In vitro cellular radiosensitivity in relationship to late normal tissue reactions in breast cancer patients: a multi-endpoint case-control study

International Journal of Radiation Biology

Volumn 92, Issue 12, 2016, Pages 823-836

  Vandevoorde, Charlot ^a,b   Depuydt, Julie ^a   Veldeman, Liv ^c   De Neve, Wilfried ^c   Sebastià, Natividad ^d   Wieme, Greet ^a   Baert, Annelot ^a   De Langhe, Sofie ^a   Philippé, Jan ^a   Thierens, Hubert ^a   Vral, Anne ^a  

^a GHENT UNIVERSITY   (Belgium)

^b NATIONAL RESEARCH FOUNDATION   (South Africa)

^c GHENT UNIVERSITY HOSPITAL   (Belgium)

^d The IISLAFE Health Research Institute   (Spain)

Author keywords

Apoptosis; breast cancer; DNA DSB repair; micronuclei; radiosensitivity; radiotherapy

Indexed keywords

HISTONE H2AX; TUMOR SUPPRESSOR P53 BINDING PROTEIN 1;

APOPTOSIS; APOPTOSIS ASSAY; ARTICLE; BLOOD SAMPLING; BREAST CANCER; CANCER PATIENT; CASE CONTROL STUDY; CD8+ T LYMPHOCYTE; CELL ASSAY; CELL CYCLE G0 PHASE; CELL CYCLE G2 PHASE; CELL DEATH; CLINICAL ARTICLE; CLINICAL EXAMINATION; CONTROLLED STUDY; DISEASE SEVERITY; DNA REPAIR; DOUBLE STRANDED DNA BREAK; FEMALE; FOLLOW UP; G2 PHASE CELL CYCLE CHECKPOINT; HUMAN; IN VITRO STUDY; INTENSITY MODULATED RADIATION THERAPY; IRRADIATION; LENT SOMA SCALE; MICRONUCLEUS TEST; PERIPHERAL LYMPHOCYTE; PRIORITY JOURNAL; RADIATION INJURY; RADIATION RESPONSE; RADIOSENSITIVITY; RETROSPECTIVE STUDY; TISSUE REACTION; TOXICITY ASSAY; ADULT; ADVERSE EFFECTS; AGED; BIOASSAY; BREAST NEOPLASMS; CONFORMAL RADIOTHERAPY; CONTROLLED CLINICAL TRIAL; DIAGNOSTIC IMAGING; LONGITUDINAL STUDY; MIDDLE AGED; OUTCOME ASSESSMENT; PATHOLOGY; PROCEDURES; RADIATION INJURIES; RADIATION TOLERANCE; RADIOTHERAPY DOSAGE; REPRODUCIBILITY; SENSITIVITY AND SPECIFICITY; TREATMENT OUTCOME;

ADULT; AGED; BREAST NEOPLASMS; CASE-CONTROL STUDIES; DOSE-RESPONSE RELATIONSHIP, RADIATION; ENDPOINT DETERMINATION; FEMALE; HUMANS; LONGITUDINAL STUDIES; MIDDLE AGED; OUTCOME ASSESSMENT (HEALTH CARE); RADIATION INJURIES; RADIATION TOLERANCE; RADIOTHERAPY DOSAGE; RADIOTHERAPY, CONFORMAL; REPRODUCIBILITY OF RESULTS; SENSITIVITY AND SPECIFICITY; TREATMENT OUTCOME;

EID: 84991447219     PISSN: 09553002     EISSN: 13623095     Source Type: Journal    
DOI: 10.1080/09553002.2016.1230238     Document Type: Article

References (76)

