Non-Conventional Fractionated Radiotherapy for Head and Neck Cancer: A Systematic Review_Chinese Journal of Evidence-Based Medicine

Authors：

WANG Xin , AI Ping , SHEN Yali , REN Ruomei ,  LI Ping

Radiotherapy Oncology Department, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

LI Ping, Email: leepingmd68@yahoo.com

Keywords：

Head and neck cancer; Non-conventional fractionated radiotherapy; Systematic review, Meta-analysis

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective 　To evaluate the efficacy and side effect of non-conventional fractionated radiotherapy for head and neck cancer.
Methods 　Trials were identified by searching CENTRAL, MEDLINE, EMBASE, Chinese Biological Medicine Database (CBMdisc) and Chinese VIP Database. We handresearched the data from 10 kinds of important Chinese journals. Two reviewers assessed and extracted the studies. The following primary outcomes were assessed: complete relief (CR), overall survival (OS), acute side effect and late side effect.
Results 　Twenty-three trials involving 8 411 patients were included. Thirteen trials were of good quality, and the rest were of poor quality. Meta-analysis of these trials showed that: (1) non-conventional fractionated radiotherapy vs conventional fractionated radiotherapy: ① Only S-HART and CAIR resulted in higher CR, RR=1.21 (95%CI 1.02 to 1.44), 3.31 (95%CI 1.16 to 9.42), respectively; ② Only HRT could improve 2-year OS (RR=1.32, 95%CI 1.13 to 1.54), but this difference wasn’t found in 5-year follow up; ③ Most of the non-conventional fractionated radiotherapy could increase acute side effects, but not the late ones; (2) non-conventional fractionated radiotherapy combined with concurrent chemotherapy vs non-conventional fractionated radiotherapy: ① Only C-HRT resulted in higher CR (RR=1.58, 95%CI 1.18 to 2.11); ② Higher 2-year OS could be gained when combined with chemotherapy (RR=1.35, 95%CI 1.18 to 1.54), and only C-HRT resulted in higher 5-year OS (RR=1.57, 95%CI 1.19 to 2.07). ③ Acute and late side effects of radiotherapy would not increase when combined with chemotherapy.
Conclusion 　It can not be concluded that non-conventional fractionated radiotherapy can improve the CR and OS of head and neck cancer, for a small number of patients, but it will get effect when combined with concurrent chemotherapy, and would not increase acute or late side effects. The effects of HRT and C-HRT should be cared specially.

Citation： WANG Xin,AI Ping,SHEN Yali,REN Ruomei,LI Ping. Non-Conventional Fractionated Radiotherapy for Head and Neck Cancer: A Systematic Review. Chinese Journal of Evidence-Based Medicine, 2007, 07(6): 433-448. doi: Copy

