Past seismic events worldwide demonstrated that damage and death
toll depend on both the strong ground motion (i.e., source effects) and the
local site effects. The variability of earthquake ground ...motion distribution
is caused by the local stratigraphic and/or topographic setting and buried
morphologies (e.g., irregular sub-interface between soft and stiff soils)
that can give rise to amplification and resonances with respect to the
ground motion expected at the reference site. Therefore, local site
conditions can affect an area with damage related to the full collapse or
loss in functionality of facilities, roads, pipelines, and other lifelines.
To this concern, the near-real-time prediction of ground motion variation over large areas
is a crucial issue to support the rescue and operational interventions. A
machine learning approach was adopted to produce ground motion prediction
maps considering both stratigraphic and morphological conditions. A set of
about 16 000 accelerometric data points and about 46 000 geological and geophysical
data points was retrieved from Italian and European databases. The intensity
measures of interest were estimated based on nine input proxies. The adopted
machine learning regression model (i.e., Gaussian process regression) allows
for improving both the precision and the accuracy in the estimation of the
intensity measures with respect to the available near-real-time prediction methods
(i.e., ground motion prediction equation and ShakeMaps). In addition,
maps with a 50 m × 50 m resolution were generated, providing a ground motion
variability in agreement with the results of advanced numerical simulations
based on detailed subsoil models.
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Retraction
The abstract by Raimondi et al entitled, “Usefulness of assessment of circulating tumor DNA(ctDNA) of cerebrospinal fluid(CSF) samples for early detection of brain metastasis ...(BrM) in patients with triple-negative breast cancer (TNBC),” published in Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021) 507-507, was retracted by the Journal of Clinical of Oncology (JCO). An Expression of Concern was previously issued by JCO on June 16, 2021.
Subsequent to publication of the abstract, questions about the data were brought to JCO’s attention. The data were provided by author Giuseppe Naso, who has since died. As the source of the data and methods of data collection cannot be verified, the abstract is being retracted.
A copy of this Retraction Notice was sent to the last known email addresses for the authors. Authors Lucrezia Raimondi, Laura Giaconi, and Gian Paolo Spinelli agreed to the retraction. Authors Rachele Lazzeroni, Laura Di Benedetto, Filippo Maria Raimondi, Arianna Di Rocco, and Luigi Rossi did not respond to our queries. Author Giuseppe Naso is deceased.
This abstract was retracted on November 9, 2021.
507
Expression of Concern The abstract by Raimondi et al entitled, “Usefulness of assessment of circulating tumor DNA(ctDNA) of cerebrospinal fluid(CSF) samples for early detection of brain metastasis (BrM) in patients with triple-negative breast cancer (TNBC),” published in Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021) 507-507, is under further review. Questions have been raised regarding the integrity of the methods, results, and analysis of the reported abstract. Until the authors and their institutions can fully provide additional information, readers should interpret the findings presented with caution. An update will be provided when our investigation is complete. Background: Despite improvements in treatments, patients diagnosed with TNBC still have poor prognosis for a higher tendency of developing BrM. Identifying patients at high risk of BrM, enabling to predict who will take advantage from appropriate additional treatment, remains a critical problem. ctDNA represents a valuable tool associated with the outcome and the aggressiveness of breast cancer but no prognostic and predictive biomarker has been identified to predict the development of BrM in TNBC. We studied the usefulness of assessment of CSF-ctDNA for early identification of the risk of BrM in TNBC. Methods: Between January 2016 and December 2020, 323 newly diagnosed non-metastatic TNBC patients who underwent neoadjuvant therapy+surgery(NACT) with complete response(CR)were prospectively enrolled. After surgery, samples of CSF measuring ctDNA were obtained from all patients: CSF-ctDNA was extracted with the QIAamp Circulating Nucleic Acid Kit (Qiagen, Valencia, CA, USA) and ctDNA levels were measured. Survival curves were estimated using the Kaplan-Meier method and compared with the Log-rank test. Multivariate Cox regression was used to identify the risk of mortality at three years. Results: After NACT, CSF-ctDNA was detectable in 126/323 (39%) patients, 101/126 (80%) were diagnosed at III stage. 