Long-term survival and prognostic factors after repeated metastasectomies in metastatic colorectal cancer: A 15-years retrospective study Giovanni Trovato, Francesco Schietroma, Laura Chiofalo, Giulia Caira, Annaluisa Bologna, Davide De Sio, Sergio Alfieri, Filippo Lococo, Dania Nachira, Stefano Margaritora, Fabio Pacelli, Francesco Ardito, Felice Giuliante, Brunella Barbaro, Antonia Strippoli, Maria Alessandra Calegari, Lisa Salvatore, Michele Basso, Giampaolo Tortora, Carmelo Pozzo Oncologist, 2025 Background Metastatic colorectal cancer (mCRC) remains a leading cause of cancer-related mortality. While metastasectomy could improve survival in selected patients, the role of repeated resections in oligorecurrent disease is less defined. Methods We retrospectively analyzed patients with mCRC treated at Fondazione Policlinico Universitario Agostino Gemelli-IRCCS (Rome, Italy) between 2010 and 2024. Eligible patients underwent ≥2 resections of metastatic lesions. Disease-free survival after second metastasectomy (DFS2) and overall survival (OS) were the coprimary end points. Prognostic factors were tested with Cox regression, and a composite risk score (Fondazione Policlinico Gemelli Risk Score [FPGRiskScore]) was developed. Results Among 1586 patients with mCRC, 396 (24.9%) received at least one metastatic surgery and 143 (9%) underwent ≥2 metastasectomies. Median DFS2 was 8.2 months (95% confidence interval [CI]: 7.3-13.1), and 5-years OS rate was 73.1% (95% CI: 64.5-83.0); after a median follow-up from the last metastasectomy of 34.3 months, 49/143 patients (34.2%) were relapse-free and median DFS after the second surgery of the metastases from the last surgery was 13.1 months (95% CI: 9.1-17.5). Patients stratified by FPGRiskScore (disease-free interval [DFI] from the first metastasectomy ≤ vs. >12 months, metastatic burden ≤ vs >5 cm, RAS/BRAF status, and Eastern Cooperative Oncology Group Performance Status [ECOG PS] scale 0 vs. ≥1) showed distinct outcomes: low-risk patients achieved a median DFS2 of 18.4 months and 5-years OS of 87.6%, compared with 7.8 months/72.0% in intermediate-risk and 4.9 months/55.3% in high-risk group. Conclusions Repeated metastasectomy offers substantial survival benefit in selected patients with oligorecurrent mCRC, with long-term disease control achievable in a subset. Prognostic stratification incorporating clinical and molecular features (FPGRiskScore) may refine patient selection and guide multidisciplinary management.
Adjuvant TRastuzumab deruxtecan plus fluoropyrimidine versus standard chemotherapy in HER2-positive gastric or gastroesophageal cancer patients with persistence of minimal residual disease in liquid biopsy after pre-operative chemotherapy and radical surgery: the multicentre, phase II randomized TRINITY trial Vincenzo Nasca, Francesca Bergamo, Luisa Foltran, Lorenzo Antonuzzo, Katia Bencardino, Emanuela Dell’Aquila, Salvatore Corallo, Andrea Spallanzani, Oronzo Brunetti, Daniele Spada, Stefano Tamberi, Chiara Alessandra Cella, Antonio Avallone, Lorenzo Fornaro, Samantha Di Donato, Antonia Strippoli, Alberto Puccini, Emiliano Tamburini, Federica Palermo, Federica Morano, Filippo Pietrantonio, Alessandra Raimondi BMC Cancer, 2025 BACKGROUND: The standard treatment for localized/locally advanced gastroesophageal adenocarcinoma (GEA) is radical surgery and peri-operative FLOT treatment (5-fluorouracil plus leucovorin, oxaliplatin, and docetaxel), but around half patients still experience disease relapse. In gastrointestinal cancers, the presence of circulating tumor DNA (ctDNA) after surgery is associated with a high risk of relapse, and the lack of ctDNA clearance after post-operative treatment is strongly associated with early relapse. Therefore, liquid biopsy may guide the selection of patients with micrometastatic disease after preoperative chemotherapy and surgery for non-cross resistant regimens in the post-operative setting. Trastuzumab deruxtecan (T-DXd) is approved in patients with HER2-positive advanced gastric or gastroesophageal