Dynamics of Mount Nyiragongo lava lake inferred from thermal imaging and infrasound array

Abstract Lava lakes provide a direct observation window into processes which usually remain hidden, such as magma convection and outgassing dynamics. We here report a coupled analysis of thermal infrared footage and infrasound array recordings at Mount Nyiragongo (D. R. Congo), and derive a conceptual model of the lava lake's convective system and outgassing mechanism. We suggest that surface flow results from a horizontal pressure gradient at the surface of the lake, driving the crust from high-pressure regions where hot upwelling magma impinges the surface, to low-pressure regions where cold downwelling magma pulls away from the surface. The ascending current of this convection cell carries gas pockets, which once at the surface, are dragged across the lake into downwelling sinks. Such sinks are characterized by persistent chaotic bubble bursting (spattering), whose intensity and position are tracked from infrasound array analysis. Fluctuations of these are observed, but have not been correlated with oscillations of the lava lake level, nor with the variations of surface velocities, both recorded from infrared footage. We also report the activity of a new eruptive vent, which opened early 2016 near an inner circular fracture of the crater's third terrace. We show that the vent's activity was intermittent, alternating between explosive strombolian activity and effusive activity. The latter produced lava flows which spread on the crater's last terrace before cascading into the active lava lake. Although no significant change in the lake behavior was witnessed while the new eruptive vent was active, increased attention should be addressed as this new activity could reflect over-pressurization of the shallow magmatic system. The variety of phenomena captured by this study complements and expands observations reported at other low-viscosity lava lakes, chiefly Kilauea (Hawai'i) and Erta Ale (Ethiopia). Despite Nyiragongo's more vigorous convective regime (where multiple convective cells can operate simultaneously), we suggest that the mechanisms controlling the surface motion and outgassing are similar at all three systems, pointing to generic processes governing the dynamics of low-viscosity lava lakes

Una máscara teatral de doble cara preservada en el museo de Lipari (Mesina): estudio y reconstrucción 3d mediante equipo portátil