1. Alsner J, Andreassen CN, Overgaard J., 2008. Genetic markers for prediction of normal tissue toxicity after radiotherapy. Semin Radiat Oncol. 18:126–135.
2. Azria D, Riou O, Castan F, Nguyen TD, Peignaux K, Lemanski C, Lagrange J-L, Kirova Y, Lartigau E, Belkacemi Y, et al. 2015. Radiation-induced CD8 T-lymphocyte apoptosis as a predictor of breast fibrosis after radiotherapy:results of the prospective multicenter French trial. EBioMedicine. 2:1965–1973.
3. Baeyens A, Thierens H, Claes K, Poppe B, Messiaen L, De Ridder L, Vral A., 2002. Chromosomal radiosensitivity in breast cancer patients with a known or putative genetic predisposition. Br J Can. 87:1379–1385.
4. Baeyens A, Claes K, Willems P, De Ruyck K, Thierens H, Vral A., 2005. Chromosomal radio sensitivity of breast cancer with a CHEK2 mutation. Cancer Gen Cytogenet. 163:106–112.
5. Ban S, Konomi C, Iwakawa M, Yamada S, Ohno T, Tsuji H, Noda S, Matui Y, Harada Y, Cologne JB, Imai T., 2004. Radiosensitivity of peripheral blood lymphocytes obtained from patients with cancers of the breast, head and neck or cervix as determined with a micronucleus assay. J Radiat Res. 45:535–541.
6. Barber JBP, Burrill W, Spreadborough AR, Levine E, Warren C, Kiltie AE, Roberts SA, Scott D., 2000a. Relationship between in vitro chromosomal radiosensitivity of peripheral blood lymphocytes and the expression of normal tissue damage following radiotherapy for breast cancer. Radiother Oncol. 55:179–186.
7. Barber JBP, West CML, Kiltie AE, Roberts SA, Scott D., 2000b. Detection of individual differences in radiation-induced apoptosis of peripheral blood lymphocytes in normal individuals, ataxia telangiectasia homozygotes and heterozygotes, and breast cancer patients after radiotherapy. Radiat Res. 153:570–578.
8. Barker CL, Routledge JA, Farnell DJJ, Swindell R, Davidson SE., 2009. The impact of radiotherapy late effects on quality of life in gynaecological cancer patients. Br J Cancer. 100:1558–1565.
9. Barnett GC, Coles CE, Elliott RM, Baynes C, Luccarini C, Conroy D, Wilkinson JS, Tyrer J, Misra V, Platte R, et al. 2012. Independent validation of genes and polymorphisms reported to be associated with radiation toxicity:a prospective analysis study. Lancet Oncol. 13:65–77.
10. Barnett GC, West CML, Dunning AM, Elliott RM, Coles CE, Pharoah PDP, Burnet NG., 2009. Normal tissue reactions to radiotherapy:towards tailoring treatment dose by genotype. Nature Rev Cancer. 9:134–142.
11. Barnett GC, Wilkinson JS, Moody AM, Wilson CB, Twyman N, Wishart GC, Burnet NG, Coles CE., 2011. The Cambridge Breast Intensity-modulated Radiotherapy Trial:patient- and treatment-related factors that influence late toxicity. Clin Oncol. 23:662–673.
12. Beaton LA, Ferrarotto C, Marro L, Samiee S, Malone S, Grimes S, Malone K, Wilkins RC., 2013. Chromosome damage and cell proliferation rates in in vitro irradiated whole blood as markers of late radiation toxicity after radiation therapy to the prostate. Int J Radiat Oncol Biol Phys. 85:1346–1352.
13. Bentzen SM, Agrawal RK, Aird EGA, Barrett JM, Barrett-Lee PJ, Bliss JM, Brown J, Dewar JA, Dobbs HJ, Haviland JS, et al. 2008. The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer:a randomised trial. Lancet Oncol. 9:331–341.
14. Bordon E, Henriquez Hernandez LA, Lara PC, Pinar B, Fontes F, Rodriguez Gallego C, Lloret M., 2009. Prediction of clinical toxicity in localized cervical carcinoma by radio-induced apoptosis study in peripheral blood lymphocytes (PBLs). Radiat Oncol. 4:58.
