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Start Over Author "Ciuffreda, L." Topic oncology
18 results on '"Ciuffreda, L."'

1. Transcription regulators and ultra-rare and other rare translocation-related sarcomas treated with trabectedin: A proof of principle from a post-hoc analysis

Author

Palmerini E., Sanfilippo R., Grignani G., Buonadonna A., Romanini A., Badalamenti G., Ferraresi V., Vincenzi B., Comandone A., Pizzolorusso A., Brunello A., Gelsomino F., De Pas T., Ibrahim T., Gurrieri L., Grosso F., Zanelli F., Pantaleo M. A., Milesi L., Ciuffreda L., Ferrari V., Marchesi E., Quattrini I., Righi A., Setola E., Carretta E., Casali P. G., Picci P., Ferrari S., Palmerini E., Sanfilippo R., Grignani G., Buonadonna A., Romanini A., Badalamenti G., Ferraresi V., Vincenzi B., Comandone A., Pizzolorusso A., Brunello A., Gelsomino F., De Pas T., Ibrahim T., Gurrieri L., Grosso F., Zanelli F., Pantaleo M.A., Milesi L., Ciuffreda L., Ferrari V., Marchesi E., Quattrini I., Righi A., Setola E., Carretta E., Casali P.G., Picci P., and Ferrari S.

Subjects
Cancer Research, sarcoma, ultra-rare, Oncology, translocation-related, soft tissue, rare
Abstract

BackgroundAmong sarcomas, which are rare cancers with an incidence of Cancers 2021; ClinicalTrials.gov Identifier: NCT02793050).MethodsA post-hoc analysis of case series to evaluate the efficacy and safety of trabectedin on patients with ultra-rare and other rare translocation-related sarcomas included in TrObs study was performed. Main outcomes comprised investigator-assessed overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and safety.ResultsThirty-six patients (18 women) with ultra-rare and other rare sarcoma and a median age of 53.0 years (range: 22-81) were included. Most patients had solitary fibrous tumor (SFT; n=11) followed by epithelioid sarcoma (n=5), malignant peripheral nerve sheath tumor (MPNST; n=4), extraskeletal myxoid chondrosarcoma (EMC; n=3), desmoplastic small round cell tumor (DSRCT; n=3), and alveolar soft part sarcoma (ASPS), rhabdomyosarcoma and clear cell sarcoma (n=2 each). Thirty-five patients had metastatic disease and 23 patients received trabectedin as a second-line treatment. Among 35 patients evaluable for response, two patients with SFT and ASPS had a partial response and one patient with DSRCT obtained a complete response, reaching an ORR of 8.6% (95% CI: 2.8-23.4%). Among patients with an ORR, 6-months PFS was 100% in patients with ASPS, 45.7% in patients with SFT and 33.3% in those with DSRCT. Two patients with epithelioid sarcoma and myoepithelioma had disease stabilization lasting >24 months. Nine patients had at least one grade 3/4 adverse event, mostly being bone marrow toxicity (n=6).ConclusionsTrabectedin has some anti-tumor activity in some ultra-rare and other rare sarcomas, particularly translocation-related sarcomas, with the well-known manageable safety profile.

Published
2022

2. Preservation of Axillary Lymph Nodes Compared with Complete Dissection in T1-2 Breast Cancer Patients Presenting One or Two Metastatic Sentinel Lymph Nodes: The SINODAR-ONE Multicenter Randomized Clinical Trial

Author

Tinterri, C., Gentile, D., Gatzemeier, W., Sagona, A., Barbieri, E., Testori, A., Errico, V., Bottini, A., Marrazzo, E., Dani, C., Dozin, B., Boni, L., Bruzzi, P., Fernandes, B., Franceschini, D., Spoto, R., Torrisi, R., Scorsetti, M., Santoro, A., Canavese, G., Custodero, O., Troilo, V. L., Taffurelli, M., Cucchi, M. C., Galluzzo, V., Cabula, C., Cabula, R., Lazzaretti, M. G., Caruso, F., Castiglione, G., Grossi, S., Tavoletta, M. S., Rossi, C., Curcio, A., Friedman, D., Fregatti, P., Magni, C., Tazzioli, G., Papi, S., Giovanazzi, R., Chifu, C., Bettini, R., Pezzella, M., Michieletto, S., Saibene, T., Roncella, M., Ghilli, M., Sibilio, A., Cariello, A., Coiro, S., Falco, G., Meli, E. Z., Fortunato, L., Ciuffreda, L., Murgo, R., Battaglia, C., Rubino, L., Biglia, N., Bounous, V., Rovera, F. A., Chiappa, C., Pollini, G., Mirandola, S., Meneghini, G., and Di Bartolo, F.

Subjects
Sentinel Lymph Node Biopsy, Breast Neoplasms, Oncology, Lymphatic Metastasis, Axilla, Humans, Lymph Node Excision, Surgery, Female, Lymph Nodes, Prospective Studies, Neoplasm Recurrence, Local, Sentinel Lymph Node, Mastectomy
Abstract

The SINODAR-ONE trial is a prospective noninferiority multicenter randomized study aimed at assessing the role of axillary lymph node dissection (ALND) in patients undergoing either breast-conserving surgery or mastectomy for T1-2 breast cancer (BC) and presenting one or two macrometastatic sentinel lymph nodes (SLNs). The endpoints were to evaluate whether SLN biopsy (SLNB) only was associated with worsening of the prognosis compared with ALND in terms of overall survival (OS) and relapse.Patients were randomly assigned (1:1 ratio) to either removal of ≥ 10 axillary level I/II non-SLNs followed by adjuvant therapy (standard arm) or no further axillary treatment (experimental arm).The trial started in April 2015 and ceased in April 2020, involving 889 patients. Median follow-up was 34.0 months. There were eight deaths (ALND, 4; SNLB only, 4), with 5-year cumulative mortality of 5.8% and 2.1% in the standard and experimental arm, respectively (p = 0.984). There were 26 recurrences (ALND 11; SNLB only, 15), with 5-year cumulative incidence of recurrence of 6.9% and 3.3% in the standard and experimental arm, respectively (p = 0.444). Only one axillary lymph node recurrence was observed in each arm. The 5-year OS rates were 98.9% and 98.8%, in the ALND and SNLB-only arm, respectively (p = 0.936).The 3-year survival and relapse rates of T1-2 BC patients with one or two macrometastatic SLNs treated with SLNB only, and adjuvant therapy, were not inferior to those of patients treated with ALND. These results do not support the use of routine ALND.

Published
2022

3. Discontinuation of first-line bevacizumab in metastatic colorectal cancer: the BEAWARE Italian Observational Study

Author

Lonardi, S., Nasti, G., Fagnani, D., Gemma, D., Ciuffreda, L., Granetto, C., Lucchesi, S., Ballestrero, A., Biglietto, M., Proserpio, I., Bergamo, F., Proietti, E., Tonini, G., and Soto Parra, H

Subjects
Adult, Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, Genotype, Bevacizumab, Colorectal cancer, First line, Angiogenesis Inhibitors, Metastatic colorectal cancer, bevacizumab, clinical practice, progression-free survival, therapy interruption, Disease-Free Survival, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Humans, Medicine, Progression-free survival, Neoplasm Metastasis, Aged, business.industry, General Medicine, Middle Aged, medicine.disease, Discontinuation, 030104 developmental biology, Italy, 030220 oncology & carcinogenesis, Mutation, Mutation (genetic algorithm), Female, Observational study, Colorectal Neoplasms, business, medicine.drug
Abstract

Aims: BEAWARE investigated the pattern of first-line bevacizumab early interruption in the Italian real-world setting of metastatic colorectal cancer. Methods: A total of 386 patients were followed for 15 months after first-line chemotherapy + bevacizumab start. The rate of bevacizumab interruption for progression or adverse drug reactions (ADRs) constituted the primary endpoint. Results: A total of 78.2% of patients interrupted bevacizumab: 56.6% for progression, 7.3% for ADRs, and 36.1% for other reasons. Median treatment duration was 6.7, 2.5, and 4.6 months, respectively. Median progression-free survival was 10.3 months; however, 35.8% of patients were not progressed and were thus censored at the data cutoff of 15 months, while 21.8% were still receiving bevacizumab. Patients discontinuing for progression/ADRs more frequently had metastases in >1 site ( p = .0001), and a shorter median progression-free survival (6.9 vs 13.9 months, p < .0001). Conclusions: In Italy, first-line bevacizumab is interrupted mainly for progression, only 7.3% due to adverse events, and about one third of cases for other reasons. In clinical practice, the attitude to treat until progression as per guidelines might be implemented. ClinicalTrials.gov Identifier: NCT01609075

Published
2019

4. Management of Italian patients with advanced non-small-cell lung cancer after second-line treatment: results of the longitudinal phase of the LIFE observational study

Author

De Marinis, Filippo, Ardizzoni, Andrea, Fontanini, Gabriella, Grossi, Francesco, Cappuzzo, Federico, Novello, Silvia, Santo, Antonio, Lorusso, Vito, Cortinovis, Diego, Iurlaro, Monica, Galetta, Domenico, Gridelli, Cesare, Pedrazzoli P, Siena S, Alabiso O, Bilancia D, Cinieri S, Cartenì G, Fasola G, Ferraù F, Milella M, Contu A, Giuffrida D, Illiano A, Ravaioli A, Zaniboni A, Bettini A, Caprioli A, Longo F, Cruciani G, Defraia E, Favaretto A, Amadori D, Clerico M, Di Costanzo F, Gamucci T, Caruso M, Iacobelli S, Pinotti G, Pozzessere D, Maiello E, Marchetti P, Passalacqua R, Pavesi L, Tortora G, Aglietta M, Brandes A, Ciuffreda L, Daniele B, Demichelis C, Romito S, Tamberi S, Barni S, Barbieri F, Giordano M, Bracarda S, Crinò L, Marzano N, Merlano M, Numico G., BIANCO, ROBERTO, De Marinis, Filippo, Ardizzoni, Andrea, Fontanini, Gabriella, Grossi, Francesco, Cappuzzo, Federico, Novello, Silvia, Santo, Antonio, Lorusso, Vito, Cortinovis, Diego, Iurlaro, Monica, Galetta, Domenico, Gridelli, Cesare, Pedrazzoli, P, Siena, S, Alabiso, O, Bilancia, D, Cinieri, S, Cartenì, G, Fasola, G, Ferraù, F, Milella, M, Contu, A, Giuffrida, D, Illiano, A, Ravaioli, A, Zaniboni, A, Bettini, A, Caprioli, A, Longo, F, Cruciani, G, Defraia, E, Favaretto, A, Amadori, D, Clerico, M, Di Costanzo, F, Gamucci, T, Caruso, M, Iacobelli, S, Pinotti, G, Pozzessere, D, Maiello, E, Marchetti, P, Passalacqua, R, Pavesi, L, Tortora, G, Aglietta, M, Bianco, Roberto, Brandes, A, Ciuffreda, L, Daniele, B, Demichelis, C, Romito, S, Tamberi, S, Barni, S, Barbieri, F, Giordano, M, Bracarda, S, Crinò, L, Marzano, N, Merlano, M, and Numico, G.

Subjects
Oncology, Male, Cancer Research, Lung Neoplasms, medicine.medical_treatment, Longitudinal Studie, medicine.disease_cause, NSCLC, Antineoplastic Agent, Chemotherapy, EGFR, Erlotinib, Third-line, Cohort Studies, Carcinoma, Non-Small-Cell Lung, 80 and over, Anaplastic lymphoma kinase, Anaplastic Lymphoma Kinase, Longitudinal Studies, Non-Small-Cell Lung, DOCETAXEL, Aged, 80 and over, Proto-Oncogene Protein, Tumor, CHEMOTHERAPY, Middle Aged, OPEN-LABEL, Receptor Protein-Tyrosine Kinase, ErbB Receptors, Italy, Cohort, Disease Progression, Female, KRAS, CLINICAL-PRACTICE GUIDELINES, medicine.drug, Human, Pulmonary and Respiratory Medicine, Adult, medicine.medical_specialty, ERLOTINIB, Antineoplastic Agents, Proto-Oncogene Proteins p21(ras), Erlotinib Hydrochloride, Internal medicine, Proto-Oncogene Proteins, medicine, Biomarkers, Tumor, Humans, Lung cancer, Aged, III TRIAL, business.industry, Carcinoma, Quinazoline, 3RD-LINE THERAPY, Receptor Protein-Tyrosine Kinases, medicine.disease, ras Protein, 1ST-LINE TREATMENT, FOLLOW-UP, Clinical trial, Lung Neoplasm, Mutation, Quinazolines, ras Proteins, Observational study, Receptor, Epidermal Growth Factor, Cohort Studie, business, Biomarkers
Abstract

Introduction/Background Patients with advanced NSCLC who experience disease progression after second-line therapy might receive further active treatment. LIFE was an Italian cohort multicenter observational study composed of a cross-sectional and a longitudinal phase. Patients and Methods In the longitudinal phase, described here, the primary aim was to determine the proportion of patients receiving third-line therapy among those who received second-line active treatment according to clinical practice. The proportion of patients receiving further treatment lines was also estimated. Results The longitudinal phase was conducted between January and August 2012. Of 464 patients who began second-line therapy outside of clinical trials within the baseline evaluation, 56 (12.1%) were still receiving second-line therapy at the end of the observation period and 17 (3.7%) withdrew during or after second-line therapy. Of the remaining 391 patients, 158 (40.4%) received third-line treatment outside of clinical trials: 93 received a third-line chemotherapy and 65 a targeted agent. The main reason for interrupting third-line treatment was disease progression or death. During the same observation period, 25 of 113 patients who completed a third-line therapy received a fourth line of treatment. From diagnosis of NSCLC to the end of observation, biomarkers were tested in 323 patients (59.7%): epidermal growth factor receptor mutations in 315 (58.2%), Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutations in 83 (15.3%) and Anaplastic lymphoma kinase (ALK) translocation in 84 (15.5%). Conclusion In Italian clinical practice, the proportion of patients with advanced NSCLC receiving more than 2 treatment lines of therapy is not negligible.

