ESMO consensus guidelines for the management of patients with metastatic colorectal cancer

Annals of Oncology

Volumn 27, Issue 8, 2016, Pages 1386-1422

  Van Cutsem, Eric ^a   Cervantes, A ^b   Adam, R ^c   Sobrero, A ^d   Van Krieken, J H ^e   Aderka, D ^f   Aranda Aguilar, E ^g   Bardelli, A ^h   Benson, A ⁱ   Bodoky, G ^j   Ciardiello, F ^k   D'Hoore, A ^a   Diaz Rubio, E ^l   Douillard, J Y ^m   Ducreux, M ⁿ   Falcone, A ^o,p   Grothey, A ^q   Gruenberger, T ^r   Haustermans, K ^a   Heinemann, V ^s   Hoff, P ^t   Kohne C H ^u   Labianca, R ^v   Laurent Puig, P ^w   Ma, B ^x   Maughan, T ^y   Muro, K ^z   Normanno, N ^aa   osterlund P ^ab,ac   Oyen, W J G ^ad   Papamichael, D ^ae   Pentheroudakis, G ^af   Pfeiffer, P ^ag   Price, T J ^ah   Punt, C ^ai   Ricke, J ^aj   Roth, A ^ak   Salazar, R ^al   Scheithauer, W ^am   Schmoll, H J ^an   Tabernero, J ^ao   Taieb J ^w   Tejpar, S ^a   Wasan, H ^ap   Yoshino, T ^aq   Zaanan, A ^w   Arnold, D ^ar   more..

^a UNIVERSITY HOSPITALS LEUVEN   (Belgium)

^b UNIVERSITY OF VALENCIA   (Spain)

^c HÔPITAL PAUL BROUSSE   (France)

^d UNIVERSITY OF GENOA   (Italy)

^e RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^f TEL AVIV UNIVERSITY   (Israel)

^g HOSPITAL UNIVERSITARIO REINA SOFÍA   (Spain)

^h UNIVERSITY OF TURIN   (Italy)

ⁱ NW Univ Feinberg School of Medicine   (United States)

^j Szent Laszlo Hospital   (Hungary)

^k SECOND UNIVERSITY OF NAPLES   (Italy)

^l HOSPITAL CLÍNICO SAN CARLOS   (Spain)

^m Institut de Cancérologie de l'Ouest ^*  (France)

ⁿ INSTITUT GUSTAVE ROUSSY   (France)

^o UNIVERSITY OF PISA   (Italy)

^p UNIVERSITY OF PISA   (Italy)

^q MAYO CLINIC   (United States)

^r KRANKENANSTALT RUDOLFSTIFTUNG   (Austria)

^s LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^t UNIVERSITY OF SÃO PAULO   (Brazil)

^u KLINIKUM OLDENBURG   (Germany)

^v Ospedale Papa Giovanni XXIII   (Italy)

^w HÔPITAL EUROPÉEN GEORGES POMPIDOU   (France)

^x CHINESE UNIVERSITY OF HONG KONG   (Hong Kong)

^y UNIVERSITY OF OXFORD   (United Kingdom)

^z AICHI CANCER CENTER HOSPITAL   (Japan)

^aa NATIONAL CANCER INSTITUTE   (Italy)

^ab HELSINKI UNIVERSITY CENTRAL HOSPITAL   (Finland)

^ac UNIVERSITY OF HELSINKI   (Finland)

^ad ROYAL MARSDEN HOSPITAL   (United Kingdom)

^ae Bank of Cyprus Group Oncology Centre   (Cyprus)

^af UNIVERSITY OF IOANNINA   (Greece)

^ag ODENSE UNIVERSITY HOSPITAL   (Denmark)

^ah QUEEN ELIZABETH HOSPITAL   (Australia)

^ai UNIVERSITY OF AMSTERDAM   (Netherlands)

^aj OVG University Clinic Magdeburg   (Germany)

^ak GENEVA UNIVERSITY HOSPITALS   (Switzerland)

^al CATALAN INSTITUTE OF ONCOLOGY   (Spain)

^am MEDICAL UNIVERSITY OF VIENNA   (Austria)

^an MARTIN LUTHER UNIVERSITÄT HALLE WITTENBERG   (Germany)

^ao VALL D HEBRON UNIVERSITY HOSPITAL   (Spain)

^ap HAMMERSMITH HOSPITAL   (United Kingdom)

^aq NATIONAL CANCER CENTER HOSPITAL EAST   (Japan)

^ar Instituto CUF de Oncologia (ICO)   (Portugal)

more..

Author keywords

Clinical practice guidelines; Colorectal cancer; Consensus; ESMO

Indexed keywords

AFLIBERCEPT; B RAF KINASE; BEVACIZUMAB; BIOLOGICAL MARKER; CAPECITABINE; CETUXIMAB; DIHYDROPYRIMIDINASE; EPIDERMAL GROWTH FACTOR RECEPTOR 2; FLUOROPYRIMIDINE; FLUOROURACIL; FOLINIC ACID; GLUCURONOSYLTRANSFERASE 1A1; IRINOTECAN; MOLECULAR MARKER; MONOCLONAL ANTIBODY; OXALIPLATIN; PANITUMUMAB; PLACEBO; RAMUCIRUMAB; REGORAFENIB; TIPIRACIL; TRIFLURIDINE; TUMOR MARKER;

ABLATION THERAPY; ADVANCED CANCER; ARTICLE; BRACHYTHERAPY; CANCER PROGNOSIS; CHEMOEMBOLIZATION; CLINICAL FEATURE; CODON; COMPUTER ASSISTED TOMOGRAPHY; CONSENSUS; CONTRAST ENHANCEMENT; DRUG EFFICACY; EVIDENCE BASED MEDICINE; EXON; GENE MUTATION; GENETIC VARIATION; HUMAN; HUMAN TISSUE; IMAGE ANALYSIS; LIVER METASTASIS; LUNG METASTASIS; LYMPH NODE METASTASIS; MAINTENANCE THERAPY; METASTATIC COLORECTAL CANCER; MOLECULAR PATHOLOGY; NUCLEAR MAGNETIC RESONANCE IMAGING; OVERALL SURVIVAL; PERITONEUM METASTASIS; PHASE 3 CLINICAL TRIAL; POSITRON EMISSION TOMOGRAPHY; PRACTICE GUIDELINE; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; RADIOEMBOLIZATION; RETROSPECTIVE STUDY; SYSTEMIC THERAPY; TREATMENT OUTCOME; COLORECTAL TUMOR; GENETICS; METASTASIS; MOLECULARLY TARGETED THERAPY; PATHOLOGY; PROGNOSIS;

BIOMARKERS, TUMOR; COLORECTAL NEOPLASMS; GUIDELINES AS TOPIC; HUMANS; MOLECULAR TARGETED THERAPY; NEOPLASM METASTASIS; PROGNOSIS;

EID: 84984985398     PISSN: 09237534     EISSN: 15698041     Source Type: Journal    
DOI: 10.1093/annonc/mdw235     Document Type: Article

References (304)

1. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 2013; 49: 1374-1403.
2. Ferlay J, Soerjomataram I, Dikshit R et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015; 136: E359-E386.
3. Schmoll HJ, Van Cutsem E, Stein A et al. ESMO consensus guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making. Ann Oncol 2012; 23: 2479-2516.
4. Dykewicz CA, Centers for Disease Control and Prevention, Infectious Diseases Society of America, American Society of Blood and Marrow Transplantation. Summary of the guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients. Clin Infect Dis 2001; 33: 139-144.
5. Van Cutsem E, Cervantes A, Nordlinger B et al. Metastatic colorectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2014; 25(Suppl 3): iii1-iii9.
6. Neumeister VM, Anagnostou V, Siddiqui S et al. Quantitative assessment of effect of preanalytic cold ischemic time on protein expression in breast cancer tissues. J Natl Cancer Inst 2012; 104: 1815-1824.
7. Portier BP, Wang Z, Downs-Kelly E et al. Delay to formalin fixation 'cold ischemia time': effect on ERBB2 detection by in-situ hybridization and immunohistochemistry. Mod Pathol 2013; 26: 1-9.
8. Engel KB, Moore HM. Effects of preanalytical variables on the detection of proteins by immunohistochemistry in formalin-fixed, paraffin-embedded tissue. Arch Pathol Lab Med 2011; 135: 537-543.
9. Arber DA. Effect of prolonged formalin fixation on the immunohistochemical reactivity of breast markers. Appl Immunohistochem Mol Morphol 2002; 10: 183-186.
10. Babic A, Loftin IR, Stanislaw S et al. The impact of pre-analytical processing on staining quality for H&E, dual hapten, dual color in situ hybridization and fluorescent in situ hybridization assays. Methods 2010; 52: 287-300.
11. Chafin D, Theiss A, Roberts E et al. Rapid two-temperature formalin fixation. PLoS One 2013; 8: e54138.
12. Kerr KM, Bubendorf L, Edelman MJ et al. Second ESMO consensus conference on lung cancer: pathology and molecular biomarkers for non-small-cell lung cancer. Ann Oncol 2014; 25: 1681-1690.
13. van Krieken JH, Jung A, Kirchner T et al. KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program. Virchows Arch 2008; 453: 417-431.
14. Dijkstra JR, Heideman DA, Meijer GA et al. KRAS mutation analysis on low percentage of colon cancer cells: the importance of quality assurance. Virchows Arch 2013; 462: 39-46.
15. Tsiatis AC, Norris-Kirby A, Rich RG et al. Comparison of Sanger sequencing, pyrosequencing, and melting curve analysis for the detection of KRAS mutations: diagnostic and clinical implications. J Mol Diagn 2010; 12: 425-432.
16. Carotenuto P, Roma C, Rachiglio AM et al. Detection of KRAS mutations in colorectal carcinoma patients with an integrated PCR/sequencing and real-time PCR approach. Pharmacogenomics 2010; 11: 1169-1179.
17. Tol J, Dijkstra JR, Vink-Borger ME et al. High sensitivity of both sequencing and real-time PCR analysis of KRAS mutations in colorectal cancer tissue. J Cell Mol Med 2010; 14: 2122-2131.
18. Etienne-Grimaldi MC, Formento JL, Francoual M et al. K-Ras mutations and treatment outcome in colorectal cancer patients receiving exclusive fluoropyrimidine therapy. Clin Cancer Res 2008; 14: 4830-4835.
19. Losi L, Benhattar J, Costa J. Stability of K-ras mutations throughout the natural history of human colorectal cancer. Eur J Cancer 1992; 28A: 1115-1120.
20. Suchy B, Zietz C, Rabes HM. K-ras point mutations in human colorectal carcinomas: relation to aneuploidy and metastasis. Int J Cancer 1992; 52: 30-33.
21. Weber JC, Meyer N, Pencreach E et al. Allelotyping analyses of synchronous primary and metastasis CIN colon cancers identified different subtypes. Int J Cancer 2007; 120: 524-532.
22. Zauber P, Sabbath-Solitare M, Marotta SP, Bishop DT. Molecular changes in the Ki-ras and APC genes in primary colorectal carcinoma and synchronous metastases compared with the findings in accompanying adenomas. Mol Pathol 2003; 56: 137-140.
23. Oudejans JJ, Slebos RJ, Zoetmulder FA et al. Differential activation of ras genes by point mutation in human colon cancer with metastases to either lung or liver. Int J Cancer 1991; 49: 875-879.
24. Al-Mulla F, Going JJ, Sowden ET et al. Heterogeneity of mutant versus wild-type Ki-ras in primary and metastatic colorectal carcinomas, and association of codon-12 valine with early mortality. J Pathol 1998; 185: 130-138.
25. Albanese I, Scibetta AG, Migliavacca M et al. Heterogeneity within and between primary colorectal carcinomas and matched metastases as revealed by analysis of Ki-ras and p53 mutations. Biochem Biophys Res Commun 2004; 325: 784-791.
26. Oliveira C, Velho S, Moutinho C et al. KRAS and BRAF oncogenic mutations in MSS colorectal carcinoma progression. Oncogene 2007; 26: 158-163.
27. Artale S, Sartore-Bianchi A, Veronese SM et al. Mutations of KRAS and BRAF in primary and matched metastatic sites of colorectal cancer. J Clin Oncol 2008; 26: 4217-4219.
28. Santini D, Loupakis F, Vincenzi B et al. High concordance of KRAS status between primary colorectal tumors and related metastatic sites: implications for clinical practice. Oncologist 2008; 13: 1270-1275.
29. Cejas P, Lopez-Gomez M, Aguayo C et al. KRAS mutations in primary colorectal cancer tumors and related metastases: a potential role in prediction of lung metastasis. PLoS One 2009; 4: e8199.
30. Garm Spindler KL, Pallisgaard N, Rasmussen AA et al. The importance of KRAS mutations and EGF61A>G polymorphism to the effect of cetuximab and irinotecan in metastatic colorectal cancer. Ann Oncol 2009; 20: 879-884.
31. Loupakis F, Pollina L, Stasi I et al. PTEN expression and KRAS mutations on primary tumors and metastases in the prediction of benefit from cetuximab plus irinotecan for patients with metastatic colorectal cancer. J Clin Oncol 2009; 27: 2622-2629.
32. Molinari F, Martin V, Saletti P et al. Differing deregulation of EGFR and downstream proteins in primary colorectal cancer and related metastatic sites may be clinically relevant. Br J Cancer 2009; 100: 1087-1094.
33. Perrone F, Lampis A, Orsenigo M et al. PI3KCA/PTEN deregulation contributes to impaired responses to cetuximab in metastatic colorectal cancer patients. Ann Oncol 2009; 20: 84-90.
34. Baldus SE, Schaefer KL, Engers R et al. Prevalence and heterogeneity of KRAS, BRAF, and PIK3CA mutations in primary colorectal adenocarcinomas and their corresponding metastases. Clin Cancer Res 2010; 16: 790-799.
35. Italiano A, Hostein I, Soubeyran I et al. KRAS and BRAF mutational status in primary colorectal tumors and related metastatic sites: biological and clinical implications. Ann Surg Oncol 2010; 17: 1429-1434.
36. Knijn N, Mekenkamp LJ, Klomp M et al. KRAS mutation analysis: a comparison between primary tumours and matched liver metastases in 305 colorectal cancer patients. Br J Cancer 2011; 104: 1020-1026.
37. Corcoran RB, Ebi H, Turke AB et al. EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition with vemurafenib. Cancer Discov 2012; 2: 227-235.
38. Maughan TS, Adams RA, Smith CG et al. Addition of cetuximab to oxaliplatinbased first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet 2011; 377: 2103-2114.
39. Swain SM, Baselga J, Kim SB et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med 2015; 372: 724-734.
40. Dancey JE, Dobbin KK, Groshen S et al. Guidelines for the development and incorporation of biomarker studies in early clinical trials of novel agents. Clin Cancer Res 2010; 16: 1745-1755.
41. Amado RG, Wolf M, Peeters M et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 2008; 26: 1626-1634.
42. Karapetis CS, Khambata-Ford S, Jonker DJ et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 2008; 359: 1757-1765.
43. Van Cutsem E, Kohne CH, Hitre E et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 2009; 360: 1408-1417.
44. Van Cutsem E, Kohne CH, Lang I et al. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol 2011; 29: 2011-2019.
45. Bokemeyer C, Bondarenko I, Makhson A et al. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol 2009; 27: 663-671.
46. Bokemeyer C, Bondarenko I, Hartmann JT et al. Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS study. Ann Oncol 2011; 22: 1535-1546.
47. Peeters M, Price TJ, Cervantes A et al. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol 2010; 28: 4706-4713.
48. Douillard JY, Oliner KS, Siena S et al. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med 2013; 369: 1023-1034.
49. Van Cutsem E, Lenz HJ, Kohne CH et al. Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer. J Clin Oncol 2015; 33: 692-700.