[EN] The new tools for 3D survey and modelling (as portable scanners and software packages), often in combination with diagnostics, are nowadays able to provide indispensable elements for the study of archaeological artefacts; their applications to museum’s heritage can be also useful to integrate the traditional graphic documentation and contribute to enhancement and dissemination. This paper shows the benefit of using the aforementioned tools to study the peculiar clay mask No. 11114-E, discovered in 1973 in the Greek necropolis of Lipára, inside tomb No. 1558. The specimen, now exhibited in the Classical Section of the Aeolian Museum, is considered unique both in the Aeolian Islands and in the ancient Greek world, as it is the only one merging two half faces attributable to different characters. This feature, unknown at the time of discovery, has been highlighted in 2018, thanks to a restoration intervention by which a hard concretion layer covering a large portion of the mask surface was removed, bringing to light a smiling young half-face next to an old one with Silenic features. In 2019, the mask was surveyed in situ through a portable and performing laser-scanner arm (the QuantumTM FaroArm by FARO) to produce a high-resolution 3D model useful to enhance the reading of the two halves (not evident enough, due to its state of preservation). The data processing was performed using the Geomagic Wrap software, able to align and merge multiple scans into a single model and to export results in multiple formats, easily shareable and viewable in free software or via the web. Finally, thanks to this method, the successful generation of a digital replica was performed; the resulting replica is useful for dissemination and as a support for the hypothetical reconstruction of the two prototypes taken as models by the craftsman who created the mask.Highlights:A 'mobile laboratory’ consisting of portable equipment has been set up to perform 3D metric surveys on a selection of artefacts preserved at the Museum of Lipari.By means of an ultra-precision laser-scanner arm, a 3D survey on a miniaturistic double-faced mask, belonging to the classical theatrical terracotta, has been performed.A geometrically accurate and realistic 3D final model has been created. This helped the study and reconstruction of the two characters composing the mask.[ES] Las nuevas herramientas para el levantamiento y el modelado en 3D (como son los escáneres portátiles y los paquetes de software), a menudo en combinación con equipos diagnósticos, pueden hoy en día proporcionar elementos indispensables para el estudio de objetos arqueológicos; sus aplicaciones al patrimonio del museo también pueden ser útiles para integrar la documentación gráfica tradicional y contribuir a su mejora y divulgación. Este artículo se refiere al estudio de un hallazgo peculiar procedente de la necrópolis griega de Lipára: la máscara de arcilla nº. 11114-E, descubierta en 1973 en el interior de la tumba nº. 1558 y ahora exhibida en la Sección Clásica del Museo Eólica. El espécimen se considera único, tanto en las Islas Eolias como en el mundo griego antiguo, ya que es la única que fusiona dos mitades atribuibles a diferentes personajes. Esta característica, desconocida en el momento del descubrimiento, se ha destacado en 2018, gracias a la intervención de restauración mediante la cual se ha eliminado una capa dura que cubre gran parte de la superficie de la máscara, sacando a la luz una media cara sonriente y joven, junto a una cara que muestra indicadores de vejez con rasgos selénicos. En 2019, la máscara se levantó in situ con un brazo de escáner láser portátil y funcional (FaroArm QuantumTM de FARO), con el objetivo de generar un modelo 3D de alta resolución útil que mejorara la lectura de las dos mitades (no visible debido a su estado de conservación). El procesamiento de datos se ha llevado a cabo empleando el software Geomagic Wrap capaz de alinear y fusionar múltiples escaneados en un solo modelo y exportarlo en múltiples formatos, fácilmente compartibles y visibles en software libre o vía web. Este método permitió, finalmente, la generación de una réplica digital que podría servir tanto para su divulgación, como de soporte que permita la reconstrucción hipotética de los dos prototipos que presumiblemente fueron de modelo para el artesano al crear la máscara.The writing of this paper was supported by the project “IDEHA-Innovation for Data Elaboration in Heritage Areas” (DUS.AD017.087).Giuffrida, D.; Mollica Nardo, V.; Adinolfi, O.; Mastelloni, MA.; Ponterio, RC. (2021). A theatrical double-faced mask preserved at the Museum of Lipari (Messina): study and 3D reconstruction through portable equipment. Virtual Archaeology Review. 