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3. The relationship between uremic toxins and symptoms in older men and women with advanced chronic kidney disease

Author

Massy Z. A., Chesnaye N. C., Larabi I. A., Dekker F. W., Evans M., Caskey F. J., Torino C., Porto G., Szymczak M., Drechsler C., Wanner C., Jager K. J., Alvarez J. C., Schneider A., Torp A., Iwig B., Perras B., Marx C., Blaser C., Emde C., Krieter D., Fuchs D., Irmler E., Platen E., Schmidt-Gurtler H., Schlee H., Naujoks H., Schlee I., Casar S., Beige J., Rothele J., Mazur J., Hahn K., Blouin K., Neumeier K., Anding-Rost K., Schramm L., Hopf M., Wuttke N., Frischmuth N., Ichtiaris P., Kirste P., Schulz P., Aign S., Biribauer S., Manan S., Roser S., Heidenreich S., Palm S., Schwedler S., Delrieux S., Renker S., Schattel S., Stephan T., Schmiedeke T., Weinreich T., Leimbach T., Stovesand T., Bahner U., Seeger W., Cupisti A., Sagliocca A., Ferraro A., Mele A., Naticchia A., Cosaro A., Ranghino A., Stucchi A., Pignataro A., De Blasio A., Pani A., Tsalouichos A., Bellasi A., Raffaele Di Iorio B., Butti A., Abaterusso C., Somma C., D'Alessandro C., Zullo C., Pozzi C., Bergamo D., Ciurlino D., Motta D., Russo D., Favaro E., Vigotti F., Ansali F., Conte F., Cianciotta F., Giacchino F., Cappellaio F., Pizzarelli F., Greco G., Bigatti G., Marinangeli G., Cabiddu G., Fumagalli G., Caloro G., Piccoli G., Capasso G., Gambaro G., Tognarelli G., Bonforte G., Conte G., Toscano G., Del Rosso G., Capizzi I., Baragetti I., Oldrizzi L., Gesualdo L., Biancone L., Magnano M., Ricardi M., Di Bari M., Laudato M., Luisa Sirico M., Ferraresi M., Provenzano M., Malaguti M., Palmieri N., Murrone P., Cirillo P., Dattolo P., Acampora P., Nigro R., Boero R., Scarpioni R., Sicoli R., Malandra R., Savoldi S., Bertoli S., Borrelli S., Maxia S., Maffei S., Mangano S., Cicchetti T., Rappa T., Palazzo V., De Simone W., Schrander A., Van Dam B., Siegert C., Gaillard C., Beerenhout C., Verburgh C., Janmaat C., Hoogeveen E., Hoorn E., Boots J., Boom H., Eijgenraam J. -W., Kooman J., Rotmans J., Vogt L., Raasveld M., Vervloet M., Van Buren M., Van Diepen M., Leurs P., Voskamp P., Blankestijn P., Van Esch S., Boorsma S., Berger S., Konings C., Aydin Z., Musiala A., Szymczak A., Olczyk E., Augustyniak-Bartosik H., Miskowiec-Wisniewska I., Manitius J., Pondel J., Jedrzejak K., Nowanska K., Nowak L., Durlik M., Dorota S., Nieszporek T., Heleniak Z., Jonsson A., Blom A. -L., Rogland B., Wallquist C., Vargas D., Dimeny E., Sundelin F., Uhlin F., Welander G., Bascaran Hernandez I., Grontoft K. -C., Stendahl M., Svensson M., Heimburger O., Kashioulis P., Melander S., Almquist T., Jensen U., Woodman A., McKeever A., Ullah A., McLaren B., Harron C., Barrett C., O'Toole C., Summersgill C., Geddes C., Glowski D., McGlynn D., Sands D., Roy G., Hirst G., King H., McNally H., Masri-Senghor H., Murtagh H., Rayner H., Turner J., Wilcox J., Berdeprado J., Wong J., Banda J., Jones K., Haydock L., Wilkinson L., Carmody M., Weetman M., Joinson M., Dutton M., Matthews M., Morgan N., Bleakley N., Cockwell P., Roderick P., Mason P., Kalra P., Sajith R., Chapman S., Navjee S., Crosbie S., Brown S., Tickle S., Mathavakkannan S., Kuan Y., Massy, Z. A., Chesnaye, N. C., Larabi, I. A., Dekker, F. W., Evans, M., Caskey, F. J., Torino, C., Porto, G., Szymczak, M., Drechsler, C., Wanner, C., Jager, K. J., Alvarez, J. C., Schneider, A., Torp, A., Iwig, B., Perras, B., Marx, C., Blaser, C., Emde, C., Krieter, D., Fuchs, D., Irmler, E., Platen, E., Schmidt-Gurtler, H., Schlee, H., Naujoks, H., Schlee, I., Casar, S., Beige, J., Rothele, J., Mazur, J., Hahn, K., Blouin, K., Neumeier, K., Anding-Rost, K., Schramm, L., Hopf, M., Wuttke, N., Frischmuth, N., Ichtiaris, P., Kirste, P., Schulz, P., Aign, S., Biribauer, S., Manan, S., Roser, S., Heidenreich, S., Palm, S., Schwedler, S., Delrieux, S., Renker, S., Schattel, S., Stephan, T., Schmiedeke, T., Weinreich, T., Leimbach, T., Stovesand, T., Bahner, U., Seeger, W., Cupisti, A., Sagliocca, A., Ferraro, A., Mele, A., Naticchia, A., Cosaro, A., Ranghino, A., Stucchi, A., Pignataro, A., De Blasio, A., Pani, A., Tsalouichos, A., Bellasi, A., Raffaele Di Iorio, B., Butti, A., Abaterusso, C., Somma, C., D'Alessandro, C., Zullo, C., Pozzi, C., Bergamo, D., Ciurlino, D., Motta, D., Russo, D., Favaro, E., Vigotti, F., Ansali, F., Conte, F., Cianciotta, F., Giacchino, F., Cappellaio, F., Pizzarelli, F., Greco, G., Bigatti, G., Marinangeli, G., Cabiddu, G., Fumagalli, G., Caloro, G., Piccoli, G., Capasso, G., Gambaro, G., Tognarelli, G., Bonforte, G., Conte, G., Toscano, G., Del Rosso, G., Capizzi, I., Baragetti, I., Oldrizzi, L., Gesualdo, L., Biancone, L., Magnano, M., Ricardi, M., Di Bari, M., Laudato, M., Luisa Sirico, M., Ferraresi, M., Provenzano, M., Malaguti, M., Palmieri, N., Murrone, P., Cirillo, P., Dattolo, P., Acampora, P., Nigro, R., Boero, R., Scarpioni, R., Sicoli, R., Malandra, R., Savoldi, S., Bertoli, S., Borrelli, S., Maxia, S., Maffei, S., Mangano, S., Cicchetti, T., Rappa, T., Palazzo, V., De Simone, W., Schrander, A., Van Dam, B., Siegert, C., Gaillard, C., Beerenhout, C., Verburgh, C., Janmaat, C., Hoogeveen, E., Hoorn, E., Boots, J., Boom, H., Eijgenraam, J. -W., Kooman, J., Rotmans, J., Vogt, L., Raasveld, M., Vervloet, M., Van Buren, M., Van Diepen, M., Leurs, P., Voskamp, P., Blankestijn, P., Van Esch, S., Boorsma, S., Berger, S., Konings, C., Aydin, Z., Musiala, A., Szymczak, A., Olczyk, E., Augustyniak-Bartosik, H., Miskowiec-Wisniewska, I., Manitius, J., Pondel, J., Jedrzejak, K., Nowanska, K., Nowak, L., Durlik, M., Dorota, S., Nieszporek, T., Heleniak, Z., Jonsson, A., Blom, A. -L., Rogland, B., Wallquist, C., Vargas, D., Dimeny, E., Sundelin, F., Uhlin, F., Welander, G., Bascaran Hernandez, I., Grontoft, K. -C., Stendahl, M., Svensson, M., Heimburger, O., Kashioulis, P., Melander, S., Almquist, T., Jensen, U., Woodman, A., Mckeever, A., Ullah, A., Mclaren, B., Harron, C., Barrett, C., O'Toole, C., Summersgill, C., Geddes, C., Glowski, D., Mcglynn, D., Sands, D., Roy, G., Hirst, G., King, H., Mcnally, H., Masri-Senghor, H., Murtagh, H., Rayner, H., Turner, J., Wilcox, J., Berdeprado, J., Wong, J., Banda, J., Jones, K., Haydock, L., Wilkinson, L., Carmody, M., Weetman, M., Joinson, M., Dutton, M., Matthews, M., Morgan, N., Bleakley, N., Cockwell, P., Roderick, P., Mason, P., Kalra, P., Sajith, R., Chapman, S., Navjee, S., Crosbie, S., Brown, S., Tickle, S., Mathavakkannan, S., Kuan, Y., Nephrology, ACS - Diabetes & metabolism, Medical Informatics, APH - Methodology, APH - Aging & Later Life, APH - Quality of Care, APH - Global Health, APH - Health Behaviors & Chronic Diseases, and ACS - Pulmonary hypertension & thrombosis

Subjects
Transplantation, Nephrology, uremic toxins, CKD, symptoms, symptom, elderly
Abstract

Background Patients with stage 4/5 chronic kidney disease (CKD) suffer from various symptoms. The retention of uremic solutes is thought to be associated with those symptoms. However, there are relatively few rigorous studies on the potential links between uremic toxins and symptoms in patients with CKD. Methods The EQUAL study is an ongoing observational cohort study of non-dialyzed patients with stage 4/5 CKD. EQUAL patients from Germany, Poland, Sweden and the UK were included in the present study (n = 795). Data and symptom self-report questionnaires were collected between April 2012 and September 2020. Baseline uric acid and parathyroid hormone and 10 uremic toxins were quantified. We tested the association between uremic toxins and symptoms and adjusted P-values for multiple testing. Results Symptoms were more frequent in women than in men with stage 4/5 CKD, while levels of various uremic toxins were higher in men. Only trimethylamine N-oxide (TMAO; positive association with fatigue), p-cresyl sulfate (PCS) with constipation and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (negative association with shortness of breath) demonstrated moderately strong associations with symptoms in adjusted analyses. The association of phenylacetylglutamine with shortness of breath was consistent in both sexes, although it only reached statistical significance in the full population. In contrast, TMAO (fatigue) and PCS and phenylacetylglutamine (constipation) were only associated with symptoms in men, who presented higher serum levels than women. Conclusion Only a limited number of toxins were associated with symptoms in persons with stage 4/5 CKD. Other uremic toxins, uremia-related factors or psychosocial factors not yet explored might contribute to symptom burden.

Published
2022

4. 227P Peripheral blood lymphocyte counts predict clinical outcomes in patients with hormone receptor-positive HER2-negative advanced breast cancer treated with CDK4/6 inhibitors

Author

Vernieri, C., primary, Zattarin, E., additional, Mariani, L., additional, Menichetti, A., additional, Leporati, R., additional, Ligorio, F., additional, Fuca, G., additional, Lobefaro, R., additional, Griguolo, G., additional, Sirico, M., additional, Bernocchi, O., additional, Marra, A., additional, Agostinetto, E., additional, Jacobs, F., additional, di Mauro, P., additional, Curigliano, G., additional, Pedersini, R., additional, Losurdo, A., additional, Generali, D., additional, and Dieci, M.V., additional

Published
2022
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5. Correction to: Treatment of metabolic acidosis with sodium bicarbonate delays progression of chronic kidney disease: the UBI Study (Journal of Nephrology, (2019), 32, 6, (989-1001), 10.1007/s40620-019-00656-5)

Author

Di Iorio B. R., Bellasi A., Raphael K. L., Santoro D., Aucella F., Garofano L., Ceccarelli M., Di Lullo L., Capolongo G., Di Iorio M., Guastaferro P., Capasso G., Barbera V., Bruzzese A., Canale V., Conte G., Crozza V., Cupisti A., DeBlasio A., DeSimone E., DiMicco L., Fiorini F., Grifa R., Nardone R., Piemontese M., Sirico M. L., Vitale F., Di Iorio, B. R., Bellasi, A., Raphael, K. L., Santoro, D., Aucella, F., Garofano, L., Ceccarelli, M., Di Lullo, L., Capolongo, G., Di Iorio, M., Guastaferro, P., Capasso, G., Barbera, V., Bruzzese, A., Canale, V., Conte, G., Crozza, V., Cupisti, A., Deblasio, A., Desimone, E., Dimicco, L., Fiorini, F., Grifa, R., Nardone, R., Piemontese, M., Sirico, M. L., and Vitale, F.

Abstract

It occurred to us that a simple but significant calculation error was made in Table 2 in the dose of bicarbonate administered. Indeed, contrary to what reported in Table 2, the dose of sodium bicarbonate administered during study was: Mean (SD) SB administered dose (mmol/kg bw/day) We sincerely apologize for the inconvenience. The updated Table 2 has been copied below: (Table presented.).

