The influence of HPV-associated p16-expression on accelerated fractionated radiotherapy in head and neck cancer: Evaluation of the randomised DAHANCA 6&7 trial

Pernille Lassen; Jesper Grau Eriksen; Annelise Krogdahl; Marianne Hamilton Therkildsen; Benedicte Parm Ulhøi; Marie Overgaard; Lena Specht; Elo Andersen; Jørgen Johansen; Lisbeth J Andersen; Cai Grau; Jens Overgaard; On behalf of the Danish Head and Neck Cancer Group (DAHANCA)

doi:10.1016/j.radonc.2011.02.010

The influence of HPV-associated p16-expression on accelerated fractionated radiotherapy in head and neck cancer: Evaluation of the randomised DAHANCA 6&7 trial

Pernille Lassen, Jesper Grau Eriksen, Annelise Krogdahl, Marianne Hamilton Therkildsen, Benedicte Parm Ulhøi, Marie Overgaard, Lena Specht, Elo Andersen, Jørgen Johansen, Lisbeth J Andersen, Cai Grau, Jens Overgaard, On behalf of the Danish Head and Neck Cancer Group (DAHANCA)

132 Citations (Scopus)

Abstract

BACKGROUND AND PURPOSE: Tumour HPV-positivity is a favourable prognostic factor in the radiotherapy of HNSCC, but the optimal radiotherapy regimen for HPV-positive HNSCC is not yet defined. Reducing overall treatment time is known to improve outcome in the radiotherapy of HNSCC as was also demonstrated in the randomised DAHANCA 6&7 trial. We aimed to assess the influence of tumour HPV-status, expressed by p16, on the response to accelerated fractionated radiotherapy in HNSCC through evaluation of the DAHANCA 6&7 trial. MATERIALS AND METHODS: Immunohistochemical detection of HPV-associated p16-expression was performed on FFPE-pre-treatment tumour-tissues from 794 patients enrolled in the DAHANCA 6&7 trial. The influence of tumour p16-status on loco-regional tumour control and survival as a function of fractionation schedule (5Fx/week vs 6Fx/week) was evaluated 5years after the completion of radiotherapy. RESULTS: The significant and independent prognostic value of tumour p16-positivity in HNSCC radiotherapy was confirmed, with adjusted hazard ratios (HR) of 0.58 [0.43-0.78], 0.47 [0.33-0.67] and 0.54 [0.42-0.68] for loco-regional control, disease-specific and overall survival, respectively. Accelerated radiotherapy significantly improved loco-regional tumour control compared to conventional radiotherapy, adjusted HR: 0.73 [0.59-0.92] and the benefit of the 6Fx/week regimen was observed both in p16-positive (HR: 0.56 [0.33-0.96]) as well as in p16-negative tumours (HR: 0.77 [0.60-0.99]). Disease-specific survival was also significantly improved with accelerated radiotherapy in the group of p16-positive tumours (adjusted HR: 0.43 [0.22-0.82]). CONCLUSION: Accelerated radiotherapy significantly improves outcome in HNSCC compared to conventional fractionation. The observed benefit is independent of tumour p16-status and the use of a moderately accelerated radiotherapy regimen seems advantageous also for HPV/p16-positive HNSCC.

Original language	English
Journal	Radiotherapy & Oncology
Volume	100
Issue number	1
Pages (from-to)	49-55
Number of pages	7
ISSN	0167-8140
DOIs	https://doi.org/10.1016/j.radonc.2011.02.010
Publication status	Published - Jul 2011

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Lassen, P., Eriksen, J. G., Krogdahl, A., Therkildsen, M. H., Ulhøi, B. P., Overgaard, M., Specht, L., Andersen, E., Johansen, J., Andersen, L. J., Grau, C., Overgaard, J., & On behalf of the Danish Head and Neck Cancer Group (DAHANCA) (2011). The influence of HPV-associated p16-expression on accelerated fractionated radiotherapy in head and neck cancer: Evaluation of the randomised DAHANCA 6&7 trial. Radiotherapy & Oncology, 100(1), 49-55. https://doi.org/10.1016/j.radonc.2011.02.010

The influence of HPV-associated p16-expression on accelerated fractionated radiotherapy in head and neck cancer: Evaluation of the randomised DAHANCA 6&7 trial. / Lassen, Pernille; Eriksen, Jesper Grau; Krogdahl, Annelise et al.

In: Radiotherapy & Oncology, Vol. 100, No. 1, 07.2011, p. 49-55.

