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The treatment paradigm of right-sided metastatic colon cancer: harboring BRAF mutation makes the difference

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

BRAF mutations represent the main negative prognostic factor for metastatic colorectal cancer and a supposed negative predictive factor of response to standard chemotherapy. We have explored survival difference in right-sided colon cancer (RCC) patients according to BRAF mutations, with the aim to identify any predictive factors of response to targeted-based therapy.

Methods

A retrospective study of RCC patients, with BRAF known mutation status, treated with chemotherapy (CT) from October 2008 to June 2019 in 5 Italian centers, was conducted.

Results

We identified 207 advanced RCC patients: 20.3% BRAF mutant and 79.7% BRAF wild type (wt). BRAF-mutant cancers were more likely to be pT4 (50.0% v 25.7%, p = 0.016), undifferentiated (71.4% v 44.0%, p = 0.004), KRAS wt (90.5% v 38.2%, p < 0.001), and MSI-H (41.7% v 16.2%, p = 0.019) tumors, with synchronous (52.4% v 31.5%, p = 0.018) and peritoneal metastases (38.1% v 22.4%, p = 0.003). Median overall survival (OS) was 16 v 27 months in BRAF mutant and BRAF wt (P = 0.020). In first-line setting, BRAF-mutant showed a 2ys OS of 80% in clinical trials, 32% in anti-VEGF, 14% in epidermial growth factor receptor (EGFR), and 0% in chemotherapy alone regimens (P = 0.009). BRAF-mutant patients demonstrated worse survival, regardless of targeted therapy administered. However, survival difference was statistically significant in the anti-EGFR-treated subgroup (16 v 28 months, P = 0.005 in BRAF mutant v BRAF wt, respectively).

Conclusions

Our study demonstrated that BRAF status makes the difference in treatment’s outcome. Therefore, the anti-EGFR should not be excluded in all advanced RCC but considered on a case-by-case basis.

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References

  1. Stewart BW, Wild CP. World cancer report 2014. World Heal Organ. 2014.

  2. Petrelli F, Tomasello G, Borgonovo K, Ghidini M, Turati L, Dallera P, Passalacqua R, Sgroi G, Barni S (2017) Prognostic survival associated with left-sided vs right-sided colon cancer a systematic review and meta-analysis. JAMA Oncol. 3:211–219. https://doi.org/10.1001/jamaoncol.2016.4227

    Article  PubMed  Google Scholar 

  3. Karim S, Brennan K, Nanji S, Berry SR, Booth CM (2017) Association between prognosis and tumor laterality in early-stage colon cancer. JAMA Oncol 3:1386–1392. https://doi.org/10.1001/jamaoncol.2017.1016

    Article  PubMed  PubMed Central  Google Scholar 

  4. Beale AL, Penney MD, Allison MC (2005) The prevalence of iron deficiency among patients presenting with colorectal cancer. Color Dis 7:398–402. https://doi.org/10.1111/j.1463-1318.2005.00789.x

    Article  CAS  Google Scholar 

  5. Cheng L, Eng C, Nieman LZ, Kapadia AS, Du XL (2011) Trends in colorectal cancer incidence by anatomic site and disease stage in the United States from 1976 to 2005. Am J Clin Oncol Cancer Clin Trials 34:573–580. https://doi.org/10.1097/COC.0b013e3181fe41ed

    Article  Google Scholar 

  6. Markowitz SD, Bertagnolli MM (2009) Molecular origins of cancer: molecular basis of colorectal cancer. N Engl J Med 361:2449–2460. https://doi.org/10.1056/NEJMra0804588

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Tran B, Kopetz S, Tie J, Gibbs P, Jiang ZQ, Lieu CH, Agarwal A, Maru DM, Sieber O, Desai J (2011) Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer. Cancer. 117:4623–4632. https://doi.org/10.1002/cncr.26086

    Article  CAS  PubMed  Google Scholar 

  8. Bufill JA (1990) Colorectal cancer: evidence for distinct genetic categories based on proximal or distal tumor location. Ann Intern Med 113:779. https://doi.org/10.7326/0003-4819-113-10-779

    Article  CAS  PubMed  Google Scholar 

  9. Iacopetta B (2002) Are there two sides to colorectal cancer? Int J Cancer 101:403–408. https://doi.org/10.1002/ijc.10635