15. Bordon E, Henriquez-Hernandez LA, Lara PC, Ruiz A, Pinar B, Rodriguez-Gallego C, Lloret M., 2010. Prediction of clinical toxicity in locally advanced head and neck cancer patients by radio-induced apoptosis in peripheral blood lymphocytes (PBLs). Radiat Oncol. 5:4.
16. Borgmann K, Haeberle D, Doerk T, Busjahn A, Stephan G, Dikomey E., 2007. Genetic determination of chromosomal radiosensitivities in G0- and G2-phase human lymphocytes. Radiother Oncol. 83:196–202.
17. Borgmann K, Hoeller U, Nowack S, Bernhard M, Roper B, Brackrock S, Petersen C, Szymczak S, Ziegler A, Feyer P, et al. 2008. Individual radiosensitivity measured with lymphocytes may predict the risk of acute reaction after radiotherapy. Int J Radiat Oncol Biol Phys. 71:256–264.
18. Borgmann K, Roper B, Abd El-Awady R, Brackrock S, Bigalke M, Dork T, Alberti W, Dikomey E, Dahm-Daphi J., 2002. Indicators of late normal tissue response after radiotherapy for head and neck cancer:fibroblasts, lymphocytes, genetics, DNA repair, and chromosome aberrations. Radiother Oncol. 64:141–152.
19. Bourton EC, Plowman PN, Smith D, Arlett CF, Parris CN., 2011. Prolonged expression of the gamma-H2AX DNA repair biomarker correlates with excess acute and chronic toxicity from radiotherapy treatment. Int J Cancer. 129:2928–2934.
20. Brzozowska K, Pinkawa M, Eble MJ, Muller WU, Wojcik A, Kriehuber R, Schmitz S., 2012. In vivo versus in vitro individual radiosensitivity analysed in healthy donors and in prostate cancer patients with and without severe side effects after radiotherapy. Int J Radiat Biol. 88:405–413.
21. Burnet NG, Nyman J, Turesson I, Wurm R, Yarnold JR, Peacock JH., 1992. Prediction of normal-tissue tolerance to radiotherapy from in-vitro cellular radiation sensitivity. Lancet. 339:1570–1571.
22. Burnet NG, Johansen J, Turesson I, Nyman J, Peacock JH., 1998. Describing patients’ normal tissue reactions:concerning the possibility of individualising radiotherapy dose prescriptions based on potential predictive assays of normal tissue radiosensitivity. Steering Committee of the BioMed2 European Union Concerted Action Programme on the Development of Predictive Tests of Normal Tissue Response to Radiation Therapy. Int J Cancer. 79:606–613.
23. Busse PM, Bose SK, Jones RW, Tolmach LJ., 1977. Action of caffeine on X-irradiated Hela-cells. 2. Synergistic lethality. Radiat Res. 71:666–677.
24. Cardinale F, Bruzzi P, Bolognesi C., 2012. Role of micronucleus test in predicting breast cancer susceptibility:a systematic review and meta-analysis. Br J Cancer. 106:780–790.
25. Carney JP., 1999. Chromosomal breakage syndromes. Curr Opin Immunol. 11:443–447.
26. Chua MLK, Horn S, Somaiah N, Davies S, Gothard L, A’Hern R, Yarnold J, Rothkamm K., 2014. DNA double-strand break repair and induction of apoptosis in ex vivo irradiated blood lymphocytes in relation to late normal tissue reactions following breast radiotherapy. Radiat Environ Biophys. 53:355–364.
27. Chua MLK, Rothkamm K., 2013. Biomarkers of radiation exposure:can they predict normal tissue radiosensitivity? Clin Oncol. 25:610–616.
28. Chua MLK, Somaiah N, A’Hern R, Davies S, Gothard L, Yarnold J, Rothkamm K., 2011. Residual DNA and chromosomal damage in ex vivo irradiated blood lymphocytes correlated with late normal tissue response to breast radiotherapy. Radiother Oncol. 99:362–366.
29. Claes K, Depuydt J, Taylor AMR, Last JI, Baert A, Schietecatte P, Vandersickel V, Poppe B, De Leeneer K, D’Hooghe M, Vral A., 2013. Variant Ataxia telangiectasia:clinical and molecular findings and evaluation of radiosensitive phenotypes in a patient and relatives. Neuromol Med. 15:447–457.
