المؤلفون: Guida M., Bartolomeo N., Quaresmini D., Quaglino P., Madonna G., Pigozzo J., Di Giacomo A. M., Minisini A. M., Tucci M., Spagnolo F., Occelli M., Ridolfi L., Queirolo P., De Risi I., Valente M., Sciacovelli A. M., Chiarion Sileni V., Ascierto P. A., Stigliano L., Strippoli S.

المساهمون: Guida, M., Bartolomeo, N., Quaresmini, D., Quaglino, P., Madonna, G., Pigozzo, J., Di Giacomo, A. M., Minisini, A. M., Tucci, M., Spagnolo, F., Occelli, M., Ridolfi, L., Queirolo, P., De Risi, I., Valente, M., Sciacovelli, A. M., Chiarion Sileni, V., Ascierto, P. A., Stigliano, L., Strippoli, S.

مصطلحات موضوعية: Checkpoint inhibitor, Metastatic melanoma, Neutrophil-to-lymphocyte ratio, Platelet-to-lymphocyte ratio, Blood Platelet, Human, Immunotherapy, Lymphocyte, Prognosi, Prospective Studie, Proto-Oncogene Proteins B-raf, Retrospective Studie, Melanoma, Neutrophils

الوصف: Background To evaluate the capability of basal and one-month differed white blood cells (WBC), neutrophil, lymphocyte and platelet values and their ratios (neutrophils-to-lymphocytes ratio, NLR, and platelets-to-lymphocytes ratio, PLR) in predicting the response to immune checkpoint inhibitors (ICI) in metastatic melanoma (MM). Methods We performed a retrospective study of 272 BRAF wild-type MM patients treated with first line ICI. Bivariable analysis was used to correlate patient/tumor characteristics with clinical outcomes. Variations between time 1 and time 0 (Delta) of blood parameters were also calculated and dichotomized using cut-off values assessed by ROC curve. Results At baseline, higher neutrophils and NLR negatively correlated with PFS, OS and disease control rate (DCR). Higher PLR was also associated with worse OS. In multivariable analysis, neutrophils (p = 0.003), WBC (p = 0.069) and LDH (p = 0.07) maintained their impact on PFS, while OS was affected by LDH (p < 0.001), neutrophils (p < 0.001) and PLR (p = 0.022), while DCR by LDH (p = 0.03) and neutrophils (p = 0.004). In the longitudinal analysis, PFS negatively correlated with higher Delta platelets (p = 0.039), Delta WBC (p < 0.001), and Delta neutrophils (p = 0.020), and with lower Delta lymphocytes (p < 0.001). Moreover, higher Delta NLR and Delta PLR identified patients with worse PFS, OS and DCR. In the multivariable model, only Delta NLR influenced PFS (p = 0.004), while OS resulted affected by higher Delta WBC (p < 0.001) and lower Delta lymphocytes (p = 0.038). Higher Delta WBC also affected the DCR (p = 0.003). When clustering patients in 4 categories using basal LDH and Delta NLR, normal LDH/lower Delta NLR showed a higher PFS than high LDH/higher Delta NLR (20 vs 5 months). Moreover, normal LDH/higher Delta lymphocytes had a higher OS than high LDH/lower Delta lymphocytes (50 vs. 10 months). Conclusions Baseline and early variations of blood cells, together with basal LDH, strongly predict the efficacy of ICI in MM. ...

وصف الملف: ELETTRONICO

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/35382857; info:eu-repo/semantics/altIdentifier/wos/WOS:000778499200004; volume:20; issue:1; firstpage:1; lastpage:15; numberofpages:15; journal:JOURNAL OF TRANSLATIONAL MEDICINE; https://hdl.handle.net/11365/1221041Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85127719534; https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-022-03359-xTest; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8981693Test/

الإتاحة: https://doi.org/10.1186/s12967-022-03359-xTest
https://hdl.handle.net/11365/1221041Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8981693Test/

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

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

مصطلحات موضوعية: immunotherapy, radiotherapy, skin neoplasms

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

وصف الملف: STAMPA

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/35701070; info:eu-repo/semantics/altIdentifier/wos/WOS:000811680400001; volume:10; issue:6; firstpage:1; lastpage:14; numberofpages:14; journal:JOURNAL FOR IMMUNOTHERAPY OF CANCER; https://hdl.handle.net/11585/904590Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85132050226; https://jitc.bmj.com/content/10/6/e004742Test

الإتاحة: https://doi.org/10.1136/jitc-2022-004742Test
https://hdl.handle.net/11585/904590Test
https://jitc.bmj.com/content/10/6/e004742Test

المؤلفون: Garutti M., Targato G., Buriolla S., Palmero L., Minisini A. M., Puglisi F.

