المؤلفون: Pinto, Carmine, Orlandi, Armando, Normanno, Nicola, Maiello, Evaristo, Calegari, Maria A., Antonuzzo, Lorenzo, Bordonaro, Roberto, Zampino, Maria G., Pini, Sara, Bergamo, Francesca, Tonini, Giuseppe, Avallone, Antonio, Latiano, Tiziana P., Rosati, Gerardo, Cogoni, Alessio Aligi, Ballestrero, Alberto, Zaniboni, Alberto, Roselli, Mario, Tamberi, Stefano, Barone, Carlo

المساهمون: Pinto, C, Orlandi, A, Normanno, N, Maiello, E, Calegari, Ma, Antonuzzo, L, Bordonaro, R, Zampino, Mg, Pini, S, Bergamo, F, Tonini, G, Avallone, A, Latiano, Tp, Rosati, G, Cogoni, Aa, Ballestrero, A, Zaniboni, A, Roselli, M, Tamberi, S, Barone, C

مصطلحات موضوعية: Settore MED/06

الوصف: purpose: the intensity of anti-EGFR-based first-line therapy for RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC), once disease control is achieved, is controversial. a de-escalation strategy with anti-EGFR monotherapy represents a potential option to maintain efficacy while reducing cytotoxicity. methods: In this multicenter, open-label, phase III trial, patients with untreated RAS/BRAF wt mCRC were randomly assigned to receive either fluorouracil, leucovorin, and irinotecan/cetuximab (FOLFIRI/Cet) until disease progression (arm A) or FOLFIRI/Cet for eight cycles followed by cet alone (arm B). the coprimary end points were a noninferior progression-free survival (PFS) in the modified per-protocol (mPP) population (>eight cycles) and a lower incidence of grade (G) 3-4 adverse events (AEs) for arm B compared with arm a. results: overall, 606 patients were randomly assigned, with 300 assigned to arm A and 306 to arm B. The median follow-up was 22.3 months. In the mPP population, 291 events occurred with a PFS of 10 versus 12.2 months for arms B and A, respectively (P of noninferiority = .43). In the intention-to-treatment (ITT, ≥one cycle) population, 503 events occurred with a PFS of 9 versus 10.7 months (P = .39). the overall survival was 35.7 versus 30.7 months (P = .119) and 31.0 versus 25.2 months (P = .32) in the mPP and ITT population, respectively. arm B had lower G3-4 AEs during the maintenance period than arm A (20.2% v 35.1%). conclusion: The ERMES study did not demonstrate noninferiority of maintenance with cet alone. despite a more favorable safety profile, maintenance with single-agent cet after induction with FOLFIRI/Cet cannot be recommended for all patients but could represent an option in selected cases.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/38181312; volume:42; issue:11; firstpage:1278; lastpage:1287; numberofpages:10; journal:JOURNAL OF CLINICAL ONCOLOGY; https://hdl.handle.net/2108/359645Test

الإتاحة: https://doi.org/10.1200/jco.23.01021Test
https://hdl.handle.net/2108/359645Test

المؤلفون: Ottaiano, Alessandro, Santorsola, Mariachiara, Diana, Anna, Belli, Andrea, Lentini Graziano, Maria Luisa, Orefice, Jessica, Patrone, Renato, Di Mauro, Annabella, Scognamiglio, Giosuè, Tatangelo, Fabiana, De Bellis, Mario, Piccirillo, Mauro, Fiore, Francesco, Stilo, Salvatore, Tarotto, Luca, Correra, Marco, Di Lorenzo, Sara, Capuozzo, Maurizio, Avallone, Antonio, Silvestro, Lucrezia, Bianco, Antonella, Granata, Vincenza, Federico, Piera, Montesarchio, Vincenzo, Daniele, Bruno, Izzo, Francesco, Nasti, Guglielmo

