22 results on '"Botticelli A"'
Search Results
2. CD137+ and regulatory T cells as independent prognostic factors of survival in advanced non-oncogene addicted NSCLC patients treated with immunotherapy as first-line
- Author
-
Alain Gelibter, Angela Asquino, Lidia Strigari, Ilaria Grazia Zizzari, Lucrezia Tuosto, Fabio Scirocchi, Angelica Pace, Marco Siringo, Elisa Tramontano, Serena Bianchini, Filippo Bellati, Andrea Botticelli, Donatella Paoli, Daniele Santini, Marianna Nuti, Aurelia Rughetti, and Chiara Napoletano
- Subjects
NSCLC ,Immune checkpoint inhibitors ,Pembrolizumab ,Immunotherapy ,CD137+ T cells ,Tregs ,Medicine - Abstract
Abstract Background Immune checkpoint inhibitors (ICIs), administered alone or combined with chemotherapy, are the standard of care in advanced non-oncogene addicted Non-Small Cell Lung Cancer (NSCLC). Despite these treatments' success, most long-term survival benefit is restricted to approximately 20% of patients, highlighting the need to identify novel biomarkers to optimize treatment strategies. In several solid tumors, immune soluble factors, the activatory CD137+ Tcells, and the immunosuppressive cell subsets Tregs and MDSCs (PMN(Lox1+)-MDSC and M-MDSCs) correlated with responses to ICIs and clinical outcomes thus becoming appealing predictive and prognostic factors. This study investigated the role of distinct CD137+ Tcell subsets, Tregs, MDSCs, and immune-soluble factors in NSCLC patients as possible biomarkers. Methods The levels of T cells, MDSCs and soluble factors were evaluated in 89 metastatic NSCLC patients who underwent ICIs as first- or second-line treatment. T cell analysis was performed by cytoflurimetry evaluating Tregs and different CD137+ Tcell subsets also combined with CD3+, CD8+, PD1+, and Ki67+ markers. Circulating cytokines and immune checkpoints were also evaluated by Luminex analysis. All these parameters were correlated with several clinical factors (age, sex, smoking status, PS and TPS), response to therapy, PFS , and OS . The analyses were conducted in the overall population and in patients treated with ICIs as first-line (naïve patients). Results In both groups of patients, high levels of circulating CD137+ and CD137+PD1+ T cells (total, CD4 and CD8) and the soluble factor LAG3 positively correlated with response to therapy. In naïve patients, PMN(Lox1+)-MDSCs negatively correlated with clinical response, and a high percentage of Tregs was associated with favorable survival. Moreover, the balance between Treg/CD137+ Tcells or PMN(Lox1+)-MDSC/CD137+ Tcells was higher in non-responding patients and was associated with poor survival. CD137+ Tcells and Tregs resulted as two positive independent prognostic factors. Conclusion High levels of CD137+, CD137+PD1+ Tcells and sLAG3 could predict the response to ICIs in NSCLC patients independently by previous therapy. Combining the evaluation of CD137+ Tcells and Tregs also as Treg/CD137+ T cells ratio it is possible to identify naive patients with longer survival.
- Published
- 2024
- Full Text
- View/download PDF
3. Weekly chemotherapy as first line treatment in frail head and neck cancer patients in the immunotherapy era
- Author
-
Botticelli, Andrea, Pomati, Giulia, Cirillo, Alessio, Mammone, Giulia, Ciurluini, Fabio, Cerbelli, Bruna, Sciattella, Paolo, Ralli, Massimo, Romeo, Umberto, De Felice, Francesca, Catalano, Carlo, Vullo, Francesco, Della Monaca, Marco, Amirhassankhani, Sasan, Tomao, Silverio, Valentini, Valentino, De Vincentiis, Marco, Tombolini, Vincenzo, Della Rocca, Carlo, Polimeni, Antonella, di Gioia, Cira, Corsi, Alessandro, D’Amati, Giulia, Mezi, Silvia, and Marchetti, Paolo
- Published
- 2021
- Full Text
- View/download PDF
4. The role of opioids in cancer response to immunotherapy
- Author
-
Botticelli, Andrea, Cirillo, Alessio, Pomati, Giulia, Cerbelli, Bruna, Scagnoli, Simone, Roberto, Michela, Gelibter, Alain, Mammone, Giulia, Calandrella, Maria Letizia, Cerbelli, Edoardo, Di Pietro, Francesca Romana, De Galitiis, Federica, Lanzetta, Gaetano, Cortesi, Enrico, Mezi, Silvia, and Marchetti, Paolo
- Published
- 2021
- Full Text
- View/download PDF
5. PD-1/PD-L1 checkpoint inhibitors during late stages of life: an ad-hoc analysis from a large multicenter cohort
- Author
-