30. Crompton NE, Miralbell R, Rutz HP, Ersoy F, Sanal O, Wellmann D, Bieri S, Coucke PA, Emery GC, Shi YQ, et al. 1999. Altered apoptotic profiles in irradiated patients with increased toxicity. Int J Radiat Oncol Biol Phys. 45:707–714.
31. Dayes I, Rumble RB, Bowen J, Dixon P, Warde P., 2012. Intensity-modulated radiotherapy in the treatment of breast cancer. Clin Oncol (R Coll Radiol). 24:488–498.
32. Deantonio L, Gambaro G, Beldi D, Masini L, Tunesi S, Magnani C, Krengli M., 2010. Hypofractionated radiotherapy after conservative surgery for breast cancer:analysis of acute and late toxicity. Radiat Oncol. 5:7.
33. De Langhe S, Mulliez T, Veldeman L, Remouchamps V, van Greveling A, Gilsoul M, De Schepper E, De Ruyck K, De Neve W, Thierens H., 2014. Factors modifying the risk for developing acute skin toxicity after whole-breast intensity modulated radiotherapy. BMC Cancer. 14:9.
34. De Neve W, De Gersem W, Madani I., 2012. Rational use of intensity-modulated radiation therapy:the importance of clinical outcome. Semin Radiat Oncol. 22:40–49.
35. Dubray B, Delanian S, Lefaix JL., 1997. Late effects of mammary radiotherapy on skin and subcutaneous tissues. Cancer Radiothér. 1:744–752.
36. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). 2011. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death:meta-analysis of individual patient data for 10801 women in 17 randomized trials. Lancet. 378:1707–1760.
37. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). 2014. Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality:meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet. 383:2127–2135.
38. Feight D, Baney T, Bruce S, McQuestion M., 2011. Putting evidence into practice:evidence-based interventions for radiation dermatitis. Clin J Oncol Nurs. 15:481–492.
39. Fenech M, Holland N, Chang WP, Zeiger E, Bonassi S., 1999. The HUman MicroNucleus Project–an international collaborative study on the use of the micronucleus technique for measuring DNA damage in humans. Mutat Res-Fundam Mol Mech Mutagen. 428:271–283.
40. Fenech M, Morley AA., 1986. Cytokinesis-block micronucleus method in human lymphocytes–effect of in vivo aging and low-dose X-irradiation. Mutat Res. 161:193–198.
41. Finnon P, Kabacik S, MacKay A, Raffy C, A’Hern R, Owen R, Badie C, Yarnold J, Bouffler S., 2012, Correlation of in vitro lymphocyte radiosensitivity and gene expression with late normal tissue reactions following curative radiotherapy for breast cancer. Radiother Oncol. 105:329–336.
42. Giotopoulos G, Symonds RP, Foweraker K, Griffin M, Peat I, Osman A, Plumb M., 2007. The late radiotherapy normal tissue injury phenotypes of telangiectasia, fibrosis and atrophy in breast cancer patients have distinct genotype-dependent causes. Br J Cancer. 96:1001–1007.
43. Harris JR, Levene MB, Svensson G, Hellman S., 1979. Analysis of cosmetic results following primary radiation therapy for stages I and II carcinoma of the breast. Int J Radiat Oncol Biol Phys. 5:257–261.
44. Hoeller U, Borgmann K, Bonacker M, Kuhlmey A, Bajrovic A, Jung H, Alberti W, Dikomey E., 2003. Individual radiosensitivity measured with lymphocytes may be used to predict the risk of fibrosis after radiotherapy for breast cancer. Radiother Oncol. 69:137–144.
45. Lavin MF, Shiloh Y., 1997. The genetic defect in ataxia-telangiectasia. Annu Rev Immunol. 15:177–202.
