Study Comparing Pathological Responses Observed on Colorectal Cancer Metastases Resected After Preoperative Bevacizumab With FOLFOX or FOLFIRI.

Summary

The study is designed to analyze the pathological tumor response on resected colorectal cancer metastases after preoperative treatment with bevacizumab combined with FOLFOX or FOLFIRI regimen in a prospective cohort and to correlate this response with patient's outcome.

Timeline

Start

2013-05

Primary completion

2019-05

Completion

2019-05

Publications

• Background Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009 Jul-Aug;59(4):225-49. doi: 10.3322/caac.20006. Epub 2009 May 27.
• Background Jamison RL, Donohue JH, Nagorney DM, Rosen CB, Harmsen WS, Ilstrup DM. Hepatic resection for metastatic colorectal cancer results in cure for some patients. Arch Surg. 1997 May;132(5):505-10; discussion 511. doi: 10.1001/archsurg.1997.01430290051008.
• Background Nordlinger B, Guiguet M, Vaillant JC, Balladur P, Boudjema K, Bachellier P, Jaeck D. Surgical resection of colorectal carcinoma metastases to the liver. A prognostic scoring system to improve case selection, based on 1568 patients. Association Francaise de Chirurgie. Cancer. 1996 Apr 1;77(7):1254-62.
• Background Rees M, Tekkis PP, Welsh FK, O'Rourke T, John TG. Evaluation of long-term survival after hepatic resection for metastatic colorectal cancer: a multifactorial model of 929 patients. Ann Surg. 2008 Jan;247(1):125-35. doi: 10.1097/SLA.0b013e31815aa2c2.
• Background Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, Bechstein WO, Primrose JN, Walpole ET, Finch-Jones M, Jaeck D, Mirza D, Parks RW, Collette L, Praet M, Bethe U, Van Cutsem E, Scheithauer W, Gruenberger T; EORTC Gastro-Intestinal Tract Cancer Group; Cancer Research UK; Arbeitsgruppe Lebermetastasen und-tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie (ALM-CAO); Australasian Gastro-Intestinal Trials Group (AGITG); Federation Francophone de Cancerologie Digestive (FFCD). 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 Mar 22;371(9617):1007-16. doi: 10.1016/S0140-6736(08)60455-9.
• Background Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004 Jun 3;350(23):2335-42. doi: 10.1056/NEJMoa032691.
• Background Saltz LB, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzen F, Cassidy J. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol. 2008 Apr 20;26(12):2013-9. doi: 10.1200/JCO.2007.14.9930.
• Background Van Cutsem E, Kohne CH, Lang I, Folprecht G, Nowacki MP, Cascinu S, Shchepotin I, Maurel J, Cunningham D, Tejpar S, Schlichting M, Zubel A, Celik I, Rougier P, Ciardiello F. 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 May 20;29(15):2011-9. doi: 10.1200/JCO.2010.33.5091. Epub 2011 Apr 18.
• Background Bokemeyer C, Van Cutsem E, Rougier P, Ciardiello F, Heeger S, Schlichting M, Celik I, Kohne CH. Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: pooled analysis of the CRYSTAL and OPUS randomised clinical trials. Eur J Cancer. 2012 Jul;48(10):1466-75. doi: 10.1016/j.ejca.2012.02.057. Epub 2012 Mar 23.