Santini, Daniele, Zeppola, Tea, Russano, Marco, Citarella, Fabrizio, Anesi, Cecilia, Buti, Sebastiano, Tucci, Marco, Russo, Alessandro, Sergi, Maria Chiara, Adamo, Vincenzo, Stucci, Luigia S., Bersanelli, Melissa, Mazzaschi, Giulia, Spagnolo, Francesco, Rastelli, Francesca, Giorgi, Francesca Chiara, Giusti, Raffaele, Filetti, Marco, Marchetti, Paolo, Botticelli, Andrea, Gelibter, Alain, Siringo, Marco, Ferrari, Marco, Marconcini, Riccardo, Vitale, Maria Giuseppa, Nicolardi, Linda, Chiari, Rita, Ghidini, Michele, Nigro, Olga, Grossi, Francesco, De Tursi, Michele, Di Marino, Pietro, Pala, Laura, Queirolo, Paola, Bracarda, Sergio, Macrini, Serena, Gori, Stefania, Inno, Alessandro, Zoratto, Federica, Tanda, Enrica T., Mallardo, Domenico, Vitale, Maria Grazia, Talbot, Thomas, Ascierto, Paolo A., Pinato, David J., Ficorella, Corrado, Porzio, Giampiero, and Cortellini, Alessio
- Published
- 2021
- Full Text
- View/download PDF
6. CD137+ and regulatory T cells as independent prognostic factors of survival in advanced non-oncogene addicted NSCLC patients treated with immunotherapy as first-line.
- Author
-
Gelibter, Alain, Asquino, Angela, Strigari, Lidia, Zizzari, Ilaria Grazia, Tuosto, Lucrezia, Scirocchi, Fabio, Pace, Angelica, Siringo, Marco, Tramontano, Elisa, Bianchini, Serena, Bellati, Filippo, Botticelli, Andrea, Paoli, Donatella, Santini, Daniele, Nuti, Marianna, Rughetti, Aurelia, and Napoletano, Chiara
- Subjects
REGULATORY T cells ,IMMUNOTHERAPY ,PROGNOSIS ,T cells ,NON-small-cell lung carcinoma ,IMMUNE checkpoint inhibitors - Abstract
Background: Immune checkpoint inhibitors (ICIs), administered alone or combined with chemotherapy, are the standard of care in advanced non-oncogene addicted Non-Small Cell Lung Cancer (NSCLC). Despite these treatments' success, most long-term survival benefit is restricted to approximately 20% of patients, highlighting the need to identify novel biomarkers to optimize treatment strategies. In several solid tumors, immune soluble factors, the activatory CD137
+ Tcells, and the immunosuppressive cell subsets Tregs and MDSCs (PMN(Lox1+ )-MDSC and M-MDSCs) correlated with responses to ICIs and clinical outcomes thus becoming appealing predictive and prognostic factors. This study investigated the role of distinct CD137+ Tcell subsets, Tregs, MDSCs, and immune-soluble factors in NSCLC patients as possible biomarkers. Methods: The levels of T cells, MDSCs and soluble factors were evaluated in 89 metastatic NSCLC patients who underwent ICIs as first- or second-line treatment. T cell analysis was performed by cytoflurimetry evaluating Tregs and different CD137+ Tcell subsets also combined with CD3+ , CD8+ , PD1+ , and Ki67+ markers. Circulating cytokines and immune checkpoints were also evaluated by Luminex analysis. All these parameters were correlated with several clinical factors (age, sex, smoking status, PS and TPS), response to therapy, PFS , and OS. The analyses were conducted in the overall population and in patients treated with ICIs as first-line (naïve patients). Results: In both groups of patients, high levels of circulating CD137+ and CD137+ PD1+ T cells (total, CD4 and CD8) and the soluble factor LAG3 positively correlated with response to therapy. In naïve patients, PMN(Lox1+ )-MDSCs negatively correlated with clinical response, and a high percentage of Tregs was associated with favorable survival. Moreover, the balance between Treg/CD137+ Tcells or PMN(Lox1+ )-MDSC/CD137+ Tcells was higher in non-responding patients and was associated with poor survival. CD137+ Tcells and Tregs resulted as two positive independent prognostic factors. Conclusion: High levels of CD137+ , CD137+ PD1+ Tcells and sLAG3 could predict the response to ICIs in NSCLC patients independently by previous therapy. Combining the evaluation of CD137+ Tcells and Tregs also as Treg/CD137+ T cells ratio it is possible to identify naive patients with longer survival. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
7. Agnostic evaluation of ipilimumab and nivolumab association: a metanalysis
- Author
-
Marchetti, Paolo, Botticelli, Andrea, Ascierto, Antonio Paolo, Curigliano, Giuseppe, and Giannarelli, Diana
- Published
- 2020
- Full Text
- View/download PDF
8. Gut metabolomics profiling of non-small cell lung cancer (NSCLC) patients under immunotherapy treatment