المساهمون: Garutti, M., Targato, G., Buriolla, S., Palmero, L., Minisini, A. M., Puglisi, F.

مصطلحات موضوعية: Abemaciclib, CDK4, CDK4/6, CDK6, melanoma, Palbociclib, Ribociclib

الوصف: Historically, metastatic melanoma was considered a highly lethal disease. However, recent advances in drug development have allowed a significative improvement in prognosis. In particular, BRAF/MEK inhibitors and anti-PD1 antibodies have completely revolutionized the management of this disease. Nonetheless, not all patients derive a benefit or a durable benefit from these therapies. To overtake this challenges, new clinically active compounds are being tested in the context of clinical trials. CDK4/6 inhibitors are drugs already available in clinical practice and preliminary evidence showed a promising activity also in melanoma. Herein we review the available literature to depict a comprehensive landscape about CDK4/6 inhibitors in melanoma. We present the molecular and genetic background that might justify the usage of these drugs, the preclinical evidence, the clinical available data, and the most promising ongoing clinical trials.

العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:000667856400001; volume:10; issue:6; firstpage:1334; journal:CELLS; http://hdl.handle.net/11390/1208046Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85107429643

الإتاحة: https://doi.org/10.3390/cells10061334Test
http://hdl.handle.net/11390/1208046Test

المؤلفون: Basile D., Gerratana L., Corvaja C., Pelizzari G., Franceschin G., Bertoli E., Palmero L., Zara D., Alberti M., Buriolla S., Da Ros L., Bonotto M., Mansutti M., Spazzapan S., Cinausero M., Minisini A. M., Fasola G., Puglisi F.

المساهمون: Basile, D., Gerratana, L., Corvaja, C., Pelizzari, G., Franceschin, G., Bertoli, E., Palmero, L., Zara, D., Alberti, M., Buriolla, S., Da Ros, L., Bonotto, M., Mansutti, M., Spazzapan, S., Cinausero, M., Minisini, A. M., Fasola, G., Puglisi, F.

مصطلحات موضوعية: CDK4/6 inhibitor, MBC, Metastatic luminal breast cancer, Treatment strategies

الوصف: Background: Endocrine therapy (ET) plus cyclin-dependent-kinases 4/6 inhibitors (CDK4/6i) represents the standard treatment for luminal-metastatic breast cancer (MBC). However, prospective head-to-head comparisons are still lacking for 1st line (L) options, and it is still crucial to define the best strategy between 1st and 2nd L. Materials and methods: 717 consecutive luminal-MBC pts treated between 2008 and 2020 were analyzed at the Oncology Department of Aviano and Udine, Italy. Differences about survival outcomes (OS, PFS and PPS) were tested by log-rank test. The attrition rate (AR) between 1st and 2ndL was calculated. Results: At 1stL, pts were treated with ET (49%), chemotherapy (CT) (31%) and ET-CDKi (20%) while, at 2ndL, 33% received ET, 33% CT and 8% ET-CDKi. Overall AR was 10%, 7% for CT, 8% for ET and 17% for ET-CDKi. By multivariate analysis, 1stL ET-CDK4/6i showed a better mPFS1 and OS. Moreover, 2ndL ET-CDK4/6i demonstrated better mPFS2 compared to ET and CT. Notably, 1stL ET-CDKi resulted in higher mPFS than 2ndL ET-CDKi. Intriguingly, 1stL ET-CDK4/6i was associated with worse mPPS compared to CT and ET. Secondarily, 1stL ET-CDK4/6i followed by CT had worse OS compared to 1stL ET-CDK4/6i followed by ET. Notably, none of baseline characteristics at 2ndL influenced 2ndL treatment choice (ET vs. CT) after ET-CDKi. Conclusion: Our real-world data demonstrated that ET-CDKi represents the best option for 1stL luminal-MBC compared to ET and CT. Also, the present study pointed out that 2ndL ET, potentially combined with other molecules, could be a feasible option after CDK4/6i failure, postponing CT on later lines.