12(24):39-48. https://doi.org/10.4995/var.2021.13916OJS39481224Alby, E., Vigouroux, E., & Elter, R. (2019). Implementation of survey and three-dimensional monitoring of archaeological excavations of the Khirbat al-Dusaq site, Jordan. The International Archives of the Photogrammetry, Remote Sensing and Spatial Information Sciences, XLII-2/W15, 41-47. https://doi.org/10.5194/isprs-archives-XLII-2-W15-41-2019Barba, S. (2008). Tecniche digitali per il rilievo di contatto. Salerno: CUES.Barba, S., Fiorillo F., Ortiz Coder P., D'Auria S., & De Feo E. (2011). An application for cultural heritage in Erasmus placement. Surveys and 3D cataloging archaeological finds, in Mérida (Spain). The International Archives of the Photogrammetry, Remote Sensing and Spatial Information Sciences, XXXVIII-5/W16, 213-218. https://doi.org/10.5194/isprsarchives-XXXVIII-5-W16-213-2011Barbanera, M. (2018). Introduzione. Nella vita sta già la morte: Ade e Dioniso sono uguali. Sapienza Università di Roma: Scienze Dell'antichità (Vol. 24.3).Barrile, V., Fotia, A., Ponterio, R., Mollica Nardo, V., Giuffrida, D., & Mastelloni, M.A. (2019). A combined study of art works preserved in the archaeological museums: 3D survey, spectroscopic approach and augmented reality. The International Archives of the Photogrammetry, Remote Sensing and Spatial Information Sciences, XLII-2/W11, 201-207. https://doi.org/10.5194/isprs-archives-XLII-2-W11-201-2019Bearzot C., Landucci F., & Zecchini G. (2007). L'Onomasticòn di Giulio Polluce: tra lessicografia e antiquaria, vita e pensiero. Italy: Vicenza.Bernabò Brea, L., & Cavalier, M. (1981). Menandro e il teatro greco nelle terracotte liparesi. Genova: SAGEP.Bernabò Brea, L., & Cavalier, M. (1991). Meligunìs Lipára, V. Scavi nella necropoli greca di Lipari. Roma: L'Erma di Bretschneider.Bernabò Brea, L., & Cavalier, M. (1965). Meligunìs Lipára, II. La necropoli greca e romana nella contrada Diana. Palermo.Bernabò Brea, L., & Cavalier, M. (2000). Meligunìs Lipára, X. Scoperte e scavi archeologici nell'area urbana e suburbana di Lipari. Roma: L'Erma di Bretschneider.Bernabò Brea, L., & Cavalier, M. (2001). Maschere e personaggi del teatro greco nelle terrecotte liparesi. Roma: L'Erma di Bretschneider.Bernabò Brea, L., & Cavalier, M. (2001). Meligunis Lipara. XI. Gli scavi nella necropoli greca e romana di Lipari nell'are del terreno vescovile. Palermo: L'Erma di Bretschneider.Bernabò Brea, L., (1974). Maschere della commedia nuova di Lipari e di Centuripe. Dioniso», 45(1971/74), 167-180.Bernabò Brea, L., Coen, C., & Descœudres J. (1992). Masks and characters of the Greek theatre in the terracottas of ancient Lipara. Mediterranean Archaeology, 5/6, 23-31. https://www.jstor.org/stable/i24666700Bertacchini, P. A., Bilotta, E., Pantano, P. S., Battiato, S., Cronin, M., Blasi, G. D., Talarico A., & Tavernise, A. (2007). Modelling and Animation of Theatrical Greek Masks in an Authoring System. Eurographics Italian Chapter Conference, Trento, Italy. https://doi.org/10.2312/LocalChapterEvents/ItalChap/ItalianChapConf2007/191-198Bitossi, G., Giorgi, R., Mauro, M., Salvadori, B., & Dei, L., (2006). Spectroscopic techniques in cultural heritage conservation: a survey. Journal Applied Spectroscopy Reviews, 40(3), 187-228. https://doi.org/10.1081/ASR-200054370Cavalier, M. 1999. La fondazione della Lipàra cnidia, in La colonisation grecque en Méditerranée occidentale, Actes de la rencontre scientifique en hommage à Georges Vallet (pp. 293-302). Rome.Clementi, C., Miliani, C., Romani, A., Santamaria, U., Morresi F., Mlynarska, K., Favaro, G. (2009). In-situ fluorimetry A powerful non-invasive diagnostic technique for natural dyes used in artefacts. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 71(5), 2057- 2062. https://doi.org/10.1016/j.saa.2008.08.006Crisà, A. 2008. Maschere teatrali nella Sicilia settentrionale: tra collezionismo antiquario e ricerca archeologica Stratagemmi. Prospettive Teatrali 8, 11-45.De Cesare, M., & Portale, E. C., (2019). Maschere e imagerie teatrale nella necropoli liparese di IV-III sec. a.C.: oggetti e immagini in contesto. Scienze dell'Antichità, 24(3), 99-139.Fatta, F., Marraffa, A. (2018). The Classical Theatre and the Material Culture. The Example of Lipari's Masks. In: Amoruso G. (eds) Putting Tradition into Practice: Heritage, Place and Design. INTBAU 2017. Lecture Notes in Civil Engineering, vol 3. Cham: Springer. https://doi.org/10.1007/978-3-319-57937-5_70Fazio, L., & Lo Brutto, M. (2020), 3D survey for the archaeological study and virtual reconstruction of the "Sanctuary of Isis" in the ancient Lilybaeum (Italy). Virtual Archaeology Review, 11(22), 1-14. https://doi.org/10.4995/var.2020.11928Giuffrida D., Mollica Nardo, V., Giacobello, F., Adinolfi, O., Mastelloni, M. A., Toscano, G., & Ponterio R. C. (2019). Combined 3D surveying and raman spectroscopy techniques on artifacts preserved at archaeological museum of Lipari. Heritage, 2, 2017-2027. https://doi.org/10.3390/heritage2030121Giuffrida, D. (2019). A double faced mask from Lipari. Retrieved from https://skfb.ly/6RuNMGraepler, D. (1997). Tofiguren in Grab. Fundkontexte hellenistischer Terrakotten aus des Nekropole von Tarant, Munich.Gonizzi Barsanti, S., & Guidi, G. (2013). 