- Author
-
Botticelli, Andrea, Vernocchi, Pamela, Marini, Federico, Quagliariello, Andrea, Cerbelli, Bruna, Reddel, Sofia, Del Chierico, Federica, Di Pietro, Francesca, Giusti, Raffaele, Tomassini, Alberta, Giampaoli, Ottavia, Miccheli, Alfredo, Zizzari, Ilaria Grazia, Nuti, Marianna, Putignani, Lorenza, and Marchetti, Paolo
- Published
- 2020
- Full Text
- View/download PDF
9. Early fatigue in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: an insight from clinical practice
- Author
-
Cortellini, Alessio, Vitale, Maria G., De Galitiis, Federica, Di Pietro, Francesca R., Berardi, Rossana, Torniai, Mariangela, De Tursi, Michele, Grassadonia, Antonino, Di Marino, Pietro, Santini, Daniele, Zeppola, Tea, Anesi, Cecilia, Gelibter, Alain, Occhipinti, Mario Alberto, Botticelli, Andrea, Marchetti, Paolo, Rastelli, Francesca, Pergolesi, Federica, Tudini, Marianna, Silva, Rosa Rita, Mallardo, Domenico, Vanella, Vito, Ficorella, Corrado, Porzio, Giampiero, and Ascierto, Paolo A.
- Published
- 2019
- Full Text
- View/download PDF
10. A nomogram to predict survival in non-small cell lung cancer patients treated with nivolumab
- Author
-
Botticelli, Andrea, Salati, Massimiliano, Di Pietro, Francesca Romana, Strigari, Lidia, Cerbelli, Bruna, Zizzari, Ilaria Grazia, Giusti, Raffaele, Mazzotta, Marco, Mazzuca, Federica, Roberto, Michela, Vici, Patrizia, Pizzuti, Laura, Nuti, Marianna, and Marchetti, Paolo
- Published
- 2019
- Full Text
- View/download PDF
11. Can IDO activity predict primary resistance to anti-PD-1 treatment in NSCLC?
- Author
-
Botticelli, Andrea, Cerbelli, Bruna, Lionetto, Luana, Zizzari, Ilaria, Salati, Massimiliano, Pisano, Annalinda, Federica, Mazzuca, Simmaco, Maurizio, Nuti, Marianna, and Marchetti, Paolo
- Published
- 2018
- Full Text
- View/download PDF
12. Early fatigue in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: an insight from clinical practice
- Author
-
Cecilia Anesi, Paolo Marchetti, Alessio Cortellini, Rossana Berardi, Mario Occhipinti, Marianna Tudini, Francesca Rastelli, Alain Gelibter, Andrea Botticelli, Rosa Rita Silva, Francesca Di Pietro, Paolo A. Ascierto, Giampiero Porzio, Mariangela Torniai, Daniele Santini, Federica De Galitiis, Corrado Ficorella, Federica Pergolesi, Pietro Di Marino, Maria Grazia Vitale, Vito Vanella, Domenico Mallardo, Michele De Tursi, Antonino Grassadonia, and Tea Zeppola
- Subjects
Adult ,Male ,medicine.medical_specialty ,Multivariate analysis ,Programmed Cell Death 1 Receptor ,lcsh:Medicine ,Kaplan-Meier Estimate ,General Biochemistry, Genetics and Molecular Biology ,B7-H1 Antigen ,Disease-Free Survival ,Young Adult ,Renal cell carcinoma ,Immune-related adverse events ,Internal medicine ,Medicine ,Humans ,Practice Patterns, Physicians' ,Adverse effect ,Fatigue ,Aged ,Cancer ,Aged, 80 and over ,IL-6 ,Performance status ,business.industry ,Melanoma ,Research ,lcsh:R ,PD-1/PD-L1 inhibitors ,General Medicine ,Middle Aged ,medicine.disease ,Clinical trial ,IL-6, PD-1/PD-L1 inhibitors ,Immunotherapy ,Multivariate Analysis ,Population study ,Female ,business - Abstract
Background Fatigue was reported as the most common any-grade adverse event (18.3%), and the most common grade 3 or higher immune-related adverse event (irAE) (0.89%) in patients receiving PD-1/PD-L1 checkpoint inhibitors in clinical trial. Methods The aim of this retrospective multicenter study was to evaluate the correlations between “early ir-fatigue”, “delayed ir-fatigue”, and clinical outcomes in cancer patients receiving PD-1/PD-L1 inhibitors in clinical practice. Results 517 patients were evaluated. After the 12-weeks landmark selection, 386 (74.7%) patients were eligible for the clinical outcomes analysis. 40.4% were NSCLC, 42.2% were melanoma, 15.3% renal cell carcinoma and 2.1% other malignancies. 76 patients (19.7%) experienced early ir-fatigue (within 1 month from treatment commencement), while 150 patients (38.9%) experienced delayed ir-fatigue. Early ir-fatigue was significantly related to shortened PFS (HR = 2.29 [95% CI 1.62–3.22], p Conclusions Early ir-fatigue seems to be negative prognostic parameter, but to proper weight its role we must to consider the predominant role of performance status, which was related to early ir-fatigue in the study population.