50. Bokemeyer C, Kohne CH, Ciardiello F et al. FOLFOX4 plus cetuximab treatment and RAS mutations in colorectal cancer. Eur J Cancer 2015; 51: 1243-1252.
51. Peeters M, Oliner KS, Price TJ et al. Analysis of KRAS/NRAS mutations in a Phase III Study of panitumumab with FOLFIRI compared with FOLFIRI alone as second-line treatment for metastatic colorectal cancer. Clin Cancer Res 2015; 21: 5469-5479.
52. Poulin-Costello M, Azoulay L, Van Cutsem E et al. An analysis of the treatment effect of panitumumab on overall survival from a phase 3, randomized, controlled, multicenter trial (20020408) in patients with chemotherapy refractory metastatic colorectal cancer. Target Oncol 2013; 8: 127-136.
53. Schwartzberg LS, Rivera F, Karthaus M et al. PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. J Clin Oncol 2014; 32: 2240-2247.
54. Stintzing S, Jung A, Rossius L et al. Mutations within the EGFR signaling pathway: influence on efficacy in FIRE-3-a randomized phase III study of FOLFIRI plus cetuximab or bevacizumab as first-line treatment for wild-type (WT) KRAS (exon 2) metastatic colorectal cancer (mCRC) patients. J Clin Oncol 2014; 32(3 Suppl): abstr 445.
55. Heinemann V, von Weikersthal LF, Decker T et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol 2014; 15: 1065-1075.
56. Sorich MJ, Wiese MD, Rowland A et al. Extended RAS mutations and anti-EGFR monoclonal antibody survival benefit in metastatic colorectal cancer: a metaanalysis of randomized, controlled trials. Ann Oncol 2015; 26: 13-21.
57. Wong NA, Gonzalez D, Salto-Tellez M et al. RAS testing of colorectal carcinoma -a guidance document from the Association of Clinical Pathologists Molecular Pathology and Diagnostics Group. J Clin Pathol 2014; 67: 751-757.
58. Tack V, Ligtenberg MJ, Tembuyser L et al. External quality assessment unravels interlaboratory differences in quality of RAS testing for anti-EGFR therapy in colorectal cancer. Oncologist 2015; 20: 257-262.
59. Kircher SM, Mohindra N, Nimeiri H. Cost estimates and economic implications of expanded RAS testing in metastatic colorectal cancer. Oncologist 2015; 20: 14-18.
60. Tran B, Kopetz S, Tie J et al. Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer. Cancer 2011; 117: 4623-4632.
61. Tveit KM, Guren T, Glimelius B et al. Phase III trial of cetuximab with continuous or intermittent fluorouracil, leucovorin, and oxaliplatin (Nordic FLOX) versus FLOX alone in first-line treatment of metastatic colorectal cancer: the NORDIC-VII study. J Clin Oncol 2012; 30: 1755-1762.
62. Venderbosch S, Nagtegaal ID, Maughan TS et al. Mismatch repair status and BRAF mutation status in metastatic colorectal cancer patients: a pooled analysis of the CAIRO, CAIRO2, COIN, and FOCUS studies. Clin Cancer Res 2014; 20: 5322-5330.
63. Tol J, Nagtegaal ID, Punt CJ. BRAF mutation in metastatic colorectal cancer. N Engl J Med 2009; 361: 98-99.
64. Peeters M, Oliner KS, Parker A et al. Massively parallel tumor multigene sequencing to evaluate response to panitumumab in a randomized phase III study of metastatic colorectal cancer. Clin Cancer Res 2013; 19: 1902-1912.
65. Seymour MT, Brown SR, Middleton G et al. Panitumumab and irinotecan versus irinotecan alone for patients with KRAS wild-type, fluorouracil-resistant advanced colorectal cancer (PICCOLO): a prospectively stratified randomised trial. Lancet Oncol 2013; 14: 749-759.
66. Pietrantonio F, Petrelli F, Coinu A et al. Predictive role of BRAF mutations in patients with advanced colorectal cancer receiving cetuximab and panitumumab: a meta-analysis. Eur J Cancer 2015; 51: 587-594.
67. Rowland A, Dias MM, Wiese MD et al. Meta-analysis of BRAF mutation as a predictive biomarker of benefit from anti-EGFR monoclonal antibody therapy for RAS wild-type metastatic colorectal cancer. Br J Cancer 2015; 112: 1888-1894.
68. Cremolini C, Loupakis F, Antoniotti C et al. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. Lancet Oncol 2015; 16: 1306-1315.
69. Sosman JA, Kim KB, Schuchter L et al. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med 2012; 366: 707-714.
70. Kopetz S, Desai J, Chan E et al. Phase II pilot study of vemurafenib in patients with metastatic BRAF-mutated colorectal cancer. J Clin Oncol 2015; 33: 4032-4038.
71. Prahallad A, Sun C, Huang S et al. Unresponsiveness of colon cancer to BRAF (V600E) inhibition through feedback activation of EGFR. Nature 2012; 483: 100-103.
72. Corcoran RB, Atreya CE, Falchook GS et al. Combined BRAF and MEK inhibition with dabrafenib and trametinib in BRAF V600-mutant colorectal cancer. J Clin Oncol 2015; 33: 4023-4031.
73. Hyman DM, Puzanov I, Subbiah V et al. Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. N Engl J Med 2015; 373: 726-736.
74. Bettstetter M, Dechant S, Ruemmele P et al. Distinction of hereditary nonpolyposis colorectal cancer and sporadic microsatellite-unstable colorectal cancer through quantification of MLH1 methylation by real-time PCR. Clin Cancer Res 2007; 13: 3221-3228.
75. Domingo E, Niessen RC, Oliveira C et al. BRAF-V600E is not involved in the colorectal tumorigenesis of HNPCC in patients with functional MLH1 and MSH2 genes. Oncogene 2005; 24: 3995-3998.
76. Loughrey MB, Waring PM, Tan A et al. Incorporation of somatic BRAF mutation testing into an algorithm for the investigation of hereditary non-polyposis colorectal cancer. Fam Cancer 2007; 6: 301-310.
77. Cremolini C, Di Bartolomeo M, Amatu A et al. BRAF codons 594 and 596 mutations identify a new molecular subtype of metastatic colorectal cancer at favorable prognosis. Ann Oncol 2015; 26: 2092-2097.
78. Des Guetz G, Uzzan B, Nicolas P et al. Microsatellite instability: a predictive marker in metastatic colorectal cancer? Target Oncol 2009; 4: 57-62.
79. Goldstein J, Tran B, Ensor J et al. Multicenter retrospective analysis of metastatic colorectal cancer (CRC) with high-level microsatellite instability (MSI-H). Ann Oncol 2014; 25: 1032-1038.
80. Muller CI, Schulmann K, Reinacher-Schick A et al. Predictive and prognostic value of microsatellite instability in patients with advanced colorectal cancer treated with a fluoropyrimidine and oxaliplatin containing first-line chemotherapy. A report of the AIO Colorectal Study Group. Int J Colorectal Dis 2008; 23: 1033-1039.
81. Nopel-Dunnebacke S, Schulmann K, Reinacher-Schick A et al. Prognostic value of microsatellite instability and p53 expression in metastatic colorectal cancer treated with oxaliplatin and fluoropyrimidine-based chemotherapy. Z Gastroenterol 2014; 52: 1394-1401.
82. des Guetz G, Mariani P, Cucherousset J et al. Microsatellite instability and sensitivitiy to FOLFOX treatment in metastatic colorectal cancer. Anticancer Res 2007; 27: 2715-2719.
83. Kim JE, Hong YS, Ryu MH et al. Association between deficient mismatch repair system and efficacy to irinotecan-containing chemotherapy in metastatic colon cancer. Cancer Sci 2011; 102: 1706-1711.
84. Le DT, Uram JN, Wang H et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 2015; 372: 2509-2520.
85. Sanoff HK, McLeod HL. Predictive factors for response and toxicity in chemotherapy: pharmacogenomics. Semin Colon Rectal Surg 2008; 19: 226-230.
86. Meulendijks D, Henricks LM, Sonke GS et al. Clinical relevance of DPYD variants c.1679T>G, c.1236G>A/HapB3, and c.1601G>A as predictors of severe fluoropyrimidine-associated toxicity: a systematic review and meta-analysis of individual patient data. Lancet Oncol 2015; 16: 1639-1650.
87. Marsh S, Hoskins JM. Irinotecan pharmacogenomics. Pharmacogenomics 2010; 11: 1003-1010.
88. Barbarino JM, Haidar CE, Klein TE, Altman RB. PharmGKB summary: very important pharmacogene information for UGT1A1. Pharmacogenet Genomics 2014; 24: 177-183.
89. Camptosar prescribing information. http://labeling.pfizer.com/ShowLabeling. aspx?id=533. 2014.
90. Olaussen KA, Mountzios G, Soria JC. ERCC1 as a risk stratifier in platinum-based chemotherapy for nonsmall-cell lung cancer. Curr Opin Pulm Med 2007; 13: 284-289.
91. Soria JC. ERCC1-tailored chemotherapy in lung cancer: the first prospective randomized trial. J Clin Oncol 2007; 25: 2648-2649.
92. Qian YY, Liu XY, Wu Q et al. The ERCC1 C118T polymorphism predicts clinical outcomes of colorectal cancer patients receiving oxaliplatin-based chemotherapy: a meta-analysis based on 22 studies. Asian Pac J Cancer Prev 2014; 15: 8383-8390.
93. Orlandi A, Di Salvatore M, Bagala C et al. ERCC1 induction after oxaliplatin exposure may depend on KRAS mutational status in colorectal cancer cell line: in vitro veritas. J Cancer 2015; 6: 70-81.
94. Peters GJ, Backus HH, Freemantle S et al. Induction of thymidylate synthase as a 5-fluorouracil resistance mechanism. Biochim Biophys Acta 2002; 1587: 194-205.
