A randomized phase III study evaluating pegylated liposomal doxorubicin versus capecitabine as first-line therapy for metastatic breast cancer: results of the PELICAN study

The PELICAN trial evaluates for the first time efficacy and safety of pegylated liposomal doxorubicin (PLD) versus capecitabine as first-line treatment of metastatic breast cancer (MBC). This randomized, phase III, open-label, multicenter trial enrolled first-line MBC patients who were ineligible for endocrine or trastuzumab therapy. Cumulative adjuvant anthracyclines of 360 mg/m(2) doxorubicin or equivalent were allowed. Left ventricular ejection fraction of > 50 % was required. Patients received PLD 50 mg/m(2) every 28 days or capecitabine 1250 mg/m(2) twice daily for 14 days every 21 days. The primary endpoint was time-to-disease progression (TTP). 210 patients were randomized (n = 105, PLD and n = 105, capecitabine). Adjuvant anthracyclines were given to 37 % (PLD) and 36 % (capecitabine) of patients. No significant difference was observed in TTP [HR = 1.21 (95 % confidence interval, 0.838-1.750)]. Median TTP was 6.0 months for both PLD and capecitabine. Comparing patients with or without prior anthracyclines, no significant difference in TTP was observed in the PLD arm (log-rank P = 0.64). For PLD versus capecitabine, respectively, overall survival (median, 23.3 months vs. 26.8 months) and time-to-treatment failure (median, 4.6 months vs. 3.7 months) were not statistically significantly different. Compared to PLD, patients on capecitabine experienced more serious adverse events (P = 0.015) and more cardiac events among patients who had prior anthracycline exposure (18 vs. 8 %;P = 0.31). Both PLD and capecitabine are effective first-line agents for MBC

EVI1 expression in early-stage breast cancer patients treated with neoadjuvant chemotherapy

Background Overexpression of the EVI1 (ecotropic viral integration site 1) oncogene has recently been implicated as a prognostic factor in breast cancer (BC), particularly in triple-negative BC (TNBC). In this study we aimed to investigate frequency and clinical relevance of EVI1 expression in newly diagnosed BC treated with neoadjuvant chemotherapy. Methods EVI1 expression was determined by immunohistochemistry using H-score as a cumulative measurement of protein expression in pretherapeutic biopsies of BC patients treated with anthracycline/taxane based neoadjuvant chemotherapy within the GeparTrio trial. EVI1 was analyzed as a continuous variable and dichotomized into low or high based on median expression. Endpoints were pathological complete response (pCR), disease-free survival (DFS) and overall survival (OS). Results Of the 993 tumors analyzed, 882 had available subtype information: 50.8% were HR + /HER2-, 15% HR + /HER2 + , 9.8% HR-/HER2 + , and 24.5% TNBC. Median EVI1 H-score was 112.16 (range 0.5–291.4). High EVI1 expression was significantly associated with smaller tumor size (p = 0.002) but not with BC subtype. Elevated EVI1 levels were not significantly associated with therapy response and survival in the entire cohort or within BC subtypes. However, TNBC patients with high EVI1 showed a trend towards increased pCR rates compared to low group (37.7% vs 27.5%, p = 0.114; odds ratio 1.60 (95%CI 0.90–2.85, p = 0.110) and numerically better DFS (HR = 0.77 [95%CI 0.48–1.23], log-rank p = 0.271) and OS (HR = 0.76 [95% 0.44–1.31], log-rank p = 0.314) without reaching statistical significance. Conclusion EVI1 was not associated with response to neoadjuvant therapy or patient survival in the overall cohort. Further analyses are needed to verify our findings especially in the pathological work-up of early-stage HER2-negative BC patients

Beam test performance of a prototype module with Short Strip ASICs for the CMS HL-LHC tracker upgrade

The Short Strip ASIC (SSA) is one of the four front-end chips designed for the upgrade of the CMS Outer Tracker for the High Luminosity LHC. Together with the Macro-Pixel ASIC (MPA) it will instrument modules containing a strip and a macro-pixel sensor stacked on top of each other. The SSA provides both full readout of the strip hit information when triggered, and, together with the MPA, correlated clusters called stubs from the two sensors for use by the CMS Level-1 (L1) trigger system. Results from the first prototype module consisting of a sensor and two SSA chips are presented. The prototype module has been characterized at the Fermilab Test Beam Facility using a 120 GeV proton beam

Test beam performance of a CBC3-based mini-module for the Phase-2 CMS Outer Tracker before and after neutron irradiation

The Large Hadron Collider (LHC) at CERN will undergo major upgrades to increase the instantaneous luminosity up to 5–7.5×10$^{34}$ cm$^{-2}$s$^{-1}$. This High Luminosity upgrade of the LHC (HL-LHC) will deliver a total of 3000–4000 fb-1 of proton-proton collisions at a center-of-mass energy of 13–14 TeV. To cope with these challenging environmental conditions, the strip tracker of the CMS experiment will be upgraded using modules with two closely-spaced silicon sensors to provide information to include tracking in the Level-1 trigger selection. This paper describes the performance, in a test beam experiment, of the first prototype module based on the final version of the CMS Binary Chip front-end ASIC before and after the module was irradiated with neutrons. Results demonstrate that the prototype module satisfies the requirements, providing efficient tracking information, after being irradiated with a total fluence comparable to the one expected through the lifetime of the experiment