- Published
- 2019
13. Weekly chemotherapy as first line treatment in frail head and neck cancer patients in the immunotherapy era
- Author
-
Francesco Vullo, Vincenzo Tombolini, Giulia d'Amati, Antonella Polimeni, Umberto Romeo, Marco Della Monaca, Sasan Amirhassankhani, Valentino Valentini, Marco de Vincentiis, Carlo Della Rocca, Carlo Catalano, Silverio Tomao, Paolo Sciattella, Bruna Cerbelli, Cira Di Gioia, Silvia Mezi, Fabio Ciurluini, Massimo Ralli, Alessio Cirillo, Francesca De Felice, Giulia Mammone, Paolo Marchetti, Giulia Pomati, Alessandro Corsi, and Andrea Botticelli
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Frail Elderly ,Alcohol abuse ,Cetuximab ,Pembrolizumab ,Docetaxel ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Frail patient population ,Medicine ,Humans ,Chemotherapy ,Head and neck cancer ,Aged ,Retrospective Studies ,Response rate (survey) ,business.industry ,Research ,General Medicine ,Immunotherapy ,medicine.disease ,cetuximab ,chemotherapy ,docetaxel ,first line ,frail patient population ,head and neck cancer ,First line ,030104 developmental biology ,Head and Neck Neoplasms ,030220 oncology & carcinogenesis ,Neoplasm Recurrence, Local ,business ,medicine.drug - Abstract
Objective First-line therapy for metastatic squamous cell carcinoma of the head and neck (R/M HNSCC) has been revolutionized by the introduction of anti-checkpoint monoclonal antibodies, which have shown a significant improvement in overall survival (OS) gaining approval in a first line setting. Efficacy and safety of first-line weekly chemotherapy, compared to 3-weeks treatment, was retrospectively evaluated in a frail patient population with R/M HNSCC with the aim to evaluate its role as part of a personalized first-line approach. Methods A total of 124 patients with locally incurable R/M HNSCC receiving weekly (21) or three-weekly (103) chemotherapy plus cetuximab in a first line setting from December 2010 to September 2020 were retrospectively reviewed. Treatment outcomes in terms of objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and toxicities were analysed. Results Patients in the three-week subgroup were ECOG PS 0 (39) and 1 (64) while patients in weekly group (21) were all PS 2. No significant differences were reported in terms of age, sex, smoking and previous alcohol abuse considering the two distinct subgroups. Moreover, no statistically significant difference was found in PFS and OS between the two treatment subgroups. The response rate was 35% (36 patients) and 34% (7 patients) in three-week and weekly treatment group, respectively. Seventy patients (68%) in the three-week group experienced chemotherapy-related toxicities, predominantly G3. In the weekly group a predominantly low-grade toxicity was found in a lower number of patients (52%). Conclusion The weekly schedule appears to be an active and safe strategy in frail patients with R/M HNSCC. Based on these data, a weekly schedule could be considered as a first line treatment in all frail patients excluded from pembrolizumab treatment and a study on the combination of weekly chemotherapy and immunotherapy should be performed.