95. Hoskins JM, Goldberg RM, Qu P et al. UGT1A1*28 genotype and irinotecaninduced neutropenia: dose matters. J Natl Cancer Inst 2007; 99: 1290-1295.
96. Misale S, Di Nicolantonio F, Sartore-Bianchi A et al. Resistance to anti-EGFR therapy in colorectal cancer: from heterogeneity to convergent evolution. Cancer Discov 2014; 4: 1269-1280.
97. Bardelli A, Siena S. Molecular mechanisms of resistance to cetuximab and panitumumab in colorectal cancer. J Clin Oncol 2010; 28: 1254-1261.
98. Mohan S, Heitzer E, Ulz P et al. Changes in colorectal carcinoma genomes under anti-EGFR therapy identified by whole-genome plasma DNA sequencing. PLoS Genet 2014; 10: e1004271.
99. Yonesaka K, Zejnullahu K, Okamoto I et al. Activation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic antibody cetuximab. Sci Transl Med 2011; 3: 99ra86.
100. Bertotti A, Migliardi G, Galimi F et al. A molecularly annotated platform of patientderived xenografts ('xenopatients') identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer. Cancer Discov 2011; 1: 508-523.
101. Douillard JY, Siena S, Cassidy J et al. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol 2010; 28: 4697-4705.
102. Stintzing S, Jung AS, Rossius L et al. Analysis of KRAS/NRAS and BRAF mutations in FIRE-3. Eur J Cancer 2013; 49(Suppl 3): abstr LBA17.
103. Valtorta E, Misale S, Sartore-Bianchi A et al. KRAS gene amplification in colorectal cancer and impact on response to EGFR-targeted therapy. Int J Cancer 2013; 133: 1259-1265.
104. Vaughn CP, Zobell SD, Furtado LV et al. Frequency of KRAS, BRAF, and NRAS mutations in colorectal cancer. Genes Chromosomes Cancer 2011; 50: 307-312.
105. Ogino S, Lochhead P, Giovannucci E et al. Discovery of colorectal cancer PIK3CA mutation as potential predictive biomarker: power and promise of molecular pathological epidemiology. Oncogene 2014; 33: 2949-2955.
106. Jhawer M, Goel S, Wilson AJ et al. PIK3CA mutation/PTEN expression status predicts response of colon cancer cells to the epidermal growth factor receptor inhibitor cetuximab. Cancer Res 2008; 68: 1953-1961.
107. Karapetis CS, Jonker D, Daneshmand M et al. PIK3CA, BRAF, and PTEN status and benefit from cetuximab in the treatment of advanced colorectal cancer- results from NCIC CTG/AGITG CO.17. Clin Cancer Res 2014; 20: 744-753.
108. Prenen H, De Schutter J, Jacobs B et al. PIK3CA mutations are not a major determinant of resistance to the epidermal growth factor receptor inhibitor cetuximab in metastatic colorectal cancer. Clin Cancer Res 2009; 15: 3184-3188.
109. Sartore-Bianchi A, Martini M, Molinari F et al. PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal antibodies. Cancer Res 2009; 69: 1851-1857.
110. Tian S, Simon I, Moreno V et al. A combined oncogenic pathway signature of BRAF, KRAS and PI3KCA mutation improves colorectal cancer classification and cetuximab treatment prediction. Gut 2013; 62: 540-549.
111. Misale S, Yaeger R, Hobor S et al. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature 2012; 486: 532-536.
112. Laurent-Puig P, Cayre A, Manceau G et al. Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer. J Clin Oncol 2009; 27: 5924-5930.
113. Kavuri SM, Jain N, Galimi F et al. HER2 activating mutations are targets for colorectal cancer treatment. Cancer Discov 2015; 5: 832-841.
114. Siena S, Sartore-Bianchi A, Lonardi S et al. Trastuzumab and lapatinib in HER2- amplified metastatic colorectal cancer patients (mCRC): the HERACLES trial. J Clin Oncol 2015; 33(15 Suppl): abstr 3508.
115. Juo YY, Johnston FM, Zhang DY et al. Prognostic value of CpG island methylator phenotype among colorectal cancer patients: a systematic review and metaanalysis. Ann Oncol 2014; 25: 2314-2327.
116. Moutinho C, Martinez-Cardus A, Santos C et al. Epigenetic inactivation of the BRCA1 interactor SRBC and resistance to oxaliplatin in colorectal cancer. J Natl Cancer Inst 2014; 106: djt322.
117. Cohen SJ, Punt CJ, Iannotti N et al. Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol 2008; 26: 3213-3221.
118. Diaz LA, Jr., Bardelli A. Liquid biopsies: genotyping circulating tumor DNA. J Clin Oncol 2014; 32: 579-586.
119. Siravegna G, Bardelli A. Genotyping cell-free tumor DNA in the blood to detect residual disease and drug resistance. Genome Biol 2014; 15: 449.
120. Montagut C, Dalmases A, Bellosillo B et al. Identification of a mutation in the extracellular domain of the Epidermal Growth Factor Receptor conferring cetuximab resistance in colorectal cancer. Nat Med 2012; 18: 221-223.
121. Aung KL, Board RE, Ellison G et al. Current status and future potential of somatic mutation testing from circulating free DNA in patients with solid tumours. Hugo J 2010; 4: 11-21.
122. Bettegowda C, Sausen M, Leary RJ et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med 2014; 6: 224ra224.
123. Dawson SJ, Tsui DW, Murtaza M et al. Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med 2013; 368: 1199-1209.
124. De Mattos-Arruda L, Weigelt B, Cortes J et al. Capturing intra-tumor genetic heterogeneity by de novo mutation profiling of circulating cell-free tumor DNA: a proof-of-principle. Ann Oncol 2014; 25: 1729-1735.
125. Diaz LA, Jr., Williams RT, Wu J et al. The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature 2012; 486: 537-540.
126. Forshew T, Murtaza M, Parkinson C et al. Noninvasive identification and monitoring of cancer mutations by targeted deep sequencing of plasma DNA. Sci Transl Med 2012; 4: 136ra168.
127. Gormally E, Caboux E, Vineis P, Hainaut P. Circulating free DNA in plasma or serum as biomarker of carcinogenesis: practical aspects and biological significance. Mutat Res 2007; 635: 105-117.
128. Higgins MJ, Jelovac D, Barnathan E et al. Detection of tumor PIK3CA status in metastatic breast cancer using peripheral blood. Clin Cancer Res 2012; 18: 3462-3469.
129. Murtaza M, Dawson SJ, Tsui DW et al. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature 2013; 497: 108-112.
130. Newman AM, Bratman SV, To J et al. An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nat Med 2014; 20: 548-554.
131. Punnoose EA, Atwal S, Liu W et al. Evaluation of circulating tumor cells and circulating tumor DNA in non-small cell lung cancer: association with clinical endpoints in a phase II clinical trial of pertuzumab and erlotinib. Clin Cancer Res 2012; 18: 2391-2401.
132. Schwarzenbach H, Hoon DS, Pantel K. Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer 2011; 11: 426-437.
133. Taly V, Pekin D, Benhaim L et al. Multiplex picodroplet digital PCR to detect KRAS mutations in circulating DNA from the plasma of colorectal cancer patients. Clin Chem 2013; 59: 1722-1731.
134. Taniguchi K, Uchida J, Nishino K et al. Quantitative detection of EGFR mutations in circulating tumor DNA derived from lung adenocarcinomas. Clin Cancer Res 2011; 17: 7808-7815.
135. Thierry AR, Mouliere F, El Messaoudi S et al. Clinical validation of the detection of KRAS and BRAF mutations from circulating tumor DNA. Nat Med 2014; 20: 430-435.
136. Li J, Mansmann UR. A microRNA molecular modeling extension for prediction of colorectal cancer treatment. BMC Cancer 2015; 15: 472.
137. Ciardiello F, Normanno N, Maiello E et al. Clinical activity of FOLFIRI plus cetuximab according to extended gene mutation status by next-generation sequencing: findings from the CAPRI-GOIM trial. Ann Oncol 2014; 25: 1756-1761.
138. Marisa L, de Reynies A, Duval A et al. Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value. PLoS Med 2013; 10: e1001453.
139. Guinney J, Dienstmann R, Wang B et al. The consensus molecular subtypes of colorectal cancer. Nat Med 2015; 21: 1350-1356.
140. Prades J, Borras JM. Shifting sands: adapting the multidisciplinary team model to technological and organizational innovations in cancer care. Future Oncol 2014; 10: 1995-1998.
141. Shah S, Arora S, Atkin G et al. Decision-making in Colorectal Cancer Tumor Board meetings: results of a prospective observational assessment. Surg Endosc 2014; 28: 2783-2788.
142. Prades J, Remue E, van Hoof E, Borras JM. Is it worth reorganising cancer services on the basis of multidisciplinary teams (MDTs)? A systematic review of the objectives and organisation of MDTs and their impact on patient outcomes. Health Policy 2015; 119: 464-474.
143. Weiser MR, Jarnagin WR, Saltz LB. Colorectal cancer patients with oligometastatic liver disease: what is the optimal approach? Oncology (Williston Park) 2013; 27: 1074-1078.
