Abstract
Doppler-free saturated-absorption Lamb dips are observed for weak vibration-rotation transitions of C
2
H
2
between 7167 and 7217 cm
−1
, using a frequency-comb assisted cavity ring-down ...spectrometer based on the use of a pair of phase-locked diode lasers. We measured the absolute center frequency of sixteen lines belonging to the 2
ν
3
+
ν
5
1
band, targeting
ortho
and
para
states of the molecule. Line pairs of the P and Q branches were selected so as to form a ‘V’-scheme, sharing the lower energy level. Such a choice made it possible to determine the rotational energy separations of the excited vibrational state for
J
-values from 11 to 20. Line-center frequencies are determined with an overall uncertainty between 3 and 13 kHz. This is over three orders of magnitude more accurate than previous experimental studies in the spectral region around the wavelength of 1.4
μ
m. The retrieved energy separations provide a stringent test of the so-called MARVEL method recently applied to acetylene.
To stratify the prognosis of patients with programmed cell death-ligand 1 (PD-L1) ≥ 50% advanced non-small-cell lung cancer (aNSCLC) treated with first-line immunotherapy.
Baseline clinical ...prognostic factors, the neutrophil-to-lymphocyte ratio (NLR), PD-L1 tumour cell expression level, lactate dehydrogenase (LDH) and their combination were investigated by a retrospective analysis of 784 patients divided between statistically powered training (n = 201) and validation (n = 583) cohorts. Cut-offs were explored by receiver operating characteristic (ROC) curves and a risk model built with validated independent factors by multivariate analysis.
NLR < 4 was a significant prognostic factor in both cohorts (P < 0.001). It represented 53% of patients in the validation cohort, with 1-year overall survival (OS) of 76.6% versus 44.8% with NLR > 4, in the validation series. The addition of PD-L1 ≥ 80% (21% of patients) or LDH < 252 U/l (25%) to NLR < 4 did not result in better 1-year OS (of 72.6% and 74.1%, respectively, in the validation cohort). Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 P < 0.001, hazard ratio (HR) 2.04, pretreatment steroids (P < 0.001, HR 1.67) and NLR < 4 (P < 0.001, HR 2.29) resulted in independent prognostic factors. A risk model with these three factors, namely, the lung immuno-oncology prognostic score (LIPS)-3, accurately stratified three OS risk-validated categories of patients: favourable (0 risk factors, 40%, 1-year OS of 78.2% in the whole series), intermediate (1 or 2 risk factors, 54%, 1-year OS 53.8%) and poor (>2 risk factors, 5%, 1-year OS 10.7%) prognosis.
We advocate the use of LIPS-3 as an easy-to-assess and inexpensive adjuvant prognostic tool for patients with PD-L1 ≥ 50% aNSCLC.
•Immunotherapy/chemoimmunotherapy combinations are currently not superior to immunotherapy alone for high PD-L1 aNSCLC.•NLR with a cut-off of 4 was validated as an independent prognostic factor for immunotherapy in high PD-L1 aNSCLC.•The addition of either PD-L1 ≥ 80% or LDH < 252 U/l to NLR < 4 did not result in better prognostic stratification.•The LIPS-3 is a validated 3-class prognostic classification based on the NLR, ECOG PS and pretreatment steroids.•The LIPS-3 is a routinely assessable adjuvant prognostic tool for high PD-L1 aNSCLC patients.
Abstract
We report on the development of a comb-assisted cavity ring-down spectrometer for trace water mole fraction determinations in high purity gases. By tuning the laser light in coincidence with ...a H
2
O absorption line at 1.3946
µ
m, we were able to determine sub-ppm relative concentrations of water vapour in N
2
with a sub-percent statistical uncertainty. The sensitivity of the spectrometer was carefully assessed, yielding a detection limit of about 2 nmol/mol.
The reaction Be(p7,γ)8B plays an important role in the Sun, where it determines the high energy component of the solar neutrino spectrum. The importance of this reaction triggered several experiments ...over the last decades. A combined analysis of their results produces an overall consistent picture for the energy dependence of the cross section, while an inflation of the quoted uncertainties is needed to accommodate the observed discrepancy in the absolute scale of the different data sets. The origin of this discrepancy needs to be understood for a reliable estimate of the astrophysical rate of Be(p7,γ)8B and its uncertainty. In addition, there is a question about possible common systematic effects, considering that all measurements performed so far share the same experimental approach, i.e. an intense proton beam impinging on a Be7 radioactive target. A direct measurement using a radioactive Be7 ion beam on a pure hydrogen gas target has been since long envisioned as a way to improve the situation. First attempts showed the feasibility of an experiment based on the use of a recoil mass separator to collect reaction products with high efficiency, but failed to reach a useful statistical significance because of the low beam intensity. Here we present the results obtained using the intense Be7 beam available at the Tandem Accelerator Laboratory at CIRCE, University of Campania, Italy coupled to the recoil mass separator ERNA in the energy range Ecm=367 to 812 keV. Our results are compatible only with a part of previous measurements, in particular those indicating a low value of the astrophysical S-factor at zero energy S17, thus exacerbating the discrepancy between existing measurements. The analysis of our data together with the results of previous data provides an estimate S17(0)=20.0±0.8 eV⋅b, where systematic uncertainties are inflated to obtain a statistically compatible data set.
This is a letter to the editor with critical appraisal of some aspects about indicators of integration of oncology and palliative care programs analyzed by David Hui et al. in a recent paper ...published on Annals Of Oncology -Ann Oncol 2015; 26(9): 1953-1959.
