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To evaluate R0/R1 resection rate in patients with colorectal liver metastases (CLM) treated with aflibercept plus FOLFIRI after failure of a prior oxaliplatin-based regimen in daily clinical practice. This French, multicentre, prospective, observational cohort (NCT05178745) included patients with CLM (alone or predominant; up to 5 lung nodules <2 cm allowed) initiating aflibercept plus FOLFIRI every 2 weeks per physician choice. Primary endpoint was R0/R1 resection rate. Secondary endpoints included overall survival (OS), progression-free survival (PFS), radiological and pathological responses, and safety. A total of 137 patients (median age 65 years, RAS/BRAF mutant 57 %/9 %) were enrolled at 22 French sites. CLM (median 4) were synchronous in 82 %, bilobar in 71 % and located in liver only in 54 %. Overall, 17 % of patients had R0/R1 resection (21 % for patients with liver-only disease). A major pathological response per Blazer score was observed in 55 % of resected patients, along with significantly longer OS (median 34.8 vs 9.1 months, p < 0.0001) and PFS (median 11.4 vs 4.9 months, p < 0.0001) compared to non-resected patients. Post-operative complications occurred in 17 % of patients (all Dindo-Clavien grade I-II) and there was no post-operative deaths. Overall, 34 % had grade ≥ 3 adverse events, mainly general health deterioration and diarrhea. Results suggest that aflibercept plus FOLFIRI, after failure of a prior oxaliplatin-based regimen, allows R0/R1 resection of CLM in almost 20 % of patients with a major pathological response in most cases and a median OS prolonged by more than 3-fold versus non-resected patients. • Most patients with metastatic colorectal cancer die because of liver metastases. • Second-line aflibercept plus FOLFIRI allows metastasis resection in 1 in 5 patients. • Pathological response in resected metastases is major in most cases. • Postoperative morbidity is low. • Survival of resected patients is 3-fold higher than non-resected patients. [ABSTRACT FROM AUTHOR]

Résumé: La radioembolisation des métastases hépatiques de cancer colorectal, ou radiothérapie interne sélective, est une technique qui consiste à délivrer par l'artère hépatique des microsphères chargées d'yttrium-90 radioactif, directement au sein des métastases hépatiques. L'effet thérapeutique de la radioembolisation est lié à la radiothérapie interne et non à l'embolisation. Elle nécessite plusieurs étapes rigoureuses, faisant intervenir des radiologues interventionnels, des médecins nucléaires, des radiopharmaciens et des radiophysiciens : une étape de simulation aux macroaggrégats d'albumine humaine, la dosimétrie, et la phase de traitement. La radio-embolisation est disponible en France depuis une dizaine d'années. Elle a été validée chez les patients ayant des métastases hépatiques exclusives réfractaires aux traitements systémiques, dans quelques études de faibles effectifs, permettant son remboursement par l'assurance maladie dans cette indication. De récentes grandes études de phase III ont évalué cette technique associée à la chimiothérapie, dès la première et deuxième ligne. En dépit d'une activité antitumorale évidente, permettant une amélioration du contrôle local, ces études n'ont en revanche pas permis de montrer un bénéfice en survie globale. Une amélioration des techniques de dosimétrie, une meilleure sélection des patients et des combinaisons avec des traitements susceptibles d'apporter des effets biologiques synergiques pourraient à l'avenir faire reconsidérer la place de la radioembolisation dans les lignes précoces de traitement. Radioembolization of colorectal cancer liver metastases, or selective internal radiation therapy, is a technique that consists of delivering radioactive yttrium-loaded microbeads through the hepatic artery directly into the liver metastases. The therapeutic effect of radioembolization is related to the internal radiotherapy and not to the embolization. It requires several rigorous steps, involving interventional radiologists, nuclear physicians, radiopharmacists and radiophysicists: A simulation step with albumin macroaggregates, dosimetry, and the treatment phase. Radioembolization is available in France for about ten years. It has been validated in patients with exclusive liver metastases and refractory to systemic treatments in few studies with small population, allowing its reimbursement in this indication. Recent large phase III studies have evaluated this technique in combination with chemotherapy, in 1st and 2nd line of treatment. Despite clear antitumor activity, showing an improvement in local control, these studies did not show any benefit in overall survival. Improved dosimetry techniques, better patient selection, and combinations with treatments likely to have synergistic biological effects could lead to reconsideration of the role of radioembolization in early-line treatment. [ABSTRACT FROM AUTHOR]

