TY - JOUR
T1 - Local Treatment of Unresectable Colorectal Liver Metastases
T2 - Results of a Randomized Phase II Trial
AU - Ruers, Theo
AU - Van Coevorden, Frits
AU - Punt, Cornelis J.A.
AU - Pierie, Jean Pierre E.N.
AU - Borel-Rinkes, Inne
AU - Ledermann, Jonathan A.
AU - Poston, Graeme
AU - Bechstein, Wolf
AU - Lentz, Marie Ange
AU - Mauer, Murielle
AU - Folprecht, Gunnar
AU - Van Cutsem, Eric
AU - Ducreux, Michel
AU - Nordlinger, Bernard
AU - Paré, Ambroise
AU - Verwaal, V. J.
AU - Gruenberger, T.
AU - Klaase, J.
AU - Falk, S.
AU - Wals, J.
AU - Jansen, R. L.
AU - Lindnér, P.
AU - Mulier, S.
AU - Bosscha, K.
AU - Jaeck, D.
AU - Arnaud, J. P.
AU - Smith, D.
AU - Sherlock, D.
AU - Ammori, B.
AU - Gillams, A.
AU - El-Serafi, M.
AU - Glimelius, B.
AU - Hellman, P.
AU - European Organisation for Research and Treatment of Cancer (EORTC) Gastro-Intestinal Tract Cancer Group
AU - Arbeitsgruppe Lebermetastasen und tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie (ALM-CAO)
AU - National Cancer Research Institute Colorectal Clinical Study Group (NCRI CCSG)
N1 - Funding Information:
The sponsor of this trial was the European Organisation for Research and Treatment of Cancer (EORTC). The trial was supported by a grant from Cancer Research UK through the Cancer Research Fund (C837/A3488) and Arbeitsgruppe Lebermetastasen und tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie (ALM-CAO), by grants from the Dutch Cancer Foundation (Commissie Klinisch Toegepast Onderzoek), by grant numbers 5U10 CA11488-32 through 5U10 CA011488-40 from the National Cancer Institute (Bethesda, MD), by a donation from the Kankerbestrijding/KWF from the Netherlands through the EORTC Charitable Trust, and by an unrestricted scientific grant from Sanofi-Aventis. Radionics, Radiotherapeutics, and Rita provided free RFA needles.
Publisher Copyright:
© 2017 The Author 2017. Published by Oxford University Press.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - Background: Tumor ablation is often employed for unresectable colorectal liver metastases. However, no survival benefit has ever been demonstrated in prospective randomized studies. Here, we investigate the long-term benefits of such an aggressive approach. Methods: In this randomized phase II trial, 119 patients with unresectable colorectal liver metastases (n < 10 and no extrahepatic disease) received systemic treatment alone or systemic treatment plus aggressive local treatment by radiofrequency ablation ± resection. Previously, we reported that the primary end point (30-month overall survival [OS] > 38%) was met. We now report on long-term OS results. All statistical tests were two-sided. The analyses were according to intention to treat. Results: At a median follow up of 9.7 years, 92 of 119 (77.3%) patients had died: 39 of 60 (65.0%) in the combined modality arm and 53 of 59 (89.8%) in the systemic treatment arm. Almost all patients died of progressive disease (35 patients in the combined modality arm, 49 patients in the systemic treatment arm). There was a statistically significant difference in OS in favor of the combined modality arm (hazard ratio [HR] = 0.58, 95% confidence interval [CI] = 0.38 to 0.88, P =. 01). Three-, five-, and eight-year OS were 56.9% (95% CI = 43.3% to 68.5%), 43.1% (95% CI = 30.3% to 55.3%), 35.9% (95% CI = 23.8% to 48.2%), respectively, in the combined modality arm and 55.2% (95% CI = 41.6% to 66.9%), 30.3% (95% CI = 19.0% to 42.4%), 8.9% (95% CI = 3.3% to 18.1%), respectively, in the systemic treatment arm. Median OS was 45.6 months (95% CI = 30.3 to 67.8 months) in the combined modality arm vs 40.5 months (95% CI = 27.5 to 47.7 months) in the systemic treatment arm. Conclusions: This phase II trial is the first randomized study demonstrating that aggressive local treatment can prolong OS in patients with unresectable colorectal liver metastases.
AB - Background: Tumor ablation is often employed for unresectable colorectal liver metastases. However, no survival benefit has ever been demonstrated in prospective randomized studies. Here, we investigate the long-term benefits of such an aggressive approach. Methods: In this randomized phase II trial, 119 patients with unresectable colorectal liver metastases (n < 10 and no extrahepatic disease) received systemic treatment alone or systemic treatment plus aggressive local treatment by radiofrequency ablation ± resection. Previously, we reported that the primary end point (30-month overall survival [OS] > 38%) was met. We now report on long-term OS results. All statistical tests were two-sided. The analyses were according to intention to treat. Results: At a median follow up of 9.7 years, 92 of 119 (77.3%) patients had died: 39 of 60 (65.0%) in the combined modality arm and 53 of 59 (89.8%) in the systemic treatment arm. Almost all patients died of progressive disease (35 patients in the combined modality arm, 49 patients in the systemic treatment arm). There was a statistically significant difference in OS in favor of the combined modality arm (hazard ratio [HR] = 0.58, 95% confidence interval [CI] = 0.38 to 0.88, P =. 01). Three-, five-, and eight-year OS were 56.9% (95% CI = 43.3% to 68.5%), 43.1% (95% CI = 30.3% to 55.3%), 35.9% (95% CI = 23.8% to 48.2%), respectively, in the combined modality arm and 55.2% (95% CI = 41.6% to 66.9%), 30.3% (95% CI = 19.0% to 42.4%), 8.9% (95% CI = 3.3% to 18.1%), respectively, in the systemic treatment arm. Median OS was 45.6 months (95% CI = 30.3 to 67.8 months) in the combined modality arm vs 40.5 months (95% CI = 27.5 to 47.7 months) in the systemic treatment arm. Conclusions: This phase II trial is the first randomized study demonstrating that aggressive local treatment can prolong OS in patients with unresectable colorectal liver metastases.
U2 - 10.1093/jnci/djx015
DO - 10.1093/jnci/djx015
M3 - Article
SN - 0027-8874
VL - 109
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 9
M1 - djx015
ER -