Published
2014

6. Addition of Either Lonidamine or Granulocyte Colony-Stimulating Factor Does Not Improve Survival in Early Breast Cancer Patients Treated With High-Dose Epirubicin and Cyclophosphamide

Author

Papaldo, P., Lopez, M., Cortesi, Enrico, Cammilluzzi, E., Antimi, M., Terzoli, E., Lepidini, G., Vici, P., Barone, C., Ferretti, G., Di Cosimo, S., Nistico, C., Carlini, P., Conti, F., Di Lauro, L., Botti, C., Vitucci, C., Fabi, A., Giannarelli, D., Marolla, P., Di Maio, M., Perrone, F., Gallo, C., Iaffaioli, R. V., Manzione, L., Piantedosi, F. V., Cigolari, S., Illiano, A., Barbera, S., Robbiati, S. F., Piazza, E., Ianniello, G. P., Frontini, L., Veltri, E., Castiglione, F., Rosetti, F., De Maio, E., Maione, P., Gridelli, C., Rossi, A., Barletta, E., Barzelloni, M. L., Signoriello, G., Bilancia, D., Dinota, A., Rosati, G., Germano, D., Lamberti, A., Pontillo, V., Brancacio, L., Crispino, C., Esposito, M., Battiloro, C., Tufano, G., Cioffi, A., Guardasole, V., Angelini, V., Guidetti, G., Renda, F., Romano, F., Volpintesta, A., Sannicolo, M., Filipazzi, V., Esani, G., Gambaro, A., Ferrario, S., Tinessa, V., Caprio, M. G., Zonato, S., Cabiddu, M., Raina, A., D'Aprile, M., Pistillucci, G., Porcile, G., Ostellino, O., Vinante, O., Azzarello, G., Gebbia, V., Borsellino, N., Testa, A., Gasparini, G., Morabito, A., Gattuso, D., Romito, S., Carrozza, F., Fava, S., Calcagno, A., Grimi, E., Bertetto, O., Ciuffreda, L., Parello, G., Maiorino, L., Santoro, A., Santoro, M., Failla, G., Aiello, R. A., Bearz, A., Sorio, R., Scalone, S., Clerici, M., Bollina, R., Belloni, P., Sacco, C., Sibau, A., Adamo, V., Altavilla, G., Scimone, A., Spatafora, M., Bellia, V., Hopps, M. R., Monfardini, S., Favaretto, A., Stefani, M., Corradini, G. M., Pavia, G., Scagliotti, G., Novello, S., Selvaggi, G., Tonato, M., Darwish, S., Michetti, G., Belometti, M. O., Labianca, R., Quadri, A., De Marinis, F., Migliorino, M. R., Martelli, O., Colucci, G., Galetta, D., Giotta, F., Isa, L., Candido, P., Rossi, N., Calandriello, A., Ferrau, F., Malaponte, E., Barni, S., Cazzaniga, M., Gebbia, N., Valerio, Mr, Belli, M., Colantuoni, G., Capuano, M. A., Angiolillo, M., Sollitto, F., Ardizzoia, A., Luporini, G., Locatelli, M. C., Pari, F., Aitini, E., Pedicini, T., Febbraro, A., Zollo, C., Di Costanzo, F., Bartolucci, R., Gasperoni, S., Gaion, F., Palazzolo, G., Galligioni, E., Caffo, O., Cortesi, E., D'Auria, G., Curcio, C., Vasta, M., Bumma, C., Celano, A., Bretti, S., Nettis, G., Anselmo, A., Mattioli, R., Aschelter, A., and Foa, P.

Subjects
Adult, Cancer Research, medicine.medical_specialty, Indazoles, Filgrastim, Cyclophosphamide, medicine.medical_treatment, Breast Neoplasms, Gastroenterology, Disease-Free Survival, chemistry.chemical_compound, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Granulocyte Colony-Stimulating Factor, medicine, Humans, Survival rate, Aged, Epirubicin, Chemotherapy, business.industry, Lonidamine, Middle Aged, medicine.disease, Metastatic breast cancer, Recombinant Proteins, Granulocyte colony-stimulating factor, Surgery, Survival Rate, Oncology, chemistry, Female, business, Follow-Up Studies, medicine.drug
Abstract

Purpose: Lonidamine (LND) can enhance the activity of anthracyclines in patients with metastatic breast cancer. A multicenter, prospective, randomized trial was designed to determine whether the association of LND with high-dose epirubicin plus cyclophosphamide (EC) could improve disease-free survival (DFS) in patients with early breast cancer (BC) compared with EC alone. Granulocyte colony-stimulating factor (G-CSF) was added to maintain the EC dose-intensity. Patients and Methods: From October 1991 to April 1994, 506 patients with stage I/II BC were randomly assigned to four groups: (A) epirubicin 120 mg/m2 and cyclophosphamide 600 mg/m2 administered intravenously on day 1 every 21 days for four cycles (124 patients); (B) EC plus LND 450 mg/d administered orally (125 patients); (C) EC plus G-CSF administered subcutaneously (129 patients); (D) EC plus LND plus G-CSF (128 patients). Results: Median follow-up was 55 months. Five-year DFS rate was similar for LND (B+D groups; 69.6%) versus non-LND arms (A+C groups; 70.3%) and G-CSF (C+D groups; 67.2%) versus non–G-CSF arms (A+B groups; 72.9%). Five-year overall survival (OS) was comparable in LND (79.1%) versus non-LND arms (81.3%) and in G-CSF (80.6%) versus non–G-CSF arms (79.6%). DFS and OS distributions in LND and G-CSF arms did not change according to tumor size, node, receptor, and menopausal status. G-CSF dramatically reduced hematologic toxicity without having a significant impact on dose-intensity (98.1% v 95.5% for C+D and A+B groups, respectively). Conclusion: EC is active and well tolerated in patients with early breast cancer. The addition of LND or G-CSF does not improve DFS or OS.

Published
2003

7. Pretreatment quality of life and functional status assessment significantly predict survival of elderly patients with advanced non-small-cell lung cancer receiving chemotherapy: a prognostic analysis of the multicenter Italian lung cancer in the elderly study

Author

Maione, P, Perrone, F, Gallo, C, Manzione, L, Piantedosi, F, Barbera, S, Cigolari, S, Rosetti, F, Piazza, E, Robbiati, Sf, Bertetto, O, Novello, S, Migliorino, Mr, Favaretto, A, Spatafora, M, Ferraù, F, Frontini, L, Bearz, A, Repetto, L, Gridelli, C, Barletta, E, Barzelloni, Ml, Iaffaioli, Rv, DE MAIO, E, DI MAIO, M, DE FEO, G, Sigoriello, G, Chiodini, P, Cioffi, A, Guardasole, V, Angelini, V, Rossi, A, Bilancia, D, Germano, D, Lamberti, A, Pontillo, V, Brancaccio, L, Renda, F, Romano, F, Esani, G, Gambaro, A, Vinante, O, Azzarello, G, Clerici, M, Bollina, R, Belloni, P, Sannicolò, M, Ciuffreda, L, Parello, G, Cabiddu, M, Sacco, C, Sibau, A, Porcile, G, Castiglione, F, Ostellino, O, Monfardini, S, Stefani, M, Scagliotti, G, Selvaggi, G, DE MARINIS, F, Martelli, O, Gasparini, G, Morabito, A, Gattuso, D, Colucci, G, Galetta, D, Giotta, F, Gebbia, V, Borsellino, N, Testa, A, Malaponte, E, Capuano, Ma, Angiolillo, M, Sollitto, F, Tirelli, U, Spazzapan, S, Adamo, V, Altavilla, G, Scimone, A, Hopps, Mr, Tartamella, F, Ianniello, Gp, Tinessa, V, Failla, G, Bordonaro, R, Gebbia, N, Valerio, Mr, D'Aprile, M, Veltri, E, Tonato, M, Darwish, S, Romito, S, Carrozza, F, Barni, S, Ardizzoia, A, Corradini, Gm, Pavia, G, Belli, M, Colantuoni, G, Galligioni, E, Caffo, O, Labianca, R, Quadri, A, Cortesi, Enrico, D'Auria, Giuliana, Fava, S, Calcagno, A, Luporini, G, Locatelli, Mc, DI COSTANZO, F, Gasperoni, S, Isa, L, Candido, P, Gaion, F, Palazzolo, G, Nettis, G, Annamaria, A, Rinaldi, M, Lopez, M, Felletti, R, DI NEGRO GB, Rossi, N, Calandriello, A, Maiorino, L, Mattioli, R, Celano, A, Schiavon, S, Illiano, A, Raucci, Ca, Caruso, M, Foa, P, Tonini, G, Curcio, C, Cazzaniga, M., MAIONE P, PERRONE F, GALLO C, MANZIONE L, PIANTEDOSI F, BARBERA S, CIGOLARI, ROSETTI F, PIAZZA E, ROBBIATI SF, BERTETTO O, NOVELLO S, MIGLIORINO MR, FAVARETTO A, SPATAFORA M, FERRAU F, FRONTINI L, BEARZ A, REPETTO L, GRIDELLI C, BARLETTA E, BARZELLONI ML, IAFFAIOLI RV, DE MAIO E, DI MAIO M, DE FEO G, SIGORIELLO G, CHIODINI P, CIOFFI A, GUARDASOLE V, ANGELINI V, ROSSI A, BILANCIA, GERMANO D, LAMBERTI A, PONTILLO V, BRANCACCIO L, RENDA F, ROMANO F, ESANI G, GAMBARO A, VINANTE O, AZZARELLO G, CLERICI M, BOLLINA R, BELLONI P, SANNICOLO M, CIUFFREDA L, PARELLO G, CABIDDU M, SACCO C, SIBAU A, PORCILE G, CASTIGLIONE F, OSTELLINO O, MONFARDINI S, STEFANI M, SCAGLIOTTI G, SELVAGGI G, DE MARINIS F, MARTELLI O, GASPARINI G, MORABITO A, GATTUSO D, COLUCCI G, GALETTA D, GIOTTA F, GEBBIA V, ET AL, Maione, P, Perrone, F, Gallo, Ciro, Manzione, L, Piantedosi, F, Barbera, S, Cigolari, S, Rosetti, F, Piazza, E, Robbiati, Sf, Bertetto, O, Novello, S, Migliorino, Mr, Favaretto, A, Spatafora, M, Ferrau, F, Frontini, L, Bearz, A, Repetto, L, and Gridelli, C.

Subjects
Male, Cancer Research, medicine.medical_specialty, Lung Neoplasms, Activities of daily living, Health Status, carcinoma, Vinblastine, Vinorelbine, Deoxycytidine, older people, Quality of life, Instrumental activitie, Carcinoma, Non-Small-Cell Lung, Internal medicine, Activities of Daily Living, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Lung cancer, Aged, Aged, 80 and over, validation, Proportional hazards model, business.industry, QLQ-C30, Age Factors, Cancer, clinical trial, Prognosis, medicine.disease, Gemcitabine, Comorbidity, humanities, comorbidity, Oncology, Quartile, Quality of Life, Physical therapy, impact, Geriatric oncology, Female, business, Randomized-trial, medicine.drug
Abstract

Purpose To study the prognostic value for overall survival of baseline assessment of functional status, comorbidity, and quality of life (QoL) in elderly patients with advanced non—small-cell lung cancer treated with chemotherapy. Patients and Methods Data from 566 patients enrolled onto the phase III randomized Multicenter Italian Lung Cancer in the Elderly Study (MILES) study were analyzed. Functional status was measured as activities of daily living (ADL) and instrumental ADL (IADL). The presence of comorbidity was assessed with a checklist of 33 items; items 29 and 30 of the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 (EORTC QLQ-C30) were used to estimate QoL. ADL was dichotomized as none versus one or more dependency. For IADL and QoL, three categories were defined using first and third quartiles as cut points. Comorbidity was summarized using the Charlson scale. Analysis was performed by Cox model, and stratified by treatment arm. Results Better values of baseline QoL (P = .0003) and IADL (P = .04) were significantly associated with better prognosis, whereas ADL (P = .44) and Charlson score (P = .66) had no prognostic value. Performance status 2 (P = .006) and a higher number of metastatic sites (P = .02) also predicted shorter overall survival. Conclusions Pretreatment global QoL and IADL scores, but not ADL and comorbidity, have significant prognostic value for survival of elderly patients with advanced non—small-cell lung cancer who were treated with chemotherapy. Using these scores in clinical practice might improve prognostic prediction for treatment planning.

