To evaluate whether two commonly used newer platinum-based regimens offer any advantage over vinorelbine-cisplatin (reference regimen) in response rate for patients with advanced non-small-cell lung ...cancer (NSCLC).
Chemotherapy-naive patients were randomized to receive gemcitabine 1,250 mg/m(2) days 1 and 8 plus cisplatin 75 mg/m(2) day 2 every 21 days (GC arm), or paclitaxel 225 mg/m(2) (3-hour infusion) then carboplatin (area under the concentration-time curve of 6 mg/mL x min), both on day 1 every 21 days (PCb arm), or vinorelbine 25 mg/m(2)/wk for 12 weeks then every other week plus cisplatin 100 mg/m(2) day 1 every 28 days (VC arm).
Six hundred twelve patients were randomized to treatment (205 GC, 204 PCb, and 203 VC). Overall response rates for the GC (30%) and PCb (32%) arms were not significantly different from that of the VC arm (30%). There were no differences in overall survival, time to disease progression, or time to treatment failure. Median survival for the GC, PCb, and VC groups was 9.8, 9.9, and 9.5 months, respectively. Neutropenia was significantly higher on the VC arm (GC 17% or PCb 35% v VC 43% of cycles, P <.001), as was thrombocytopenia on the GC arm (GC 16% v VC 0.1% of cycles, P <.001). Alopecia and peripheral neurotoxicity were most common on the PCb arm, as was nausea/vomiting on the VC arm (P <.05).
Efficacy end points were not significantly different between experimental and reference arms, although toxicities showed differences. These findings suggest that chemotherapy in NSCLC has reached a therapeutic plateau.
Dihydropyrimidine dehydrogenase (DPD) catabolises ∼85% of the administered dose of fluoropyrimidines. Functional DPYD gene variants cause reduced/abrogated DPD activity. DPYD variants analysis may ...help for defining individual patients' risk of fluoropyrimidine-related severe toxicity.
The TOSCA Italian randomised trial enrolled colon cancer patients for 3 or 6 months of either FOLFOX-4 or XELOX adjuvant chemotherapy. In an ancillary pharmacogenetic study, 10 DPYD variants (*2A rs3918290 G>A, *13 rs55886062 T>G, rs67376798 A>T, *4 rs1801158 G>A, *5 rs1801159 A>G, *6 rs1801160 G>A, *9A rs1801265 T>C, rs2297595 A>G, rs17376848 T>C, and rs75017182 C>G), were retrospectively tested for associations with ⩾grade 3 fluoropyrimidine-related adverse events (FAEs). An association analysis and a time-to-toxicity (TTT) analysis were planned. To adjust for multiple testing, the Benjamini and Hochberg's False Discovery Rate (FDR) procedure was used.
FAEs occurred in 194 out of 508 assessable patients (38.2%). In the association analysis, FAEs occurred more frequently in *6 rs1801160 A allele carriers (FDR=0.0083). At multivariate TTT analysis, significant associations were found for *6 rs1801160 A allele carriers (FDR<0.0001), *2A rs3918290 A allele carriers (FDR<0.0001), and rs2297595 GG genotype carriers (FDR=0.0014). Neutropenia was the most common FAEs (28.5%). *6 rs1801160 (FDR<0.0001), and *2A rs3918290 (FDR=0.0004) variant alleles were significantly associated with time to neutropenia.
This study adds evidence on the role of DPYD pharmacogenetics for safety of patients undergoing fluoropyrimidine-based chemotherapy.
Abstract
This work presents the first measurements performed on the Timespot1 ASIC. As the second prototype developed for the TimeSPOT project, the ASIC features a 32 × 32 channels hybrid-pixel ...matrix. Targeted to space-time tracking applications in High Energy Physics experiments, the system aims to achieve a time resolution of 30 ps or better at a maximum event rate of 3 MHz/channel with a data driven interface. Power consumption can be programmed to range between 1.2 W/cm
2
and 2.6 W/cm
2
. The presented results include a description of the ASIC operation and a first characterization of its performance in terms of time resolution.
Background: Vinorelbine prolongs survival and improves quality of life in elderly patients with advanced non-small-cell lung cancer (NSCLC). Some studies have also suggested that gemcitabine is well ...tolerated and effective in such patients. We compared the effectiveness and toxicity of the combination of vinorelbine plus gemcitabine with those of each drug given alone in an open-label, randomized phase III trial in elderly patients with advanced NSCLC. Methods: Patients aged 70 years and older, enrolled between December 1997 and November 2000, were randomly assigned to receive intravenous vinorelbine (30 mg/m2 of body surface area), gemcitabine (1200 mg/m2), or vinorelbine (25 mg/m2) plus gemcitabine (1000 mg/m2). All treatments were delivered on days 1 and 8 every 3 weeks for a maximum of six cycles. The primary endpoint was survival. Survival curves were drawn using the Kaplan–Meier method and analyzed by the Mantel–Haenszel test. Secondary endpoints were quality of life and toxicity. Results: Of 698 patients available for intention-to-treat analysis, 233 were assigned to receive vinorelbine, 233 to gemcitabine, and 232 to vinorelbine plus gemcitabine. Compared with each single drug, the combination treatment did not improve survival. The hazard ratio of death for patients receiving the combination treatment was 1.17 (95% confidence interval CI = 0.95 to 1.44) that of patients receiving vinorelbine and 1.06 (95% CI = 0.86 to 1.29) that of patients receiving gemcitabine. Although quality of life was similar across the three treatment arms, the combination treatment was more toxic than the two drugs given singly. Conclusion: The combination of vinorelbine plus gemcitabine is not more effective than single-agent vinorelbine or gemcitabine in the treatment of elderly patients with advanced NSCLC.