- Published
- 2021
14. PD-1/PD-L1 checkpoint inhibitors during late stages of life: an ad-hoc analysis from a large multicenter cohort
- Author
-
Paola Queirolo, Rita Chiari, Pietro Di Marino, Maria Vitale, Francesco Grossi, Sebastiano Buti, Vincenzo Adamo, Maria Giuseppa Vitale, David J. Pinato, Serena Macrini, Marco Russano, Fabrizio Citarella, Alessandro Russo, Melissa Bersanelli, Olga Nigro, Michele Ghidini, Linda Nicolardi, Marco Ferrari, Maria Chiara Sergi, Giampiero Porzio, Luigia Stefania Stucci, Francesco Spagnolo, Michele De Tursi, Daniele Santini, Corrado Ficorella, Andrea Botticelli, Marco Tucci, Paolo A. Ascierto, Paolo Marchetti, Sergio Bracarda, Raffaele Giusti, Laura Pala, Marco Siringo, Domenico Mallardo, Giulia Mazzaschi, Riccardo Marconcini, Stefania Gori, Alessio Cortellini, Enrica Teresa Tanda, Alain Gelibter, Cecilia Anesi, Francesca Rastelli, Federica Zoratto, Francesca Giorgi, Thomas Talbot, Marco Filetti, Alessandro Inno, and Tea Zeppola
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Palliative care ,Lung Neoplasms ,medicine.medical_treatment ,Immune checkpoint inhibitors ,Programmed Cell Death 1 Receptor ,General Biochemistry, Genetics and Molecular Biology ,appropriateness ,end-of-life ,immune checkpoint inhibitors ,immunotherapy ,palliative care ,humans ,Italy ,programmed cell death 1 receptor ,B7-H1 antigen ,lung neoplasms ,B7-H1 Antigen ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,PD-L1 ,medicine ,Humans ,Appropriateness ,Medical prescription ,Immune Checkpoint Inhibitors ,Chemotherapy ,biology ,business.industry ,Research ,End-of-life ,Immunotherapy ,General Medicine ,Short life ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cohort ,biology.protein ,Population study ,Medicine ,business - Abstract
Background The favourable safety profile and the increasing confidence with immune checkpoint inhibitors (ICIs) might have boosted their prescription in frail patients with short life expectancies, who usually are not treated with standard chemotherapy. Methods The present analysis aims to describe clinicians’ attitudes towards ICIs administration during late stages of life within a multicenter cohort of advanced cancer patients treated with single agent PD-1/PD-L1 checkpoint inhibitors in Italy. Results Overall, 1149 patients with advanced cancer who received single agent PD-1/PD-L1 checkpoint inhibitors were screened. The final study population consisted of 567 deceased patients. 166 patients (29.3%) had received ICIs within 30 days of death; among them there was a significantly higher proportion of patients with ECOG-PS ≥ 2 (28.3% vs 11.5%, p Conclusion Our results confirmed a trend toward an increasing ICIs prescription in frail patients, during the late stages of life. Caution should be exercised when evaluating an ICI treatment for patients with a poor PS and a high burden of disease.
- Published
- 2021
15. Gut metabolomics profiling of non-small cell lung cancer (NSCLC) patients under immunotherapy treatment
- Author
-
Bruna Cerbelli, Andrea Botticelli, Andrea Quagliariello, Federica Del Chierico, Alberta Tomassini, Pamela Vernocchi, Alfredo Miccheli, Federico Marini, Raffaele Giusti, Ilaria Grazia Zizzari, Marianna Nuti, Francesca Di Pietro, Sofia Reddel, Paolo Marchetti, Lorenza Putignani, and Ottavia Giampaoli
- Subjects
0301 basic medicine ,Lung Neoplasms ,medicine.medical_treatment ,lcsh:Medicine ,non-small cell lung cancer (NSCLC) ,Gut flora ,NSCLC ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,Metabolomics ,Cancer immunotherapy ,Carcinoma, Non-Small-Cell Lung ,Metabolome ,medicine ,Humans ,Progression-free survival ,biology ,business.industry ,Research ,lcsh:R ,General Medicine ,Immunotherapy ,immunotherapy ,gut metabolomics profiling ,medicine.disease ,biology.organism_classification ,Gastrointestinal Microbiome ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,Nivolumab ,business - Abstract
Background Despite the efficacy of immune checkpoint inhibitors (ICIs) only the 20–30% of treated patients present long term benefits. The metabolic changes occurring in the gut microbiota metabolome are herein proposed as a factor potentially influencing the response to immunotherapy. Methods The metabolomic profiling of gut microbiota was characterized in 11 patients affected by non-small cell lung cancer (NSCLC) treated with nivolumab in second-line treatment with anti-PD-1 nivolumab. The metabolomics analyses were performed by GC–MS/SPME and 1H-NMR in order to detect volatile and non-volatile metabolites. Metabolomic data were processed by statistical profiling and chemometric analyses. Results Four out of 11 patients (36%) presented early progression, while the remaining 7 out of 11 (64%) presented disease progression after 12 months. 2-Pentanone (ketone) and tridecane (alkane) were significantly associated with early progression, and on the contrary short chain fatty acids (SCFAs) (i.e., propionate, butyrate), lysine and nicotinic acid were significantly associated with long-term beneficial effects. Conclusions Our preliminary data suggest a significant role of gut microbiota metabolic pathways in affecting response to immunotherapy. The metabolic approach could be a promising strategy to contribute to the personalized management of cancer patients by the identification of microbiota-linked “indicators” of early progressor and long responder patients.