3D digitization of museum content within the 3dicons project. ISPRS Annals of the Photogrammetry, Remote Sensing and Spatial Information Sciences, II-5/W1. https://doi.org/10.5194/isprsannals-II-5-W1-151-2013Hess, M., & Robson, S. (2012). 3D imaging for museum artefacts: a portable test object for heritage and museum documentation of small objects. The International Archives of the Photogrammetry, Remote Sensing and Spatial Information Sciences, XXXIX-B5,103-108. https://doi.org/10.5194/isprsarchives-XXXIX-B5-103-2012Ingoglia, C., (2007). La necropoli greco-romana di Lipari: storia degli scavi e prospettive di ricerca. Sicilia Antiqua, 4.La Torre, G. F. (2019). Theatrical masks and the cult of Dionysus in Lipari. Mediterranean Journal of Clinical Psychology, 7(1) Suppl. https://doi.org/10.6092/2282-1619/2019.7.2243Marraffa, A. (2017). La Cultura Materiale del Mediterraneo Studio e Analisi Delle Maschere Liparote di Argomento Teatrale Della Coroplastica Magno-Greca per la Compilazione di un Protocollo (digitale) e di Integrazione Dati. Ph.D. Thesis, Università Mediterranea di Reggio Calabria, Italy.Martinelli, M. C., & Vilardo, R. (2019). Through the theatrical mask. The Archaeological Museum of Lipari. Mediterranean Journal of Clinical Psychology, 7(1) Suppl. https://doi.org/10.6092/2282-1619/2019.7.2245Martinelli, M. C., & Mastelloni, M. A. (2015). Isole Eolie. Il museo archeologico. Palermo: Assessorato dei Beni Culturali e dell'Iidentità Siciliana.Mastelloni, M. A. (2018). Le maschere fittili di Lipari: nuove riflessioni sulle espressioni artigianali liparesi di IV e III sec. a.C., Dialoghi sull'Archeologia della Magna Grecia e del Mediterraneo (pp. 709-720). Pandemos Editore: Paestum, Italy.Mastelloni, M. A., & Spigo U. (1998). Agli albori della ricerca archeologica nelle Eolie: scavi e scoperte a Lipari nel XIX secolo. Palermo: Regione siciliana.Mastelloni, M. A. (2015). Volti divini e figure umane a Lipára, in Eadem (a cura di). In Lipára ed il teatro in età tardoclassica ed ellenistica (pp. 13-38). Palermo: Regione siciliana.Montusiewicz, J., Barszcz, M., & Dziedzic, K. (2019). Photorealistic 3D Digital Reconstruction of a Clay Pitcher. Advances in Science and Technology Research Journal, 13(4), 255-263. https://doi.org/10.12913/22998624/113276Musumeci, A. (2010). Le terracotte figurate dalla necropoli di contrada Casino in Centuripe (pp. 39-114). Enna: IBAM Istituto per i Beni Archeologici e Monumentali CNR.Nishanbaev, I. (2020). A web repository for geo-located 3D digital cultural heritage models. Digital Applications in Archaeology and Cultural Heritage, 16, e00139, https://doi.org/10.1016/j.daach.2020.e00139Ridgway, D. (2004). The Archaeology of the Aeolian Islands. The Classical Review, 54(1), 214-215. https://doi.org/10.1093/cr/54.1.214Russo, M., Remondino, F., & Guidi, G. (2011). Principali tecniche e strumenti per il rilievo tridimensionale in ambito archeologico. Archeologia e calcolatori, 22, 169-198.Schwarzmaier, A., (2011). Die Masken aus der Nekropole von Lipari: Palilia 21. Wiesbaden: Reichert Verlag.Santos, P., Ritz, M., Fuhrmann, C., & Fellner, D. (2017). 3D mass digitization: a milestone for archeological documentation. Virtual Archaeology Review, 8(16), 1-11. https://doi.org/10.4995/var.2017.6321Simon, K., Michelle, A., & Scott, C. (2009). Close-Range 3D Laser Scanning and Virtual Museums: Beyond Wonder Chambers and Cabinets of Curiosity? In: Computer Applications and Quantitative Methods in Archaeology (CAA), Williamsburg, Virginia.Tucci, G., Cini, D. & Nobile, A. (2011). Effective 3D digitization of archaeological artifacts for interactive virtual museum. The International Archives of the Photogrammetry, Remote Sensing and Spatial Information Sciences, XXXVIII-5/W, 413-420. https://doi.org/10.5194/isprsarchives-XXXVIII-5-W16-413-2011Vernant, J. P., & Vidal Naquet, P. (1985). Mito e tragedia. Torino: Einaudi.White, S. 2015. Virtual Archaeology - The NextEngine desktop laser scanner. Archaeology International, 18, 41-44. http://doi.org/10.5334/ai.180

