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Flexible fully organic indirect detector for megaelectronvolts proton beams

Authors: Calvi Sabrina; Basirico Laura; Carturan Sara M.; Fratelli Ilaria; Valletta Antonio; Aloisio Alberto; De Rosa Stefania; Pino Felix; Campajola Marcello; Ciavatti Andrea; Tortora Luca; Rapisarda Matteo; Moretto Sandra; Verdi Matteo; Bertoldo Stefano; Cesarini Olivia; Di Meo Paolo; Chiari Massimo; Tommasino Francesco; Sarnelli Ettore; Mariucci Luigi; Branchini Paolo; Quaranta Alberto; Fraboni Beatrice; Basiricò Laura

Journal: NPJ FLEXIBLE ELECTRONICS

Published: 2023

DOI: 10.1038/s41528-022-00229-w

A flexible, fully organic detector for proton beams is presented here. The detector operates in the indirect mode and is composed of a polysiloxane-based scintillating layer coupled to an organic phototransistor, that is assessed for flexibility and low-voltage operation (V = −1 V), with a limit of detection of 0.026 Gy min−1. We present a kinetic model able to precisely reproduce the dynamic response of the device under irradiation and to provide further insight into the physical processes controlling it. This detector is designed to target real-time and in-situ dose monitoring during proton therapy and demonstrates mechanical flexibility and low power operation, assessing its potential employment as a personal dosimeter with high comfort and low risk for the patient. The results show how such a proton detector represents a promising tool for real-time particle detection over a large area and irregular surfaces, suitable for many applications, from experimental scientific research to innovative theranostics.

Volume: 7

Author Correction: The repertoire of mutational signatures in human cancer (Nature, (2020), 578, 7793, (94-101), 10.1038/s41586-020-1943-3)

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6602603515

Journal: NATURE

Published: 2023

DOI: 10.1038/s41586-022-05600-5

In the published version of this paper, the members of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium were listed in the Supplementary Information; however, these members should have been included in the main paper. The original Article has been corrected to include the members and affiliations of the PCAWG Consortium in the main paper; the corrections have been made to the HTML version of the Article but not the PDF version. Additional minor corrections to affiliations have been made to the PDF and HTML versions of the original Article for consistency of information between the PCAWG list and the main paper.

Volume: 614 Pages: E41-E41

Author Correction: The evolutionary history of 2,658 cancers (Nature, (2020), 578, 7793, (122-128), 10.1038/s41586-019-1907-7)

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Journal: NATURE

Published: 2023

DOI: 10.1038/s41586-022-05601-4

In the published version of this paper, the members of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium were listed in the Supplementary Information; however, these members should have been included in the main paper. The original Article has been corrected to include the members and affiliations of the PCAWG Consortium in the main paper; the corrections have been made to the HTML version of the Article but not the PDF version. Additional minor corrections to affiliations have been made to the PDF and HTML versions of the original Article for consistency of information between the PCAWG list and the main paper.

Volume: 614 Pages: E42-E42

Author Correction: Butler enables rapid cloud-based analysis of thousands of human genomes (Nature Biotechnology, (2020), 38, 3, (288-292), 10.1038/s41587-019-0360-3)

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Journal: NATURE BIOTECHNOLOGY

Published: 2023

DOI: 10.1038/s41587-022-01554-1

Correction to: Nature Biotechnology, published online 5 February 2020. In the published version of this paper, the members of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium were listed in the Supplementary Information; however, these members should have been included in the main paper. The original Article has been corrected to include the members and affiliations of the PCAWG Consortium in the main paper; the corrections have been made to the HTML version of the Article but not the PDF version. Additional minor corrections to affiliations have been made to the PDF and HTML versions of the original Article for consistency of information between the PCAWG list and the main paper, and in the PCAWG Technical Working Group, the two affiliations for Miguel Vazquez have been changed from Massachusetts General Hospital, Boston, MA, USA and Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain to Barcelona Supercomputing Center, Barcelona, Spain and Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.