Published
2005

8. An international expanded-access programme of everolimus: Addressing safety and efficacy in patients with metastatic renal cell carcinoma who progress after initial vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy

Author

Grünwald, V, Karakiewicz, P, Bavbek, S, Miller, K, Machiels, J, Lee, S, Larkin, J, Bono, P, Rha, S, Castellano, D, Blank, C, Knox, J, Hawkins, R, Anak, O, Rosamilia, M, Booth, J, Pirotta, N, Bodrogi, I, Romedi, M, Ferrandini, S, Rondinon, M, Pittman, K, Goldstein, D, Shapiro, J, Troon, S, Yip, D, Mainwaring, P, Zigeuner, R, Loidl, W, Greil, R, Schmidinger, M, De Grève, J, Rottey, S, Vermorken, J, Gil, T, Gennigens, C, Roumeguere, T, Barrios, C, Mathias, C, Assi, H, Hotte, S, Spadafora, S, Wood, L, Zalewski, P, Mackensie, M, Bjarnason, G, Lalancette, A, Chan, A, Higgins, B, North, S, Soulieres, D, Asselah, J, Sperlich, C, Miller, W, Yadav, S, El Maraghi, R, Godoy, J, Prausová, J, Katolicka, J, Petruzelka, L, Kiss, I, Lapela, M, Bergmann, L, Beck, J, Jäger, E, Kindler, M, Overkamp, F, Wirth, M, Hölzer, W, Gschwend, J, Stenzl, A, Gauler, T, Niederwieser, D, Marschner, N, Lück, A, Tessen, H, Eichelberg, C, Steiner, T, Goebell, P, Kettner, E, Bakhshandeh Bath, A, Wilhelm, M, Schmitz, S, Jacob, A, Bierer, S, Kube, U, Staehler, M, Engel, E, Frambach, M, Schellenberger, U, Albers, P, Simon, J, Gleissler, M, Klotz, T, Repp, R, Kröning, H, Westermann, J, Rebmann, U, Brehmer, B, Niederle, N, Grund, C, Verpoort, K, Fonara, P, Rassweiler, J, Bamias, A, Fountzilas, G, Razis, E, Mouratidou, D, Georgoulias, V, Samantas, E, Mangel, L, Szanto, J, Berger, R, Pe'Er, A, Sella, A, Ben Yosef, R, Nechushtan, H, Crinò, L, Bracarda, S, Ciuffreda, L, Graiff, C, Falcone, A, Roselli, M, Sternberg, C, Santoro, A, Ruggeri, E, Bearz, A, Venturini, M, Aglietta, M, Amadori, D, Di Costanzo, F, Bari, M, Gebbia, N, Conte, P, Bonetti, A, Bordonaro, R, Cascinu, S, Contu, A, Cruciani, G, Gasparro, D, Nardi, M, Lelli, G, Lo Re, G, Boccardo, F, Lorusso, V, Maiello, E, Manente, P, Passalacqua, R, Piantedosi, F, Porta, C, Sacco, C, Tondini, C, De Placido, S, Carteni, G, Dogliotto, L, Rosti, G, Milella, M, Roila, F, Amoroso, D, Farina, G, Al Khatib, H, Kim, T, Ahn, J, Lim, H, Chung, I, Kim, J, Chung, J, Ghosn, M, Shameseddine, A, Lugo, R, Cabrera, P, Osanto, S, Groenewegen, G, van den Eertwegh, F, van Herpen, C, Oosting, S, Soetekouw, P, Lilleby, W, Klepp, O, Guren, T, Alcedo, J, Karlov, P, Nosov, D, Roman, L, Rusakov, I, Bazarbashi, S, Toh, C, Mardiak, J, del Muro Solans, F, Ray, J, Mollins, J, Martinez, I, Gonzalez, B, Santasusana, M, Piqueras, M, Fuentes, J, Larriba, J, Caro, R, Garcia, A, Aparicio, L, Lopez, N, Aragon, V, Morales, C, Figueiras, M, Ibanez, J, Billalabeitia, G, Estrada, E, Arranz, J, Sorrosal, J, Lozano, A, de Villena, M, Espinosa, E, Lopez, R, Perez, J, Laurell, A, Stierner, U, Cwikiel, M, Borner, M, Dietrich, P, Rothermundt, C, Pu, Y, Chang, Y, Ou, Y, Chuang, C, Liao, Y, Srimuninnimit, V, Sriuranpong, V, Buyukberber, S, Yalcin, B, Goker, E, Yalcin, S, Geldart, T, Wagstaff, J, Nicholson, S, Chowdhury, S, Bahl, A, Jones, R, Azzabi, A, Chao, D, Fife, K, Mead, G, Nathan, P, Pandha, H, Hajdenberg, J, Gabrail, N, Nimeh, N, Logan, T, Flaig, T, Schraeder, R, Rini, B, O'Rourke, M, Alemany, C, Kessinger, A, Amin, A, Arriaga, M, Rodriguez, J, Gauler, Thomas (Beitragende*r), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Interne Geneeskunde, and Laboratory of Molecular and Medical Oncology

Subjects
Nephrology, Oncology, Male, Cancer Research, mTOR inhibitor, Settore MED/06 - Oncologia Medica, Medizin, Advanced kidney cancer, RAD001, REACT, 0302 clinical medicine, Renal cell carcinoma, Receptors, 80 and over, Treatment Failure, Neoplasm Metastasis, Aged, 80 and over, 0303 health sciences, Vascular Endothelial Growth Factor, Sirolimus, Young Adult, Antineoplastic Agents, Humans, Aged, Immunosuppressive Agents, Protein Kinase Inhibitors, Receptors, Vascular Endothelial Growth Factor, Kidney Neoplasms, Adult, Carcinoma, Renal Cell, Middle Aged, Female, 3. Good health, 030220 oncology & carcinogenesis, Safety, medicine.drug, medicine.medical_specialty, SECOND LINE THERPAY, Second-line therapy, Everolimus, 03 medical and health sciences, Internal medicine, medicine, Adverse effect, 030304 developmental biology, business.industry, Carcinoma, Renal Cell, medicine.disease, Surgery, Clinical trial, Expanded access, business, Kidney cancer
Abstract

BACKGROUND AND OBJECTIVES: The RECORD-1 trial established the clinical benefit of everolimus in patients with metastatic renal cell carcinoma (mRCC) after failure of initial vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFr-TKI) therapy. The REACT (RAD001 Expanded Access Clinical Trial in RCC) study was initiated to address an unmet medical need by providing everolimus prior to commercial availability, and also to further assess the safety and efficacy of everolimus in patients with VEGFr-TKI-refractory mRCC. PATIENTS AND METHODS: REACT (Clinicaltrials.gov: NCT00655252) was a global, open-label, expanded-access programme in patients with mRCC who were intolerant of, or who had progressed on or after stopping treatment with, any available VEGFr-TKI therapy. Patients received everolimus 10mg once daily, with dose and schedule modifications allowed for toxicity. Patients were closely monitored for the development of serious and grades 3/4 adverse events (AEs). Response was assessed by RECIST every 3months for the first year and every 6months thereafter. RESULTS: A total of 1367 patients were enroled. Safety findings and tumour responses were consistent with those observed in RECORD-1, with no new safety issues identified. The most commonly reported serious AEs were dyspnoea (5.0%), pneumonia (4.7%) and anaemia (4.1%), and the most commonly reported grades 3/4 AEs were anaemia (13.4%), fatigue (6.7%) and dyspnoea (6.5%). Best overall response was stable disease in 51.6% and partial response in 1.7% of patients. Median everolimus treatment duration was 14weeks. CONCLUSION: Everolimus is well tolerated in patients with mRCC and demonstrates a favourable risk-benefit ratio.

Published
2012

9. Supportive care in patients with advanced non-small-cell lung cancer

Author

DI MAIO, Massimo, Perrone, F, Gallo, C, Iaffaioli, Rv, Manzione, L, Piantedosi, Fv, Cigolari, S, Illiano, A, Barbera, S, Robbiati, Sf, Piazza, E, Ianniello, Gp, Frontini, L, Veltri, E, Castiglione, F, Rosetti, F, De Maio, E, Maione, P, Gridelli, C, Rossi, A, Barletta, E, Barzelloni, Ml, Signoriello, G, Bilancia, D, Dinota, A, Rosati, G, Germano, D, Lamberti, A, Pontillo, V, Brancacio, L, Crispino, C, Esposito, M, Battiloro, C, Tufano, G, Cioffi, A, Guardasole, V, Angelini, V, Guidetti, G, Renda, F, Romano, F, Volpintesta, A, Sannicolò, M, Filipazzi, V, Esani, G, Gambaro, A, Ferrario, S, Tinessa, V, Caprio, Mg, Zonato, S, Cabiddu, M, Raina, A, D'Aprile, M, Pistillucci, G, Porcile, G, Ostellino, O, Vinante, O, Azzarello, G, Gebbia, V, Borsellino, N, Testa, A, Gasparini, G, Morabito, A, Gattuso, D, Romito, S, Carrozza, F, Fava, S, Calcagno, A, Grimi, E, Bertetto, O, Ciuffreda, L, Parello, G, Maiorino, L, Santoro, A, Santoro, M, Failla, G, Aiello, Ra, Bearz, A, Sorio, R, Scalone, S, Clerici, M, Bollina, R, Belloni, P, Sacco, C, Sibau, A, Adamo, V, Altavilla, G, Scimone, A, Spatafora, M, Bellia, V, Hopps, Mr, Monfardini, S, Favaretto, A, Stefani, M, Corradini, Gm, Pavia, G, Scagliotti, Giorgio Vittorio, Novello, Silvia, Selvaggi, G, Tonato, M, Darwish, S, Michetti, G, Belometti, Mo, Labianca, R, Quadri, A, De Marinis, F, Migliorino, Mr, Martelli, O, Colucci, G, Galetta, D, Giotta, F, Isa, L, Candido, P, Rossi, N, Calandriello, A, Ferraù, F, Malaponte, E, Barni, S, Cazzaniga, M, Gebbia, N, Valerio, Mr, Belli, M, Colantuoni, G, Capuano, Ma, Angiolillo, M, Sollitto, F, Ardizzoia, A, Luporini, G, Locatelli, Mc, Pari, F, Aitini, E, Pedicini, T, Febbraro, A, Zollo, C, Di Costanzo, F, Bartolucci, R, Gasperoni, S, Gaion, F, Palazzolo, G, Galligioni, E, Caffo, O, Cortesi, E, D'Auria, G, Curcio, C, Vasta, M, Bumma, C, Celano, A, Bretti, S, Nettis, G, Anselmo, A, Mattioli, R, Nisticò, C, Aschelter, A, Foa, P., DI MAIO, M, Perrone, F, Gallo, Ciro, Iaffaioli, Rv, Manzione, L, Piantedosi, Fv, Cigolari, S, Illiano, A, Barbera, S, Robbiati, Sf, Piazza, E, Ianniello, Gp, Frontini, L, Veltri, E, Castiglione, F, Rosetti, F, DE MAIO, E, Maione, P, and Gridelli, C.

Subjects
Adult, Male, concomitant drugs, Cancer Research, medicine.medical_specialty, Aging, Palliative care, Lung Neoplasms, medicine.medical_treatment, Vinorelbine, Vinblastine, Deoxycytidine, Clinical, Quality of life, Internal medicine, Carcinoma, Non-Small-Cell Lung, Antineoplastic Combined Chemotherapy Protocols, polypharmacotherapy, medicine, Humans, Lung cancer, Survival rate, Aged, Randomized Controlled Trials as Topic, Aged, 80 and over, Chemotherapy, Performance status, business.industry, Palliative Care, Middle Aged, medicine.disease, Gemcitabine, Surgery, Survival Rate, supportive care, lung cancer, Oncology, Concomitant, Quality of Life, Antiemetics, Female, Cisplatin, business, medicine.drug
Abstract

The present study describes supportive care (SC) in patients with advanced non-small-cell lung cancer (NSCLC), evaluating whether it is affected by concomitant chemotherapy, patient's performance status (PS) and age. Data of patients enrolled in three randomised trials of first-line chemotherapy, conducted between 1996 and 2001, were pooled. The analysis was limited to the first three cycles of treatment. Supportive care data were available for 1185 out of 1312 (90%) enrolled patients. Gastrointestinal drugs (45.7%), corticosteroids (33.4%) and analgesics (23.8%) were the most frequently observed categories. The mean number of drugs per patient was 2.43; 538 patients (45.4%) assumed three or more supportive drugs. Vinorelbine does not produce substantial variations in the SC pattern, while cisplatin-based treatment requires an overall higher number of supportive drugs, with higher use of antiemetics (41 vs 27%) and antianaemics (10 vs 4%). Patients with worse PS are more exposed to corticosteroids (42 vs 30%). Elderly patients require drugs against concomitant diseases significantly more than adults (20 vs 7%) and are less frequently exposed to antiemetics (12 vs 27%). In conclusion, polypharmacotherapy is a relevant issue in patients with advanced NSCLC. Chemotherapy does not remarkably affect the pattern of SC, except for some drugs against side effects. Elderly patients assume more drugs for concomitant diseases and receive less antiemetics than adults.