144. Khattak MA, Martin HL, Beeke C et al. Survival differences in patients with metastatic colorectal cancer and with single site metastatic disease at initial presentation: results from South Australian clinical registry for advanced colorectal cancer. Clin Colorectal Cancer 2012; 11: 247-254.
145. Price TJ, Townsend AR, Beeke C et al. 'Watchful waiting' for metastatic colorectal cancer, antediluvian or an option to be considered again? Asia Pac J Clin Oncol 2012; 8: 10-13.
146. Yaeger R, Cercek A, Chou JF et al. BRAF mutation predicts for poor outcomes after metastasectomy in patients with metastatic colorectal cancer. Cancer 2014; 120: 2316-2324.
147. Ohrling K, Edler D, Hallstrom M, Ragnhammar P. Expression of thymidylate synthase in liver and lung metastases of colorectal cancer and their matched primary tumours. Anticancer Res 2008; 28: 1741-1747.
148. Adam R, De Gramont A, Figueras J et al. The oncosurgery approach to managing liver metastases from colorectal cancer: a multidisciplinary international consensus. Oncologist 2012; 17: 1225-1239.
149. Clavien PA, Petrowsky H, DeOliveira ML, Graf R. Strategies for safer liver surgery and partial liver transplantation. N Engl J Med 2007; 356: 1545-1559.
150. Zorzi D, Laurent A, Pawlik TM et al. Chemotherapy-associated hepatotoxicity and surgery for colorectal liver metastases. Br J Surg 2007; 94: 274-286.
151. Jones RP, Stattner S, Sutton P et al. Controversies in the oncosurgical management of liver limited stage IV colorectal cancer. Surg Oncol 2014; 23: 53-60.
152. Kanas GP, Taylor A, Primrose JN et al. Survival after liver resection in metastatic colorectal cancer: review and meta-analysis of prognostic factors. Clin Epidemiol 2012; 4: 283-301.
153. Fong Y, Fortner J, Sun RL et al. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg 1999; 230: 309-318; discussion 318-321.
154. Floriani I, Torri V, Rulli E et al. Performance of imaging modalities in diagnosis of liver metastases from colorectal cancer: a systematic review and meta-analysis. J Magn Reson Imaging 2010; 31: 19-31.
155. Bartolotta TV, Taibbi A, Midiri M et al. Characterisation of focal liver lesions undetermined at grey-scale US: contrast-enhanced US versus 64-row MDCT and MRI with liver-specific contrast agent. Radiol Med 2010; 115: 714-731.
156. Niekel MC, Bipat S, Stoker J. Diagnostic imaging of colorectal liver metastases with CT, MR imaging, FDG PET, and/or FDG PET/CT: a meta-analysis of prospective studies including patients who have not previously undergone treatment. Radiology 2010; 257: 674-684.
157. Zech CJ, Korpraphong P, Huppertz A et al. Randomized multicentre trial of gadoxetic acid-enhanced MRI versus conventional MRI or CT in the staging of colorectal cancer liver metastases. Br J Surg 2014; 101: 613-621.
158. Hendlisz A, Golfinopoulos V, Garcia C et al. Serial FDG-PET/CT for early outcome prediction in patients with metastatic colorectal cancer undergoing chemotherapy. Ann Oncol 2012; 23: 1687-1693.
159. Moulton C, Levine MN, Law C et al. An Ontario Clinical Oncology Group (OCOG) randomized controlled trial (RCT) assessing FDG PET/CT in resectable liver colorectal adenocarcinoma metastases (CAM). J Clin Oncol 2011; 29(Suppl): abstr 3520.
160. Petersen RK, Hess S, Alavi A, Hoilund-Carlsen PF. Clinical impact of FDG-PET/CT on colorectal cancer staging and treatment strategy. Am J Nucl Med Mol Imaging 2014; 4: 471-482.
161. Maffione AM, Lopci E, Bluemel C et al. Diagnostic accuracy and impact on management of (18)F-FDG PET and PET/CT in colorectal liver metastasis: a meta-analysis and systematic review. Eur J Nucl Med Mol Imaging 2015; 42: 152-163.
162. Tomlinson JS, Jarnagin WR, DeMatteo RP et al. Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol 2007; 25: 4575-4580.
163. Nordlinger B, Sorbye H, Glimelius B et al. Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. Lancet Oncol 2013; 14: 1208-1215.
164. Nordlinger B, Sorbye H, Glimelius B et al. Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet 2008; 371: 1007-1016.
165. Primrose J, Falk S, Finch-Jones M et al. Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis: the New EPOC randomised controlled trial. Lancet Oncol 2014; 15: 601-611.
166. Mitry E, Fields AL, Bleiberg H et al. Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer: a pooled analysis of two randomized trials. J Clin Oncol 2008; 26: 4906-4911.
167. Kemeny N, Capanu M, D'Angelica M et al. Phase I trial of adjuvant hepatic arterial infusion (HAI) with floxuridine (FUDR) and dexamethasone plus systemic oxaliplatin, 5-fluorouracil and leucovorin in patients with resected liver metastases from colorectal cancer. Ann Oncol 2009; 20: 1236-1241.
168. Adam R, Delvart V, Pascal G et al. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival. Ann Surg 2004; 240: 644-657; discussion 657-658.
169. Adam R, Barroso E, Laurent C et al. Impact of the type and modalities of preoperative chemotherapy on the outcome of liver resection for colorectal metastases. J Clin Oncol 2011; 29(15 Suppl): abstr 3519.
170. Chun YS, Vauthey JN, Boonsirikamchai P et al. Association of computed tomography morphologic criteria with pathologic response and survival in patients treated with bevacizumab for colorectal liver metastases. JAMA 2009; 302: 2338-2344.
171. Adam R, Bhangui P, Poston G et al. Is perioperative chemotherapy useful for solitary, metachronous, colorectal liver metastases? Ann Surg 2010; 252: 774-787.
172. Nordlinger B, Van Cutsem E, Gruenberger T et al. Combination of surgery and chemotherapy and the role of targeted agents in the treatment of patients with colorectal liver metastases: recommendations from an expert panel. Ann Oncol 2009; 20: 985-992.
173. Nordlinger B, Van Cutsem E, Rougier P et al. Does chemotherapy prior to liver resection increase the potential for cure in patients with metastatic colorectal cancer? A report from the European Colorectal Metastases Treatment Group. Eur J Cancer 2007; 43: 2037-2045.
174. Van Cutsem E, Nordlinger B, Adam R et al. Towards a pan-European consensus on the treatment of patients with colorectal liver metastases. Eur J Cancer 2006; 42: 2212-2221.
175. Folprecht G, Grothey A, Alberts S et al. Neoadjuvant treatment of unresectable colorectal liver metastases: correlation between tumour response and resection rates. Ann Oncol 2005; 16: 1311-1319.
176. Folprecht G, Gruenberger T, Bechstein WO et al. Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial. Lancet Oncol 2010; 11: 38-47.
177. Ye LC, Liu TS, Ren L et al. Randomized controlled trial of cetuximab plus chemotherapy for patients with KRAS wild-type unresectable colorectal liverlimited metastases. J Clin Oncol 2013; 31: 1931-1938.
178. Gruenberger T, Bridgewater J, Chau I et al. Bevacizumab plus mFOLFOX-6 or FOLFOXIRI in patients with initially unresectable liver metastases from colorectal cancer: the OLIVIA multinational randomised phase II trial. Ann Oncol 2014; 26: 702-708.
179. Masi G, Loupakis F, Salvatore L et al. Bevacizumab with FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, and folinate) as first-line treatment for metastatic colorectal cancer: a phase 2 trial. Lancet Oncol 2010; 11: 845-852.
180. Folprecht G, Gruenberger T, Bechstein W et al. Survival of patients with initially unresectable colorectal liver metastases treated with FOLFOX/cetuximab or FOLFIRI/cetuximab in a multidisciplinary concept (CELIM study). Ann Oncol 2014; 25: 1018-1025.
181. Falcone A, Ricci S, Brunetti I et al. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol 2007; 25: 1670-1676.
182. Loupakis F, Cremolini C, Masi G et al. Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med 2014; 371: 1609-1618.
183. Douillard JY, Siena S, Cassidy J et al. Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer. Ann Oncol 2014; 25: 1346-1355.
184. Okines A, Puerto OD, Cunningham D et al. Surgery with curative-intent in patients treated with first-line chemotherapy plus bevacizumab for metastatic colorectal cancer First BEAT and the randomised phase-III NO16966 trial. Br J Cancer 2009; 101: 1033-1038.
185. Venook A, Niedzwiecki D, Lenz HJ et al. CALGB/SWOG 80405: Phase III trial of irinotecan/5-FU/leucovorin (FOLFIRI) or oxaliplatin/5-FU/leucovorin (mFOLFOX6) with bevacizumab (BV) or cetuximab (CET) for patients (pts) with KRAS wild-type (wt) untreated metastatic adenocarcinoma of the colon or rectum (MCRC). J Clin Oncol 2014; 32(15 Suppl): abstr LBA 3.
186. Piessevaux H, Buyse M, Schlichting M et al. Use of early tumor shrinkage to predict long-term outcome in metastatic colorectal cancer treated with cetuximab. J Clin Oncol 2013; 31: 3764-3775.