Volume: 41 Pages: 577

Author Correction: Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer (Nature Genetics, (2020), 52, 3, (294-305), 10.1038/s41588-019-0564-y)

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Journal: NATURE GENETICS

Published: 2023

DOI: 10.1038/s41588-023-01318-w

In the published version of this paper, the members of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium were listed in the Supplementary Information; however, these members should have been included in the main paper. The original Article has been corrected to include the members and affiliations of the PCAWG Consortium in the main paper; the corrections have been made to the HTML version of the Article but not the PDF version. Additional corrections to affiliations have been made to the PDF and HTML versions of the original Article for consistency of information between the PCAWG list and the main paper.

Volume: 55 Pages: 1079-1079

Italian Guidelines for the Management of Prolactinomas

Authors: Cozzi Renato; Auriemma Renata Simona; De Menis Ernesto; Esposito Felice; Ferrante Emanuele; Iati Giuseppe; Mazzatenta Diego; Poggi Maurizio; Ruda Roberta; Tortora Fabio; Cruciani Fabio; Mitrova Zuzana; Saulle Rosella; Vecchi Simona; Basile Michele; Cappabianca Paolo; Paoletta Agostino; Papini Enrico; Persichetti Agnese; Samperi Irene; Scoppola Alessandro; Bozzao Alessandro; Caputo Marco; Doglietto Francesco; Ferrau Francesco; Lania Andrea Gerardo; Laureti Stefano; Lello Stefano; Locatelli Davide; Maffei Pietro; Minniti Giuseppe; Peri Alessandro; Ruini Chiara; Settanni Fabio; Silvani Antonio; Veronese Nadia; Grimaldi Franco; Attanasio Roberto; Iatì Giuseppe; Rudà Roberta; Ferraù Francesco

Journal: ENDOCRINE METABOLIC & IMMUNE DISORDERS-DRUG TARGETS

Published: 2023

DOI: 10.2174/1871530323666230511104045

Introduction: This guideline (GL) is aimed at providing a reference for the management of prolactin (PRL)-secreting pituitary adenoma in adults. However, pregnancy is not considered. Methods: This GL has been developed following the methods described in the Manual of the Italian National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinologi (AME) has identified potentially relevant outcomes, which have then been rated for their impact on therapeutic choices. Only outcomes classified as “critical” and “important” have been considered in the systematic review of evidence and only those classified as “critical” have been considered in the formulation of recommendations. Results: The present GL provides recommendations regarding the role of pharmacological and neurosurgical treatment in the management of prolactinomas. We recommend cabergoline (Cab) vs. bromocriptine (Br) as the first-choice pharmacological treatment to be employed at the minimal effective dose capable of achieving the regression of the clinical picture. We suggest that medication and surgery are offered as suitable alternative first-line treatments to patients with non-invasive PRL-secreting adenoma, regardless of size. We suggest Br as an alternative drug in patients who are intolerant to Cab and are not candidates for surgery. We recommend pituitary tumor resection in patients 1) without any significant neuro-ophthalmologic improvement within two weeks from the start of Cab, 2) who are resistant or do not tolerate Cab or other dopamine-agonist drugs (DA), 3) who escape from previous efficacy of DA, and 4) who are unwilling to undergo a chronic DA treatment. We recommend that patients with progressive disease notwithstanding previous tumor resection and ongoing DA should be managed by a multidisciplinary team with specific expertise in pituitary diseases using a multimodal approach that includes repeated surgery, radiother-apy, DA, and possibly, the use of temozolomide. Conclusion: The present GL is directed to endocrinologists, neurosurgeons, and gynecologists working in hospitals, in territorial services or private practice, and to general practitioners and patients.

