Exploratory Analysis of Mutations in Circulating Tumour DNA as Biomarkers of Treatment Response for Patients with Relapsed High-Grade Serous Ovarian Carcinoma: A Retrospective Study

James Brenton and colleagues reveal tumour burden and prognosis correlations from circulating DNA analysis in high grade serous ovarian carcinoma.

Vyšlo v časopise: Exploratory Analysis of Mutations in Circulating Tumour DNA as Biomarkers of Treatment Response for Patients with Relapsed High-Grade Serous Ovarian Carcinoma: A Retrospective Study. PLoS Med 13(12): e32767. doi:10.1371/journal.pmed.1002198
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pmed.1002198


James Brenton and colleagues reveal tumour burden and prognosis correlations from circulating DNA analysis in high grade serous ovarian carcinoma.


1. Crowley E, Di Nicolantonio F, Loupakis F, Bardelli A. Liquid biopsy: monitoring cancer-genetics in the blood. Nat Rev Clin Oncol. 2013;10(8):472–84. doi: 10.1038/nrclinonc.2013.110 23836314

2. Aebersold R, Anderson L, Caprioli R, Druker B, Hartwell L, Smith R. Perspective: a program to improve protein biomarker discovery for cancer. J Proteome Res. 2005;4(4):1104–9. doi: 10.1021/pr050027n 16083259

3. Jacobs I, Oram D, Fairbanks J, Turner J, Frost C, Grudzinskas JG. A risk of malignancy index incorporating CA 125, ultrasound and menopausal status for the accurate preoperative diagnosis of ovarian cancer. Br J Obstet Gynaecol. 1990;97(10):922–9. 2223684

4. Sturgeon CM, Duffy MJ, Stenman UH, Lilja H, Brunner N, Chan DW, et al. National Academy of Clinical Biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers. Clin Chem. 2008;54(12):e11–79. doi: 10.1373/clinchem.2008.105601 19042984

5. Soletormos G, Duffy MJ, Othman Abu Hassan S, Verheijen RH, Tholander B, Bast RC Jr, et al. Clinical use of cancer biomarkers in epithelial ovarian cancer: updated guidelines from the European Group on Tumor Markers. Int J Gynecol Cancer. 2016;26(1):43–51. doi: 10.1097/IGC.0000000000000586 26588231

6. Buys SS, Partridge E, Black A, Johnson CC, Lamerato L, Isaacs C, et al. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA. 2011;305(22):2295–303. doi: 10.1001/jama.2011.766 21642681

7. Jacobs IJ, Menon U, Ryan A, Gentry-Maharaj A, Burnell M, Kalsi JK, et al. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet. 2016;387(10022):945–56. doi: 10.1016/S0140-6736(15)01224-6 26707054

8. Saygili U, Guclu S, Uslu T, Erten O, Dogan E. The effect of ascites, mass volume, and peritoneal carcinomatosis on serum CA125 levels in patients with ovarian carcinoma. Int J Gynecol Cancer. 2002;12(5):438–42. 12366659

9. Gupta D, Lis CG. Role of CA125 in predicting ovarian cancer survival—a review of the epidemiological literature. J Ovarian Res. 2009;2:13. doi: 10.1186/1757-2215-2-13 19818123

10. Gadducci A, Cosio S, Tana R, Genazzani AR. Serum and tissue biomarkers as predictive and prognostic variables in epithelial ovarian cancer. Crit Rev Oncol Hematol. 2009;69(1):12–27. doi: 10.1016/j.critrevonc.2008.05.001 18595727

11. To EW, Chan KC, Leung SF, Chan LY, To KF, Chan AT, et al. Rapid clearance of plasma Epstein-Barr virus DNA after surgical treatment of nasopharyngeal carcinoma. Clin Cancer Res. 2003;9(9):3254–9. 12960110

12. Diehl F, Schmidt K, Choti MA, Romans K, Goodman S, Li M, et al. Circulating mutant DNA to assess tumor dynamics. Nat Med. 2008;14(9):985–90. doi: 10.1038/nm.1789 18670422

13. Sorenson GD, Pribish DM, Valone FH, Memoli VA, Bzik DJ, Yao SL. Soluble normal and mutated DNA sequences from single-copy genes in human blood. Cancer Epidemiol Biomarkers Prev. 1994;3(1):67–71. 8118388

