We present the precision calibration of 35 Hamamatsu R11410-22 photomultiplier tubes (PMTs) with xenon scintillation light centred near 175 nm. This particular PMT variant was developed specifically ...for the LUX-ZEPLIN (LZ) dark matter experiment. A room-temperature xenon scintillation cell coupled to a vacuum cryostat was used to study the full-face PMT response at both room and low temperature ( ∼ −100 °C), in particular to determine the quantum efficiency (QE) and double photoelectron emission (DPE) probability in LZ operating conditions. For our sample with an average QE of (32.4 ± 2.9)% at room temperature, we find a relative improvement of (17.9 ± 5.2)% upon cooling (where uncertainty values refer to the sample standard deviation). The mean DPE probability in response to single vacuum ultraviolet (VUV) photons is (22.6 ± 2.0)% at low temperature; the DPE increase relative to room temperature, measured here for the first time, was (12.2 ± 3.9)%. Evidence of a small triple photoelectron emission probability ( ∼ 0.6%) has also been observed. Useful correlations are established between these parameters and the QE as measured by the manufacturer. The single VUV photon response is also measured for one ETEL D730/9829QB, a PMT with a more standard bialkali photocathode used in the ZEPLIN-III experiment, for which we obtained a cold DPE fraction of (9.1 ± 0.1)%. Hence, we confirm that this effect is not restricted to the low-temperature bialkali photocathode technology employed by Hamamatsu. This highlights the importance of considering this phenomenon in the interpretation of data from liquid xenon scintillation and electroluminescence detectors, and from many other optical measurements in this wavelength region.
Noble liquid radiation detectors have long been afflicted by spurious electron emission from their cathodic electrodes. This phenomenon must be understood and mitigated in the next generation of ...liquid xenon (LXe) experiments searching for WIMP dark matter or neutrinoless double beta decay, and in the large liquid argon (LAr) detectors for the long-baseline neutrino programmes. We present a systematic study of this spurious emission involving a series of slow voltage-ramping tests on fine metal wires immersed in a two-phase xenon time projection chamber with single electron sensitivity. Emission currents as low as 10−18 A can thus be detected by electron counting, a vast improvement over previous dedicated measurements. Emission episodes were recorded at surface fields as low as ∼ 10 kV/cm in some wires and observed to have complex emission patterns, with average rates of 10–200 counts per second (c/s) and outbreaks as high as ∼ 106 c/s. A fainter, less variable type of emission was also present in all untreated samples. There is evidence of a partial conditioning effect, with subsequent tests yielding on average fewer emitters occurring at different fields for the same wire. We find no evidence for an intrinsic threshold particular to the metal-LXe interface which might have limited previous experiments up to fields of at least 160 kV/cm. The general phenomenology is not consistent with enhanced field emission from microscopic filaments, but it appears instead to be related to the quality of the wire surface in terms of corrosion and the nature of its oxide layer. This study concludes that some surface treatments, in particular nitric acid cleaning applied to stainless steel wires, can bring about at least order-of-magnitude improvements in overall electron emission rates, and this should help the next generation of detectors achieve the required electrostatic performance.
Background
Persistent alopecia (PA) after docetaxel has been recently described. The aim of our study is to establish the incidence and characteristics of PA following adjuvant docetaxel for breast ...cancer (BC) and to test the ability of scalp cooling in prevention.
Patients and methods
BC patients receiving adjuvant chemotherapy followed or not by endocrine therapy (and a control group receiving only endocrine therapy) were interviewed in a single institution at 1.5 to 5 years following primary diagnosis searching for PA. A confirmatory prevalence study was later performed in other two institutions. Finally, a prevention study using prophylactic scalp cooling (PSC) with ELASTO-GEL hypothermia caps in patients receiving adjuvant docetaxel was performed.
Results
In the initial prevalence study (492 patients), minor forms of PA (grade 1) were recorded with all chemotherapy regimens and aromatase inhibitors. Patients receiving docetaxel regimens at cumulative dose (CD) ≥ 400 mmg/m
2
presented a significantly higher prevalence of grades 1 PA (33–52%) and 2 PA (5–12%). Prevalence of grade 2 PA with docetaxel CD ≥ 400 mmg/m
2
was confirmed in two other institutions. Overall, grade 2 PA was seen in 10.06% (95% CI 7.36–13.61) of 358 patients with docetaxel regimens reaching CD ≥ 400 mmg/m
2
, but not in patients with lower docetaxel CD, other chemotherapy regimens, or endocrine therapy alone. In prevention trial, no grade 2 PA occurred among 116 patients receiving adjuvant docetaxel (≥ 400 mmg/m
2
) and PSC followed-up after a 96 months median time. PSC was well tolerated. No scalp relapses were seen among 30 patients (22% of all inclusions) having disease relapse.
Conclusion
Adjuvant treatment with docetaxel (CD ≥ 400 mmg/m
2
) is associated with a significant rate of grade 2 PA, leading to wearing a wig, in around 10% of patients. This toxicity was completely prevented with scalp cooling. Clinical Trial Reference: NCT00515762.
The bCTC count is a well-established prognostic biomarker in mCRC, as well as in other tumor types. The aim of this analysis was to evaluate the prognostic/predictive role of the bCTC count (≥3 vs. ...<3) in previously untreated mCRC.