187. Mansmann UR, Laubender RP, Giessen CA et al. Validating the prognostic relevance of initial change in tumor size using a series of therapeutic regimens for patients with metastatic colorectal cancer (mCRC). J Clin Oncol 2012; 30 (Suppl 4): abstr 580.
188. Mansmann UR, Laubender RP, Sartorius U et al. Improved early prediction of individual prognosis for patients with mCRC: joint modeling of tumor shrinkage with volume data for PFS and OS. J Clin Oncol 2012; 30(Suppl 15): abstr 3603.
189. Piessevaux H, Buyse M, De Roock W et al. Radiological tumor size decrease at week 6 is a potent predictor of outcome in chemorefractory metastatic colorectal cancer treated with cetuximab (BOND trial). Ann Oncol 2009; 20: 1375-1382.
190. Cremolini C, Loupakis F, Antoniotti C et al. Early tumor shrinkage and depth of response predict long-term outcome in metastatic colorectal cancer patients treated with first-line chemotherapy plus bevacizumab: results from phase III TRIBE trial by the Gruppo Oncologico del Nord Ovest. Ann Oncol 2015; 26: 1188-1194.
191. Cremolini C, Loupakis F, Falcone A. FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med 2015; 372: 291-292.
192. Cremolini C, Loupakis F, Masi G et al. FOLFOXIRI/bevacizumab versus FOLFIRI/ bevacizumab as first-line treatment in unresectable metastatic colorectal cancer: results of phase III TRIBE trial by GONO Group. Ann Oncol 2014; 24(Suppl 4): abstr O-0026.
193. Stintzing S, Modest DP, Fischer von Weikersthal L et al. Independent radiological evaluation of objective response, early tumor shrinkage, and depth of response in FIRE-3 (AIO KRK-0306) in the final RAS evaluable population. Ann Oncol 2014; 25(Suppl 5): abstr LBA11.
194. Rivera F, Karthaus M, Hecht JR et al. First-line treatment with modified FOLFOX6 (mFOLFOX6) + panitumumab or bevacizumab in patients with RAS/BRAF wildtype (WT) metastatic colorectal carcinoma (mCRC). Ann Oncol 2015; 26(Suppl 4): abstr PD-014.
195. Bhutiani N, Akinwande O, Martin RC, 2nd. Efficacy and toxicity of hepatic intraarterial drug-eluting (irinotecan) bead (DEBIRI) therapy in irinotecan-refractory unresectable colorectal liver metastases. World J Surg 2015.
196. Liu DM, Thakor AS, Baerlocher M et al. A review of conventional and drug-eluting chemoembolization in the treatment of colorectal liver metastases: principles and proof. Future Oncol 2015; 11: 1421-1428.
197. Martin RC, 2nd, Scoggins CR, Schreeder M et al. Randomized controlled trial of irinotecan drug-eluting beads with simultaneous FOLFOX and bevacizumab for patients with unresectable colorectal liver-limited metastasis. Cancer 2015; 121: 3649-3658.
198. Ruers T, Punt C, Van Coevorden F et al. Radiofrequency ablation (RFA) combined with chemotherapy for unresectable colorectal liver metastases (CRC LM): long-term survival results of a randomized phase II study of the EORTC-NCRI CCSG-ALM Intergroup 40004 (CLOCC). J Clin Oncol 2015; 33 (15 Suppl): abstr 3501.
199. Tanis E, Nordlinger B, Mauer M et al. Local recurrence rates after radiofrequency ablation or resection of colorectal liver metastases. Analysis of the European Organisation for Research and Treatment of Cancer #40004 and #40983. Eur J Cancer 2014; 50: 912-919.
200. Ruers T, Punt C, Van Coevorden F et al. Radiofrequency ablation combined with systemic treatment versus systemic treatment alone in patients with nonresectable colorectal liver metastases: a randomized EORTC Intergroup phase II study (EORTC 40004). Ann Oncol 2012; 23: 2619-2626.
201. Evrard S, Poston G, Kissmeyer-Nielsen P et al. Combined ablation and resection (CARe) as an effective parenchymal sparing treatment for extensive colorectal liver metastases. PLoS One 2014; 9: e114404.
202. Lencioni R, Crocetti L, Cioni R et al. Response to radiofrequency ablation of pulmonary tumours: a prospective, intention-to-treat, multicentre clinical trial (the RAPTURE study). Lancet Oncol 2008; 9: 621-628.
203. Petre EN, Jia X, Thornton RH et al. Treatment of pulmonary colorectal metastases by radiofrequency ablation. Clin Colorectal Cancer 2013; 12: 37-44.
204. Kashima M, Yamakado K, Takaki H et al. Complications after 1000 lung radiofrequency ablation sessions in 420 patients: a single center's experiences. Am J Roentgenol 2011; 197: W576-W580.
205. Schlijper RC, Grutters JP, Houben R et al. What to choose as radical local treatment for lung metastases from colo-rectal cancer: surgery or radiofrequency ablation? Cancer Treat Rev 2014; 40: 60-67.
206. Ricke J, Mohnike K, Pech M et al. Local response and impact on survival after local ablation of liver metastases from colorectal carcinoma by computed tomography-guided high-dose-rate brachytherapy. Int J Radiat Oncol Biol Phys 2010; 78: 479-485.
207. Sterzing F, Brunner TB, Ernst I et al. Stereotactic body radiotherapy for liver tumors: principles and practical guidelines of the DEGRO Working Group on Stereotactic Radiotherapy. Strahlenther Onkol 2014; 190: 872-881.
208. Collettini F, Schnapauff D, Poellinger A et al. Percutaneous CT-guided high-dose brachytherapy (CT-HDRBT) ablation of primary and metastatic lung tumors in nonsurgical candidates. Rofo 2012; 184: 316-323.
209. Comito T, Cozzi L, Clerici E et al. Stereotactic Ablative Radiotherapy (SABR) in inoperable oligometastatic disease from colorectal cancer: a safe and effective approach. BMC Cancer 2014; 14: 619.
210. Filippi AR, Badellino S, Guarneri A et al. Outcomes of single fraction stereotactic ablative radiotherapy for lung metastases. Technol Cancer Res Treat 2014; 13: 37-45.
211. Tselis N, Ferentinos K, Kolotas C et al. Computed tomography-guided interstitial high-dose-rate brachytherapy in the local treatment of primary and secondary intrathoracic malignancies. J Thorac Oncol 2011; 6: 545-552.
212. Peters N, Wieners G, Pech M et al. CT-guided interstitial brachytherapy of primary and secondary lung malignancies: results of a prospective phase II trial. Strahlenther Onkol 2008; 184: 296-301.
213. Blomgren H, Lax I, Naslund I, Svanstrom R. Stereotactic high dose fraction radiation therapy of extracranial tumors using an accelerator. Clinical experience of the first thirty-one patients. Acta Oncol 1995; 34: 861-870.
214. Wada H, Takai Y, Nemoto K, Yamada S. Univariate analysis of factors correlated with tumor control probability of three-dimensional conformal hypofractionated high-dose radiotherapy for small pulmonary or hepatic tumors. Int J Radiat Oncol Biol Phys 2004; 58: 1114-1120.
215. Wulf J, Guckenberger M, Haedinger U et al. Stereotactic radiotherapy of primary liver cancer and hepatic metastases. Acta Oncol 2006; 45: 838-847.
216. Ambrosino G, Polistina F, Costantin G et al. Image-guided robotic stereotactic radiosurgery for unresectable liver metastases: preliminary results. Anticancer Res 2009; 29: 3381-3384.
217. Goodman KA, Wiegner EA, Maturen KE et al. Dose-escalation study of singlefraction stereotactic body radiotherapy for liver malignancies. Int J Radiat Oncol Biol Phys 2010; 78: 486-493.
218. Hoyer M, Roed H, Traberg Hansen A et al. Phase II study on stereotactic body radiotherapy of colorectal metastases. Acta Oncol 2006; 45: 823-830.
219. Lee MT, Kim JJ, Dinniwell R et al. Phase I study of individualized stereotactic body radiotherapy of liver metastases. J Clin Oncol 2009; 27: 1585-1591.
220. Mendez Romero A, Wunderink W, Hussain SM et al. Stereotactic body radiation therapy for primary and metastatic liver tumors: a single institution phase i-ii study. Acta Oncol 2006; 45: 831-837.
221. Rusthoven KE, Kavanagh BD, Cardenes H et al. Multi-institutional phase I/II trial of stereotactic body radiation therapy for liver metastases. J Clin Oncol 2009; 27: 1572-1578.
222. Scorsetti M, Arcangeli S, Tozzi A et al. Is stereotactic body radiation therapy an attractive option for unresectable liver metastases? A preliminary report from a phase 2 trial. Int J Radiat Oncol Biol Phys 2013; 86: 336-342.
223. Fumagalli I, Bibault JE, Dewas S et al. A single-institution study of stereotactic body radiotherapy for patients with unresectable visceral pulmonary or hepatic oligometastases. Radiat Oncol 2012; 7: 164.
224. Fiorentini G, Aliberti C, Tilli M et al. Intra-arterial infusion of irinotecan-loaded drug-eluting beads (DEBIRI) versus intravenous therapy (FOLFIRI) for hepatic metastases from colorectal cancer: final results of a phase III study. Anticancer Res 2012; 32: 1387-1395.
225. Hendlisz A, Van den Eynde M, Peeters M et al. Phase III trial comparing protracted intravenous fluorouracil infusion alone or with yttrium-90 resin microspheres radioembolization for liver-limited metastatic colorectal cancer refractory to standard chemotherapy. J Clin Oncol 2010; 28: 3687-3694.
