Browsing by Author "Siena, Salvatore"

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    Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines
    (Elsevier, 2023) Cavestro, Giulia Martina; Mannucci, Alessandro; Balaguer, Francesc; Hampel, Heather; Kupfer, Sonia S.; Repici, Alessandro; Sartore-Bianchi, Andrea; Seppälä, Toni T.; Valentini, Vincenzo; Boland, Clement Richard; Brand, Randall E.; Buffart, Tineke E.; Burke, Carol A.; Caccialanza, Riccardo; Cannizzaro, Renato; Cascinu, Stefano; Cercek, Andrea; Crosbie, Emma J.; Danese, Silvio; Dekker, Evelien; Daca-Alvarez, Maria; Deni, Francesco; Dominguez-Valentin, Mev; Eng, Cathy; Goel, Ajay; Guillem, Josè G.; Houwen, Britt B. S. L.; Kahi, Charles; Kalady, Matthew F.; Kastrinos, Fay; Kühn, Florian; Laghi, Luigi; Latchford, Andrew; Liska, David; Lynch, Patrick; Malesci, Alberto; Mauri, Gianluca; Meldolesi, Elisa; Møller, Pål; Monahan, Kevin J.; Möslein, Gabriela; Murphy, Caitlin C.; Nass, Karlijn; Ng, Kimmie; Oliani, Cristina; Papaleo, Enrico; Patel, Swati G.; Puzzono, Marta; Remo, Andrea; Ricciardiello, Luigi; Ripamonti, Carla Ida; Siena, Salvatore; Singh, Satish K.; Stadler, Zsofia K.; Stanich, Peter P.; Syngal, Sapna; Turi, Stefano; Urso, Emanuele Damiano; Valle, Laura; Vanni, Valeria Stella; Vilar, Eduardo; Vitellaro, Marco; You, Yi-Qian Nancy; Yurgelun, Matthew B.; Zuppardo, Raffaella Alessia; Stoffel, Elena M.; Associazione Italiana Familiarità Ereditarietà Tumori; Collaborative Group of the Americas on Inherited Gastrointestinal Cancer; European Hereditary Tumour Group; International Society for Gastrointestinal Hereditary Tumours; Medicine, School of Medicine
    Background & aims: Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), composed of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC. Methods: After reviewing the published literature, a Delphi methodology was used to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of ≥80%. Results: The DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery. On the basis of current evidence, endoscopic, surgical, and oncologic treatment of eoCRC should not differ from later-onset CRC, except for individuals with pathogenic or likely pathogenic germline variants. The evidence on chemotherapy is not sufficient to recommend changes to established therapeutic protocols. Fertility preservation and sexual health are important to address in eoCRC survivors. The DIRECt group highlighted areas with knowledge gaps that should be prioritized in future research efforts, including age at first screening for the general population, use of fecal immunochemical tests, chemotherapy, endoscopic therapy, and post-treatment surveillance for eoCRC patients. Conclusions: The DIRECt group produced the first consensus recommendations on eoCRC. All statements should be considered together with the accompanying comments and literature reviews. We highlighted areas where research should be prioritized. These guidelines represent a useful tool for clinicians caring for patients with eoCRC.
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    The subgroups of the phase III RECOURSE trial of trifluridine/tipiracil (TAS-102) versus placebo with best supportive care in patients with metastatic colorectal cancer
    (Elsevier, 2017-12-01) Cutsem, Eric Van; Mayer, Robert J.; Laurent, Stéphanie; Winkler, Robert; Grávalos, Cristina; Benavides, Manuel; Longo-Munoz, Federico; Portales, Fabienne; Ciardiello, Fortunato; Siena, Salvatore; Yamaguchi, Kensei; Muro, Kei; Denda, Tadamichi; Tsuji, Yasushi; Makris, Lukas; Loehrer, Patrick; Lenz, Heinz-Josef; Ohtsu, Atsushi; Medicine, School of Medicine
    Background: In the phase III RECOURSE trial, trifluridine/tipiracil (TAS-102) extended overall survival (OS) and progression-free survival (PFS) with an acceptable toxicity profile in patients with metastatic colorectal cancer refractory or intolerant to standard therapies. The present analysis investigated the efficacy and safety of trifluridine/tipiracil in RECOURSE subgroups. Methods: Primary and key secondary end-points were evaluated using a Cox proportional hazards model in prespecified subgroups, including geographical subregion (United States of America [USA], European Union [EU], Japan), age (<65 years, ≥65 years) and v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homologue (KRAS) status (wild type, mutant). Safety and tolerability were reported with descriptive statistics. Results: Eight-hundred patients were enrolled: USA, n = 99; EU, n = 403; Japan, n = 266. Patients aged ≥65 years and those with mutant KRAS tumours comprised 44% and 51% of all patients in the subregions, respectively. Final OS analysis (including 89% of events, compared with 72% in the initial analysis) confirmed the survival benefit associated with trifluridine/tipiracil, with a hazard ratio (HR) of 0.69 (95% confidence interval [CI] 0.59–0.81; P = 0.0001). Median OS in the three regions was 6.5–7.8 months in the trifluridine/tipiracil arm and 4.3–6.7 months in the placebo arm (USA: HR 0.56; 95% CI 0.34–0.94; P = 0.0277; EU: HR 0.62; 95% CI 0.48–0.80; P = 0.0002; Japan: HR 0.75; 95% CI 0.57–1.00; P = 0.0470). Median PFS was 2.0–2.8 months for trifluridine/tipiracil and 1.7–1.8 months for placebo; HRs favoured trifluridine/tipiracil in all regions. Similar clinical benefits of trifluridine/tipiracil were observed in elderly patients and in those with mutant KRAS tumours. There were no marked differences among subregions in terms of safety and tolerability. Conclusions: Trifluridine/tipiracil was effective in all subgroups, regardless of age, geographical origin or KRAS status.