Genetic Variants Predict Optimal Timing of Radiotherapy to Reduce Side-effects in Breast Cancer Patients

K. Johnson; J. Chang-claude; A.-m. Critchley; C. Kyriacou; S. Lavers; T. Rattay; P. Seibold; A. Webb; C. West; R.p. Symonds; C.j. Talbot; David Azria; Anthony Brookes; Jenny Chang-claude; Dirk De Ruysscher; Alison Dunning; Sara Gutiérrez Enríquez; Philippe Lambin; Tiziana Rancati; Barry Rosenstein; Petra Seibold; R. Paul Symonds; Hubert Thierens; Riccardo Valdagni; Ana Vega; Liv Veldeman; Frederik Wenz; C. West

doi:10.1016/j.clon.2018.10.001

Genetic Variants Predict Optimal Timing of Radiotherapy to Reduce Side-effects in Breast Cancer Patients

K. Johnson, J. Chang-claude, A.-m. Critchley, C. Kyriacou, S. Lavers, T. Rattay, P. Seibold, A. Webb, C. West, R.p. Symonds, C.j. Talbot, David Azria, Anthony Brookes, Jenny Chang-claude, Dirk De Ruysscher, Alison Dunning, Sara Gutiérrez Enríquez, Philippe Lambin, Tiziana Rancati, Barry RosensteinPetra Seibold, R. Paul Symonds, Hubert Thierens, Riccardo Valdagni, Ana Vega, Liv Veldeman, Frederik Wenz, C. West

Division of Cancer Sciences (L5)

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND

Radiotherapy is an important treatment for many types of cancer, but a minority of patients suffer long-term side effects of treatment. Multiple lines of evidence suggest a role for circadian rhythm in the development of radiotherapy late side effects.

METHODS

We performed a study to examine the effect of radiotherapy timing in two breast cancer patient cohorts. The retrospective LeND cohort comprised 535 patients scored for late effects using the LENT-SOMA scale. Acute effects were assessed prospectively in 343 patients from the REQUITE study using the CTCAE v4 scales. Genotyping was carried out for candidate circadian rhythm variants.

RESULTS

In the LeND cohort patients who had radiotherapy in the morning had a significantly increased incidence of late toxicity in univariate (p=0.03) and multivariate analysis (p=0.01). Acute effects in the REQUITE group were also significantly increased in univariate analysis following morning treatment (p=0.03).

Increased late effects in the LeND group receiving morning radiotherapy was associated with carriage of PER3 VNTR 4/4 genotype (p=6.0x10-3) and NOCT rs131116075 AA genotype (p=5x10-3).

CONCLUSION

Our results suggest that it may be possible to reduce toxicity associated with breast cancer radiotherapy by identifying gene variants that affect circadian rhythm and scheduling for appropriate morning or afternoon radiotherapy.

Original language	English
Pages (from-to)	9-16
Journal	Clinical Oncology
Volume	31
Issue number	1
Early online date	30 Oct 2018
DOIs	https://doi.org/10.1016/j.clon.2018.10.001
Publication status	Published - 2019

Research Beacons, Institutes and Platforms

Manchester Cancer Research Centre

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https://linkinghub.elsevier.com/retrieve/pii/S093665551830462X

Cite this

Johnson, K., Chang-claude, J., Critchley, A., Kyriacou, C., Lavers, S., Rattay, T., Seibold, P., Webb, A., West, C., Symonds, R. P., Talbot, C. J., Azria, D., Brookes, A., Chang-claude, J., De Ruysscher, D., Dunning, A., Gutiérrez Enríquez, S., Lambin, P., Rancati, T., ... West, C. (2019). Genetic Variants Predict Optimal Timing of Radiotherapy to Reduce Side-effects in Breast Cancer Patients. Clinical Oncology, 31(1), 9-16. https://doi.org/10.1016/j.clon.2018.10.001

@article{93c8b2e4d7e7425398959e1d998b7c13,

title = "Genetic Variants Predict Optimal Timing of Radiotherapy to Reduce Side-effects in Breast Cancer Patients",

abstract = "BACKGROUNDRadiotherapy is an important treatment for many types of cancer, but a minority of patients suffer long-term side effects of treatment. Multiple lines of evidence suggest a role for circadian rhythm in the development of radiotherapy late side effects.METHODSWe performed a study to examine the effect of radiotherapy timing in two breast cancer patient cohorts. The retrospective LeND cohort comprised 535 patients scored for late effects using the LENT-SOMA scale. Acute effects were assessed prospectively in 343 patients from the REQUITE study using the CTCAE v4 scales. Genotyping was carried out for candidate circadian rhythm variants.RESULTSIn the LeND cohort patients who had radiotherapy in the morning had a significantly increased incidence of late toxicity in univariate (p=0.03) and multivariate analysis (p=0.01). Acute effects in the REQUITE group were also significantly increased in univariate analysis following morning treatment (p=0.03).Increased late effects in the LeND group receiving morning radiotherapy was associated with carriage of PER3 VNTR 4/4 genotype (p=6.0x10-3) and NOCT rs131116075 AA genotype (p=5x10-3).CONCLUSIONOur results suggest that it may be possible to reduce toxicity associated with breast cancer radiotherapy by identifying gene variants that affect circadian rhythm and scheduling for appropriate morning or afternoon radiotherapy.",

