Table 2.
Clinical studies correlating functional in vitro assay data with adverse normal-tissue reaction to radiotherapy (RT).
| Fibroblasts | |||||
|---|---|---|---|---|---|
| Endpoint | RT site | N.T effect | # pat. | signif. | Reference |
| SF | mastect. | early | n=6 | (*) | [173] Burnet et al., 1992 |
| SF | H&N (+br.) | early | n=27 | n.s. | [174] Geara et al., 1993 |
| SF | mastect. | early | n=8 | n.s. | [178] Brock et al. 1995 |
| SF | breast | early | n=23 | n.s. | [179] Oppitz et al., 2002 |
| SF | mastect. | late | n=6 | (*) | [173] Burnet et al., 1992 |
| SF | H&N (+br.) | late | n=27 | * | [174] Geara et al., 1993 |
| SF | mastect. | fibr. | n=12 | * | [175] Johansen et al., 1994 |
| SF | mastect. | late | n=9 | n.s. | [178] Brock et al., 1995 |
| SF | mastect. | fibr. | n=31 | * | [176] Johansen et al., 1996 |
| SF | breast | fibr. | n=79 | n.s. | [181] Russell et al., 1998 |
| SF | H&N | late | n=23 | n.s. | [180] Rudat et al., 1999 |
| SF | breast | br.appear. | n=104 | n.s. | [182] Peacock et al., 2000 |
| SF | H&N | late | n=14 | n.s. | [177] Borgmann et al., 2002 |
| Repair/comet | breast | early | n=24 | n.s. | [179] Oppitz et al., 2002 |
| DSB Repair | breast | fibr., late | n=39 | * | [183] Kiltie et al., 1999 |
| DSB Repair | breast | fibr., late | n=49 | n.s. | [165] Dickson et al., 2002 |
| DSB Repair | H&N | late | n=14 | n.s. | [177] Borgmann et al., 2002 |
| MN | breast | late, | n=36 | n.s. | [184] Johansen et al., 1998 |
| MN | various | early, late | n=4-10 | n.s. | [185] Sprung et al., 2005 |
| Lymphocytes | |||||
|---|---|---|---|---|---|
| Endpoint | RT site | N.T effect | # pat. | signif. | Reference |
| SF | H&N (+br.) | early | n=27 | n.s. | [174] Geara et al., 1993 |
| SF | breast | early | n=15 | (*) | [186] West et al., 1995 |
| SF | H&N (+br.) | late | n=27 | n.s. | [174] Geara et al., 1993 |
| SF | breast | late | n=14 | (*) | [186] West et al., 1995 |
| SF | cervix | late | n=83 | * | [187] West et al., 2001 |
| Apoptosis | various | early | n=30 | n.s. | [149] Greve et al., 2012 |
| Apoptosis | various | early | n=89 | * | [196] Pouliliou et al., 2015 |
| Apoptosis | breast | late | n=31 | n.s. | [207] Barber et al., 2000b |
| Apoptosis | various | late | n=399 | * | [212] Ozsahin et al., 2005 |
| Apoptosis | H&N | late | n=79 | * | [213] Bordon et al., 2010 |
| Apoptosis | breast | late | n=26 | (*) | [194] Henriquez-Hern. et al., 2011 |
| Apoptosis | breast | br.appear. | n=59 | n.s. | [151] Finnon et al., 2012 |
| Apoptosis | breast | br.appear. | n=16 | n.s. | [190] Chua et al., 2014 |
| Repair/comet | breast | early | n=30 | * | [179] Oppitz et al., 2002 |
| Repair/comet | various | early, late | n=30 | * | [188] Müller et al., 2001 |
| DSB repair | various | early | n=18 | n.s. | [199] Vasireddy et al., 2010 |
| DSB repair | H&N | early | n=31 | n.s. | [198] Fleckenstein et al., 2011 |
| DSB repair | H&N | early | n=54 | * | [193] Goutham et al., 2012 |
| DSB repair | various | early | n=30 | n.s. | [149] Greve et al., 2012 |
| DSB repair | various | early | n=57 | * | [192] Djuzenova et al., 2013 |
| DSB repair | breast | early | n=80 | * | [195] Mumbrekar et al., 2014 |
| DSB repair | various | early | n=89 | * | [196] Pouliliou et al., 2015 |
| DSB repair | various | early, late | n=22 | * | [189] Bourton et al., 2011 |
| DSB repair | prostate | early, late | n=50 | n.s. | [197] Brzozowska et al., 2012 |
| DSB repair | various | late | n=22 | n.s. | [199] Vasireddy et al., 2010 |
| DSB repair | breast | late | n=26 | (*) | [194] Henriquez-Hern. et al., 2011 |
| DSB repair | breast | br.appear. | n=59 | n.s. | [151] Finnon et al., 2012 |
| DSB repair | breast | br.appear. | n=16 | * | [190] Chua et al., 2014 |
| DSB repair | prostate | late | n=61 | * | [152] van Oorschot et al., 2014 |
| Chr.aberr. | breast | early | n=123 | * | [201] Barber et al., 2000a |
| Chr.aberr. | various | early | n=52 | n.s. | [202] Borgmann et al., 2008 |
| Chr.aberr. | breast | early | n=87 | * | [202] Borgmann et al., 2008 |
| Chr.aberr. | various | early, late | n=66 | * | [203] Neubauer et al., 1997 |
| Chr.aberr. | prostate | early, late | n=50 | n.s. | [197] Brzozowska et al., 2012 |
| Chr.aberr. | breast | late | n=19 | n.s. | [201] Barber et al., 2000a |
| Chr.aberr. | H&N | late | n=16 | * | [177] Borgmann et al., 2002 |
| Chr.aberr. | breast | fibr. | n=86 | n.s. | [206] Höller et al, 2003 |
| Chr.aberr. | gynaecol. | late | n=29 | * | [205] Werbrouck et al., 2010 |
| Chr.aberr. | breast | late | n=14 | * | [191] Chua et al., 2011 |
| Chr. aberr. | breast | br.appear. | n=59 | n.s. | [151] Finnon et al., 2012 |
| Chr.aberr. | prostate | late | n=30 | * | [204] Beaton et al., 2013 |
| MN | breast | early | n=116 | n.s. | [201] Barber et al., 2000a |
| MN | various | early, late | n=9-22 | n.s. | [185] Sprung et al., 2005 |
| MN | breast | late | n=47 | (*) | [201] Barber et al., 2000a |
| MN | breast | br.appear. | n=59 | n.s. | [151] Finnon et al., 2012 |
Culture conditions, techniques for detecting and quantifying the in vitro endpoints varied between the different studies. Abbreviations: SF (surviving fraction measured by colony formation assay); DSB (DNA double-strand break); MN (micronucleus assay); Chr.aberr. (chromosome aberrations); mastect. (post-mastectomy RT); H&N (head-and-neck); br. (breast); N.T. (normal tissue); fibr. (fibrosis); br.appear. (breast appearance); # pat. (number of RT patients); signif. (statistical significance); * (P<0.05); n.s. (not significant). Brackets (*) signify borderline significance or limited inference.