    Article  CAS  PubMed  Google Scholar 

  10. Distler P, Holt PR (1997) Are right- and left-sided colon neoplasms distinct tumors? Dig Dis 15:302–311. https://doi.org/10.1159/000171605

    Article  CAS  PubMed  Google Scholar 

  11. Nosho K, Irahara N, Shima K, Kure S, Kirkner GJ, Schernhammer ES, Hazra A, Hunter DJ, Quackenbush J, Spiegelman D, Giovannucci EL, Fuchs CS, Ogino S (2008) Comprehensive biostatistical analysis of CpG island methylator phenotype in colorectal cancer using a large population-based sample. PLoS One 3:e3698. https://doi.org/10.1371/journal.pone.0003698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Samowitz WS, Albertsen H, Herrick J et al (2005) Evaluation of a large, population-based sample supports a CpG island methylator phenotype in colon cancer. Gastroenterology

  13. Meguid RA, Slidell MB, Wolfgang CL, Chang DC, Ahuja N (2008) Is there a difference in survival between right- versus left-sided colon cancers? Ann Surg Oncol 15:2388–2394. https://doi.org/10.1245/s10434-008-0015-y

    Article  PubMed  PubMed Central  Google Scholar 

  14. Weiss JM, Pfau PR, O’Connor ES et al (2011) Mortality by stage for right- versus left-sided colon cancer: analysis of surveillance, epidemiology, and end results-Medicare data. J Clin Oncol 29:4401–4409. https://doi.org/10.1200/JCO.2011.36.4414

    Article  PubMed  PubMed Central  Google Scholar 

  15. Warschkow R, Sulz MC, Marti L, Tarantino I, Schmied BM, Cerny T, Güller U (2016) Better survival in right-sided versus left-sided stage I - III colon cancer patients. BMC Cancer 16:554. https://doi.org/10.1186/s12885-016-2412-0

    Article  PubMed  PubMed Central  Google Scholar 

  16. Schrag D, Weng S, Brooks G, Meyerhardt JA, Venook AP (2016) The relationship between primary tumor sidedness and prognosis in colorectal cancer. J Clin Oncol 34:3505. https://doi.org/10.1200/jco.2016.34.15_suppl.3505

    Article  Google Scholar 

  17. Kennecke HF, Speers C, Davies JM, Cheung WY, Lee-Ying RM (2016) Differences in relapse-free survival (RFS) and survival after relapse (SAR) in right (R) versus left (L) stage I-III colon cancer (CCa). J Clin Oncol 34:3578. https://doi.org/10.1200/jco.2016.34.15_suppl.3578

    Article  Google Scholar 

  18. Tejpar S, Stintzing S, Ciardiello F et al (2017) Prognostic and predictive relevance of primary tumor location in patients with ras wild-type metastatic colorectal cancer retrospective analyses of the CRYSTAL and FIRE-3 trials. In: JAMA Oncology. https://doi.org/10.1001/jamaoncol.2016.3797

    Chapter  Google Scholar 

  19. Venook AP, Niedzwiecki D, Innocenti F, Fruth B, Greene C, O'Neil BH, Shaw JE, Atkins JN, Horvath LE, Polite BN, Meyerhardt JA, O'Reilly EM, Goldberg RM, Hochster HS, Blanke CD, Schilsky RL, Mayer RJ, Bertagnolli MM, Lenz HJ (2016) Impact of primary (1o) tumor location on overall survival (OS) and progression-free survival (PFS) in patients (pts) with metastatic colorectal cancer (mCRC): analysis of CALGB/SWOG 80405 (Alliance). J Clin Oncol 34:3504. https://doi.org/10.1200/jco.2016.34.15_suppl.3504

    Article  Google Scholar 

  20. Lee GH, Malietzis G, Askari A, Bernardo D, Al-Hassi HO, Clark SK (2015) Is right-sided colon cancer different to left-sided colorectal cancer? - a systematic review. Eur J Surg Oncol 41:300–308. https://doi.org/10.1016/j.ejso.2014.11.001

    Article  CAS  PubMed  Google Scholar 

  21. Benedix F, Schmidt U, Mroczkowski P, Gastinger I, Lippert H, Kube R (2011) Colon carcinoma - classification into right and left sided cancer or according to colonic subsite? - analysis of 29 568 patients. Eur J Surg Oncol 37:134–139. https://doi.org/10.1016/j.ejso.2010.12.004