Volume: 23 Pages: 1459-1479

Keywords: bromocriptine; cabergo-line; cost-efficacy analysis; macroprolactinoma; microprolactinoma; neurosurgery; prolactin-secreting tumor; Prolactinoma; radiotherapy; temozolomide;

Development of a nomogram for predicting pathological complete response in luminal breast cancer patients following neoadjuvant chemotherapy

Authors: Garufi Giovanna; Carbognin Luisa; Sperduti Isabella; Miglietta Federica; Dieci Maria Vittoria; Mazzeo Roberta; Orlandi Armando; Gerratana Lorenzo; Palazzo Antonella; Fabi Alessandra; Paris Ida; Franco Antonio; Franceschini Gianluca; Fiorio Elena; Pilotto Sara; Guarneri Valentina; Puglisi Fabio; Conte Pierfranco; Milella Michele; Scambia Giovanni; Tortora Giampaolo; Bria Emilio

Journal: THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY

Published: 2023

DOI: 10.1177/17588359221138657

Background: Given the low chance of response to neoadjuvant chemotherapy (NACT) in luminal breast cancer (LBC), the identification of predictive factors of pathological complete response (pCR) represents a challenge. A multicenter retrospective analysis was performed to develop and validate a predictive nomogram for pCR, based on pre-treatment clinicopathological features. Methods: Clinicopathological data from stage I–III LBC patients undergone NACT and surgery were retrospectively collected. Descriptive statistics was adopted. A multivariate model was used to identify independent predictors of pCR. The obtained log-odds ratios (ORs) were adopted to derive weighting factors for the predictive nomogram. The receiver operating characteristic analysis was applied to determine the nomogram accuracy. The model was internally and externally validated. Results: In the training set, data from 539 patients were gathered: pCR rate was 11.3% [95% confidence interval (CI): 8.6–13.9] (luminal A-like: 5.3%, 95% CI: 1.5–9.1, and luminal B-like: 13.1%, 95% CI: 9.8–13.4). The optimal Ki67 cutoff to predict pCR was 44% (area under the curve (AUC): 0.69; p < 0.001). Clinical stage I–II (OR: 3.67, 95% CI: 1.75–7.71, p = 0.001), Ki67 ⩾44% (OR: 3.00, 95% CI: 1.59–5.65, p = 0.001), and progesterone receptor (PR) 1%, and Ki67 <44% to 53.3% for clinical stage I–II, PR < 1%, and Ki67 ⩾44% (accuracy: AUC, 0.73; p < 0.0001). In the validation set (248 patients), the predictive performance of the model was confirmed (AUC: 0.7; p < 0.0001). Conclusion: The combination of commonly available clinicopathological pre-NACT factors allows to develop a nomogram which appears to reliably predict pCR in LBC.

Volume: 15

Keywords: factors of response; luminal breast cancer; neoadjuvant chemotherapy; pathological complete response; predictive model;

Initial Panitumumab Plus Fluorouracil, Leucovorin, and Oxaliplatin or Plus Fluorouracil and Leucovorin in Elderly Patients with RAS and BRAF Wild-Type Metastatic Colorectal Cancer: The PANDA Trial by the GONO Foundation

Authors: Lonardi Sara; Rasola Cosimo; Lobefaro Riccardo; Rossini Daniele; Formica Vincenzo; Scartozzi Mario; Frassineti Giovanni Luca; Boscolo Giorgia; Cinieri Saverio; Di Donato Samantha; Pella Nicoletta; Bergamo Francesca; Raimondi Alessandra; Arnoldi Ermenegildo; Antonuzzo Lorenzo; Granetto Cristina; Zustovich Fable; Ronzoni Monica; Leo Silvana; Morano Federica; Loupakis Fotios; Buggin Federica; Zagonel Vittorina; Fassan Matteo; Cremolini Chiara; Boni Luca; Pietrantonio Filippo