Published
2004

10. Oxaliplatin plus fluoropyrimidines as adjuvant therapy for colon cancer in older patients: A subgroup analysis from the TOSCA trial

Author

Gerardo Rosati, Sara Lonardi, Fabio Galli, Maria Di Bartolomeo, Monica Ronzoni, Maria G. Zampino, Maria Banzi, Alberto Zaniboni, Felice Pasini, Silvia Bozzarelli, Silvio K. Garattini, Daris Ferrari, Vincenzo Montesarchio, Andrea Mambrini, Libero Ciuffreda, Francesca Galli, Valeria Pusceddu, Chiara Carlomagno, Paolo Bidoli, Domenico Amoroso, Anna M. Bochicchio, Luca Frassineti, Domenico Corsi, Domenico Bilancia, Alessandro Pastorino, Alfonso De Stefano, Roberto Labianca, D. Bilancia, G. Rosati, V. Montesarchio, R.V. Iaffaioli, G. Nasti, B. Daniele, V. Zagonel, S. Lonardi, N. Pella, G. Aprile, F. Pasini, Roma P. Marchetti, A. Romiti, L. Ciuffreda, D. Ferrari, P. Foa, A. Zaniboni, R. Labianca, S. Mosconi, A. Sobrero, P. Bidoli, M. Cazzaniga, G.D. Beretta, D.C. Corsi, E. Cortesi, S. Barni, F. Petrelli, P. Allione, A.M. D'Arco, G. Valmadre, E. Piazza, E. Veltri, G. Vietti Ramus, L. Giustini, S. Tumulo, S. Cascinu, C. Granetto, F. Testore, M. Giordano, M. Moroni, M. Di Seri, A. Nuzzo, L. Angelelli, S. Gori, G. Farina, M. Aglietta, R. Franchi, M. Comandé, P. Giordani, G. Tonini, E. Bucci, A. Ballestrero, M. Benasso, C. Graiff, S. Bravi, O. Caffo, R.R. Silva, L. Frontini, S. Rota, L. Cozzi, M. Cantore, E. Maiello, S. Cinieri, N. Silvestris, S. Romito, V. Gebbia, M. Banzi, A. Santoro, F. Artioli, R. Mattioli, A. Contu, F. Di Costanzo, F. Leonardi, L. Cavanna, R. Passalacqua, D. Amoroso, P. Sozzi, M. D'Amico, D. Amadori, L. Frassineti, D. Turci, A. Ravaioli, E. Pasquini, A. Gambi, M. Faedi, G. Cruciani, E. Bajetta, M. Di Bartolomeo, L. Gianni, M. Ronzoni, M.T. Ionta, B. Massidda, M. Scartozzi, M.G. Zampino, A.M. Bochicchio, A. Ciarlo, A. Di Leo, S. Frustaci, G. Rangoni, A. Arizzoia, L. Pavesi, C. Verusio, G. Pinotti, A. Iop, S. De Placido, C. Carlomagno, V. Adamo, C. Ficorella, D. Natale, E. Greco, E. Rulli, F. Galli, D. Poli, L. Porcu, V. Torri, Rosati, G, Lonardi, S, Galli, F, Di Bartolomeo, M, Ronzoni, M, Zampino, M, Banzi, M, Zaniboni, A, Pasini, F, Bozzarelli, S, Garattini, S, Ferrari, D, Montesarchio, V, Mambrini, A, Ciuffreda, L, Pusceddu, V, Carlomagno, C, Bidoli, P, Amoroso, D, Bochicchio, A, Frassineti, L, Corsi, D, Bilancia, D, Pastorino, A, De Stefano, A, Labianca, R, Iaffaioli, R, Nasti, G, Daniele, B, Zagonel, V, Pella, N, Aprile, G, Marchetti, R, Romiti, A, Foa, P, Mosconi, S, Sobrero, A, Cazzaniga, M, Beretta, G, Cortesi, E, Barni, S, Petrelli, F, Allione, P, D'Arco, A, Valmadre, G, Piazza, E, Veltri, E, Ramus, G, Giustini, L, Tumulo, S, Cascinu, S, Granetto, C, Testore, F, Giordano, M, Moroni, M, Di Seri, M, Nuzzo, A, Angelelli, L, Gori, S, Farina, G, Aglietta, M, Franchi, R, Comande, M, Giordani, P, Tonini, G, Bucci, E, Ballestrero, A, Benasso, M, Graiff, C, Bravi, S, Caffo, O, Silva, R, Frontini, L, Rota, S, Cozzi, L, Cantore, M, Maiello, E, Cinieri, S, Silvestris, N, Romito, S, Gebbia, V, Santoro, A, Artioli, F, Mattioli, R, Contu, A, Di Costanzo, F, Leonardi, F, Cavanna, L, Passalacqua, R, Sozzi, P, D'Amico, M, Amadori, D, Turci, D, Ravaioli, A, Pasquini, E, Gambi, A, Faedi, M, Cruciani, G, Bajetta, E, Gianni, L, Ionta, M, Massidda, B, Scartozzi, M, Ciarlo, A, Di Leo, A, Frustaci, S, Rangoni, G, Arizzoia, A, Pavesi, L, Verusio, C, Pinotti, G, Iop, A, De Placido, S, Adamo, V, Ficorella, C, Natale, D, Greco, E, Rulli, E, Poli, D, Porcu, L, Torri, V, Rosati, G., Lonardi, S., Galli, F., Di Bartolomeo, M., Ronzoni, M., Zampino, M. G., Banzi, M., Zaniboni, A., Pasini, F., Bozzarelli, S., Garattini, S. K., Ferrari, D., Montesarchio, V., Mambrini, A., Ciuffreda, L., Pusceddu, V., Carlomagno, C., Bidoli, P., Amoroso, D., Bochicchio, A. M., Frassineti, L., Corsi, D., Bilancia, D., Pastorino, A., De Stefano, A., Labianca, R., Iaffaioli, R. V., Nasti, G., Daniele, B., Zagonel, V., Pella, N., Aprile, G., Marchetti, R. P., Romiti, A., Foa, P., Mosconi, S., Sobrero, A., Cazzaniga, M., Beretta, G. D., Cortesi, E., Barni, S., Petrelli, F., Allione, P., D'Arco, A. M., Valmadre, G., Piazza, E., Veltri, E., Ramus, G. V., Giustini, L., Tumulo, S., Cascinu, S., Granetto, C., Testore, F., Giordano, M., Moroni, M., Di Seri, M., Nuzzo, A., Angelelli, L., Gori, S., Farina, G., Aglietta, M., Franchi, R., Comande, M., Giordani, P., Tonini, G., Bucci, E., Ballestrero, A., Benasso, M., Graiff, C., Bravi, S., Caffo, O., Silva, R. R., Frontini, L., Rota, S., Cozzi, L., Cantore, M., Maiello, E., Cinieri, S., Silvestris, N., Romito, S., Gebbia, V., Santoro, A., Artioli, F., Mattioli, R., Contu, A., Di Costanzo, F., Leonardi, F., Cavanna, L., Passalacqua, R., Sozzi, P., D'Amico, M., Amadori, D., Turci, D., Ravaioli, A., Pasquini, E., Gambi, A., Faedi, M., Cruciani, G., Bajetta, E., Gianni, L., Ionta, M. T., Massidda, B., Scartozzi, M., Ciarlo, A., Di Leo, A., Frustaci, S., Rangoni, G., Arizzoia, A., Pavesi, L., Verusio, C., Pinotti, G., Iop, A., De Placido, S., Adamo, V., Ficorella, C., Natale, D., Greco, E., Rulli, E., Poli, D., Porcu, L., Torri, V., and Corsi, D. C.

Subjects
0301 basic medicine, Oncology, Male, Cancer Research, Colorectal cancer, Leucovorin, Efficacy, Older patient, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Stage (cooking), Aged, 80 and over, Colonic Neoplasm, Prognostic factor, Middle Aged, Prognosis, Colon cancer, Survival Rate, Oxaliplatin, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Colonic Neoplasms, Female, Fluorouracil, medicine.drug, Human, Compliance, Adult, medicine.medical_specialty, Prognosi, Adjuvant chemotherapy, Older patients, Prognostic factors, Subgroup analysis, Follow-Up Studie, 03 medical and health sciences, Internal medicine, Post-hoc analysis, medicine, Adjuvant therapy, Humans, Capecitabine, Cancer staging, Aged, Antineoplastic Combined Chemotherapy Protocol, business.industry, medicine.disease, 030104 developmental biology, Neoplasm Recurrence, Local, business, Follow-Up Studies
Abstract

Background: Previous studies on oxaliplatin and fluoropyrimidines as adjuvant therapy in older patients with stage III colon cancer (CC) produced conflicting results. Patients and methods: We assessed the impact of age on time to tumour recurrence (TTR), disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) in 2360 patients with stage III CC (1667 aged

Published
2021

11. Trabectedin for patients with advanced soft tissue sarcoma: A non-interventional, retrospective, multicenter study of the italian sarcoma group

Author

Giuseppe Badalamenti, Irene Quattrini, Alberto Righi, F. Zanelli, Libero Ciuffreda, Angela Buonadonna, Elisabetta Setola, Piero Picci, Roberta Sanfilippo, Vittorio Ferrari, Fabio Gelsomino, Antonella Romanini, Toni Ibrahim, Maria Abbondanza Pantaleo, Laura Milesi, Giovanni Grignani, Emanuela Marchesi, Federica Grosso, Emanuela Palmerini, Elisa Carretta, Alessandro Comandone, Virginia Ferraresi, Bruno Vincenzi, Stefano Ferrari, Antonio Pizzolorusso, Antonella Brunello, Tommaso De Pas, Palmerini E., Sanfilippo R., Grignani G., Buonadonna A., Romanini A., Badalamenti G., Ferraresi V., Vincenzi B., Comandone A., Pizzolorusso A., Brunello A., Gelsomino F., De Pas T., Ibrahim T., Grosso F., Zanelli F., Pantaleo M.A., Milesi L., Ciuffreda L., Ferrari V., Marchesi E., Quattrini I., Righi A., Setola E., Carretta E., Picci P., and Ferrari S.

Subjects
0301 basic medicine, Leiomyosarcoma, Cancer Research, medicine.medical_specialty, Dacarbazine, lcsh:RC254-282, Gastroenterology, Article, Pazopanib, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Progression-free survival, Observational, Trabectedin, Soft tissue sarcoma, Performance status, business.industry, Real-life, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Sarcoma, business, medicine.drug
Abstract

The Italian Sarcoma Group performed this retrospective analysis of patients with advanced soft tissue sarcoma, pretreated with ≥1 anthracycline-based treatment, and treated with trabectedin every three weeks. Primary endpoint was to describe real-life use of trabectedin across Italy. Secondary endpoints included objective response rate (ORR) and safety. Overall, 512 patients from 20 Italian centers were evaluated. Leiomyosarcoma (37.7%)/liposarcoma (30.3%) were the most prevalent histological types (abbreviated as L-sarcoma). Patients received a median of four trabectedin cycles (range: 1–40), mostly as a second-line treatment (~60% of patients). The ORR was 13.7% superior (p &lt, 0.0001) in patients with L-sarcoma compared with patients with non-L-sarcoma (16.6% vs. 9.0%). Median progression-free survival (PFS) was 5.1 months, whereas median overall survival (OS) was 21.6 months. Significantly better PFS and OS were observed in patients with L-sarcoma, those with objective responses and/or disease stabilization, treated in an early line and treated with reduced dose. Bone marrow toxicity (61.4%) and transaminase increases (21.9%) were the most common grade 3/4 adverse events. The results of this real-life study suggest that trabectedin is an active treatment, which is mostly given as a second-line treatment to patients with a good performance status and high-grade, metastatic L-sarcoma (clinical trial information: NCT02793050).

Published
2021

12. Nivolumab and brain metastases in patients with advanced non-squamous non-small cell lung cancer

Author

Francovito Piantedosi, Antonio Santo, Claudia Proto, Antonio Frassoldati, Angelo Delmonte, Filippo de Marinis, Libero Ciuffreda, Enrico Cortesi, Paolo Bidoli, Graziella Pinotti, Marco Bregni, Riccardo Samaritani, Federico Cappuzzo, Lucio Crinò, Alfonso Illiano, Paola Cravero, Elisa Minenza, Giuseppe Tonini, Diana Giannarelli, Gianmauro Numico, Stefano Tamberi, Maria Giuseppina Sarobba, Francesco Grossi, Marina Chiara Garassino, Giuseppe Bronte, Crino, L, Bronte, G, Bidoli, P, Cravero, P, Minenza, E, Cortesi, E, Garassino, M, Proto, C, Cappuzzo, F, Grossi, F, Tonini, G, Sarobba, M, Pinotti, G, Numico, G, Samaritani, R, Ciuffreda, L, Frassoldati, A, Bregni, M, Santo, A, Piantedosi, F, Illiano, A, De Marinis, F, Tamberi, S, Giannarelli, D, and Delmonte, A

Subjects
0301 basic medicine, Oncology, Male, Cancer Research, Lung Neoplasms, 0302 clinical medicine, Antineoplastic Agents, Immunological, Non-small cell lung cancer, Carcinoma, Non-Small-Cell Lung, Aged, 80 and over, education.field_of_study, Brain Neoplasms, Brain metastasis, Immune checkpoint inhibitors, Nivolumab, Non-squamous, Middle Aged, Treatment Outcome, Italy, 030220 oncology & carcinogenesis, Disease Progression, Female, Immunotherapy, medicine.symptom, Pulmonary and Respiratory Medicine, Adult, medicine.medical_specialty, Population, Socio-culturale, Asymptomatic, 03 medical and health sciences, Internal medicine, medicine, Humans, Lung cancer, education, Cancer staging, Aged, brain metastasis, immune checkpoint inhibitors, nivolumab, non-small cell lung cancer, non-squamous, business.industry, medicine.disease, Survival Analysis, 030104 developmental biology, Expanded access, Concomitant, business
Abstract

Objectives Brain metastases are common among patients with non-squamous non-small-cell lung cancer (NSCLC) and result in a poor prognosis. Consequently, such patients are often excluded from clinical trials. In Italy an expanded access program (EAP) was used to evaluate nivolumab efficacy and safety in this subpopulation outside a clinical trial. Materials and methods In this EAP, nivolumab was available for patients with non-squamous NSCLC in progression after at least one systemic treatment for stage IIIB/IV disease. Nivolumab 3 mg/kg was administered intravenously every 2 weeks. Patients with brain metastases could be included if they were asymptomatic, neurologically stable and either off corticosteroids or on a stable or decreasing dose of ≤10 mg/day prednisone. Results 409 out of 1588 patients included had asymptomatic or controlled brain metastases. A median of 7 doses (range 1–45) were delivered. Median follow-up was 6.1 months (range 0.1–21.9). The disease control rate was 39%: 4 patients had a complete response, 64 a partial response and 96 showed stable disease. At baseline, 118 patients were on corticosteroids and 74 were undergoing concomitant radiotherapy. The median overall survival in this subpopulation was 8.6 months (95% CI: 6.4–10.8). 337 discontinued treatment for various reasons, 23 (7%) of whom due to adverse events, in line with that observed in the overall population and in previous studies. Conclusions Our results confirm that nivolumab is active in non-squamous NSCLC patients with brain metastases, despite their poor prognosis. Its safety profile is also concordant with results in the EAP overall population and in patients with other malignancies.