Published
2020

6. Canakinumab as treatment for COVID-19-related pneumonia: A prospective case-control study

Author

Generali, Daniele, Bosio, Giacomo, Malberti, F., Cuzzoli, A., Testa, S., Romanini, L., Fioravanti, A., Morandini, Piero Angelo, Pianta, L., Giannotti, G., Viola, E. M., Giorgi-Pierfranceschi, M., Foramitti, M., Tira, R. A., Zangrandi, I., Chiodelli, Giulia, Machiavelli, A., Cappelletti, M. R., Giossi, A., De Giuli, V., Costanzi, Carla, Campana, C., Bernocchi, O., Sirico, M., Zoncada, A., Molteni, A., Venturini, Sergio, Giudici, F., Scaltriti, M., Pan, A., Generali D. (ORCID:0000-0003-2480-3855), Bosio G., Morandini A., Chiodelli G., Costanzi C., Venturini S. (ORCID:0000-0002-6574-3337), Generali, Daniele, Bosio, Giacomo, Malberti, F., Cuzzoli, A., Testa, S., Romanini, L., Fioravanti, A., Morandini, Piero Angelo, Pianta, L., Giannotti, G., Viola, E. M., Giorgi-Pierfranceschi, M., Foramitti, M., Tira, R. A., Zangrandi, I., Chiodelli, Giulia, Machiavelli, A., Cappelletti, M. R., Giossi, A., De Giuli, V., Costanzi, Carla, Campana, C., Bernocchi, O., Sirico, M., Zoncada, A., Molteni, A., Venturini, Sergio, Giudici, F., Scaltriti, M., Pan, A., Generali D. (ORCID:0000-0003-2480-3855), Bosio G., Morandini A., Chiodelli G., Costanzi C., and Venturini S. (ORCID:0000-0002-6574-3337)

Abstract

Objectives: Canakinumab is an IL-1? antibody that neutralises the activity of IL-1?. This study examined the efficacy and safety of canakinumab in patients with moderate COVID-19-related pneumonia. Design: This study aimed to evaluate the reduction in duration of hospitalisation with adequate oxygen status. Forty-eight patients with moderate COVID-19-related pneumonia were asked to participate in the prospective case-control study: 33 patients (cases) signed informed consent and received canakinumab (Cohort 1) and 15 patients (Controls) refused to receive the experimental drug and received institutional standard of care (Cohort 2). Results: Hospital discharge within 21 days was seen in 63% of patients in Cohort 1 vs. 0% in Cohort 2 (median 14 vs. 26 days, respectively; p < 0.001). There was significant clinical improvement in ventilation regimes following administration of canakinumab compared with Cohort 2 (Stuart-Maxwell test for paired data, p < 0.001). Patients treated with canakinumab experienced a significant increase in PaO2: FiO2 (p < 0.001) and reduction in lung damage by CT (p = 0.01), along with significant decreases in immune/inflammation markers that were not observed in Cohort 2. Only mild side-effects were seen in patients treated with canakinumab; survival at 60 days was 90.0% (95% CI 71.9?96.7) in patients treated with canakinumab and 73.3% (95% CI 43.6?89.1) for Cohort 2. Conclusions: Treatment with canakinumab in patients with COVID-19-related pneumonia rapidly restored normal oxygen status, decreased the need for invasive mechanical ventilation, and was associated with earlier hospital discharge and favourable prognosis versus standard of care. ? 2021 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc

Published
2021

7. Treatment of metabolic acidosis with sodium bicarbonate delays progression of chronic kidney disease: the UBI Study

Author

Di Iorio, B. R., Bellasi, A., Raphael, K. L., Santoro, D., Aucella, F., Garofano, L., Ceccarelli, M., Di Lullo, L., Capolongo, G., Di Iorio, M., Guastaferro, P., Capasso, G., Barbera, V., Bruzzese, A., Canale, V., Conte, G., Crozza, V., Cupisti, A., Deblasio, A., Desimone, E., Dimicco, L., Fiorini, F., Grifa, R., Nardone, R., Piemontese, M., Sirico, M. L., Vitale, F., Di Iorio, B. R., Bellasi, A., Raphael, K. L., Santoro, D., Aucella, F., Garofano, L., Ceccarelli, M., Di Lullo, L., Capolongo, G., Di Iorio, M., Guastaferro, P., Capasso, G., Barbera, V., Bruzzese, A., Canale, V., Conte, G., Crozza, V., Cupisti, A., Deblasio, A., Desimone, E., Dimicco, L., Fiorini, F., Grifa, R., Nardone, R., Piemontese, M., Sirico, M. L., and Vitale, F.

Subjects
Nephrology, Male, medicine.medical_specialty, medicine.medical_treatment, Renal function, Kidney, Gastroenterology, chemistry.chemical_compound, Internal medicine, Chronic kidney disease, medicine, Humans, Metabolic acidosis, Sodium bicarbonate, Renal replacement therapy, Renal Insufficiency, Chronic, Dialysis, Aged, Creatinine, Metabolic acidosi, business.industry, Correction, medicine.disease, Survival Rate, Acidosi, chemistry, Italy, Disease Progression, Female, business, Acidosis, Kidney disease, Glomerular Filtration Rate, Human
Abstract

Background Metabolic acidosis is associated with accelerated progression of chronic kidney disease (CKD). Whether treatment of metabolic acidosis with sodium bicarbonate improves kidney and patient survival in CKD is unclear. Methods We conducted a randomized (ratio 1:1). open-label, controlled trial (NCT number: NCT01640119. www.clinicaltrials.gov) to determine the effect in patients with CKD stage 3–5 of treatment of metabolic acidosis with sodium bicarbonate (SB) on creatinine doubling (primary endpoint), all-cause mortality and time to renal replacement therapy compared to standard care (SC) over 36-months. Parametric, non-parametric tests and survival analyses were used to assess the effect of SB on these outcomes. Results A total of 376 and 364 individuals with mean (SD) age 67.8 (14.9) years, creatinine clearance 30 (12) ml/min, and serum bicarbonate 21.5 (2.4) mmol/l were enrolled in SB and SC, respectively. Mean (SD) follow-up was 29.6 (9.8) vs 30.3 (10.7) months in SC and SB. respectively. The mean (SD) daily doses of SB was 1.13 (0.10). 1.12 (0.11). and 1.09 (0.12) mmol/kg*bw/day in the first, second and third year of follow-up, respectively. A total of 87 participants reached the primary endpoint [62 (17.0%) in SC vs 25 (6.6%) in SB, p Conclusion In persons with CKD 3–5 without advanced stages of chronic heart failure, treatment of metabolic acidosis with sodium bicarbonate is safe and improves kidney and patient survival.

Published
2019

9. Immune system and angiogenesis-related potential surrogate biomarkers of response to everolimus-based treatment in hormone receptor-positive breast cancer: an exploratory study

Author

Schettini, F, Sobhani, N, Ianza, A, Triulzi, T, Molteni, A, Lazzari, MC, Strina, C, Milani, M, Corona, SP, Sirico, M, Bernocchi, O, Giudici, F, Cappelletti, MR, Ciruelos, E, Jerusalem, G, Loi, S, Fox, SB, Generali, D, Schettini, F, Sobhani, N, Ianza, A, Triulzi, T, Molteni, A, Lazzari, MC, Strina, C, Milani, M, Corona, SP, Sirico, M, Bernocchi, O, Giudici, F, Cappelletti, MR, Ciruelos, E, Jerusalem, G, Loi, S, Fox, SB, and Generali, D

Abstract

PURPOSE: mTOR inhibitor everolimus is used for hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (mBC). No reliable predictive biomarker of response is available. Following evidences from other solid tumors, we aimed to assess the association between treatment-associated immune system features and everolimus activity. METHODS: We retrospectively explored a correlation with the therapeutic activity of everolimus and tumor-associated immune pathways with ingenuity pathway analysis (IPA), neutrophil-to-lymphocyte ratio (NLR), circulating lymphocytes, and endothelial cells (CECs) in 3 different HR+ mBC studies, including the BALLET phase IIIb study. RESULTS: The circulating levels of CD3+/CD8+, CD3+/CD4+, and overall T lymphocytes were higher in responders versus non-responders at baseline (p = 0.017, p < 0.001, p = 0.034) and after treatment (p = 0.01, p = 0.003, p = 0.023). Reduced CECs, a tumor neoangiogenesis marker, were observed in responders after treatment (p < 0.001). Patients with low NLR (≤ 4.4) showed a better progression-free survival compared to patients with high NLR (> 4.4) (p = 0.01). IPA showed that the majority of immunity-related genes were found upregulated in responders compared to non-responders before treatment, but not after. CONCLUSIONS: Lymphocytes subpopulations, CECs and NLR could be interesting biomarkers predictive of response to everolimus-based regimens, potentially useful in daily clinical practice to select/monitor everolimus-based treatment in mBC. Further studies to confirm such hypotheses are warranted.

Published
2020

10. Impact of BMI on the outcome of metastatic breast cancer patients treated with everolimus: A retrospective exploratory analysis of the BALLET study

Author

Corona, S., primary, Giudici, F., additional, Jerusalem, G., additional, Ciruelos, E., additional, Strina, C., additional, Sirico, M., additional, Bernocchi, O., additional, Milani, M., additional, Dester, M., additional, Ziglioli, N., additional, Barbieri, G., additional, Cervoni, V., additional, Montemurro, F., additional, and Generali, D., additional

Published
2020
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11. 300P Association between the neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios and efficacy of CDK 4/6 inhibitors in advanced breast cancer: The observational multicenter Italian PALMARES study

Author

Zattarin, E., primary, Fabbroni, C., additional, Ligorio, F., additional, Marra, A., additional, Corti, C., additional, Bernocchi, O., additional, Sirico, M., additional, Generali, D.G., additional, Curigliano, G., additional, Bianchi, G., additional, Capri, G., additional, Rivoltini, L., additional, De Braud, F.G.M., additional, and Vernieri, C., additional

Published
2020
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12. ΔKi67 proliferation index as independent predictive and prognostic factor of outcome in luminal breast cancer: data from neoadjuvant letrozole-based treatment

Author

Ianza, A, primary, Giudici, F, additional, Pinello, C, additional, Corona, SP, additional, Strina, C, additional, Bernocchi, O, additional, Bortul, M, additional, Milani, M, additional, Sirico, M, additional, Allevi, G, additional, Aguggini, S, additional, Cocconi, A, additional, Azzini, C, additional, Dester, M, additional, Cervoni, V, additional, Bottini, A, additional, Cappelletti, M, additional, and Generali, D, additional

Published
2020
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13. Pazienti con insufficienza renale cronica:risultati dallo studio Nefrodata®

Author

Cupisti, A., Bottai, A., Bellizzi, V., Brunori, G., Cianciaruso, B., De Nicola, L., Oldrizzi, L., Quintaliani, G., Santoro, D., Rapisarda, Francesco, Di Iorio, B., NefroData Study Group: Loreto Gesualdo, Castellino, Dea Saulle P., Fatuzzo, Pasquale Mario, Bonofiglio, F. Rapisarda R., Lofaro, D., Rosati, F. Armentano A., Coppola, G. Rosso S. Chimienti S., De Blasio, Cesaro A. L. Bozzoli A., Sirico, M., and Di Micco, L.

Subjects
malattia renale cronica, dieta, ckd, epidemiologia, terapia, ckd, dieta, epidemiologia, malattia renale cronica, terapia
Published
2015

14. Daily dialysis reduces pulse wave velocity in chronic haemodialysis patients

Author

Di Micco, L., Torraca, S., Sirico, M. L., Morrone, L., Bellasi, A., Di Iorio, B., RUSSO, DOMENICO, Di Micco, L., Torraca, S., Sirico, M. L., Morrone, L., Bellasi, A., Russo, Domenico, and Di Iorio, B.