Research output: Contribution to journal › Journal article › Research › peer-review

Lassen, P, Eriksen, JG, Krogdahl, A, Therkildsen, MH, Ulhøi, BP, Overgaard, M, Specht, L, Andersen, E, Johansen, J, Andersen, LJ, Grau, C, Overgaard, J & On behalf of the Danish Head and Neck Cancer Group (DAHANCA) 2011, 'The influence of HPV-associated p16-expression on accelerated fractionated radiotherapy in head and neck cancer: Evaluation of the randomised DAHANCA 6&7 trial', Radiotherapy & Oncology, vol. 100, no. 1, pp. 49-55. https://doi.org/10.1016/j.radonc.2011.02.010

@article{c8aef0645b26400985dbc5bdad5e9514,

title = "The influence of HPV-associated p16-expression on accelerated fractionated radiotherapy in head and neck cancer: Evaluation of the randomised DAHANCA 6&7 trial",

abstract = "BACKGROUND AND PURPOSE: Tumour HPV-positivity is a favourable prognostic factor in the radiotherapy of HNSCC, but the optimal radiotherapy regimen for HPV-positive HNSCC is not yet defined. Reducing overall treatment time is known to improve outcome in the radiotherapy of HNSCC as was also demonstrated in the randomised DAHANCA 6&7 trial. We aimed to assess the influence of tumour HPV-status, expressed by p16, on the response to accelerated fractionated radiotherapy in HNSCC through evaluation of the DAHANCA 6&7 trial. MATERIALS AND METHODS: Immunohistochemical detection of HPV-associated p16-expression was performed on FFPE-pre-treatment tumour-tissues from 794 patients enrolled in the DAHANCA 6&7 trial. The influence of tumour p16-status on loco-regional tumour control and survival as a function of fractionation schedule (5Fx/week vs 6Fx/week) was evaluated 5years after the completion of radiotherapy. RESULTS: The significant and independent prognostic value of tumour p16-positivity in HNSCC radiotherapy was confirmed, with adjusted hazard ratios (HR) of 0.58 [0.43-0.78], 0.47 [0.33-0.67] and 0.54 [0.42-0.68] for loco-regional control, disease-specific and overall survival, respectively. Accelerated radiotherapy significantly improved loco-regional tumour control compared to conventional radiotherapy, adjusted HR: 0.73 [0.59-0.92] and the benefit of the 6Fx/week regimen was observed both in p16-positive (HR: 0.56 [0.33-0.96]) as well as in p16-negative tumours (HR: 0.77 [0.60-0.99]). Disease-specific survival was also significantly improved with accelerated radiotherapy in the group of p16-positive tumours (adjusted HR: 0.43 [0.22-0.82]). CONCLUSION: Accelerated radiotherapy significantly improves outcome in HNSCC compared to conventional fractionation. The observed benefit is independent of tumour p16-status and the use of a moderately accelerated radiotherapy regimen seems advantageous also for HPV/p16-positive HNSCC.",

author = "Pernille Lassen and Eriksen, {Jesper Grau} and Annelise Krogdahl and Therkildsen, {Marianne Hamilton} and Ulh{\o}i, {Benedicte Parm} and Marie Overgaard and Lena Specht and Elo Andersen and J{\o}rgen Johansen and Andersen, {Lisbeth J} and Cai Grau and Jens Overgaard and Therkildsen, {Marianne Hamilton}",

year = "2011",

month = jul,

doi = "10.1016/j.radonc.2011.02.010",

language = "English",

volume = "100",

pages = "49--55",

journal = "Radiotherapy & Oncology",

issn = "0167-8140",

publisher = "Elsevier Ireland Ltd",

number = "1",

}

TY - JOUR

T1 - The influence of HPV-associated p16-expression on accelerated fractionated radiotherapy in head and neck cancer: Evaluation of the randomised DAHANCA 6&7 trial

AU - Lassen, Pernille

AU - Eriksen, Jesper Grau

AU - Krogdahl, Annelise

AU - Therkildsen, Marianne Hamilton

AU - Ulhøi, Benedicte Parm

AU - Overgaard, Marie

AU - Specht, Lena

AU - Andersen, Elo

AU - Johansen, Jørgen

AU - Andersen, Lisbeth J

AU - Grau, Cai

AU - Overgaard, Jens

AU - On behalf of the Danish Head and Neck Cancer Group (DAHANCA)

