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1. Achievement of Target Gain Larger than Unity in an Inertial Fusion Experiment

Author

Abu-Shawareb, H, Acree, R, Adams, P, Adams, J, Addis, B, Aden, R, Adrian, P, Afeyan, BB, Aggleton, M, Aghaian, L, Aguirre, A, Aikens, D, Akre, J, Albert, F, Albrecht, M, Albright, BJ, Albritton, J, Alcala, J, Alday, C, Alessi, DA, Alexander, N, Alfonso, J, Alfonso, N, Alger, E, Ali, SJ, Ali, ZA, Allen, A, Alley, WE, Amala, P, Amendt, PA, Amick, P, Ammula, S, Amorin, C, Ampleford, DJ, Anderson, RW, Anklam, T, Antipa, N, Appelbe, B, Aracne-Ruddle, C, Araya, E, Archuleta, TN, Arend, M, Arnold, P, Arnold, T, Arsenlis, A, Asay, J, Atherton, LJ, Atkinson, D, Atkinson, R, Auerbach, JM, Austin, B, Auyang, L, Awwal, AAS, Aybar, N, Ayers, J, Ayers, S, Ayers, T, Azevedo, S, Bachmann, B, Back, CA, Bae, J, Bailey, DS, Bailey, J, Baisden, T, Baker, KL, Baldis, H, Barber, D, Barberis, M, Barker, D, Barnes, A, Barnes, CW, Barrios, MA, Barty, C, Bass, I, Batha, SH, Baxamusa, SH, Bazan, G, Beagle, JK, Beale, R, Beck, BR, Beck, JB, Bedzyk, M, Beeler, RG, Behrendt, W, Belk, L, Bell, P, Belyaev, M, Benage, JF, Bennett, G, Benedetti, LR, Benedict, LX, Berger, RL, Bernat, T, Bernstein, LA, Berry, B, Bertolini, L, Besenbruch, G, Betcher, J, and Bettenhausen, R

Subjects
Nuclear and Plasma Physics, Physical Sciences, Indirect Drive ICF Collaboration, Mathematical Sciences, Engineering, General Physics, Mathematical sciences, Physical sciences
Abstract

On December 5, 2022, an indirect drive fusion implosion on the National Ignition Facility (NIF) achieved a target gain G_{target} of 1.5. This is the first laboratory demonstration of exceeding "scientific breakeven" (or G_{target}>1) where 2.05 MJ of 351 nm laser light produced 3.1 MJ of total fusion yield, a result which significantly exceeds the Lawson criterion for fusion ignition as reported in a previous NIF implosion [H. Abu-Shawareb et al. (Indirect Drive ICF Collaboration), Phys. Rev. Lett. 129, 075001 (2022)PRLTAO0031-900710.1103/PhysRevLett.129.075001]. This achievement is the culmination of more than five decades of research and gives proof that laboratory fusion, based on fundamental physics principles, is possible. This Letter reports on the target, laser, design, and experimental advancements that led to this result.

Published
2024

3. Lawson Criterion for Ignition Exceeded in an Inertial Fusion Experiment

Author

Abu-Shawareb, H, Acree, R, Adams, P, Adams, J, Addis, B, Aden, R, Adrian, P, Afeyan, BB, Aggleton, M, Aghaian, L, Aguirre, A, Aikens, D, Akre, J, Albert, F, Albrecht, M, Albright, BJ, Albritton, J, Alcala, J, Alday, C, Alessi, DA, Alexander, N, Alfonso, J, Alfonso, N, Alger, E, Ali, SJ, Ali, ZA, Alley, WE, Amala, P, Amendt, PA, Amick, P, Ammula, S, Amorin, C, Ampleford, DJ, Anderson, RW, Anklam, T, Antipa, N, Appelbe, B, Aracne-Ruddle, C, Araya, E, Arend, M, Arnold, P, Arnold, T, Asay, J, Atherton, LJ, Atkinson, D, Atkinson, R, Auerbach, JM, Austin, B, Auyang, L, Awwal, AS, Ayers, J, Ayers, S, Ayers, T, Azevedo, S, Bachmann, B, Back, CA, Bae, J, Bailey, DS, Bailey, J, Baisden, T, Baker, KL, Baldis, H, Barber, D, Barberis, M, Barker, D, Barnes, A, Barnes, CW, Barrios, MA, Barty, C, Bass, I, Batha, SH, Baxamusa, SH, Bazan, G, Beagle, JK, Beale, R, Beck, BR, Beck, JB, Bedzyk, M, Beeler, RG, Behrendt, W, Belk, L, Bell, P, Belyaev, M, Benage, JF, Bennett, G, Benedetti, LR, Benedict, LX, Berger, R, Bernat, T, Bernstein, LA, Berry, B, Bertolini, L, Besenbruch, G, Betcher, J, Bettenhausen, R, Betti, R, Bezzerides, B, Bhandarkar, SD, and Bickel, R

Subjects
Nuclear and Plasma Physics, Engineering, Physical Sciences, Affordable and Clean Energy, Indirect Drive ICF Collaboration, Mathematical Sciences, General Physics, Mathematical sciences, Physical sciences
Abstract

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion.

Published
2022

5. Real-world EGFR testing practices for non-small-cell lung cancer by thoracic pathology laboratories across Europe

Author

Hofman, P., Calabrese, F., Kern, I., Adam, J., Alarcão, A., Alborelli, I., Anton, N.T., Arndt, A., Avdalyan, A., Barberis, M., Bégueret, H., Bisig, B., Blons, H., Boström, P., Brcic, L., Bubanovic, G., Buisson, A., Caliò, A., Cannone, M., Carvalho, L., Caumont, C., Cayre, A., Chalabreysse, L., Chenard, M.P., Conde, E., Copin, M.C., Côté, J.F., D’Haene, N., Dai, H.Y., de Leval, L., Delongova, P., Denčić-Fekete, M., Fabre, A., Ferenc, F., Forest, F., de Fraipont, F., Garcia-Martos, M., Gauchotte, G., Geraghty, R., Guerin, E., Guerrero, D., Hernandez, S., Hurník, P., Jean-Jacques, B., Kashofer, K., Kazdal, D., Lantuejoul, S., Leonce, C., Lupo, A., Malapelle, U., Matej, R., Merlin, J.L., Mertz, K.D., Morel, A., Mutka, A., Normanno, N., Ovidiu, P., Panizo, A., Papotti, M.G., Parobkova, E., Pasello, G., Pauwels, P., Pelosi, G., Penault-Llorca, F., Picot, T., Piton, N., Pittaro, A., Planchard, G., Poté, N., Radonic, T., Rapa, I., Rappa, A., Roma, C., Rot, M., Sabourin, J.C., Salmon, I., Prince, S. Savic, Scarpa, A., Schuuring, E., Serre, I., Siozopoulou, V., Sizaret, D., Smojver-Ježek, S., Solassol, J., Steinestel, K., Stojšić, J., Syrykh, C., Timofeev, S., Troncone, G., Uguen, A., Valmary-Degano, S., Vigier, A., Volante, M., Wahl, S.G.F., Stenzinger, A., and Ilié, M.

Published
2023
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6. Clinicopathological characteristics of multiple-classifier endometrial cancers: a cohort study and systematic review

Author

De Vitis, L, Schivardi, G, Caruso, G, Fumagalli, C, Vacirca, D, Achilarre, M, Aloisi, A, Garbi, A, Zanagnolo, V, Aletti, G, Guerini-Rocco, E, Mariani, A, Maggioni, A, Barberis, M, Bogani, G, Colombo, N, Multinu, F, Betella, I, De Vitis L. A., Schivardi G., Caruso G., Fumagalli C., Vacirca D., Achilarre M. T., Aloisi A., Garbi A., Zanagnolo V., Aletti G., Guerini-Rocco E., Mariani A., Maggioni A., Barberis M., Bogani G., Colombo N., Multinu F., Betella I., De Vitis, L, Schivardi, G, Caruso, G, Fumagalli, C, Vacirca, D, Achilarre, M, Aloisi, A, Garbi, A, Zanagnolo, V, Aletti, G, Guerini-Rocco, E, Mariani, A, Maggioni, A, Barberis, M, Bogani, G, Colombo, N, Multinu, F, Betella, I, De Vitis L. A., Schivardi G., Caruso G., Fumagalli C., Vacirca D., Achilarre M. T., Aloisi A., Garbi A., Zanagnolo V., Aletti G., Guerini-Rocco E., Mariani A., Maggioni A., Barberis M., Bogani G., Colombo N., Multinu F., and Betella I.

Abstract

Background Endometrial cancers with more than one molecular feature—POLE mutations (POLEmut), mismatch repair protein deficiency (MMRd), p53 abnormality (p53abn)—are called ‘multiple classifiers’. Objective To describe our cohort of multiple classifiers and to report the results of a review on their incidence and the techniques used to identify them. Methods Multiple classifiers identified at the European Institute of Oncology, Milan, between April 2019 and Decmber 2022, were included. Clinicopathological, molecular characteristics, and oncologic outcomes were summarized and compared between single and multiple classifiers sharing common features. Studies on molecular classification of endometrial cancer were searched in the PubMed Database to collect data on the incidence of multiple classifiers and the techniques used for classification. Results Among 422 patients, 48 (11.4%) were multiple classifiers: 15 (3.6%) POLEmut-p53abn, 2 (0.5%) POLEmut-MMRd, 28 (6.6%) MMRd-p53abn, and 3 (0.7%) POLEmut-MMRd-p53abn. MMRd-p53abn and MMRd differed in histotype (non-endometrioid: 14.8% vs 2.0%, p=0.006), grade (high-grade: 55.6% vs 22.2%, p=0.001), and MMR proteins expression, whereas they differed from p53abn in histotype (non-endometrioid: 14.8% vs 50.0%, p=0.006). POLEmut-p53abn and POLEmut differed only in grade (high-grade: 66.7% vs 22.7%, p=0.008), while they differed from p53abn in age (56.1 vs 66.7 years, p=0.003), stage (advanced: 6.7% vs 53.4%, p=0.001), and histotype (non-endometrioid: 6.7% vs 50.0%, p=0.002). Two (7.1%) patients with MMRd-p53abn, 4 (4.0%) with MMRd, and 25 (34.3%) with p53abn had a recurrence. No recurrences were observed in POLEmut-p53abn and POLEmut. TP53 sequencing allowed the detection of additional 7 (18.9%) multiple classifiers with normal p53 immunostaining. The incidence of multiple classifiers ranged from 1.8% to 9.8% in 10 published studies including >100 patients. When only p53 immunohistochemistry was performed, the highest incidence

Published
2024

7. Clinical actionability of BRCA2 alterations in uterine leiomyosarcoma: a molecular tumor board case report and a cBioPortal comprehensive analysis

Author

Bielo, L, Repetto, M, Crimini, E, Belli, C, Setola, E, Parma, G, Fusco, N, Barberis, M, Rocco, E, Marra, A, Colombo, N, Curigliano, G, Bielo L. B., Repetto M., Crimini E., Belli C., Setola E., Parma G., Fusco N., Barberis M., Rocco E. G., Marra A., Colombo N., Curigliano G., Bielo, L, Repetto, M, Crimini, E, Belli, C, Setola, E, Parma, G, Fusco, N, Barberis, M, Rocco, E, Marra, A, Colombo, N, Curigliano, G, Bielo L. B., Repetto M., Crimini E., Belli C., Setola E., Parma G., Fusco N., Barberis M., Rocco E. G., Marra A., Colombo N., and Curigliano G.

Abstract

Background: Uterine leiomyosarcoma (uLMS) represents one of the most common sarcoma histotypes, demonstrating an overall dismal prognosis. Previous studies reported uLMS to carry recurrent somatic BRCA2 homozygous deletions, related to significant clinical benefits from the use of PARP inhibitors. Methods: To investigate the prevalence in uLMS of genomic alterations (alt) in BRCA2 and other homologous recombination (HR) and DNA damage response (DDR) genes, cBioPortal was accessed and data were retrieved from studies including pan-sarcoma histologies. HR-/DDR-genes included BRCA1, BRCA2, ATM, BARD1, BRIP1, CHEK1, CHEK2, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, NBN, PALB2, RAD51C, RAD51D, RAD50, and ATR. Only oncogenic/likely oncogenic alterations were included according to OncoKB. Clinical Report and Results: We reported a clinical case of a patient affected by a highly pretreated uLMS discussed at the European Institute of Oncology Molecular Tumor Board. A targeted next-generation sequencing panel demonstrated a somatic BRCA2 homozygous deletion (homDel). Upon access to Niraparib, a remarkable response of 15 months was observed before experiencing disease progression. In the genomic query, among 2393 cases, uLMS (n = 193) displayed 9 of all 31 BRCA2alt observed, representing the only sarcoma histotype showing an enrichment in BRCA2alt (4.66%; q < 0.001). All of 9 BRCA2alt were represented by homDel, which related to a high fraction of genome altered. Conclusion: uLMS displays a significant frequency of somatic BRCA2alt homDel. Considering their dismal prognosis, further investigation is warranted to test the use of PARPi in uLMS, and particularly in the setting of BRCA1/2 alterations.