    Article  CAS  PubMed  Google Scholar 

  22. Loupakis F, Yang D, Yau L, Feng S, Cremolini C, Zhang W, Maus MKH, Antoniotti C, Langer C, Scherer SJ, Müller T, Hurwitz HI, Saltz L, Falcone A, Lenz HJ (2015) Primary tumor location as a prognostic factor in metastatic colorectal cancer. J Natl Cancer Inst 107. https://doi.org/10.1093/jnci/dju427

  23. Lee HM, Morris V, Napolitano S, Kopetz S (2019) Evolving strategies for the management of BRAF-mutant metastatic colorectal cancer. Oncol (United States)

  24. Taieb J, Lapeyre-Prost A, Laurent Puig P, Zaanan A (2019) Exploring the best treatment options for BRAF-mutant metastatic colon cancer. Br J Cancer 121:434–442. https://doi.org/10.1038/s41416-019-0526-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Morris V, Overman MJ, Jiang ZQ, Garrett C, Agarwal S, Eng C, Kee B, Fogelman D, Dasari A, Wolff R, Maru D, Kopetz S (2014) Progression-free survival remains poor over sequential lines of systemic therapy in patients with BRAF-mutated colorectal cancer. Clin Colorectal Cancer 13:164–171. https://doi.org/10.1016/j.clcc.2014.06.001

    Article  PubMed  PubMed Central  Google Scholar 

  26. Cremolini C, Loupakis F, Antoniotti C, Lupi C, Sensi E, Lonardi S, Mezi S, Tomasello G, Ronzoni M, Zaniboni A, Tonini G, Carlomagno C, Allegrini G, Chiara S, D'Amico M, Granetto C, Cazzaniga M, Boni L, Fontanini G, Falcone A (2015) 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 16:1306–1315. https://doi.org/10.1016/S1470-2045(15)00122-9

    Article  CAS  PubMed  Google Scholar 

  27. Ledys F, Derangère V, Réda M, Guion JF, Milliex R, Roux V, Limagne E, Arnould L, Bengrine L, Ghiringhelli F, Rébé C (2019) Anti-MEK and anti-EGFR mAbs in RAS-mutant metastatic colorectal cancer: case series and rationale. Adv Ther 36:1480–1484. https://doi.org/10.1007/s12325-019-00949-y

    Article  CAS  PubMed  Google Scholar 

  28. Bendell JC, Atreya CE, André T, Tabernero J, Gordon MS, Bernards R, van Cutsem E, Tejpar S, Sidhu R, Go WY, Allred A, Motwani M, Suttle BB, Wu Y, Hoos A, Orford KW, Corcoran RB, Schellens JHM (2014) Efficacy and tolerability in an open-label phase I/II study of MEK inhibitor trametinib (T), BRAF inhibitor dabrafenib (D), and anti-EGFR antibody panitumumab (P) in combination in patients (pts) with BRAF V600E mutated colorectal cancer (CRC). J Clin Oncol 32:3515. https://doi.org/10.1200/jco.2014.32.15_suppl.3515

    Article  Google Scholar 

  29. Corcoran RB, Atreya CE, Falchook GS et al (2015) Combined BRAF and MEK inhibition with dabrafenib and trametinib in BRAF V600-mutant colorectal cancer. In: Journal of Clinical Oncology. https://doi.org/10.1200/JCO.2015.63.2471

    Chapter  Google Scholar 

  30. Kopetz S, Grothey A, Yaeger R, van Cutsem E, Desai J, Yoshino T, Wasan H, Ciardiello F, Loupakis F, Hong YS, Steeghs N, Guren TK, Arkenau HT, Garcia-Alfonso P, Pfeiffer P, Orlov S, Lonardi S, Elez E, Kim TW, Schellens JHM, Guo C, Krishnan A, Dekervel J, Morris V, Calvo Ferrandiz A, Tarpgaard LS, Braun M, Gollerkeri A, Keir C, Maharry K, Pickard M, Christy-Bittel J, Anderson L, Sandor V, Tabernero J (2019) Encorafenib, binimetinib, and cetuximab in BRAF V600E–mutated colorectal cancer. N Engl J Med 381:1632–1643. https://doi.org/10.1056/NEJMoa1908075

    Article  CAS  PubMed  Google Scholar 

  31. Brulé SY, Jonker DJ, Karapetis CS et al (2015) Location of colon cancer (right-sided versus left-sided) as a prognostic factor and a predictor of benefit from cetuximab in NCIC CO.17. Eur J Cancer. https://doi.org/10.1016/j.ejca.2015.03.015