Published
2019

13. Assessment of Ramucirumab plus paclitaxel as switch maintenance versus continuation of first-line chemotherapy in patients with advanced HER-2 negative gastric or gastroesophageal junction cancers: The ARMANI phase III trial

Author

Marta Caporale, Salvatore Corallo, Alberto Gianluigi Luporini, Andrea Spallanzani, Michele Basso, Maria Di Bartolomeo, Mario Scartozzi, Federica Morano, Evaristo Maiello, Davide Tassinari, Andrea Bonetti, Graziella Pinotti, Filippo de Braud, Saverio Cinieri, Sergio Bracarda, Giovanni Gerardo Cardellino, Alessandro Bertolini, Claudio Verusio, Gianluca Tomasello, Hector Soto Parra, Alberto Zaniboni, Giampaolo Tortora, Samantha Di Donato, Sara Lonardi, Vincenzo Catalano, Francesco Di Costanzo, Raffaella Longarini, Libero Ciuffreda, Ferdinando De Vita, Francesco Giuliani, Maria Antista, Lorenza Rimassa, Rossana Berardi, Filippo Pietrantonio, Monica Niger, Stefano Tamberi, Lorenzo Fornaro, Giorgio V. Scagliotti, Giovanni Luca Frassineti, Di Bartolomeo, M., Niger, M., Morano, F., Corallo, S., Antista, M., Tamberi, S., Lonardi, S., Di Donato, S., Berardi, R., Scartozzi, M., Cardellino, G. G., Di Costanzo, F., Rimassa, L., Luporini, A. G., Longarini, R., Zaniboni, A., Bertolini, A., Tomasello, G., Pinotti, G., Scagliotti, G., Tortora, G., Bonetti, A., Spallanzani, A., Frassineti, G. L., Tassinari, D., Giuliani, F., Cinieri, S., Maiello, E., Verusio, C., Bracarda, S., Catalano, V., Basso, M., Ciuffreda, L., De Vita, F., Parra, H. S., Fornaro, L., Caporale, M., De Braud, F., and Pietrantonio, F.

Subjects
0301 basic medicine, Oncology, Male, Cancer Research, Receptor, ErbB-2, medicine.medical_treatment, chemistry.chemical_compound, Study Protocol, ErbB-2, 0302 clinical medicine, Quality of life, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, Antibodies, Monoclonal, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Clinical trial, First line, Maintenance, Metastatic gastric cancer, Ramucirumab, Drug Administration Schedule, Esophagogastric Junction, Female, Humans, Maintenance Chemotherapy, Paclitaxel, Progression-Free Survival, Quality of Life, Stomach Neoplasms, Treatment Outcome, 030220 oncology & carcinogenesis, Receptor, medicine.drug, Human, medicine.medical_specialty, Antibodies, Monoclonal, Humanized, lcsh:RC254-282, Antibodies, 03 medical and health sciences, Stomach Neoplasm, Internal medicine, Genetics, medicine, Chemotherapy, Antineoplastic Combined Chemotherapy Protocol, business.industry, Oxaliplatin, Regimen, 030104 developmental biology, chemistry, business
Abstract

Platinum/fluoropyrimidine regimens are the backbone of first-line chemotherapy for advanced gastric cancer (AGC). However response rates to first line chemotherapy range from 30 to 50% and disease progression occurs after 4–6 cycles. The optimal duration of first-line therapy is still unknown and its continuation until disease progression represents the standard. However this strategy is often associated with cumulative toxicity and rapid development of drug resistance. Moreover, only about 40% of AGC pts. are eligible for second-line treatment. This is a randomized, open-label, multicenter phase III trial. It aims at assessing whether switch maintenance to ramucirumab plus paclitaxel will extend the progression-free survival (PFS) of subjects with HER-2 negative AGC who have not progressed after 3 months of a first-line with a platinum/fluoropyrimidine regimen (either FOLFOX4, mFOLFOX6 or XELOX). The primary endpoint is to compare Progression-Free Survival (PFS) of patients in ARM A (switch maintenance to ramucirumab and placlitaxel) versus ARM B (continuation of the same first-line therapy with oxaliplatin/fluoropyrimidine). Secondary endpoints are: overall survival, time-to-treatment failure, overall response rate, duration of response, percentage of patients that will receive a second line therapy according to arm treatment, safety, quality of life. Exploratory studies including Next-Generation Sequencing (NGS) in archival tumor tissues are planned in order to identify potential biomarkers of primary resistance and prognosis. The ARMANI study estimates if patients treated with early swich with ramucirumab plus paclitaxel received benefit when compared to those treated with continuation of first line therapy. The hypothesis is that the early administration of an active, non-cross resistant second-line regimen such as ramucirumab plus paclitaxel may prolong the time in which patients are progression-free, and consequently have a better quality of life. Moreover, this strategy may rescue all those subjects that become ineligible for second-line therapy due to the rapid deterioration of health status after the first disease progression. ARMANI is registered at ClinicalTrials.gov ( NCT02934464 , October 17, 2016) and EudraCT(2016–001783-12, April 202,016).

Published
2019

14. Prospective validation of a lymphocyte infiltration prognostic test in stage III colon cancer patients treated with adjuvant FOLFOX