Published
2024

9. Implementation of preventive and predictive BRCA testing in patients with breast, ovarian, pancreatic, and prostate cancer: a position paper of Italian Scientific Societies

Author

Beretta, Giordano, Bella, Maria Angela, Bracarda, Sergio, Colombo, Nicoletta, Conteduca, Vincenza, Del Mastro, Lucia, Galvano, Antonio, Gristina, Valerio, Guarneri, Valentina, La Verde, Nicla, Lorusso, Domenica, Marchetti, Paolo, Normanno, Nicola, Ottini, Laura, Pensabene, Matilde, Pignata, Sandro, Procopio, Giuseppe, Ricevuto, Enrico, Silvestris, Nicola, Tassone, Pierfrancesco, Tucci, Marcello, Donato, Vittorio, Carrara, Silvia, Paiella, Salvatore, Gentilini, Oreste, Gunelli, Roberta, Nicolis, Fabrizio, Buttitta, Fiamma, Colecchia, Maurizio, Fassan, Matteo, Malapelle, Umberto, Marchetti, Antonio, Marchiò, Caterina, Scarpa, Aldo, Truini, Mauro, Zamboni, Giuseppe, Gion, Massimo, Trevisiol, Chiara, Gronchi, Alessandro, Danesi, Romano, Di Marco, Vito, Carrera, Paola, Ghiorzo, Paola, Pasini, Barbara, Varesco, Liliana, Artibani, Walter, Ludovico, Giuseppe, Campanella, Ornella, Vatrano, Simona, Tagliafico, Enrico, Russo, A., Incorvaia, L., Capoluongo, E., Tagliaferri, P., Gori, S., Cortesi, L., Genuardi, M., Turchetti, D., De Giorgi, U., Di Maio, M., Barberis, M., Dessena, M., Del Re, M., Lapini, A., Luchini, C., Jereczek-Fossa, B.A., Sapino, A., and Cinieri, S.

Published
2022
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10. European experts consensus: BRCA/homologous recombination deficiency testing in first-line ovarian cancer

Author

Vergote, I., Ausems, M., Brasiuniene, B., Brenton, J., Büttner, R., Colombo, N., González-Martín, A., Harter, P., Lambrechts, D., Lorusso, D., Madry, R., Mirza, M.R., Pujol, P., Ray-Coquard, I., Abreu, M., Balboni, S., Banerjee, S., Barberis, M., Barretina Ginesta, M.P., Baurain, J.-F., Bignami, M., Bjorge, L., Blecharz, P., Bruchim, I., Capilna, M., Cerana, N., Cicchetti, A., Collins, D., Concin, N., D’Incalci, M., Davidson, B., de la Motte Rouge, T., De Iaco, P., Demirkiran, F., Denys, H., Doerk, T., Dorum, A., Ferrero, A., Fidalgo, A.P., Genuardi, M., Gladieff, L., Glasspool, R., Grimm, C., Gultekin, M., Hahnen, E., Hasenburg, A., Hegmane, A., Heinzelmann, V., Hogdall, E., Janavicius, R., Jarmalaite, S., Kalachand, R., Kaneva, R., Kilickap, S., Kocian, R., Kolencik, D., Kristeleit, R., Kryzhanivska, A., Leary, A., Lemley, B., Ligtenberg, M., López-Guerrero, J.A., Lord, C.J., Avall-Lundqvist, E., Maenpaa, J., Mahner, S., Marmé, F., Marth, C., McNeish, I., Merkelbach-Bruse, S., Mourits, M., Normanno, N., Oaknin, A., Ojamaa, K., Papdimitriou, C., Penault-Llorca, F., Perrone, A.M., Pignata, S., Pikarsky, E., Rouleau, E., Rubio, M., Sapino, A., Schmalfeldt, B., Sehouli, J., Shapira, R., Steffensen, K.D., Sukhin, V., Syrios, J., Szallasi, Z., Taskiran, C., Terzic, M., Tischkowitz, M., Toth, I., Van de Vijver, K., Vardar, M.A., Wasag, B., Wimberger, P., Witteveen, E., Brenton, J.D., and Ausems, M.G.E.M.

Published
2022
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12. Clinical management of patients with thymic epithelial tumors: the recommendations endorsed by the Italian Association of Medical Oncology (AIOM)

Author

Conforti, F., Marino, M., Vitolo, V., Spaggiari, L., Mantegazza, R., Zucali, P., Ruffini, E., di Tommaso, L., Pelosi, G., Barberis, M., Petrini, I., Palmieri, G., Pasello, G., Galli, G., Berardi, R., Garassino, M., Filosso, P., Alloisio, M., Scorsetti, M., Orecchia, R., Pala, L., Abatedaga, L., Cinieri, S., and De Pas, T.

Published
2021
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13. Clinical and molecular practice of European thoracic pathology laboratories during the COVID-19 pandemic. The past and the near future

Author

Hofman, P., Ilié, M., Chamorey, E., Brest, P., Schiappa, R., Nakache, V., Antoine, M., Barberis, M., Begueret, H., Bibeau, F., Bonnetaud, C., Boström, P., Brousset, P., Bubendorf, L., Carvalho, L., Cathomas, G., Cazes, A., Chalabreysse, L., Chenard, M.-P., Copin, M.-C., Côté, J.-F., Damotte, D., de Leval, L., Delongova, P., Thomas de Montpreville, V., de Muret, A., Dema, A., Dietmaier, W., Evert, M., Fabre, A., Forest, F., Foulet, A., Garcia, S., Garcia-Martos, M., Gibault, L., Gorkiewicz, G., Jonigk, D., Gosney, J., Hofman, A., Kern, I., Kerr, K., Kossai, M., Kriegsmann, M., Lassalle, S., Long-Mira, E., Lupo, A., Mamilos, A., Matěj, R., Meilleroux, J., Ortiz-Villalón, C., Panico, L., Panizo, A., Papotti, M., Pauwels, P., Pelosi, G., Penault-Llorca, F., Pop, O., Poté, N., Cajal, S.R.Y., Sabourin, J.-C., Salmon, I., Sajin, M., Savic-Prince, S., Schildhaus, H.-U., Schirmacher, P., Serre, I., Shaw, E., Sizaret, D., Stenzinger, A., Stojsic, J., Thunnissen, E., Timens, W., Troncone, G., Werlein, C., Wolff, H., Berthet, J.-P., Benzaquen, J., Marquette, C.-H., Hofman, V., and Calabrese, F.

Published
2021
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14. A Transcriptomic Analysis of Laryngeal Dysplasia

Author

Maffini, F, Lepanto, D, Chu, F, Tagliabue, M, Vacirca, D, De Berardinis, R, Gandini, S, Vignati, S, Ranghiero, A, Taormina, S, Rappa, A, Cossu Rocca, M, Alterio, D, Chiocca, S, Barberis, M, Preda, L, Pagni, F, Fusco, N, Ansarin, M, Maffini, Fausto, Lepanto, Daniela, Chu, Francesco, Tagliabue, Marta, Vacirca, Davide, De Berardinis, Rita, Gandini, Sara, Vignati, Silvano, Ranghiero, Alberto, Taormina, Sergio, Rappa, Alessandra, Cossu Rocca, Maria, Alterio, Daniela, Chiocca, Susanna, Barberis, Massimo, Preda, Lorenzo, Pagni, Fabio, Fusco, Nicola, Ansarin, Mohssen, Maffini, F, Lepanto, D, Chu, F, Tagliabue, M, Vacirca, D, De Berardinis, R, Gandini, S, Vignati, S, Ranghiero, A, Taormina, S, Rappa, A, Cossu Rocca, M, Alterio, D, Chiocca, S, Barberis, M, Preda, L, Pagni, F, Fusco, N, Ansarin, M, Maffini, Fausto, Lepanto, Daniela, Chu, Francesco, Tagliabue, Marta, Vacirca, Davide, De Berardinis, Rita, Gandini, Sara, Vignati, Silvano, Ranghiero, Alberto, Taormina, Sergio, Rappa, Alessandra, Cossu Rocca, Maria, Alterio, Daniela, Chiocca, Susanna, Barberis, Massimo, Preda, Lorenzo, Pagni, Fabio, Fusco, Nicola, and Ansarin, Mohssen

Abstract

This article describes how the transcriptional alterations of the innate immune system divide dysplasias into aggressive forms that, despite the treatment, relapse quickly and more easily, and others where the progression is slow and more treatable. It elaborates on how the immune system can change the extracellular matrix, favoring neoplastic progression, and how infections can enhance disease progression by increasing epithelial damage due to the loss of surface immunoglobulin and amplifying the inflammatory response. We investigated whether these dysregulated genes were linked to disease progression, delay, or recovery. These transcriptional alterations were observed using the RNA-based next-generation sequencing (NGS) panel Oncomine Immune Response Research Assay (OIRRA) to measure the expression of genes associated with lymphocyte regulation, cytokine signaling, lymphocyte markers, and checkpoint pathways. During the analysis, it became apparent that certain alterations divide dysplasia into two categories: progressive or not. In the future, these biological alterations are the first step to provide new treatment modalities with different classes of drugs currently in use in a systemic or local approach, including classical chemotherapy drugs such as cisplatin and fluorouracile, older drugs like fenretinide, and new checkpoint inhibitor drugs such as nivolumab and pembrolizumab, as well as newer options like T cell therapy (CAR-T). Following these observed alterations, it is possible to differentiate which dysplasias progress or not or relapse quickly. This information could, in the future, be the basis for determining a close follow-up, minimizing surgical interventions, planning a correct and personalized treatment protocol for each patient and, after specific clinical trials, tailoring new drug treatments.

Published
2024

16. 95P Italian national policy to access molecular tumor boards: Opportunity or restraint for precision oncology?

Author

Crimini, E., primary, Bielo, L. Boscolo, additional, Marra, A., additional, Repetto, M., additional, Rocco, E. Guerini, additional, Ascione, L., additional, Zanzottera, C., additional, Ranghiero, A., additional, Belli, C., additional, Trapani, D., additional, Criscitiello, C., additional, Esposito, A., additional, Pravettoni, G., additional, Piperno, G., additional, Alterio, D., additional, Jemos, C., additional, Malengo, D., additional, Salè, E. Omodeo, additional, Barberis, M., additional, and Curigliano, G., additional

Published
2024
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19. Role of microsatellite instability and HER2 positivity in locally advanced esophago-gastric cancer patients treated with peri-operative chemotherapy

Author

Gervaso, L, Bottiglieri, L, Meneses-Medina, M, Pellicori, S, Biffi, R, Fumagalli Romario, U, De Pascale, S, Sala, I, Bagnardi, V, Barberis, M, Cella, C, Fazio, N, Gervaso L., Bottiglieri L., Meneses-Medina M. I., Pellicori S., Biffi R., Fumagalli Romario U., De Pascale S., Sala I., Bagnardi V., Barberis M., Cella C. A., Fazio N., Gervaso, L, Bottiglieri, L, Meneses-Medina, M, Pellicori, S, Biffi, R, Fumagalli Romario, U, De Pascale, S, Sala, I, Bagnardi, V, Barberis, M, Cella, C, Fazio, N, Gervaso L., Bottiglieri L., Meneses-Medina M. I., Pellicori S., Biffi R., Fumagalli Romario U., De Pascale S., Sala I., Bagnardi V., Barberis M., Cella C. A., and Fazio N.

Abstract

Purpose: Neoadjuvant chemotherapy (NAC) significantly improved the prognosis of patients with locally advanced gastric cancer (LAGC). Several biomarkers, including HER2 and MMR/MSI are crucial for treatment decisions in the advanced stage but, currently, no biomarkers can guide the choice of NAC in clinical practice. Our aim was to evaluate the role of MSI and HER2 status on clinical outcomes. Methods: We retrospectively collected LAGC patients treated with NAC and surgery +/- adjuvant chemotherapy from 2006 to 2018. HER2 and MSI were assessed on endoscopic and surgical samples. Pathologic complete response (pCR) rate, overall survival (OS), and event‐free survival (EFS) were estimated and evaluated for association with downstaging and MSI. Results: We included 76 patients, 8% were classified as MSI-H, entirely consistent between endoscopic and surgical samples. Six percent of patients were HER2 positive on endoscopic and 4% on surgical samples. Tumor downstaging was observed in 52.5% of cases, with three pCR (5.1%), none in MSI-H cancers. According to MSI status, event-free survival (EFS) and overall survival (OS) were higher for MSI-H patients to MSS [EFS not reached vs 30.0 months, p = 0.08; OS not reached vs 39.6 months, p = 0.10]. Conclusion: Our work confirms the positive prognostic effect of MSI-H in the curative setting of LAGC, not correlated with pathologic tumor downstaging. Prospective ad-hoc trial and tumor molecular profiling are eagerly needed.

Published
2023

20. Genetic Alterations of Melanoma Brain Metastases: A Systematic Review and Meta-Analysis

Author

Pala, L, Bagnardi, V, Tettamanzi, F, Barberis, M, Mazzarol, G, Casali, C, De Pas, T, Pennacchioli, E, Coppola, S, Baldini, F, Cocorocchio, E, Ferrucci, P, Patane', D, Saponara, M, Queirolo, P, Conforti, F, Pala L., Bagnardi V., Tettamanzi F., Barberis M., Mazzarol G., Casali C., De Pas T., Pennacchioli E., Coppola S., Baldini F., Cocorocchio E., Ferrucci P., Patane' D., Saponara M., Queirolo P., Conforti F., Pala, L, Bagnardi, V, Tettamanzi, F, Barberis, M, Mazzarol, G, Casali, C, De Pas, T, Pennacchioli, E, Coppola, S, Baldini, F, Cocorocchio, E, Ferrucci, P, Patane', D, Saponara, M, Queirolo, P, Conforti, F, Pala L., Bagnardi V., Tettamanzi F., Barberis M., Mazzarol G., Casali C., De Pas T., Pennacchioli E., Coppola S., Baldini F., Cocorocchio E., Ferrucci P., Patane' D., Saponara M., Queirolo P., and Conforti F.