46. Lee TK, Allison RR, O’Brien KF, Johnke RM, Christie KI, Naves JL, Kovacs CJ, Arastu H, Karlsson UL., 2003. Lymphocyte radiosensitivity correlated with pelvic radiotherapy morbidity. Int J Radiat Oncol Biol Phys. 57:222–229.
47. LENT-SOMA (Late effects on normal tissue–subjective symptoms, objective signs, management, and analytical measures) tables. 1995. Radiother Oncol. 35:17–60.
48. Lilla C, Ambrosone CB, Kropp S, Helmbold I, Schmezer P, von Fournier D, Haase W, Sautter-Bihl ML, Wenz F, Chang-Claude J., 2007. Predictive factors for late normal tissue complications following radiotherapy for breast cancer. Breast Cancer Res Treatment. 106:143–150.
49. Liu Q, Cao J, Liu Y, Lu YM, Qin B, Jiang B, Jiang LP, Fu BH, Zhao FL, Jiang EH, et al. 2010. Follow-up study by chromosome aberration analysis and micronucleus assays in victims accidentaly exposed to Co-60 radiation. Health Phys. 98:885–888.
50. Lopez E, Guerrero R, Nunez MI, del Moral R, Villalobos M, Martinez-Galan J, Valenzuela MT, Munoz-Gamez J, Oliver FJ, Martin-Oliva D, de Almodovar JMR., 2005. Early and late skin reactions to radiotherapy for breast cancer and their correlation with radiation-induced DNA damage in lymphocytes. Breast Cancer Res. 7:R690–698.
51. Natarajan TG, Ganesan N, Carter-Nolan P, Tucker CA, Shields PG, Adams-Campbell LL., 2006. gamma-radiation-induced chromosomal mutagen sensitivity is associated with breast cancer risk in African-American women:caffeine modulates the outcome of mutagen sensitivity assay. Cancer Epidemiol Biomarkers Prevent. 15:437–442.
52. Ozsahin M, Azria D., 2014. Radiation-induced sequelae measured by lymphocyte apoptosis. Int J Radiat Oncol Biol Phys. 90:470–470.
53. Ozsahin M, Crompton NEA, Gourgou S, Kramar A, Li L, Shi YQ, Sozzi WJ, Zouhair A, Mirimanoff RO, Azria D., 2005. CD4 and CD8 T-lymphocyte apoptosis can predict radiation-induced late toxicity:a prospective study in 399 patients. Clin Cancer Res. 11:7426–7433.
54. Padjas A, Kedzierawski P, Florek A, Kukolowicz P, Kuszewski T, Gozdz S, Lankoff A, Wojcik A, Lisowska H., 2012. Comparative analysis of three functional predictive assays in lymphocytes of patients with breast and gynaecological cancer treated by radiotherapy. J Contemp Brachyther. 4:219–226.
55. Pavy JJ, Denekamp J, Letschert J, Littbrand B, Mornex F, Bernier J, Gonzales-Gonzales D, Horiot JC, Bolla M, Bartelink H., 1995. EORTC Late Effects Working Group. Late effects toxicity scoring:the SOMA scale. Radiother Oncol. 35:11–15.
56. Peters LJ., 1996. Radiation therapy tolerance limits. For one or for all? Janeway Lecture. Cancer. 77:2379–2385.
57. Pujol M, Puig R, Caballin MR, Barrios L, Barquinero JF., 2012. The use of caffeine to assess high dose exposures to ionising radiation by dicentric analysis. Radiat Protect Dosimetry. 149:392–398.
58. Rached E, Schindler R, Beer KT, Vetterli D, Greiner RH., 1998. No predictive value of the micronucleus assay for patients with severe acute reaction of normal tissue after radiotherapy. Eur J Cancer. 34:378–383.
59. Sarkaria JN, Busby EC, Tibbetts RS, Roos P, Taya Y, Karnitz LM, Abraham RT., 1999. Inhibition of ATM and ATR kinase activities by the radiosensitizing agent, caffeine. Cancer Res. 59:4375–4382.
60. Schnarr K, Boreham D, Sathya J, Julian J, Dayes IS., 2009. Radiation-induced lymphocyte apoptosis to predict radiation therapy late toxicity in prostate cancer patients. Int J Radiat Oncol Biol Phys. 74:1424–1430.
61. Sokal RR, Rohlf FJ., 2012. Biometry:the principles and practice of statistics in biological research. 4th ed. New York:W. H. Freeman and Company. 915p.