  32. Boeckx N, Janssens K, Van Camp G et al (2018) The predictive value of primary tumor location in patients with metastatic colorectal cancer: a systematic review. Crit Rev Oncol Hematol 121:1–10. https://doi.org/10.1016/j.critrevonc.2017.11.003

    Article  PubMed  Google Scholar 

  33. Benson AB, Venook AP, Al-Hawary MM et al (2018) NCCN guidelines insights: colon cancer, version 2. J Natl Compr Cancer Netw. https://doi.org/10.6004/jnccn.2018.0021

  34. Loupakis F, Intini R, Cremolini C, Orlandi A, Sartore-Bianchi A, Pietrantonio F, Pella N, Spallanzani A, Dell’Aquila E, Scartozzi M, de Luca E, Rimassa L, Formica V, Leone F, Calvetti L, Aprile G, Antonuzzo L, Urbano F, Prenen H, Negri F, di Donato S, Buonandi P, Tomasello G, Avallone A, Zustovich F, Moretto R, Antoniotti C, Salvatore L, Calegari MA, Siena S, Morano F, Ongaro E, Cascinu S, Santini D, Ziranu P, Schirripa M, Buggin F, Prete AA, Depetris I, Biason P, Lonardi S, Zagonel V, Fassan M, di Maio M (2019) A validated prognostic classifier for V600EBRAF-mutated metastatic colorectal cancer: the ‘BRAF BeCool’ study. Eur J Cancer 118:121–130. https://doi.org/10.1016/j.ejca.2019.06.008

    Article  CAS  PubMed  Google Scholar 

  35. Gowarty JL, Durham C, Wong L, Chen W (2019) Survival outcomes of left-sided versus right-sided colon cancer. J Clin Oncol 37:502. https://doi.org/10.1200/jco.2019.37.4_suppl.502

    Article  Google Scholar 

  36. Akgül Ö, Çetinkaya E, Ersöz Ş, Tez M (2014) Role of surgery in colorectal cancer liver metastases. World J Gastroenterol 20:6113–6122. https://doi.org/10.3748/wjg.v20.i20.6113

    Article  PubMed  PubMed Central  Google Scholar 

  37. Stintzing S, Miller-Phillips L, Modest DP, Fischer von Weikersthal L, Decker T, Kiani A, Vehling-Kaiser U, al-Batran SE, Heintges T, Kahl C, Seipelt G, Kullmann F, Stauch M, Scheithauer W, Held S, Moehler M, Jagenburg A, Kirchner T, Jung A, Heinemann V (2017) Impact of BRAF and RAS mutations on first-line efficacy of FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab: analysis of the FIRE-3 (AIO KRK-0306) study. Eur J Cancer 79:50–60. https://doi.org/10.1016/j.ejca.2017.03.023

    Article  CAS  PubMed  Google Scholar 

  38. Modest DP, Ricard I, Heinemann V, Hegewisch-Becker S, Schmiegel W, Porschen R, Stintzing S, Graeven U, Arnold D, von Weikersthal LF, Giessen-Jung C, Stahler A, Schmoll HJ, Jung A, Kirchner T, Tannapfel A, Reinacher-Schick A (2016) Outcome according to KRAS-, NRAS- and BRAF-mutation as well as KRAS mutation variants: pooled analysis of five randomized trials in metastatic colorectal cancer by the AIO colorectal cancer study group. Ann Oncol 27:1746–1753. https://doi.org/10.1093/annonc/mdw261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Boeckx N, Koukakis R, de Beeck KO et al (2017) Primary tumor sidedness has an impact on prognosis and treatment outcome in metastatic colorectal cancer: results from two randomized first-line panitumumab studies. Ann Oncol 28:1862–1868. https://doi.org/10.1093/annonc/mdx119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Boeckx N, Koukakis R, Op de Beeck K (2018) et al, Effect of primary tumor location on second- or later-line treatment outcomes in patients with RAS wild-type metastatic colorectal cancer and all treatment lines in patients with RAS mutations in four randomized panitumumab studies. Clin Colorectal Cancer. https://doi.org/10.1016/j.clcc.2018.03.005

  41. Cremolini C, Antoniotti C, Lonardi S et al (2018) Primary tumor sidedness and benefit from FOLFOXIRI plus bevacizumab as initial therapy for metastatic colorectal cancer. Retrospective analysis of the TRIBE trial by GONO. Ann Oncol. https://doi.org/10.1093/annonc/mdy140