adenocarcinoma after failure of at least one prior trastuzumab-based regimen. The DESTINY-Gastric01 and 02 trials showed remarkable activity and efficacy of T-DXd, thus supporting the investigation of this agent in early-stage disease to increase the chance of achieving disease eradication. Finally, the DESTINY-Gastric03 trial showed the safety profile and feasibility, with preliminary promising activity results of the combination of T-DXd with a fluoropyrimidine. TRIAL DESIGN: TRINITY is an ongoing multicentre, randomized, open-label, interventional phase II study which will enroll approximately 46 patients with HER2-positive GEA, treated with pre-operative FLOT and radical surgery, and with the persistence of minimal residual disease detected by the Signatera™ assay in a liquid biopsy collected between 2 and 6 weeks after surgery. The trial is designed with an observational phase enrolling patients with HER2-positive GEA eligible for standard treatment with peri-operative FLOT and surgery. Eligible patients will be randomized on a 1:1 basis to the experimental treatment arm consisting of adjuvant T-DXd (6.4 mg/kg IV on day 1) plus either capecitabine (1000 mg/sqm BID orally on days 1-14) or 5-fluorouracil (600 mg/sqm continuous IV infusion on days 1-5) Q3 W for 6 cycles, or to the control arm with standard post-operative FLOT (at the same dose used during the last pre-operative cycle) for 4 cycles. Patients non-eligible for the interventional trial will continue the standard therapy and follow-up in the frame of the observational phase with collection of exploratory longitudinal liquid biopsies. The primary objective is ctDNA clearance at 1 year after randomization. Considering alpha- and beta-errors of 0.10 and 0.20 and hypothesizing a ctDNA clearance of 10% and 35% in the control and experimental arm, respectively, 23 patients per arm are required to prove the superiority of the experimental strategy. Secondary endpoints include disease-free survival, overall survival, metastases-free survival, patient-reported outcomes and safety. The trial also represents a translational platform, including extensive analysis of circulating, tissue, and immune biomarkers as exploratory endpoints. Enrollment is active and ongoing. TRIAL REGISTRATION: TRINITY is registered at ClinicalTrials.gov (NCT06253650).
Real-world outcomes of Adjuvant De Gramont versus Xelox chemotherapy in reSected gasTric cancER: a propensity score-matched analysis (ASTER study) Ina Valeria Zurlo, Fausto Rosa, Diana Giannarelli, Giovanni Trovato, Massimiliano Salati, Andrea Spallanzani, Michele Basso, Carmelo Pozzo, Sergio Alfieri, Giampaolo Tortora, Antonia Strippoli Cancer Gene Therapy, 2025 The role of adjuvant chemotherapy (aCT) in gastric and esophago-gastric junction cancer (GC/EGJC) remains controversial. This study (ASTER study) aimed to compare the clinical outcomes of De Gramont (DG) versus XELOX/FOLFOX (OXA) regimens in a European real-world setting. This retrospective, bicentric study included patients treated with aCT between January 2001 and January 2018. A propensity score-matched (PSM) analysis was performed to compare oncological outcomes between DG and OXA regimens. Primary endpoints were disease-free survival (DFS) and overall survival (OS). Statistical analyses included the chi-square test, Kaplan–Meier method, and Cox proportional hazards modeling. Among 255 patients (127 DG, 128 OXA), 160 were matched (80 per arm) by PSM. Median DFS and OS did not differ significantly between groups (mDFS: 102.3 vs. 85.4 months, p = 0.91; mOS: 119.5 vs. 89.8 months, p = 0.69). In PSM-adjusted analysis, DG showed a trend towards longer DFS (p = 0.052) and significantly improved OS (p = 0.016). Multivariate analysis confirmed age, ECOG PS, resection margins, and stage as major prognostic factors. DG and OXA regimens demonstrated similar efficacy in the adjuvant treatment of resected GC/GEJC in a European cohort. Further prospective studies are warranted to optimize regimen selection and refine patient stratification.