Author

Jean-François Emile, Catherine Julié, Karine Le Malicot, Come Lepage, Josep Tabernero, Enrico Mini, Gunnar Folprecht, Jean-Luc Van Laethem, Stéphanie Dimet, Camille Boulagnon-Rombi, Marc-Antoine Allard, Frédérique Penault-Llorca, Jaafar Bennouna, Pierre Laurent-Puig, Julien Taieb, Josef Thaler, Richard Greil, Johannes Gaenzer, Wolfgang Eisterer, Joerg Tschmelitsch, Felix Keil, Hellmut Samonigg, August Zabernigg, Franz Schmid, Günther Steger, Robert Steinacher, Johannes Andel, Björn Jagdt, Alois Lang, Michael Fridrik, Reinhold Függer, Friedrich Hofbauer, Ewald Woell, Dietmar Geissler, Alfred Lenauer, Manfred Prager, Geert D'Haens, Gauthier Demolin, Joseph Kerger, Guido Deboever, Gilbert Ghillebert, Marc Polus, Eric Van Cutsem, Hassan Rezaie Kalantari, Thierry Delaunoit, Jean Charles Goeminne, Marc Peeters, Philippe Vergauwe, Ghislain Houbiers, Yves Humblet, Jos Janssens, Dirk Schrijvers, Erik Vanderstraeten, Jan Vermorken, Daniel Van Daele, Michel Ferrante, Frederic Forget, Alain Hendlisz, Mette Yilmaz, Svend Erik Nielsen, Lene Vestermark, Jim Larsen, Mohamed-Ayman Zawadi, Olivier Bouche, Laurent Mineur, Jaafar Bennouna-Louridi, Louis Marie Dourthe, Marc Ychou, Eveline Boucher, Denis Pezet, Francoise Desseigne, Michel Ducreux, Patrick Texereau, Laurent Miglianico, Philippe Rougier, Serge Fratte, Charles-Briac Levache, Yacine Merrouche, Stephen Ellis, Christophe Locher, Jean-Francois Ramee, Claire Garnier, Frederic Viret, Bruno Chauffert, Isabelle Cojean-Zelek, Pierre Michel, Cedric Lecaille, Christian Borel, Jean-Francois Seitz, Denis Smith, Catherine Lombard-Bohas, Thierry Andre, Jean-Marc Gornet, Francine Fein, Marie-Aude Coulon-Sfairi, Marie-Christine Kaminsky, Jean-Paul Lagasse, Dominique Luet, Pierre-Luc Etienne, Mohamed Gasmi, Andre Vanoli, Suzanne Nguyen, Thomas Aparicio, Hervé Perrier, Noel Stremsdoerfer, Philippe Laplaige, Dominique Arsene, Dominique Auby, Laurent Bedenne, Romain Coriat, Bernard Denis, Patrick Geoffroy, Gilles Piot, Yves Becouarn, Gilbert Bordes, Gael Deplanque, Olivier Dupuis, Frederic Fruge, Rosine Guimbaud, Thierry Lecomte, Gérard Lledo, Iradej Sobhani, Amani Asnacios, Ahmed Azzedine, Christophe Desauw, Marie-Pierre Galais, Dany Gargot, You-Heng Lam, Abakar Abakar-Mahamat, Jean-Francois Berdah, Sylviane Catteau, Marie-Christine Clavero-Fabri, Jean-Francois Codoul, Jean-Louis Legoux, Denis Goldfain, Pierre Guichard, Denis Pere Verge, Jocelyne Provencal, Bruno Vedrenne, Catherine Brezault-Bonnet, Denis Cleau, Jean-Paul Desir, David Fallik, Bruno Garcia, Marie-Hélène Gaspard, Dominique Genet, Johannes Hartwig, Yves Krummel, Tamara Matysiak Budnik, Vanessa Palascak-Juif, Harizo Randrianarivelo, Yves Rinaldi, Albert Aleba, Ariane Darut-Jouve, Aimery de Gramont, Herve Hamon, Frederic Wendehenne, Axel Matzdorff, Michael Konrad Stahl, Wolfgang Schepp, Martin Burk, Lothar Mueller, Michael Geissler, Luisa Mantovani-Loeffler, Thomas Hoehler, Walter Asperger, Hendrik Kroening, Ludwig Fischer von Weikersthal, Stefan Fuxius, Matthias Groschek, Johannes Meiler, Tanja Trarbach, Jacqueline Rauh, Nicolas Ziegenhagen, Albrecht Kretzschmar, Ullrich Graeven, Arnd Nusch, Goetz von Wichert, Ralf-Dieter Hofheinz, Gerhard Kleber, Karl-Heinz Schmidt, Ursula Vehling-Kaiser, Claudia Baum, Jochen Schuette, Georg Martin Haag, Wilhelm Holtkamp, Jochen Potenberg, Tobias Reiber, Georg Schliesser, Hans-Joachim Schmoll, Wolfgang Schneider-Kappus, Wolfgang Abenhardt, Claudio Denzlinger, Jan Henning, Bartscht Marxsen, Hans Guenter Derigs, Helmut Lambertz, Ingulf Becker-Boost, Karel Caca, Christian Constantin, Thomas Decker, Henning Eschenburg, Sigrun Gabius, Holger Hebart, Albrecht Hoffmeister, Heinz-August Horst, Stephan Kremers, Malte Leithaeuser, Sebastian Mueller, Siegfried Wagner, Severin Daum, Frank Schlegel, Martina Stauch, Volker Heinemann, Evaristo Maiello, Luciano Latini, Alberto Zaniboni, Dino Amadori, Giuseppe Aprile, Sandro Barni, Rodolfo Mattioli, Andrea Martoni, Rodolfo Passalacqua, Mario Nicolini, Enzo Pasquini, Carla Rabbi, Enrico Aitini, Alberto Ravaioli, Carlo Barone, Guido Biasco, Stefano Tamberi, Angelo Gambi, Claudio Verusio, Marina Marzola, Giorgio Lelli, Corrado Boni, Stefano Cascinu, Paolo Bidoli, Massimo Vaghi, Giorgio Cruciani, Francesco Di Costanzo, Alberto Sobrero, Roberto Petrioli, Massimo Aglietta, Oscar Alabiso, Federico Capuzzo, Alfredo Falcone, Domenico Cristi Corsi, Roberto Labianca, Stefania Salvagni, Silvana Chiara, Libero Ciuffreda, Francesco Ferraù, Francesco Giuliani, Sara Lonardi, Nicola Gebbia, Giovanni Mantovani, Evaristo Sanches, Juan Carlos Mellidez, Pedro Santos, Joao Freire, Cristina Sarmento, Luis Costa, Antonio Moreira Pinto, Sergio Barroso, Jorge Espirito Santo, Fátima Guedes, Amélia Monteiro, Anabela Sa, Irene Furtado, Ramon Salazar, Enrique Aranda Aguilar, Fernando Rivera Herrero, Javier Sastre Valera, Manuel Valladares Ayerbes, Jaime Feliu Batlle, Silvia Gil, Albert Abad Esteve, Carlos Garcia-Giron, Guillermo Lopez Vivanco, Antonia Salud Salvia, Vicente Alonso Orduña, Ruth Vera Garcia, Javier Gallego, Bartomeu Massuti Sureda, Jordi Remon, Maria Jose Safont Aguilera, Luis Cirera Nogueras, Bernado Queralt Merino, Cristina Gravalos Castro, Purificacion Martinez de Prado, Carlos Pijaume Pericay, Manuel Constenla Figueiras, Inmaculada Guasch Jordan, Maria Jose Gome Reina, Amelia Lopez-Ladron Garcia, Antonio Arrivi Garcia-Ramos, Andres Cervantes, Carlos Fernandez Martos, Eugenio Marcuello Gaspar, Ines Cabezas Montero, Pilar Escudero Emperador, Ana Leon Carbonero, Manuel Gallen Castillo, Teresa Garcia Garcia, Jose Garcia Lopez, Encarnacion Gonzalez Flores, Monica Guillot Morales, Marta Llanos Muñoz, Ana López Martín, Joan Maurel, Juan Carlos Camara, Rosario Dueñas Garcia, Mercedes Salgado, Isabel Hernandez Busquier, Teresa Checa Ruiz, Adelaida Lacasta Muñoa, Miquel Nogue Aliguer, Amalia Velasco Ortiz de Taranco, Miguel Mendez Ureña, Ferran Losa Gaspa, Jose Juan Ponce, Carlos Bosch Roig, Pedro Valero Jimenez, Antonio Galan Brotons, Santiago Albiol Rodriguez, Jose Ales Martinez, Liliana Canosa Ruiz, Margarita Centelles Ruiz, John Bridgewater, Rob Glynne-Jones, Saad Tahir, Tamas Hickish, Jim Cassidy, Leslie Samuel, UE 1373 Fourrages Environnement Ruminants Lusignan, Institut National de la Recherche Agronomique ( INRA ) -Physiologie Animale et Systèmes d'Elevage ( PHASE ) -Environnement et Agronomie ( E.A. ) -Biologie et Amélioration des Plantes ( BAP ) -Fourrages Environnement Ruminants Lusignan ( FERLUS ), Service de pathologie [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Service de Biostatistique, Fédération Francophone de la Cancérologie Digestive, FFCD, Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Vall d'Hebron University Hospital [Barcelona], Dpt of Internal Medicine, Section of Immunoallergology and Respiratory [Florence] Diseases, University of Florence, Carl Gustav Carus University Hospital, Erasme Hospital, Brussels, Centre Hepato-Biliaire, AP-HP Hôpital Paul Brousse, Modèles de Cellules Souches Malignes et Thérapeutiques, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne ( IMoST ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Clermont Auvergne ( UCA ), Institut de cancérologie de l'Ouest - Nantes ( ICO Nantes ), CRLCC Paul Papin-CRLCC René Gauducheau, Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers ( CRCINA ), Université d'Angers ( UA ) -Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche en Santé de l'Université de Nantes ( IRS-UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ), Université de Nantes ( UN ), Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique ( MEPPOT - U1147 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Klinikum Wels Grieskirchen, Oncology department [Salzburg], Salzburger Landesklinikum - Uniklinikum Salzburg ( SALK ), Institute of Chemical Reaction Engineering, Hamburg University of Technology, Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung ( AWI ), Department of Medical Oncology, Medical University Vienna, Department of Internal Medicine, Hospital of Steyr, Department Internal Medicine 3, Centre for Hematology and Medical Oncology, General Hospital Linz, Department Medicine LKH, Institut für Festköperfirschung, Institut des Sciences Moléculaires de Marseille ( ISM2 ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Centrale de Marseille ( ECM ) -Aix Marseille Université ( AMU ), University Hospitals Leuven [Leuven], Katholieke Universiteit Leuven ( KU Leuven ), Pharmacology and Toxicology, Ahvaz Jundishapur University of Medical Sciences, Institut de Biologie Computationnelle ( IBC ), Centre de Coopération Internationale en Recherche Agronomique pour le Développement ( CIRAD ) -Institut National de la Recherche Agronomique ( INRA ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut des Sciences Moléculaires ( ISM ), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique ( CNRS ), Faculty of Veterinary Medicine, Ghent University [Belgium] ( UGENT ), Medical Oncology, Antwerp University Hospital [Edegem], Recombinaison et Expression Génétique, Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier de L'Ardenne (Libramont), Department of Cardiology [Sivas, Turkey], Cumhuriyet University [Sivas, Turkey], Department of Earth Sciences, Durham University, Department of Oncology, Rigshospitalet [Copenhagen], Odense Hospital, CP Kelco ApS, Centre Hospitalier Universitaire de Reims ( CHU Reims ), Institut de Recherche en Cancérologie de Montpellier ( IRCM - U1194 Inserm - UM ), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Université du Québec à Montréal ( UQAM ), Université Panthéon-Sorbonne ( UP1 ), École nationale supérieure d'architecture de Nantes ( ENSA Nantes ), Department of Hepatogastroenterology and Oncology, Hopital Ambroise Pare, 9, Avenue Charles de Gaulle, 92104, Boulogne Cedex, France., Hôpital Ambroise Paré, CH Belfort-Montbéliard, Polyclinique Francheville, Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne ( CHU de Saint-Etienne ), Centre Hospitalier de Meaux, Service d'hématologie, Clinique Catherine de Sienne, Unité de recherche sur les Biopolymères, Interactions Assemblages ( BIA ), Institut National de la Recherche Agronomique ( INRA ), Université de la Méditerranée - Aix-Marseille 2, Centre hospitalier universitaire d'Amiens ( CHU Amiens-Picardie ), CHU Amiens-Picardie, Pôle oncologie médicale, Hôpital des Diaconesses, Génétique du cancer et des maladies neuropsychiatriques ( GMFC ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Bretagne Occidentale - École de sages-femmes ( UBO UFR MSS ESF ), Université de Brest ( UBO ) -Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Service d'Oncologie Médicale [Centre hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Service d'Oncologie Médicale [CHU Saint -Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), Service Gastro-Entérologie, CHU Besançon, Université de Franche-Comté ( UFC ) -Université de Franche-Comté ( UFC ), Centre Alexis Vautrin ( CAV ), Ecophysiologie Végétale, Agronomie et Nutritions ( EVA ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Recherche Agronomique ( INRA ), Image et ville ( IV ), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique ( CNRS ), Département informatique ( INFO ), Université européenne de Bretagne ( UEB ) -Télécom Bretagne-Institut Mines-Télécom [Paris], Service de Gastro-entérologie [Avicenne], Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Agence de l'Environnement et de la Maîtrise de l'Energie - ADEME, Service d'hépato-gastroentérologie, CHU Caen-Hôpital côte de nacre, Département de Médecine, Centre hospitalier de Libourne, Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Fondation FondaMental, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor, Variabilité de réponse aux psychotropes ( VariaPsy - U1144 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Diderot - Paris 7 ( UPD7 ), Département d'oncologie digestive, Institut Bergonié - CRLCC Bordeaux, Hôpital St Joseph, Service de Gynécologie et d'Obstétrique ( CHU Lyon ), Hospices Civils de Lyon ( HCL ), Gastro - Entérologie et Nutrition, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Génétique, Immunothérapie, Chimie et Cancer ( GICC ), Université de Tours-Centre National de la Recherche Scientifique ( CNRS ), Université Montpellier 1 ( UM1 ), Service de gastro-entérologie - Hôpital Henri Mondor, Laboratoire Matière et Systèmes Complexes ( Laboratoire MSC ), Université Paris Diderot - Paris 7 ( UPD7 ) -UFR de Physique, France, Amériques, Espagne – Sociétés, pouvoirs, acteurs ( FRAMESPA ), Université Toulouse - Jean Jaurès ( UT2J ) -Centre National de la Recherche Scientifique ( CNRS ), Regional Hospital of Orleans, Histoire, Archéologie et littératures des Mondes chrétiens et musulmans médiévaux ( CIHAM ), École normale supérieure - Lyon ( ENS Lyon ) -Université Lumière - Lyon 2 ( UL2 ) -École des hautes études en sciences sociales ( EHESS ) -Université Jean Moulin - Lyon III ( UJML ) -Université d'Avignon et des Pays de Vaucluse ( UAPV ) -Centre National de la Recherche Scientifique ( CNRS ), Neurobiologie des signaux intercellulaires ( NSI ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Dept Med Genet, Hôpital Erasme (Bruxelles), Polyclinique de Limoges - site François Chénieux [Limoges], Clinique Médicale B, CHU Strasbourg, Service de gastro-entérologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Hôpital Européen [Fondation Ambroise Paré - Marseille], Asklepios Klinikum Uckermark GmbH, DESY, Notkestr 85, D-22607 Hamburg, Germany, NASA Ames Research Center ( ARC ), Department of Chemistry, Center for Structural Biology, Vanderbilt University [Nashville], Biostatistique et Processus Spatiaux ( BIOSP ), Institute of Ecology [Jena], Friedrich-Schiller-Universität Jena, University of Rostock [Germany], Universität Stuttgart [Stuttgart], Oneonta, Zentrum für Innere Medizin, Klinikum Schwäbisch Gmünd/Stauferklinik, Physiopathologie du stress pancréatique, Institut Armand Frappier ( INRS-IAF ), Institut National de la Recherche Scientifique [Québec] ( INRS ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut Armand Frappier, Institut de Mathématiques de Marseille ( I2M ), Aix Marseille Université ( AMU ) -Ecole Centrale de Marseille ( ECM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Department of Computer Science [Freiburg], University of Freiburg [Freiburg], Institut für Mathematik [Berlin], Technische Universität Berlin ( TUB ), Department of Information Engineering, Computer Science and Mathematics, Università degli Studi dell'Aquila [L'Aquila] ( UNIVAQ.IT ), Department of Animal Sciences, North Carolina Agricultural and Technical State University, FEEM, Romagna Cancer Registry, IRST, Luigi Pierantoni Hospital, Observatoire sociologique du changement ( OSC ), Sciences Po-Centre National de la Recherche Scientifique ( CNRS ), Dipartimento di Chimica, Fisica e Ambiente, Università degli Studi di Udine - University of Udine [Italie], Department of Nuclear Medicine, PET/CT Centre, Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Clinica di Oncologia Medica, AO Ospedali Riuniti, Università Politecnica delle Marche [Ancona] ( UNIVPM ), Universidade Nova de Lisboa ( UNINOVA ), Ottawa Hospital Research Institute [Ottawa] ( OHRI ), Oncologia Medica, Ospedali Riuniti, Ospedale 'San Vincenzo', NIPE, CIPES, European Synchrotron Radiation Facility ( ESRF ), Departamento de Engenharia Informática, Faculdade de Engenharia [Porto] ( FEUP ), Universidade do Porto [Porto]-Universidade do Porto [Porto], 3Decide, Unité de recherche Amélioration, Génétique et Physiologie Forestières ( UAGPF ), Universidade Federal de Campina Grande [Campina Grande] ( UFCG ), Instituto de Engenharia de Sistemas e Computadores ( INESC ), Departamento de Ciências Biológicas, Universidade Regional do Cariri ( URCA Brasil ), Department of Biochemistry and Molecular Biology [Barcelona, Spain], Universitat de Barcelona ( UB ), Associated Unit to Consejo Superior de Investigaciones Científicas - CSIC [Barcelona, Spain], University of Barcelona-Institute of Biomedicine - IBUB [Barcelona, Spain], IRCELYON-Caractérisation et remédiation des polluants dans l'air et l'eau ( CARE ), Institut de recherches sur la catalyse et l'environnement de Lyon ( IRCELYON ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'analyse et d'architecture des systèmes [Toulouse] ( LAAS ), Centre National de la Recherche Scientifique ( CNRS ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse ( INSA Toulouse ), Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Institut National Polytechnique [Toulouse] ( INP ), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier ( ICGM ICMMM ), Université Montpellier 1 ( UM1 ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Ecole Nationale Supérieure de Chimie de Montpellier ( ENSCM ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Instituto de Ciencia de Materiales de Madrid [Madrid] ( ICMM ), Interactions, Corpus, Apprentissages, Représentations ( ICAR ), École normale supérieure - Lyon ( ENS Lyon ) -Université Lumière - Lyon 2 ( UL2 ) -INRP-Ecole Normale Supérieure Lettres et Sciences Humaines-Centre National de la Recherche Scientifique ( CNRS ), Institut d'Investigacions Biomèdiques August Pi i Sunyer ( IDIBAPS ), North Region Cancer Registry of Portugal, UMR 5805 Environnements et Paléoenvironnements Océaniques et Continentaux ( EPOC ), Observatoire aquitain des sciences de l'univers ( OASU ), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -École pratique des hautes études ( EPHE ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Paediatrics and Intensive Care, Hospital Universitari Sant Joan de Deu, Laboratoire de Psychologie Sociale ( LPS ), Aix Marseille Université ( AMU ), Universitat de València ( UV ), Instituto de Cienca de Materiales de Madrid [Madrid] ( ICMM ), Biology, New Mexico State University, New Mexico State University, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ), Centre de recherche sur les Ions, les MAtériaux et la Photonique ( CIMAP - UMR 6252 ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Supérieure d'Ingénieurs de Caen ( ENSICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ), Institut d'Electronique et de Télécommunications de Rennes ( IETR ), Université de Nantes ( UN ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), Computer Science Department - Carnegie Mellon University, University of Pittsburgh, Laboratoire de Sciences Actuarielle et Financière ( SAF ), Université de Lyon-Université de Lyon, Instituto de Oncologia Corachan ( IDOC ), Laboratoire d'informatique de l'école normale supérieure ( LIENS ), École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ), Experimental Quantum Optics and Photonics Group, University of Strathclyde, Institut de recherches Asiatiques ( IrAsia ), Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Européen de Réalité Virtuelle ( CERV ), École Nationale d'Ingénieurs de Brest ( ENIB ), Sol Agro et hydrosystème Spatialisation ( SAS ), Institut National de la Recherche Agronomique ( INRA ) -AGROCAMPUS OUEST, Grenoble Institut des Neurosciences ( GIN ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Grenoble-Université Joseph Fourier - Grenoble 1 ( UJF ), Centre de recherche cerveau et cognition ( CERCO ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Laboratoire Géomatériaux et Environnement ( LGE ), Université Paris-Est Marne-la-Vallée ( UPEM ), Hôpital Ambroise Paré [AP-HP], Université Paris-Saclay, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Centre hépato-biliaire (CHB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Université de Nantes (UN), Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Salzburger Landesklinikum - Uniklinikum Salzburg (SALK), Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung (AWI), Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Institut de Biologie Computationnelle (IBC), Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Moléculaires (ISM), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Universiteit Gent = Ghent University [Belgium] (UGENT), Antwerp University Hospital [Edegem] (UZA), Hillerød Hospital, Copenhagen University Hospital-Copenhagen University Hospital, Centre Hospitalier Universitaire de Reims (CHU Reims), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université du Québec à Montréal = University of Québec in Montréal (UQAM), Université Paris 1 Panthéon-Sorbonne (UP1), École nationale supérieure d'architecture de Nantes (ENSA Nantes), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bretagne Occidentale - École de sages-femmes (UBO UFR MSS ESF), Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Alexis Vautrin (CAV), Ecophysiologie Végétale, Agronomie et Nutritions (EVA), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Recherche Agronomique (INRA), Image et ville (IV), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Département informatique (INFO), Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Agence de l'Environnement et de la Maîtrise de l'Energie (ADEME), Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Libourne, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation FondaMental [Créteil], Variabilité de réponse aux Psychotropes (VariaPsy - U1144), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Service de Gynécologie et d'Obstétrique (CHU Lyon), Hospices Civils de Lyon (HCL), Génétique, immunothérapie, chimie et cancer (GICC), UMR 7292 CNRS [2012-2017] (GICC UMR 7292 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1), Service de gastro-entérologie [Henri Mondor AP-HP, Créteil], Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Hôpital privé Toulon Hyères : Sainte Marguerite, Clinique des Quatre Pavillons, Lormont, France, Neurobiologie des signaux intercellulaires (NSI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), NASA Ames Research Center (ARC), Biostatistique et Processus Spatiaux (BioSP), Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], University of Rostock, State University of New York at Oneonta (SUNY Oneonta), State University of New York (SUNY), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Armand Frappier (INRS-IAF), Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), Institut de Mathématiques de Marseille (I2M), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Klinikum Deggendorf, Technische Universität Berlin (TU), Università degli Studi dell'Aquila (UNIVAQ), North Carolina A&T State University, University of North Carolina System (UNC)-University of North Carolina System (UNC), Observatoire sociologique du changement (OSC), Sciences Po (Sciences Po)-Centre National de la Recherche Scientifique (CNRS), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Università Politecnica delle Marche [Ancona] (UNIVPM), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Ottawa Hospital Research Institute [Ottawa] (OHRI), European Synchrotron Radiation Facility (ESRF), Departamento de Engenharia Informática [Porto], Faculdade de Engenharia da Universidade do Porto (FEUP), Universidade do Porto-Universidade do Porto, Universidade Federal de Campina Grande [Campina Grande] (UFCG), Instituto de Engenharia de Sistemas e Computadores (INESC), Universidade Regional do Cariri (URCA Brasil), Universitat de Barcelona (UB), IRCELYON-Catalytic and Atmospheric Reactivity for the Environment (CARE), Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), Instituto de Ciencia de Materiales de Madrid (ICMM), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Interactions, Corpus, Apprentissages, Représentations (ICAR), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-INRP-Ecole Normale Supérieure Lettres et Sciences Humaines (ENS LSH)-Centre National de la Recherche Scientifique (CNRS), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), UMR 5805 Environnements et Paléoenvironnements Océaniques et Continentaux (EPOC), Observatoire aquitain des sciences de l'univers (OASU), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Hospital Universitario de Valme, Anenida de Bellavista s/n, Sevilla 41014, Spain, Hospital Son Llatzer, Universitat de València (UV), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hospital Universitari Son Espases, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Instituto de Oncologia Corachan (IDOC), Laboratoire d'informatique de l'école normale supérieure (LIENS), École normale supérieure - Paris (ENS Paris), Institut de recherches Asiatiques (IrAsia), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre Européen de Réalité Virtuelle (CERV), École Nationale d'Ingénieurs de Brest (ENIB), Sol Agro et hydrosystème Spatialisation (SAS), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Géomatériaux et Environnement (LGE), Université Paris-Est Marne-la-Vallée (UPEM), Fédération Francophone de Cancérologie Digestive (FFCD), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service d'Oncologie Médicale [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Recherche Agronomique (INRA)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Department of Information Engineering, Computer Science and Mathematics = Dipartimento di Ingegneria e Scienze dell'Informazione e Matematica [L'Aquila] (DISIM), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Département d'informatique - ENS Paris (DI-ENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU), Institute of Biomedicine - IBUB [Barcelona, Spain]-University of Barcelona, Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Université Sciences et Technologies - Bordeaux 1-Université Montesquieu - Bordeaux 4-Institut de Chimie du CNRS (INC), AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Physiologie Animale et Systèmes d'Elevage (PHASE), Institut National de la Recherche Agronomique (INRA)-Environnement et Agronomie (E.A.)-Biologie et Amélioration des Plantes (BAP)-Fourrages Environnement Ruminants Lusignan (FERLUS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré, University of Florence (UNIFI), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Institut de cancérologie de l'Ouest - Nantes (ICO Nantes), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique (CNRS), Ghent University [Belgium] (UGENT), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université du Québec à Montréal (UQAM), Université Panthéon-Sorbonne (UP1), Centre hospitalier universitaire d'Amiens (CHU Amiens-Picardie), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Franche-Comté (UFC)-Université de Franche-Comté (UFC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Avicenne, Optimisation Thérapeutique en Neuropsychopharmacologie (VariaPsy - U1144), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Biostatistique et Processus Spatiaux (BIOSP), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Technische Universität Berlin (TUB), Università degli Studi dell'Aquila [L'Aquila] (UNIVAQ.IT), Universidade Nova de Lisboa (NOVA), Faculdade de Engenharia [Porto] (FEUP), Unité de recherche Amélioration, Génétique et Physiologie Forestières (UAGPF), IRCELYON-Caractérisation et remédiation des polluants dans l'air et l'eau (CARE), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Consejo Superior de Investigaciones Científicas [Spain] (CSIC), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-INRP-Ecole Normale Supérieure Lettres et Sciences Humaines-Centre National de la Recherche Scientifique (CNRS), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM), Emile, J, Julie, C, Le Malicot, K, Lepage, C, Tabernero, J, Mini, E, Folprecht, G, Van Laethem, J, Dimet, S, Boulagnon-Rombi, C, Allard, M, Penault-Llorca, F, Bennouna, J, Laurent-Puig, P, Taieb, J, Bidoli, P, Emile, J. -F., Julie, C., Le Malicot, K., Lepage, C., Tabernero, J., Mini, E., Folprecht, G., Van Laethem, J. -L., Dimet, S., Boulagnon-Rombi, C., Allard, M. -A., Penault-Llorca, F., Bennouna, J., Laurent-Puig, P., Taieb, J., Thaler, J., Greil, R., Gaenzer, J., Eisterer, W., Tschmelitsch, J., Keil, F., Samonigg, H., Zabernigg, A., Schmid, F., Steger, G., Steinacher, R., Andel, J., Jagdt, B., Lang, A., Fridrik, M., Fugger, R., Hofbauer, F., Woell, E., Geissler, D., Lenauer, A., Prager, M., D'Haens, G., Demolin, G., Kerger, J., Deboever, G., Ghillebert, G., Polus, M., Van Cutsem, E., Kalantari, H. R., Delaunoit, T., Goeminne, J. C., Peeters, M., Vergauwe, P., Houbiers, G., Humblet, Y., Janssens, J., Schrijvers, D., Vanderstraeten, E., Vermorken, J., Van Daele, D., Ferrante, M., Forget, F., Hendlisz, A., Yilmaz, M., Nielsen, S. E., Vestermark, L., Larsen, J., Zawadi, M. -A., Bouche, O., Mineur, L., Bennouna-Louridi, J., Dourthe, L. M., Ychou, M., Boucher, E., Pezet, D., Desseigne, F., Ducreux, M., Texereau, P., Miglianico, L., Rougier, P., Fratte, S., Levache, C. -B., Merrouche, Y., Ellis, S., Locher, C., Ramee, J. -F., Garnier, C., Viret, F., Chauffert, B., Cojean-Zelek, I., Michel, P., Lecaille, C., Borel, C., Seitz, J. -F., Smith, D., Lombard-Bohas, C., Andre, T., Gornet, J. -M., Fein, F., Coulon-Sfairi, M. -A., Kaminsky, M. -C., Lagasse, J. -P., Luet, D., Etienne, P. -L., Gasmi, M., Vanoli, A., Nguyen, S., Aparicio, T., Perrier, H., Stremsdoerfer, N., Laplaige, P., Arsene, D., Auby, D., Bedenne, L., Coriat, R., Denis, B., Geoffroy, P., Piot, G., Becouarn, Y., Bordes, G., Deplanque, G., Dupuis, O., Fruge, F., Guimbaud, R., Lecomte, T., Lledo, G., Sobhani, I., Asnacios, A., Azzedine, A., Desauw, C., Galais, M. -P., Gargot, D., Lam, Y. -H., Abakar-Mahamat, A., Berdah, J. -F., Catteau, S., Clavero-Fabri, M. -C., Codoul, J. -F., Legoux, J. -L., Goldfain, D., Guichard, P., Verge, D. P., Provencal, J., Vedrenne, B., Brezault-Bonnet, C., Cleau, D., Desir, J. -P., Fallik, D., Garcia, B., Gaspard, M. -H., Genet, D., Hartwig, J., Krummel, Y., Budnik, T. M., Palascak-Juif, V., Randrianarivelo, H., Rinaldi, Y., Aleba, A., Darut-Jouve, A., de Gramont, A., Hamon, H., Wendehenne, F., Matzdorff, A., Stahl, M. K., Schepp, W., Burk, M., Mueller, L., Geissler, M., Mantovani-Loeffler, L., Hoehler, T., Asperger, W., Kroening, H., von Weikersthal, L. F., Fuxius, S., Groschek, M., Meiler, J., Trarbach, T., Rauh, J., Ziegenhagen, N., Kretzschmar, A., Graeven, U., Nusch, A., von Wichert, G., Hofheinz, R. -D., Kleber, G., Schmidt, K. -H., Vehling-Kaiser, U., Baum, C., Schuette, J., Haag, G. M., Holtkamp, W., Potenberg, J., Reiber, T., Schliesser, G., Schmoll, H. -J., Schneider-Kappus, W., Abenhardt, W., Denzlinger, C., Henning, J., Marxsen, B., Derigs, H. G., Lambertz, H., Becker-Boost, I., Caca, K., Constantin, C., Decker, T., Eschenburg, H., Gabius, S., Hebart, H., Hoffmeister, A., Horst, H. -A., Kremers, S., Leithaeuser, M., Mueller, S., Wagner, S., Daum, S., Schlegel, F., Stauch, M., Heinemann, V., Maiello, E., Latini, L., Zaniboni, A., Amadori, D., Aprile, G., Barni, S., Mattioli, R., Martoni, A., Passalacqua, R., Nicolini, M., Pasquini, E., Rabbi, C., Aitini, E., Ravaioli, A., Barone, C., Biasco, G., Tamberi, S., Gambi, A., Verusio, C., Marzola, M., Lelli, G., Boni, C., Cascinu, S., Bidoli, P., Vaghi, M., Cruciani, G., Di Costanzo, F., Sobrero, A., Petrioli, R., Aglietta, M., Alabiso, O., Capuzzo, F., Falcone, A., Corsi, D. C., Labianca, R., Salvagni, S., Chiara, S., Ciuffreda, L., Ferrau, F., Giuliani, F., Lonardi, S., Gebbia, N., Mantovani, G., Sanches, E., Mellidez, J. C., Santos, P., Freire, J., Sarmento, C., Costa, L., Pinto, A. M., Barroso, S., Santo, J. E., Guedes, F., Monteiro, A., Sa, A., Furtado, I., Salazar, R., Aguilar, E. A., Herrero, F. R., Valera, J. S., Ayerbes, M. V., Batlle, J. F., Gil, S., Esteve, A. A., Garcia-Giron, C., Vivanco, G. L., Salvia, A. S., Orduna, V. A., Garcia, R. V., Gallego, J., Sureda, B. M., Remon, J., Safont Aguilera, M. J., Nogueras, L. C., Merino, B. Q., Castro, C. G., de Prado, P. M., Pericay, C. P., Figueiras, M. C., Jordan, I. G., Gome Reina, M. J., Garcia, A. L. -L., Garcia-Ramos, A. A., Cervantes, A., Martos, C. F., Gaspar, E. M., Montero, I. C., Emperador, P. E., Carbonero, A. L., Castillo, M. G., Garcia, T. G., Lopez, J. G., Flores, E. G., Morales, M. G., Munoz, M. L., Martin, A. L., Maurel, J., Camara, J. C., Garcia, R. D., Salgado, M., Busquier, I. H., Ruiz, T. C., Munoa, A. L., Aliguer, M. N., de Taranco, A. V. O., Urena, M. M., Gaspa, F. L., Ponce, J. J., Roig, C. B., Jimenez, P. V., Brotons, A. G., Rodriguez, S. A., Martinez, J. A., Ruiz, L. C., Ruiz, M. C., Bridgewater, J., Glynne-Jones, R., Tahir, S., Hickish, T., Cassidy, J., and Samuel, L.