The study involved 589 untreated mCRC patients included in the intention-to-treat population of 2 randomized clinical trials (phase III VISNU-1 NCT01640405 and phase II VISNU-2 NCT01640444 studies).
Of the 589 patients, 349 (59.2%) had bCTC≥3 and 240 (40.7%) had bCTC<3. Multivariate analysis showed that the bCTC count is an independent prognostic factor for overall survival (OS) (HR 0.59, 95% CI 0.48-0.72; P = 0.000) and potential for progression-free survival (PFS) (P = 0.0549). Median OS was 32.9 and 19.5 months in patients with bCTC<3 and bCTC≥3 (P <0.001), respectively. This effect was also observed comparing OS in RASwt patients from both studies. Other prognostic factors were: ECOG-PS, primary tumor site, number of metastatic sites and surgery of the primary tumor. Median OS was lower for patients treated with anti-VEGF versus anti-EGFR (22.3 vs. 33.3 months, P <0.0001) while there were no significant differences in PFS according to the targeted treatment received.
This post-hoc analysis of 2 randomized studies confirms the poor prognosis of patients with bCTC≥3 but this is not associated with other adverse independent prognostic factors such as RAS/BRAF mutations.
Baseline circulating tumor cell (bCTC ) enumeration is an established biomarker in metastatic colorectal cancer (mCRC). A total of 589 untreated mCRC patients from 2 randomized clinical trials were included for evaluation of the prognostic/predictive role of the bCTC count (≥3 vs. <3). Our results confirm the poor prognosis of patients with bCTC≥3 but this is not associated with other adverse prognostic factors such as RAS/BRAF mutations.
We explored the influence of BRAF and PIK3CA mutational status on the efficacy of bevacizumab or cetuximab plus 5-fluorouracil/leucovorin and irinotecan (FOLFIRI) as first-line therapy in patients ...with RAS wild-type metastatic colorectal cancer (mCRC).
VISNÚ-2 was a multicentre, randomised, phase II study. Patients with RAS wild-type mCRC and <3 circulating tumour cells/7.5 ml blood were stratified by BRAF/PIK3CA status (wild-type versus mutated) and number of affected organs (1 versus >1), and allocated to bevacizumab (5 mg/kg every 2 weeks) or cetuximab (400 mg/m2 then 250 mg/m2 weekly) plus FOLFIRI irinotecan 180 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil 400 mg/m2 (bolus) then 2400 mg/m2 (46-h continuous infusion) every 2 weeks. The primary endpoint was progression-free survival (PFS). All analyses were exploratory.
Two hundred and forty patients with BRAF/PIK3CA wild-type (n = 196) or BRAF- and/or PIK3CA-mutated tumours (n = 44) were enrolled. Median PFS was 12.7 and 8.8 months in patients with BRAF/PIK3CA wild-type and BRAF/PIK3CA-mutated tumours, respectively hazard ratio (HR) = 1.22; 95% confidence interval (CI) 0.80-1.85; P = 0.3602. In the BRAF- and/or PIK3CA-mutated cohort, median PFS was 2.8, 8.8 and 15.0 months in patients with BRAF/PI3KCA-mutated (n = 8), BRAF-mutated/PI3KCA wild-type (n = 16) and BRAF wild-type/PI3KCA-mutated (n = 20) tumours, respectively (P = 0.0002). PFS was similar with bevacizumab plus FOLFIRI versus cetuximab plus FOLFIRI in BRAF/PIK3CA wild-type (HR = 0.99; 95% CI 0.67-1.45; P = 0.9486) and BRAF/PIK3CA-mutated tumours (HR = 1.11; 95% CI 0.53-2.35; P = 0.7820). The most common grade 3/4 treatment-related adverse events were neutropenia, diarrhoea and asthenia in both treatment groups.
BRAF/PIK3CA status influences outcomes in patients with RAS wild-type mCRC but does not appear to assist with the selection of first-line targeted therapy.
•This study examined if BRAF/PIK3CA mutational status can guide therapy in RAS wild-type mCRC.•BRAF mutations were associated with poorer survival outcomes, and were potentiated by PI3KCA mutations.•Bevacizumab-FOLFIRI versus cetuximab-FOLFIRI had similar outcomes in BRAF /PIK3CA wild-type and BRAF /PIK3CA-mutated tumours.•BRAF and PI3KCA mutations have a role as prognostic but not predictive factors.
The management of patients with pancreatic cancer has advanced over the last few years. We convey a multidisciplinary group of experts in an attempt to stablish practical guidelines for the ...diagnoses, staging and management of these patients. This paper summarizes the main conclusions of the working group. Patients with suspected pancreatic ductal adenocarcinoma should be rapidly evaluated and referred to high-volume centers. Multidisciplinary supervision is critical for proper diagnoses, staging and to frame a treatment plan. Surgical resection together with chemotherapy offers the highest chance for cure in early stage disease. Patients with advanced disease should be classified in treatment groups to guide systemic treatment. New chemotherapeutic regimens have resulted in improved survival. Symptomatic management is critical in this disease. Enrollment in a clinical trial is, in general, recommended.
In the original publication of the article, Table 1 was published with incorrect caption and values. The Table 1 with corrected caption and values is given in this Correction.
PDF