Abstract

Background: Data on molecular alterations harbored by melanoma brain metastases (MBMs) are limited, and this has hampered the development of more effective therapeutic strategies. We conducted a systematic review and meta-analysis of all the studies reporting DNA sequencing data of MBMs, in order to identify recurrently mutated genes and molecular pathways significantly enriched for genetic alterations. Methods: We searched PubMed, Embase and Scopus for articles published from the inception of each database to June 30, 2021. We included in the analysis all the studies that reported individual patient data on DNA sequencing of MBMs, assessing single nucleotide variants (SNVs) and/or gene copy number variations (CNVs) in at least five tumor samples. Meta-analysis was performed for genes evaluated for SNVs and/or CNVs in at least two studies. Pooled proportions of samples with SNVs and/or CNVs was calculated by applying random-effect models based on the DerSimonian–Laird method. Gene-set enrichment analysis (GSEA) was performed to identify molecular pathways significantly enriched for mutated genes. Results: Ten studies fulfilled the inclusion criteria and were included in the analysis, for a total of 531 samples of MBMs evaluated. Twenty-seven genes were found recurrently mutated with a meta-analytic rate of SNVs higher than 5%. GSEA conducted on the list of these 27 recurrently mutated genes revealed vascular endothelial growth factor-activated receptor activity and transmembrane receptor protein tyrosine kinase activity to be among the top 10 gene ontology (GO) molecular functions significantly enriched for mutated genes, while regulation of apoptosis and cell proliferation were among the top 10 significantly enriched GO biological processes. Notably, a high meta-analytic rate of SNVs was found in several actionable cancer-associated genes, such as all the vascular endothelial growth factor (VEGF) receptor isoforms (i.e., Flt1 and Flt2 genes, for both SNV rate: 0.22

Published
2023

21. Complex connections with trivial holonomy

Author

Andrada, A., Barberis, M. L., and Dotti, I. G.

Subjects
Mathematics - Differential Geometry, Primary 53C15, Secondary 53B05
Abstract

Given an almost complex manifold (M, J), we study complex connections with trivial holonomy and such that the corresponding torsion is either of type (2,0) or of type (1,1) with respect to J. Such connections arise naturally when considering Lie groups, and quotients by discrete subgroups, equipped with bi-invariant and abelian complex structures., Comment: 13 pages

Published
2011

22. Classification of abelian complex structures on 6-dimensional Lie algebras

Author

Andrada, A., Barberis, M. L., and Dotti, I. G.

Subjects
Mathematics - Rings and Algebras, Mathematics - Differential Geometry, 17B30, 53C15
Abstract

We classify the 6-dimensional Lie algebras that can be endowed with an abelian complex structure and parameterize, on each of these algebras, the space of such structures up to holomorphic isomorphism., Comment: v4: The proof of Theorem 3.2 and the statement of Theorem 3.4 have been fixed, and one remark was added. v5: The statement of Theorem 4.4 (assertions (1) and (2)) was fixed and the proof was modified accordingly. Some arguments were clarified

Published
2009
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25. New HKT manifolds arising from quaternionic representations

Author

Barberis, M. L. and Fino, A.

Subjects
Mathematics - Differential Geometry, 53C26, 22E60, 22F50
Abstract

We give a procedure for constructing an $8n$-dimensional HKT Lie algebra starting from a $4n$-dimensional one by using a quaternionic representation of the latter. The strong (respectively, weak, hyper-K\"ahler, balanced) condition is preserved by our construction. As an application of our results we obtain a new compact HKT manifold with holonomy in $SL(n,\Bbb H)$ which is not a nilmanifold. We find in addition new compact strong HKT manifolds. We also show that every K\"ahler Lie algebra equipped with a flat, torsion-free complex connection gives rise to an HKT Lie algebra. We apply this method to two distinguished 4-dimensional K\"ahler Lie algebras, thereby obtaining two conformally balanced HKT metrics in dimension 8. Both techniques prove to be an effective tool for giving the explicit expression of the corresponding HKT metrics., Comment: 21 pages, to be published in Mathematische Zeitschrift

Published
2008

26. Lie bialgebras of complex type and associated Poisson Lie groups

Author

Andrada, A., Barberis, M. L., and Ovando, G.

Subjects
Mathematics - Differential Geometry, Mathematical Physics, Mathematics - Quantum Algebra, 17B62, 53D17
Abstract

In this work we study a particular class of Lie bialgebras arising from Hermitian structures on Lie algebras such that the metric is ad-invariant. We will refer to them as Lie bialgebras of complex type. These give rise to Poisson Lie groups G whose corresponding duals G* are complex Lie groups. We also prove that a Hermitian structure on the Lie algebra $\mathfrak{g}$ with ad-invariant metric induces a structure of the same type on the double Lie algebra ${\mathcal D}\mathfrak{g}= \mathfrak{g}\oplus\mathfrak{g}^*$, with respect to the canonical ad-invariant metric of neutral signature on ${\mathcal D}\mathfrak{g}$. We show how to construct a 2n-dimensional Lie bialgebra of complex type starting with one of dimension 2(n-2). This allows us to determine all solvable Lie algebras of dimension $\leq 6$ admitting a Hermitian structure with ad-invariant metric. We exhibit some examples in dimension 4 and 6, including two one-parameter families, where we identify the Lie-Poisson structures on the associated simply connected Lie groups, obtaining also their symplectic foliations.

Published
2006

27. Hermitian structures on cotangent bundles of four dimensional solvable Lie groups

Author

de Andrés, L. C., Barberis, M. L., Dotti, I., and Fernández, M.

Subjects
Mathematics - Differential Geometry, 17B30, 53C15, 22E25, 53C55, 53D17
Abstract

We study hermitian structures, with respect to the standard neutral metric on the cotangent bundle $T^*G$ of a 2n-dimensional Lie group $G$, which are left invariant with respect to the Lie group structure on $T^*G$ induced by the coadjoint action. These are in one-to-one correspondence with left invariant generalized complex structures on $G$. Using this correspondence and results of Cavalcanti-Gualtieri and Fern\'andez-Gotay-Gray, it turns out that when $G$ is nilpotent and four or six dimensional, the cotangent bundle $T^*G$ always has a hermitian structure. However, we prove that if $G$ is a four dimensional solvable Lie group admitting neither complex nor symplectic structures, then $T^*G$ has no hermitian structure or, equivalently, $G$ has no left invariant generalized complex structure., Comment: 26 pages. Typos corrected

Published
2006

28. Hyper-K\'ahler quotients of solvable Lie groups

Author

Barberis, M. L., Dotti, I., and Fino, A.

Subjects
Mathematics - Differential Geometry, Mathematical Physics, 53C26, 22E25, 53D20
Abstract

In this paper we apply the hyper-K\"ahler quotient construction to Lie groups with a left invariant hyper-K\"ahler structure under the action of a closed abelian subgroup by left multiplication. This is motivated by the fact that some known hyper-K\"ahler metrics can be recovered in this way by considering different Lie group structures on $\H^p \times \H^q$ ($\H$: the quaternions). We obtain new complete hyper-K\"ahler metrics on Euclidean spaces and give their local expressions., Comment: 18 pages

Published
2004

29. Product structures on four dimensional solvable Lie algebras

Author

Andrada, A., Barberis, M. L., Dotti, I., and Ovando, G.

Subjects
Mathematics - Rings and Algebras, Mathematics - Differential Geometry, 22E25, 53C15
Abstract

It is the aim of this work to study product structures on four dimensional solvable Lie algebras. We determine all possible paracomplex structures and consider the case when one of the subalgebras is an ideal. These results are applied to the case of Manin triples and complex product structures. We also analyze the three dimensional subalgebras., Comment: 25 pages

Published
2004

30. Complex structures on affine motion groups

Author

Barberis, M. L. and Dotti, I.

Subjects
Mathematics - Differential Geometry, Mathematics - Rings and Algebras, 53C15, 17B30
Abstract

We study existence of complex structures on semidirect products $\g \oplus_{\rho} \v$ where $\g$ is a real Lie algebra and $\rho$ is a representation of $\g$ on $\v$. Our first examples, the Euclidean algebra $\e(3)$ and the Poincar\'e algebra $ \e(2,1)$, carry complex structures obtained by deformation of a regular complex structure on $\sl (2, \c)$. We also exhibit a complex structure on the Galilean algebra $\G(3,1)$. We construct next a complex structure on $\g \oplus_{\rho} \v$ starting with one on $\g$ under certain compatibility assumptions on $\rho$. As an application of our results we obtain that there exists $k\in \{0,1\}$ such that $(S^1)^k \times E(n)$ admits a left invariant complex structure, where $S^1$ is the circle and E(n) denotes the Euclidean group. We also prove that the Poincar\'e group $P^{4k+3}$ has a natural left invariant complex structure. In case $\dim \g= \dim \v$, then there is an adapted complex structure on $\g\oplus_{\rho} \v$ precisely when $\rho$ determines a flat, torsion-free connection on $\g$. If $\rho$ is self-dual, $\g \oplus_{\rho}\v$ carries a natural symplectic structure as well. If, moreover, $\rho$ comes from a metric connection then $\g\oplus_{\rho} \v$ possesses a pseudo-K\"ahler structure. We prove that the tangent bundle $TG$ of a Lie group $G$ carrying a flat torsion free connection $\nabla$ and a parallel complex structure possesses a hypercomplex structure. More generally, by an iterative procedure, we can obtain Lie groups carrying a family of left invariant complex structures which generate any prescribed real Clifford algebra., Comment: 15 pages

Published
2003

31. Abelian complex structures on solvable Lie algebras

Author

Barberis, M. L. and Dotti, I.

Subjects
Mathematics - Rings and Algebras, Mathematics - Differential Geometry, 17B30, 32M10, 53C15
Abstract

We obtain a characterization of the real Lie algebras admitting abelian complex structures in terms of certain affine Lie algebras $\frak a \frak f \frak f (A)$, where $A$ is a commutative algebra. These affine Lie algebras are natural generalizations of $\frak a \frak f \frak f (\Bbb C)$ and the corresponding Lie groups are complex affine manifolds. It turns out that all 4-dimensional Lie algebras carrying abelian complex structures are central extensions of such affine Lie algebras., Comment: 8 pages

Published
2002

32. Gastroenteropancreatic grade 3 neuroendocrine tumors: a single entity or a heterogeneous group? A retrospective analysis

Author

Laffi, A, Spada, F, Bagnardi, V, Frassoni, S, Pisa, E, Rubino, M, Barberis, M, Fazio, N, Laffi A., Spada F., Bagnardi V., Frassoni S., Pisa E., Rubino M., Barberis M., Fazio N., Laffi, A, Spada, F, Bagnardi, V, Frassoni, S, Pisa, E, Rubino, M, Barberis, M, Fazio, N, Laffi A., Spada F., Bagnardi V., Frassoni S., Pisa E., Rubino M., Barberis M., and Fazio N.

Abstract

Purpose: Grade 3 neuroendocrine tumor (NET G3) is a novel pathologic category within gastro-entero-pancreatic (GEP) neuroendocrine neoplasms (NENs) but its clinical behavior and therapeutic management still remain challenging. Prognostic and predictive factors aiding NET G3 management are needed. Patients and methods: We performed a retrospective analysis from 2015 to 2020 of all patients with > 20% Ki-67, well-differentiated NETs evaluated within our NEN-dedicated multidisciplinary team. We divided the sample according the timing of NET G3 diagnosis, the radiotracers distribution and Ki-67. We analyzed the correlation between these NET G3 features and clinical outcomes. Results: Among 3238 multidisciplinary discussion reports, we selected 55 patients, 48 from GEP and 7 from an occult GEP origin. In 45 patients, NET G3 diagnosis occurred at the beginning of clinical history (upfront-NET G3), whereas in 10, during the NET G1-G2 clinical history (late-NET G3). Patients with ≤ 30% (34/55) vs. > 30% Ki-67 (21/55) had a better overall survival (OS) (p = 0.042); patients with a homogeneous vs. inhomogeneous/negative 68Gallium(68Ga)-DOTA-Peptide Positron Emission Tomography (PET)/computed tomography (CT) showed a trend to a better OS, and a significant better progression-free survival (PFS) (p = 0.033). A better OS was observed for negative/inhomogeneous vs. homogeneous 18-fluorodeoxyglucose (18FDG)-PET/CT (p = 0.027). A trend to a better OS was reported in late- vs. upfront-NET G3, while the latter showed a significantly better response rate (RR) (p = 0.048). Conclusion: Our findings suggested that Ki-67 cutoff, functional imaging and the timing to NET G3 diagnosis may help clinicians in more accurate selection of NET G3 management. Prospective studies are needed.

