Final results of the real-life observational VICTOR-6 study on metronomic chemotherapy in elderly metastatic breast cancer (MBC) patients.

Nowadays, treatment of metastatic breast cancer (MBC) has been enriched with novel therapeutical strategies. Metronomic chemotherapy (mCHT) is a continuous and frequent administration of chemotherapy at a lower dose and so whit less toxicity. Thus, this strategy could be attractive for elderly MBC patients. Aim of this analysis is to provide insights into mCHT's activity in a real-life setting of elderly MBC patients. Data of patients ≥ 75 years old included in VICTOR-6 study were analyzed. VICTOR-6 is a multicentre, Italian, retrospective study, which collected data on mCHT in MBC patients treated between 2011 and 2016. A total of 112 patients were included. At the beginning of mCHT, median age was 81 years (75-98) and in 33% of the patients mCHT was the first line choice. Overall Response Rate (ORR) and Disease Control Rate (DCR) were 27.9% and 79.3%, respectively. Median PFS ranged between 7.6 and 9.1 months, OS between 14.1 and 18.5 months. The most relevant toxicity was the hematological one (24.1%); severe toxicity (grade 3-4) ranged from 0.9% for skin toxicity up to 8% for hematologic one. This is a large study about mCHT in elderly MBC patients, providing insights to be further investigated in this subgroup of frail patients.

Metronomic chemotherapy (mCHT) in metastatic triple-negative breast cancer (TNBC) patients: results of the VICTOR-6 study.

PURPOSE: Triple-negative breast cancer (TNBC) represents a subtype of breast cancer which lacks the expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2): TNBC accounts for approximately 20% of newly diagnosed breast cancers and is associated with younger age at diagnosis, greater recurrence risk and shorter survival time. Therapeutic options are very scarce. Aim of the present analysis is to provide further insights into the clinical activity of metronomic chemotherapy (mCHT), in a real-life setting. METHODS: We used data included in the VICTOR-6 study for the present analysis. VICTOR-6 is an Italian multicentre retrospective cohort study, which collected data of metastatic breast cancer (MBC) patients who have received mCHT between 2011 and 2016. Amongst the 584 patients included in the study, 97 were triple negative. In 40.2% of the TNBC patients, mCHT was the first chemotherapy treatment, whereas 32.9% had received 2 or more lines of treatment for the metastatic disease. 45.4% out of 97 TNBC patients received a vinorelbine (VRL)-based regimen, which resulted in the most used type of mCHT, followed by cyclophosphamide (CTX)-based regimens (30.9%) and capecitabine (CAPE)-based combinations (22.7%). RESULTS: Overall response rate (ORR) and disease control rate (DCR) were 17.5% and 64.9%, respectively. Median progression free survival (PFS) and overall survival (OS) were 6.0 months (95% CI: 4.9-7.2) and 12.1 months (95% CI: 9.6-16.7). Median PFS was 6.9 months for CAPE-based regimens (95% CI: 5.0-18.4), 6.1 months (95% CI: 4.0-8.9) for CTX-based and 5.3 months (95% CI: 4.1-9.5) for VRL-based ones. Median OS was 18.2 months (95% CI: 9.1-NE) for CAPE-based regimens and 11.8 months for VRL- (95% CI: 9.3-16.7 and CTX-based ones (95%CI: 8.7-52.8). Tumour response, PFS and OS decreased proportionally in later lines. CONCLUSION: This analysis represents the largest series of TNBC patients treated with mCHT in a real-life setting and provides further insights into the advantages of using this strategy even in this poor prognosis subpopulation.

Metronomic chemotherapy for advanced breast cancer patients in the real world practice: Final results of the VICTOR-6 study.

Metronomic chemotherapy (mCHT) refers to the minimum biologically effective dose of a chemotherapy agent given as a continuous dosing regimen, with no prolonged drug-free breaks, that leads to antitumor activity. Aim of the present study is to describe the use of mCHT in a retrospective cohort of metastatic breast cancer (MBC) patients in order to collect data regarding the different types and regimens of drugs employed, their efficacy and safety. Between January 2011 and December 2016, data of 584 metastatic breast cancer patients treated with mCHT were collected. The use of VRL-based regimens increased during the time of observation (2011: 16.8% - 2016: 29.8%), as well as CTX-based ones (2011: 17.1% - 2016: 25.6%), whereas CAPE-based and MTX-based regimens remained stable. In the 1st-line setting, the highest ORR and DCR were observed for VRL-based regimens (single agent: 44% and 88%; combination: 36.7% and 82.4%, respectively). Assuming VRL-single agent as the referee treatment (median PFS: 7.2 months, 95% CI: 5.3-10.3), the longest median PFS were observed in VRL-combination regimens (9.5, 95%CI 88.8-11.3, HR = 0.72) and in CAPE-single agent (10.7, 95%CI 8.3-15.8, HR = 0.70). The VICTOR-6 study provides new data coming from the real-life setting, by adding new information regarding the use of mCHT as an option of treatment for MBC patients.