Evaluating the Long-Term Impact of Cytoreductive Surgery for Gastric Cancer with Peritoneal Metastasis: Are We on the Right Path? Cecilia Orsini, Matteo Aulicino, Giorgio D’Annibale, Marianna Cantelmo, Sara Totaro Aprile, Paolo Catania, Lorenzo Barberis, Federica Ferracci, Miriam Attalla El Halabieh, Carlo Abatini, Claudio Lodoli, Andrea Di Giorgio, Antonia Strippoli, Fabio Pacelli, Francesco Santullo Journal of Personalized Medicine, 2025 Background: Peritoneal metastases from gastric cancer (GCPM) represent a significant clinical challenge in terms of therapeutic options and prognosis. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has demonstrated promising survival benefits within a multimodal approach, particularly in carefully selected patients. Methods: This retrospective single-center study evaluated outcomes in patients with synchronous GCPM treated with CRS + HIPEC following neoadjuvant chemotherapy. The primary endpoints included overall survival (OS), disease-free survival (DFS), and identification of prognostic factors associated with poor outcomes. Additionally, we sought to characterize patients achieving long-term survival (OS ≥ 24 months). Results: The median OS and DFS were 18 and 13 months, respectively. A peritoneal cancer index (PCI) ≥ 7 and major postoperative complications were independently associated with reduced survival. Recurrence was significantly linked to PCI ≥ 7 and signet ring cell histology. Stratification by survival outcome identified PCI ≥ 7 as the only statistically significant variable differentiating average- and long-survival groups. Moreover, elevated PCI was independently associated with a higher incidence of major postoperative complications. Conclusions: CRS + HIPEC may offer a survival advantage over the use of systemic therapy exclusively in appropriately selected patients, particularly those with limited peritoneal disease burden. These results underscore the importance of accurate patient selection to balance surgical risks and maximize oncological benefits in the treatment of GCPM.
Impact of age and sex on the efficacy and safety of ramucirumab plus paclitaxel as switch maintenance versus continuation of first-line oxaliplatin-based chemotherapy: a subgroup analysis of the ARMANI phase III trial R. Fazio, G. Randon, F. Bergamo, F. Palermo, S. Tamberi, E. Giommoni, S. Di Donato, L. Fornaro, O. Brunetti, F. De Vita, M. Valgiusti, S.M. Gobba, A. Spallanzani, S. Murgioni, V. Bethaz, A. Strippoli, T.P. Latiano, G.G. Cardellino, C. Ceccon, A. Raimondi, M. Prisciandaro, C.C. Pircher, M. Ambrosini, P. Manca, M. Fassan, M. Di Bartolomeo, M. Di Maio, F. Pietrantonio ESMO Open, 2025 BACKGROUND: There is a growing interest in optimizing the therapeutic management of older cancer patients as well as understanding the sex-specific differences in terms of efficacy and safety of cancer treatments. However, limited data are available on the initial therapy of patients with advanced gastro-oesophageal cancer. MATERIALS AND METHODS: The ARMANI phase III trial showed progression-free survival (PFS) and overall survival (OS) benefit with paclitaxel plus ramucirumab switch maintenance (arm A) versus the continuation of first-line oxaliplatin and fluoropyrimidine (arm B) in patients with advanced human epidermal growth factor receptor 2-negative gastric or gastro-oesophageal junction cancer. We conducted a subgroup analysis aimed at assessing the differences in efficacy, safety and quality of life (QoL) according to age (<70 versus ≥70 years) and sex. RESULTS: No significant differences in terms of PFS (P = 0.757), OS (P = 0.588) and overall response rates (ORRs) (P = 0.238) were observed between older and younger patients. No significant differences in PFS (P = 0.646), OS (P = 0.858) and ORRs (P = 0.649) were observed between females and males. The effect of treatment arm on survival outcomes was similar across age (P = 0.094) and sex groups (P = 0.469). Looking at specific adverse events, peripheral neuropathy occurred more frequently in younger patients (P = 0.020), anaemia in older patients (P = 0.044) and hand-foot syndrome in women (P = 0.021). Older patients were less likely to receive a post-discontinuation treatment (P = 0.010), especially in arm B (P = 0.026). The impact on QoL was better in arm A, irrespective of age and sex. CONCLUSION: The ARMANI trial supported the benefit of the investigated switch maintenance strategy irrespective of age and sex.