• Background Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocakova I, Ruff P, Blasinska-Morawiec M, Smakal M, Canon JL, Rother M, Oliner KS, Wolf M, Gansert J. 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 Nov 1;28(31):4697-705. doi: 10.1200/JCO.2009.27.4860. Epub 2010 Oct 4.
• Background Khatri VP, Chee KG, Petrelli NJ. Modern multimodality approach to hepatic colorectal metastases: solutions and controversies. Surg Oncol. 2007 Jul;16(1):71-83. doi: 10.1016/j.suronc.2007.05.001. Epub 2007 May 29.
• Background de Gramont A, Tournigand C, Andre T, Larsen AK, Louvet C. Adjuvant therapy for stage II and III colorectal cancer. Semin Oncol. 2007 Apr;34(2 Suppl 1):S37-40. doi: 10.1053/j.seminoncol.2007.01.004.
• Background Andre T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, Topham C, Zaninelli M, Clingan P, Bridgewater J, Tabah-Fisch I, de Gramont A; Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) Investigators. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004 Jun 3;350(23):2343-51. doi: 10.1056/NEJMoa032709.
• Background Gruenberger B, Tamandl D, Schueller J, Scheithauer W, Zielinski C, Herbst F, Gruenberger T. Bevacizumab, capecitabine, and oxaliplatin as neoadjuvant therapy for patients with potentially curable metastatic colorectal cancer. J Clin Oncol. 2008 Apr 10;26(11):1830-5. doi: 10.1200/JCO.2007.13.7679.
• Background Klinger M, Tamandl D, Eipeldauer S, Hacker S, Herberger B, Kaczirek K, Dorfmeister M, Gruenberger B, Gruenberger T. Bevacizumab improves pathological response of colorectal cancer liver metastases treated with XELOX/FOLFOX. Ann Surg Oncol. 2010 Aug;17(8):2059-65. doi: 10.1245/s10434-010-0972-9. Epub 2010 Feb 23.
• Background Folprecht G, Gruenberger T, Bechstein WO, Raab HR, Lordick F, Hartmann JT, Lang H, Frilling A, Stoehlmacher J, Weitz J, Konopke R, Stroszczynski C, Liersch T, Ockert D, Herrmann T, Goekkurt E, Parisi F, Kohne CH. Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial. Lancet Oncol. 2010 Jan;11(1):38-47. doi: 10.1016/S1470-2045(09)70330-4. Epub 2009 Nov 26.
• Background Ribero D, Wang H, Donadon M, Zorzi D, Thomas MB, Eng C, Chang DZ, Curley SA, Abdalla EK, Ellis LM, Vauthey JN. Bevacizumab improves pathologic response and protects against hepatic injury in patients treated with oxaliplatin-based chemotherapy for colorectal liver metastases. Cancer. 2007 Dec 15;110(12):2761-7. doi: 10.1002/cncr.23099.
• Background Kesmodel SB, Ellis LM, Lin E, Chang GJ, Abdalla EK, Kopetz S, Vauthey JN, Rodriguez-Bigas MA, Curley SA, Feig BW. Preoperative bevacizumab does not significantly increase postoperative complication rates in patients undergoing hepatic surgery for colorectal cancer liver metastases. J Clin Oncol. 2008 Nov 10;26(32):5254-60. doi: 10.1200/JCO.2008.17.7857. Epub 2008 Oct 14.
• Background D'Angelica M, Kornprat P, Gonen M, Chung KY, Jarnagin WR, DeMatteo RP, Fong Y, Kemeny N, Blumgart LH, Saltz LB. Lack of evidence for increased operative morbidity after hepatectomy with perioperative use of bevacizumab: a matched case-control study. Ann Surg Oncol. 2007 Feb;14(2):759-65. doi: 10.1245/s10434-006-9074-0. Epub 2006 Nov 11.