Published
2022

33. In-house testing for homologous recombination repair deficiency (HRD) testing in ovarian carcinoma: a feasibility study comparing AmoyDx HRD Focus panel with Myriad myChoiceCDx assay

Author

Fumagalli, C, Betella, I, Ranghiero, A, Guerini-Rocco, E, Bonaldo, G, Rappa, A, Vacirca, D, Colombo, N, Barberis, M, Fumagalli C., Betella I., Ranghiero A., Guerini-Rocco E., Bonaldo G., Rappa A., Vacirca D., Colombo N., Barberis M., Fumagalli, C, Betella, I, Ranghiero, A, Guerini-Rocco, E, Bonaldo, G, Rappa, A, Vacirca, D, Colombo, N, Barberis, M, Fumagalli C., Betella I., Ranghiero A., Guerini-Rocco E., Bonaldo G., Rappa A., Vacirca D., Colombo N., and Barberis M.

Abstract

Background. Homologous recombination repair (HRR) is the main mechanism of repair of DNA double-strand breaks. Its deficiency (HRD) is a common feature of epithelial ovarian cancers (EOCs). BRCA1/2 mutations and/or other aberrations in genes of HRR are well known causes of HRD and genomic instability. Poly ADP-ribose polymerase inhibitors (PARPi) have revolutionized the management of BRCA mutant EOCs and demonstrated activity in HRD tumor cells. Determining HRD status can provide informations on the magnitude of benefit for PARPi therapy. Myriad MyChoice CDx is a next generation sequencing- based in vitro diagnostic test that assesses the Genomic Instability Score (GIS) which is an algorithmic measurement of loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions using DNA isolated from formalin-fixed paraffin embedded tumor tissue specimens. However Myriad MyChoice CDx, is a centrally performed and costly assay, with no reimbursement scheduled, at least in Italy. Methods. In this report, we described our experience in performing the HRD Focus AmoyDx (Amoy Diagnostics Ltd, Xiamen, Fujian, China) on the same samples of EOCs evaluated with Myriad MyChoiceCDx assay. Results. The overall percent agreement between AmoyDx and Myriad was 87.8% (65 of 74 tumors tested). All the 36 AmoyDx negative cases were confirmed to be negative by Myriad (negative predictive value, 100%). Conclusions. The concordance of the results with the gold standard Myriad MyChoice CDx assay suggest the feasibility and reliability of HRD testing in diagnostic laboratories with high-throughput NGS platforms and qualified personnel.

Published
2022

34. Implementation of preventive and predictive BRCA testing in patients with breast, ovarian, pancreatic, and prostate cancer: a position paper of Italian Scientific Societies

Author

Russo, A, Incorvaia, L, Capoluongo, E, Tagliaferri, P, Gori, S, Cortesi, L, Genuardi, M, Turchetti, D, De Giorgi, U, Di Maio, M, Barberis, M, Dessena, M, Del Re, M, Lapini, A, Luchini, C, Jereczek-Fossa, B, Sapino, A, Cinieri, S, Beretta, G, Bella, M, Bracarda, S, Colombo, N, Conteduca, V, Del Mastro, L, Galvano, A, Gristina, V, Guarneri, V, La Verde, N, Lorusso, D, Marchetti, P, Normanno, N, Ottini, L, Pensabene, M, Pignata, S, Procopio, G, Ricevuto, E, Silvestris, N, Tassone, P, Tucci, M, Donato, V, Carrara, S, Paiella, S, Gentilini, O, Gunelli, R, Nicolis, F, Buttitta, F, Colecchia, M, Fassan, M, Malapelle, U, Marchetti, A, Marchio, C, Scarpa, A, Truini, M, Zamboni, G, Gion, M, Trevisiol, C, Gronchi, A, Danesi, R, Di Marco, V, Carrera, P, Ghiorzo, P, Pasini, B, Varesco, L, Artibani, W, Ludovico, G, Campanella, O, Vatrano, S, Tagliafico, E, Russo A., Incorvaia L., Capoluongo E., Tagliaferri P., Gori S., Cortesi L., Genuardi M., Turchetti D., De Giorgi U., Di Maio M., Barberis M., Dessena M., Del Re M., Lapini A., Luchini C., Jereczek-Fossa B. A., Sapino A., Cinieri S., Beretta G., Bella M. A., Bracarda S., Colombo N., Conteduca V., Del Mastro L., Galvano A., Gristina V., Guarneri V., La Verde N., Lorusso D., Marchetti P., Normanno N., Ottini L., Pensabene M., Pignata S., Procopio G., Ricevuto E., Silvestris N., Tassone P., Tucci M., Donato V., Carrara S., Paiella S., Gentilini O., Gunelli R., Nicolis F., Buttitta F., Colecchia M., Fassan M., Malapelle U., Marchetti A., Marchio C., Scarpa A., Truini M., Zamboni G., Gion M., Trevisiol C., Gronchi A., Danesi R., Di Marco V., Carrera P., Ghiorzo P., Pasini B., Varesco L., Artibani W., Ludovico G., Campanella O., Vatrano S., Tagliafico E., Russo, A, Incorvaia, L, Capoluongo, E, Tagliaferri, P, Gori, S, Cortesi, L, Genuardi, M, Turchetti, D, De Giorgi, U, Di Maio, M, Barberis, M, Dessena, M, Del Re, M, Lapini, A, Luchini, C, Jereczek-Fossa, B, Sapino, A, Cinieri, S, Beretta, G, Bella, M, Bracarda, S, Colombo, N, Conteduca, V, Del Mastro, L, Galvano, A, Gristina, V, Guarneri, V, La Verde, N, Lorusso, D, Marchetti, P, Normanno, N, Ottini, L, Pensabene, M, Pignata, S, Procopio, G, Ricevuto, E, Silvestris, N, Tassone, P, Tucci, M, Donato, V, Carrara, S, Paiella, S, Gentilini, O, Gunelli, R, Nicolis, F, Buttitta, F, Colecchia, M, Fassan, M, Malapelle, U, Marchetti, A, Marchio, C, Scarpa, A, Truini, M, Zamboni, G, Gion, M, Trevisiol, C, Gronchi, A, Danesi, R, Di Marco, V, Carrera, P, Ghiorzo, P, Pasini, B, Varesco, L, Artibani, W, Ludovico, G, Campanella, O, Vatrano, S, Tagliafico, E, Russo A., Incorvaia L., Capoluongo E., Tagliaferri P., Gori S., Cortesi L., Genuardi M., Turchetti D., De Giorgi U., Di Maio M., Barberis M., Dessena M., Del Re M., Lapini A., Luchini C., Jereczek-Fossa B. A., Sapino A., Cinieri S., Beretta G., Bella M. A., Bracarda S., Colombo N., Conteduca V., Del Mastro L., Galvano A., Gristina V., Guarneri V., La Verde N., Lorusso D., Marchetti P., Normanno N., Ottini L., Pensabene M., Pignata S., Procopio G., Ricevuto E., Silvestris N., Tassone P., Tucci M., Donato V., Carrara S., Paiella S., Gentilini O., Gunelli R., Nicolis F., Buttitta F., Colecchia M., Fassan M., Malapelle U., Marchetti A., Marchio C., Scarpa A., Truini M., Zamboni G., Gion M., Trevisiol C., Gronchi A., Danesi R., Di Marco V., Carrera P., Ghiorzo P., Pasini B., Varesco L., Artibani W., Ludovico G., Campanella O., Vatrano S., and Tagliafico E.

Abstract

Constitutional BRCA1/BRCA2 pathogenic or likely pathogenic variants (PVs) are associated with an increased risk for developing breast and ovarian cancers. Current evidence indicates that BRCA1/2 PVs are also associated with pancreatic cancer, and that BRCA2 PVs are associated with prostate cancer risk. The identification of carriers of constitutional PVs in the BRCA1/2 genes allows the implementation of individual and family prevention pathways, through validated screening programs and risk-reducing strategies. According to the relevant and increasing therapeutic predictive implications, the inclusion of BRCA testing in the routine management of patients with breast, ovarian, pancreatic and prostate cancers represent a key requirement to optimize medical or surgical therapeutic and prevention decision-making, and access to specific anticancer therapies. Therefore, accurate patient selection, the use of standardized and harmonized procedures, and adherence to homogeneous testing criteria, are essential elements to implement BRCA testing in clinical practice. This consensus position paper has been developed and approved by a multidisciplinary Expert Panel of 64 professionals on behalf of the AIOM–AIRO–AISP–ANISC–AURO–Fondazione AIOM–SIAPEC/IAP–SIBioC–SICO–SIF–SIGE–SIGU–SIU–SIURO–UROP Italian Scientific Societies, and a patient association (aBRCAdaBRA Onlus). The working group included medical, surgical and radiation oncologists, medical and molecular geneticists, clinical molecular biologists, surgical and molecular pathologists, organ specialists such as gynecologists, gastroenterologists and urologists, and pharmacologists. The manuscript is based on the expert consensus and reports the best available evidence, according to the current eligibility criteria for BRCA testing and counseling, it also harmonizes with current Italian National Guidelines and Clinical Recommendations.

Published
2022

35. Next generation diagnostic algorithm in non-small cell lung cancer predictive molecular pathology: The KWAY Italian multicenter cost evaluation study

Author

Pisapia, P, Pepe, F, Baggi, A, Barberis, M, Galvano, A, Gristina, V, Mastrilli, F, Novello, S, Pagni, F, Pasini, S, Perrone, G, Righi, D, Russo, A, Troncone, G, Malapelle, U, Pisapia P., Pepe F., Baggi A., Barberis M., Galvano A., Gristina V., Mastrilli F., Novello S., Pagni F., Pasini S., Perrone G., Righi D., Russo A., Troncone G., Malapelle U., Pisapia, P, Pepe, F, Baggi, A, Barberis, M, Galvano, A, Gristina, V, Mastrilli, F, Novello, S, Pagni, F, Pasini, S, Perrone, G, Righi, D, Russo, A, Troncone, G, Malapelle, U, Pisapia P., Pepe F., Baggi A., Barberis M., Galvano A., Gristina V., Mastrilli F., Novello S., Pagni F., Pasini S., Perrone G., Righi D., Russo A., Troncone G., and Malapelle U.

Abstract

Aims: The KWAY project aims to investigate the economic sustainability of the up-front NGS technologies adoption in the analysis of clinically relevant molecular alterations in NSCLC patients. Methods: The diagnostic workflow and the related sustained costs of five Italian referral centers were assessed in four different evolving scenarios were analyzed. For each scenario, two alternative testing strategies were evaluated: the Maximized Standard strategy and the Maximized NGS strategy. Results: For each center, the robustness of obtained results was verified through a deterministic sensitivity analysis, observing the variation of total costs based on a variation of ±20 % of the input parameters and ensuring that results would present a consistent behavior compared to the original ones. Conclusions: our project, highlighted that the adoption of NGS allows to save personnel time dedicated to testing activities and to reduce the overall cost of testing per patient.

Published
2022

36. Avelumab plus axitinib in unresectable or metastatic type B3 thymomas and thymic carcinomas (CAVEATT): a single-arm, multicentre, phase 2 trial

Author

Conforti, F, Zucali, P, Pala, L, Catania, C, Bagnardi, V, Sala, I, Della Vigna, P, Perrino, M, Zagami, P, Corti, C, Stucchi, S, Barberis, M, Guerini-Rocco, E, Di Venosa, B, De Vincenzo, F, Cordua, N, Santoro, A, Giaccone, G, Martino De Pas, T, Conforti F., Zucali P. A., Pala L., Catania C., Bagnardi V., Sala I., Della Vigna P., Perrino M., Zagami P., Corti C., Stucchi S., Barberis M., Guerini-Rocco E., Di Venosa B., De Vincenzo F., Cordua N., Santoro A., Giaccone G., Martino De Pas T., Conforti, F, Zucali, P, Pala, L, Catania, C, Bagnardi, V, Sala, I, Della Vigna, P, Perrino, M, Zagami, P, Corti, C, Stucchi, S, Barberis, M, Guerini-Rocco, E, Di Venosa, B, De Vincenzo, F, Cordua, N, Santoro, A, Giaccone, G, Martino De Pas, T, Conforti F., Zucali P. A., Pala L., Catania C., Bagnardi V., Sala I., Della Vigna P., Perrino M., Zagami P., Corti C., Stucchi S., Barberis M., Guerini-Rocco E., Di Venosa B., De Vincenzo F., Cordua N., Santoro A., Giaccone G., and Martino De Pas T.