Tremelimumab and durvalumab as neoadjuvant or non-operative management strategy of patients with microsatellite instability-high resectable gastric or gastroesophageal junction adenocarcinoma: the INFINITY study by GONO A. Raimondi, S. Lonardi, S. Murgioni, G.G. Cardellino, S. Tamberi, A. Strippoli, F. Palermo, G. De Manzoni, M. Bencivenga, A. Bittoni, C. Chiodoni, D. Lorenzini, K. Todoerti, P. Manca, S. Sangaletti, M. Prisciandaro, G. Randon, F. Nichetti, F. Bergamo, S. Brich, A. Belfiore, A. Bertolotti, D. Stetco, A. Guidi, T. Torelli, A. Vingiani, R.P. Joshi, M. Khoshdeli, N. Beaubier, M.C. Stumpe, F. Nappo, A.G. Leone, C.C. Pircher, G. Leoncini, G. Sabella, L. Airo’ Farulla, A. Alessi, F. Morano, A. Martinetti, M. Niger, M. Fassan, M. Di Maio, K. Kaneva, M. Milione, H. Nimeiri, C. Sposito, L. Agnelli, V. Mazzaferro, M. Di Bartolomeo, F. Pietrantonio Annals of Oncology, 2025
Symptoms, nutritional outcomes and quality of life after total gastrectomy with Roux-en-Y reconstruction: results of a cross-sectional study conducted on 80 long-term survivors Annamaria Agnes, Alberto Biondi, Marina Carannante, Antonia Strippoli, Francesco Belia, Laura Lorenzon, Roberto Pezzuto, Flavio Tirelli, Lorenzo Ferri, Ilaria Neri, Domenico D’Ugo, Roberto Persiani Updates in Surgery, 2025 Impaired functional outcomes are common issues after total gastrectomy, although seldom explored at a long distance from surgery. The primary aim of this study was to investigate the long-term postoperative functional and nutritional results after Roux-en-Y total gastrectomy (RYTG). Patients with gastric neoplasms or CDH1 mutation undergoing RYTG between 2000 and 2021, with a minimum follow-up of 12 months, were interviewed to assess their functional and nutritional status and to measure their quality of life (QoL) with the GIQLI, EORTC-QLQ20 and EORTC-STO22 questionnaires. Statistical analysis was used to present these results and assess variables associated with body weight variation (BWV), dumping syndrome and QoL. Eighty patients were selected out of 265 RYTGs performed. The mean BWV was − 19.4% ± 9.4. The prevalence of dumping syndrome was 27.5%, the prevalence of food intake disturbances and reflux were 33.8% and 46.2%, respectively. The prevalence of anemia was 27.5%. A higher preoperative BMI and a longer follow-up time were associated with BWV. The only predictor of dumping syndrome was a lower age at surgery. Patients with dumping reported significantly lower GIQLI score [median 132 (IQR 123–138) vs 111 (82–123), p < 0.001], and a lower GIQLI score was associated with higher preoperative BMI, with the interaction between dumping syndrome and BWV, and with food intake disturbances. RYTG is associated with a long-term decrease in body weight and a high rate of compromised functional outcomes, with a possible significant effect on QoL. To prevent these occurrences, alternative reconstruction methods to RYTG could be considered.