Cancer patient-centered home care: a new model for health care in oncology

Patient-centered home care is a new model of assistance, which may be integrated with more traditional hospital-centered care especially in selected groups of informed and trained patients. Patient-centered care is based on patients’ needs rather than on prognosis, and takes into account the emotional and psychosocial aspects of the disease. This model may be applied to elderly patients, who present comorbid diseases, but it also fits with the needs of younger fit patients. A specialized multidisciplinary team coordinated by experienced medical oncologists and including pharmacists, psychologists, nurses, and social assistance providers should carry out home care. Other professional figures may be required depending on patients’ needs. Every effort should be made to achieve optimal coordination between the health professionals and the reference hospital and to employ shared evidence-based guidelines, which in turn guarantee safety and efficacy. Comprehensive care has to be easily accessible and requires a high level of education and knowledge of the disease for both the patients and their caregivers. Patient-centered home care represents an important tool to improve quality of life and help cancer patients while also being cost effective

Metabolic Escape Routes of Cancer Stem Cells and Therapeutic Opportunities

Although improvement in early diagnosis and treatment ameliorated life expectancy of cancer patients, metastatic disease still lacks effective therapeutic approaches. Resistance to anticancer therapies stems from the refractoriness of a subpopulation of cancer cells—termed cancer stem cells (CSCs)—which is endowed with tumor initiation and metastasis formation potential. CSCs are heterogeneous and diverge by phenotypic, functional and metabolic perspectives. Intrinsic as well as extrinsic stimuli dictated by the tumor microenvironment (TME)have critical roles in determining cell metabolic reprogramming from glycolytic toward an oxidative phenotype and vice versa, allowing cancer cells to thrive in adverse milieus. Crosstalk between cancer cells and the surrounding microenvironment occurs through the interchange of metabolites, miRNAs and exosomes that drive cancer cells metabolic adaptation. Herein, we identify the metabolic nodes of CSCs and discuss the latest advances in targeting metabolic demands of both CSCs and stromal cells with the scope of improving current therapies and preventing cancer progression

BRIEF REPORT Proteasome Inhibitors Synergize with Tumor Necrosis Factor-Related Apoptosis-Induced Ligand to Induce Anaplastic Thyroid Carcinoma Cell Death