124 of 126 (98.4%) ctDNA+ patients subsequently developed BrM. In contrast, only 2 (2/197, 1%) ctDNA- patients subsequently developed BrM and the 195 other patients remain in a CR (p < 0.001, Fisher's exact test). CSF-ctDNA did associate with PFS and OS: undetectable ctDNA was associated with superior PFS (HR 0.3; p = 0.002) and OS (HR 0.2; p < 0.01), indicating survival is largely determined by the onset of BrM. With a median follow-up of 3 years, median PFS of ctDNA+ vs ctDNA- patients was 13 months vs not reach, p = 0.004 (by Log-rank test). Median OS for ctDNA+ vs ctDNA- patients was 16 months after NACT vs not reach, p = 0.0016 (by Log-rank test). At multivariate analysis detectable CSF-ctDNA emerged as the best predictor of the develop of BrM and 24-month mortality (HR:3.62; p < 0.0001). Age, stage, Ki67% and response to chemotherapy were not significantly associated with the prognosis. Conclusions: After NACT, detectable CSF-ctDNA significantly associates with PFS and OS, identifying early at-risk patients to develop BrM in TNBC.
Abstract
Background. mTOR inhibitors are currently used in the treatment of solid malignancies. Since their approval, several cases of pulmonary toxicity (PT) have been described. This analysis aims ...to report the incidence and the risk of PT in published randomized controlled trials. Material and methods. PubMed and Scopus were reviewed for phase II-III randomized controlled trials with temsirolimus and everolimus. The characteristic of each study and incidence of all- and high-grades PT were collected. Results. A total of 2233 patients were available for meta-analysis: 989 had breast cancer, 833 had neuroendocrine tumor and 411 had metastatic renal cell carcinoma. In patients taking mTOR inhibitors, the incidence of all- and high-grades PT was 10.4% and 2.4%, respectively. Compared to controls, the relative risk for all- and high-grades PT was 31- and 8.8-folds, respectively. No significant heterogeneity was observed between the studies. Not any relationship was found between the incidence of lung metastases, treatment exposure and the incidence of PT. Conclusions. The high grade PT is a rare event and 10% of patients may experience mild grade toxicity with a worsening of quality of life and interruption of therapy in some cases. We recommend monitoring of PT in patients treated with mTOR inhibitors.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The paper summarizes the results of a multidisciplinary study aimed at seismic microzonation of the Central Archeological Area of Rome including the Palatine hill, Roman Forum and Coliseum. A large ...amount of subsoil data, available mainly from adjacent subway lines and from the archaeological superintendence, were collected and used to plan new multidisciplinary investigations, carried out in 2010–2011. First, the paper describes the integrated subsoil model aimed at numerical modeling of site effects. The results of equivalent linear 2D site response analyses carried out on seven representative cross-sections of the area are then presented and discussed. Ground motion amplification factors defined in terms of Housner Intensity were computed in different ranges of period, covering the different fundamental vibration periods pertaining to the monuments and structures. The contouring of amplification factor values from all the numerical simulations, based on morphological and geological constrains, eventually allowed to create microzonation maps. Finally, a sensitivity study was carried out to investigate the effects of uncertainties of input parameters and soil heterogeneity on microzonation.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
An integrated investigation including geological, geomorphological, geophysical and structural survey, tephra analyses, 14C and 40Ar/39Ar dating, as well as paleoseismic trenching along the N-Matese ...fault system is presented. The study allowed the characterization of the tectonic mobility of this structure as well as the associated Bojano basin sedimentary-tectonic evolution since the early Middle Pleistocene, providing also new clues concerning the fault historical activity and the associated Mw>6.5 earthquakes. We have found lines of evidence for >1mm/yr slip rate along the presently buried Bojano fault during the mid Middle Pleistocene, and similar rates for the main fault segments paralleling the Matese flanks. The buried Bojano fault significantly slowed down during the last 300kyr, ceasing its activity before the Holocene. In turn, the segments outcropping along the Matese flanks reactivated at the onset of Late Pleistocene, after a long period of quiescence (480–110ka), with robust slip rates that would seem even accelerating in post LGM times. Paleoseismic data suggest the occurrence of four Mw>6.6 earthquakes in the past 3ka, three of which match the little known 280 BC event, and the devastating 1456 and 1805 earthquakes.