Subjects
0301 basic medicine, Oncology, Male, Cancer Research, Organoplatinum Compounds, Colorectal cancer, medicine.medical_treatment, Medizin, Leucovorin, Prospective cohort study, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, FOLFOX, Organoplatinum Compounds/therapeutic use, Antineoplastic Combined Chemotherapy Protocols, tudy, Lymphocytes, Prospective Studies, Leucovorin/therapeutic use, Middle Aged, Prognosis, 3. Good health, Colorectal carcinoma, Fluorouracil, 030220 oncology & carcinogenesis, Predictive value of tests, Colonic Neoplasms, Biomarker (medicine), Lymphocytes/pathology, Female, Adjuvant, medicine.drug, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Fluorouracil/therapeutic use, Biomarkers, Tumor/analysis, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, Predictive Value of Tests, Biomarker, Immune response, Internal medicine, medicine, Biomarkers, Tumor, Humans, Survival analysis, Aged, business.industry, medicine.disease, Survival Analysis, Surgery, 030104 developmental biology, Prospective cohort&nbsp, Multivariate Analysis, Colonic Neoplasms/diagnosis, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, business
Abstract

IF 6.029; International audience; BackgroundThe prognostic value of lymphocyte infiltration (LI) of colorectal carcinoma (CC) has been demonstrated by several groups. However, no validated test is currently available for clinical practice. We previously described an automated and reproducible method for testing LI and aimed to validate it for clinical use.Patients and methodsAccording to National Institutes of Health criteria, we designed a prospective validation of this biomarker in patients included in the PETACC8 phase III study. Primary objective was to compare percentage of patients alive and without recurrence at 2 years in patients with high versus low LI (#NCT02364024). Associations of LI with patient recurrence and survival were analysed, and multivariable models were adjusted for treatment and relevant factors. Automated testing of LI was performed on virtual slides without access to clinical data.ResultsAmong the 1220 CC patients enrolled, LI was high, low and not evaluable in 241 (19.8%), 790 (64.8%) and 189 (15.5%), respectively. Primary objective was met with a 2-year recurrence rate of 14.4% versus 21.1% in patients with high and low LI, respectively (p = 0.02). Patients with high LI also had better disease free survival (DFS) and overall survival (OS). Tumour stage, grade, RAS status and BRAF status were with LI the only prognostic markers in multivariable analysis for OS. Subgroup analyses revealed that high LI had better DFS and OS in mismatch repair (MMR) proficient patients, and in patients without RAS mutation, but not in MMR deficient and RAS mutated patients.ConclusionAlthough this is the first validation with high level of evidence (IIB) of the prognostic value of a LI test in colon cancers, it still needs to be confirmed in independent series of colon cancer patients.