Combined Nabpaclitaxel pressurized intraPeritoneal aerosol chemotherapy with systemic Nabpaclitaxel-Gemcitabine chemotherapy for pancreatic cancer peritoneal metastases: protocol of single-arm, open-label, phase II trial (Nab-PIPAC trial) Andrea Di Giorgio, Federica Ferracci, Cinzia Bagalà, Carmine Carbone, Lisa Salvatore, Antonia Strippoli, Miriam Attalla El Halabieh, Carlo Abatini, Sergio Alfieri, Fabio Pacelli, Giampaolo Tortora Pleura and Peritoneum, 2024 Objectives Current therapies show limited efficacy against peritoneal metastases (PM) from pancreatic cancer. Pressurized intra-peritoneal aerosol chemotherapy (PIPAC) has emerged as a novel intraperitoneal drug delivery method. Recently, a dose-escalation study identified the safe dose of Nabpaclitaxel for PIPAC administration, an ideal intraperitoneal chemotherapy agent against pancreatic cancer. Combining systemic NabPaclitaxel-Gemcitabine with NabPaclitaxel-PIPAC may enhance disease control in pancreatic cancer patients with PM. Methods The Nab-PIPAC trial is a single-center, prospective, open-label, phase II study (ClinicalTrials.gov identifier: NCT05371223). Its primary goal is to evaluate the antitumor activity of the combined treatment based on Disease Control Rate (DCR) using RECISTv.1.1 criteria. Secondary objectives include feasibility, safety, pathological response, progression-free and overall survival, nutritional status, quality of life, pharmacokinetics of NabPaclitaxel-PIPAC, and PM molecular evolution via translational research. The treatment protocol consists of three courses, each with two cycles of intravenous NabPaclitaxel-Gemcitabine and one cycle of NabPaclitaxel-PIPAC, with standard metastatic pancreatic cancer doses for the former and 112.5 mg/m2 for the latter. Sample size follows Simon’s two-stage design: 12 patients in stage one and 26 in stage two (80 % power, 0.1 alpha). Results Partial results will be available after first stage enrollment. Conclusions This trial aims to determine the antitumor efficacy and safety of combining NabPaclitaxel-PIPAC with systemic NabPaclitaxel-Gemcitabine in pancreatic cancer patients with PM.
The Impact of NUTRItional Status at First Medical Oncology Visit on Clinical Outcomes: The NUTRIONCO Study Maurizio Muscaritoli, Alessandra Modena, Matteo Valerio, Paolo Marchetti, Roberto Magarotto, Silvia Quadrini, Filomena Narducci, Giuseppe Tonini, Teresa Grassani, Luigi Cavanna, Camilla Di Nunzio, Chiara Citterio, Marcella Occelli, Antonia Strippoli, Bruno Chiurazzi, Antonio Frassoldati, Giuseppe Altavilla, Antonio Lucenti, Fabrizio Nicolis, Stefania Gori Cancers, 2023
Results of the observational prospective RealFLOT study Elisa Giommoni, Daniele Lavacchi, Giuseppe Tirino, Lorenzo Fornaro, Francesco Iachetta, Carmelo Pozzo, Maria Antonietta Satolli, Andrea Spallanzani, Marco Puzzoni, Silvia Stragliotto, Michele Sisani, Vincenzo Formica, Filippo Giovanardi, Antonia Strippoli, Michele Prisciandaro, Samantha Di Donato, Luca Pompella, Irene Pecora, Alessandra Romagnani, Sara Fancelli, Marco Brugia, Serena Pillozzi, Ferdinando De Vita, Lorenzo Antonuzzo BMC Cancer, 2021
The impact of multidisciplinary team management on outcome of hepatic resection in liver-limited colorectal metastases Michele Basso, Salvatore Corallo, Maria Alessandra Calegari, Ina Valeria Zurlo, Francesco Ardito, Maria Vellone, Silvio Marchesani, Armando Orlandi, Vincenzo Dadduzio, Giovanni Fucà, Carmela Di Dio, Caterina Mele, Brunella Barbaro, Antonia Strippoli, Alessandro Coppola, Alessandra Cassano, Emilio Bria, Carlo Antonio Barone, Felice Giuliante Scientific Reports, 2020