author = "K. Johnson and J. Chang-claude and A.-m. Critchley and C. Kyriacou and S. Lavers and T. Rattay and P. Seibold and A. Webb and C. West and R.p. Symonds and C.j. Talbot and David Azria and Anthony Brookes and Jenny Chang-claude and {De Ruysscher}, Dirk and Alison Dunning and {Guti{\'e}rrez Enr{\'i}quez}, Sara and Philippe Lambin and Tiziana Rancati and Barry Rosenstein and Petra Seibold and Symonds, {R. Paul} and Hubert Thierens and Riccardo Valdagni and Ana Vega and Liv Veldeman and Frederik Wenz and C. West",

year = "2019",

doi = "10.1016/j.clon.2018.10.001",

language = "English",

volume = "31",

pages = "9--16",

journal = "Clinical Oncology",

issn = "0936-6555",

publisher = "W.B. Saunders Co. Ltd",

number = "1",

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Johnson, K, Chang-claude, J, Critchley, A, Kyriacou, C, Lavers, S, Rattay, T, Seibold, P, Webb, A, West, C, Symonds, RP, Talbot, CJ, Azria, D, Brookes, A, Chang-claude, J, De Ruysscher, D, Dunning, A, Gutiérrez Enríquez, S, Lambin, P, Rancati, T, Rosenstein, B, Seibold, P, Symonds, RP, Thierens, H, Valdagni, R, Vega, A, Veldeman, L, Wenz, F & West, C 2019, 'Genetic Variants Predict Optimal Timing of Radiotherapy to Reduce Side-effects in Breast Cancer Patients', Clinical Oncology, vol. 31, no. 1, pp. 9-16. https://doi.org/10.1016/j.clon.2018.10.001

TY - JOUR

T1 - Genetic Variants Predict Optimal Timing of Radiotherapy to Reduce Side-effects in Breast Cancer Patients

AU - Johnson, K.

AU - Chang-claude, J.

AU - Critchley, A.-m.

AU - Kyriacou, C.

AU - Lavers, S.

AU - Rattay, T.

AU - Seibold, P.

AU - Webb, A.

AU - West, C.

AU - Symonds, R.p.

AU - Talbot, C.j.

AU - Azria, David

AU - Brookes, Anthony

AU - Chang-claude, Jenny

AU - De Ruysscher, Dirk

AU - Dunning, Alison

AU - Gutiérrez Enríquez, Sara

AU - Lambin, Philippe

AU - Rancati, Tiziana

AU - Rosenstein, Barry

AU - Seibold, Petra

AU - Symonds, R. Paul

AU - Thierens, Hubert

AU - Valdagni, Riccardo

AU - Vega, Ana

AU - Veldeman, Liv

AU - Wenz, Frederik

AU - West, C.

PY - 2019

Y1 - 2019

N2 - BACKGROUNDRadiotherapy is an important treatment for many types of cancer, but a minority of patients suffer long-term side effects of treatment. Multiple lines of evidence suggest a role for circadian rhythm in the development of radiotherapy late side effects.METHODSWe performed a study to examine the effect of radiotherapy timing in two breast cancer patient cohorts. The retrospective LeND cohort comprised 535 patients scored for late effects using the LENT-SOMA scale. Acute effects were assessed prospectively in 343 patients from the REQUITE study using the CTCAE v4 scales. Genotyping was carried out for candidate circadian rhythm variants.RESULTSIn the LeND cohort patients who had radiotherapy in the morning had a significantly increased incidence of late toxicity in univariate (p=0.03) and multivariate analysis (p=0.01). Acute effects in the REQUITE group were also significantly increased in univariate analysis following morning treatment (p=0.03).Increased late effects in the LeND group receiving morning radiotherapy was associated with carriage of PER3 VNTR 4/4 genotype (p=6.0x10-3) and NOCT rs131116075 AA genotype (p=5x10-3).CONCLUSIONOur results suggest that it may be possible to reduce toxicity associated with breast cancer radiotherapy by identifying gene variants that affect circadian rhythm and scheduling for appropriate morning or afternoon radiotherapy.

AB - BACKGROUNDRadiotherapy is an important treatment for many types of cancer, but a minority of patients suffer long-term side effects of treatment. Multiple lines of evidence suggest a role for circadian rhythm in the development of radiotherapy late side effects.METHODSWe performed a study to examine the effect of radiotherapy timing in two breast cancer patient cohorts. The retrospective LeND cohort comprised 535 patients scored for late effects using the LENT-SOMA scale. Acute effects were assessed prospectively in 343 patients from the REQUITE study using the CTCAE v4 scales. Genotyping was carried out for candidate circadian rhythm variants.RESULTSIn the LeND cohort patients who had radiotherapy in the morning had a significantly increased incidence of late toxicity in univariate (p=0.03) and multivariate analysis (p=0.01). Acute effects in the REQUITE group were also significantly increased in univariate analysis following morning treatment (p=0.03).Increased late effects in the LeND group receiving morning radiotherapy was associated with carriage of PER3 VNTR 4/4 genotype (p=6.0x10-3) and NOCT rs131116075 AA genotype (p=5x10-3).CONCLUSIONOur results suggest that it may be possible to reduce toxicity associated with breast cancer radiotherapy by identifying gene variants that affect circadian rhythm and scheduling for appropriate morning or afternoon radiotherapy.

U2 - 10.1016/j.clon.2018.10.001

DO - 10.1016/j.clon.2018.10.001

M3 - Article

SN - 0936-6555

VL - 31

SP - 9

EP - 16

JO - Clinical Oncology

JF - Clinical Oncology

IS - 1

ER -

Genetic Variants Predict Optimal Timing of Radiotherapy to Reduce Side-effects in Breast Cancer Patients

Abstract

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