- Published
- 2020
16. Can IDO activity predict primary resistance to anti-PD-1 treatment in NSCLC?
- Author
-
Luana Lionetto, Annalinda Pisano, Marianna Nuti, Ilaria Grazia Zizzari, Maurizio Simmaco, Andrea Botticelli, Massimiliano Salati, Paolo Marchetti, Mazzuca Federica, and Bruna Cerbelli
- Subjects
0301 basic medicine ,Oncology ,Male ,medicine.medical_specialty ,Lung Neoplasms ,Pleural effusion ,medicine.medical_treatment ,Programmed Cell Death 1 Receptor ,lcsh:Medicine ,Kaplan-Meier Estimate ,General Biochemistry, Genetics and Molecular Biology ,IDO ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,medicine ,Humans ,Indoleamine-Pyrrole 2,3,-Dioxygenase ,Progression-free survival ,Kynurenine ,Aged ,Performance status ,business.industry ,Research ,lcsh:R ,Tryptophan ,General Medicine ,Immunotherapy ,Quinolinic Acid ,medicine.disease ,Anti-PD-1 ,030104 developmental biology ,Nivolumab ,chemistry ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Multivariate Analysis ,Disease Progression ,Female ,business ,Quinolinic acid - Abstract
Background Immune checkpoint inhibitors have revolutionized the treatment paradigm of highly lethal malignancies like advanced non-small cell lung cancer (NSCLC), demonstrating long-term tumour control and extended patient survival. Unfortunately, only 25–30% of patients experience a durable benefit, while the vast majority demonstrate primary or acquired resistance. Recently, indoleamine 2,3-dioxygenase (IDO) activity has been proposed as a possible mechanism of resistance to anti-PD-1 treatment leading to an immunosuppressive microenvironment. Methods Pre-treatment serum concentrations of tryptophan (trp) and kynurenine (kyn) were measured by high-performance liquid chromatography tandem mass spectrometry in NSCLC patients treated with second-line nivolumab. The IDO activity was expressed with kyn/trp ratio. The associations between kyn/trp ratio and early progression, performance status (PS), age, sex, brain metastases, pleural effusion, progression free survival (PFS) and overall survival (OS) were analyzed using Spearman test and Mann–Whitney test. Results Twenty-six NSCLC patients were included in our study; 14 of them (54%) presented early progression (
- Published
- 2018
17. Weekly chemotherapy as first line treatment in frail head and neck cancer patients in the immunotherapy era
- Author
-
Andrea Botticelli, Giulia Pomati, Alessio Cirillo, Giulia Mammone, Fabio Ciurluini, Bruna Cerbelli, Paolo Sciattella, Massimo Ralli, Umberto Romeo, Francesca De Felice, Carlo Catalano, Francesco Vullo, Marco Della Monaca, Sasan Amirhassankhani, Silverio Tomao, Valentino Valentini, Marco De Vincentiis, Vincenzo Tombolini, Carlo Della Rocca, Antonella Polimeni, Cira di Gioia, Alessandro Corsi, Giulia D’Amati, Silvia Mezi, and Paolo Marchetti
- Subjects
Head and neck cancer ,Docetaxel ,Cetuximab ,Chemotherapy ,First line ,Frail patient population ,Medicine - Abstract
Abstract Objective First-line therapy for metastatic squamous cell carcinoma of the head and neck (R/M HNSCC) has been revolutionized by the introduction of anti-checkpoint monoclonal antibodies, which have shown a significant improvement in overall survival (OS) gaining approval in a first line setting. Efficacy and safety of first-line weekly chemotherapy, compared to 3-weeks treatment, was retrospectively evaluated in a frail patient population with R/M HNSCC with the aim to evaluate its role as part of a personalized first-line approach. Methods A total of 124 patients with locally incurable R/M HNSCC receiving weekly (21) or three-weekly (103) chemotherapy plus cetuximab in a first line setting from December 2010 to September 2020 were retrospectively reviewed. Treatment outcomes in terms of objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and toxicities were analysed. Results Patients in the three-week subgroup were ECOG PS 0 (39) and 1 (64) while patients in weekly group (21) were all PS 2. No significant differences were reported in terms of age, sex, smoking and previous alcohol abuse considering the two distinct subgroups. Moreover, no statistically significant difference was found in PFS and OS between the two treatment subgroups. The response rate was 35% (36 patients) and 34% (7 patients) in three-week and weekly treatment group, respectively. Seventy patients (68%) in the three-week group experienced chemotherapy-related toxicities, predominantly G3. In the weekly group a predominantly low-grade toxicity was found in a lower number of patients (52%). Conclusion The weekly schedule appears to be an active and safe strategy in frail patients with R/M HNSCC. Based on these data, a weekly schedule could be considered as a first line treatment in all frail patients excluded from pembrolizumab treatment and a study on the combination of weekly chemotherapy and immunotherapy should be performed.