226. van Hazel GA, Heinemann V, Sharma NK et al. SIRFLOX: randomized phase iii trial comparing first-line mFOLFOX6 (plus or minus bevacizumab) versus mFOLFOX6 (plus or minus bevacizumab) plus selective internal radiation therapy in patients with metastatic colorectal cancer. J Clin Oncol 2016; 34: 1723-1731.
227. Garlipp B, de Baere T, Damm R et al. Left-liver hypertrophy after therapeutic right-liver radioembolization is substantial but less than after portal vein embolization. Hepatology 2014; 59: 1864-1873.
228. Cao C, Yan TD, Black D, Morris DL. A systematic review and meta-analysis of cytoreductive surgery with perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis of colorectal origin. Ann Surg Oncol 2009; 16: 2152-2165.
229. Cotte E, Passot G, Mohamed F et al. Management of peritoneal carcinomatosis from colorectal cancer: current state of practice. Cancer J 2009; 15: 243-248.
230. Elias D, Lefevre JH, Chevalier J et al. Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. J Clin Oncol 2009; 27: 681-685.
231. Elias D, Mariani A, Cloutier AS et al. Modified selection criteria for complete cytoreductive surgery plus HIPEC based on peritoneal cancer index and small bowel involvement for peritoneal carcinomatosis of colorectal origin. Eur J Surg Oncol 2014; 40: 1467-1473.
232. Turaga K, Levine E, Barone R et al. Consensus guidelines from The American Society of Peritoneal Surface Malignancies on standardizing the delivery of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal cancer patients in the United States. Ann Surg Oncol 2014; 21: 1501-1505.
233. Prada-Villaverde A, Esquivel J, Lowy AM et al. The American Society of Peritoneal Surface Malignancies evaluation of HIPEC with mitomycin C versus oxaliplatin in 539 patients with colon cancer undergoing a complete cytoreductive surgery. J Surg Oncol 2014; 110: 779-785.
234. de Gramont A, Figer A, Seymour M et al. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 2000; 18: 2938-2947.
235. Douillard JY, Group VS. Irinotecan and high-dose fluorouracil/leucovorin for metastatic colorectal cancer. Oncology (Williston Park) 2000; 14: 51-55.
236. de Gramont A, Bosset JF, Milan C et al. Randomized trial comparing monthly low-dose leucovorin and fluorouracil bolus with bimonthly high-dose leucovorin and fluorouracil bolus plus continuous infusion for advanced colorectal cancer: a French intergroup study. J Clin Oncol 1997; 15: 808-815.
237. Meta-Analysis Group in CancerLevy E, Piedbois P et al. Toxicity of fluorouracil in patients with advanced colorectal cancer: effect of administration schedule and prognostic factors. J Clin Oncol 1998; 16: 3537-3541.
238. Van Cutsem E, Hoff PM, Harper P et al. Oral capecitabine vs intravenous 5- fluorouracil and leucovorin: integrated efficacy data and novel analyses from two large, randomised, phase III trials. Br J Cancer 2004; 90: 1190-1197.
239. Cassidy J, Clarke S, Diaz-Rubio E et al. Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol 2008; 26: 2006-2012.
240. Fuchs CS, Marshall J, Mitchell E et al. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C Study. J Clin Oncol 2007; 25: 4779-4786.
241. Kohne CH, De Greve J, Hartmann JT et al. Irinotecan combined with infusional 5- fluorouracil/folinic acid or capecitabine plus celecoxib or placebo in the first-line treatment of patients with metastatic colorectal cancer. EORTC study 40015. Ann Oncol 2008; 19: 920-926.
242. Schmiegel W, Reinacher-Schick A, Arnold D et al. Capecitabine/irinotecan or capecitabine/oxaliplatin in combination with bevacizumab is effective and safe as first-line therapy for metastatic colorectal cancer: a randomized phase II study of the AIO colorectal study group. Ann Oncol 2013; 24: 1580-1587.
243. Moosmann N, von Weikersthal LF, Vehling-Kaiser U et al. Cetuximab plus capecitabine and irinotecan compared with cetuximab plus capecitabine and oxaliplatin as first-line treatment for patients with metastatic colorectal cancer: AIO KRK-0104-a randomized trial of the German AIO CRC study group. J Clin Oncol 2011; 29: 1050-1058.
244. Hurwitz H, Fehrenbacher L, Novotny W et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004; 350: 2335-2342.
245. Saltz LB, Clarke S, Diaz-Rubio E et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 2008; 26: 2013-2019.
246. Souglakos J, Androulakis N, Syrigos K et al. FOLFOXIRI (folinic acid, 5- fluorouracil, oxaliplatin and irinotecan) vs FOLFIRI (folinic acid, 5-fluorouracil and irinotecan) as first-line treatment in metastatic colorectal cancer (MCC): a multicentre randomised phase III trial from the Hellenic Oncology Research Group (HORG). Br J Cancer 2006; 94: 798-805.
247. Cunningham D, Lang I, Marcuello E et al. Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol 2013; 14: 1077-1085.
248. Kabbinavar F, Irl C, Zurlo A, Hurwitz H. Bevacizumab improves the overall and progression-free survival of patients with metastatic colorectal cancer treated with 5-fluorouracil-based regimens irrespective of baseline risk. Oncology 2008; 75: 215-223.
249. Tebbutt NC, Wilson K, Gebski VJ et al. Capecitabine, bevacizumab, and mitomycin in first-line treatment of metastatic colorectal cancer: results of the Australasian Gastrointestinal Trials Group Randomized Phase III MAX Study. J Clin Oncol 2010; 28: 3191-3198.
250. Passardi A, Nanni O, Tassinari D et al. Effectiveness of bevacizumab added to standard chemotherapy in metastatic colorectal cancer: final results for first-line treatment from the ITACa randomized clinical trial. Ann Oncol 2015; 26: 1201-1207.
251. Souglakos J, Ziras N, Kakolyris S et al. Randomised phase-II trial of CAPIRI (capecitabine, irinotecan) plus bevacizumab vs FOLFIRI (folinic acid, 5- fluorouracil, irinotecan) plus bevacizumab as first-line treatment of patients with unresectable/metastatic colorectal cancer (mCRC). Br J Cancer 2012; 106: 453-459.
252. Yamazaki K, Nagase M, Tamagawa H et al. A randomized phase III trial of mFOLFOX6 plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment for metastatic colorectal cancer: West Japan Oncology Group study 4407G (WJOG4407G). J Clin Oncol 2014; 32(15 Suppl): abstr 3534.
253. Kozloff M, Yood MU, Berlin J et al. Clinical outcomes associated with bevacizumab-containing treatment of metastatic colorectal cancer: the BRiTE observational cohort study. Oncologist 2009; 14: 862-870.
254. Van Cutsem E, Rivera F, Berry S et al. Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann Oncol 2009; 20: 1842-1847.
255. European Medicines Agency. CHMP summary of opinion-erbitux. http://www. ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion/human/ 000558/WC500155463.pdf (6 January 2015, date last accessed).
256. European Medicines Agency. CHMP summary of opinion-vectibix. http://www. ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion/human/ 000741/WC500144827.pdf (6 January 2015, date last accessed).
257. Grothey A, Sargent D, Goldberg RM, Schmoll HJ. Survival of patients with advanced colorectal cancer improves with the availability of fluorouracilleucovorin, irinotecan, and oxaliplatin in the course of treatment. J Clin Oncol 2004; 22: 1209-1214.
258. Grothey A, Sargent D. Overall survival of patients with advanced colorectal cancer correlates with availability of fluorouracil, irinotecan, and oxaliplatin regardless of whether doublet or single-agent therapy is used first line. J Clin Oncol 2005; 23: 9441-9442.
259. Heinemann V, Modest DP, Fischer von Weikersthal L et al. Independent radiological evaluation of objective response, early tumor shrinkage, and depth of response in FIRE-3 (AIO KRK-0306). Ann Oncol 2014; 25(Suppl 2): abstr O-0030.
260. Lenz HJ, Niedzwiecki D, Innocenti F et al. CALGB/SWOG 80405: phase III trial of irinotecan/5-FU/leucovorin (FOLFIRI) or oxaliplatin/5-FU/leucovorin (mFOLFOX6) with bevacizumab (BV) or cetuximab (CET) for patients (pts) with expanded RAS analyses untreated metastatic adenocarcinoma of the colon or rectum (mCRC). Ann Oncol 2014; 25(Suppl 5): abstr 501O.
261. Maughan TS, James RD, Kerr DJ et al. Comparison of intermittent and continuous palliative chemotherapy for advanced colorectal cancer: a multicentre randomised trial. Lancet 2003; 361: 457-464.
262. Labianca R, Sobrero A, Isa L et al. Intermittent versus continuous chemotherapy in advanced colorectal cancer: a randomised 'GISCAD' trial. Ann Oncol 2011; 22: 1236-1242.
263. Tournigand C, Cervantes A, Figer A et al. OPTIMOX1: a randomized study of FOLFOX4 or FOLFOX7 with oxaliplatin in a stop-and-go fashion in advanced colorectal cancer-a GERCOR study. J Clin Oncol 2006; 24: 394-400.