  42. Mik M, Berut M, Dziki L, Trzcinski R, Dziki A (2017) Right-and left-sided colon cancer-clinical and pathological differences of the disease entity in one organ. Arch Med Sci 1:157–162. https://doi.org/10.5114/aoms.2016.58596

    Article  Google Scholar 

  43. Guan X, Chen W, Liu Z et al (2016) Whether regional lymph nodes evaluation should be equally required for both right and left colon cancer. Oncotarget. https://doi.org/10.18632/oncotarget.11007

  44. Bilimoria KY, Palis B, Stewart AK, Bentrem DJ, Freel AC, Sigurdson ER, Talamonti MS, Ko CY (2008) Impact of tumor location on nodal evaluation for colon cancer. Dis Colon Rectum 51:154–161. https://doi.org/10.1007/s10350-007-9114-2

    Article  PubMed  Google Scholar 

  45. Shen H, Yang J, Huang Q, Jiang MJ, Tan YN, Fu JF, Zhu LZ, Fang XF, Yuan Y (2015) Different treatment strategies and molecular features between right-sided and left-sided colon cancers. World J Gastroenterol 21:6470–6478. https://doi.org/10.3748/wjg.v21.i21.6470

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Sargent DJ, Marsoni S, Monges G, Thibodeau SN, Labianca R, Hamilton SR, French AJ, Kabat B, Foster NR, Torri V, Ribic C, Grothey A, Moore M, Zaniboni A, Seitz JF, Sinicrope F, Gallinger S (2010) Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol 28:3219–3226. https://doi.org/10.1200/JCO.2009.27.1825

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Llosa NJ, Cruise M, Tam A, Wicks EC, Hechenbleikner EM, Taube JM, Blosser RL, Fan H, Wang H, Luber BS, Zhang M, Papadopoulos N, Kinzler KW, Vogelstein B, Sears CL, Anders RA, Pardoll DM, Housseau F (2015) The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints. Cancer Discov 5:43–51. https://doi.org/10.1158/2159-8290.CD-14-0863

    Article  CAS  PubMed  Google Scholar 

  48. Lukish JR, Muro K, DeNobile J, Katz R, Williams J, Cruess DF, Drucker W, Kirsch I, Hamilton SR (1998) Prognostic significance of DNA replication errors in young patients with colorectal cancer. Ann Surg 227:51–56. https://doi.org/10.1097/00000658-199801000-00008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Benatti P, Gafà R, Barana D et al (2005) Microsatellite instability and colorectal cancer prognosis. Clin Cancer Res 11:8332–8340. https://doi.org/10.1158/1078-0432.CCR-05-1030

    Article  CAS  PubMed  Google Scholar 

  50. Merok MA, Ahlquist T, Røyrvik EC, Tufteland KF, Hektoen M, Sjo OH, Mala T, Svindland A, Lothe RA, Nesbakken A (2013) Microsatellite instability has a positive prognostic impact on stage II colorectal cancer after complete resection: results from a large, consecutive Norwegian series. Ann Oncol 24:1274–1282. https://doi.org/10.1093/annonc/mds614

    Article  CAS  PubMed  Google Scholar 

  51. Samowitz WS, Coleman LW, Leppert M et al (2001) Microsatellite instability in sporadic colon cancer is associated with an improved prognosis at the population level. Cancer Epidemiol Biomarkers Prev

  52. Popat S, Hubner R, Houlston RS (2005) Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol 23:609–618. https://doi.org/10.1200/JCO.2005.01.086

    Article  CAS  PubMed  Google Scholar 

  53. Ross PJ, Srikandarajah K, de Naurois J (2018) Right versus left-sided colon cancer: is it time to consider these as different diseases? AIMS Med Sci. https://doi.org/10.3934/medsci.2018.3.303

  54. Karapetis CS, Khambata-Ford S, Jonker DJ, O'Callaghan CJ, Tu D, Tebbutt NC, Simes RJ, Chalchal H, Shapiro JD, Robitaille S, Price TJ, Shepherd L, Au HJ, Langer C, Moore MJ, Zalcberg JR (2008) K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 359:1757–1765. https://doi.org/10.1056/NEJMoa0804385