• Background Reddy SK, Morse MA, Hurwitz HI, Bendell JC, Gan TJ, Hill SE, Clary BM. Addition of bevacizumab to irinotecan- and oxaliplatin-based preoperative chemotherapy regimens does not increase morbidity after resection of colorectal liver metastases. J Am Coll Surg. 2008 Jan;206(1):96-106. doi: 10.1016/j.jamcollsurg.2007.06.290. Epub 2007 Sep 17.
• Background Klinger M, Eipeldauer S, Hacker S, Herberger B, Tamandl D, Dorfmeister M, Koelblinger C, Gruenberger B, Gruenberger T. Bevacizumab protects against sinusoidal obstruction syndrome and does not increase response rate in neoadjuvant XELOX/FOLFOX therapy of colorectal cancer liver metastases. Eur J Surg Oncol. 2009 May;35(5):515-20. doi: 10.1016/j.ejso.2008.12.013. Epub 2009 Feb 5.
• Background van der Pool AE, Marsman HA, Verheij J, Ten Kate FJ, Eggermont AM, Ijzermans JN, Verhoef C. Effect of bevacizumab added preoperatively to oxaliplatin on liver injury and complications after resection of colorectal liver metastases. J Surg Oncol. 2012 Dec;106(7):892-7. doi: 10.1002/jso.23142. Epub 2012 May 2.
• Background Mandard AM, Dalibard F, Mandard JC, Marnay J, Henry-Amar M, Petiot JF, Roussel A, Jacob JH, Segol P, Samama G, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer. 1994 Jun 1;73(11):2680-6. doi: 10.1002/1097-0142(19940601)73:113.0.co;2-c.
• Background Swisher SG, Hofstetter W, Wu TT, Correa AM, Ajani JA, Komaki RR, Chirieac L, Hunt KK, Liao Z, Phan A, Rice DC, Vaporciyan AA, Walsh GL, Roth JA. Proposed revision of the esophageal cancer staging system to accommodate pathologic response (pP) following preoperative chemoradiation (CRT). Ann Surg. 2005 May;241(5):810-7; discussion 817-20. doi: 10.1097/01.sla.0000161983.82345.85.
• Background Ajani JA, Mansfield PF, Crane CH, Wu TT, Lunagomez S, Lynch PM, Janjan N, Feig B, Faust J, Yao JC, Nivers R, Morris J, Pisters PW. Paclitaxel-based chemoradiotherapy in localized gastric carcinoma: degree of pathologic response and not clinical parameters dictated patient outcome. J Clin Oncol. 2005 Feb 20;23(6):1237-44. doi: 10.1200/JCO.2005.01.305.
• Background Rodel C, Martus P, Papadoupolos T, Fuzesi L, Klimpfinger M, Fietkau R, Liersch T, Hohenberger W, Raab R, Sauer R, Wittekind C. Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol. 2005 Dec 1;23(34):8688-96. doi: 10.1200/JCO.2005.02.1329. Epub 2005 Oct 24.
• Background Bouzourene H, Bosman FT, Seelentag W, Matter M, Coucke P. Importance of tumor regression assessment in predicting the outcome in patients with locally advanced rectal carcinoma who are treated with preoperative radiotherapy. Cancer. 2002 Feb 15;94(4):1121-30.
• Background Rubbia-Brandt L, Giostra E, Brezault C, Roth AD, Andres A, Audard V, Sartoretti P, Dousset B, Majno PE, Soubrane O, Chaussade S, Mentha G, Terris B. Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neo-adjuvant chemotherapy followed by liver surgery. Ann Oncol. 2007 Feb;18(2):299-304. doi: 10.1093/annonc/mdl386. Epub 2006 Oct 23.