Abstract

Introduction. We have already demonstrated that in chronic HD patients the cyclic variations in both hydration status and blood pressure are responsible for changes in Pulse Wave Velocity (PWV); and that the cyclic variation of PWV influences mortality in dialysis patients. The aim of this study is to verify if is possible reduce the PWV modifying the three time a week dialysis to daily dialysis. Material and Methods. This is a controlled, randomized, cross-over study. We studied 60 oligo-anuric (urinary output

Published
2011

18. Predicting Kidney Failure, Cardiovascular Disease and Death in Advanced CKD Patients

Author

Chava L. Ramspek, Rosemarijn Boekee, Marie Evans, Olof Heimburger, Charlotte M. Snead, Fergus J. Caskey, Claudia Torino, Gaetana Porto, Maciej Szymczak, Magdalena Krajewska, Christiane Drechsler, Christoph Wanner, Nicholas C. Chesnaye, Kitty J. Jager, Friedo W. Dekker, Maarten G.J. Snoeijs, Joris I. Rotmans, Merel van Diepen, Adamasco Cupisti, Adelia Sagliocca, Alberto Ferraro, Aleksandra Musiała, Alessandra Mele, Alessandro Naticchia, Alex Còsaro, Alistair Woodman, Andrea Ranghino, Andrea Stucchi, Andreas Jonsson, Andreas Schneider, Angelo Pignataro, Anita Schrander, Anke Torp, Anna McKeever, Anna Szymczak, Anna-Lena Blom, Antonella De Blasio, Antonello Pani, Aris Tsalouichos, Asad Ullah, Barbara McLaren, Bastiaan van Dam, Beate Iwig, Bellasi Antonio, Biagio Raffaele Di Iorio, Björn Rogland, Boris Perras, Butti Alessandra, Camille Harron, Carin Wallquist, Carl Siegert, Carla Barrett, Carlo Gaillard, Carlo Garofalo, Cataldo Abaterusso, Charles Beerenhout, Charlotte O'Toole, Chiara Somma, Christian Marx, Christina Summersgill, Christof Blaser, Claudia D'alessandro, Claudia Emde, Claudia Zullo, Claudio Pozzi, Colin Geddes, Cornelis Verburgh, Daniela Bergamo, Daniele Ciurlino, Daria Motta, Deborah Glowski, Deborah McGlynn, Denes Vargas, Detlef Krieter, Domenico Russo, Dunja Fuchs, Dympna Sands, Ellen Hoogeveen, Ellen Irmler, Emöke Dimény, Enrico Favaro, Eva Platen, Ewelina Olczyk, Ewout Hoorn, Federica Vigotti, Ferruccio Ansali, Ferruccio Conte, Francesca Cianciotta, Francesca Giacchino, Francesco Cappellaio, Francesco Pizzarelli, Fredrik Sundelin, Fredrik Uhlin, Gaetano Greco, Geena Roy, Giada Bigatti, Giancarlo Marinangeli, Gianfranca Cabiddu, Gillian Hirst, Giordano Fumagalli, Giorgia Caloro, Giorgina Piccoli, Giovanbattista Capasso, Giovanni Gambaro, Giuliana Tognarelli, Giuseppe Bonforte, Giuseppe Conte, Giuseppe Toscano, Goffredo Del Rosso, Gunilla Welander, Hanna Augustyniak-Bartosik, Hans Boots, Hans Schmidt-Gürtler, Hayley King, Helen McNally, Hendrik Schlee, Henk Boom, Holger Naujoks, Houda Masri-Senghor, Hugh Murtagh, Hugh Rayner, Ilona Miśkowiec-Wiśniewska, Ines Schlee, Irene Capizzi, Isabel Bascaran Hernandez, Ivano Baragetti, Jacek Manitius, Jane Turner, Jan-Willem Eijgenraam, Jeroen Kooman, Joachim Beige, Joanna Pondel, Joanne Wilcox, Jocelyn Berdeprado, Jochen Röthele, Jonathan Wong, Joris Rotmans, Joyce Banda, Justyna Mazur, Kai Hahn, Kamila Jędrzejak, Katarzyna Nowańska, Katja Blouin, Katrin Neumeier, Kirsteen Jones, Kirsten Anding-Rost, Knut-Christian Gröntoft, Lamberto Oldrizzi, Lesley Haydock, Liffert Vogt, Lily Wilkinson, Loreto Gesualdo, Lothar Schramm, Luigi Biancone, Łukasz Nowak, Maarten Raasveld, Magdalena Durlik, Manuela Magnano, Marc Vervloet, Marco Ricardi, Margaret Carmody, Maria Di Bari, Maria Laudato, Maria Luisa Sirico, Maria Stendahl, Maria Svensson, Maria Weetman, Marjolijn van Buren, Martin Joinson, Martina Ferraresi, Mary Dutton, Michael Matthews, Michele Provenzano, Monika Hopf, Moreno Malaguti, Nadja Wuttke, Neal Morgan, Nicola Palmieri, Nikolaus Frischmuth, Nina Bleakley, Paola Murrone, Paul Cockwell, Paul Leurs, Paul Roderick, Pauline Voskamp, Pavlos Kashioulis, Pawlos Ichtiaris, Peter Blankestijn, Petra Kirste, Petra Schulz, Phil Mason, Philip Kalra, Pietro Cirillo, Pietro Dattolo, Pina Acampora, Rincy Sajith, Rita Nigro, Roberto Boero, Roberto Scarpioni, Rosa Sicoli, Rosella Malandra, Sabine Aign, Sabine Cäsar, Sadie van Esch, Sally Chapman, Sandra Biribauer, Santee Navjee, Sarah Crosbie, Sharon Brown, Sheila Tickle, Sherin Manan, Silke Röser, Silvana Savoldi, Silvio Bertoli, Silvio Borrelli, Siska Boorsma, Stefan Heidenreich, Stefan Melander, Stefania Maxia, Stefano Maffei, Stefano Mangano, Stephanie Palm, Stijn Konings, Suresh Mathavakkannan, Susanne Schwedler, Sylke Delrieux, Sylvia Renker, Sylvia Schättel, Szyszkowska Dorota, Teresa Cicchetti, Teresa Nieszporek, Theresa Stephan, Thomas Schmiedeke, Thomas Weinreich, Til Leimbach, Tiziana Rappa, Tora Almquist, Torsten Stövesand, Udo Bahner, Ulrika Jensen, Valentina Palazzo, Walter De Simone, Wolfgang Seeger, Ying Kuan, Zbigniew Heleniak, Zeynep Aydin, Vascular Surgery, MUMC+: MA Med Staf Spec Vaatchirurgie (9), RS: Carim - V03 Regenerative and reconstructive medicine vascular disease, Ramspek, C. L., Boekee, R., Evans, M., Heimburger, O., Snead, C. M., Caskey, F. J., Torino, C., Porto, G., Szymczak, M., Krajewska, M., Drechsler, C., Wanner, C., Chesnaye, N. C., Jager, K. J., Dekker, F. W., Snoeijs, M. G. J., Rotmans, J. I., van Diepen, M., Cupisti, A., Sagliocca, A., Ferraro, A., Musiala, A., Mele, A., Naticchia, A., Cosaro, A., Woodman, A., Ranghino, A., Stucchi, A., Jonsson, A., Schneider, A., Pignataro, A., Schrander, A., Torp, A., Mckeever, A., Szymczak, A., Blom, A. -L., De Blasio, A., Pani, A., Tsalouichos, A., Ullah, A., Mclaren, B., van Dam, B., Iwig, B., Antonio, B., Di Iorio, B. R., Rogland, B., Perras, B., Alessandra, B., Harron, C., Wallquist, C., Siegert, C., Barrett, C., Gaillard, C., Garofalo, C., Abaterusso, C., Beerenhout, C., O'Toole, C., Somma, C., Marx, C., Summersgill, C., Blaser, C., D'Alessandro, C., Emde, C., Zullo, C., Pozzi, C., Geddes, C., Verburgh, C., Bergamo, D., Ciurlino, D., Motta, D., Glowski, D., Mcglynn, D., Vargas, D., Krieter, D., Russo, D., Fuchs, D., Sands, D., Hoogeveen, E., Irmler, E., Dimeny, E., Favaro, E., Platen, E., Olczyk, E., Hoorn, E., Vigotti, F., Ansali, F., Conte, F., Cianciotta, F., Giacchino, F., Cappellaio, F., Pizzarelli, F., Sundelin, F., Uhlin, F., Greco, G., Roy, G., Bigatti, G., Marinangeli, G., Cabiddu, G., Hirst, G., Fumagalli, G., Caloro, G., Piccoli, G., Capasso, G., Gambaro, G., Tognarelli, G., Bonforte, G., Conte, G., Toscano, G., Del Rosso, G., Welander, G., Augustyniak-Bartosik, H., Boots, H., Schmidt-Gurtler, H., King, H., Mcnally, H., Schlee, H., Boom, H., Naujoks, H., Masri-Senghor, H., Murtagh, H., Rayner, H., Miskowiec-Wisniewska, I., Schlee, I., Capizzi, I., Hernandez, I. B., Baragetti, I., Manitius, J., Turner, J., Eijgenraam, J. -W., Kooman, J., Beige, J., Pondel, J., Wilcox, J., Berdeprado, J., Rothele, J., Wong, J., Rotmans, J., Banda, J., Mazur, J., Hahn, K., Jedrzejak, K., Nowanska, K., Blouin, K., Neumeier, K., Jones, K., Anding-Rost, K., Grontoft, K. -C., Oldrizzi, L., Haydock, L., Vogt, L., Wilkinson, L., Gesualdo, L., Schramm, L., Biancone, L., Nowak, L., Raasveld, M., Durlik, M., Magnano, M., Vervloet, M., Ricardi, M., Carmody, M., Di Bari, M., Laudato, M., Sirico, M. L., Stendahl, M., Svensson, M., Weetman, M., van Buren, M., Joinson, M., Ferraresi, M., Dutton, M., Matthews, M., Provenzano, M., Hopf, M., Malaguti, M., Wuttke, N., Morgan, N., Palmieri, N., Frischmuth, N., Bleakley, N., Murrone, P., Cockwell, P., Leurs, P., Roderick, P., Voskamp, P., Kashioulis, P., Ichtiaris, P., Blankestijn, P., Kirste, P., Schulz, P., Mason, P., Kalra, P., Cirillo, P., Dattolo, P., Acampora, P., Sajith, R., Nigro, R., Boero, R., Scarpioni, R., Sicoli, R., Malandra, R., Aign, S., Casar, S., van Esch, S., Chapman, S., Biribauer, S., Navjee, S., Crosbie, S., Brown, S., Tickle, S., Manan, S., Roser, S., Savoldi, S., Bertoli, S., Borrelli, S., Boorsma, S., Heidenreich, S., Melander, S., Maxia, S., Maffei, S., Mangano, S., Palm, S., Konings, S., Mathavakkannan, S., Schwedler, S., Delrieux, S., Renker, S., Schattel, S., Dorota, S., Cicchetti, T., Nieszporek, T., Stephan, T., Schmiedeke, T., Weinreich, T., Leimbach, T., Rappa, T., Almquist, T., Stovesand, T., Bahner, U., Jensen, U., Palazzo, V., De Simone, W., Seeger, W., Kuan, Y., Heleniak, Z., Aydin, Z., Medical Informatics, APH - Aging & Later Life, APH - Methodology, APH - Quality of Care, Nephrology, ACS - Microcirculation, APH - Health Behaviors & Chronic Diseases, APH - Global Health, ACS - Pulmonary hypertension & thrombosis, ACS - Diabetes & metabolism, and Internal Medicine

Subjects
SDG 3 - Good Health and Well-being, external validation, Nephrology, cardiovascular disease, death, CKD, kidney failure, prognostic model
Abstract

Introduction: Predicting the timing and occurrence of kidney replacement therapy (KRT), cardiovascular events, and death among patients with advanced chronic kidney disease (CKD) is clinically useful and relevant. We aimed to externally validate a recently developed CKD G4+ risk calculator for these outcomes and to assess its potential clinical impact in guiding vascular access placement. Methods: We included 1517 patients from the European Quality (EQUAL) study, a European multicentre prospective cohort study of nephrology-referred advanced CKD patients aged ≥65 years. Model performance was assessed based on discrimination and calibration. Potential clinical utility for timing of referral for vascular access placement was studied with diagnostic measures and decision curve analysis (DCA). Results: The model showed a good discrimination for KRT and “death after KRT,” with 2-year concordance (C) statistics of 0.74 and 0.76, respectively. Discrimination for cardiovascular events (2-year C-statistic: 0.70) and overall death (2-year C-statistic: 0.61) was poorer. Calibration was fairly accurate. Decision curves illustrated that using the model to guide vascular access referral would generally lead to less unused arteriovenous fistulas (AVFs) than following estimated glomerular filtration rate (eGFR) thresholds. Conclusion: This study shows moderate to good predictive performance of the model in an older cohort of nephrology-referred patients with advanced CKD. Using the model to guide referral for vascular access placement has potential in combating unnecessary vascular surgeries.