Background: After curative-intent surgery for colorectal liver metastases (CRLM), liver recurrence occurs in more than 60% of patients, despite the administration of perioperative or adjuvant chemotherapy. This risk is even higher after resection of more than three CRLM. As CRLM are mostly supplied by arterial blood flow, hepatic arterial infusion (HAI) of chemotherapeutic agents after resection of CRLM is an attractive approach. Oxaliplatin-based HAI chemotherapy, in association with systemic fluoropyrimidines, has been shown to be safe and highly active in patients with CRLM. In a retrospective series of 98 patients at high risk of hepatic recurrence (≥4 resected CRLM), adjuvant HAI oxaliplatin combined with systemic chemotherapy was feasible and significantly improved disease-free survival compared to adjuvant, 'modern' systemic chemotherapy alone., Methods/design: This study is designed as a multicentre, randomized, phase II/III trial. The first step is a non-comparative randomized phase II trial (power, 95%; one-sided alpha risk, 10%). Patients will be randomly assigned in a 1:1 ratio to adjuvant systemic FOLFOX (control arm) or adjuvant HAI oxaliplatin plus systemic LV5FU2 (experimental arm). A total 114 patients will need to be included. The main objective of this trial is to evaluate the potential survival benefit of adjuvant HAI with oxaliplatin after resection of at least 4 CRLM (primary endpoint: 18-month hepatic recurrence-free survival rate). We also aim to assess the feasibility of delivering at least 4 cycles of HAI (or i.v.) oxaliplatin after surgical treatment of at least 4 CRLM, the toxicity (NCI-CTC v4.0) of adjuvant HAI plus systemic chemotherapy, including HAI catheter-related complications, compared to systemic chemotherapy alone, and the efficacy of adjuvant HAI on hepatic and extra-hepatic recurrence-free (survival and overall survival)., Discussion: If 18-month hepatic recurrence-free survival is greater than 50% in the experimental arm, the study will be pursued in phase III, for which the primary endpoint will be 3-year recurrence-free survival rate. Patients randomized in the phase II will be included in the phase III, with an additional number of 106 patients., Trial Registration: ClinicalTrials.gov, NCT02494973 . Trial registration date: July 10, 2015.

Background: Neuroendocrine tumors (NETs) are the second most common gastrointestinal malignancy after colon cancer. Up to 90% of patients with NETs develop liver metastases, which are a major determinant of symptoms and survival. Current guidelines recommend embolotherapy for progressive or symptomatic NET liver metastases, but the optimal technique among bland embolization, lipiodol chemoembolization, and drug-eluting bead chemoembolization remains unknown and controversial., Methods/design: A prospective, open-label, multicenter randomized controlled trial will be conducted in patients with progressive or symptomatic unresectable NET liver metastases. Patients will be randomized to treatment with bland embolization, lipiodol chemoembolization, or drug-eluting microsphere chemoembolization, with 60 enrollees per arm. The primary endpoint will be hepatic progression-free survival (HPFS) following initial embolotherapy by RECIST criteria. The sample size is powered to detect an HR of 1.78 for HPFS following chemoembolization compared with bland embolization, which was estimated on the basis of existing retrospective studies. Secondary endpoints include overall progression-free survival, duration of symptom control, quality of life, rate of adverse events, and interval between embolotherapy cycles. Interim safety analyses will be performed at 10 and 30 patients per arm., Discussion: The RETNET trial is a prospective, multicenter randomized controlled trial designed to determine the optimal embolotherapy technique for NET liver metastases., Trial Registration: ClinicalTrials.gov, NCT02724540 . Registered on March 31, 2016.