    Article  CAS  PubMed  Google Scholar 

  55. Allegra CJ, Jessup JM, Somerfield MR, Hamilton SR, Hammond EH, Hayes DF, McAllister PK, Morton RF, Schilsky RL (2009) American society of clinical oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy. J Clin Oncol 27:2091–2096. https://doi.org/10.1200/JCO.2009.21.9170

    Article  PubMed  Google Scholar 

  56. Sartore-Bianchi A, Di Nicolantonio F, Nichelatti M et al (2009) Multi-determinants analysis of molecular alterations for predicting clinical benefit to EGFR-targeted monoclonal antibodies in colorectal cancer. PLoS One 4:e7287. https://doi.org/10.1371/journal.pone.0007287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Laurent-Puig P, Cayre A, Manceau G, Buc E, Bachet JB, Lecomte T, Rougier P, Lievre A, Landi B, Boige V, Ducreux M, Ychou M, Bibeau F, Bouché O, Reid J, Stone S, Penault-Llorca F (2009) Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer. J Clin Oncol 27:5924–5930. https://doi.org/10.1200/JCO.2008.21.6796

    Article  CAS  PubMed  Google Scholar 

  58. Roepman P, Schlicker A, Tabernero J, Majewski I, Tian S, Moreno V, Snel MH, Chresta CM, Rosenberg R, Nitsche U, Macarulla T, Capella G, Salazar R, Orphanides G, Wessels LFA, Bernards R, Simon IM (2013) Colorectal cancer intrinsic subtypes predict chemotherapy benefit, deficient mismatch repair and epithelial-to-mesenchymal transition. Int J Cancer 134:552–562. https://doi.org/10.1002/ijc.28387

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Perez Villamil B, Romera Lopez A, Hernandez Prieto S, Lopez Campos G, Calles A, Lopez Asenjo JA, Sanz Ortega J, Fernandez Perez C, Sastre J, Alfonso R, Caldes T, Martin Sanchez F, Diaz Rubio E (2012) Colon cancer molecular subtypes identified by expression profiling and associated to stroma, mucinous type and different clinical behavior. BMC Cancer 12. https://doi.org/10.1186/1471-2407-12-260

  60. Sadanandam A, Lyssiotis CA, Homicsko K, Collisson EA, Gibb WJ, Wullschleger S, Ostos LCG, Lannon WA, Grotzinger C, del Rio M, Lhermitte B, Olshen AB, Wiedenmann B, Cantley LC, Gray JW, Hanahan D (2013) A colorectal cancer classification system that associates cellular phenotype and responses to therapy. Nat Med 19:619–625. https://doi.org/10.1038/nm.3175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Clinical and Molecular Medicine, Oncology Unit, Sant’ Andrea Hospital, University “La Sapienza”, Rome, Italy

    Michela Roberto, Paolo Marchetti, Giulia Arrivi, Francesca Romana Di Pietro, Andrea Botticelli & Federica Mazzuca

  2. Department of Radiology, Oncology and Pathology, Policlinico Umberto I, Sapienza University, Rome, Italy

    Paolo Marchetti, Federica Urbano, Maria Letizia Calandrella & Andrea Botticelli

  3. Department of Oncology and Hematology, Division of Oncology, University Hospital of Modena, Modena, Italy

    Stefano Cascinu, Fabio Gelsomino, Francesco Caputo & Krisida Cerma

  4. Oncology Unit, Oncology Department, ASST of Cremona, Cremona, Italy

    Michele Ghidini, Margherita Ratti & Claudio Pizzo

  5. Department of Biotechnological and Applied Clinical Sciences, Medical Oncology, St. Salvatore Hospital, University of L’Aquila, L’Aquila, Italy

    Corrado Ficorella, Alessandro Parisi & Alessio Cortellini

  6. Oncologia Medica, Policlinico Universitario “Campus Bio-Medico di Roma”, Rome, Italy

    Emanuela Dell’Aquila, Alessandro Minelli & Claudia Fulgenzi

  7. Department of Clinical and Molecular Medicine, UOC Anatomia Patologica, Sant’ Andrea Hospital, University “La Sapienza”, Rome, Italy

    Andrea Montori & Emanuela Pilozzi

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Correspondence to Paolo Marchetti.

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Roberto, M., Marchetti, P., Arrivi, G. et al. The treatment paradigm of right-sided metastatic colon cancer: harboring BRAF mutation makes the difference. Int J Colorectal Dis 35, 1513–1527 (2020). https://doi.org/10.1007/s00384-020-03589-9

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