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Clin Colorectal Cancer. 2018 Dec;17(4):e617-e629. doi: 10.1016/j.clcc.2018.06.001. Epub 2018 Jun 12.

Effect of Primary Tumor Side on Survival Outcomes in Untreated Patients With Metastatic Colorectal Cancer When Selective Internal Radiation Therapy Is Added to Chemotherapy: Combined Analysis of Two Randomized Controlled Studies.

Collaborators (200)

Brown M, Burge M, Cardaci G, Clarke S, Eliadis P, Ferguson T, Ganju V, Gibbs P, van Hazel G, James P, Karapetis C, Liauw W, Marx G, Matos M, Nott L, Pavlakis N, Powell A, Price T, Ransom D, Segelov E, Shannon J, Singhal N, Strickland A, Walpole E, Craninx M, Delaunoit T, Deleporte A, Ferrante M, Geboes K, Hendlisz A, Hendrickx K, De Man M, Monsaert E, Moons V, Peeters M, Polus M, Boucher E, Balosso J, Chevallier P, Louafi S, Pracht M, Rebischung C, Smith D, Taieb J, Terrebonne E, Bruch HR, Gehbauer G, Heinemann V, Helmberger T, Ko YD, Kröning H, Lammert F, Nusch A, Pluntke S, Ridwelski K, Riera-Knorrenschild J, Riess H, Riera JR, Ricke J, Sauerbruch T, Scheidhauer K, Stötzer O, Tatsch K, Vehling-Kaiser U, Vogl T, Beny A, Geva R, Shacham-Shmueli E, Stemmer S, Tichler T, Wolf I, Angelelli B, Martoni A, Findlay MPN, Isaacs R, O'Donnell A, Perez D, Robinson BA, Rodríguez J, Vera-Garcia R, Amin P, Bloomgarden D, Bui J, Carlisle J, Chai S, Chen YJ, Chuong M, Coveler A, Facchini F, Frenette G, Frick J, Garofalo M, George B, Gordon M, Gulec S, Hannigan J, Holtzman M, Kaubisch A, Kaiser A, Kooy T, Limentani S, Margolis J, Martin R, Ozer H, Padia S, Rilling W, Savin M, Schneiderman E, Seeger G, Sharma N, Shibata S, Smith R, Wang E, Whiting S, Aghmesheh M, Burge M, Cooray P, Feeney K, Ferguson T, Ganju V, Gibbs P, van Hazel G, Lim L, Matos M, Nott L, Singh M, Singhal N, Strickland A, Underhill C, Walpole E, Deleporte A, Hendlisz A, Hendrickx K, De Man M, Monsaert E, Peeters M, Polus M, Boucher E, Durand A, Faivre S, Ferru A, Hammel P, Louafi S, Pracht M, Rebischung C, Smith D, Taieb J, Terrebonne E, Bremer C, De Wit M, Kröning H, Ayala H, Beny A, Geva R, Heching N, Shani A, Tichler T, Angelelli B, Granetto C, Masi G, Mosconi S, Numico G, Trogu A, Kim YH, Sae-Won H, Findlay MPN, Isaacs R, Jackson C, O'Donnell A, Fragoso M, Tan I, Casado AR, Vera-Garcia R, Liang JT, Liu JH, Ades S, Auber M, Bloomgarden D, Boland P, Bowers C, Bui J, Carlisle J, Chai S, Chuong M, Crain M, Dowling K, Facchini F, Frenette G, Frick J, Holtzman M, Iyer R, Kaiser A, Kaubisch A, Limentani S, Ratner L, Sanchez F, Sharma N, Stoltzfus P, Wang E, Westcott M.

Author information

Department of Oncology, Western Hospital, Footscray, VIC, Australia. Electronic address:
Comprehensive Cancer Center, Ludwig Maximilian University of Munich, Munich, Germany.
University of Maryland Medical Center, Baltimore, MD.
Department of Gastroenterology and Gastrointestinal Oncology, Paris Descartes University, Georges Pompidou European Hospital, Paris, France.
Department of Radiology, Ludwig Maximilian University of Munich, Munich, Germany.
Department of Oncology, Antwerp University Hospital, Antwerp, Belgium.
Auckland City Hospital and Cancer Trials, Auckland, New Zealand.
Oncology Service, Christchurch Hospital, Christchurch, New Zealand.
University of Otago, Dunedin, New Zealand.
Medical Oncology Hospital, Monash Medical Centre, Clayton, VIC, Australia.
National Health and Medical Research Council Clinical Trials Centre, Camperdown, NSW, Australia.
Data Reduction LLC, Chester, NJ.
School of Medicine and Pharmacology, University of Western Australia, West Perth, WA, Australia.



The primary tumor side is emerging as a major prognostic factor for patients with metastatic colorectal cancer (mCRC). We examined the survival data from 2 randomized studies to determine whether the outcomes differ between patients with mCRC with right-sided primary (RSP) tumors and those with left-sided primary (LSP) tumors after selective internal radiation therapy (SIRT) plus mFOLFOX6 (folinic acid [leucovorin], 5-fluorouracil, oxaliplatin) chemotherapy, versus chemotherapy alone.


Separate and combined analyses were performed on the data from the SIRFLOX and FOXFIRE global trials, which compared chemotherapy plus SIRT with chemotherapy alone for patients with mCRC liver metastases. The primary tumor side data were prospectively collected. The principal outcome measure was overall survival (OS) stratified by treatment and primary tumor side.


In the combined analysis of all 739 patients enrolled, SIRT had no effect on OS (median OS, 24.3 vs. 24.6 months; hazard ratio [HR], 1.021; P = .810). For the 179 patients (24.2%) with a RSP tumor, OS was improved with the addition of SIRT (median, 22.0 vs. 17.1 months HR, 0.641; P = .008). The addition of SIRT was not associated with a significant difference in OS among the 540 patients with a LSP tumor (median, 24.6 vs. 26.6 months; HR, 1.120; P = .264). A test of treatment interaction by primary tumor side was statistically significant for RSP and SIRT (P = .002).


The addition of SIRT for patients with RSP tumors, but not for those with LSP tumors, was associated with a statistically and clinically significant OS gain.


Left-sided primary; Overall survival; Right-sided primary; SIRT; mCRC

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