFS (HR = 8.84; 95 % CI 1.85-42) and OS (HR = 11.02; 95 % CI 1.76-68.7). CONCLUSIONS: Despite their rarity, NEOCs remain a highly curable group of neoplasm. In our series, a more conservative treatment approach in ovarian GCTs revealed comparable OS outcomes to SCST. No new risk factors that would help in patient stratification were identified.