المساهمون: Ministero della Salute

المصدر: Cancer Medicine ; volume 13, issue 4 ; ISSN 2045-7634 2045-7634

الوصف: Background and Aims Cholangiocarcinoma (CCA), a rare and aggressive hepatobiliary malignancy, presents significant clinical management challenges. Despite rising incidence and evolving treatment options, prognosis remains poor, motivating the exploration of real‐world data for enhanced understanding and patient care. Methods This multicenter study analyzed data from 120 metastatic CCA patients at three institutions from 2016 to 2023. Kaplan–Meier curves assessed overall survival (OS), while univariate and multivariate analyses evaluated links between clinical variables (age, gender, tumor site, metastatic burden, ECOG performance status, response to first‐line chemotherapy) and OS. Genetic profiling was conducted selectively. Results Enrolled patients had a median age of 68.5 years, with intrahepatic tumors predominant in 79 cases (65.8%). Among 85 patients treated with first‐line chemotherapy, cisplatin and gemcitabine (41.1%) was the most common regimen. Notably, one‐third received no systemic treatment. After a median 14‐month follow‐up, 81 CCA‐related deaths occurred, with a median survival of 13.1 months. Two clinical variables independently predicted survival: response to first‐line chemotherapy (disease control vs. no disease control; HR: 0.27; 95% CI: 0.14–0.50; p < 0.0001) and metastatic involvement (>1 site vs. 1 site; HR: 1.99; 95% CI: 1.04–3.80; p = 0.0366). The three most common genetic alterations involved the ARID1A , tp53 , and CDKN2A genes. Conclusions Advanced CCA displays aggressive clinical behavior, emphasizing the need for treatments beyond chemotherapy. Genetic diversity supports potential personalized therapies. Collaborative research and deeper CCA biology understanding are crucial to enhance patient outcomes in this challenging malignancy.

الإتاحة: https://doi.org/10.1002/cam4.6892Test

المؤلفون: Ciardiello, Davide, Napolitano, Stefania, Famiglietti, Vincenzo, Esposito, Lucia, De Falco, Vincenzo, Di Liello, Alessandra, Avallone, Antonio, Maiello, Evaristo, Pietrantonio, Filippo, Cremolini, Chiara, Zampino, Maria Giulia, Fazio, Nicola, Troiani, Teresa, Martinelli, Erika, Ciardiello, Fortunato, Martini, Giulia

المساهمون: Ciardiello, Davide, Napolitano, Stefania, Famiglietti, Vincenzo, Esposito, Lucia, De Falco, Vincenzo, Di Liello, Alessandra, Avallone, Antonio, Maiello, Evaristo, Pietrantonio, Filippo, Cremolini, Chiara, Zampino, Maria Giulia, Fazio, Nicola, Troiani, Teresa, Martinelli, Erika, Ciardiello, Fortunato, Martini, Giulia

مصطلحات موضوعية: anti-EGFR drug, liquid biopsy, metastatic colorectal cancer, rechallenge therapy

الوصف: Rechallenge with epidermal growth factor (EGFR) inhibitors represents a promising therapeutic strategy in patients with refractory RAS/BRAF wild-type metastatic colorectal cancer (mCRC). The maximal benefit is observed in patients without resistance mutation at the baseline plasma circulating tumor DNA (ctDNA) evaluation. In the CAVE and VELO clinical trials, 1 out of 4 patients had ctDNA RAS/BRAF mutant disease at pretreatment liquid biopsy assessment. There was no direct association between the length of anti-EGFR drug-free interval and the presence of plasma ctDNA RAS/BRAF mutations at pretreatment liquid biopsy analysis. Interestingly, even the disappearance of mutant clones was time-dependent, and resistance mutations were found at liquid biopsy analysis in approximately 15% of patients after 18 or more months of anti-EGFR drug-free window. These results support the use of liquid biopsy to appropriately select amenable patients to EGFR inhibitor rechallenge. Rechallenge with anti-EGFR drugs represents a promising strategy in refractory RAS/BRAF wild-type (WT) metastatic colorectal cancer (mCRC). We performed the pooled analysis of the CAVE and VELO studies to evaluate the percentage of patients with WT circulating tumor DNA (ctDNA) tumors and the association of mutational status with time from the last anti-EGFR drug administration. At baseline, 97/129 patients had RAS/BRAF WT plasma ctDNA, while 32/129 had RAS/BRAF mutated plasma ctDNA. Median anti-EGFR drug-free interval was 10.6 (CI 95%, 8.9-13.4) months in the plasma RAS/BRAF mutant group as compared to 13.0 (CI 95%, 11.1-16.6) months in RAS/BRAF WT group (p = 0.169). To investigate the time window of the RAS/BRAF mutant cancer cell clone disappearance, descriptive analysis using different time points was performed. No difference in the proportion of patients whose baseline plasma ctDNA was RAS/BRAF WT or mutated was found between 4 and 18 months since the last administration of anti-EGFR drugs. In contrast, 38/44 of patients with anti-EGFR drug-free ...