Abstract

Background: Patients with advanced type B3 thymoma and thymic carcinoma resistant to chemotherapy have few treatment options. We report the efficacy and safety results of the combination of the anti-PD-L1 inhibitor avelumab with the anti-angiogenesis drug axitinib in patients with advanced type B3 thymoma and thymic carcinoma. Methods: CAVEATT was a single-arm, multicentre, phase 2 trial, conducted in two Italian centres (the European Instituteof Oncology and the Humanitas Institute, Milan) in patients with histologically confirmed type B3 thymoma or thymic carcinoma, with advanced stage of disease who had progressed after at least one line of platinum-based chemotherapy. Previous treatment with an anti-angiogenesis drug was allowed but not with immune checkpoint inhibitors. Other inclusion criteria were age 18 years or older, an Eastern Cooperative Oncology Group performance status of 0–2, progressive disease, and presence of measurable disease according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1. Patients received avelumab 10 mg/kg intravenously every 2 weeks and axitinib 5 mg orally twice daily until disease progression or unacceptable toxicity. The primary endpoint was the centrally assessed overall response rate according to RECIST version 1.1. Patients who received at least one cycle of treatment and had at least one CT scan after treatment start at scheduled time point by protocol were judged assessable for response and were included in efficacy and safety analyses. This study is registered with EUDRACT, 2017–004048–38; enrolment is completed and follow-up is ongoing. Findings: Between April 22, 2019, and June 30, 2021, 32 patients were enrolled. 27 patients had a thymic carcinoma, three a type B3 thymoma, and two a mixed type B3 thymoma and thymic carcinoma. 29 (91%) of 32 patients had stage IVB disease and 13 (41%) of 32 had been pretreated with an anti-angiogenesis drug. 11 of 32 patients had an overall response; thus the overall

Published
2022

37. Different Response to Immunotherapy According to Melanoma Histologic Subtype

Author

Pala, L, Conforti, F, Pagan, E, Bagnardi, V, De Pas, T, Mazzarol, G, Barberis, M, Pennacchioli, E, Orsolini, G, Prestianni, P, Zagami, P, Nicolo', E, Patane, D, Saponara, M, Queirolo, P, Pala L., Conforti F., Pagan E., Bagnardi V., De Pas T. M., Mazzarol G., Barberis M., Pennacchioli E., Orsolini G., Prestianni P., Zagami P., Nicolo' E., Patane D., Saponara M., Queirolo P., Pala, L, Conforti, F, Pagan, E, Bagnardi, V, De Pas, T, Mazzarol, G, Barberis, M, Pennacchioli, E, Orsolini, G, Prestianni, P, Zagami, P, Nicolo', E, Patane, D, Saponara, M, Queirolo, P, Pala L., Conforti F., Pagan E., Bagnardi V., De Pas T. M., Mazzarol G., Barberis M., Pennacchioli E., Orsolini G., Prestianni P., Zagami P., Nicolo' E., Patane D., Saponara M., and Queirolo P.

Abstract

Superficial spreading melanoma (SSM) and nodular melanoma (NM) are the most common melanoma histologic subtypes and are characterized by different biological features. We retrospectively analyzed all consecutive patients with advanced melanoma, treated with anti-PD-1 and/or anti-CTLA-4 at our center, with data available on primary tumor subtype. The primary objective was to assess the association between histologic subtype and patients' outcomes. In addition, we analyzed whole-exome and whole-transcriptome sequencing data of a cohort of advanced melanoma to identify genes and related pathways, characterized by significant differences between NMs and SSMs. Twenty-one patients with NM and 39 with SSM, treated with anti-PD-1(53/60) as monotherapy or combined with anti-CTLA-4 (7/60), were analyzed. All known clinical-pathologic prognostic factors were well balanced between NM and SSM groups, except for the ECOG-PS score. The overall response rate was 52.4% (95% confidence interval, 29.8-74.3) in the NMs group versus 20.5% (9.3-36.5) in the SSMs group (P-value=0.02). The median progression-free survival and overall survival were, respectively, 13.9 and 44.5 months in the NMs group versus only 3.2 and 12 months in SSMs group (progression-free survival P-value=0.032; overall survival P-value=0.002). Multivariable analysis adjusting for the ECOG-PS, confirmed similar results. Whole-exome and whole-transcriptome data of 28 NMs and 21 SSMs were analyzed. No significant differences were observed in terms of both TMB and frequency of mutation in any gene. A total of 266 genes were overexpressed in NMs as compared with SSMs, and enrichment-analysis revealed a significant enrichment (false discovery rate<0.05) of genes belonging to immune-related pathways involved in antigens presentation mechanisms, response to interferon gamma and neutrophil activation. We provided clinical evidences suggesting a relevant association between melanoma histologic subtype and response to immuno

Published
2022

38. European experts consensus: BRCA/homologous recombination deficiency testing in first-line ovarian cancer

Author

Vergote, I, Gonzalez-Martin, A, Ray-Coquard, I, Harter, P, Colombo, N, Pujol, P, Lorusso, D, Mirza, M, Brasiuniene, B, Madry, R, Brenton, J, Ausems, M, Buttner, R, Lambrechts, D, Abreu, M, Balboni, S, Banerjee, S, Barberis, M, Barretina Ginesta, M, Baurain, J, Bignami, M, Bjorge, L, Blecharz, P, Bruchim, I, Capilna, M, Cerana, N, Cicchetti, A, Collins, D, Concin, N, D'Incalci, M, Davidson, B, de la Motte Rouge, T, De Iaco, P, Demirkiran, F, Denys, H, Doerk, T, Dorum, A, Ferrero, A, Fidalgo, A, Genuardi, M, Gladieff, L, Glasspool, R, Grimm, C, Gultekin, M, Hahnen, E, Hasenburg, A, Hegmane, A, Heinzelmann, V, Hogdall, E, Janavicius, R, Jarmalaite, S, Kalachand, R, Kaneva, R, Kilickap, S, Kocian, R, Kolencik, D, Kristeleit, R, Kryzhanivska, A, Leary, A, Lemley, B, Ligtenberg, M, Lopez-Guerrero, J, Lord, C, Avall-Lundqvist, E, Maenpaa, J, Mahner, S, Marme, F, Marth, C, Mcneish, I, Merkelbach-Bruse, S, Mourits, M, Normanno, N, Oaknin, A, Ojamaa, K, Papdimitriou, C, Penault-Llorca, F, Perrone, A, Pignata, S, Pikarsky, E, Rouleau, E, Rubio, M, Sapino, A, Schmalfeldt, B, Sehouli, J, Shapira, R, Steffensen, K, Sukhin, V, Syrios, J, Szallasi, Z, Taskiran, C, Terzic, M, Tischkowitz, M, Toth, I, Van de Vijver, K, Vardar, M, Wasag, B, Wimberger, P, Witteveen, E, Vergote I., Gonzalez-Martin A., Ray-Coquard I., Harter P., Colombo N., Pujol P., Lorusso D., Mirza M. R., Brasiuniene B., Madry R., Brenton J. D., Ausems M. G. E. M., Buttner R., Lambrechts D., Ausems M., Brenton J., Abreu M., Balboni S., Banerjee S., Barberis M., Barretina Ginesta M. P., Baurain J. -F., Bignami M., Bjorge L., Blecharz P., Bruchim I., Capilna M., Cerana N., Cicchetti A., Collins D., Concin N., D'Incalci M., Davidson B., de la Motte Rouge T., De Iaco P., Demirkiran F., Denys H., Doerk T., Dorum A., Ferrero A., Fidalgo A. P., Genuardi M., Gladieff L., Glasspool R., Grimm C., Gultekin M., Hahnen E., Hasenburg A., Hegmane A., Heinzelmann V., Hogdall E., Janavicius R., Jarmalaite S., Kalachand R., Kaneva R., Kilickap S., Kocian R., Kolencik D., Kristeleit R., Kryzhanivska A., Leary A., Lemley B., Ligtenberg M., Lopez-Guerrero J. A., Lord C. J., Avall-Lundqvist E., Maenpaa J., Mahner S., Marme F., Marth C., McNeish I., Merkelbach-Bruse S., Mourits M., Normanno N., Oaknin A., Ojamaa K., Papdimitriou C., Penault-Llorca F., Perrone A. M., Pignata S., Pikarsky E., Rouleau E., Rubio M., Sapino A., Schmalfeldt B., Sehouli J., Shapira R., Steffensen K. D., Sukhin V., Syrios J., Szallasi Z., Taskiran C., Terzic M., Tischkowitz M., Toth I., Van de Vijver K., Vardar M. A., Wasag B., Wimberger P., Witteveen E., Vergote, I, Gonzalez-Martin, A, Ray-Coquard, I, Harter, P, Colombo, N, Pujol, P, Lorusso, D, Mirza, M, Brasiuniene, B, Madry, R, Brenton, J, Ausems, M, Buttner, R, Lambrechts, D, Abreu, M, Balboni, S, Banerjee, S, Barberis, M, Barretina Ginesta, M, Baurain, J, Bignami, M, Bjorge, L, Blecharz, P, Bruchim, I, Capilna, M, Cerana, N, Cicchetti, A, Collins, D, Concin, N, D'Incalci, M, Davidson, B, de la Motte Rouge, T, De Iaco, P, Demirkiran, F, Denys, H, Doerk, T, Dorum, A, Ferrero, A, Fidalgo, A, Genuardi, M, Gladieff, L, Glasspool, R, Grimm, C, Gultekin, M, Hahnen, E, Hasenburg, A, Hegmane, A, Heinzelmann, V, Hogdall, E, Janavicius, R, Jarmalaite, S, Kalachand, R, Kaneva, R, Kilickap, S, Kocian, R, Kolencik, D, Kristeleit, R, Kryzhanivska, A, Leary, A, Lemley, B, Ligtenberg, M, Lopez-Guerrero, J, Lord, C, Avall-Lundqvist, E, Maenpaa, J, Mahner, S, Marme, F, Marth, C, Mcneish, I, Merkelbach-Bruse, S, Mourits, M, Normanno, N, Oaknin, A, Ojamaa, K, Papdimitriou, C, Penault-Llorca, F, Perrone, A, Pignata, S, Pikarsky, E, Rouleau, E, Rubio, M, Sapino, A, Schmalfeldt, B, Sehouli, J, Shapira, R, Steffensen, K, Sukhin, V, Syrios, J, Szallasi, Z, Taskiran, C, Terzic, M, Tischkowitz, M, Toth, I, Van de Vijver, K, Vardar, M, Wasag, B, Wimberger, P, Witteveen, E, Vergote I., Gonzalez-Martin A., Ray-Coquard I., Harter P., Colombo N., Pujol P., Lorusso D., Mirza M. R., Brasiuniene B., Madry R., Brenton J. D., Ausems M. G. E. M., Buttner R., Lambrechts D., Ausems M., Brenton J., Abreu M., Balboni S., Banerjee S., Barberis M., Barretina Ginesta M. P., Baurain J. -F., Bignami M., Bjorge L., Blecharz P., Bruchim I., Capilna M., Cerana N., Cicchetti A., Collins D., Concin N., D'Incalci M., Davidson B., de la Motte Rouge T., De Iaco P., Demirkiran F., Denys H., Doerk T., Dorum A., Ferrero A., Fidalgo A. P., Genuardi M., Gladieff L., Glasspool R., Grimm C., Gultekin M., Hahnen E., Hasenburg A., Hegmane A., Heinzelmann V., Hogdall E., Janavicius R., Jarmalaite S., Kalachand R., Kaneva R., Kilickap S., Kocian R., Kolencik D., Kristeleit R., Kryzhanivska A., Leary A., Lemley B., Ligtenberg M., Lopez-Guerrero J. A., Lord C. J., Avall-Lundqvist E., Maenpaa J., Mahner S., Marme F., Marth C., McNeish I., Merkelbach-Bruse S., Mourits M., Normanno N., Oaknin A., Ojamaa K., Papdimitriou C., Penault-Llorca F., Perrone A. M., Pignata S., Pikarsky E., Rouleau E., Rubio M., Sapino A., Schmalfeldt B., Sehouli J., Shapira R., Steffensen K. D., Sukhin V., Syrios J., Szallasi Z., Taskiran C., Terzic M., Tischkowitz M., Toth I., Van de Vijver K., Vardar M. A., Wasag B., Wimberger P., and Witteveen E.

Abstract

Background: Homologous recombination repair (HRR) enables fault-free repair of double-stranded DNA breaks. HRR deficiency is predicted to occur in around half of high-grade serous ovarian carcinomas. Ovarian cancers harbouring HRR deficiency typically exhibit sensitivity to poly-ADP ribose polymerase inhibitors (PARPi). Current guidelines recommend a range of approaches for genetic testing to identify predictors of sensitivity to PARPi in ovarian cancer and to identify genetic predisposition. Design: To establish a European-wide consensus for genetic testing (including the genetic care pathway), decision making and clinical management of patients with recently diagnosed advanced ovarian cancer, and the validity of biomarkers to predict the effectiveness of PARPi in the first-line setting. The collaborative European experts’ consensus group consisted of a steering committee (n = 14) and contributors (n = 84). A (modified) Delphi process was used to establish consensus statements based on a systematic literature search, conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Results: A consensus was reached on 34 statements amongst 98 caregivers (including oncologists, pathologists, clinical geneticists, genetic researchers, and patient advocates). The statements concentrated on (i) the value of testing for BRCA1/2 mutations and HRR deficiency testing, including when and whom to test; (ii) the importance of developing new and better HRR deficiency tests; (iii) the importance of germline non-BRCA HRR and mismatch repair gene mutations for predicting familial risk, but not for predicting sensitivity to PARPi, in the first-line setting; (iv) who should be able to inform patients about genetic testing, and what training and education should these caregivers receive. Conclusion: These consensus recommendations, from a multidisciplinary panel of experts from across Europe, provide clear guidance on the use of BRCA and HRR de

Published
2022

39. Integrated molecular profiling of patient-derived ovarian cancer models identifies clinically relevant signatures and tumor vulnerabilities

Author

Lupia, M, Melocchi, V, Bizzaro, F, Lo Riso, P, Dama, E, Baronio, M, Ranghiero, A, Barberis, M, Bernard, L, Bertalot, G, Giavazzi, R, Testa, G, Bianchi, F, Cavallaro, U, Lupia M., Melocchi V., Bizzaro F., Lo Riso P., Dama E., Baronio M., Ranghiero A., Barberis M., Bernard L., Bertalot G., Giavazzi R., Testa G., Bianchi F., Cavallaro U., Lupia, M, Melocchi, V, Bizzaro, F, Lo Riso, P, Dama, E, Baronio, M, Ranghiero, A, Barberis, M, Bernard, L, Bertalot, G, Giavazzi, R, Testa, G, Bianchi, F, Cavallaro, U, Lupia M., Melocchi V., Bizzaro F., Lo Riso P., Dama E., Baronio M., Ranghiero A., Barberis M., Bernard L., Bertalot G., Giavazzi R., Testa G., Bianchi F., and Cavallaro U.