•New radiometric ages constrain the Pleistocene tectonic evolution of the Bojano Basin.•Slip rates of the northern Matese fault system varied during Middle-Late Pleistocene.•Paleoseismic analyses provide evidence for four Mw >6.6 earthquakes in the past 3ka.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The GONO-FOLFOXIRI regimen improved the rate of R0 secondary resection of metastases in initially unresectable metastatic colorectal cancer. The objective of this study was to evaluate the long-term ...outcome of resected patients and the impact of FOLFOXIRI on perioperative morbidities, mortality, and chemotherapy induced hepatotoxicity.
Overall, 196 patients with initially unresectable metastatic colorectal cancer were treated with FOLFOXIRI in 2 phase II and 1 phase III trial. This regimen was associated with an elevated response rate (70.4%) and 37 patients (19%) could undergo a secondary R0 surgery on metastases. This study was registered with the Australian New Zealand Clinical Trials Registry Database at http://www.anzctr.org.au/Statistics.aspx and has ID number ACTRN12608000615381.
Main characteristics of the 37 radically resected patients were: median age 64 years (45-73), Eastern Cooperative Oncology Group Performance Status (ECOG) PS > or = 1 in 30%, synchronous metastases in 65%, multiple sites of disease in 22%, and metastases confined to the liver in 68%. Preoperative FOLFOXIRI was administered for a median of 5.5 months. There was no perioperative mortality and all morbidities (27% of patients) resolved without sequelae. After a median follow up of 67 months, 5-year and 8-year survival are 42% and 33% respectively. At 5 years, 29% of patients are free of disease. The analysis of treatment-induced liver injury showed neither G3 vascular toxicity nor G4 steatosis, and steato-hepatitis in only 5% of patients.
The GONO-FOLFOXIRI regimen allow an R0 surgery in approximately 1 out of 5 unselected patients with initially unresectable metastatic colorectal cancer, and the long-term survival of resected patients is considerable. Neoadjuvant FOLFOXIRI for 3-6 months is safe and not associated with severe liver injury.
T-DM1 improves progression-free survival (PFS) and overall survival (OS) in patients with metastatic human epidermal growth factor receptor 2-positive (HER2+) breast cancer progressing on prior ...trastuzumab plus a taxane. A paucity of data is available on T-DM1 efficacy after dual anti-HER2 blockade with pertuzumab and trastuzumab plus a taxane, which represents the current first-line standard of care. The present study is a retrospective/prospective evaluation of the efficacy and activity of second-line T-DM1 after front-line pertuzumab-based therapy.
Eligible patients were identified within the Gruppo Italiano Mammella (GIM) 14/BIOMETA study, a retrospective/prospective multicenter study on treatment patterns and outcomes of patients with metastatic breast cancer (ClinicalTrials.gov Identifier: NCT02284581). We searched for patients who received second-line T-DM1 after taxane plus trastuzumab and pertuzumab between November 15, 2013 and May 31, 2018. We calculated median PFS, median time to treatment failure (TTF), prolonged duration of therapy (PDT), objective response rate (ORR), and 1-year OS.