العلاقة: volume:57; firstpage:104; lastpage:112; numberofpages:9; journal:THE BREAST; http://hdl.handle.net/11390/1207516Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85104980676

الإتاحة: https://doi.org/10.1016/j.breast.2021.02.015Test
http://hdl.handle.net/11390/1207516Test

المؤلفون: Guida M., Bartolomeo N., Quaglino P., Madonna G., Pigozzo J., Di Giacomo A. M., Minisini A. M., Tucci M., Spagnolo F., Occelli M., Ridolfi L., Queirolo P., De Risi I., Quaresmini D., Gambale E., Sileni V. C., Ascierto P. A., Stigliano L., Strippoli S.

المساهمون: Guida, M., Bartolomeo, N., Quaglino, P., Madonna, G., Pigozzo, J., Di Giacomo, A. M., Minisini, A. M., Tucci, M., Spagnolo, F., Occelli, M., Ridolfi, L., Queirolo, P., De Risi, I., Quaresmini, D., Gambale, E., Sileni, V. C., Ascierto, P. A., Stigliano, L., Strippoli, S.

مصطلحات موضوعية: Checkpoint inhibitor, Immunotherapy, Melanoma, NRAS mutation

الوصف: Neuroblastoma RAS Viral Oncogen Homolog (NRAS) mutant melanoma is usually considered more aggressive and more responsive to checkpoint inhibitor immunotherapy (CII) than NRAS wildtype. We retrospectively recruited 331 metastatic melanoma patients treated with CII as first line: 162 NRAS-mutant/BRAF wild-type and 169 wt/wt. No substantial differences were observed among the two cohorts regarding the melanoma onset and disease-free interval. Also, overall response to CII, progression-free survival and overall survival were similar in the two groups. Therefore, our data do not show increased aggressiveness and higher responsiveness to CII in NRAS-mutant melanoma. The controversy in the published data could be due to different patient characteristics and treatment heterogeneity. We believe our data adds evidence to clear up these controversial issues. Aims: It is debated whether the NRAS-mutant melanoma is more aggressive than NRAS wildtype. It is equally controversial whether NRAS-mutant metastatic melanoma (MM) is more responsive to checkpoint inhibitor immunotherapy (CII). 331 patients treated with CII as first-line were retrospectively recruited: 162 NRAS-mutant/BRAF wild-type (mut/wt) and 169 wt/wt. We compared the two cohorts regarding the characteristics of primary and metastatic disease, disease-free interval (DFI) and outcome to CII. No substantial differences were observed between the two groups at melanoma onset, except for a more frequent ulceration in the wt/wt group (p = 0.03). Also, the DFI was very similar in the two cohorts. In advanced disease, we only found lung and brain progression more frequent in the wt/wt group. Regarding the outcomes to CII, no significant differences were reported in overall response rate (ORR), disease control rate (DCR), progression free survival (PFS) or overall survival (OS) (42% versus 37%, 60% versus 59%, 12 (95% CI, 7-18) versus 9 months (95% CI, 6-16) and 32 (95% CI, 23-49) versus 27 months (95% CI, 16-35), respectively). Irrespectively of mutational status, a ...

وصف الملف: ELETTRONICO

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/33530579; info:eu-repo/semantics/altIdentifier/wos/WOS:000615004300001; volume:13; issue:3; firstpage:1; lastpage:15; numberofpages:15; journal:CANCERS; https://hdl.handle.net/11365/1233247Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85099938582; https://www.mdpi.com/2072-6694/13/3/475Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865301Test/

الإتاحة: https://doi.org/10.3390/cancers13030475Test
https://hdl.handle.net/11365/1233247Test
https://www.mdpi.com/2072-6694/13/3/475Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865301Test/

المؤلفون: Fasola G., Pelizzari G., Zara D., Targato G., Petruzzellis G., Minisini A. M., Bin A., Donato R., Mansutti M., Comuzzi C., Candoni A., Sperotto A., Fanin R.

المساهمون: Fasola, G., Pelizzari, G., Zara, D., Targato, G., Petruzzellis, G., Minisini, A. M., Bin, A., Donato, R., Mansutti, M., Comuzzi, C., Candoni, A., Sperotto, A., Fanin, R.