Abstract

High-grade serous ovarian carcinoma (HGSOC) is a highly aggressive and intractable neoplasm, mainly because of its rapid dissemination into the abdominal cavity, a process that is favored by tumor-associated peritoneal ascites. The precise molecular alterations involved in HGSOC onset and progression remain largely unknown due to the high biological and genetic heterogeneity of this tumor. We established a set of different tumor samples (termed the As11-set) derived from a single HGSOC patient, consisting of peritoneal ascites, primary tumor cells, ovarian cancer stem cells (OCSC) and serially propagated tumor xenografts. The As11-set was subjected to an integrated RNA-seq and DNA-seq analysis which unveiled molecular alterations that marked the different types of samples. Our profiling strategy yielded a panel of signatures relevant in HGSOC and in OCSC biology. When such signatures were used to interrogate the TCGA dataset from HGSOC patients, they exhibited prognostic and predictive power. The molecular alterations also identified potential vulnerabilities associated with OCSC, which were then tested functionally in stemness-related assays. As a proof of concept, we defined PI3K signaling as a novel druggable target in OCSC.

Published
2022

40. Tumor BRCA Testing in Epithelial Ovarian Cancers: Past and Future—Five-Years’ Single-Institution Experience of 762 Consecutive Patients

Author

Fumagalli, C, Betella, I, Rappa, A, Di Giminiani, M, Gaiano, M, De Vitis, L, Zambetti, B, Vacirca, D, Multinu, F, Venetis, K, Colombo, N, Barberis, M, Rocco, E, Fumagalli C., Betella I., Rappa A., Di Giminiani M., Gaiano M., De Vitis L. A., Zambetti B., Vacirca D., Multinu F., Venetis K., Colombo N., Barberis M., Rocco E. G., Fumagalli, C, Betella, I, Rappa, A, Di Giminiani, M, Gaiano, M, De Vitis, L, Zambetti, B, Vacirca, D, Multinu, F, Venetis, K, Colombo, N, Barberis, M, Rocco, E, Fumagalli C., Betella I., Rappa A., Di Giminiani M., Gaiano M., De Vitis L. A., Zambetti B., Vacirca D., Multinu F., Venetis K., Colombo N., Barberis M., and Rocco E. G.

Abstract

The establishment of PARP inhibitors in the treatment of epithelial ovarian carcinoma (EOC) has prompt BRCA assessment at the time of diagnosis. We described our five years of experience of tumor BRCA testing, as part of a multidisciplinary workflow for the management of EOC patients. We used a BRCA next-generation sequencing (NGS) test for profiling formalin-fixed, paraffin-embedded (FFPE) EOCs of 762 consecutive patients, with a success rate of 99.7% and a median turnaround time of 12 days. We found 178 (23.4%) cases with pathogenic/likely pathogenic (P/LP) mutations, 74 (9.7%) cases with variants of uncertain significance and 508 (66.8%) wild type tumors. Among 174 patients without P/LP mutations and investigated with multiple-ligation probe-amplification analysis on peripheral blood, two (1.1%) were positive for large rearrangements. Patients with P/LP alterations and/or with positive family history were referred to genetic counselling. Comparing tumor and blood NGS test results of 256 patients, we obtained a tumor test negative predictive value of 100% and we defined 76% of P/LP alterations as germline and 24% as somatic variants. The proposed workflow may successfully identify EOC patients with BRCA1/2 alteration, guiding both therapeutic and risk assessment clinical decisions.

Published
2022

41. Author Correction: Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology (Nature Genetics, (2021), 53, 12, (1636-1648), 10.1038/s41588-021-00973-1)