- Published
- 2021
- Full Text
- View/download PDF
18. PD-1/PD-L1 checkpoint inhibitors during late stages of life: an ad-hoc analysis from a large multicenter cohort
- Author
-
Daniele Santini, Tea Zeppola, Marco Russano, Fabrizio Citarella, Cecilia Anesi, Sebastiano Buti, Marco Tucci, Alessandro Russo, Maria Chiara Sergi, Vincenzo Adamo, Luigia S. Stucci, Melissa Bersanelli, Giulia Mazzaschi, Francesco Spagnolo, Francesca Rastelli, Francesca Chiara Giorgi, Raffaele Giusti, Marco Filetti, Paolo Marchetti, Andrea Botticelli, Alain Gelibter, Marco Siringo, Marco Ferrari, Riccardo Marconcini, Maria Giuseppa Vitale, Linda Nicolardi, Rita Chiari, Michele Ghidini, Olga Nigro, Francesco Grossi, Michele De Tursi, Pietro Di Marino, Laura Pala, Paola Queirolo, Sergio Bracarda, Serena Macrini, Stefania Gori, Alessandro Inno, Federica Zoratto, Enrica T. Tanda, Domenico Mallardo, Maria Grazia Vitale, Thomas Talbot, Paolo A. Ascierto, David J. Pinato, Corrado Ficorella, Giampiero Porzio, and Alessio Cortellini
- Subjects
Immunotherapy ,Immune checkpoint inhibitors ,End-of-life ,Palliative care ,Appropriateness ,Medicine - Abstract
Abstract Background The favourable safety profile and the increasing confidence with immune checkpoint inhibitors (ICIs) might have boosted their prescription in frail patients with short life expectancies, who usually are not treated with standard chemotherapy. Methods The present analysis aims to describe clinicians’ attitudes towards ICIs administration during late stages of life within a multicenter cohort of advanced cancer patients treated with single agent PD-1/PD-L1 checkpoint inhibitors in Italy. Results Overall, 1149 patients with advanced cancer who received single agent PD-1/PD-L1 checkpoint inhibitors were screened. The final study population consisted of 567 deceased patients. 166 patients (29.3%) had received ICIs within 30 days of death; among them there was a significantly higher proportion of patients with ECOG-PS ≥ 2 (28.3% vs 11.5%, p
- Published
- 2021
- Full Text
- View/download PDF
19. The role of opioids in cancer response to immunotherapy
- Author
-
Andrea Botticelli, Alessio Cirillo, Giulia Pomati, Bruna Cerbelli, Simone Scagnoli, Michela Roberto, Alain Gelibter, Giulia Mammone, Maria Letizia Calandrella, Edoardo Cerbelli, Francesca Romana Di Pietro, Federica De Galitiis, Gaetano Lanzetta, Enrico Cortesi, Silvia Mezi, and Paolo Marchetti
- Subjects
Immunotherapy ,Opioids ,Opioid receptors ,Prognostic factor ,Predictive factor ,Early progression ,Medicine - Abstract
Abstract Background The response to immunotherapy can be impaired by several factors including external intervention such as drug interactions with immune system. We aimed to examine the immunomodulatory action of opioids, since immune cells express opioid receptors able to negatively influence their activities. Methods This observational, multicenter, retrospective study, recruited patients with different metastatic solid tumors, who have received immunotherapy between September 2014 and September 2019. Immunotherapy was administered according to the standard schedule approved for each primary tumor and line of treatment. The concomitant intake of antibiotics, antifungals, corticosteroids and opioids were evaluated in all included patients. The relationship between tumor response to immunotherapy and the oncological outcomes were evaluated. A multivariate Cox-proportional hazard model was used to identify independent prognostic factors for survival. Results One hundred ninety-three patients were recruited. Overall, progression-free survival (PFS) and overall survival (OS) were significantly shorter in those patients taking opioids than in those who didn’t (median PFS, 3 months vs. 19 months, HR 1.70, 95% CI 1.37–2.09, p
- Published
- 2021
- Full Text
- View/download PDF
20. Gut metabolomics profiling of non-small cell lung cancer (NSCLC) patients under immunotherapy treatment
- Author
-
Andrea Botticelli, Pamela Vernocchi, Federico Marini, Andrea Quagliariello, Bruna Cerbelli, Sofia Reddel, Federica Del Chierico, Francesca Di Pietro, Raffaele Giusti, Alberta Tomassini, Ottavia Giampaoli, Alfredo Miccheli, Ilaria Grazia Zizzari, Marianna Nuti, Lorenza Putignani, and Paolo Marchetti
- Subjects
Medicine - Abstract
Abstract Background Despite the efficacy of immune checkpoint inhibitors (ICIs) only the 20–30% of treated patients present long term benefits. The metabolic changes occurring in the gut microbiota metabolome are herein proposed as a factor potentially influencing the response to immunotherapy. Methods The metabolomic profiling of gut microbiota was characterized in 11 patients affected by non-small cell lung cancer (NSCLC) treated with nivolumab in second-line treatment with anti-PD-1 nivolumab. The metabolomics analyses were performed by GC–MS/SPME and 1H-NMR in order to detect volatile and non-volatile metabolites. Metabolomic data were processed by statistical profiling and chemometric analyses. Results Four out of 11 patients (36%) presented early progression, while the remaining 7 out of 11 (64%) presented disease progression after 12 months. 2-Pentanone (ketone) and tridecane (alkane) were significantly associated with early progression, and on the contrary short chain fatty acids (SCFAs) (i.e., propionate, butyrate), lysine and nicotinic acid were significantly associated with long-term beneficial effects. Conclusions Our preliminary data suggest a significant role of gut microbiota metabolic pathways in affecting response to immunotherapy. The metabolic approach could be a promising strategy to contribute to the personalized management of cancer patients by the identification of microbiota-linked “indicators” of early progressor and long responder patients.