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/37046778; info:eu-repo/semantics/altIdentifier/wos/WOS:000969447400001; volume:15; issue:7; numberofpages:11; journal:CANCERS; https://hdl.handle.net/11568/1193427Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85152418538

الإتاحة: https://doi.org/10.3390/cancers15072117Test
https://hdl.handle.net/11568/1193427Test

المؤلفون: Napolitano, Stefania, De Falco, Vincenzo, Martini, Giulia, Ciardiello, Davide, Martinelli, Erika, Della Corte, Carminia Maria, Esposito, Lucia, Famiglietti, Vincenzo, Di Liello, Alessandra, Avallone, Antonio, Cardone, Claudia, De Stefano, Alfonso, Montesarchio, Vincenzo, Zampino, Maria Giulia, Bordonaro, Roberto, Scartozzi, Mario, Santini, Daniele, Di Maio, Massimo, De Vita, Ferdinando, Altucci, Lucia, Marrone, Francesca, Ciardiello, Fortunato, Troiani, Teresa

المساهمون: Napolitano, Stefania, De Falco, Vincenzo, Martini, Giulia, Ciardiello, Davide, Martinelli, Erika, Della Corte, Carminia Maria, Esposito, Lucia, Famiglietti, Vincenzo, Di Liello, Alessandra, Avallone, Antonio, Cardone, Claudia, De Stefano, Alfonso, Montesarchio, Vincenzo, Zampino, Maria Giulia, Bordonaro, Roberto, Scartozzi, Mario, Santini, Daniele, Di Maio, Massimo, De Vita, Ferdinando, Altucci, Lucia, Marrone, Francesca, Ciardiello, Fortunato, Troiani, Teresa

مصطلحات موضوعية: Aged, Antibodies, Monoclonal, Antineoplastic Agent, Antineoplastic Combined Chemotherapy Protocol, Colonic Neoplasm, Colorectal Neoplasm, Female, Human, Male, Panitumumab, Proto-Oncogene Proteins B-raf, Rectal Neoplasm, Trifluridine

الوصف: Importance: Current third-line therapies for patients with metastatic colorectal cancer (MCRC) have limited efficacy. Rechallenge with epidermal growth factor receptor (EGFR) inhibitors for RAS wild-type (WT) MCRC may be valuable for these patients. Objective: To compare the anti-EGFR monoclonal antibody panitumumab plus standard-of-care trifluridine-tipiracil with trifluridine-tipiracil alone as third-line therapy for RAS WT MCRC. Design, setting, and participants: This phase 2 randomized clinical trial (RCT) was conducted in 7 Italian centers from June 2019 to April 2022. Patients with refractory RAS WT MCRC who had a partial or complete response to first-line chemotherapy plus an anti-EGFR monoclonal antibody and an anti-EGFR drug-free interval of 4 or more months during second-line therapy were included. Interventions: Patients were randomized 1:1 to receive panitumumab plus trifluridine-tipiracil or trifluridine-tipiracil alone. Main outcomes and measures: The primary end point was progression-free survival (PFS). Circulating tumor DNA (ctDNA) extended sequence variation analysis was performed in a subgroup of patients. Results: Of 62 included patients, 31 received panitumumab plus trifluridine-tipiracil (19 [61.3%] male; median age, 65 years [range, 39-81 years]) and 31 received trifluridine-tipiracil alone (17 [54.8%] male; median age, 66 years [range, 32-82 years]). The primary end point was met. Median PFS was 4.0 months (95% CI, 2.8-5.3 months) in the panitumumab plus trifluridine-tipiracil arm vs 2.5 months (95% CI, 1.4-3.6 months) in the trifluridine-tipiracil only (hazard ratio [HR], 0.48; 95% CI, 0.28-0.82; P = .007). Pretreatment plasma RAS/BRAF WT ctDNA identified patients obtaining prolonged clinical benefit with panitumumab plus trifluridine-tipiracil compared with trifluridine-tipiracil, with PFS rates at 6 months of 38.5% vs 13.0% and at 12 months of 15.4% vs 0%. A ctDNA liquid-biopsy extended mutation analysis by FoundationOne Liquid CDx (profiling 324 genes) was performed in a subgroup of ...