Published
2022

19. Associations between depressive symptoms and disease progression in older patients with chronic kidney disease

Author

Eveleens Maarse, Boukje C., Chesnaye, Nicholas C., Robbert, Schouten, Michels, Wieneke M., Bos, Willem Jan W., Maciej, Szymczak, Magdalena, Krajewska, Marie Evans, Olof Heimburger, Caskey, Fergus J., Christoph, Wanner, Jager, Kitty J., Dekker, Friedo W., Yvette, Meuleman, Andreas, Schneider, Anke, Torp, Beate, Iwig, Boris, Perras, Christian, Marx, Christiane, Drechsler, Christof, Blaser, Claudia, Emde, Detlef, Krieter, Dunja, Fuchs, Ellen, Irmler, Eva, Platen, Hans, Schmidt-Gürtler, Hendrik, Schlee, Holger, Naujoks, Ines, Schlee, Sabine, Cäsar, Joachim, Beige, Jochen, Röthele, Justyna, Mazur, Kai, Hahn, Katja, Blouin, Katrin, Neumeier, Kirsten, Anding-Rost, Lothar, Schramm, Monika, Hopf, Nadja, Wuttke, Nikolaus, Frischmuth, Pawlos, Ichtiaris, Petra, Kirste, Petra, Schulz, Sabine, Aign, Sandra, Biribauer, Sherin, Manan, Silke, Röser, Stefan, Heidenreich, Stephanie, Palm, Susanne, Schwedler, Sylke, Delrieux, Sylvia, Renker, Sylvia, Schättel, Theresa, Stephan, Thomas, Schmiedeke, Thomas, Weinreich, Til, Leimbach, Torsten, Stövesand, Udo, Bahner, Wolfgang, Seeger, Cupisti, Adamasco, Adelia, Sagliocca, Alberto, Ferraro, Alessandra, Mele, Alessandro, Naticchia, Alex, Còsaro, Andrea, Ranghino, Andrea, Stucchi, Angelo, Pignataro, Antonella De Blasio, Antonello, Pani, Aris, Tsalouichos, Bellasi, Antonio, Biagio Raffaele Di Iorio, Butti, Alessandra, Cataldo, Abaterusso, Chiara, Somma, Claudia, D'Alessandro, Claudia, Torino, Claudia, Zullo, Claudio, Pozzi, Daniela, Bergamo, Daniele, Ciurlino, Daria, Motta, Domenico, Russo, Enrico, Favaro, Federica, Vigotti, Ferruccio, Ansali, Ferruccio, Conte, Francesca, Cianciotta, Francesca, Giacchino, Francesco, Cappellaio, Francesco, Pizzarelli, Gaetano, Greco, Gaetana, Porto, Giada, Bigatti, Giancarlo, Marinangeli, Gianfranca, Cabiddu, Giordano, Fumagalli, Giorgia, Caloro, Giorgina, Piccoli, Giovanbattista, Capasso, Giovanni, Gambaro, Giuliana, Tognarelli, Giuseppe, Bonforte, Giuseppe, Conte, Giuseppe, Toscano, Goffredo Del Rosso, Irene, Capizzi, Ivano, Baragetti, Lamberto, Oldrizzi, Loreto, Gesualdo, Luigi, Biancone, Manuela, Magnano, Marco, Ricardi, Maria Di Bari, Maria, Laudato, Maria Luisa Sirico, Martina, Ferraresi, Maurizio, Postorino, Michele, Provenzano, Moreno, Malaguti, Nicola, Palmieri, Paola, Murrone, Pietro, Cirillo, Pietro, Dattolo, Pina, Acampora, Rita, Nigro, Roberto, Boero, Roberto, Scarpioni, Rosa, Sicoli, Rosella, Malandra, Silvana, Savoldi, Silvio, Bertoli, Silvio, Borrelli, Stefania, Maxia, Stefano, Maffei, Stefano, Mangano, Teresa, Cicchetti, Tiziana, Rappa, Valentina, Palazzo, Walter De Simone, Anita, Schrander, Bastiaan van Dam, Carl, Siegert, Carlo, Gaillard, Charles, Beerenhout, Cornelis, Verburgh, Cynthia, Janmaat, Ellen, Hoogeveen, Ewout, Hoorn, Friedo, Dekker, Johannes, Boots, Henk, Boom, Jan-Willem, Eijgenraam, Jeroen, Kooman, Joris, Rotmans, Kitty, Jager, Liffert, Vogt, Maarten, Raasveld, Marc, Vervloet, Marjolijn van Buren, Merel van Diepen, Nicholas, Chesnaye, Paul, Leurs, Pauline, Voskamp, Peter, Blankestijn, Sadie van Esch, Siska, Boorsma, Stefan, Berger, Constantijn, Konings, Zeynep, Aydin, Aleksandra, Musiała, Anna, Szymczak, Ewelina, Olczyk, Hanna, Augustyniak-Bartosik, Ilona, Miśkowiec-Wiśniewska, Jacek, Manitius, Joanna, Pondel, Kamila, Jędrzejak, Katarzyna, Nowańska, Łukasz, Nowak, Magdalena, Durlik, Szyszkowska, Dorota, Teresa, Nieszporek, Zbigniew, Heleniak, Andreas, Jonsson, Anna-Lena, Blom, Björn, Rogland, Carin, Wallquist, Denes, Vargas, Emöke, Dimény, Fredrik, Sundelin, Fredrik, Uhlin, Gunilla, Welander, Isabel Bascaran Hernandez, Knut-Christian, Gröntoft, Maria, Stendahl, Maria, Svensson, Marie, Evans, Olof, Heimburger, Pavlos, Kashioulis, Stefan, Melander, Tora, Almquist, Ulrika, Jensen, Alistair, Woodman, Anna, Mckeever, Asad, Ullah, Barbara, Mclaren, Camille, Harron, Carla, Barrett, Charlotte, O'Toole, Christina, Summersgill, Colin, Geddes, Deborah, Glowski, Deborah, Mcglynn, Dympna, Sands, Fergus, Caskey, Geena, Roy, Gillian, Hirst, Hayley, King, Helen, Mcnally, Houda, Masri-Senghor, Hugh, Murtagh, Hugh, Rayner, Jane, Turner, Joanne, Wilcox, Jocelyn, Berdeprado, Jonathan, Wong, Joyce, Banda, Kirsteen, Jones, Lesley, Haydock, Lily, Wilkinson, Margaret, Carmody, Maria, Weetman, Martin, Joinson, Mary, Dutton, Michael, Matthews, Neal, Morgan, Nina, Bleakley, Paul, Cockwell, Paul, Roderick, Phil, Mason, Philip, Kalra, Rincy, Sajith, Sally, Chapman, Santee, Navjee, Sarah, Crosbie, Sharon, Brown, Sheila, Tickle, Suresh, Mathavakkannan, Ying, Kuan, Internal medicine, Nephrology, ACS - Diabetes & metabolism, Medical Informatics, APH - Methodology, APH - Aging & Later Life, Graduate School, APH - Quality of Care, ACS - Microcirculation, APH - Health Behaviors & Chronic Diseases, APH - Global Health, ACS - Pulmonary hypertension & thrombosis, Eveleens Maarse, B. C., Chesnaye, N. C., Schouten, R., Michels, W. M., Bos, W. J. W., Szymczak, M., Krajewska, M., Evans, M., Heimburger, O., Caskey, F. J., Wanner, C., Jager, K. J., Dekker, F. W., Meuleman, Y., Schneider, A., Torp, A., Iwig, B., Perras, B., Marx, C., Drechsler, C., Blaser, C., Emde, C., Krieter, D., Fuchs, D., Irmler, E., Platen, E., Schmidt-Gurtler, H., Schlee, H., Naujoks, H., Schlee, I., Casar, S., Beige, J., Rothele, J., Mazur, J., Hahn, K., Blouin, K., Neumeier, K., Anding-Rost, K., Schramm, L., Hopf, M., Wuttke, N., Frischmuth, N., Ichtiaris, P., Kirste, P., Schulz, P., Aign, S., Biribauer, S., Manan, S., Roser, S., Heidenreich, S., Palm, S., Schwedler, S., Delrieux, S., Renker, S., Schattel, S., Stephan, T., Schmiedeke, T., Weinreich, T., Leimbach, T., Stovesand, T., Bahner, U., Seeger, W., Cupisti, A., Sagliocca, A., Ferraro, A., Mele, A., Naticchia, A., Cosaro, A., Ranghino, A., Stucchi, A., Pignataro, A., De Blasio, A., Pani, A., Tsalouichos, A., Antonio, B., Raffaele Di Iorio, B., Alessandra, B., Abaterusso, C., Somma, C., D'Alessandro, C., Torino, C., Zullo, C., Pozzi, C., Bergamo, D., Ciurlino, D., Motta, D., Russo, D., Favaro, E., Vigotti, F., Ansali, F., Conte, F., Cianciotta, F., Giacchino, F., Cappellaio, F., Pizzarelli, F., Greco, G., Porto, G., Bigatti, G., Marinangeli, G., Cabiddu, G., Fumagalli, G., Caloro, G., Piccoli, G., Capasso, G., Gambaro, G., Tognarelli, G., Bonforte, G., Conte, G., Toscano, G., Del Rosso, G., Capizzi, I., Baragetti, I., Oldrizzi, L., Gesualdo, L., Biancone, L., Magnano, M., Ricardi, M., Di Bari, M., Laudato, M., Luisa Sirico, M., Ferraresi, M., Postorino, M., Provenzano, M., Malaguti, M., Palmieri, N., Murrone, P., Cirillo, P., Dattolo, P., Acampora, P., Nigro, R., Boero, R., Scarpioni, R., Sicoli, R., Malandra, R., Savoldi, S., Bertoli, S., Borrelli, S., Maxia, S., Maffei, S., Mangano, S., Cicchetti, T., Rappa, T., Palazzo, V., De Simone, W., Schrander, A., Van Dam, B., Siegert, C., Gaillard, C., Beerenhout, C., Verburgh, C., Janmaat, C., Hoogeveen, E., Hoorn, E., Boots, J., Boom, H., Eijgenraam, J. -W., Kooman, J., Rotmans, J., Vogt, L., Raasveld, M., Vervloet, M., Van Buren, M., Van Diepen, M., Leurs, P., Voskamp, P., Blankestijn, P., Van Esch, S., Boorsma, S., Berger, S., Konings, C., Aydin, Z., Musiala, A., Szymczak, A., Olczyk, E., Augustyniak-Bartosik, H., Miskowiec-Wisniewska, I., Manitius, J., Pondel, J., Jedrzejak, K., Nowanska, K., Nowak, L., Durlik, M., Dorota, S., Nieszporek, T., Heleniak, Z., Jonsson, A., Blom, A. -L., Rogland, B., Wallquist, C., Vargas, D., Dimeny, E., Sundelin, F., Uhlin, F., Welander, G., Bascaran Hernandez, I., Grontoft, K. -C., Stendahl, M., Svensson, M., Kashioulis, P., Melander, S., Almquist, T., Jensen, U., Woodman, A., Mckeever, A., Ullah, A., Mclaren, B., Harron, C., Barrett, C., O'Toole, C., Summersgill, C., Geddes, C., Glowski, D., Mcglynn, D., Sands, D., Roy, G., Hirst, G., King, H., Mcnally, H., Masri-Senghor, H., Murtagh, H., Rayner, H., Turner, J., Wilcox, J., Berdeprado, J., Wong, J., Banda, J., Jones, K., Haydock, L., Wilkinson, L., Carmody, M., Weetman, M., Joinson, M., Dutton, M., Matthews, M., Morgan, N., Bleakley, N., Cockwell, P., Roderick, P., Mason, P., Kalra, P., Sajith, R., Chapman, S., Navjee, S., Crosbie, S., Brown, S., Tickle, S., Mathavakkannan, S., and Kuan, Y.

Subjects
Transplantation, prospective cohort study, depressive symptoms, nephrology care, Nephrology, clinical outcome, chronic kidney disease, clinical trial, epidemiology, joint model, survival analysis, depressive symptom
Abstract

Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (≥65 years; estimated glomerular filtration rate ≤20 mL/min/1.73 m2) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off ≤70; 0–100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was –0.12 mL/min/1.73 m2/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03–1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men.

Published
2022

20. Clinical, Radiometabolic and Immunologic Effects of Olaparib in Locally Advanced Triple Negative Breast Cancer: The OLTRE Window of Opportunity Trial

Author

Francesco Schettini, Silvia Paola Corona, Fabiola Giudici, Carla Strina, Marianna Sirico, Ottavia Bernocchi, Manuela Milani, Nicoletta Ziglioli, Sergio Aguggini, Carlo Azzini, Giuseppina Barbieri, Valeria Cervoni, Maria Rosa Cappelletti, Alfredo Molteni, Maria Chiara Lazzari, Giuseppina Ferrero, Marco Ungari, Elena Marasco, Alice Bruson, Luciano Xumerle, Elisa Zago, Davide Cerra, Marco Loddo, Gareth H. Williams, Ida Paris, Giovanni Scambia, Daniele Generali, Schettini, F., Corona, S. P., Giudici, F., Strina, C., Sirico, M., Bernocchi, O., Milani, M., Ziglioli, N., Aguggini, S., Azzini, C., Barbieri, G., Cervoni, V., Cappelletti, M. R., Molteni, A., Lazzari, M. C., Ferrero, G., Ungari, M., Marasco, E., Bruson, A., Xumerle, L., Zago, E., Cerra, D., Loddo, M., Williams, G. H., Paris, I., Scambia, G., and Generali, D.

Subjects
PD-L1, Oncology, Cancer Research, medicine.medical_specialty, olaparib (Lynparza™), medicine.medical_treatment, BRCA, Locally advanced, window of opportunity clinical trial, Olaparib, chemistry.chemical_compound, Basal (phylogenetics), Germline mutation, Internal medicine, medicine, homologous recombination deficiency, neoadjuvant, TILs, triple negative breast cancer, Triple-negative breast cancer, RC254-282, Original Research, Chemotherapy, biology, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, TIL, chemistry, biology.protein, business, CD8
Abstract

IntroductionOlaparib is effective in metastatic triple negative breast cancer (TNBC) carrying germline mutations in DNA damage repair (DDR) genes BRCA1/2 (gBRCA-mut). The OLTRE window-of-opportunity trial preliminarily investigated potential pathologic, radiometabolic and immune biomarkers of early-response to olaparib in gBRCA-wild-type (wt) TNBC and, as proof-of-concept in gBRCA-mut HER2-negative BC.MethodsPatients received olaparib for 3 weeks (3w) before standard neoadjuvant chemotherapy and underwent multiple FDG18-PET/CT scan (basal, after olaparib), clinical assessments (basal, every 3w), tumor biopsies and blood samplings (baseline, after olaparib). Clinical and radiometabolic responses were evaluated according to RECIST1.1 and PERCIST criteria.Results27 patients with gBRCA-wt TNBC and 8 with gBRCA-mut BC (6 TNBC, 2 HR+/HER2-negative) were enrolled. Three (11.1%) patients showed mutations in non-BRCA1/2 DDR genes and 4 (14.8%) in other genes. 3w olaparib induced 16/35 and 15/27 partial clinical and radiometabolic responses, including in 40.7% and 50.0% gBRCA-wt patients. gBRCA-mut tumors presented numerically higher tumor-infiltrating lymphocytes (TILs) levels and PD-L1 positive tumors. Clinical responders experienced a reduction in T-regs/T-eff ratio (p=0.05), B and NK lymphocytes (p=0.003 both), with an average increase in T-helpers rate (pBRCA status and type of response.ConclusionsEarly-stage TNBC might be a target population for olaparib, irrespective of gBRCA mutations. Future trials should combine TILs, PD-L1 and gBRCA status to better identify candidates for escalated/de-escalated treatment strategies including olaparib.