An ecotoxicological approach to evaluate the effects of tourism impacts in the Marine Protected Area of La Maddalena (Sardinia, Italy).

In the Marine Protected Area of La Maddalena Archipelago, environmental protection rules and safeguard measures for nautical activities have helped in reducing anthropogenic pressure; however, tourism related activities remain particularly significant in summer. With the aim of evaluating their impacts, the biomarker approach using transplanted Mytilus galloprovincialis as sentinel organisms coupled with POCIS deployment was applied. Mussels, translocated to four marine areas differently impacted by tourism activities, were sampled before, during and after the tourist season. Moreover, endocrine disruptors in passive samplers POCIS and the cellular toxicity of whole POCIS extracts on mussel haemocytes were evaluated to integrate ecotoxicological information. Lysosomal biomarkers, condition index and mortality rate, as well as metals in tissues suggested an alteration of the health status of mussels transplanted to the most impacted sites. The cellular toxicity of POCIS extracts was pointed out, notwithstanding the concentrations of the examined compounds were always below the detection limits.

Microbiological environmental monitoring in high-risk departments during building activities in a hospital site.

BACKGROUND: This study examines the microbial and fungal contamination associated with the presence of renovation works in a hospital site in Sardinia (Italy). METHODS: Microbiological environmental monitoring was carried out before, during and at the conclusion of the works in the Ophthalmology Department in view of a risk assessment procedure. RESULTS: Although the median values of microbial and fungal counts were found raised during the works, protective measures set out by the internal procedures limited the contamination level. CONCLUSIONS: This study emphasizes the benefits of environmental surveillance for airborne contamination to help prevent outbreaks of nosocomial mycosis associated with construction work.

Metal measurement in aquatic environments by passive sampling methods: Lessons learning from an in situ intercomparison exercise.

Passive sampling devices (PS) are widely used for pollutant monitoring in water, but estimation of measurement uncertainties by PS has seldom been undertaken. The aim of this work was to identify key parameters governing PS measurements of metals and their dispersion. We report the results of an in situ intercomparison exercise on diffusive gradient in thin films (DGT) in surface waters. Interlaboratory uncertainties of time-weighted average (TWA) concentrations were satisfactory (from 28% to 112%) given the number of participating laboratories (10) and ultra-trace metal concentrations involved. Data dispersion of TWA concentrations was mainly explained by uncertainties generated during DGT handling and analytical procedure steps. We highlight that DGT handling is critical for metals such as Cd, Cr and Zn, implying that DGT assembly/dismantling should be performed in very clean conditions. Using a unique dataset, we demonstrated that DGT markedly lowered the LOQ in comparison to spot sampling and stressed the need for accurate data calculation.

An ecotoxicological approach for the Boka Kotorska Bay (south-eastern Adriatic Sea): first evaluation of lysosomal responses and metallothionein induction in mussels.

Mytilus galloprovincialis was used as a biomonitoring organism in Boka Kotorska Bay, a coastal transitional ecosystem in south-western Montenegro. Native mussels were collected in June 2008 at four sites thought to be differently impacted. Biological effects were investigated analysing both generic and specific biomarkers at cellular level (metallothionein content, lysosomal membrane stability, lipofuscin and neutral lipid accumulation, lysosomal structural changes). Trace element levels in mussels were quite low, only Cu and Zn exhibiting slight increases in the two sampling sites of Tivat Bay, the first one in front of a small working dockyard and the other in the water area of a former Naval dockyard. Mussels collected from these sites exhibited the highest values in neutral lipid and lysosomal volume density and the lowest neutral red retention times. Metallothionein content was always low, reflecting the minor body burden of the trace elements and suggesting a non-relevant environmental induction.

Measurement of environmental trace-metal levels in Mediterranean coastal areas with transplanted mussels and DGT techniques.