264. Adams RA, Meade AM, Seymour MT et al. Intermittent versus continuous oxaliplatin and fluoropyrimidine combination chemotherapy for first-line treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet Oncol 2011; 12: 642-653.
265. Chibaudel B, Maindrault-Goebel F, Lledo G et al. Can chemotherapy be discontinued in unresectable metastatic colorectal cancer? The GERCOR OPTIMOX2 Study. J Clin Oncol 2009; 27: 5727-5733.
266. Tournigand C, Chibaudel B, Samson B et al. Bevacizumab with or without erlotinib as maintenance therapy in patients with metastatic colorectal cancer (GERCOR DREAM; OPTIMOX3): a randomised, open-label, phase 3 trial. Lancet Oncol 2015; 16: 1493-1505.
267. Diaz-Rubio E, Gomez-Espana A, Massuti B et al. First-line XELOX plus bevacizumab followed by XELOX plus bevacizumab or single-agent bevacizumab as maintenance therapy in patients with metastatic colorectal cancer: the phase III MACRO TTD study. Oncologist 2012; 17: 15-25.
268. Hegewisch-Becker S, Graeven U, Lerchenmuller CA et al. Maintenance strategies after first-line oxaliplatin plus fluoropyrimidine plus bevacizumab for patients with metastatic colorectal cancer (AIO 0207): a randomised, non-inferiority, openlabel, phase 3 trial. Lancet Oncol 2015; 16: 1355-1369.
269. Koeberle D, Betticher DC, von Moos R et al. Bevacizumab continuation versus no continuation after first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer: a randomized phase III non-inferiority trial (SAKK 41/06). Ann Oncol 2015; 26: 709-714.
270. Simkens LH, van Tinteren H, May A et al. Maintenance treatment with capecitabine and bevacizumab in metastatic colorectal cancer (CAIRO3): a phase 3 randomised controlled trial of the Dutch Colorectal Cancer Group. Lancet 2015; 385: 1843-1852.
271. Wasan H, Meade AM, Adams R et al. Intermittent chemotherapy plus either intermittent or continuous cetuximab for first-line treatment of patients with KRAS wild-type advanced colorectal cancer (COIN-B): a randomised phase 2 trial. Lancet Oncol 2014; 15: 631-639.
272. Johnsson A, Hagman H, Frodin JE et al. A randomized phase III trial on maintenance treatment with bevacizumab alone or in combination with erlotinib after chemotherapy and bevacizumab in metastatic colorectal cancer: the Nordic ACT Trial. Ann Oncol 2013; 24: 2335-2341.
273. Stein A, Atanackovic D, Hildebrandt B et al. Upfront FOLFOXIRI+bevacizumab followed by fluoropyrimidin and bevacizumab maintenance in patients with molecularly unselected metastatic colorectal cancer. Br J Cancer 2015; 113: 872-877.
274. Garcia Alfonso P, Benavides M, Sanchez Ruiz A et al. Phase II study of first-line mFOLFOX plus cetuximab (C) for 8 cycles followed by mFOLFOX plus C or single agent (S/A) C as maintenance therapy in patients (P) with metastatic colorectal cancer (mCRC): The MACRO-2 trial (Spanish Cooperative Group for the Treatment of Digestive Tumors [TTD]). Ann Oncol 2014; 25(Suppl 4): abstr 499O.
275. Cunningham D, Pyrhonen S, James RD et al. Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer. Lancet 1998; 352: 1413-1418.
276. Rougier P, Lepille D, Bennouna J et al. Antitumour activity of three second-line treatment combinations in patients with metastatic colorectal cancer after optimal 5-FU regimen failure: a randomised, multicentre phase II study. Ann Oncol 2002; 13: 1558-1567.
277. Rougier P, Van Cutsem E, Bajetta E et al. Randomised trial of irinotecan versus fluorouracil by continuous infusion after fluorouracil failure in patients with metastatic colorectal cancer. Lancet 1998; 352: 1407-1412.
278. Haller DG, Rothenberg ML, Wong AO et al. Oxaliplatin plus irinotecan compared with irinotecan alone as second-line treatment after single-agent fluoropyrimidine therapy for metastatic colorectal carcinoma. J Clin Oncol 2008; 26: 4544-4550.
279. Koopman M, Antonini NF, Douma J et al. Sequential versus combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (CAIRO): a phase III randomised controlled trial. Lancet 2007; 370: 135-142.
280. Seymour MT, Maughan TS, Ledermann JA et al. Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial. Lancet 2007; 370: 143-152.
281. Tournigand C, Andre T, Achille E et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 2004; 22: 229-237.
282. Giantonio BJ, Catalano PJ, Meropol NJ et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 2007; 25: 1539-1544.
283. Bennouna J, Sastre J, Arnold D et al. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol 2013; 14: 29-37.
284. Beretta GD, Petrelli F, Stinco S et al. FOLFIRI + bevacizumab as second-line therapy for metastatic colorectal cancer pretreated with oxaliplatin: a pooled analysis of published trials. Med Oncol 2013; 30: 486.
285. Lievre A, Samalin E, Mitry E et al. Bevacizumab plus FOLFIRI or FOLFOX in chemotherapy-refractory patients with metastatic colorectal cancer: a retrospective study. BMC Cancer 2009; 9: 347.
286. Masi G, Salvatore L, Boni L et al. Continuation or reintroduction of bevacizumab beyond progression to first-line therapy in metastatic colorectal cancer: final results of the randomized BEBYP trial. Ann Oncol 2015; 26: 724-730.
287. Van Cutsem E, Tabernero J, Lakomy R et al. Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatinbased regimen. J Clin Oncol 2012; 30: 3499-3506.
288. Tabernero J, Van Cutsem E, Lakomy R et al. Aflibercept versus placebo in combination with fluorouracil, leucovorin and irinotecan in the treatment of previously treated metastatic colorectal cancer: prespecified subgroup analyses from the VELOUR trial. Eur J Cancer 2014; 50: 320-331.
289. Tabernero J, Yoshino T, Cohn AL et al. Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study. Lancet Oncol 2015; 16: 499-508.
290. Sobrero AF, Maurel J, Fehrenbacher L et al. EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol 2008; 26: 2311-2319.
291. Cascinu S, Lonardi S, Rosati G et al. A phase III multicenter trial comparing two different sequences of second/third line therapy (cetuximab/irinotecan followed by FOLFOX versus FOLFOX followed by cetuximab/irinotecan) in metastatic KRAS wt colorectal cancer (mCC) patients, refractory to FOLFIRI/Bevacizumab. Eur J Cancer 2015; 51(Suppl S3): abstr 2006.
292. Hecht JR, Cohn A, Dakhil S et al. SPIRITT: a randomized, multicenter, phase II study of panitumumab with FOLFIRI and bevacizumab with FOLFIRI as secondline treatment in patients with unresectable wild type KRAS metastatic colorectal cancer. Clin Colorectal Cancer 2015; 14: 72-80.
293. Cunningham D, Humblet Y, Siena S et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004; 351: 337-345.
294. Geva R, Vecchione L, Tejpar S et al. Bevacizumab plus chemotherapy as salvage treatment in chemorefractory patients with metastatic colorectal cancer. Onco Targets Ther 2013; 6: 53-58.
295. Hecht JR, Patnaik A, Berlin J et al. Panitumumab monotherapy in patients with previously treated metastatic colorectal cancer. Cancer 2007; 110: 980-988.
296. Price TJ, Peeters M, Kim TW et al. Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 study. Lancet Oncol 2014; 15: 569-579.
297. Grothey A, Van Cutsem E, Sobrero A et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013; 381: 303-312.
298. Li J, Qin S, Xu R et al. Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2015; 16: 619-629.
299. Mayer RJ, Van Cutsem E, Falcone A et al. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med 2015; 372: 1909-1919.
300. Yoshino T, Mizunuma N, Yamazaki K et al. TAS-102 monotherapy for pretreated metastatic colorectal cancer: a double-blind, randomised, placebo-controlled phase 2 trial. Lancet Oncol 2012; 13: 993-1001.
301. Papamichael D, Audisio RA, Glimelius B et al. Treatment of colorectal cancer in older patients: International Society of Geriatric Oncology (SIOG) consensus recommendations 2013. Ann Oncol 2015; 26: 463-476.
302. Gruenberger B, Tamandl D, Schueller J et al. Bevacizumab, capecitabine, and oxaliplatin as neoadjuvant therapy for patients with potentially curable metastatic colorectal cancer. J Clin Oncol 2008; 26: 1830-1835.
303. Garufi C, Torsello A, Tumolo S et al. Cetuximab plus chronomodulated irinotecan, 5-fluorouracil, leucovorin and oxaliplatin as neoadjuvant chemotherapy in colorectal liver metastases: POCHER trial. Br J Cancer 2010; 103: 1542-1547.
304. Wong R, Cunningham D, Barbachano Y et al. A multicentre study of capecitabine, oxaliplatin plus bevacizumab as perioperative treatment of patients with poor-risk colorectal liver-only metastases not selected for upfront resection. Ann Oncol 2011; 22: 2042-2048.