Journal: JOURNAL OF CLINICAL ONCOLOGY

Published: 2023

DOI: 10.1200/JCO.23.00506

PURPOSETo verify whether both doublet chemotherapy with a modified schedule of fluorouracil, leucovorin, and oxaliplatin (mFOLFOX) and monochemotherapy with fluorouracil plus leucovorin (5-FU + LV) achieve satisfactory efficacy when both regimens are combined with panitumumab (PAN) as initial treatment of elderly patients with RAS/BRAF wild-type metastatic colorectal cancer (mCRC).PATIENTS AND METHODSPANDA (ClinicalTrials.gov identifier: NCT02904031) was an open-label, randomized phase II noncomparative trial in previously untreated patients age 70 years and older with unresectable RAS/BRAF wild-type mCRC. Patients were randomly assigned 1:1 to mFOLFOX + PAN (arm A) or 5-FU + LV + PAN (arm B) for up to 12 cycles, followed by PAN maintenance. The primary end point was progression-free survival (PFS). In each arm, assuming a null hypothesis of median PFS time ≤6 months and target PFS ≥9.65, 90 patients per arm were needed to achieve 90% power and 5% type I error (one-sided Brookmeyer-Crowley test).RESULTSBetween July 2016 and April 2019, 91 patients were randomly assigned to arm A and 92 to arm B. At a median follow-up of 50.0 months (IQR, 45.6-56.4), median PFS was 9.6 and 9.0 months for arm A and B, respectively (P 2 chemotherapy-related adverse events was 60% and 37%, respectively. Baseline G8 and Chemotherapy Risk Assessment Scale for High-Age Patients scores were prognostic, but they were not associated with efficacy and safety of the two arms.CONCLUSIONBoth mFOLFOX and 5-FU + LV + PAN are reasonable options as initial therapy of elderly patients with RAS/BRAF wild-type mCRC. 5-FU + LV + PAN is associated with a better safety profile.

Volume: 41 Pages: 5263-+

The role of antiplatelet therapies on incidence and mortality of hepatocellular carcinoma

Authors: Lai Quirino; De Matthaeis Nicoletta; Finotti Michele; Galati Giovanni; Marrone Giuseppe; Melandro Fabio; Morisco Filomena; Nicolini Daniele; Pravisani Riccardo; Giannini Edoardo G.

Journal: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION

Published: 2023

DOI: 10.1111/eci.13870

Aim: To evaluate the impact of antiplatelet therapy (APT)on the incidence of hepatocellular carcinoma (HCC) and mortality following its treatment. Methods: A systematic literature search was performed using PubMed and Cochrane Central Register of Controlled Trials Databases. Two HCC clinical settings were explored: (i) incidence, and (ii) death after any HCC treatment. Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated to compare the pooled data between patients who received or did not receive APT. Results: A total of 20 studies were identified, of whom 15 focused on HCC incidence, including 2,685,009 patients, and five on post-treatment death, including 3281 patients. APT was associated with an overall reduced risk of HCC incidence (OR: 0.63; 95%CI = 0.51–0.79; p < 0.001) as well as of post-treatment mortality (OR: 0.54; 95%CI = 0.35–0.83; p = 0.006). Conclusions: Current data suggest that APT correlated with higher HCC incidence and poor overall survival following tumour treatment.

Volume: 53

Keywords: aspirin; clopidogrel; incidence; occurrence; survival;

Author Correction: Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing (Nature Genetics, (2020), 52, 3, (331-341), 10.1038/s41588-019-0576-7)

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Journal: NATURE GENETICS

Published: 2023

DOI: 10.1038/s41588-023-01315-z

Correction to: Nature Genetics, published online 05 February 2020. In the published version of this paper, the members of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium were listed in the Supplementary Information; however, these members should have been included in the main paper. The original Article has been corrected to include the members and affiliations of the PCAWG Consortium in the main paper; the corrections have been made to the HTML version of the Article but not the PDF version. Additional corrections to affiliations have been made to the PDF and HTML versions of the original Article for consistency of information between the PCAWG list and the main paper.

Volume: 55 Pages: 1076-1076