62. Stone HB, Coleman CN, Anscher MS, McBride WH., 2003. Effects of radiation on normal tissue:consequences and mechanisms. Lancet Oncol. 4:529–536.
63. Taghavi-Dehaghani M, Mohammadi S, Ziafazeli T, Sardari-Kermani M., 2005. A study on differences between radiation-induced micronuclei and apoptosis of lymphocytes in breast cancer patients after radiotherapy. Zeitschrift Fur Naturforschung C (J Biosci.). 60:938–942.
64. Thierens H, Vral A, Morthier R, Aousalah B, De Ridder L., 2000. Cytogenetic monitoring of hospital workers occupationally exposed to ionizing radiation using the micronucleus centromere assay. Mutagenesis. 15:245–249.
65. Tucker SL, Turesson I, Thames HD., 1992. Evidence for individual differences in the radiosensitivity of human skin. Eur J Cancer. 28:1783–1791.
66. Turesson I, Nyman J, Holmberg E, Oden A., 1996. Prognostic factors for acute and late skin reactions in radiotherapy patients. Int J Radiat Oncol Biol Phys. 36:1065–1075.
67. Vandevoorde C, Gomolka M, Roessler U, Samaga D, Lindholm C, Fernet M, Hall J, Pernot E, El-Saghire H, Baatout S, et al. 2015. EPI-CT:in vitro assessment of the applicability of the gamma-H2AX-foci assay as cellular biomarker for exposure in a multicentre study of children in diagnostic radiology. Int J Radiat Biol. 91:653–663.
68. Veldeman L, Madani I, Hulstaert F, De Meerleer G, Mareel M, De Neve W., 2008. Evidence behind use of intensity-modulated radiotherapy:a systematic review of comparative clinical studies. Lancet Oncol. 9:367–375.
69. Vodicka P, Polivkova Z, Sytarova S, Demova H, Kucerova M, Vodickova L, Polakova V, Naccarati A, Smerhovsky Z, Ambrus M, et al. 2010. Chromosomal damage in peripheral blood lymphocytes of newly diagnosed cancer patients and healthy controls. Carcinogenesis. 31:1238–1241.
70. Waljee JF, Hu ES, Ubel PA, Smith DM, Newman LA, Alderman AK., 2008. Effect of esthetic outcome after breast-conserving surgery on psychosocial functioning and quality of life. J Clin Oncol. 26:3331–3337.
71. Wang ZD, Zhang XQ, Du J, Lu X, Wang Y, Tian R, Liu QJ, Chen Y., 2015. Continuous cytogenetic follow-up, over 5 years, of three individuals accidentally irradiated by a cobalt-60 source. Mutat Res–Genet Toxicol Environ Mutagen. 779:1–4.
72. Werbrouck J, De Ruyck K, Beels L, Vral A, Van Eijkeren M, De Neve W, Thierens H., 2010. Prediction of late normal tissue complications in RT treated gynaecological cancer patients:potential of the gamma-H2AX foci assay and association with chromosomal radiosensitivity. Oncol Rep. 23:571–578.
73. West CM, Barnett GC., 2011. Genetics and genomics of radiotherapy toxicity:towards prediction. Genome Med. 3:52.
74. Widel M, Jedrus S, Lukaszczyk B, Raczek-Zwierzycka K, Swierniak A., 2003. Radiation-induced micronucleus frequency in peripheral blood lymphocytes is correlated with normal tissue damage in patients with cervical carcinoma undergoing radiotherapy. Radiat Res. 159:713–721.
75. Willems P, August L, Slabbert J, Romm H, Oestreicher U, Thierens H, Vral A., 2010. Automated micronucleus (MN) scoring for population triage in case of large scale radiation events. Int J Radiat Biol. 86:2–11.
76. Wolff HA, Hennies S, Herrmann MKA, Rave-Frank M, Eickelmann D, Virsik P, Jung K, Schirmer M, Ghadimi M, Hess CF, et al. 2011. Comparison of the micronucleus and chromosome aberration techniques for the documentation of cytogenetic damage in radiochemotherapy-treated patients with rectal cancer. Strahlenther Onkol. 187:52–58.