- Published
- 2020
- Full Text
- View/download PDF
21. Early fatigue in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: an insight from clinical practice
- Author
-
Alessio Cortellini, Maria G. Vitale, Federica De Galitiis, Francesca R. Di Pietro, Rossana Berardi, Mariangela Torniai, Michele De Tursi, Antonino Grassadonia, Pietro Di Marino, Daniele Santini, Tea Zeppola, Cecilia Anesi, Alain Gelibter, Mario Alberto Occhipinti, Andrea Botticelli, Paolo Marchetti, Francesca Rastelli, Federica Pergolesi, Marianna Tudini, Rosa Rita Silva, Domenico Mallardo, Vito Vanella, Corrado Ficorella, Giampiero Porzio, and Paolo A. Ascierto
- Subjects
Fatigue ,Cancer ,Immune-related adverse events ,IL-6 ,PD-1/PD-L1 inhibitors ,Immunotherapy ,Medicine - Abstract
Abstract Background Fatigue was reported as the most common any-grade adverse event (18.3%), and the most common grade 3 or higher immune-related adverse event (irAE) (0.89%) in patients receiving PD-1/PD-L1 checkpoint inhibitors in clinical trial. Methods The aim of this retrospective multicenter study was to evaluate the correlations between “early ir-fatigue”, “delayed ir-fatigue”, and clinical outcomes in cancer patients receiving PD-1/PD-L1 inhibitors in clinical practice. Results 517 patients were evaluated. After the 12-weeks landmark selection, 386 (74.7%) patients were eligible for the clinical outcomes analysis. 40.4% were NSCLC, 42.2% were melanoma, 15.3% renal cell carcinoma and 2.1% other malignancies. 76 patients (19.7%) experienced early ir-fatigue (within 1 month from treatment commencement), while 150 patients (38.9%) experienced delayed ir-fatigue. Early ir-fatigue was significantly related to shortened PFS (HR = 2.29 [95% CI 1.62–3.22], p
- Published
- 2019
- Full Text
- View/download PDF
22. Can IDO activity predict primary resistance to anti-PD-1 treatment in NSCLC?
- Author
-
Andrea Botticelli, Bruna Cerbelli, Luana Lionetto, Ilaria Zizzari, Massimiliano Salati, Annalinda Pisano, Mazzuca Federica, Maurizio Simmaco, Marianna Nuti, and Paolo Marchetti
- Subjects
IDO ,Immunotherapy ,Nivolumab ,Kynurenine ,Anti-PD-1 ,Medicine - Abstract
Abstract Background Immune checkpoint inhibitors have revolutionized the treatment paradigm of highly lethal malignancies like advanced non-small cell lung cancer (NSCLC), demonstrating long-term tumour control and extended patient survival. Unfortunately, only 25–30% of patients experience a durable benefit, while the vast majority demonstrate primary or acquired resistance. Recently, indoleamine 2,3-dioxygenase (IDO) activity has been proposed as a possible mechanism of resistance to anti-PD-1 treatment leading to an immunosuppressive microenvironment. Methods Pre-treatment serum concentrations of tryptophan (trp) and kynurenine (kyn) were measured by high-performance liquid chromatography tandem mass spectrometry in NSCLC patients treated with second-line nivolumab. The IDO activity was expressed with kyn/trp ratio. The associations between kyn/trp ratio and early progression, performance status (PS), age, sex, brain metastases, pleural effusion, progression free survival (PFS) and overall survival (OS) were analyzed using Spearman test and Mann–Whitney test. Results Twenty-six NSCLC patients were included in our study; 14 of them (54%) presented early progression (
- Published
- 2018
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.