Vulvar cancer in Germany: increase in incidence and change in tumour biological characteristics from 1974 to 2013

<p><b>Background:</b> The incidence of vulvar cancer in Germany is increasing. Moreover, gynaecological oncologists reported observing increasing numbers of women presenting with small tumours. The aim of the present study is to validate this observation on a population level and to extend available incidence data.</p> <p><b>Material and methods:</b> Data from the population-based Saarland Cancer Registry were used and included 1136 women diagnosed with invasive vulvar cancer (ICD-9 codes: 181.1-181.4, ICD-10 code: C51) between 1974 and 2013. Multiple imputation methodology was used to overcome loss of precision and potential bias resulting from incomplete data. Incidence trends were investigated with regard to age at diagnosis, tumour size and clinical stage, morphology and histopathologic grade.</p> <p><b>Results:</b> The age-standardised incidence rate of vulvar cancer increased from 1.6 cases per 100,000 women per year in 1974–78 to 7.9 in 2009–13, representing an increase across all age groups. Since 1989–93, an almost exclusive increase in the incidence of small tumours ≤2 cm in the greatest dimension from 1.2 to 6.6 and of squamous cell carcinomas from 1.7 to 7.1 was observed, whereas the number of larger tumours and other invasive cancers remained rather constant. Patients aged ≥75 years generally suffered from more advanced tumours at the time of diagnosis.</p> <p><b>Conclusions:</b> An increase in vulvar cancer incidence of a size as observed in this study has not been reported thus far for any other European region. Furthermore, the analyses confirmed the observation of increasing numbers of women presenting with small tumours. The results of the age-specific analyses point to both human papillomavirus infection and non-infectious factors as explanations for the observed increase in squamous cell carcinomas.</p

Modification of Dargent's radical vaginal trachelectomy to facilitate ureteral dissection: description of technique

Objective Radical vaginal trachelectomy is the fertility-preserving surgery for patients with early stage cervical cancer. However, it has not gained widespread approval by gynecologic oncologists because of difficulties in the dissection of the bladder pillars and identification of the ureter during the vaginal portion of the surgery. Method We describe a modification of radical vaginal trachelectomy for easier dissection of the bladder pillar. Following pelvic lymphadenectomy, the vesicovaginal space is widely opened laparoscopically. After identification of the uterine arteries, one should proceed along the course of the arteries laterally and, thus, visualize the overcrossing of the artery with the ureter. The medial aspect of the supraureteric bladder pillar is transected and the ureter marked with vessel loops on both sides close to its entry into the bladder. The lateral portion of the supraureteric bladder pillar remains intact. During the vaginal part of radical vaginal trachelectomy, the ureter may be easily found by grasping the formerly placed vessel loop and dissection of the infraureteric bladder pillar may be done without risk of ureteral injury. Results Between October 2018 and August 2019 our group has performed radical vaginal trachelectomy using this modified ureteral dissection in 12 patients. Median operation time was 239 min (range 127-290) and median blood loss was 25 mL (range 10-100). No intra- or post-operative urologic complication occurred. Median time to normal bladder function was 4 days (range 3-13). Conclusion The vaginal portion of radical vaginal trachelectomy may be simplified using this technique, especially when difficult circumstances such as endometriosis, prior operations, or unusual anatomy in nulliparous women are encountered

Comparison of surgical and pathological parameters after laparoscopic transperitoneal pelvic/para-aortic lymphadenectomies

Objective Lymphadenectomy is an integral part of surgical staging and treatment for patients with gynecologic malignancies. Since its introduction, laparoscopic lymphadenectomy has proved feasible, safe, and oncologically adequate compared with open surgery while morbidity is lower and hospital stay considerably shorter. The aim of this study was to examine if surgical outcomes may be improved after the initial learning curve is complete. Methods An analysis of 2535 laparoscopic pelvic and/or para-aortic lymphadenectomies was performed between July 1994 and March 2018 by one team of gynecologic oncology surgeons but with the consistent supervision of a consultant surgeon. Data were collected prospectively evaluating operative time, intra-operative and post-operative complications, number of lymph nodes, and body mass index (BMI). Previously published data of 650 patients treated after introduction of the method (period 1, 1994-2003) were compared with the latter 524 patients (period 2, 2014-2018). Results The median age of the 2535 patients was 43 years (IQR 34-57). The most common indication for pelvic and/or para-aortic lymphadenectomy was cervical cancer (n=1893). Operative time for para-aortic lymph node dissection was shorter in period 2 (68 vs 100 min, p<0.001). The number of harvested lymph nodes was increased for pelvic (19.2 (range 2-52) vs 21.9 (range 4-87)) and para-aortic lymphadenectomy (10.8 (range 1-52) vs 14.4 (range 4-64)), p<0.001. BMI did not have a significant influence on node count or operative time, with BMI ranging from 14.6 to 54.1 kg/m(2). In contrast to period 1 (n=18, 2.9%), there were no intra-operative complications in period 2 (n=0, 0.0%, p<0.001) whereas post-operative complications were similar (n=35 (5.8%) in period 1; n=38 (7.6%) in period 2; p=0.32). Conclusion In this large cohort of patients who underwent laparoscopic transperitoneal lymphadenectomy, lymph node count and peri-operative complications improved after the initial learning curve