Of 445 patients with HER2+ metastatic breast cancer, 77 were eligible for the analysis. At a median follow-up of 7 months, median PFS was 6.3 months (95% confidence intervals CI, 4.8-7.7 months), and median TTF was 6.2 months (95% CI, 4-8.6 months). More than one-third of patients (37.6%; n = 29) experienced PDT with an ORR of 27.1%. At data cutoff, the median OS was not reached, and the 1-year OS was 82%.
Our results show meaningful activity of T-DM1 after front-line pertuzumab plus trastuzumab and a taxane, with about 27% of patients having an objective response and 40% of patients achieving durable disease control.
We evaluated efficacy and activity of second-line T-DM1 in 77 patients with human epidermal growth factor receptor 2-positive metastatic breast cancer progressing on front-line pertuzumab-based therapy. The median progression-free survival was inferior as compared with that in the EMILIA trial, which enrolled patients not treated with previous pertuzumab. However, about one-third of patients experienced objective response and durable disease control, suggesting T-DM1 should be considered a valuable option after pertuzumab.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Breast cancer is the most common tumour in women and the first cause of death for cancer in the female population. Preserving the quality of life has therefore become an important objective in the ...management of the disease. The benefits of adjuvant chemotherapy in patients with HR+ HER2- early breast cancer should always be balanced against its potential short and long-term adverse effects, and identifying the appropriate patients for whom chemotherapy can offer the highest clinical benefit is critical. Besides clinical and pathological factors, today four multigene tests able to guide the choice of the adjuvant therapy early breast cancer are available in Italy: Oncotype DX
, EndoPredict
, MammaPrint
e Prosigna
. This review evaluates the main characteristics of these diagnostic tests, the studies on clinical utility, their economic impact and their inclusion in international and national guidelines. The Oncotype DX Breast Recurrence Score
test is the only multigene test validated, with level IA evidence, to guide the adjuvant therapy decisions: hormone therapy alone for most patients with RS results 0-25, and chemotherapy for patients with RS results 26-100. Clinical data demonstrate that the Oncotype DX test is able to significantly impact therapeutic decisions, reducing chemotherapy use up to 49% and supporting the use of chemotherapy (up to 12%) in potentially under-treated patients. Based on the level of clinical evidence and established clinical utility, several multigene tests have been included in the main international guidelines, with recommendations ranging from "strong" to "moderate".
The prognosis of metastatic cancer patients is still largely affected by treatment failure, mainly due to drug resistance. The hypothesis that chemotherapy might miss circulating tumour cells (CTCs) ...and particularly a subpopulation of more aggressive, stem‐like CTCs, characterized by multidrug resistance, has been recently raised. We investigated the prognostic value of drug resistance and stemness markers in CTCs from metastatic colorectal cancer patients treated with oxaliplatin (L‐OHP) and 5‐fluoruracil (5‐FU) based regimens. Forty patients with metastatic colorectal cancer were enrolled. CTCs were isolated from peripheral blood and analysed for the expression of aldheyde dehydrogenase 1 (ALDH1), CD44, CD133 (used as markers of stemness), multidrug resistance related protein 5 (MRP5 used as marker of resistance to 5‐FU and L‐OHP) and survivin (used as a marker of apoptosis resistance). CTCs were found in 27/40 (67%) patients. No correlation was found between the expression of either CD44 and CD133 in CTCs and the outcome of patients, while a statistically significant shorter progression‐free survival was found in patients with CTCs positive for the expression of ALDH1, survivin and MRP5. These results support the idea that isolating survivin and MRP5+ CTCs may help in the selection of metastatic colorectal cancer patients resistant to standard 5‐FU and L‐OHP based chemotherapy, for which alternative regimens may be appropriate.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Nowadays, modeling of tephra fallout hazard is coupled with probabilistic analysis that takes into account the natural variability of the volcanic phenomena in terms of eruption probability, eruption ...sizes, vent position, and meteorological conditions. In this framework, we present a prototypal methodology to carry out the long-term tephra fallout hazard assessment in southern Italy from the active Neapolitan volcanoes: Somma-Vesuvius, Campi Flegrei, and Ischia.
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