Context: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive types of cancer characterized by complete refractoriness to multimodal treatment approaches. Therapeutic strategies based on the simultaneous use of proteasome inhibitors and death receptor ligands have been shown to induce apoptosis in several tumor types but have not yet been explored in ATC. Objective and Methods: The aim of this study was to investigate the ability of the proteasome inhibitor Bortezomib to induce apoptosis in ATC cell lines. Bortezomib was used as a single agent or in combination with TNF-related apoptosis-induced ligand (TRAIL), a member of the TNF family that selectively induces tumor cell apoptosis. The molecular effects of Bortezomib were investigated by analyzing the expression of key regulators of cell cycle and apoptosis and the activation of different apoptotic pathways. Results: Bortezomib induced apoptosis in ATC cells at doses achieved in the clinical setting, differently from conventional chemotherapeutic agents. Simultaneous treatment with low doses of Bortezomib and TRAIL had a synergistic effect in inducing massive ATC cell apoptosis. Bortezomib increased the expression of cytotoxic TRAIL receptors, p21 (WAF/CIP1) and proapoptotic second mitochondria-derived activator of caspases/direct inhibitor of apoptosis binding protein with low pI, and reduced the expression of antiapoptotic mediators such as cellular Fas-associated death domain-like IL-1␤ converting enzyme inhibitory protein, Bcl-2, Bcl-X L , and inhibitor of apoptosis-1, thus resulting in cell death induction through the mitochondrial apoptotic pathway. Conclusions: The combination of proteasome inhibitors and TRAIL synergizes to induce the destruction of chemoresistant neoplastic thyrocytes and could represent a promising therapeutic strategy for the treatment of anaplastic thyroid carcinoma. (J Clin Endocrinol Metab 92: 1938 -1942, 2007

BRIEF REPORT Proteasome Inhibitors Synergize with Tumor Necrosis Factor-Related Apoptosis-Induced Ligand to Induce Anaplastic Thyroid Carcinoma Cell Death

Context: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive types of cancer characterized by complete refractoriness to multimodal treatment approaches. Therapeutic strategies based on the simultaneous use of proteasome inhibitors and death receptor ligands have been shown to induce apoptosis in several tumor types but have not yet been explored in ATC. Objective and Methods: The aim of this study was to investigate the ability of the proteasome inhibitor Bortezomib to induce apoptosis in ATC cell lines. Bortezomib was used as a single agent or in combination with TNF-related apoptosis-induced ligand (TRAIL), a member of the TNF family that selectively induces tumor cell apoptosis. The molecular effects of Bortezomib were investigated by analyzing the expression of key regulators of cell cycle and apoptosis and the activation of different apoptotic pathways. Results: Bortezomib induced apoptosis in ATC cells at doses achieved in the clinical setting, differently from conventional chemotherapeutic agents. Simultaneous treatment with low doses of Bortezomib and TRAIL had a synergistic effect in inducing massive ATC cell apoptosis. Bortezomib increased the expression of cytotoxic TRAIL receptors, p21 (WAF/CIP1) and proapoptotic second mitochondria-derived activator of caspases/direct inhibitor of apoptosis binding protein with low pI, and reduced the expression of antiapoptotic mediators such as cellular Fas-associated death domain-like IL-1␤ converting enzyme inhibitory protein, Bcl-2, Bcl-X L , and inhibitor of apoptosis-1, thus resulting in cell death induction through the mitochondrial apoptotic pathway. Conclusions: The combination of proteasome inhibitors and TRAIL synergizes to induce the destruction of chemoresistant neoplastic thyrocytes and could represent a promising therapeutic strategy for the treatment of anaplastic thyroid carcinoma. (J Clin Endocrinol Metab 92: 1938 -1942, 2007

Epidemiology of gastroenteropancreatic neuroendocrine neoplasms: a review and protocol presentation for bridging tumor registry data with the Italian association for neuroendocrine tumors (Itanet) national database

: Neuroendocrine neoplasms (NENs) are rare tumors with diverse clinical behaviors. Large databases like the Surveillance, Epidemiology, and End Results (SEER) program and national NEN registries have provided significant epidemiological knowledge, but they have limitations given the recent advancements in NEN diagnostics and treatments. For instance, newer imaging techniques and therapies have revolutionized NEN management, rendering older data less representative. Additionally, crucial parameters, like the Ki67 index, are missing from many databases. Acknowledging these gaps, the Italian Association for Neuroendocrine Tumors (Itanet) initiated a national multicenter prospective database in 2019, aiming to gather data on newly-diagnosed gastroenteropancreatic neuroendocrine (GEP) NENs. This observational study, coordinated by Itanet, includes patients from 37 Italian centers. The database, which is rigorously maintained and updated, focuses on diverse parameters including age, diagnostic techniques, tumor stage, treatments, and survival metrics. As of October 2023, data from 1,600 patients have been recorded, with an anticipation of reaching 3600 by the end of 2025. This study aims at understanding the epidemiology, clinical attributes, and treatment strategies for GEP-NENs in Italy, and to introduce the Itanet database project. Once comprehensive follow-up data will be acquired, the goal will be to discern predictors of treatment outcomes and disease prognosis. The Itanet database will offer an unparalleled, updated perspective on GEP-NENs, addressing the limitations of older databases and aiding in optimizing patient care. STUDY REGISTRATION: This protocol was registered in clinicaltriasl.gov (NCT04282083)

