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

详细信息    查看全文

• 作者：Pernille Lassen^a ; ^{pernille@oncology.dk"" rel=""nofollow} ; ^{pernlass@rm.dk"" rel=""nofollow} ; Jesper G. Eriksen^a ; Annelise Krogdahl^b ; Marianne Hamilton Therkildsen^c ; Benedicte P. Ulhø ; i^d ; Marie Overgaard^e ; Lena Specht^f ; Elo Andersen^g ; Jø ; rgen Johansen^h ; Lisbeth J. Andersenⁱ ; Cai Grau^e ; Jens Overgaard^a ; On behalf of the Danish Head ; Neck Cancer Group (DAHANCA)
• 关键词：HPV ; p16 ; HNSCC ; Accelerated fractionation ; Radiotherapy
• 刊名：Radiotherapy and Oncology
• 出版年：2011
• 出版时间：July 2011
• 年：2011
• 卷：100
• 期：1
• 页码：49-55
• 全文大小：324 K

文摘

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 (5 Fx/week vs 6 Fx/week) was evaluated 5 years 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 6 Fx/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.