مصطلحات موضوعية: Cancer, Containment measure, COVID-19, SARS-CoV-2, Triage

الوصف: Background: Triage procedures have been implemented to limit hospital access and minimize infection risk among patients with cancer during the coronavirus disease (COVID-19) outbreak. In the absence of prospective evidence, we aimed to evaluate the predictive performance of a triage system in the oncological setting. Materials and Methods: This retrospective cohort study analyzes hospital admissions to the oncology and hematology department of Udine, Italy, during the COVID-19 pandemic (March 30 to April 30, 2020). A total of 3,923 triage procedures were performed, and data of 1,363 individual patients were reviewed. Results: A self-report triage questionnaire identified 6% of triage-positive procedures, with a sensitivity of 66.7% (95% confidence interval [CI], 43.0%–85.4%), a specificity of 94.3% (95% CI, 93.5%–95.0%), and a positive predictive value of 5.9% (95% CI, 4.3%–8.0%) for the identification of patients who were not admitted to the hospital after medical review. Patients with thoracic cancer (odds ratio [OR], 1.69; 95% CI, 1.13–2.53, p =.01), younger age (OR, 1.52; 95% CI, 1.15–2.01, p <.01), and body temperature at admission ≥37°C (OR, 9.52; 95% CI, 5.44–16.6, p <.0001) had increased risk of positive triage. Direct hospital access was warranted to 93.5% of cases, a further 6% was accepted after medical evaluation, whereas 0.5% was refused at admission. Conclusion: A self-report questionnaire has a low positive predictive value to triage patients with cancer and suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) symptoms. Differential diagnosis with tumor- or treatment-related symptoms is always required to avoid unnecessary treatment delays. Body temperature measurement improves the triage process's overall sensitivity, and widespread SARS-CoV-2 testing should be implemented to identify asymptomatic carriers. Implications for Practice: This is the first study to provide data on the predictive performance of a triage system in the oncological setting during the coronavirus ...

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/33539583; info:eu-repo/semantics/altIdentifier/wos/WOS:000619546100001; volume:26; issue:4; firstpage:e694; lastpage:e703; journal:THE ONCOLOGIST; https://hdl.handle.net/11380/1294024Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85101212226

الإتاحة: https://doi.org/10.1002/onco.13706Test
https://hdl.handle.net/11380/1294024Test

المؤلفون: Biganzoli L., Cinieri S., Berardi R., Pedersini R., McCartney A., Minisini A. M., Caremoli E. R., Spazzapan S., Magnolfi E., Brunello A., Risi E., Palumbo R., Leo S., Colleoni M., Donati S., De Placido S., Orlando L., Pistelli M., Parolin V., Mislang A., Becheri D., Puglisi F., Sanna G., Zafarana E., Boni L., Mottino G.

المساهمون: Biganzoli, L., Cinieri, S., Berardi, R., Pedersini, R., Mccartney, A., Minisini, A. M., Caremoli, E. R., Spazzapan, S., Magnolfi, E., Brunello, A., Risi, E., Palumbo, R., Leo, S., Colleoni, M., Donati, S., De Placido, S., Orlando, L., Pistelli, M., Parolin, V., Mislang, A., Becheri, D., Puglisi, F., Sanna, G., Zafarana, E., Boni, L., Mottino, G.

مصطلحات موضوعية: Breast cancer, Functional decline, Metastatic, Nab-paclitaxel, Older adult, Toxicity