Mussels (Mytilus galloprovincialis) and diffusive gradients in thin films (DGT) devices were deployed together for three one-month periods in coastal waters of Sardinia (Italy), in order to assess the levels of Cd, Cu, Ni, and Pb in areas differently affected by anthropogenic activities. DGT devices were more sensitive than mussels in detecting differences in metal concentrations between sites, while interpretation of the biomonitoring data revealed difficulties related to the biotic and abiotic factors that can influence the measurements. Regression analysis showed a significant correlation between Cd and Pb concentrations measured in the mussel tissues and bioavailable metal levels in seawater. Moreover transplanted mussels did not accumulate Cu and Ni following pre-exposure, although DGT showed significant concentrations of bioavailable forms of these metals in seawater. The results provided an estimate of the water quality with respect to dissolved metals and pointed out the usefulness of a combination of biomonitoring and DGT techniques for a better understanding of trace metal availability in coastal waters.

Moss (Bryum radiculosum) as a bioindicator of trace metal deposition around an industrialised area in Sardinia (Italy).

The moss Bryum radiculosum (Brid.), a species typical of dry and coastal environments, was used as a bioindicator for the estimation of atmospheric trace metal deposition around the industrial site of Portoscuso (Sardinia, Italy), which includes a lead-zinc smelter, two power plants, and aluminium production factories. For Cd, Pb, Zn, and V the results showed very similar patterns with extremely high values in the immediate surroundings of the industrial area. Copper and Cr showed somewhat different patterns, but still pointing to local pollution sources. The levels of metals at distance of about 13 km from the industrial site were still higher than in background samples. In order to evaluate the suitability of B. radiculosum for monitoring studies, trace metal concentrations in moss were compared with bulk deposition measurements in the same area. Correlation was significant only for Pb, Cd, and Zn. For Cr, Cu, and V the results showed high variability, mainly to be ascribed to soil factors.

Critical analysis of radiochemical methodologies for the assessment of sediment pollution and dynamics in the lagoon of Venice (Italy).

Aquatic sediments are the ultimate sink of wastes dispersed in freshwater and soil. They are therefore a useful tool for investigating polluted ecosystems. Lagoon environments are very difficult to study due to their unstable morphology. Under these circumstances, even an excellent environmental investigation of a restricted lagoon area would still be inadequate to appreciate the characteristics of the entire system. The Venice lagoon is a very complex ecosystem whose morphology is complicated further by extensive anthropic intervention. A good environmental representation of the area was obtained with a preliminary radiochemical survey of airborne radionuclides, a unique tool in evaluating the homogeneity of the entire sedimentary system. It must be stressed, however, that the significance of the data depends substantially on the use of qualified procedures. Based on this, a detailed study was carried out on selected homogeneous areas, reconstructing the inventories and fluxes of pollutants in the sediments. In this work the radiochemical approach to the environmental study of the Venice lagoon is examined.

[G6PD phenotype and red blood cell sensitivity to the oxidising action of chlorites in drinking water]. / Fenotipo G6PD e sensibilità degli eritrociti all'azione ossidante dei cloriti nelle acque potabili.

Chlorine dioxide is widely used to replace sodium hypochlorite in the disinfection of surface waters for human consumption, in order to avoid or reduce the formation of organohalogenated compounds with mutagenic and carcinogenic activity. However, chlorine dioxide may lead to the formation of by-products, such as chlorites and chlorates, that have an oxidative effect on the blood corpuscled fraction. In this investigation, blood crasis was assessed in relation to the G6PD phenotype and the consumption of tap water, disinfected with chlorine dioxide, or bottled mineral water from non-disinfected underground sources. The results show that the effect of oxidative stress resulting from the uptake of chlorites with drinking water is not additive to the effect due to G6PD deficiency. The observed change in haematological parameters, including those related to the G6PD polymorphism, is always within the normal range. However, it is still possible that more relevant changes would follow exposure to chlorites concentrations greater than that observed in the present study.

[Trihalomethanes and chlorites in finished drinking water in Sardinia (Italy) and possible health effects]. / Trialometani e cloriti dalla disinfezione delle acque in Sardegna: valutazioni igienico-sanitarie.

A five years monitoring was carried out in central and southern Sardinia (Italy) to assess the levels of two disinfection by-products (DBPs)--total thrialomethanes (TTHMs) and chlorites--in drinking water Between 1997 and 2002, about 1900 drinking water samples were analysed for both of them. The results showed that TTHMs exceeded very often the maximum admissible concentration. Chlorite concentration was found rising in all the distribution networks since the utilization of chlorine dioxide as disinfectant in 1999, exceeding the maximum contaminant level goals suggested by the World Health Organization. These results are relevant for epidemiological studies on health effects from DBPs exposure.