14. Vasioukhin V, Anker P, Maurice P, Lyautey J, Lederrey C, Stroun M. Point mutations of the N-ras gene in the blood plasma DNA of patients with myelodysplastic syndrome or acute myelogenous leukaemia. Br J Haematol. 1994;86(4):774–9. 7918071

15. Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014;6(224):224ra24. doi: 10.1126/scitranslmed.3007094 24553385

16. Dawson SJ, Tsui DW, Murtaza M, Biggs H, Rueda OM, Chin SF, et al. Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med. 2013;368(13):1199–209. doi: 10.1056/NEJMoa1213261 23484797

17. Newman AM, Bratman SV, To J, Wynne JF, Eclov NC, Modlin LA, et al. An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nat Med. 2014;20(5):548–54. doi: 10.1038/nm.3519 24705333

18. 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;15(6):2076–84. doi: 10.1158/1078-0432.CCR-08-2622 19276259

19. Diaz LA Jr, Bardelli A. Liquid biopsies: genotyping circulating tumor DNA. J Clin Oncol. 2014;32(6):579–86. doi: 10.1200/JCO.2012.45.2011 24449238

20. Diehl F, Li M, Dressman D, He Y, Shen D, Szabo S, et al. Detection and quantification of mutations in the plasma of patients with colorectal tumors. Proc Natl Acad Sci U S A. 2005;102(45):16368–73. doi: 10.1073/pnas.0507904102 16258065

21. Forshew T, Murtaza M, Parkinson C, Gale D, Tsui DW, Kaper F, et al. Noninvasive identification and monitoring of cancer mutations by targeted deep sequencing of plasma DNA. Sci Transl Med. 2012;4(136):136ra68. doi: 10.1126/scitranslmed.3003726 22649089

22. Tie J, Kinde I, Wang Y, Wong HL, Roebert J, Christie M, et al. Circulating tumor DNA as an early marker of therapeutic response in patients with metastatic colorectal cancer. Ann Oncol. 2015;26(8):1715–22. doi: 10.1093/annonc/mdv177 25851626

23. Ahmed AA, Etemadmoghadam D, Temple J, Lynch AG, Riad M, Sharma R, et al. Driver mutations in TP53 are ubiquitous in high grade serous carcinoma of the ovary. J Pathol. 2010;221(1):49–56. doi: 10.1002/path.2696 20229506

24. Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature. 2011;474(7353):609–15. doi: 10.1038/nature10166 21720365

25. Köbel M, Piskorz AM, Lee S, Lui S, LePage C, Marass F, et al. Optimized p53 immunohistochemistry is an accurate predictor of TP53 mutation in ovarian carcinoma. J Pathol Clin Res. 2016;2(4):247–58. doi: 10.1002/cjp2.53 27840695

26. Bast RC Jr, Feeney M, Lazarus H, Nadler LM, Colvin RB, Knapp RC. Reactivity of a monoclonal antibody with human ovarian carcinoma. J Clin Invest. 1981;68(5):1331–7. doi: 10.1172/JCI110380 7028788

27. Moore RG, MacLaughlan S, Bast RC Jr. Current state of biomarker development for clinical application in epithelial ovarian cancer. Gynecol Oncol. 2010;116(2):240–5. doi: 10.1016/j.ygyno.2009.09.041 19879639

28. Swisher EM, Wollan M, Mahtani SM, Willner JB, Garcia R, Goff BA, et al. Tumor-specific p53 sequences in blood and peritoneal fluid of women with epithelial ovarian cancer. Am J Obstet Gynecol. 2005;193(3 Pt 1):662–7.