الوصف: Background: Limited data are available regarding the use of nab-paclitaxel in older patients with breast cancer. A weekly schedule is recommended, but there is a paucity of evidence regarding the optimal dose. We evaluated the efficacy of two different doses of weekly nab-paclitaxel, with a specific focus on their corresponding impact on patient function, in order to address the lack of data specifically relating to the older population. Methods: EFFECT is an open-label, phase II trial wherein 160 women with advanced breast cancer aged ≥ 65 years were enrolled from 15 institutions within Italy. Patients were randomly assigned 1:1 to receive nab-paclitaxel 100 mg/m2 (arm A) or 125 mg/m2 (arm B) on days 1, 8, and 15 on a 28-day cycle, as first-line treatment for advanced disease. The primary endpoint was event-free survival (EFS), wherein an event was defined as disease progression (PD), functional decline (FD), or death. In each arm, the null hypothesis that the median EFS would be ≤ 7 months was tested against a one-sided alternative according to the Brookmeyer Crowley test. Secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and safety. Results: After a median follow-up of 32.6 months, 140 events were observed in 158 evaluable patients. Median EFS was 8.2 months (90% CI, 5.9-8.9; p = 0.188) in arm A vs 8.3 months (90% CI, 6.2-9.7, p = 0.078) in arm B. Progression-free survival, overall survival, and response rates were similar in both groups. A higher percentage of dose reductions and discontinuations due to adverse events (AEs) was noted in arm B. The most frequently reported non-haematological AEs were fatigue (grade [G] 2-3 toxicity occurrence in arm A vs B, 43% and 51%, respectively) and peripheral neuropathy (G2-3 arm A vs B, 19% and 38%, respectively). Conclusion: Pre-specified outcomes were similar in both treatment arms. However, 100 mg/m2 was significantly better tolerated with fewer neurotoxicity-related ...

العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:000560788200001; volume:22; issue:1; firstpage:83; journal:BREAST CANCER RESEARCH; http://hdl.handle.net/11390/1189175Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85089170533

الإتاحة: https://doi.org/10.1186/s13058-020-01319-1Test
http://hdl.handle.net/11390/1189175Test

المؤلفون: Garutti M., Buriolla S., Bertoli E., Vitale M. G., Rossi E., Schinzari G., Minisini A. M., Puglisi F.

المساهمون: Garutti, M., Buriolla, S., Bertoli, E., Vitale, M. G., Rossi, E., Schinzari, G., Minisini, A. M., Puglisi, F.

مصطلحات موضوعية: Adjuvant, BRAF, Immunotherapy, MEK, Melanoma, Neoadjuvant

الوصف: Despite surgical resection and adjuvant therapies, stage III melanomas still have a substantial risk of relapse. Neoadjuvant therapy is an emerging strategy that might offer superior efficacy compared to adjuvant therapy. Moreover, neoadjuvant therapy has some virtual advantages: it might allow for less demolitive surgery, permit the in vivo evaluation of drug efficacy, help tailor adjuvant treatments, and play a crucial role in innovative translational research. Herein, we review the available literature to explore the scientific background behind the neoadjuvant approach. We also discuss published clinical trials with a focus on predictive biomarkers and ongoing studies. Finally, we outline a possible framework for future neoadjuvant clinical trial development based on the International Neoadjuvant Melanoma Consortium guidelines.

العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:000554179400001; volume:12; issue:7; firstpage:1; lastpage:19; numberofpages:19; journal:CANCERS; http://hdl.handle.net/11390/1188798Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85088412916

الإتاحة: https://doi.org/10.3390/cancers12071941Test
http://hdl.handle.net/11390/1188798Test

المؤلفون: Galardi, Francesca, De Luca, Francesca, Biagioni, Chiara, Migliaccio, Ilenia, Curigliano, Giuseppe, Minisini, Alessandro M, Bonechi, Martina, Moretti, Erica, Risi, Emanuela, McCartney, Amelia, Benelli, Matteo, Romagnoli, Dario, Cappadona, Silvia, Gabellini, Stefano, Guarducci, Cristina, Conti, Valerio, Biganzoli, Laura, Di Leo, Angelo, Malorni, Luca

المساهمون: F. Galardi, F. De Luca, C. Biagioni, I. Migliaccio, G. Curigliano, A.M. Minisini, M. Bonechi, E. Moretti, E. Risi, A. Mccartney, M. Benelli, D. Romagnoli, S. Cappadona, S. Gabellini, C. Guarducci, V. Conti, L. Biganzoli, A. Di Leo, L. Malorni

مصطلحات موضوعية: Biomarker, CDK4/6 inhibitor, CTC, Liquid biopsy, Luminal breast cancer, Metastatic, Palbociclib, ddPCR, Settore MED/06 - Oncologia Medica