Published
2017

15. PTEN status is a crucial determinant of the functional outcome of combined MEK and mTOR inhibition in cancer

Author

Donatella Del Bufalo, Isabella Sperduti, Italia Falcone, Michele Milella, Giovanni Blandino, Anais Del Curatolo, Ruggero De Maria, Vincenzo Corbo, Michele Simbolo, Teresa De Luca, Matilde Todaro, Andrea Sacconi, Giorgio Stassi, Marina Konopleva, Ludovica Ciuffreda, Ursula Cesta Incani, Aldo Scarpa, Antonina Benfante, Silvia Matteoni, Fabiana Conciatori, Federico Malusa, Adriana Eramo, Chiara Bazzichetto, Francesco Cognetti, Giovanni Sette, James A. McCubrey, Michael Andreeff, Milella, M., Falcone, I., Conciatori, F., Matteoni, S., Sacconi, A., De Luca, T., Bazzichetto, C., Corbo, V., Simbolo, M., Sperduti, I., Benfante, A., Del Curatolo, A., Cesta Incani, U., Malusa, F., Eramo, A., Sette, G., Scarpa, A., Konopleva, M., Andreeff, M., Mccubrey, J., Blandino, G., Todaro, M., Stassi, G., De Maria, R., Cognetti, F., Del Bufalo, D., and Ciuffreda, L.

Subjects
0301 basic medicine, MAPK/ERK pathway, PTEN, RNA interference, protein Kinase inhibitors, RNA, Small Interfering, humans, Phosphoinositide-3 Kinase Inhibitors, Animals, cell line, tumor, drug synergism, everolimus, female, Janus Kinase 1, MAP Kinase Kinase Kinases, mice, neoplastic stem cells, PTEN phosphohydrolase, phosphatidylinositol 3-Kinases, proto-oncogene Proteins c-akt, Pyridones, Pyrimidinones, RNA Interference, STAT3 Transcription Factor, TOR Serine-Threonine Kinases, Multidisciplinary, MAPK/PI3K pathway inhibition, oncology, MAPK/PI3K pathway inhibition, cell line, MAPK/PI3K, inhibition, oncology. inhibition. PTEN, gene, mRNA, cancer cell lines, MEK/mTOR, oncology, mTOR, tumor, Mice, Nude, Biology, Small Interfering, Article, 03 medical and health sciences, Mediator, Settore MED/04 - PATOLOGIA GENERALE, Cell Line, Tumor, medicine, PI3K/AKT/mTOR pathway, Settore MED/06 - ONCOLOGIA MEDICA, RPTOR, Cancer, medicine.disease, Blockade, 030104 developmental biology, Cancer research, biology.protein, RNA
Abstract

Combined MAPK/PI3K pathway inhibition represents an attractive, albeit toxic, therapeutic strategy in oncology. Since PTEN lies at the intersection of these two pathways, we investigated whether PTEN status determines the functional response to combined pathway inhibition. PTEN (gene, mRNA, and protein) status was extensively characterized in a panel of cancer cell lines and combined MEK/mTOR inhibition displayed highly synergistic pharmacologic interactions almost exclusively in PTEN-loss models. Genetic manipulation of PTEN status confirmed a mechanistic role for PTEN in determining the functional outcome of combined pathway blockade. Proteomic analysis showed greater phosphoproteomic profile modification(s) in response to combined MEK/mTOR inhibition in PTEN-loss contexts and identified JAK1/STAT3 activation as a potential mediator of synergistic interactions. Overall, our results show that PTEN-loss is a crucial determinant of synergistic interactions between MAPK and PI3K pathway inhibitors, potentially exploitable for the selection of cancer patients at the highest chance of benefit from combined therapeutic strategies.

Published
2017

16. Liquid Biopsy Testing Can Improve Selection of Advanced Non-Small-Cell Lung Cancer Patients to Rechallenge With Gefitinib

Author

Filippo de Marinis, Alessandra Sacco, Rita Chiari, Giovanna Finocchiaro, Nicola Normanno, Federico Cappuzzo, Laura Giannetta, Ciro Battiloro, Raffaella Pasquale, Alessandro Morabito, Libero Ciuffreda, Marcello Tiseo, Maria Carmela Piccirillo, Roberta Buosi, Paolo Bidoli, Luisa Foltran, Riziero Esposito Abate, Gianpiero Fasola, G. Romano, Antonio Frassoldati, Esposito Abate, R, Pasquale, R, Sacco, A, Piccirillo, M, Morabito, A, Bidoli, P, Finocchiaro, G, Chiari, R, Foltran, L, Buosi, R, Tiseo, M, Giannetta, L, Battiloro, C, Fasola, G, Romano, G, Ciuffreda, L, Frassoldati, A, de Marinis, F, Cappuzzo, F, and Normanno, N

Subjects
0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, medicine.drug_class, rechallenge, Socio-culturale, lcsh:RC254-282, Article, Tyrosine-kinase inhibitor, resistance, 03 medical and health sciences, 0302 clinical medicine, Gefitinib, Liquid biopsy, Non-small-cell lung cancer, P.T790M, Rechallenge, Resistance, Internal medicine, Medicine, Epidermal growth factor receptor, Liquid biopsy, Lung cancer, liquid biopsy, biology, business.industry, p.T790M, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, respiratory tract diseases, 030104 developmental biology, non-small-cell lung cancer, Tolerability, 030220 oncology & carcinogenesis, biology.protein, Biomarker (medicine), EGFR Activating Mutation, business, medicine.drug
Abstract

The ICARUS trial is a phase II, open label, multicenter, single arm study conducted to investigate the efficacy, safety, and tolerability of a rechallenge treatment with the first-generation tyrosine kinase inhibitor (TKI) gefitinib in advanced non-small-cell lung cancer (NSCLC) patients carrying activating mutations of the epidermal growth factor receptor (EGFR). The ICARUS trial enrolled 61 patients who were rechallenged with gefitinib at progression after second-line chemotherapy. Serum-derived circulating cell-free DNA (cfDNA) collected before the rechallenge from a cohort of 29 patients, was retrospectively analyzed for the EGFR exon 19 deletions and for the p.L858R and p.T790M single nucleotide variants (SNV). The analysis of cfDNA detected the same EGFR activating mutation reported in the tumor tissue in 20/29 patients, with a sensitivity of 69%. Moreover, a p.T790M variant was found in 14/29 patients (48.3%). The median progression-free survival (PFS) was 2.7 months for p.T790M positive patients (CI 95% 1.4&ndash, 3.1 months) versus 3.5 months for the p.T790M negative patients (CI 95% 1.6&ndash, 5.3 months), resulting in a statistically significant difference (Long rank test p = 0.0180). These findings confirmed the role of the p.T790M mutation in the resistance to first-generation TKIs. More importantly, our data suggest that TKI rechallenge should be guided by biomarker testing.

Published
2019

17. Observational study on quality of life, safety, and effectiveness of first-line cetuximab plus chemotherapy in KRAS wild-type metastatic colorectal cancer patients: the ObservEr Study

Author

Antonio Frassoldati, Giovanni Rosti, Carlo Signorelli, Patrizia Racca, Elena Benincasa, Giovanna Campanella, Giovanni Pietro Ianniello, Libero Ciuffreda, Maria Elena Stroppolo, Francesco Di Costanzo, Carmine Pinto, Gerardo Rosati, Enzo Maria Ruggeri, Ivan Lolli, Paolo Tralongo, Francesca Di Fabio, Daris Ferrari, Silvana Chiara, Oscar Alabiso, Domenico Bilancia, Raimondo Ferrara, Giovanni Lo Re, Pinto, C., Di Fabio, F., Rosati, G., Lolli, I. R., Ruggeri, E. M., Ciuffreda, L., Ferrari, D., Lo Re, G., Rosti, G., Tralongo, P., Ferrara, R., Alabiso, O., Chiara, S., Ianniello, G. P., Frassoldati, A., Bilancia, D., Campanella, G. A., Signorelli, C., Racca, P., Benincasa, E., Stroppolo, M. E., and Di Costanzo, F.

Subjects
Oncology, Adult, Male, Cancer Research, medicine.medical_specialty, Colorectal cancer, skin reactions, Cetuximab, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, Economica, Quality of life, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, Medicine, Humans, Radiology, Nuclear Medicine and imaging, 030212 general & internal medicine, Neoplasm Metastasis, Original Research, Aged, Neoplasm Staging, Aged, 80 and over, metastatic colorectal cancer, quality of life, business.industry, Dermatology Life Quality Index, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Chemotherapy regimen, Survival Analysis, digestive system diseases, Oxaliplatin, Clinical trial, Treatment Outcome, 030220 oncology & carcinogenesis, ras Proteins, Female, business, Colorectal Neoplasms, Cancer Prevention, medicine.drug
Abstract

Cetuximab improves efficacy when added to chemotherapy for metastatic colorectal cancer (mCRC). Effective management of skin reactions from cetuximab improves quality of life (QoL), and treatment compliance in clinical trials. No data are available from real‐world settings. The ObservEr observational, multicenter, prospective study evaluated QoL, the incidence of skin reactions, and management of chemotherapy plus cetuximab in first‐line for mCRC. The primary endpoint was QoL measured with the Dermatology Life Quality Index (DLQI) and EORTC QLQ‐C30. Secondary endpoints were the incidence of skin and serious adverse events, median overall and progression‐free survival, tumor response, and resection rates. Between May 2011 and November 2012, 228 patients with KRASwt mCRC were enrolled at 28 Italian centers, 225 evaluable, median age 65 years. QoL did not change during treatment and was not affected by the choice of prophylactic or reactive skin management. The incidence of cetuximab‐specific grade ≥3 skin reactions was 14%, with no grade 4/5 events. Skin reactions correlated with survival (P = 0.016), and their incidence was influenced by chemotherapy regimen (oxaliplatin vs. irinotecan—Incidence rate ratio [IRR] 1.72, P

Published
2016

18. Overcoming resistance to molecularly targeted anticancer therapies: Rational drug combinations based on EGFR and MAPK inhibition for solid tumours and haematologic malignancies

Author

Giampaolo Tortora, Francesco Cognetti, Agostino Tafuri, Maria Rosaria Ricciardi, Michele Milella, Fortunato Ciardiello, Gennaro Daniele, James A. McCubrey, Ludovica Ciuffreda, Roberto Bianco, Tortora, Giampaolo, Bianco, Roberto, Daniele, Gennaro, Ciardiello, F, Mccubrey, Ja, Ricciardi, Mr, Ciuffreda, L, Cognetti, F, Tafuri, A, Milella, M., Tortora, G, Bianco, R, Daniele, G, and Ciardiello, Fortunato

Subjects
MAPK/ERK pathway, Cancer Research, medicine.medical_treatment, EGFR, Drug resistance, Article, Targeted therapy, resistance, Drug Delivery Systems, Neoplasms, Signal Transduction Inhibition, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Pharmacology (medical), Epidermal growth factor receptor, EGFR inhibitors, Pharmacology, biology, Cell growth, Drug Synergism, Targeted anticancer agents, MAPK, Cell biology, ErbB Receptors, Infectious Diseases, Oncology, Drug Resistance, Neoplasm, Hematologic Neoplasms, Cancer research, biology.protein, aml, combination therapy, drug resistance, egfr, igfr1, mapk, mek inhibitors, molecular markers, targeted therapy, Mitogen-Activated Protein Kinases, Signal transduction, Signal Transduction
Abstract

Accumulating evidence suggests that cancer can be envisioned as a "signaling disease", in which alterations in the cellular genome affect the expression and/or function of oncogenes and tumour suppressor genes. This ultimately disrupts the physiologic transmission of biochemical signals that normally regulate cell growth, differentiation and programmed cell death (apoptosis). From a clinical standpoint, signal transduction inhibition as a therapeutic strategy for human malignancies has recently achieved remarkable success. However, as additional drugs move forward into the clinical arena, intrinsic and acquired resistance to "targeted" agents becomes an issue for their clinical utility. One way to overcome resistance to targeted agents is to identify genetic and epigenetic aberrations underlying sensitivity/resistance, thus enabling the selection of patients that will most likely benefit from a specific therapy. Since resistance often ensues as a result of the concomitant activation of multiple, often overlapping, signaling pathways, another possibility is to interfere with multiple, cross-talking pathways involved in growth and survival control in a rational, mechanism-based, fashion. These concepts may be usefully applied, among others, to agents that target two major signal transduction pathways: the one initiated by epidermal growth factor receptor (EGFR) signaling and the one converging on mitogen-activated protein kinase (MAPK) activation. Here, we review the molecular mechanisms of sensitivity/resistance to EGFR inhibitors, as well as the rationale for combining them with other targeted agents, in an attempt to overcome resistance. In the second part of the paper, we review MAPK-targeted agents, focusing on their therapeutic potential in haematologic malignancies, and examine the prospects for combinations of MAPK inhibitors with cytotoxic agents or other signal transduction-targeted agents to obtain synergistic anti-tumour effects.

Published
2007

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