Association of Upfront Peptide Receptor Radionuclide Therapy With Progression-Free Survival Among Patients With Enteropancreatic Neuroendocrine Tumors

open57noIMPORTANCE Data about the optimal timing for the initiation of peptide receptor radionuclide therapy (PRRT) for advanced, well-differentiated enteropancreatic neuroendocrine tumors are lacking. OBJECTIVE To evaluate the association of upfront PRRT vs upfront chemotherapy or targeted therapy with progression-free survival (PFS) among patients with advanced enteropancreatic neuroendocrine tumors who experienced disease progression after treatment with somatostatin analogues (SSAs). DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study analyzed the clinical records from 25 Italian oncology centers for patients aged 18 years or older who had unresectable, locally advanced or metastatic, well-differentiated, grades 1 to 3 enteropancreatic neuroendocrine tumors and received either PRRT or chemotherapy or targeted therapy after experiencing disease progression after treatment with SSAs between January 24, 2000, and July 1, 2020. Propensity score matching was done to minimize the selection bias. EXPOSURES Upfront PRRT or upfront chemotherapy or targeted therapy. MAIN OUTCOMES AND MEASURES The main outcome was the difference in PFS among patients who received upfront PRRT vs among those who received upfront chemotherapy or targeted therapy. A secondary outcome was the difference in overall survival between these groups. Hazard ratios (HRs) were fitted in a multivariable Cox proportional hazards regression model to adjust for relevant factors associated with PFS and were corrected for interaction with these factors. RESULTS Of 508 evaluated patients (mean ([SD] age, 55.7 [0.5] years; 278 [54.7%] were male), 329 (64.8%) received upfront PRRT and 179 (35.2%) received upfront chemotherapy or targeted therapy. The matched group included 222 patients (124 [55.9%] male; mean [SD] age, 56.1 [0.8] years), with 111 in each treatment group. Median PFS was longer in the PRRT group than in the chemotherapy or targeted therapy group in the unmatched (2.5 years [95%CI, 2.3-3.0 years] vs 0.7 years [95%CI, 0.5-1.0 years]; HR, 0.35 [95%CI, 0.28-0.44; P < .001]) and matched (2.2 years [95% CI, 1.8-2.8 years] vs 0.6 years [95%CI, 0.4-1.0 years]; HR, 0.37 [95%CI, 0.27-0.51; P < .001]) populations. No significant differences were shown in median overall survival between the PRRT and chemotherapy or targeted therapy groups in the unmatched (12.0 years [95%CI, 10.7-14.1 years] vs 11.6 years [95%CI, 9.1-13.4 years]; HR, 0.81 [95%CI, 0.62-1.06; P = .11]) and matched (12.2 years [95% CI, 9.1-14.2 years] vs 11.5 years [95%CI, 9.2-17.9 years]; HR, 0.83 [95%CI, 0.56-1.24; P = .36]) populations. The use of upfront PRRT was independently associated with improved PFS (HR, 0.37; 95%CI, 0.26-0.51; P < .001) in multivariable analysis. After adjustment of values for interaction, upfront PRRT was associated with longer PFS regardless of tumor functional status (functioning: adjusted HR [aHR], 0.39 [95%CI, 0.27-0.57]; nonfunctioning: aHR, 0.29 [95%CI, 0.16-0.56]), grade of 1 to 2 (grade 1: aHR, 0.21 [95%CI, 0.12-0.34]; grade 2: aHR, 0.52 [95%CI, 0.29-0.73]), and site of tumor origin (pancreatic: aHR, 0.41 [95%CI, 0.24-0.61]; intestinal: aHR, 0.19 [95%CI, 0.11-0.43]) (P < .001 for all). Conversely, the advantage was not retained in grade 3 tumors (aHR, 0.31; 95%CI, 0.12-1.37; P = .13) or in tumors with a Ki-67 proliferation index greater than 10% (aHR, 0.73; 95%CI, 0.29-1.43; P = .31). CONCLUSIONS AND RELEVANCE In this cohort study, treatment with upfront PRRT in patients with enteropancreatic neuroendocrine tumors who had experienced disease progression with SSA treatment was associated with significantly improved survival outcomes compared with upfront chemotherapy or targeted therapy. Further research is needed to investigate the correct strategy, timing, and optimal specific sequence of these therapeutic options.openPusceddu, Sara; Prinzi, Natalie; Tafuto, Salvatore; Ibrahim, Toni; Filice, Angelina; Brizzi, Maria Pia; Panzuto, Francesco; Baldari, Sergio; Grana, Chiara M.; Campana, Davide; Davì, Maria Vittoria; Giuffrida, Dario; Zatelli, Maria Chiara; Partelli, Stefano; Razzore, Paola; Marconcini, Riccardo; Massironi, Sara; Gelsomino, Fabio; Faggiano, Antongiulio; Giannetta, Elisa; Bajetta, Emilio; Grimaldi, Franco; Cives, Mauro; Cirillo, Fernando; Perfetti, Vittorio; Corti, Francesca; Ricci, Claudio; Giacomelli, Luca; Porcu, Luca; Di Maio, Massimo; Seregni, Ettore; Maccauro, Marco; Lastoria, Secondo; Bongiovanni, Alberto; Versari, Annibale; Persano, Irene; Rinzivillo, Maria; Pignata, Salvatore Antonio; Rocca, Paola Anna; Lamberti, Giuseppe; Cingarlini, Sara; Puliafito, Ivana; Ambrosio, Maria Rosaria; Zanata, Isabella; Bracigliano, Alessandra; Severi, Stefano; Spada, Francesca; Andreasi, Valentina; Modica, Roberta; Scalorbi, Federica; Milione, Massimo; Sabella, Giovanna; Coppa, Jorgelina; Casadei, Riccardo; Di Bartolomeo, Maria; Falconi, Massimo; de Braud, FilippoPusceddu, Sara; Prinzi, Natalie; Tafuto, Salvatore; Ibrahim, Toni; Filice, Angelina; Brizzi, Maria Pia; Panzuto, Francesco; Baldari, Sergio; Grana, Chiara M.; Campana, Davide; Davì, Maria Vittoria; Giuffrida, Dario; Zatelli, Maria Chiara; Partelli, Stefano; Razzore, Paola; Marconcini, Riccardo; Massironi, Sara; Gelsomino, Fabio; Faggiano, Antongiulio; Giannetta, Elisa; Bajetta, Emilio; Grimaldi, Franco; Cives, Mauro; Cirillo, Fernando; Perfetti, Vittorio; Corti, Francesca; Ricci, Claudio; Giacomelli, Luca; Porcu, Luca; Di Maio, Massimo; Seregni, Ettore; Maccauro, Marco; Lastoria, Secondo; Bongiovanni, Alberto; Versari, Annibale; Persano, Irene; Rinzivillo, Maria; Pignata, Salvatore Antonio; Rocca, Paola Anna; Lamberti, Giuseppe; Cingarlini, Sara; Puliafito, Ivana; Ambrosio, Maria Rosaria; Zanata, Isabella; Bracigliano, Alessandra; Severi, Stefano; Spada, Francesca; Andreasi, Valentina; Modica, Roberta; Scalorbi, Federica; Milione, Massimo; Sabella, Giovanna; Coppa, Jorgelina; Casadei, Riccardo; Di Bartolomeo, Maria; Falconi, Massimo; de Braud, Filipp