• Background Blazer DG 3rd, Kishi Y, Maru DM, Kopetz S, Chun YS, Overman MJ, Fogelman D, Eng C, Chang DZ, Wang H, Zorzi D, Ribero D, Ellis LM, Glover KY, Wolff RA, Curley SA, Abdalla EK, Vauthey JN. Pathologic response to preoperative chemotherapy: a new outcome end point after resection of hepatic colorectal metastases. J Clin Oncol. 2008 Nov 20;26(33):5344-51. doi: 10.1200/JCO.2008.17.5299. Epub 2008 Oct 20.
• Background Maru DM, Kopetz S, Boonsirikamchai P, Agarwal A, Chun YS, Wang H, Abdalla EK, Kaur H, Charnsangavej C, Vauthey JN, Loyer EM. Tumor thickness at the tumor-normal interface: a novel pathologic indicator of chemotherapy response in hepatic colorectal metastases. Am J Surg Pathol. 2010 Sep;34(9):1287-94. doi: 10.1097/PAS.0b013e3181eb2f7b.
• Background Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
• Background Young H, Baum R, Cremerius U, Herholz K, Hoekstra O, Lammertsma AA, Pruim J, Price P. Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Eur J Cancer. 1999 Dec;35(13):1773-82. doi: 10.1016/s0959-8049(99)00229-4.
• Background Rubbia-Brandt L, Audard V, Sartoretti P, Roth AD, Brezault C, Le Charpentier M, Dousset B, Morel P, Soubrane O, Chaussade S, Mentha G, Terris B. Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Ann Oncol. 2004 Mar;15(3):460-6. doi: 10.1093/annonc/mdh095.
• Background Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, Tosolini M, Camus M, Berger A, Wind P, Zinzindohoue F, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Pages F. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006 Sep 29;313(5795):1960-4. doi: 10.1126/science.1129139.
• Background Galon J, Fridman WH, Pages F. The adaptive immunologic microenvironment in colorectal cancer: a novel perspective. Cancer Res. 2007 Mar 1;67(5):1883-6. doi: 10.1158/0008-5472.CAN-06-4806.
• Background Mlecnik B, Tosolini M, Kirilovsky A, Berger A, Bindea G, Meatchi T, Bruneval P, Trajanoski Z, Fridman WH, Pages F, Galon J. Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. J Clin Oncol. 2011 Feb 20;29(6):610-8. doi: 10.1200/JCO.2010.30.5425. Epub 2011 Jan 18.
• Background Pages F, Berger A, Camus M, Sanchez-Cabo F, Costes A, Molidor R, Mlecnik B, Kirilovsky A, Nilsson M, Damotte D, Meatchi T, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Galon J. Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med. 2005 Dec 22;353(25):2654-66. doi: 10.1056/NEJMoa051424.
• Background Pages F, Kirilovsky A, Mlecnik B, Asslaber M, Tosolini M, Bindea G, Lagorce C, Wind P, Marliot F, Bruneval P, Zatloukal K, Trajanoski Z, Berger A, Fridman WH, Galon J. In situ cytotoxic and memory T cells predict outcome in patients with early-stage colorectal cancer. J Clin Oncol. 2009 Dec 10;27(35):5944-51. doi: 10.1200/JCO.2008.19.6147. Epub 2009 Oct 26.
• Background Butterfield LH, Disis ML, Fox BA, Lee PP, Khleif SN, Thurin M, Trinchieri G, Wang E, Wigginton J, Chaussabel D, Coukos G, Dhodapkar M, Hakansson L, Janetzki S, Kleen TO, Kirkwood JM, Maccalli C, Maecker H, Maio M, Malyguine A, Masucci G, Palucka AK, Potter DM, Ribas A, Rivoltini L, Schendel D, Seliger B, Selvan S, Slingluff CL Jr, Stroncek DF, Streicher H, Wu X, Zeskind B, Zhao Y, Zocca MB, Zwierzina H, Marincola FM. A systematic approach to biomarker discovery; preamble to "the iSBTc-FDA taskforce on immunotherapy biomarkers". J Transl Med. 2008 Dec 23;6:81. doi: 10.1186/1479-5876-6-81.