29. Otsuka J, Okuda T, Sekizawa A, Amemiya S, Saito H, Okai T, et al. Detection of p53 mutations in the plasma DNA of patients with ovarian cancer. Int J Gynecol Cancer. 2004;14(3):459–64. doi: 10.1111/j.1048-891x.2004.014305.x 15228418

30. Pereira E, Camacho-Vanegas O, Anand S, Sebra R, Catalina Camacho S, Garnar-Wortzel L, et al. Personalized circulating tumor DNA biomarkers dynamically predict treatment response and survival in gynecologic cancers. PLoS ONE. 2015;10(12):e0145754. doi: 10.1371/journal.pone.0145754 26717006

31. von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. PLoS Med. 2007;4(10):e296. doi: 10.1371/journal.pmed.0040296 17941714

32. McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM, et al. Reporting recommendations for tumor marker prognostic studies (REMARK). J Natl Cancer Inst. 2005;97(16):1180–4. doi: 10.1093/jnci/dji237 16106022

33. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47. doi: 10.1016/j.ejca.2008.10.026 19097774

34. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, et al. The consensus coding sequences of human breast and colorectal cancers. Science. 2006;314(5797):268–74. doi: 10.1126/science.1133427 16959974

35. Archibald KM, Kulbe H, Kwong J, Chakravarty P, Temple J, Chaplin T, et al. Sequential genetic change at the TP53 and chemokine receptor CXCR4 locus during transformation of human ovarian surface epithelium. Oncogene. 2012;31(48):4987–95. doi: 10.1038/onc.2011.653 22266861

36. Rustin GJ, Quinn M, Thigpen T, du Bois A, Pujade-Lauraine E, Jakobsen A, et al. Re: new guidelines to evaluate the response to treatment in solid tumors (ovarian cancer). J Natl Cancer Inst. 2004;96(6):487–8.

37. No JH, Kim K, Park KH, Kim YB. Cell-free DNA level as a prognostic biomarker for epithelial ovarian cancer. Anticancer Res. 2012;32(8):3467–71. 22843932

38. Tissot C, Toffart AC, Villar S, Souquet PJ, Merle P, Moro-Sibilot D, et al. Circulating free DNA concentration is an independent prognostic biomarker in lung cancer. Eur Respir J. 2015;46(6):1773–80. doi: 10.1183/13993003.00676-2015 26493785

39. R Core Team. R: a language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2016 [cited 2016 Nov 18]. Available from: https://www.R-project.org/.

40. Rockall AG, Avril N, Lam R, Iannone R, Mozley PD, Parkinson C, et al. Repeatability of quantitative FDG-PET/CT and contrast-enhanced CT in recurrent ovarian carcinoma: test-retest measurements for tumor FDG uptake, diameter, and volume. Clin Cancer Res. 2014;20(10):2751–60. doi: 10.1158/1078-0432.CCR-13-2634 24573555

41. Andreopoulou E, Andreopoulos D, Adamidis K, Fountzila-Kalogera A, Fountzilas G, Dimopoulos MA, et al. Tumor volumetry as predictive and prognostic factor in the management of ovarian cancer. Anticancer Res. 2002;22(3):1903–8. 12168891

42. Eisenhauer EA, Vermorken JB, van Glabbeke M. Predictors of response to subsequent chemotherapy in platinum pretreated ovarian cancer: a multivariate analysis of 704 patients. Ann Oncol. 1997;8(10):963–8. 9402168

43. Mayoral M, Fernandez-Martinez A, Vidal L, Fuster D, Aya F, Pavia J, et al. Prognostic value of (18)F-FDG PET/CT volumetric parameters in recurrent epithelial ovarian cancer. Rev Esp Med Nucl Imagen Mol. 2016;35(2):88–95. doi: 10.1016/j.remn.2015.08.005 26541072

44. Vargas HA, Burger IA, Goldman DA, Micco M, Sosa RE, Weber W, et al. Volume-based quantitative FDG PET/CT metrics and their association with optimal debulking and progression-free survival in patients with recurrent ovarian cancer undergoing secondary cytoreductive surgery. Eur Radiol. 2015;25(11):3348–53. doi: 10.1007/s00330-015-3729-9 25916387

45. Van Gorp T, Cadron I, Despierre E, Daemen A, Leunen K, Amant F, et al. HE4 and CA125 as a diagnostic test in ovarian cancer: prospective validation of the Risk of Ovarian Malignancy Algorithm. Br J Cancer. 2011;104(5):863–70. doi: 10.1038/sj.bjc.6606092 21304524

46. Blackledge G, Lawton F, Redman C, Kelly K. Response of patients in phase II studies of chemotherapy in ovarian cancer: implications for patient treatment and the design of phase II trials. Br J Cancer. 1989;59(4):650–3. 2713253