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/37200022; info:eu-repo/semantics/altIdentifier/wos/WOS:000992548600002; volume:9; issue:7; firstpage:966; lastpage:970; numberofpages:5; journal:JAMA ONCOLOGY; https://hdl.handle.net/11584/360998Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85164196905

الإتاحة: https://doi.org/10.1001/jamaoncol.2023.0655Test
https://hdl.handle.net/11584/360998Test

المؤلفون: André, Thierry, Pietrantonio, Filippo, Avallone, Antonio, Gumus, Mahmut, Wyrwicz, Lucjan, Kim, Jong Gwang, Yalcin, Suayib, Kwiatkowski, Mariusz, Lonardi, Sara, Zolnierek, Jakub, Odeleye-Ajakaye, Amos, Leconte, Pierre, Fogelman, David, Kim, Tae Won

المساهمون: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA

المصدر: Future Oncology ; volume 19, issue 37, page 2445-2452 ; ISSN 1479-6694 1744-8301

الإتاحة: https://doi.org/10.2217/fon-2022-1105Test

المؤلفون: Napolitano, Stefania, Ciardiello, Davide, De Falco, Vincenzo, Martini, Giulia, Martinelli, Erika, Della Corte, Carminia Maria, Esposito, Lucia, Famiglietti, Vincenzo, Di Liello, Alessandra, Avallone, Antonio, Cardone, Claudia, De Stefano, Alfonso, Montesarchio, Vincenzo, Zampino, Maria Giulia, Fazio, Nicola, Di Maio, Massimo, Del Tufo, Sara, De Vita, Ferdinando, Altucci, Lucia, Marrone, Francesca, Ciardiello, Fortunato, Troiani, Teresa

المساهمون: Regione Campania

المصدر: International Journal of Cancer ; volume 153, issue 8, page 1520-1528 ; ISSN 0020-7136 1097-0215

الوصف: The randomized phase II VELO trial showed that the addition of panitumumab to trifluridine/tipiracil significantly improves progression‐free survival (PFS) as compared to trifluridine/tipiracil in third‐line therapy in patients with refractory RAS wild‐type (WT) metastatic colorectal cancer (mCRC). With longer follow‐up, final overall survival results and posttreatment subgroup analysis are presented. Sixty‐two patients with refractory RAS WT mCRC were randomly assigned to receive, as third‐line therapy, trifluridine/tipiracil alone (arm A) or in combination with panitumumab (arm B). Primary endpoint was PFS; secondary endpoints included overall survival (OS) and overall response rate (ORR). Median OS was 13.1 months (95% CI 9.5‐16.7) in arm A compared to 11.6 months (95% CI 6.3‐17.0) in arm B (HR: 0.96, 95% CI 0.54‐1.71, P = .9). To evaluate the impact of subsequent lines of treatment, subgroup analysis was performed for the 24/30 patients in arm A, that received fourth‐line therapy after disease progression. Median PFS was 4.1 months (95% CI 1.44‐6.83) for 17 patients treated with anti‐EGFR rechallenge as compared to 3.0 months (95% CI 1.61‐4.31) for seven patients that received other therapies (HR: 0.29, 95% CI 0.10‐0.85, P = .024). Median OS from the start of fourth‐line treatment was 13.6 months (95% CI 7.2‐20), and 5.1 months (95% CI 1.8‐8.3) for patients treated with anti‐EGFR rechallenge vs other therapies, respectively (HR: 0.30, 95% CI 0.11‐0.81, P = .019). Final results of the VELO trial support the role of anti‐EGFR rechallenge in the continuum of care of patients with RAS/BRAF WT mCRC.

الإتاحة: https://doi.org/10.1002/ijc.34632Test

المؤلفون: Oh, Do-Youn, He, Aiwu Ruth, Qin, Shukui, Chen, Li-Tzong, Okusaka, Takuji, Vogel, Arndt, Kim, Jin Won, Suksombooncharoen, Thatthan, Lee, Myung Ah, Kitano, Masayuki, Burris, Howard, Bouattour, Mohamed, Tanasanvimon, Suebpong, McNamara, Mairead G., Zaucha, Renata, Avallone, Antonio, Tan, Benjamin, Cundom, Juan, Lee, Choong-kun, Takahashi, Hidenori, Ikeda, Masafumi, Chen, Jen-Shi, Wang, Julie, Makowsky, Mallory, Rokutanda, Nana, Żotkiewicz, Magdalena, Kurland, John F., Cohen, Gordon, Valle, Juan W.