• Background Butterfield LH, Palucka AK, Britten CM, Dhodapkar MV, Hakansson L, Janetzki S, Kawakami Y, Kleen TO, Lee PP, Maccalli C, Maecker HT, Maino VC, Maio M, Malyguine A, Masucci G, Pawelec G, Potter DM, Rivoltini L, Salazar LG, Schendel DJ, Slingluff CL Jr, Song W, Stroncek DF, Tahara H, Thurin M, Trinchieri G, van Der Burg SH, Whiteside TL, Wigginton JM, Marincola F, Khleif S, Fox BA, Disis ML. Recommendations from the iSBTc-SITC/FDA/NCI Workshop on Immunotherapy Biomarkers. Clin Cancer Res. 2011 May 15;17(10):3064-76. doi: 10.1158/1078-0432.CCR-10-2234. Epub 2011 May 10.
• Background Tahara H, Sato M, Thurin M, Wang E, Butterfield LH, Disis ML, Fox BA, Lee PP, Khleif SN, Wigginton JM, Ambs S, Akutsu Y, Chaussabel D, Doki Y, Eremin O, Fridman WH, Hirohashi Y, Imai K, Jacobson J, Jinushi M, Kanamoto A, Kashani-Sabet M, Kato K, Kawakami Y, Kirkwood JM, Kleen TO, Lehmann PV, Liotta L, Lotze MT, Maio M, Malyguine A, Masucci G, Matsubara H, Mayrand-Chung S, Nakamura K, Nishikawa H, Palucka AK, Petricoin EF, Pos Z, Ribas A, Rivoltini L, Sato N, Shiku H, Slingluff CL, Streicher H, Stroncek DF, Takeuchi H, Toyota M, Wada H, Wu X, Wulfkuhle J, Yaguchi T, Zeskind B, Zhao Y, Zocca MB, Marincola FM. Emerging concepts in biomarker discovery; the US-Japan Workshop on Immunological Molecular Markers in Oncology. J Transl Med. 2009 Jun 17;7:45. doi: 10.1186/1479-5876-7-45.
• Background Bindea G, Mlecnik B, Fridman WH, Pages F, Galon J. Natural immunity to cancer in humans. Curr Opin Immunol. 2010 Apr;22(2):215-22. doi: 10.1016/j.coi.2010.02.006. Epub 2010 Mar 6.
• Background Pages F, Galon J, Dieu-Nosjean MC, Tartour E, Sautes-Fridman C, Fridman WH. Immune infiltration in human tumors: a prognostic factor that should not be ignored. Oncogene. 2010 Feb 25;29(8):1093-102. doi: 10.1038/onc.2009.416. Epub 2009 Nov 30.
• Background Broussard EK, Disis ML. TNM staging in colorectal cancer: T is for T cell and M is for memory. J Clin Oncol. 2011 Feb 20;29(6):601-3. doi: 10.1200/JCO.2010.32.9078. Epub 2011 Jan 18. No abstract available.
• Background Halama N, Michel S, Kloor M, Zoernig I, Benner A, Spille A, Pommerencke T, von Knebel DM, Folprecht G, Luber B, Feyen N, Martens UM, Beckhove P, Gnjatic S, Schirmacher P, Herpel E, Weitz J, Grabe N, Jaeger D. Localization and density of immune cells in the invasive margin of human colorectal cancer liver metastases are prognostic for response to chemotherapy. Cancer Res. 2011 Sep 1;71(17):5670-7. doi: 10.1158/0008-5472.CAN-11-0268. Epub 2011 Aug 16.
• Background Camus M, Tosolini M, Mlecnik B, Pages F, Kirilovsky A, Berger A, Costes A, Bindea G, Charoentong P, Bruneval P, Trajanoski Z, Fridman WH, Galon J. Coordination of intratumoral immune reaction and human colorectal cancer recurrence. Cancer Res. 2009 Mar 15;69(6):2685-93. doi: 10.1158/0008-5472.CAN-08-2654. Epub 2009 Mar 3.
• Background Tesniere A, Apetoh L, Ghiringhelli F, Joza N, Panaretakis T, Kepp O, Schlemmer F, Zitvogel L, Kroemer G. Immunogenic cancer cell death: a key-lock paradigm. Curr Opin Immunol. 2008 Oct;20(5):504-11. doi: 10.1016/j.coi.2008.05.007. Epub 2008 Jun 23.