Published
2021

21. Role of the IGF-1 Axis in Overcoming Resistance in Breast Cancer

Author

Anna Ianza, Marianna Sirico, Ottavia Bernocchi, Daniele Generali, Ianza, A., Sirico, M., Bernocchi, O., and Generali, D.

Subjects
breast cancer, clinical trial, IGF-1R, IGF1, therapy resistance, business.industry, Mini Review, Estrogen regulation, Endocrine therapy, Tumor cells, Cell Biology, medicine.disease, Metastasis, Clinical trial, Cell and Developmental Biology, Breast cancer, lcsh:Biology (General), Cancer research, medicine, Target therapy, Receptor, business, lcsh:QH301-705.5, Developmental Biology
Abstract

Over the last two decades, many studies have demonstrated that the insulin-like growth factor-1 (IGF-1) is involved in a number of patho-physiological processes, as well as in the development of different types of solid tumors, including breast cancer (BC). Preclinical and clinical data showed that IGF-1 receptor (R) is overexpressed and hyper-phosphorylated in several subtypes of BCs. The central implications of this pathway in tumor cell proliferation and metastasis make it an important therapeutic target. Moreover, the IGF-1 axis has shown strong interconnection with estrogen regulation and endocrine therapy, suggesting a possible solution to anti-estrogen resistance. IGF-1R might also interfere with other pivotal therapeutic strategies, such as anti HER2 treatments and mTOR inhibitors; several clinical trials are ongoing evaluating the role of IGF-1R inhibition in modulating resistance mechanisms to target therapies. Our aim is to offer an overview of the most recent and significant field of application of IGF-1 inhibitors and relevant therapeutic strategies, weighing their possible future impact on clinical practice.

Published
2021

22. Moving beyond parp inhibition: Current state and future perspectives in breast cancer

Author

Ugo De Giorgi, Marianna Sirico, Alessandra Virga, Paola Ulivi, Michela Palleschi, Gianluca Tedaldi, Palleschi M., Tedaldi G., Sirico M., Virga A., Ulivi P., and De Giorgi U.

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, QH301-705.5, medicine.medical_treatment, Antineoplastic Agents, Breast Neoplasms, Review, Synthetic lethality, Poly(ADP-ribose) Polymerase Inhibitors, Poly (ADP-Ribose) Polymerase Inhibitor, Catalysis, Inorganic Chemistry, Antineoplastic Agent, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Internal medicine, medicine, Animals, Humans, Biology (General), Physical and Theoretical Chemistry, QD1-999, PARP inhibitors, Molecular Biology, Spectroscopy, Neoadjuvant therapy, Therapeutic strategy, business.industry, Animal, Organic Chemistry, General Medicine, medicine.disease, Neoadjuvant Therapy, Computer Science Applications, Clinical trial, Chemistry, 030104 developmental biology, PARP inhibitor, 030220 oncology & carcinogenesis, PARP inhibitor resistance, Female, business, Adjuvant, Breast Neoplasm, Human
Abstract

Breast cancer is the most frequent and lethal tumor in women and finding the best therapeutic strategy for each patient is an important challenge. PARP inhibitors (PARPis) are the first, clinically approved drugs designed to exploit synthetic lethality in tumors harboring BRCA1/2 mutations. Recent evidence indicates that PARPis have the potential to be used both in monotherapy and combination strategies in breast cancer treatment. In this review, we show the mechanism of action of PARPis and discuss the latest clinical applications in different breast cancer treatment settings, including the use as neoadjuvant and adjuvant approaches. Furthermore, as a class, PARPis show many similarities but also certain critical differences which can have essential clinical implications. Finally, we report the current knowledge about the resistance mechanisms to PARPis. A systematic PubMed search, using the entry terms “PARP inhibitors” and “breast cancer”, was performed to identify all published clinical trials (Phase I-II-III) and ongoing trials (ClinicalTrials.gov), that have been reported and discussed in this review.

Published
2021

23. Canakinumab as treatment for COVID-19-related pneumonia: A prospective case-control study

Author

Chiara Costanzi, Daniele Generali, Ilaria Zangrandi, Valeria De Giuli, Fabio Malberti, Maria Rosa Cappelletti, Giancarlo Bosio, Andrea Machiavelli, Marianna Sirico, Antonio Fioravanti, Guglielmo Giannotti, Angelo Pan, Sophie Testa, Ottavia Bernocchi, Fabiola Giudici, Alessia Giossi, Erika Maria Viola, Alfredo Molteni, Marina Foramitti, Alessandro Morandini, Antonio Cuzzoli, Matteo Giorgi-Pierfranceschi, Maurizio Scaltriti, Sergio Venturini, Giulia Chiodelli, Chiara Campana, Alessia Zoncada, Luca Pianta, Laura Romanini, Rosa Angela Tira, Generali, D., Bosio, G., Malberti, F., Cuzzoli, A., Testa, S., Romanini, L., Fioravanti, A., Morandini, A., Pianta, L., Giannotti, G., Viola, E. M., Giorgi-Pierfranceschi, M., Foramitti, M., Tira, R. A., Zangrandi, I., Chiodelli, G., Machiavelli, A., Cappelletti, M. R., Giossi, A., De Giuli, V., Costanzi, C., Campana, C., Bernocchi, O., Sirico, M., Zoncada, A., Molteni, A., Venturini, S., Giudici, F., Scaltriti, M., and Pan, A.

Subjects
0301 basic medicine, Male, medicine.medical_treatment, Cohort Studies, 0302 clinical medicine, Monoclonal, 80 and over, 030212 general & internal medicine, Viral, Prospective Studies, Prospective cohort study, Humanized, Aged, 80 and over, General Medicine, Middle Aged, Hospitalization, Infectious Diseases, medicine.anatomical_structure, Treatment Outcome, Settore SECS-S/01 - STATISTICA, Cohort, Female, Case-Control Studie, medicine.drug, Cohort study, Human, Microbiology (medical), Adult, medicine.medical_specialty, Canakinumab, 030106 microbiology, Pneumonia, Viral, Antibodies, Monoclonal, Humanized, Article, Antibodies, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Internal medicine, medicine, Humans, lcsh:RC109-216, Aged, Mechanical ventilation, Lung, business.industry, SARS-CoV-2, Case-control study, COVID-19, Pneumonia, medicine.disease, Prospective Studie, Case-Control Studies, Cohort Studie, business
Abstract

Highlights • Canakinumab is an IL-1β antibody that neutralizes the activity of IL-1β. • The effects of canakinumab in patients with COVID-19-related pneumonia were studied. • 33 patients received canakinumab and 15 received institutional standard of care. • Treatment with canakinumab rapidly restored normal oxygen status. • Canakinumab was also associated with favorable prognosis versus SoC., Objectives Canakinumab is an IL-1β antibody that neutralizes the activity of IL-1β. We studied the efficacy and safety of canakinumab in patients with moderate COVID-19-related pneumonia. Design The aim of our study was to evaluate the reduction in duration of hospitalization with adequate oxygen status. Forty-eight patients with moderate COVID-19-related pneumonia were asked to participate in the prospective case-control study; 33 patients (Cases) signed informed consent and received canakinumab (Cohort 1); 15 patients (Controls) refused to receive the experimental drug and received institutional standard of care (SoC), (Cohort 2). Results Hospital discharge within 21 days was seen in 63% of patients in Cohort 1 vs. 0% in Cohort 2 (median 14 vs 26 days, respectively; p

Published
2021

24. ΔKi67 proliferation index as independent predictive and prognostic factor of outcome in luminal breast cancer: data from neoadjuvant letrozole-based treatment

Author

Anna Ianza, Sergio Aguggini, C. Azzini, Alberto Bottini, Carla Strina, Silvia Paola Corona, Fabiola Giudici, G Allevi, Ottavia Bernocchi, V Cervoni, Marianna Sirico, Manuela Milani, Daniele Generali, Maria Rosa Cappelletti, C Pinello, M Dester, A. Cocconi, Marina Bortul, Ianza, A., Giudici, F., Pinello, C., Corona, S. P., Strina, C., Bernocchi, O., Bortul, M., Milani, M., Sirico, M., Allevi, G., Aguggini, S., Cocconi, A., Azzini, C., Dester, M., Cervoni, V., Bottini, A., Cappelletti, M., and Generali, D.

Subjects
neoadjuvant systemic therapy, 0301 basic medicine, Oncology, Sorafenib, medicine.medical_specialty, Proliferation index, Cyclophosphamide, Breast Neoplasms, clinical response, Disease-Free Survival, 03 medical and health sciences, breast cancer, 0302 clinical medicine, Breast cancer, Internal medicine, Ki67, proliferation index, Biopsy, medicine, Humans, Cell Lineage, RC254-282, Aged, Cell Proliferation, Predictive marker, medicine.diagnostic_test, Dose-Response Relationship, Drug, business.industry, Letrozole, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, General Medicine, medicine.disease, Prognosis, Neoadjuvant Therapy, Gene Expression Regulation, Neoplastic, 030104 developmental biology, Ki-67 Antigen, Treatment Outcome, Response Evaluation Criteria in Solid Tumors, 030220 oncology & carcinogenesis, Female, business, medicine.drug
Abstract

A key tool for monitoring breast cancer patients under neoadjuvant treatment is the identification of reliable predictive markers. Ki67 has been identified as a prognostic and predictive marker in ER-positive breast cancer. Ninety ER-positive, HER2 negative locally advanced breast cancer patients received letrozole (2.5 mg daily) and cyclophosphamide (50 mg daily) with/without Sorafenib (400 mg/bid daily) for 6 months before undergoing surgery. Ki67 expression and tumor size measured with caliber were determined at baseline, after 30 days of treatment and at the end of treatment. Patients were assigned to a clinical response category according to Response Evaluation Criteria in Solid Tumors, both at 30 days and before surgery and further classified as high-responder and low-responder according to the median variation of Ki67 values between biopsy and 30 days and between biopsy and surgery time. The predictive role of Ki67 and its changes with regard to clinical response and survival was analyzed. No differences in terms of survival outcomes emerged between the arms of treatment, while we observed a higher percentage of women with progression or stable disease in arm with the combination containing Sorafenib (20.5% vs 7.1%, p = 0.06). Clinical complete responders experienced a greater overall variation in Ki67 when compared with partial responders and patients with progressive/stable disease (66.7% vs 30.7%, p = 0.009). High responders showed a better outcome than low responders in terms of both disease-free survival ( p = 0.009) and overall survival ( p = 0.002). ΔKi67 score evaluated between basal and residual tumor at definitive surgery showed to be highly predictive of clinical complete response, and a potential parameter to be used for predicting disease-free survival and overall survival in luminal breast cancer treated with neoadjuvant endocrine-based therapy.

Published
2020

25. Early changes of the standardized uptake values (SUVmax) predict the efficacy of everolimus-exemestane in patients with hormone receptor-positive metastatic breast cancer

Author

Federico Nichetti, Carla Strina, Marianna Sirico, Giulia Bianchi, Maria Rosa Cappelletti, Silvia P. Corona, Valeria Cervoni, Manuela Milani, Filippo de Braud, Navid Sobhani, Giuseppina Barbieri, Daniele Generali, Martina Dester, Fabiola Giudici, Claudio Vernieri, Ottavia Bernocchi, Nicoletta Ziglioli, Sirico, M., Bernocchi, O., Sobhani, N., Giudici, F., Corona, S. P., Vernieri, C., Nichetti, F., Cappelletti, M. R., Milani, M., Strina, C., Cervoni, V., Barbieri, G., Ziglioli, N., Dester, M., Bianchi, G. V., Braud, F. D., and Generali, D.