Author

van Rheenen W., van Rheenen, W, van der Spek, R, Bakker, M, van Vugt, J, Hop, P, Zwamborn, R, de Klein, N, Westra, H, Bakker, O, Deelen, P, Shireby, G, Hannon, E, Moisse, M, Baird, D, Restuadi, R, Dolzhenko, E, Dekker, A, Gawor, K, Westeneng, H, Tazelaar, G, van Eijk, K, Kooyman, M, Byrne, R, Doherty, M, Heverin, M, Al Khleifat, A, Iacoangeli, A, Shatunov, A, Ticozzi, N, Cooper-Knock, J, Smith, B, Gromicho, M, Chandran, S, Pal, S, Morrison, K, Shaw, P, Hardy, J, Orrell, R, Sendtner, M, Meyer, T, Basak, N, van der Kooi, A, Ratti, A, Fogh, I, Gellera, C, Lauria, G, Corti, S, Cereda, C, Sproviero, D, D'Alfonso, S, Soraru, G, Siciliano, G, Filosto, M, Padovani, A, Chio, A, Calvo, A, Moglia, C, Brunetti, M, Canosa, A, Grassano, M, Beghi, E, Pupillo, E, Logroscino, G, Nefussy, B, Osmanovic, A, Nordin, A, Lerner, Y, Zabari, M, Gotkine, M, Baloh, R, Bell, S, Vourc'H, P, Corcia, P, Couratier, P, Millecamps, S, Meininger, V, Salachas, F, Mora Pardina, J, Assialioui, A, Rojas-Garcia, R, Dion, P, Ross, J, Ludolph, A, Weishaupt, J, Brenner, D, Freischmidt, A, Bensimon, G, Brice, A, Durr, A, Payan, C, Saker-Delye, S, Wood, N, Topp, S, Rademakers, R, Tittmann, L, Lieb, W, Franke, A, Ripke, S, Braun, A, Kraft, J, Whiteman, D, Olsen, C, Uitterlinden, A, Hofman, A, Rietschel, M, Cichon, S, Nothen, M, Amouyel, P, Comi, G, Riva, N, Lunetta, C, Gerardi, F, Cotelli, M, Rinaldi, F, Chiveri, L, Guaita, M, Perrone, P, Ceroni, M, Diamanti, L, Ferrarese, C, Tremolizzo, L, Delodovici, M, Bono, G, Manera, U, Vasta, R, Bombaci, A, Casale, F, Fuda, G, Salamone, P, Iazzolino, B, Peotta, L, Cugnasco, P, De Marco, G, Torrieri, M, Palumbo, F, Gallone, S, Barberis, M, Sbaiz, L, Gentile, S, Mauro, A, Mazzini, L, De Marchi, F, Corrado, L, Bertolotto, A, Gionco, M, Leotta, D, Odddenino, E, Imperiale, D, Cavallo, R, Pignatta, P, De Mattei, M, Geda, C, Papurello, D, Gusmaroli, G, Comi, C, Labate, C, Ruiz, L, Ferrandi, D, Rota, E, Aguggia, M, Di Vito, N, Meineri, P, Ghiglione, P, Launaro, N, Dotta, M, Di Sapio, A, Giardini, G, Tiloca, C, Peverelli, S, Taroni, F, Pensato, V, Castellotti, B, Del Bo, R, Gagliardi, S, Raggi, F, Simoncini, C, Lo Gerfo, A, Inghilleri, M, Ferlini, A, Simone, I, Passarella, B, Guerra, V, Zoccolella, S, Nozzoli, C, Mundi, C, Leone, M, Zarrelli, M, Tamma, F, Valluzzi, F, Calabrese, G, Boero, G, Rini, A, Traynor, B, Singleton, A, Mitne Neto, M, Cauchi, R, Ophoff, R, Wiedau-Pazos, M, Lomen-Hoerth, C, van Deerlin, V, Grosskreutz, J, Roediger, A, Gaur, N, Jork, A, Barthel, T, Theele, E, Ilse, B, Stubendorff, B, Witte, O, Steinbach, R, Hubner, C, Graff, C, Brylev, L, Fominykh, V, Demeshonok, V, Ataulina, A, Rogelj, B, Koritnik, B, Zidar, J, Ravnik-Glavac, M, Glavac, D, Stevic, Z, Drory, V, Povedano, M, Blair, I, Kiernan, M, Benyamin, B, Henderson, R, Furlong, S, Mathers, S, Mccombe, P, Needham, M, Ngo, S, Nicholson, G, Pamphlett, R, Rowe, D, Steyn, F, Williams, K, Mather, K, Sachdev, P, Henders, A, Wallace, L, de Carvalho, M, Pinto, S, Petri, S, Weber, M, Rouleau, G, Silani, V, Curtis, C, Breen, G, Glass, J, Brown, R, Landers, J, Shaw, C, Andersen, P, Groen, E, van Es, M, Pasterkamp, R, Fan, D, Garton, F, Mcrae, A, Davey Smith, G, Gaunt, T, Eberle, M, Mill, J, Mclaughlin, R, Hardiman, O, Kenna, K, Wray, N, Tsai, E, Runz, H, Franke, L, Al-Chalabi, A, Van Damme, P, van den Berg, L, Veldink, J, van Rheenen W., van der Spek R. A. A., Bakker M. K., van Vugt J. J. F. A., Hop P. J., Zwamborn R. A. J., de Klein N., Westra H. -J., Bakker O. B., Deelen P., Shireby G., Hannon E., Moisse M., Baird D., Restuadi R., Dolzhenko E., Dekker A. M., Gawor K., Westeneng H. -J., Tazelaar G. H. P., van Eijk K. R., Kooyman M., Byrne R. P., Doherty M., Heverin M., Al Khleifat A., Iacoangeli A., Shatunov A., Ticozzi N., Cooper-Knock J., Smith B. N., Gromicho M., Chandran S., Pal S., Morrison K. E., Shaw P. J., Hardy J., Orrell R. W., Sendtner M., Meyer T., Basak N., van der Kooi A. J., Ratti A., Fogh I., Gellera C., Lauria G., Corti S., Cereda C., Sproviero D., D'Alfonso S., Soraru G., Siciliano G., Filosto M., Padovani A., Chio A., Calvo A., Moglia C., Brunetti M., Canosa A., Grassano M., Beghi E., Pupillo E., Logroscino G., Nefussy B., Osmanovic A., Nordin A., Lerner Y., Zabari M., Gotkine M., Baloh R. H., Bell S., Vourc'h P., Corcia P., Couratier P., Millecamps S., Meininger V., Salachas F., Mora Pardina J. S., Assialioui A., Rojas-Garcia R., Dion P. A., Ross J. P., Ludolph A. C., Weishaupt J. H., Brenner D., Freischmidt A., Bensimon G., Brice A., Durr A., Payan C. A. M., Saker-Delye S., Wood N. W., Topp S., Rademakers R., Tittmann L., Lieb W., Franke A., Ripke S., Braun A., Kraft J., Whiteman D. C., Olsen C. M., Uitterlinden A. G., Hofman A., Rietschel M., Cichon S., Nothen M. M., Amouyel P., Comi G., Riva N., Lunetta C., Gerardi F., Cotelli M. S., Rinaldi F., Chiveri L., Guaita M. C., Perrone P., Ceroni M., Diamanti L., Ferrarese C., Tremolizzo L., Delodovici M. L., Bono G., Manera U., Vasta R., Bombaci A., Casale F., Fuda G., Salamone P., Iazzolino B., Peotta L., Cugnasco P., De Marco G., Torrieri M. C., Palumbo F., Gallone S., Barberis M., Sbaiz L., Gentile S., Mauro A., Mazzini L., De Marchi F., Corrado L., Bertolotto A., Gionco M., Leotta D., Odddenino E., Imperiale D., Cavallo R., Pignatta P., De Mattei M., Geda C., Papurello D. M., Gusmaroli G., Comi C., Labate C., Ruiz L., Ferrandi D., Rota E., Aguggia M., Di Vito N., Meineri P., Ghiglione P., Launaro N., Dotta M., Di Sapio A., Giardini G., Tiloca C., Peverelli S., Taroni F., Pensato V., Castellotti B., Comi G. P., Del Bo R., Gagliardi S., Raggi F., Simoncini C., Lo Gerfo A., Inghilleri M., Ferlini A., Simone I. L., Passarella B., Guerra V., Zoccolella S., Nozzoli C., Mundi C., Leone M., Zarrelli M., Tamma F., Valluzzi F., Calabrese G., Boero G., Rini A., Traynor B. J., Singleton A. B., Mitne Neto M., Cauchi R. J., Ophoff R. A., Wiedau-Pazos M., Lomen-Hoerth C., van Deerlin V. M., Grosskreutz J., Roediger A., Gaur N., Jork A., Barthel T., Theele E., Ilse B., Stubendorff B., Witte O. W., Steinbach R., Hubner C. A., Graff C., Brylev L., Fominykh V., Demeshonok V., Ataulina A., Rogelj B., Koritnik B., Zidar J., Ravnik-Glavac M., Glavac D., Stevic Z., Drory V., Povedano M., Blair I. P., Kiernan M. C., Benyamin B., Henderson R. D., Furlong S., Mathers S., McCombe P. A., Needham M., Ngo S. T., Nicholson G. A., Pamphlett R., Rowe D. B., Steyn F. J., Williams K. L., Mather K. A., Sachdev P. S., Henders A. K., Wallace L., de Carvalho M., Pinto S., Petri S., Weber M., Rouleau G. A., Silani V., Curtis C. J., Breen G., Glass J. D., Brown R. H., Landers J. E., Shaw C. E., Andersen P. M., Groen E. J. N., van Es M. A., Pasterkamp R. J., Fan D., Garton F. C., McRae A. F., Davey Smith G., Gaunt T. R., Eberle M. A., Mill J., McLaughlin R. L., Hardiman O., Kenna K. P., Wray N. R., Tsai E., Runz H., Franke L., Al-Chalabi A., Van Damme P., van den Berg L. H., Veldink J. H., van Rheenen W., van Rheenen, W, van der Spek, R, Bakker, M, van Vugt, J, Hop, P, Zwamborn, R, de Klein, N, Westra, H, Bakker, O, Deelen, P, Shireby, G, Hannon, E, Moisse, M, Baird, D, Restuadi, R, Dolzhenko, E, Dekker, A, Gawor, K, Westeneng, H, Tazelaar, G, van Eijk, K, Kooyman, M, Byrne, R, Doherty, M, Heverin, M, Al Khleifat, A, Iacoangeli, A, Shatunov, A, Ticozzi, N, Cooper-Knock, J, Smith, B, Gromicho, M, Chandran, S, Pal, S, Morrison, K, Shaw, P, Hardy, J, Orrell, R, Sendtner, M, Meyer, T, Basak, N, van der Kooi, A, Ratti, A, Fogh, I, Gellera, C, Lauria, G, Corti, S, Cereda, C, Sproviero, D, D'Alfonso, S, Soraru, G, Siciliano, G, Filosto, M, Padovani, A, Chio, A, Calvo, A, Moglia, C, Brunetti, M, Canosa, A, Grassano, M, Beghi, E, Pupillo, E, Logroscino, G, Nefussy, B, Osmanovic, A, Nordin, A, Lerner, Y, Zabari, M, Gotkine, M, Baloh, R, Bell, S, Vourc'H, P, Corcia, P, Couratier, P, Millecamps, S, Meininger, V, Salachas, F, Mora Pardina, J, Assialioui, A, Rojas-Garcia, R, Dion, P, Ross, J, Ludolph, A, Weishaupt, J, Brenner, D, Freischmidt, A, Bensimon, G, Brice, A, Durr, A, Payan, C, Saker-Delye, S, Wood, N, Topp, S, Rademakers, R, Tittmann, L, Lieb, W, Franke, A, Ripke, S, Braun, A, Kraft, J, Whiteman, D, Olsen, C, Uitterlinden, A, Hofman, A, Rietschel, M, Cichon, S, Nothen, M, Amouyel, P, Comi, G, Riva, N, Lunetta, C, Gerardi, F, Cotelli, M, Rinaldi, F, Chiveri, L, Guaita, M, Perrone, P, Ceroni, M, Diamanti, L, Ferrarese, C, Tremolizzo, L, Delodovici, M, Bono, G, Manera, U, Vasta, R, Bombaci, A, Casale, F, Fuda, G, Salamone, P, Iazzolino, B, Peotta, L, Cugnasco, P, De Marco, G, Torrieri, M, Palumbo, F, Gallone, S, Barberis, M, Sbaiz, L, Gentile, S, Mauro, A, Mazzini, L, De Marchi, F, Corrado, L, Bertolotto, A, Gionco, M, Leotta, D, Odddenino, E, Imperiale, D, Cavallo, R, Pignatta, P, De Mattei, M, Geda, C, Papurello, D, Gusmaroli, G, Comi, C, Labate, C, Ruiz, L, Ferrandi, D, Rota, E, Aguggia, M, Di Vito, N, Meineri, P, Ghiglione, P, Launaro, N, Dotta, M, Di Sapio, A, Giardini, G, Tiloca, C, Peverelli, S, Taroni, F, Pensato, V, Castellotti, B, Del Bo, R, Gagliardi, S, Raggi, F, Simoncini, C, Lo Gerfo, A, Inghilleri, M, Ferlini, A, Simone, I, Passarella, B, Guerra, V, Zoccolella, S, Nozzoli, C, Mundi, C, Leone, M, Zarrelli, M, Tamma, F, Valluzzi, F, Calabrese, G, Boero, G, Rini, A, Traynor, B, Singleton, A, Mitne Neto, M, Cauchi, R, Ophoff, R, Wiedau-Pazos, M, Lomen-Hoerth, C, van Deerlin, V, Grosskreutz, J, Roediger, A, Gaur, N, Jork, A, Barthel, T, Theele, E, Ilse, B, Stubendorff, B, Witte, O, Steinbach, R, Hubner, C, Graff, C, Brylev, L, Fominykh, V, Demeshonok, V, Ataulina, A, Rogelj, B, Koritnik, B, Zidar, J, Ravnik-Glavac, M, Glavac, D, Stevic, Z, Drory, V, Povedano, M, Blair, I, Kiernan, M, Benyamin, B, Henderson, R, Furlong, S, Mathers, S, Mccombe, P, Needham, M, Ngo, S, Nicholson, G, Pamphlett, R, Rowe, D, Steyn, F, Williams, K, Mather, K, Sachdev, P, Henders, A, Wallace, L, de Carvalho, M, Pinto, S, Petri, S, Weber, M, Rouleau, G, Silani, V, Curtis, C, Breen, G, Glass, J, Brown, R, Landers, J, Shaw, C, Andersen, P, Groen, E, van Es, M, Pasterkamp, R, Fan, D, Garton, F, Mcrae, A, Davey Smith, G, Gaunt, T, Eberle, M, Mill, J, Mclaughlin, R, Hardiman, O, Kenna, K, Wray, N, Tsai, E, Runz, H, Franke, L, Al-Chalabi, A, Van Damme, P, van den Berg, L, Veldink, J, van Rheenen W., van der Spek R. A. A., Bakker M. K., van Vugt J. J. F. A., Hop P. J., Zwamborn R. A. J., de Klein N., Westra H. -J., Bakker O. B., Deelen P., Shireby G., Hannon E., Moisse M., Baird D., Restuadi R., Dolzhenko E., Dekker A. M., Gawor K., Westeneng H. -J., Tazelaar G. H. P., van Eijk K. R., Kooyman M., Byrne R. P., Doherty M., Heverin M., Al Khleifat A., Iacoangeli A., Shatunov A., Ticozzi N., Cooper-Knock J., Smith B. N., Gromicho M., Chandran S., Pal S., Morrison K. E., Shaw P. J., Hardy J., Orrell R. W., Sendtner M., Meyer T., Basak N., van der Kooi A. J., Ratti A., Fogh I., Gellera C., Lauria G., Corti S., Cereda C., Sproviero D., D'Alfonso S., Soraru G., Siciliano G., Filosto M., Padovani A., Chio A., Calvo A., Moglia C., Brunetti M., Canosa A., Grassano M., Beghi E., Pupillo E., Logroscino G., Nefussy B., Osmanovic A., Nordin A., Lerner Y., Zabari M., Gotkine M., Baloh R. H., Bell S., Vourc'h P., Corcia P., Couratier P., Millecamps S., Meininger V., Salachas F., Mora Pardina J. S., Assialioui A., Rojas-Garcia R., Dion P. A., Ross J. P., Ludolph A. C., Weishaupt J. H., Brenner D., Freischmidt A., Bensimon G., Brice A., Durr A., Payan C. A. M., Saker-Delye S., Wood N. W., Topp S., Rademakers R., Tittmann L., Lieb W., Franke A., Ripke S., Braun A., Kraft J., Whiteman D. C., Olsen C. M., Uitterlinden A. G., Hofman A., Rietschel M., Cichon S., Nothen M. M., Amouyel P., Comi G., Riva N., Lunetta C., Gerardi F., Cotelli M. S., Rinaldi F., Chiveri L., Guaita M. C., Perrone P., Ceroni M., Diamanti L., Ferrarese C., Tremolizzo L., Delodovici M. L., Bono G., Manera U., Vasta R., Bombaci A., Casale F., Fuda G., Salamone P., Iazzolino B., Peotta L., Cugnasco P., De Marco G., Torrieri M. C., Palumbo F., Gallone S., Barberis M., Sbaiz L., Gentile S., Mauro A., Mazzini L., De Marchi F., Corrado L., Bertolotto A., Gionco M., Leotta D., Odddenino E., Imperiale D., Cavallo R., Pignatta P., De Mattei M., Geda C., Papurello D. M., Gusmaroli G., Comi C., Labate C., Ruiz L., Ferrandi D., Rota E., Aguggia M., Di Vito N., Meineri P., Ghiglione P., Launaro N., Dotta M., Di Sapio A., Giardini G., Tiloca C., Peverelli S., Taroni F., Pensato V., Castellotti B., Comi G. P., Del Bo R., Gagliardi S., Raggi F., Simoncini C., Lo Gerfo A., Inghilleri M., Ferlini A., Simone I. L., Passarella B., Guerra V., Zoccolella S., Nozzoli C., Mundi C., Leone M., Zarrelli M., Tamma F., Valluzzi F., Calabrese G., Boero G., Rini A., Traynor B. J., Singleton A. B., Mitne Neto M., Cauchi R. J., Ophoff R. A., Wiedau-Pazos M., Lomen-Hoerth C., van Deerlin V. M., Grosskreutz J., Roediger A., Gaur N., Jork A., Barthel T., Theele E., Ilse B., Stubendorff B., Witte O. W., Steinbach R., Hubner C. A., Graff C., Brylev L., Fominykh V., Demeshonok V., Ataulina A., Rogelj B., Koritnik B., Zidar J., Ravnik-Glavac M., Glavac D., Stevic Z., Drory V., Povedano M., Blair I. P., Kiernan M. C., Benyamin B., Henderson R. D., Furlong S., Mathers S., McCombe P. A., Needham M., Ngo S. T., Nicholson G. A., Pamphlett R., Rowe D. B., Steyn F. J., Williams K. L., Mather K. A., Sachdev P. S., Henders A. K., Wallace L., de Carvalho M., Pinto S., Petri S., Weber M., Rouleau G. A., Silani V., Curtis C. J., Breen G., Glass J. D., Brown R. H., Landers J. E., Shaw C. E., Andersen P. M., Groen E. J. N., van Es M. A., Pasterkamp R. J., Fan D., Garton F. C., McRae A. F., Davey Smith G., Gaunt T. R., Eberle M. A., Mill J., McLaughlin R. L., Hardiman O., Kenna K. P., Wray N. R., Tsai E., Runz H., Franke L., Al-Chalabi A., Van Damme P., van den Berg L. H., and Veldink J. H.

Abstract

In the version of this article initially published, the affiliation for Nazli Başak appeared incorrectly. Nazli Başak is at Koç University, School of Medicine, KUTTAM-NDAL, Istanbul, Turkey, and not Bogazici University. The error has been corrected in the HTML and PDF versions of the article.

Published
2022

42. 71P Molecular Tumor Board at the European Institute of Oncology: An early Italian precision oncology experience

Author

Crimini, E., primary, Repetto, M., additional, Boscolo Bielo, L., additional, Guerini-Rocco, E., additional, Ascione, L., additional, Zanzottera, C., additional, Mazzarella, L., additional, Ranghiero, A., additional, Belli, C., additional, Criscitiello, C., additional, Esposito, A., additional, Barberis, M., additional, and Curigliano, G., additional

Published
2023
Full Text
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43. The HFE p.H63D (p.His63Asp) Polymorphism Is a Modifier of ALS Outcome in Italian and French Patients with SOD1 Mutations

Author

Canosa, A, Calvo, A, Mora, G, Moglia, C, Brunetti, M, Barberis, M, Borghero, G, Caponnetto, C, Trojsi, F, Spataro, R, Volanti, P, Simone, I, Salvi, F, Logullo, F, Riva, N, Tremolizzo, L, Giannini, F, Mandrioli, J, Tanel, R, Murru, M, Mandich, P, Conforti, F, Zollino, M, Sabatelli, M, Tarlarini, C, Lunetta, C, Mazzini, L, D'Alfonso, S, Guy, N, Meininger, V, Clavelou, P, Camu, W, Chiò, A, Canosa, Antonio, Calvo, Andrea, Mora, Gabriele, Moglia, Cristina, Brunetti, Maura, Barberis, Marco, Borghero, Giuseppe, Caponnetto, Claudia, Trojsi, Francesca, Spataro, Rossella, Volanti, Paolo, Simone, Isabella Laura, Salvi, Fabrizio, Logullo, Francesco Ottavio, Riva, Nilo, Tremolizzo, Lucio, Giannini, Fabio, Mandrioli, Jessica, Tanel, Raffaella, Murru, Maria Rita, Mandich, Paola, Conforti, Francesca Luisa, Zollino, Marcella, Sabatelli, Mario, Tarlarini, Claudia, Lunetta, Christian, Mazzini, Letizia, D'Alfonso, Sandra, Guy, Nathalie, Meininger, Vincent, Clavelou, Pierre, Camu, William, Chiò, Adriano, Canosa, A, Calvo, A, Mora, G, Moglia, C, Brunetti, M, Barberis, M, Borghero, G, Caponnetto, C, Trojsi, F, Spataro, R, Volanti, P, Simone, I, Salvi, F, Logullo, F, Riva, N, Tremolizzo, L, Giannini, F, Mandrioli, J, Tanel, R, Murru, M, Mandich, P, Conforti, F, Zollino, M, Sabatelli, M, Tarlarini, C, Lunetta, C, Mazzini, L, D'Alfonso, S, Guy, N, Meininger, V, Clavelou, P, Camu, W, Chiò, A, Canosa, Antonio, Calvo, Andrea, Mora, Gabriele, Moglia, Cristina, Brunetti, Maura, Barberis, Marco, Borghero, Giuseppe, Caponnetto, Claudia, Trojsi, Francesca, Spataro, Rossella, Volanti, Paolo, Simone, Isabella Laura, Salvi, Fabrizio, Logullo, Francesco Ottavio, Riva, Nilo, Tremolizzo, Lucio, Giannini, Fabio, Mandrioli, Jessica, Tanel, Raffaella, Murru, Maria Rita, Mandich, Paola, Conforti, Francesca Luisa, Zollino, Marcella, Sabatelli, Mario, Tarlarini, Claudia, Lunetta, Christian, Mazzini, Letizia, D'Alfonso, Sandra, Guy, Nathalie, Meininger, Vincent, Clavelou, Pierre, Camu, William, and Chiò, Adriano