[Coliphages as indicators of fecal contamination in sea water]. / I colifagi come indice di contaminazione fecale nelle acque marine.

Assessment of water quality has traditionally relied on faecal indicator organisms, which however do not necessarily correlate well with the presence of pathogenic organisms. Coliphages are regarded as possible alternative indicators. Although they can be detected in water by rapid, simple and reliable procedures, any agreement about a standard method has not yet been reached. Moreover guidelines for the levels of bacteriophages have not yet been set as for coliform bacteria, making difficult to evaluate results. In this work both bacteriophages anti E. coli and traditional indicators of fecal contamination were detected on 274 seawater samples taken from 23 sampling stations located along the coast of southern Sardinia (Italy). The results confirm the usefulness of coliphages as indicators of fecal contamination and suggest a level which could be considered a guideline value for their presence in seawater.

Aluminum fractions in drinking water from reservoirs.

To provide insight into aluminum speciation in raw and in finished water and to investigate the factors that can affect it, specific aluminum fractions have been isolated and analyzed in water samples from three drinking water reservoirs in Sardinia (Italy) and at the outlet of their treatment plants. All water treatment plants employed polyaluminum chloride as coagulant. The results demonstrate that the treatment of raw water with the aluminum-based coagulant did not increase the concentration of the metal in the finished water. Aluminum fractions were quite different in raw water and in finished water. More than 80% of the aluminum in raw water was in the particulate form. In the dissolved fraction, organic forms were present at higher concentrations in the raw water, while following water treatment (coagulation, flocculation, filtration) most of the aluminum was in the inorganic form. Most of the dissolved Al in raw water was strongly bound or polymeric colloidal, while percentages of monomeric Al ranging from 40 to 62% were present in the finished water.

Monitoring of labile zinc in cultures of Skeletonema costatum using a salt groundwater.

Labile Zn concentration was monitored by differential pulse anodic stripping voltammetry (DPASV) throughout the exponential growth phase of the marine diatom Skeletonema costatum (Grev.) Cleve. Algal blooms were induced both under natural conditions and in laboratory experiments using a salt groundwater (salinity 33) from the Bay of Bourgneuf, northwest coast of France. Salt groundwater is a very complex medium containing high concentrations of dissolved organic matter and other trace metal adsorbents, such as phosphate, iron oxyhydroxides, and manganese and silicon oxides, which can bind metal ions, reducing their availability and toxicity to algae. Besides metal uptake by algae and complexation of Zn by algal exudates, the rapid decrease in the labile Zn concentration during the algal blooms was ascribed mainly to the adsorption or coprecipitation of Zn ion onto freshly formed iron hydroxides.

Organomercury determination in biological reference materials: application to a study on mercury speciation in marine mammals off the Faröe Islands.

The potential use of graphite furnace atomic absorption spectrometry (GF-AAS) for the organic mercury determination in marine biological tissues was evaluated. Following its isolation by acid extraction in toluene, organic mercury was recovered in aqueous thiosulfate and measured by GF-AAS. The detection limit was 0.01 microgram Hg/g (as methyl mercury). Analyses were conducted on three reference standard materials certified for their methyl mercury content, DOLT-1, DORM-1, and TORT-1, provided by the National Research Council of Canada. The method resulted in very good recovery and reproducibility, indicating that GF-AAS can provide results comparable to those obtained by using more expensive and time consuming analytical techniques. The method was applied to the analysis of liver tissues of pilot whale specimens (Globicephala melas) from the drive fishery of the Faröe Islands (northeast Atlantic). The results provided useful information on the proportion of different mercury forms in the liver of these marine mammals.

A practical isolation of methyl mercury in natural waters.

A simple method to isolate both organic and inorganic mercury in natural waters is described. The mercuric compounds were quantitatively extracted with dithizone from six different kinds of water spiked at nanogram levels with radioactive mercuric chloride and methylmercuric chloride. After the separation from the inorganic mercury with sodium nitrite, methyl mercury was transferred to aqueous medium with sodium thiosulfate. The method provides a high recovery of organic as well as inorganic mercury to an aqueous medium, prior to their determination by gold-trap cold vapor atomic absorption spectrophotometry. This method is easy, rapid, and inexpensive. Furthermore, the limited number of analytical steps should reduce loss and contamination.