Abstract Hydrogenated amorphous silicon (a-Si:H) is a material with a very good radiation hardness and with the possibility of deposition on flexible substrates like Polyimide (PI). Exploiting these ...properties, the HASPIDE (Hydrogenated Amorphous Silicon PIxels DEtectors) project has the goal of developing a-Si:H detectors on flexible substrates for beam dosimetry and profile monitoring, neutron detection and space experiments. The detectors for this experiment will be developed in two different structures: the n-i-p diode structure, which has been used up to now for the construction of the planar a-Si:H detectors, and the recently developed charge selective contact structure. In the latter the doped layers (n or p) are replaced with charge selective materials namely electron-selective conductive metal-oxides (TiO 2 or Al:ZnO) and hole-selective conductive metal oxides (MoO x ). In this paper preliminary data on the capabilities of these detectors to measure X-ray and electron fluxes will be presented. In particular, the linearity, the sensitivity, the stability and dark current in various conditions will be discussed.
The Patient Reported Outcome for Fighting FInancial Toxicity (PROFFIT) questionnaire was developed to measure financial toxicity (FT) and identify its determinants. The aim of the present study was ...to confirm its validity in a prospective cohort of patients receiving anticancer treatment.
From March 2021 to July 2022, 221 patients were enrolled at 10 Italian centres. Selected items of the EORTC-QLQ-C30 questionnaire represented the anchors, specifically, question 28 (Q-28) on financial difficulties, and questions 29-30 measuring global health status/quality of life (HR-QOL). The study had 80% power to detect a 0.20 correlation coefficient (r) between anchors and PROFFIT-score (items 1-7, range 0-100, 100 indicating maximum FT) with bilateral alpha 0.05 and 80% power. Confirmatory factor analysis was conducted. FT determinants (items 8-16) were described.
Median age of patients was 65 years, 116 (52.5%) were females, 96 (43.4%) had low education level. Confirmatory factor analysis confirmed goodness of fit of the PROFFIT-score. Significant partial correlation of PROFFIT-score was found with Q-28 (r = 0.51) and HR-QOL (r = -0.23). Mean (SD) PROFFIT-score at baseline was 36.5 (24.9); it was statistically significantly higher for patients living in South Italy, those with lower education level, those who were freelancer/unemployed at diagnosis and those who reported significant economic impact from the COVID-19 pandemic. Mean (SD) scores of determinants ranged from 17.6 (27.1) for item 14 (support from medical staff) to 49.0 (36.3) for item 10 (expenses for medicines or supplements). PROFFIT-score significantly increased with worsening response to determinants.
External validation of PROFFIT-score in an independent sample of patients was successful. The instrument is now being used in clinical studies.
This paper describes the AM06 chip, which is a highly parallel processor for pattern recognition in the ATLAS high energy physics experiment. The AM06 contains memory banks that store data organized ...in 18 bit words; a group of 8 words is called “pattern”. Each AM06 chip can store up to 131 072 patterns. The AM06 is a large chip, designed in 65 nm CMOS, and it combines full-custom memory arrays, standard logic cells and serializer/deserializer IP blocks at 2 Gbit/s for input/output communication. The overall silicon area is 168 mm2 and the chip contains about 421 million transistors. The AM06 receives the detector data for each event accepted by Level-1 trigger, up to 100 kHz, and it performs a track reconstruction based on hit information from channels of the ATLAS silicon detectors. Thanks to the design of a new associative memory cell and to the layout optimization, the AM06 consumption is only about 1 fJ/bit per comparison. The AM06 has been fabricated and successfully tested with a dedicated test system.
Pain is a highly distressing symptom for patients with advanced cancer. WHO analgesic ladder is widely accepted as a guideline for its treatment. Our aim was to describe pain prevalence among ...patients diagnosed with advanced non-small-cell lung cancer (NSCLC), impact of pain on quality of life (QoL) and adequacy of pain management. Data of 1021 Italian patients enrolled in three randomised trials of chemotherapy for NSCLC were pooled. QoL was assessed by EORTC QLQ-C30 and LC-13. Analgesic consumption during the 3 weeks following QoL assessment was recorded. Adequacy of pain management was evaluated by the Pain Management Index (PMI). Some pain was reported by 74% of patients (42% mild, 24% moderate and 7% severe); 50% stated pain was affecting daily activities (30% a little, 16% quite a bit, 3% very much). Bone metastases strongly affected presence of pain. Mean global QoL linearly decreased from 64.9 to 36.4 from patients without pain to those with severe pain (P<0.001). According to PMI, 616 out of 752 patients reporting pain (82%) received inadequate analgesic treatment. Bone metastases were associated with improved adequacy and worst pain with reduced adequacy at multivariate analysis. In conclusion, pain is common in patients with advanced NSCLC, significantly affects QoL, and is frequently undertreated. We recommend that: (i). pain self-assessment should be part of oncological clinical practice; (ii). pain control should be a primary goal in clinical practice and in clinical trials; (iii). physicians should receive more training in pain management; (iv). analgesic treatment deserves greater attention in protocols of anticancer treatment.
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