المصدر: Future Oncology ; volume 19, issue 34, page 2277-2289 ; ISSN 1479-6694 1744-8301

الإتاحة: https://doi.org/10.2217/fon-2023-0468Test

المؤلفون: Ascierto, Paolo A., Avallone, Antonio, Bifulco, Carlo, Bracarda, Sergio, Brody, Joshua D., Emens, Leisha A., Ferris, Robert L., Formenti, Silvia C., Hamid, Omid, Johnson, Douglas B., Kirchhoff, Tomas, Klebanoff, Christopher A., Lesinski, Gregory B., Monette, Anne, Neyns, Bart, Odunsi, Kunle, Paulos, Chrystal M., Powell, Daniel J., Rezvani, Katayoun, Segal, Brahm H., Singh, Nathan, Sullivan, Ryan J., Fox, Bernard A., Puzanov, Igor

المصدر: Journal of Translational Medicine ; volume 21, issue 1 ; ISSN 1479-5876

مصطلحات موضوعية: General Biochemistry, Genetics and Molecular Biology, General Medicine

الوصف: The discovery and development of novel treatments that harness the patient’s immune system and prevent immune escape has dramatically improved outcomes for patients across cancer types. However, not all patients respond to immunotherapy, acquired resistance remains a challenge, and responses are poor in certain tumors which are considered to be immunologically cold. This has led to the need for new immunotherapy-based approaches, including adoptive cell transfer (ACT), therapeutic vaccines, and novel immune checkpoint inhibitors. These new approaches are focused on patients with an inadequate response to current treatments, with emerging evidence of improved responses in various cancers with new immunotherapy agents, often in combinations with existing agents. The use of cell therapies, drivers of immune response, and trends in immunotherapy were the focus of the Immunotherapy Bridge (November 30th–December 1st, 2022), organized by the Fondazione Melanoma Onlus, Naples, Italy, in collaboration with the Society for Immunotherapy of Cancer.

الإتاحة: https://doi.org/10.1186/s12967-023-04329-7Test

المؤلفون: Granata, Vincenza, Fusco, Roberta, Setola, Sergio Venanzio, Galdiero, Roberta, Maggialetti, Nicola, Patrone, Renato, Ottaiano, Alessandro, Nasti, Guglielmo, Silvestro, Lucrezia, Cassata, Antonio, Grassi, Francesca, Avallone, Antonio, Izzo, Francesco, Petrillo, Antonella

المصدر: Infectious Agents and Cancer ; volume 18, issue 1 ; ISSN 1750-9378

مصطلحات موضوعية: Cancer Research, Infectious Diseases, Oncology, Epidemiology

الإتاحة: https://doi.org/10.1186/s13027-023-00508-9Test

المؤلفون: Granata, Vincenza, Fusco, Roberta, Setola, Sergio Venanzio, Galdiero, Roberta, Maggialetti, Nicola, Patrone, Renato, Ottaiano, Alessandro, Nasti, Guglielmo, Silvestro, Lucrezia, Cassata, Antonio, Grassi, Francesca, Avallone, Antonio, Izzo, Francesco, Petrillo, Antonella

المصدر: Infectious Agents and Cancer ; volume 18, issue 1 ; ISSN 1750-9378

مصطلحات موضوعية: Cancer Research, Infectious Diseases, Oncology, Epidemiology

الوصف: In this narrative review, we reported un up-to-date on the role of radiomics to assess prognostic features, which can impact on the liver metastases patient treatment choice. In the liver metastases patients, the possibility to assess mutational status (RAS or MSI), the tumor growth pattern and the histological subtype (NOS or mucinous) allows a better treatment selection to avoid unnecessary therapies. However, today, the detection of these features require an invasive approach. Recently, radiomics analysis application has improved rapidly, with a consequent growing interest in the oncological field. Radiomics analysis allows the textural characteristics assessment, which are correlated to biological data. This approach is captivating since it should allow to extract biological data from the radiological images, without invasive approach, so that to reduce costs and time, avoiding any risk for the patients. Several studies showed the ability of Radiomics to identify mutational status, tumor growth pattern and histological type in colorectal liver metastases. Although, radiomics analysis in a non-invasive and repeatable way, however features as the poor standardization and generalization of clinical studies results limit the translation of this analysis into clinical practice. Clear limits are data-quality control, reproducibility, repeatability, generalizability of results, and issues related to model overfitting.

الإتاحة: https://doi.org/10.1186/s13027-023-00495-xTest