Subjects
Oncology, 18F-FDG PET/CT, Cancer Research, medicine.medical_specialty, medicine.drug_class, ∆SUV%, lcsh:RC254-282, Article, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Exemestane, Internal medicine, medicine, Everolimus, Prospective cohort study, Predictive marker, Aromatase inhibitor, business.industry, F-FDG PET/CT, Metastatic breast cancer, Predictive biomarker, Retrospective cohort study, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Everolimu, chemistry, Hormone receptor, 030220 oncology & carcinogenesis, business, medicine.drug
Abstract

Background: The mTORC1 inhibitor everolimus has been approved in combination with the aromatase inhibitor exemestane for the treatment of hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2&minus, ) metastatic breast cancer (HR+ mBC) progressing on prior therapy with a non-steroidal aromatase inhibitor. To date, no predictive biomarkers of tumor sensitivity/resistance for everolimus-based treatments have been identified. We hypothesized that precocious changes in the Standardized Uptake Volume (∆SUV%), as assessed by 18F-Fluorodeoxyglucosepositron-emission tomography (18F-FDG PET/CT), may be a marker of everolimus efficacy. Methods: This was a retrospective study including 31 HR+ HER2- patients treated with everolimus and exemestane in two Italian centers between 2013 and 2018. The objective of the study was to investigate ∆SUV% as a predictive marker of everolimus antitumor efficacy. 18F-FDG PET/CT scans were performed at baseline and after three months of treatment. Patients were defined as long responders (LRs) if disease progression occurred at least 10 months after treatment initiation and long survivors (LSs) if death occurred later than 36 months after starting therapy. ROC analysis was used to determine the optimal cut-off values of ∆SUV% to distinguish LRs from non-LRs and LSs from non-LSs. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan&ndash, Meier method. Results: The SUVmax values decreased significantly from baseline to 3 months after therapy (p = 0.003). Dynamic changes of SUVmax (Delta SUV) had a higher accuracy in discriminating long-responders from non-long-responders (AUC = 0.67, Delta SUV cut-off = 28.8%) respects to its ability to identify long survivors from no-long survivors (AUC = 0.60, Delta SUV cut-off = 53.8%). Patients were divided into groups according to the Delta SUV cut-offs and survival outcomes were evaluated: patients with a decrease of ∆SUV% &ge, 28.8% had significantly better PFS (10 months-PFS: 63.2%, 95% CI: 37.9&ndash, 80.4% and 16.7%, 95% CI: 2.7&ndash, 41.3% respectively, p = 0.005). As regard as OS, patients with ∆SUV% &ge, 53.8% had longer OS when compared to patients with ∆SUV% &lt, 53.8% (36 month-OS: 82.5% vs. 45.9% vs. p = 0.048). Conclusion: We found two precocious ∆SUV% thresholds capable of identifying HR+ HER2-mBC patients, which would achieve long-term benefit or long-term survival during everolimus-exemestane therapy. These results warrant further validation in prospective studies and should be integrated with molecular biomarkers related to tumor metabolism and mTORC1 signaling.

Published
2020

26. Impact of BMI on the outcome of metastatic breast cancer patients treated with everolimus: A retrospective exploratory analysis of the BALLET study

Author

Giuseppina Barbieri, Martina Dester, Marianna Sirico, Eva Ciruelos, Manuela Milani, Fabiola Giudici, Daniele Generali, Silvia Paola Corona, Valeria Cervoni, Carla Strina, Guy Jerusalem, Filippo Montemurro, Nicoletta Ziglioli, Ottavia Bernocchi, Corona, S, Giudici, F, Jerusalem, G, Ciruelos, E, Strina, C, Sirico, M, Bernocchi, O, Milani, M, Dester, M, Ziglioli, N, Barbieri, G, Cervoni, V, Montemurro, F, and Generali, D

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Ballet, outcomes, BMI, Weight loss, Internal medicine, medicine, Retrospective analysis, Everolimus, business.industry, biomarkers, weight, Exploratory analysis, everolimus, medicine.disease, Metastatic breast cancer, mTOR inhibition, metastatic breast cancer, biomarker, medicine.symptom, Weight Decrease, business, Exposure duration, Research Paper, medicine.drug
Abstract

Introduction Reliable biomarkers of response to mTOR inhibition are yet to be identified. As mTOR is heavily implicated in cell-metabolism, we investigated the relation between BMI variation and outcomes in metastatic breast cancer (mBC) patients treated with everolimus. Results we found a linear correlation between everolimus exposure duration and BMI/weight decrease. Patients exhibiting >2 kg weight loss or >3% BMI decrease from baseline at the end of treatment (EOT) had a statistically significant improvement in PFS. Interestingly, a similar BMI/weight decrease within the first 8 weeks of therapy identified patients at higher risk of progression. Patients and methods we performed a retrospective analysis of patients enrolled in the BALLET trial who progressed during the study. Primary end-point was progression-free survival (PFS). Secondary end-point was the identification of other predictors of response. Conclusion A >3% weight loss at EOT is associated with better outcome in mBC patients treated with everolimus. On the contrary, a significant early weight loss represents a predictor of poor survival and could therefore be used as an early negative prognostic marker. As PI3K-inhibition also converges onto mTOR, these findings might extend to patients treated with selective PI3K inhibitors and warrant further investigation.

Published
2020

27. Efficacy of extended aromatase inhibitors for hormone-receptor–positive breast cancer: A literature-based meta-analysis of randomized trials

Author

G Allevi, Sergio Aguggini, Pietro Rosellini, Fabiola Giudici, Manuela Milani, M. Francaviglia, Mariarosa Cappelletti, Silvia Paola Corona, C. Azzini, Giandomenico Roviello, A. Cocconi, Daniele Generali, Daniele Zanoni, Marianna Sirico, Olivia Pagani, Carla Strina, Francesco Meani, Marina Bortul, S. Madaro, Fabrizio Zanconati, Corona, S., Roviello, G., Strina, C., Milani, M., Madaro, S., Zanoni, D., Allevi, G., Aguggini, S., Cappelletti, M. R., Francaviglia, M., Azzini, C., Cocconi, A., Sirico, M., Bortul, M., Zanconati, F., Giudici, F., Rosellini, P., Meani, F., Pagani, O., and Generali, D.

Subjects
Oncology, medicine.medical_specialty, Hormone-positive BC, Antineoplastic Agents, Hormonal, Receptor, ErbB-2, AIs, Extended adjuvant AIs, Subgroup analysis, Breast Neoplasms, Cochrane Library, Disease-Free Survival, law.invention, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Adjuvant endocrine therapy, Randomized controlled trial, law, Aromatase inhibitors, Extended adjuvant endocrine treatment, HR+, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Adjuvant therapy, Humans, 030212 general & internal medicine, Proportional Hazards Models, Randomized Controlled Trials as Topic, business.industry, Hazard ratio, General Medicine, Aromatase inhibitor, medicine.disease, Tamoxifen, Treatment Outcome, Chemotherapy, Adjuvant, AI, 030220 oncology & carcinogenesis, Meta-analysis, Extended adjuvant AI, Surgery, Female, business, medicine.drug
Abstract

Background Endocrine treatment with Tamoxifen and aromatase inhibitors (AIs) is a staple in the management of hormone receptor positive breast cancer (HR + BC). It has become clear that HR + BC carries a consistent risk of relapse up to 15 years post-diagnosis. While increasing evidence supports the use of extended adjuvant Tamoxifen over 5 years, controversial data are available on the optimal duration of extended AIs adjuvant treatment. We performed a meta-analysis to assess the real impact of extended adjuvant therapy with AIs on disease-free survival (DFS). Methods A literature-based meta-analysis of randomized controlled trials (RCTs) was undertaken. Relevant publications from PubMed, the Cochrane Library, and abstracts from American Society of Clinical Oncology (ASCO) and San Antonio Breast Cancer (SABCS) symposia were searched. Primary and secondary endpoints were Disease Free Survival (DFS) and overall survival (OS) respectively. A subgroup analysis was also performed to elucidate the impact of nodal involvement. Results The pooled analysis revealed a significant increase in DFS in the extended AIs group (hazard ratio (HR): 0.78, 95% CI: 0.68–0.90; P = 0.0006). The subgroup analysis according to nodal status showed a greater DFS benefit with extended AIs in patients with positive nodes (HR = 0.67 versus 0.80). Our analysis also demonstrated no improvement in OS with extended AIs (HR = 0.99, 95%CI: 0.87–1.12; P = 0.84). Conclusion This work confirmed the efficacy of extended adjuvant treatment with AIs for HR + early breast cancer, with a 22% increase in DFS, but no impact on OS. Greater efficacy was observed in women with positive nodal status.

Published
2019

28. 266 Poster - Impact of BMI on the outcome of metastatic breast cancer patients treated with everolimus: A retrospective exploratory analysis of the BALLET study.

Author

Corona, S., Giudici, F., Jerusalem, G., Ciruelos, E., Strina, C., Sirico, M., Bernocchi, O., Milani, M., Dester, M., Ziglioli, N., Barbieri, G., Cervoni, V., Montemurro, F., and Generali, D.

Subjects
*BREAST tumors, *CANCER patients, *CONFERENCES & conventions, *BODY mass index, *TREATMENT effectiveness, *EVEROLIMUS, *EVALUATION
Published
2020
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29. A translational approach to micro-inflammation in end-stage renal disease: molecular effects of low levels of interleukin-6

Author

Memoli, Salerno, Procino, Postiglione, Morelli, Sirico, M.L., Giordano, Ricciardone, Drioli, Andreucci, De Bartolo, Memoli, Bruno, Salerno, S., Procino, A, Postiglione, Loredana, Morelli, S., Sirico, M., Giordano, F., Ricciardone, M., Drioli, E., Andreucci, V., and De Bartolo, L.

Subjects
Adult, Male, STAT3 Transcription Factor, alpha-2-HS-Glycoprotein, medicine.medical_treatment, Inflammation, Disease, Bioinformatics, urologic and male genital diseases, micro-inflammation, End stage renal disease, Hepcidins, Hepcidin, Renal Dialysis, medicine, Cytokine Receptor gp130, Humans, ESRD, Interleukin 6, Cells, Cultured, Microscopy, Confocal, biology, business.industry, Interleukin-6, General Medicine, Blood Proteins, Middle Aged, medicine.disease, Receptors, Interleukin-6, Genetic translation, Recombinant Proteins, fetuin-A, Cytokine, C-Reactive Protein, Gene Expression Regulation, Immunology, biology.protein, Hepatocytes, Cytokines, Kidney Failure, Chronic, Female, hepcidin, medicine.symptom, business, Kidney disease, Antimicrobial Cationic Peptides
Abstract

Inflammation plays a key role in the progression of cardiovascular disease, the leading cause of mortality in ESRD (end-stage renal disease). Over recent years, inflammation has been greatly reduced with treatment, but mortality remains high. The aim of the present study was to assess whether low (

Published
2010

31. Patient-Derived Organoids: A Game-Changer in Personalized Cancer Medicine.

Author

Abbasian MH, Sobhani N, Sisakht MM, D'Angelo A, Sirico M, and Roudi R

Abstract

Research on cancer therapies has benefited from predictive tools capable of simulating treatment response and other disease characteristics in a personalized manner, in particular three-dimensional cell culture models. Such models include tumor-derived spheroids, multicellular spheroids including organotypic multicellular spheroids, and tumor-derived organoids. Additionally, organoids can be grown from various cancer cell types, such as pluripotent stem cells and induced pluripotent stem cells, progenitor cells, and adult stem cells. Although patient-derived xenografts and genetically engineered mouse models replicate human disease in vivo, organoids are less expensive, less labor intensive, and less time-consuming, all-important aspects in high-throughput settings. Like in vivo models, organoids mimic the three-dimensional structure, cellular heterogeneity, and functions of primary tissues, with the advantage of representing the normal oxygen conditions of patient organs. In this review, we summarize the use of organoids in disease modeling, drug discovery, toxicity testing, and precision oncology. We also summarize the current clinical trials using organoids., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Published
2024
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32. Local treatment for oligoprogressive metastatic sites of breast cancer: efficacy, toxicities and future perspectives.

Author

Merloni F, Palleschi M, Gianni C, Sirico M, Serra R, Casadei C, Sarti S, Cecconetto L, Di Menna G, Mariotti M, Maltoni R, Montanari D, Romeo A, and De Giorgi U

Abstract

Metastatic breast cancer (MBC) is still an incurable disease, which eventually develops resistance mechanisms against systemic therapies. While most patients experience widespread disease progression during systemic treatment (ST), in some cases, progression may occur at a limited number of metastatic sites. Evidence from other malignancies suggests that local treatment with stereotactic ablative radiotherapy (SABR) of oligoprogressive disease (OPD) may allow effective disease control without the need to modify ST. Available evidence regarding local treatment of oligoprogressive breast cancer is limited, mostly consisting of retrospective studies. The only randomized data come from the randomized CURB trial, which enrolled patients with oligoprogressive disease, including both small cell lung cancer and breast cancer patients, and did not show a survival benefit from local treatment in the latter group. However, local treatment of oligoprogressive MBC is still considered in clinical practice, especially to delay the switch to more toxic STs. This review aims to identify patients who may benefit from this approach based on the current available knowledge, focusing also on the potential risks associated with the combination of radiotherapy (RT) and ST, as well as on possible future scenarios., (© 2024. The Author(s).)

Published
2024
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33. Next-generation sequencing-based evaluation of the actionable landscape of genomic alterations in solid tumors: the "MOZART" prospective observational study.