One of the major challenges related to solvent-based taxanes administration in clinical practice is the high rate of hypersensitivity reactions (HSRs). Nab-paclitaxel is a solvent-free, ...albumin-bound, paclitaxel, which minimize the risk of HSR occurrence. In this single-institution, retrospective analysis, we evaluated stage IIIc–IV epithelial ovarian cancer (EOC) patients, treated with first-line carboplatin/nab-paclitaxel (± bevacizumab), after the occurrence of an HSR with solvent-based paclitaxel (and/or docetaxel). Between April 2012 and December 2018, ten patients (20.8%) received carboplatin/nab-paclitaxel (± bevacizumab) after the occurrence of an HSR to solvent-based taxanes. Among the evaluable patients, ORR was 100%. At median follow-up of 28.5 months, median PFS was 16.7 months, and median OS was 65.4 months, respectively. Median received dose intensity (DI) was 86% and 80% of the projected DI for nab-paclitaxel and carboplatin, respectively. There were no treatment-related grade 4 adverse events. Most relevant treatment-related grade 3 adverse events were: asthenia (10%), hypertransaminasemia (10%), neutropenia (20%), thrombocytopenia (20%), and anemia (10%). No HSR recurrence was observed. The high rate of HSR occurrence could limit first-line treatment options in clinical practice. Carboplatin/nab-paclitaxel association could represent a valid treatment option in this setting.
.
A new detection array called GASTLY (GAs-Silicon Two-Layer sYstem) has been designed to detect and identify low-energy light particles emitted in nuclear reactions of astrophysical interest. ...Devoted to the measurement of nanobarn cross-sections, the system is optimised for large solid angle coverage and for low-energy detection thresholds. The array consists of eight modules, each comprising an ionisation chamber and a large area silicon strip detector. Its modularity and versatility allow for use in a variety of experiments. Here we report on the performance of the array as obtained during its commissioning phase with standard
α
-particle sources and during in-beam tests with an intense
12
C beam. Typical energy resolutions
Δ
E
(
FWHM
)
/
E
of about 3% and 2% were obtained for the ionisation chambers and the silicon detectors, respectively. The status of the development of individual strip readout, based on ASIC technology, is also presented.
Background
In most cases, T790M
EGFR
-positive NSCLC patients receiving osimertinib developed “non-drugable” progression, as the patients with common
EGFR
-sensitizing mutations were treated with ...first-line osimertinib. In both settings, chemotherapy represents the standard treatment and local ablative treatments (LATs) are potential useful options in the case of oligo-progression.
Methods
We conducted a study on “post-progression” (pp) outcomes of T790M
EGFR
-positive NSCLC patients treated with osimertinib, according to the therapeutic strategy applied: osimertinib beyond progression (± LATs), “switched therapies” or best supportive care only (BSC).
Results
144 consecutive patients were evaluated: 53 (36.8%) did not received post-progression treatments (BSC), while 91 (63.2%) patients received at least 1 subsequent treatment; 50 patients (54.9%) received osimertinib beyond disease progression 19 (20.9%) of them with adjunctive LATs and 41 (45.1%) a switched therapy. Median ppPFS (progression-free survival) and median ppOS (overall survival) of patients who received osimertinib beyond progression vs. switched therapies were 6.4 months vs. 4.7 months, respectively HR 0.57 (95% CI 0.35–0.92),
p
= 0.0239 and 11.3 months vs 7.8 months, respectively HR 0.57 (95% CI 0.33–0.98),
p
= 0.0446. Among patients who received osimertinib beyond progression with and without LATs median ppPFS was 6.4 months and 5.7 months, respectively HR 0.90 (95% CI 0.68–1.18),
p
= 0.4560, while median ppOS was 20.2 months and 9.9 months, respectively HR 0.73 (95% CI 0.52–1.03),
p
= 0.0748. At the univariate analysis, the only factor significantly related to the ppPFS was the therapeutic strategy in favor of osimertinib beyond progression (± LATs). Moreover, the only variable which was significantly related to ppOS at the multivariate analysis was osimertinib beyond progression (± LATs).
Conclusion
Our study confirmed that in clinical practice, in case of “non-druggable” disease progression, maintaining osimertinib beyond progression (with adjunctive LATs) is an effective option.
The World Health Organization (WHO) guidelines for the treatment of cancer pain recommend nonopioid analgesics as first-line therapy, so-called “weak” analgesics combined with nonopioid analgesics as ...second-line therapy, and so-called “strong” opioids (with nonopioid analgesics) only as third-line therapy. However, these guidelines can be questioned with regard to the extent of efficacy as well as the rationale for not using strong opioids as first-line treatment, especially in terminal cancer patients. The purpose of this randomized study was to prospectively compare the efficacy and tolerability of strong opioids as first-line agents with the recommendations of the WHO in terminal cancer patients. One hundred patients with mild–moderate pain were randomized to treatment according to WHO guidelines or to treatment with strong opioids. Evaluated outcomes included pain intensity, need for change in therapy, quality of life, Karnofsky Performance Status, general condition of the patient, and adverse events. No between-treatment differences were observed for changes in quality of life or performance status, but patients started on strong opioids had significantly better pain relief than patients treated according to WHO guidelines (P
=
0.041). Additionally, patients started on strong opioids required significantly fewer changes in therapy, had greater reduction in pain when a change was initiated, and reported greater satisfaction with treatment than the comparator group (
P
=
0.041). Strong opioids were safe and well-tolerated, with no development of tolerance or serious adverse events. These data suggest the utility of strong opioids for first-line treatment of pain in patients with terminal cancer.
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