• Background Ghiringhelli F, Menard C, Puig PE, Ladoire S, Roux S, Martin F, Solary E, Le Cesne A, Zitvogel L, Chauffert B. Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunol Immunother. 2007 May;56(5):641-8. doi: 10.1007/s00262-006-0225-8. Epub 2006 Sep 8.
• Background Machiels JP, Reilly RT, Emens LA, Ercolini AM, Lei RY, Weintraub D, Okoye FI, Jaffee EM. Cyclophosphamide, doxorubicin, and paclitaxel enhance the antitumor immune response of granulocyte/macrophage-colony stimulating factor-secreting whole-cell vaccines in HER-2/neu tolerized mice. Cancer Res. 2001 May 1;61(9):3689-97.
• Background Mlecnik B, Tosolini M, Charoentong P, Kirilovsky A, Bindea G, Berger A, Camus M, Gillard M, Bruneval P, Fridman WH, Pages F, Trajanoski Z, Galon J. Biomolecular network reconstruction identifies T-cell homing factors associated with survival in colorectal cancer. Gastroenterology. 2010 Apr;138(4):1429-40. doi: 10.1053/j.gastro.2009.10.057. Epub 2009 Nov 10.
• Background Branford S. Chronic myeloid leukemia: molecular monitoring in clinical practice. Hematology Am Soc Hematol Educ Program. 2007:376-83. doi: 10.1182/asheducation-2007.1.376.
• Background Campbell PJ, Stephens PJ, Pleasance ED, O'Meara S, Li H, Santarius T, Stebbings LA, Leroy C, Edkins S, Hardy C, Teague JW, Menzies A, Goodhead I, Turner DJ, Clee CM, Quail MA, Cox A, Brown C, Durbin R, Hurles ME, Edwards PA, Bignell GR, Stratton MR, Futreal PA. Identification of somatically acquired rearrangements in cancer using genome-wide massively parallel paired-end sequencing. Nat Genet. 2008 Jun;40(6):722-9. doi: 10.1038/ng.128. Epub 2008 Apr 27.
• Background Diehl F, Schmidt K, Choti MA, Romans K, Goodman S, Li M, Thornton K, Agrawal N, Sokoll L, Szabo SA, Kinzler KW, Vogelstein B, Diaz LA Jr. Circulating mutant DNA to assess tumor dynamics. Nat Med. 2008 Sep;14(9):985-90. doi: 10.1038/nm.1789. Epub 2007 Jul 31.
• Background Yung TK, Chan KC, Mok TS, Tong J, To KF, Lo YM. Single-molecule detection of epidermal growth factor receptor mutations in plasma by microfluidics digital PCR in non-small cell lung cancer patients. Clin Cancer Res. 2009 Mar 15;15(6):2076-84. doi: 10.1158/1078-0432.CCR-08-2622. Epub 2009 Mar 10.
• Background Leary RJ, Kinde I, Diehl F, Schmidt K, Clouser C, Duncan C, Antipova A, Lee C, McKernan K, De La Vega FM, Kinzler KW, Vogelstein B, Diaz LA Jr, Velculescu VE. Development of personalized tumor biomarkers using massively parallel sequencing. Sci Transl Med. 2010 Feb 24;2(20):20ra14. doi: 10.1126/scitranslmed.3000702.
• Background McBride DJ, Orpana AK, Sotiriou C, Joensuu H, Stephens PJ, Mudie LJ, Hamalainen E, Stebbings LA, Andersson LC, Flanagan AM, Durbecq V, Ignatiadis M, Kallioniemi O, Heckman CA, Alitalo K, Edgren H, Futreal PA, Stratton MR, Campbell PJ. Use of cancer-specific genomic rearrangements to quantify disease burden in plasma from patients with solid tumors. Genes Chromosomes Cancer. 2010 Nov;49(11):1062-9. doi: 10.1002/gcc.20815.

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