Author

Schettini F, Sirico M, Loddo M, Williams GH, Hardisty KM, Scorer P, Thatcher R, Rivera P, Milani M, Strina C, Ferrero G, Ungari M, Bottin C, Zanconati F, de Manzini N, Aguggini S, Tancredi R, Fiorio E, Fioravanti A, Scaltriti M, and Generali D

Abstract

Background: The identification of the most appropriate targeted therapies for advanced cancers is challenging. We performed a molecular profiling of metastatic solid tumors utilizing a comprehensive next-generation sequencing (NGS) assay to determine genomic alterations' type, frequency, actionability, and potential correlations with PD-L1 expression., Methods: A total of 304 adult patients with heavily pretreated metastatic cancers treated between January 2019 and March 2021 were recruited. The CLIA-/UKAS-accredit Oncofocus assay targeting 505 genes was used on newly obtained or archived biopsies. Chi-square, Kruskal-Wallis, and Wilcoxon rank-sum tests were used where appropriate. Results were significant for P < .05., Results: A total of 237 tumors (78%) harbored potentially actionable genomic alterations. Tumors were positive for PD-L1 in 68.9% of cases. The median number of mutant genes/tumor was 2.0 (IQR: 1.0-3.0). Only 34.5% were actionable ESCAT Tier I-II with different prevalence according to cancer type. The DNA damage repair (14%), the PI3K/AKT/mTOR (14%), and the RAS/RAF/MAPK (12%) pathways were the most frequently altered. No association was found among PD-L1, ESCAT, age, sex, and tumor mutational status. Overall, 62 patients underwent targeted treatment, with 37.1% obtaining objective responses. The same molecular-driven treatment for different cancer types could be associated with opposite clinical outcomes., Conclusions: We highlight the clinical value of molecular profiling in metastatic solid tumors using comprehensive NGS-based panels to improve treatment algorithms in situations of uncertainty and facilitate clinical trial recruitment. However, interpreting genomic alterations in a tumor type-specific manner is critical., (© The Author(s) 2024. Published by Oxford University Press.)

Published
2024
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35. Peripheral blood lymphocytes predict clinical outcomes in hormone receptor-positive HER2-negative advanced breast cancer patients treated with CDK4/6 inhibitors.

Author

Zattarin E, Mariani L, Menichetti A, Leporati R, Provenzano L, Ligorio F, Fucà G, Lobefaro R, Lalli L, Vingiani A, Nichetti F, Griguolo G, Sirico M, Bernocchi O, Marra A, Corti C, Zagami P, Agostinetto E, Jacobs F, Di Mauro P, Presti D, Sposetti C, Giorgi CA, Guarneri V, Pedersini R, Losurdo A, Generali D, Curigliano G, Pruneri G, de Braud F, Dieci MV, and Vernieri C

Abstract

Background: Cyclin-Dependent Kinase 4/6 inhibitors (CDK4/6i) combined with Endocrine Therapy (ET) are the standard treatment for patients with Hormone Receptor-positive/HER2-negative advanced breast cancer (HR+/HER2- aBC)., Objectives: While CDK4/6i are known to reduce several peripheral blood cells, such as neutrophils, lymphocytes and platelets, the impact of these modulations on clinical outcomes is unknown., Design: A multicenter, retrospective-prospective Italian study., Methods: We investigated the association between baseline peripheral blood cells, or their early modifications (i.e. 2 weeks after treatment initiation), and the progression-free survival (PFS) of HR+/HER2- aBC patients treated with ETs plus CDK4/6i. Random Forest models were used to select covariates associated with patient PFS among a large list of patient- and tumor-related variables., Results: We evaluated 638 HR+/HER2- aBC patients treated with ET plus CDK4/6i at six Italian Institutions between January 2017 and May 2021. High baseline lymphocyte counts were independently associated with longer PFS [median PFS (mPFS) 20.1 versus 13.2 months in high versus low lymphocyte patients, respectively; adjusted Hazard Ratio (aHR): 0.78; 95% confidence interval (CI): 0.66-0.92; p = 0.0144]. Moreover, patients experiencing a lower early reduction of lymphocyte counts had significantly longer PFS when compared to patients undergoing higher lymphocyte decrease (mPFS 18.1 versus 14.5 months; aHR: 0.82; 95% CI: 0.73-0.93; p = 0.0037). Patients with high baseline lymphocytes and undergoing a lower reduction, or even an increase, of lymphocyte counts during CDK4/6i therapy experienced the longest PFS, while patients with lower baseline lymphocytes and undergoing a higher decrease of lymphocytes had the lowest PFS (mPFS 21.4 versus 11 months, respectively)., Conclusion: Baseline and on-treatment modifications of peripheral blood lymphocytes have independent prognostic value in HR+/HER2- aBC patients. This study supports the implementation of clinical strategies to boost antitumor immunity in patients with HR+/HER2- aBC treated with ETs plus CDK4/6i., (© The Author(s), 2023.)

Published
2023
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36. Cancer management during the COVID-19 world pandemic.

Author

Sobhani N, Mondani G, Roviello G, Catalano M, Sirico M, D'Angelo A, Scaggiante B, and Generali D

Subjects
Humans, SARS-CoV-2, Pandemics, Peptidyl-Dipeptidase A, COVID-19, Neoplasms epidemiology, Neoplasms therapy
Abstract

Since 2019, the world has been experiencing an outbreak of a novel beta-coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV)-2. The worldwide spread of this virus has been a severe challenge for public health, and the World Health Organization declared the outbreak a public health emergency of international concern. As of June 8, 2023, the virus' rapid spread had caused over 767 million infections and more than 6.94 million deaths worldwide. Unlike previous SARS-CoV-1 and Middle East respiratory syndrome coronavirus outbreaks, the COVID-19 outbreak has led to a high death rate in infected patients; this has been caused by multiorgan failure, which might be due to the widespread presence of angiotensin-converting enzyme 2 (ACE2) receptors-functional receptors of SARS-CoV-2-in multiple organs. Patients with cancer may be particularly susceptible to COVID-19 because cancer treatments (e.g., chemotherapy, immunotherapy) suppress the immune system. Thus, patients with cancer and COVID-19 may have a poor prognosis. Knowing how to manage the treatment of patients with cancer who may be infected with SARS-CoV-2 is essential. Treatment decisions must be made on a case-by-case basis, and patient stratification is necessary during COVID-19 outbreaks. Here, we review the management of COVID-19 in patients with cancer and focus on the measures that should be adopted for these patients on the basis of the organs or tissues affected by cancer and by the tumor stage., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Published
2023
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37. Real-world clinical outcomes of patients with stage I HER2-positive breast cancer treated with adjuvant paclitaxel and trastuzumab.

Author

Debien V, Marta GN, Agostinetto E, Sirico M, Jacobs F, Molinelli C, Moreau M, Paesmans M, De Giorgi U, Santoro A, Taylor D, Duhoux FP, Botticelli A, Barchiesi G, Speranza I, Lambertini M, Wildiers H, Azambuja E, and Piccart M

Subjects
Humans, Female, Trastuzumab therapeutic use, Paclitaxel, Retrospective Studies, Receptor, ErbB-2 genetics, Receptor, ErbB-2 metabolism, Treatment Outcome, Disease-Free Survival, Adjuvants, Immunologic, Chemotherapy, Adjuvant, Antineoplastic Combined Chemotherapy Protocols adverse effects, Breast Neoplasms pathology
Abstract

Up to 20% of breast cancer overexpress HER2 protein, making it a reliable target for antibody-based treatments. In early HER2-positive breast cancer avoiding anthracycline-based chemotherapy is a challenge. Based on the single-arm phase II APT trial results, adjuvant paclitaxel/trastuzumab is an accepted regimen for patients with stage I HER2-positive disease. In our retrospective study of 240 patients, the median tumor size was 12.0 mm (IQR 9 -15), and 204 (85%) had estrogen receptor-positive disease. After a median follow-up of 4.6 years, 3-year real-world disease-free survival, distant DFS, and overall survival were 98.8% (95% confidence interval (CI), 96.2-99.6), 99.2% (95% CI, 96.7-99.8), and 98.3% (95% CI, 96.2-99.6), respectively. In a real-world setting, an adjuvant paclitaxel/trastuzumab regimen was associated with low recurrence rates among women with stage I, HER2-positive breast cancer. Additionally, we reviewed other treatment optimization strategies attempted or ongoing in HER2-positive breast cancer., Competing Interests: Declaration of Competing Interest VD, MS, FJ, MM, MP, IS, WH: none. GNM: Travel grants for meetings from Roche and Bayer, outside the submitted work. EA: Speaking fee/consultancy: Eli Lilly, Sandoz, AstraZeneca. Support to attend medical conferences from Eli Lilly, Roche, Novartis, Genetics, Istituto Gentili, Daiichi Sankyo (all outside the present work). CM: receive fees from Novartis and Lilly outside the submitted work.Ugo De Giorgi received honoraria for advisory boards or speaker fees for Pfizer, BMS, MSD, PharmaMar, Astellas, Bayer, Ipsen, Roche, Novartis, Clovis, GSK, AstraZeneca, Institutional research grants from AstraZeneca, Sanofi and Roche all outside the submitted work. UDG: Advisory boards: Astellas, Bayer, BMS, Ipsen, MSD, Novartis, Pfizer, PharmaMar, Roche; Institutional research grant: AstraZeneca, Roche, Sanofi. AS: Advisory Board: BMS (BRISTOL-MYERS-SQUIBB), Servier,Gilead, Pfizer, Eisai, Bayer, MSD (MERCK SHARP & DOHME); Consultancy: Arqule, Sanofi, Incyte; Speaker’s Bureau: Takeda, BMS, Roche, Abbvie, Amgen, Celgene, Servier, Gilead, Astrazeneca, Pfizer, Arqule, Lilly, Sandoz, Eisai, Novartis, Bayer, MSD. DT: advisory board: Agendia, AstraZeneca, Daiichi Sankyo, Eli Lilly, Medscape, MSD, Novartis, Roche; Travel: AstraZeneca,Pfizer, Roche. FPD: Advisory Board: Amgen, AstraZeneca, Daiichi Sankyo, Gilead Sceince, Lilly, Novartis, Pfizer, Pierre Fabre, Roche, Seagen; Contracted Research: Fondation belge contre le cancer; Institutional grant: AstraZeneca. AB: Advisory board: Argen, BMS, Eli-Lilly, MSD, Novartis, Pfizer, Roche. GB: Advisory board: BMS, Eli Lilly, MSD, Novartis, Pfizer, Roche; Travel: BMS, Eli Lilly, MSD, Novartis, Pfizer, Roche. ML: reports advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Gilead, MSD and Exact Sciences; speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo and Takeda; Travel Grants from Gilead; Research funding (to the Institution) from Gilead outside the submitted work. EdA: Honoraria and/or advisory board from Roche/GNE, Novartis, SeaGen, Zodiac, Libbs, Pierre Fabre, Lilly, Astra-Zeneca; travel grants from Roche/GNE and Astra-Zeneca; Research grant to my institution from Roche/GNE, AstraZeneca, and GSK/Novartis. MP: Board Member (Scientific Board): Oncolytics; Consultant (honoraria): AstraZeneca, Camel-IDS/Precirix, Gilead, Immunomedics, Lilly, Menarini, MSD, Novartis, Pfizer, Roche-Genentech, Seattle Genetics, Immutep, Seagen, NBE Therapeutics, Frame Therapeutics; Research grants to my Institute: AstraZeneca, Immunomedics, Lilly, Menarini, MSD, Novartis, Pfizer, Radius, Roche-Genentech, Servier, Synthon., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Published
2023
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38. Unexpected Durable Complete Response With Anti-PD-L1 Blockade in Metastatic Undifferentiated Pleomorphic Sarcoma: A Case Report With Host and Tumor Biomarker Analysis.

Author

Pesántez D, Indacochea A, Angelats L, Sirico M, Victoria I, Sanfeliu E, Teixido C, González-Navarro AE, Galván P, Brasó-Maristany F, Jares P, Juan M, Prat A, Schettini F, and García-Corbacho J

Subjects
Humans, Remission Induction, B7-H1 Antigen antagonists & inhibitors, Biomarkers, Tumor analysis, Sarcoma drug therapy, Sarcoma pathology, Immune Checkpoint Inhibitors therapeutic use
Published
2023
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39. Prognostic significance of HER2-low status in HR-positive/HER2-negative advanced breast cancer treated with CDK4/6 inhibitors.

Author

Zattarin E, Presti D, Mariani L, Sposetti C, Leporati R, Menichetti A, Corti C, Benvenuti C, Fucà G, Lobefaro R, Ligorio F, Provenzano L, Vingiani A, Del Vecchio M, Griguolo G, Sirico M, Bernocchi O, Marra A, Zagami P, Agostinetto E, Jacobs F, Di Mauro P, Esposito A, Giorgi CA, Lalli L, Boldrini L, Giacchetti PPB, Schianca AC, Guarneri V, Pedersini R, Losurdo A, Zambelli A, Generali D, Criscitiello C, Curigliano G, Pruneri G, de Braud F, Dieci MV, and Vernieri C

Abstract

Whether Human Epidermal growth factor Receptor 2 (HER2)-low status has prognostic significance in HR + /HER2- advanced Breast Cancer (aBC) patients treated with first-line Endocrine Therapy plus CDK 4/6 inhibitors remains unclear. In 428 patients evaluated, HER2-low status was independently associated with significantly worse PFS and OS when compared with HER2-0 status. Based on our findings, HER2-low status could become a new prognostic biomarker in this clinical setting., (© 2023. The Author(s).)

Published
2023
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40. Oligometastatic breast cancer and metastasis-directed treatment: an aggressive multimodal approach to reach the cure.