Abstract

Background: Data from published studies about the effect of HFE polymorphisms on ALS risk, phenotype, and survival are still inconclusive. We aimed at evaluating whether the p.H63D polymorphism is a modifier of phenotype and survival in SOD1-mutated patients. Methods: We included 183 SOD1-mutated ALS patients. Mutations were classified as severe or mild according to the median survival of the study population. Patients were screened for the HFE p.H63D polymorphism. Survival was calculated using the Kaplan–Meier modeling, and differences were measured by the log-rank test. Multivariable analysis was performed with the Cox proportional hazards model (stepwise backward). Results: SOD1 severe mutation carriers show more frequent familial history for ALS and shorter survival compared to mild mutation carriers. Carriers and non-carriers of the p.H63D polymorphism did not differ in terms of sex ratio, frequency of positive familial history, age at onset, and bulbar/spinal ratio. In univariate and in Cox multivariable analysis using sex, age at onset, site of onset, family history, country of origin, and mutation severity as covariates, p.H63D carriers had a longer survival (p = 0.034 and p = 0.004). Conclusions: We found that SOD1-mutated ALS patients carrying the p.H63D HFE polymorphism have a longer survival compared to non-carriers, independently of sex, age and site of onset, family history, nation of origin, and severity of mutations, suggesting a possible role as disease progression modifier for the p.H63D HFE polymorphism in SOD1-ALS.

Published
2023

44. The molecular landscape of breast mucoepidermoid carcinoma

Author

Venetis, K, Sajjadi, E, Ivanova, M, Andaloro, S, Pessina, S, Zanetti, C, Ranghiero, A, Citelli, G, Rossi, C, Lucioni, M, Malapelle, U, Pagni, F, Barberis, M, Guerini-Rocco, E, Viale, G, Fusco, N, Venetis, Konstantinos, Sajjadi, Elham, Ivanova, Mariia, Andaloro, Silvia, Pessina, Simona, Zanetti, Chiara, Ranghiero, Alberto, Citelli, Gabriele, Rossi, Chiara, Lucioni, Marco, Malapelle, Umberto, Pagni, Fabio, Barberis, Massimo, Guerini-Rocco, Elena, Viale, Giuseppe, Fusco, Nicola, Venetis, K, Sajjadi, E, Ivanova, M, Andaloro, S, Pessina, S, Zanetti, C, Ranghiero, A, Citelli, G, Rossi, C, Lucioni, M, Malapelle, U, Pagni, F, Barberis, M, Guerini-Rocco, E, Viale, G, Fusco, N, Venetis, Konstantinos, Sajjadi, Elham, Ivanova, Mariia, Andaloro, Silvia, Pessina, Simona, Zanetti, Chiara, Ranghiero, Alberto, Citelli, Gabriele, Rossi, Chiara, Lucioni, Marco, Malapelle, Umberto, Pagni, Fabio, Barberis, Massimo, Guerini-Rocco, Elena, Viale, Giuseppe, and Fusco, Nicola

Abstract

Mucoepidermoid carcinoma (MEC) of the breast is an extremely rare salivary gland-type tumor characterized by epidermoid, basaloid, intermediate, and/or mucinous cells arranged in solid and cystic patterns. Despite their triple-negative phenotype, breast MECs are generally considered low-risk malignancies but their biology is largely unexplored; therefore, guidelines for clinical management are lacking. Here, we sought to characterize the molecular landscape of breast MECs. Thirteen cases were histologically reviewed, characterized for tumor-infiltrating lymphocytes (TILs), and were subjected to immunohistochemistry for programmed death-ligand 1 (PD-L1, clone 22C3), EGFR, and amphiregulin (AREG). Rearrangements in MAML2 and EWSR1 were investigated by fluorescent in situ hybridization. Targeted next-generation sequencing of 161 genes was performed on eight cases. Most MECs had low histological grade (n = 10, 77%), with the presence of TILs (n = 9/12; 75%) and PD-L1 combined positive score ranging from 10 to 20 (n = 4/6; 67%). All cases showed EGFR and AREG overexpression and were fusion negative. Enrichment of genetic alterations was observed in PI3K/AKT/mTOR and cell cycle regulation pathways, while only one case harbored TP53 mutations. This is the first study providing extensive molecular data on breast MECs and the largest collection of cases available to date in the literature. Breast MECs lack TP53 mutations found in high-grade forms of triple-negative breast cancers and MAML2 or EWSR1 rearrangements pathognomonic of salivary MECs. Triple-negativity and PD-L1 positivity suggest a window of opportunity for immunotherapy in these patients. The EGFR/AREG axis activation, coupled with the mutational patterns in PI3K/AKT/mTOR and cell cycle pathways warrants caution in considering MECs as low-risk neoplasms.

Published
2023

46. 579P A multicenter evaluation of a low pass whole genome sequencing-based solution for homologous recombination deficiency detection

Author

Buisson, A., primary, Saintigny, P., additional, Pujade-Lauraine, E., additional, Montoto Grillot, C., additional, Varcica, D., additional, Barberis, M., additional, Colombo, N., additional, Harlé, A., additional, Gilson, P., additional, Roma, C., additional, Bergantino, F., additional, Harter, P., additional, Pignata, S., additional, Gonzalez Martin, A.J., additional, Schauer, C., additional, Fujiwara, K., additional, Vergote, I.B., additional, Juhler-Nottrup, T.J., additional, Just, P-A., additional, and Ray-Coquard, I.L., additional

Published
2022
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49. Nationwide multidisciplinary consensus on the clinical management of Merkel cell carcinoma: a Delphi panel

Author

Spada F., Bossi P., Caraco C., Sileni V. C., Dei Tos A. P., Fazio N., Grignani G., Maio M., Quaglino P., Queirolo P., Ascierto P. A., Antonini Cappellini G. C., Antonuzzo L., Badalamenti G., Barberis M., Bassetto F., Berardi R., Berruti A., Bongiovanni A., Bonomo P., Borgognoni L., Borzillo V., Bruder F., Campana D., Consoli F., Cordova A., Depenni R., Di Giacomo A. M., Fabbrocini G., Fargnoli M. C., Ferraresi V., Ferrau F., Fierro M. T., Gatti M., Gelsomino F., Giuffrida D., Graziano P., Gregorelli C., Guida M., Massi D., Mazzarotto R., Milesi L., Minisini A. M., Morgese F., Muto P., Palmieri G., Patuzzo R., Pellacani G., Picciotto F., Pigozzo J., Pimpinelli N., Poletti P., Repetto L., Rinaldi G., Rubegni P., Rubino G., Spagnolo F., Tagliaferri L., Tanda E., Tronconi M. C., Tucci M., Valente M., Vincenzi B., Zalaudek I., Spada F., Bossi P., Caraco C., Sileni V.C., Dei Tos A.P., Fazio N., Grignani G., Maio M., Quaglino P., Queirolo P., Ascierto P.A., Antonini Cappellini G.C., Antonuzzo L., Badalamenti G., Barberis M., Bassetto F., Berardi R., Berruti A., Bongiovanni A., Bonomo P., Borgognoni L., Borzillo V., Bruder F., Campana D., Consoli F., Cordova A., Depenni R., Di Giacomo A.M., Fabbrocini G., Fargnoli M.C., Ferraresi V., Ferrau F., Fierro M.T., Gatti M., Gelsomino F., Giuffrida D., Graziano P., Gregorelli C., Guida M., Massi D., Mazzarotto R., Milesi L., Minisini A.M., Morgese F., Muto P., Palmieri G., Patuzzo R., Pellacani G., Picciotto F., Pigozzo J., Pimpinelli N., Poletti P., Repetto L., Rinaldi G., Rubegni P., Rubino G., Spagnolo F., Tagliaferri L., Tanda E., Tronconi M.C., Tucci M., Valente M., Vincenzi B., and Zalaudek I.

Subjects
Pharmacology, Cancer Research, Skin Neoplasms, Immunology, Carcinoma, Carcinoma, Merkel Cell, Oncology, Italy, Merkel cell polyomavirus, Merkel Cell, Molecular Medicine, Immunology and Allergy, immunotherapy, radiotherapy, skin neoplasms, Humans, Immunotherapy
Abstract

Merkel cell carcinoma (MCC) is a rare and highly aggressive cutaneous neuroendocrine carcinoma. The MCC incidence rate has rapidly grown over the last years, with Italy showing the highest increase among European countries. This malignancy has been the focus of active scientific research over the last years, focusing mainly on pathogenesis, new therapeutic trials and diagnosis. A national expert board developed 28 consensus statements that delineated the evolution of disease management and highlighted the paradigm shift towards the use of immunological strategies, which were then presented to a national MCC specialists panel for review. Sixty-five panelists answered both rounds of the questionnaire. The statements were divided into five areas: a high level of agreement was reached in the area of guidelines and multidisciplinary management, even if in real life the multidisciplinary team was not always represented by all the specialists. In the diagnostic pathway area, imaging played a crucial role in diagnosis and initial staging, planning for surgery or radiation therapy, assessment of treatment response and surveillance of recurrence and metastases. Concerning diagnosis, the usefulness of Merkel cell polyomavirus is recognized, but the agreement and consensus regarding the need for cytokeratin evaluation appears greater. Regarding the areas of clinical management and follow-up, patients with MCC require customized treatment. There was a wide dispersion of results and the suggestion to increase awareness about the adjuvant radiation therapy. The panelists unanimously agreed that the information concerning avelumab provided by the JAVELIN Merkel 200 study is adequate and reliable and that the expanded access program data could have concrete clinical implications. An immunocompromised patient with advanced MCC can be treated with immunotherapy after multidisciplinary risk/benefit assessment, as evidenced by real-world analysis and highlighted in the guidelines. A very high consensus regarding the addition of radiotherapy to treat the ongoing focal progression of immunotherapy was observed. This paper emphasizes the importance of collaboration and communication among the interprofessional team members and encourages managing patients with MCC within dedicated multidisciplinary teams. New insights in the treatment of this challenging cancer needs the contribution of many and different experts.

Published
2022

50. A retrospective analysis of the correlation between functional imaging and clinical outcomes in grade 3 neuroendocrine tumors (Nets g3)

Author

Laffi, A, Colandrea, M, Buonsanti, G, Frassoni, S, Bagnardi, V, Spada, F, Pisa, E, Barberis, M, Rubino, M, Grana, C, Ceci, F, Fazio, N, Laffi A., Colandrea M., Buonsanti G., Frassoni S., Bagnardi V., Spada F., Pisa E., Barberis M., Rubino M., Grana C. M., Ceci F., Fazio N., Laffi, A, Colandrea, M, Buonsanti, G, Frassoni, S, Bagnardi, V, Spada, F, Pisa, E, Barberis, M, Rubino, M, Grana, C, Ceci, F, Fazio, N, Laffi A., Colandrea M., Buonsanti G., Frassoni S., Bagnardi V., Spada F., Pisa E., Barberis M., Rubino M., Grana C. M., Ceci F., and Fazio N.

Abstract

Grade 3 (G3) neuroendocrine tumors (NETs) are a novel category among digestive neuroen-docrine neoplasms, characterized by Ki-67 >20% and a well-differentiated morphology, presenting high intra-tumor heterogeneity. We aimed to explore the role of dual-tracer PET imaging (68 Gallium (Ga)-DOTATOC and18 Fluorodeoxyglucose (FDG)) as overall survival (OS) predictor in NET G3 patients. We performed a retrospective analysis in NET G3 patients treated at our institution between 2003 and 2021. Accordingly, 30 NET G3 patients were analyzed.68 Ga-DOTA-TOC and18 F-FDG uptake were assessed by tumor/non-tumor (T-nonT) ratio. We reported a slightly better OS for patients with ≥75% concordance between68 Ga-DOTA-TOC and18 F-FDG PET/CT (p = 0.42). Among patients with discordant functional imaging, we reported a better 5-y OS rate for patients with a prevalent68 Ga-DOTATOC vs.18 F-FDG PET/CT (p = 0.016). In positive18 F-FDG PET/CT cases, we reported a better OS for <4 vs. ≥4 T/non-T ratio (p = 0.021). Among upfront-NET G3 patients with concordant exams, 5-y OS rate was 83.3% (95% CI: 27.3–97.5). Among patients with discordant exams, 5-y OS rate was 81.3% (52.5–93.5), 100% for those with prevalent receptor expression, and 50% (11.1–80.4) for those with prevalent18 F-FDG uptake. Our findings suggest that dual-tracer PET/CT can be considered as a predictor of patient outcome, able to stratify NET G3 patients with poorer prognosis.

Published
2021

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