PY - 2011/7

Y1 - 2011/7

N2 - BACKGROUND AND PURPOSE: Tumour HPV-positivity is a favourable prognostic factor in the radiotherapy of HNSCC, but the optimal radiotherapy regimen for HPV-positive HNSCC is not yet defined. Reducing overall treatment time is known to improve outcome in the radiotherapy of HNSCC as was also demonstrated in the randomised DAHANCA 6&7 trial. We aimed to assess the influence of tumour HPV-status, expressed by p16, on the response to accelerated fractionated radiotherapy in HNSCC through evaluation of the DAHANCA 6&7 trial. MATERIALS AND METHODS: Immunohistochemical detection of HPV-associated p16-expression was performed on FFPE-pre-treatment tumour-tissues from 794 patients enrolled in the DAHANCA 6&7 trial. The influence of tumour p16-status on loco-regional tumour control and survival as a function of fractionation schedule (5Fx/week vs 6Fx/week) was evaluated 5years after the completion of radiotherapy. RESULTS: The significant and independent prognostic value of tumour p16-positivity in HNSCC radiotherapy was confirmed, with adjusted hazard ratios (HR) of 0.58 [0.43-0.78], 0.47 [0.33-0.67] and 0.54 [0.42-0.68] for loco-regional control, disease-specific and overall survival, respectively. Accelerated radiotherapy significantly improved loco-regional tumour control compared to conventional radiotherapy, adjusted HR: 0.73 [0.59-0.92] and the benefit of the 6Fx/week regimen was observed both in p16-positive (HR: 0.56 [0.33-0.96]) as well as in p16-negative tumours (HR: 0.77 [0.60-0.99]). Disease-specific survival was also significantly improved with accelerated radiotherapy in the group of p16-positive tumours (adjusted HR: 0.43 [0.22-0.82]). CONCLUSION: Accelerated radiotherapy significantly improves outcome in HNSCC compared to conventional fractionation. The observed benefit is independent of tumour p16-status and the use of a moderately accelerated radiotherapy regimen seems advantageous also for HPV/p16-positive HNSCC.

AB - BACKGROUND AND PURPOSE: Tumour HPV-positivity is a favourable prognostic factor in the radiotherapy of HNSCC, but the optimal radiotherapy regimen for HPV-positive HNSCC is not yet defined. Reducing overall treatment time is known to improve outcome in the radiotherapy of HNSCC as was also demonstrated in the randomised DAHANCA 6&7 trial. We aimed to assess the influence of tumour HPV-status, expressed by p16, on the response to accelerated fractionated radiotherapy in HNSCC through evaluation of the DAHANCA 6&7 trial. MATERIALS AND METHODS: Immunohistochemical detection of HPV-associated p16-expression was performed on FFPE-pre-treatment tumour-tissues from 794 patients enrolled in the DAHANCA 6&7 trial. The influence of tumour p16-status on loco-regional tumour control and survival as a function of fractionation schedule (5Fx/week vs 6Fx/week) was evaluated 5years after the completion of radiotherapy. RESULTS: The significant and independent prognostic value of tumour p16-positivity in HNSCC radiotherapy was confirmed, with adjusted hazard ratios (HR) of 0.58 [0.43-0.78], 0.47 [0.33-0.67] and 0.54 [0.42-0.68] for loco-regional control, disease-specific and overall survival, respectively. Accelerated radiotherapy significantly improved loco-regional tumour control compared to conventional radiotherapy, adjusted HR: 0.73 [0.59-0.92] and the benefit of the 6Fx/week regimen was observed both in p16-positive (HR: 0.56 [0.33-0.96]) as well as in p16-negative tumours (HR: 0.77 [0.60-0.99]). Disease-specific survival was also significantly improved with accelerated radiotherapy in the group of p16-positive tumours (adjusted HR: 0.43 [0.22-0.82]). CONCLUSION: Accelerated radiotherapy significantly improves outcome in HNSCC compared to conventional fractionation. The observed benefit is independent of tumour p16-status and the use of a moderately accelerated radiotherapy regimen seems advantageous also for HPV/p16-positive HNSCC.

U2 - 10.1016/j.radonc.2011.02.010

DO - 10.1016/j.radonc.2011.02.010

M3 - Journal article

SN - 0167-8140

VL - 100

SP - 49

EP - 55

JO - Radiotherapy & Oncology

JF - Radiotherapy & Oncology

IS - 1

ER -

The influence of HPV-associated p16-expression on accelerated fractionated radiotherapy in head and neck cancer: Evaluation of the randomised DAHANCA 6&7 trial

Abstract

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