Author

Merloni F, Palleschi M, Casadei C, Romeo A, Curcio A, Casadei R, Stella F, Ercolani G, Gianni C, Sirico M, Cima S, Sarti S, Cecconetto L, Di Menna G, and De Giorgi U

Abstract

Metastatic breast cancer (BC) is considered an incurable disease and is usually treated with palliative intent. However, about 50% of metastatic BCs present with only a few metastatic lesions and are characterized by longer overall survival. These patients, defined as oligometastatic, could benefit from a multimodal approach, which combines systemic therapy with metastasis-directed treatment (stereotactic ablative therapy or surgery). The current definition of oligometastatic seems incomplete since it is based only on imaging findings and does not include biological features, and the majority of relevant data supporting this strategy comes from retrospective or non-randomized studies. However, the chance of reaching long-term complete remission or even a cure has led to the development of randomized trials investigating the impact of combined treatment in oligometastatic BC (OMBC). The SABR-COMET trial, the first randomized study to include BC patients, showed promising results from a combination of stereotactic ablative radiotherapy and systemic therapy. Considering the randomized trial's results, multidisciplinary teams should be set up to select OMBC patients who could achieve long-term survival with aggressive multimodal treatment., Competing Interests: Dr. De Giorgi received honoraria for advisory boards or speaker fees for Pfizer, BMS, MSD, PharmaMar, Astellas, Bayer, Ipsen, Roche, Novartis, Clovis, GSK, AstraZeneca, Institutional research grants from AstraZeneca, Sanofi, and Roche Dr. Michela Palleschi has received advisory board fees from Novartis., (© The Author(s), 2023.)

Published
2023
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41. Locoregional treatment of de novo stage IV breast cancer in the era of modern oncology.

Author

Merloni F, Palleschi M, Gianni C, Casadei C, Curcio A, Romeo A, Rocchi M, Cima S, Sirico M, Sarti S, Cecconetto L, Mariotti M, Di Menna G, and De Giorgi U

Abstract

Approximately 6% of metastatic breast cancers arise de novo . While systemic therapy (ST) remains the treatment backbone as for patients with metachronous metastases, locoregional treatment (LRT) of the primary tumor remains a controversial method. The removal of the primary has an established role for palliative purposes, but it is unclear if it could also determine a survival benefit. Retrospective evidence and pre-clinical studies seem to support the removal of the primary as an effective approach to improve survival. On the other hand, most randomized evidence suggests avoiding LRT. Both retrospective and prospective studies suffer several limitations, ranging from selection bias and outdated ST to a small sample of patients. In this review we discuss available data and try to identify subgroups of patients which could benefit the most from LRT of the primary, to facilitate clinical practice decisions, and to hypothesize future studies design on this topic., Competing Interests: UD received honoraria for advisory boards or speaker fees for Pfizer, BMS, MSD, PharmaMar, Astellas, Bayer, Ipsen, Roche, Novartis, Clovis, GSK, AstraZeneca, Institutional research grants from AstraZeneca, Sanofi and Roche. MP has received advisory board fees from Novartis. All other authors confirm that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Merloni, Palleschi, Gianni, Casadei, Curcio, Romeo, Rocchi, Cima, Sirico, Sarti, Cecconetto, Mariotti, Di Menna and De Giorgi.)

Published
2023
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42. Current State and Future Challenges for PI3K Inhibitors in Cancer Therapy.

Author

Sirico M, D'Angelo A, Gianni C, Casadei C, Merloni F, and De Giorgi U

Abstract

The phosphoinositide 3 kinase (PI3K)-protein kinase B (PKB/AKT)-mammalian target of the rapamycin (mTOR) axis is a key signal transduction system that links oncogenes and multiple receptor classes which are involved in many essential cellular functions. Aberrant PI3K signalling is one of the most commonly mutated pathways in cancer. Consequently, more than 40 compounds targeting key components of this signalling network have been tested in clinical trials among various types of cancer. As the oncogenic activation of the PI3K/AKT/mTOR pathway often occurs alongside mutations in other signalling networks, combination therapy should be considered. In this review, we highlight recent advances in the knowledge of the PI3K pathway and discuss the current state and future challenges of targeting this pathway in clinical practice.

Published
2023
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43. Neoadjuvant endocrine therapy for luminal breast tumors: State of the art, challenges and future perspectives.

Author

Sirico M, Virga A, Conte B, Urbini M, Ulivi P, Gianni C, Merloni F, Palleschi M, Gasperoni M, Curcio A, Saha D, Buono G, Muñoz M, De Giorgi U, and Schettini F

Subjects
Humans, Female, Mastectomy, Chemotherapy, Adjuvant, Receptor, ErbB-2, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Neoadjuvant Therapy, Breast Neoplasms genetics
Abstract

Neoadjuvant endocrine treatment (NET) associates to satisfactory rates of breast conservative surgery and conversions from inoperable to operable hormone receptor-positive (HR+)/HER2-negative breast cancer (BC), with less toxicities than neoadjuvant chemotherapy (NACT) and similar outcomes. Hence, it has been proposed as a logical alternative to NACT in patients with HR+/HER2- BC candidate to a neoadjuvant approach. Nevertheless, potential barriers to the widespread use of NET include the heterogeneous nature of patient response coupled with the long duration needed to achieve a clinical response. However, interest in NET has significantly increased in the last decade, owing to more in-depth investigation of several biomarkers for a more adequate patient selection and on-treatment benefit monitoring, such as PEPI score, Ki67 and genomic assays. This review is intended to describe the state-of-the-art regarding NET, its future perspectives and potential integration with molecular biomarkers for the optimal selection of patients, regimen and duration of (neo)adjuvant treatments., Competing Interests: Declaration of Competing Interest MP, received advisory board fees from Novartis. GB received honoraria or speaker’s fee from Novartis, GSK, Eli-Lilly, Pfizer, Astra-Zeneca, Roche and Genetic Spa. UDG received honoraria for advisory boards or invited speaker fees from Pfizer, BMS, MSD, PharmaMar, Astellas, Bayer, Ipsen, Novartis, Roche, Clovis, AstraZeneca, institutional research grants from AstraZeneca, Sanofi and Roche. The other authors declare no conflict of interests., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Published
2023
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44. Potential Impact of Preoperative Circulating Biomarkers on Individual Escalating/de-Escalating Strategies in Early Breast Cancer.

Author

Gianni C, Palleschi M, Merloni F, Bleve S, Casadei C, Sirico M, Di Menna G, Sarti S, Cecconetto L, Mariotti M, and De Giorgi U

Abstract

The research on non-invasive circulating biomarkers to guide clinical decision is in wide expansion, including the earliest disease settings. Several new intensification/de-intensification strategies are approaching clinical practice, personalizing the treatment for each patient. Moreover, liquid biopsy is revealing its potential with multiple techniques and studies available on circulating biomarkers in the preoperative phase. Inflammatory circulating cells, circulating tumor cells (CTCs), cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), and other biological biomarkers are improving the armamentarium for treatment selection. Defining the escalation and de-escalation of treatments is a mainstay of personalized medicine in early breast cancer. In this review, we delineate the studies investigating the possible application of these non-invasive tools to give a more enlightened approach to escalating/de-escalating strategies in early breast cancer.

Published
2022
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46. Cell-Free DNA Fragmentomics: A Promising Biomarker for Diagnosis, Prognosis and Prediction of Response in Breast Cancer.

Author

Gianni C, Palleschi M, Merloni F, Di Menna G, Sirico M, Sarti S, Virga A, Ulivi P, Cecconetto L, Mariotti M, and De Giorgi U

Subjects
Humans, Female, Biomarkers, Tumor genetics, Liquid Biopsy, Cell-Free Nucleic Acids genetics, Breast Neoplasms diagnosis, Breast Neoplasms genetics, Breast Neoplasms pathology, Circulating Tumor DNA
Abstract

Identifying novel circulating biomarkers predictive of response and informative about the mechanisms of resistance, is the new challenge for breast cancer (BC) management. The integration of omics information will gradually revolutionize the clinical approach. Liquid biopsy is being incorporated into the diagnostic and decision-making process for the treatment of BC, in particular with the analysis of circulating tumor DNA, although with some relevant limitations, including costs. Circulating cell-free DNA (cfDNA) fragmentomics and its integrity index may become a cheaper, noninvasive biomarker that could provide significant additional information for monitoring response to systemic treatments in BC. The purpose of our review is to focus on the available research on cfDNA integrity and its features as a biomarker of diagnosis, prognosis and response to treatments in BC, highlighting new perspectives and critical issues for future applications.

Published
2022
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47. An update on antibody-drug conjugates in urothelial carcinoma: state of the art strategies and what comes next.

Author

D'Angelo A, Chapman R, Sirico M, Sobhani N, Catalano M, Mini E, and Roviello G

Subjects
Humans, Immune Checkpoint Inhibitors, Antineoplastic Agents therapeutic use, Carcinoma, Transitional Cell drug therapy, Immunoconjugates adverse effects, Urinary Bladder Neoplasms drug therapy
Abstract

In recent years, considerable progress has been made in increasing the knowledge of tumour biology and drug resistance mechanisms in urothelial cancer. Therapeutic strategies have significantly advanced with the introduction of novel approaches such as immune checkpoint inhibitors and Fibroblast Growth Factor Receptor inhibitors. However, despite these novel agents, advanced urothelial cancer is often still progressive in spite of treatment and correlates with a poor prognosis. The introduction of antibody-drug conjugates consisting of a target-specific monoclonal antibody covalently linked to a payload (cytotoxic agent) is a novel and promising therapeutic strategy. In December 2019, the US Food and Drug Administration (FDA) granted accelerated approval to the nectin-4-targeting antibody-drug conjugate, enfortumab vedotin, for the treatment of advanced or metastatic urothelial carcinomas that are refractory to both immune checkpoint inhibitors and platinum-based treatment. Heavily pre-treated urothelial cancer patients reported a significant, 40% response to enfortumab vedotin while other antibody-drug conjugates are currently still under investigation in several clinical trials. We have comprehensively reviewed the available treatment strategies for advanced urothelial carcinoma and outlined the mechanism of action of antibody-drug conjugate agents, their clinical applications, resistance mechanisms and future strategies for urothelial cancer., (© 2022. Crown.)

Published
2022
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48. Circulating inflammatory cells in patients with metastatic breast cancer: Implications for treatment.

Author

Gianni C, Palleschi M, Schepisi G, Casadei C, Bleve S, Merloni F, Sirico M, Sarti S, Cecconetto L, Di Menna G, Schettini F, and De Giorgi U

Abstract

Adaptive and innate immune cells play a crucial role as regulators of cancer development. Inflammatory cells in blood flow seem to be involved in pro-tumor activities and contribute to breast cancer progression. Circulating lymphocyte ratios such as the platelet-lymphocytes ratio (PLR), the monocyte-lymphocyte ratio (MLR) and the neutrophil-lymphocyte ratio (NLR) are new reproducible, routinely feasible and cheap biomarkers of immune response. These indexes have been correlated to prognosis in many solid tumors and there is growing evidence on their clinical applicability as independent prognostic markers also for breast cancer. In this review we give an overview of the possible value of lymphocytic indexes in advanced breast cancer prognosis and prediction of outcome. Furthermore, targeting the immune system appear to be a promising therapeutic strategy for breast cancer, especially macrophage-targeted therapies. Herein we present an overview of the ongoing clinical trials testing systemic inflammatory cells as therapeutic targets in breast cancer., Competing Interests: This research received no external funding. MP has received advisory board fees from Novartis. UD has received advisory board or consultant fees from Merck Sharp and Dohme, Bristol Myers Squibb, Janssen, Astellas, Sanofi, Bayer, Pfizer, Ipsen, Novartis, and Pharmamar and institutional research grants from Astrazeneca, Sanofi, and Roche. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gianni, Palleschi, Schepisi, Casadei, Bleve, Merloni, Sirico, Sarti, Cecconetto, Di Menna, Schettini and De Giorgi.)

Published
2022
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49. Immunotherapeutic treatments in hepatocellular carcinoma; achievements, challenges and future prospects.

Author

Roudi R, D'Angelo A, Sirico M, and Sobhani N

Subjects
Animals, Antineoplastic Agents, Immunological therapeutic use, Carcinoma, Hepatocellular immunology, Humans, Liver Neoplasms immunology, Carcinoma, Hepatocellular therapy, Immunotherapy methods, Liver Neoplasms therapy
Abstract

Hepatocellular carcinoma (HCC) is one of the most common and fatal malignancies with an alarming trend all around the world. Common therapeutic approaches in the early stage of disease are surgical resection, ablation, and liver transplantation. Due to the insidious identity of HCC, the majority of the patients are diagnosed at advanced stages, where tumor spreading, or distant metastasis unfortunately have already occurred. Immunotherapeutic options have elicited a promising approach in some malignancies with Food and Drug Administration (FDA) approving the first checkpoint inhibitor anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) ipilimumab for the treatment of melanoma ten years ago. In the past decade, many clinical trials have been investigating anti-CTLA-4 as well as anti-programmed cell death protein 1 (PD-1) therapies in various solid tumors, including HCC. In this mini-review we will discuss the latest clinical data from clinical trials for immune-checkpoint inhibitors for the treatment of HCC., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Published
2021
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