الوصف: Background Circulating tumor cells (CTCs) are prognostic in patients with advanced breast cancer (ABC). However, no data exist about their use in patients treated with palbociclib. We analyzed the prognostic role of CTC counts in patients enrolled in the cTREnd study, a pre-planned translational sub-study of TREnd (NCT02549430), that randomized patients with ABC to palbociclib alone or palbociclib plus the endocrine therapy received in the prior line of treatment. Moreover, we evaluated RB1 gene expression on CTCs and explored its prognostic role within the cTREnd subpopulation. Methods Forty-six patients with ER-positive, HER2-negative ABC were analyzed. Blood samples were collected before starting palbociclib treatment (timepoint T0), after the first cycle of treatment (timepoint T1), and at disease progression (timepoint T2). CTCs were isolated and counted by CellSearch (R) System using the CellSearch (TM) Epithelial Cell kit. Progression-free survival (PFS), clinical benefit (CB) during study treatment, and time to treatment failure (TTF) after study treatment were correlated with CTC counts. Samples with >= 5 CTCs were sorted by DEPArray system (R) (DA). RB1 and GAPDH gene expression levels were measured by ddPCR. Results All 46 patients were suitable for CTCs analysis. CTC count at T0 did not show significant prognostic value in terms of PFS and CB. Patients with at least one detectable CTC at T1 (n = 26) had a worse PFS than those with 0 CTCs (n = 16) (p = 0.02). At T1, patients with an increase of at least three CTCs showed reduced PFS compared to those with no increase (mPFS = 3 versus 9 months, (p = 0.004). Finally, patients with >= 5 CTCs at T2 (n = 6/23) who received chemotherapy as post-study treatment had a shorter TTF (p = 0.02). Gene expression data for RB1 were obtained from 19 patients. CTCs showed heterogeneous RB1 expression. Patients with detectable expression of RB1 at any timepoint showed better, but not statistically significant, outcomes than those with undetectable levels. ...

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/33761970; info:eu-repo/semantics/altIdentifier/wos/WOS:000634797700002; volume:23; issue:1; numberofpages:12; journal:BREAST CANCER RESEARCH; http://hdl.handle.net/2434/828433Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85103354230

الإتاحة: https://doi.org/10.1186/s13058-021-01415-wTest
http://hdl.handle.net/2434/828433Test

المؤلفون: Pelizzari G., Bertoli E., Buriolla S., Vitale M. G., Basile D., Palmero L., Zara D., Iacono D., Andrea F., Pascoletti G., Bolzonello S., Garutti M., Fasola G., Puglisi F., Minisini A. M.

المساهمون: Pelizzari, G., Bertoli, E., Buriolla, S., Vitale, M. G., Basile, D., Palmero, L., Zara, D., Iacono, D., Andrea, F., Pascoletti, G., Bolzonello, S., Garutti, M., Fasola, G., Puglisi, F., Minisini, A. M.

الوصف: Patients with melanoma brain metastases (MBM) have poor prognosis, albeit advances in locoregional and systemic treatments. The melanoma-specific Graded Prognostic Assessment (GPA) effectively stratifies survival for patients with MBM. Nevertheless, lactate dehydrogenase (LDH), a well known prognostic factor for patients with melanoma, is not represented in the GPA scores and might add prognostic information for patients with MBM. In this study, 150 consecutive patients with MBM were retrospectively analyzed with the aim of evaluating independent prognostic factors for MBM patients, including LDH. Furthermore, we implemented a disease-specific prognostic score and estimated survival according to treatment modalities. On the basis of multivariable Cox regression analyses, six prognostic factors (age, BRAF status, number of MBM, number of extracranial metastatic sites, performance status, and LDH level) resulted statistically significant in terms of survival and were combined in a prognostic score to stratify patients in distinct prognostic groups ( P < 0.0001). Among treatment modalities, a multimodal approach with stereotactic radiosurgery or neurosurgery associated with systemic therapy showed the best outcome (median overall survival: 12.32 months, 95% confidence interval, 7.92-25.30). This is the first study to demonstrate that LDH has independent prognostic value for patients with MBM and might be used to improve prognostic stratification, albeit external validation is mandatory. Survival of patients with MBM is affected by both disease-specific risk factors and treatment modalities, with locoregional treatments associated with better outcomes.

العلاقة: volume:33; issue:5; firstpage:398; lastpage:405; numberofpages:8; journal:MELANOMA RESEARCH; https://hdl.handle.net/11390/1259565Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85169294961

الإتاحة: https://doi.org/10.1097/CMR.0000000000000907Test
https://hdl.handle.net/11390/1259565Test