47. Markman M, Rothman R, Hakes T, Reichman B, Hoskins W, Rubin S, et al. Second-line platinum therapy in patients with ovarian cancer previously treated with cisplatin. J Clin Oncol. 1991;9(3):389–93. doi: 10.1200/jco.1991.9.3.389 1999708

48. Markman M, Markman J, Webster K, Zanotti K, Kulp B, Peterson G, et al. Duration of response to second-line, platinum-based chemotherapy for ovarian cancer: implications for patient management and clinical trial design. J Clin Oncol. 2004;22(15):3120–5. doi: 10.1200/JCO.2004.05.195 15284263

49. Lee CK, Simes RJ, Brown C, Gebski V, Pfisterer J, Swart AM, et al. A prognostic nomogram to predict overall survival in patients with platinum-sensitive recurrent ovarian cancer. Ann Oncol. 2013;24(4):937–43. doi: 10.1093/annonc/mds538 23104722

50. Eng KH, Hanlon BM, Bradley WH, Szender JB. Prognostic factors modifying the treatment-free interval in recurrent ovarian cancer. Gynecol Oncol. 2015;139(2):228–35. doi: 10.1016/j.ygyno.2015.09.011 26383827

51. Lee CK, Friedlander M, Brown C, Gebski VJ, Georgoulopoulos A, Vergote I, et al. Early decline in cancer antigen 125 as a surrogate for progression-free survival in recurrent ovarian cancer. J Natl Cancer Inst. 2011;103(17):1338–42. doi: 10.1093/jnci/djr282 21840849

52. Wilbaux M, Henin E, Oza A, Colomban O, Pujade-Lauraine E, Freyer G, et al. Dynamic modeling in ovarian cancer: an original approach linking early changes in modeled longitudinal CA-125 kinetics and survival to help decisions in early drug development. Gynecol Oncol. 2014;133(3):460–6. doi: 10.1016/j.ygyno.2014.04.003 24726614

53. Yoshikawa T, Takano M, Kita T, Kudoh K, Sasaki N, Kato M, et al. Normal serum CA125 half-life and normal serum nadir CA125 level in patients with ovarian cancers. Eur J Gynaecol Oncol. 2012;33(3):269–73. 22873097

54. Chien J, Sicotte H, Fan JB, Humphray S, Cunningham JM, Kalli KR, et al. TP53 mutations, tetraploidy and homologous recombination repair defects in early stage high-grade serous ovarian cancer. Nucleic Acids Res. 2015;43(14):6945–58. doi: 10.1093/nar/gkv111 25916844

55. Schwarz RF, Ng CK, Cooke SL, Newman S, Temple J, Piskorz AM, et al. Spatial and temporal heterogeneity in high-grade serous ovarian cancer: a phylogenetic analysis. PLoS Med. 2015;12(2):e1001789. doi: 10.1371/journal.pmed.1001789 25710373

56. Jamal-Hanjani M, Wilson GA, Horswell S, Mitter R, Sakarya O, Constantin T, et al. Detection of ubiquitous and heterogeneous mutations in cell-free DNA from patients with early-stage non-small-cell lung cancer. Ann Oncol. 2016;27(5):862–7. doi: 10.1093/annonc/mdw037 26823523

57. de Bruin EC, McGranahan N, Mitter R, Salm M, Wedge DC, Yates L, et al. Spatial and temporal diversity in genomic instability processes defines lung cancer evolution. Science. 2014;346(6206):251–6. doi: 10.1126/science.1253462 25301630

58. Smerage JB, Barlow WE, Hortobagyi GN, Winer EP, Leyland-Jones B, Srkalovic G, et al. Circulating tumor cells and response to chemotherapy in metastatic breast cancer: SWOG S0500. J Clin Oncol. 2014;32(31):3483–9. doi: 10.1200/JCO.2014.56.2561 24888818

59. Wason JM, Abraham JE, Baird RD, Gournaris I, Vallier AL, Brenton JD, et al. A Bayesian adaptive design for biomarker trials with linked treatments. Br J Cancer. 2015;113(5):699–705. doi: 10.1038/bjc.2015.278 26263479

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