1.	Horiot JC, Le Fur R, N’Guyen T, et al. Hyperfractionation versus conventional fractionation in oropharyngeal carcinoma: final analysis of a randomized trial of the EORTC cooperative group of radiotherapy. Radiother Oncol, 1992, 25(4): 231-241.
2.	Horiot JC, Bontemps P, van den Bogaert W, et al. Accelerated fractionation (AF) compared to conventional fractionation (CF) improves loco-regional control in the radiotherapy of advanced head and neck cancers: results of the EORTC 22851 randomized trial. Radiother Oncol, 1997, 44(2):111-121.
3.	Beck-Bornholdt HP, Dubben HH, Liertz-Petersen C, et al. Hyperfractionation: where do we stand? Radiother Oncol. 1997, 43(1): 1-21.
4.	Pignon JP, Bourhis J, Domenge C, et al. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet, 2000, 355(9208): 949-955.
5.	Datta NR, Choudhry AD, Gupta S. Twice a day versus once a day radiation therapy in head and neck cancer (Abstr). Int J Radia Oncol BiolPhys, 1989, 17(suppl.1): 132–133.
6.	Van den Bogaert W, van der Schueren E, Horiot JC, et al. The EORTC randomized trial on three fractions per day and misonidazole (trial no. 22811) in advanced head and neck cancer: long-term results and side effects. Radiother Oncol, 1995, 35(2): 91-99.
7.	Saunders MI, Dische S, Barrett A, et al. Randomnised multicentre rials of CHART vs conventional radiotherapy in head and neck and non-small-cell lung cancer: an interim report. Br J Cancer, 1995, 73: 1455–1462.
8.	Bourhis J, Calais G, Lapeyre M, et al. Concomitant radiochemotherapy or accelerated radiotherapy: analysis of two randomized trials of the French Head and Neck Cancer Group (GORTEC). Semin Oncol, 2004, 31(6): 822-826.
9.	Brizel DM, Albers ME, Fisher SR, et al. Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer. N Engl J Med, 1998, 338(25): 1798-1804.
10.	Budach V, Stuschke M, Budach W, et al. Hyperfractionated accelerated chemoradiation with concurrent fluorouracil-mitomycin is more effective than dose-escalated hyperfractionated accelerated radiation therapy alone in locally advanced head and neck cancer: final results of the radiotherapy cooperative clinical trials grouPof the German Cancer Society 95-06Prospective Randomized Trial. J Clin Oncol, 2005, 23(6): 1125–1135.
11.	Dobrowsky W, Naude J. Continuous hyperfractionated accelerated radiotherapy with/ without mitomycin C in head and neck cancers. Radiother Oncol, 2000, 57(2): 119–124.
12.	Fu KK, Pajack TF, Trotti A, et al. A radiation therapy oncolo Gy grouP (RTOG) Phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinoma: first report of RTOG 9003. Int J Radia Oncol BiolPhys, 2000, 48(1): 7–16.
13.	Hehr T, Classen J, Schreck U. Hyperfractionated accelerated radiotherapy alone and with concomitant chemotherapy to the head and neck: treated within and outside of randomized clinical trials. Int J Radiat Oncol BiolPhys, 2004, 58(5): 1424–1430.
14.	Jeremic B, Shibamoto Y, Milicic B, et al. Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplantin in locally advanced squamous cell carcinoma of the head and neck: aProspective randomized trial. J Clin Oncol, 2000, 18(7): 1458–1464.
15.	Marcial VA, Pajak TF, Chu C, et al. HyperfractionatedPhoton radiation therapy in the treatment of advanced squamous cell carcinoma of the oral cavity, Pharyx, larynx and sinuses, using radiation therapy as the onlyPlanned modality: (preliminary report) by the Radiation Therapy Oncolo Gy Group (RTOG). Int J Radia Oncol BiolPhys, 1987, 13: 41–47.
16.	Poulsen MG, Denham JW, Peters LJ, et al. A randomised trial of accelerated and conventional radiotherapy for stage III and IV squamous carcinoma of the head and neck: a Trans-Tasman Radiation Oncolo Gy GrouPStudy. Radiother Oncol, 2001, 60(2): 113–122.
17.	Sanchiz F, Milla A, Tormer J, et al. Single fractionPer day versus two fractionsPer day versus radiotherapy in the treatment of head and neck cancer. Int J Radia Oncol BiolPhys, 1990, 19: 1375–1350.
18.	Skladoeski K, Maciejeuski B, Golen M, et al. Randomized clinical trial on 7-day-continuous accelerated irradiation (CAIR) of head and neck cancer-report on 3-year tumor control and normal tissue toxicity. Radiother Oncol, 2000, 55: 101–110.
19.	Wendt TG, Grabenbauer GG, Rodel CM, et al. Simultaneous radiochemotherapy versus radiotherapy alone in advanced head and neck cancer: aandomized multicenter study. J Clin Oncol, 1998, 16(4): 1318–1324.
20.	Jackson SM, Weir LM, Hay JH, et al. A randomized trial of accelerated versus conventional radiotherapy in head and neck cancer. Radiother Oncol, 1997, 43: 39–46.
21.	OlmiP, Crispino S, Fallai C, et al. Locoregionally advancer carcinoma of the oropharynx: conventional radiotherapy vs accelerated hyperfractionated radiotherapy vs concomitant radiotherapy and chemotherapy -a multicenter randomized trial. Int J Radia Oncol BiolPhys, 2003, 55(1): 78–92.
22.	Pinto LHJ, CanaryPCV, Araujo CMM, et al. Prospective randomized trial comparing hyperfractionated versus conventional radiotherapy in stages III and IV oropharyngeal carcinoma. Int J Radia Oncol BiolPhys, 1991, 21: 557–562.
23.	HugueninP, Beer KT, Allarl A, et al. Concomitant cisplatin significantly improves locoregional control in advanced head and neck cancer treated with hyperfractionated radiotherapy. J Clin Oncol, 2004, 22: 4613–4621.
24.	Staar S, Rudat V, Stuetzer H, et al. Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy -results of a multicenteric randomized German trial in advanced head-and-neck cancer. Int J Radia Oncol BiolPhys, 2001, 50(5): 1161–1167.
25.	Overgaard J, Hausen HS, Speche L, et al. Five compared with six fractionsPer week of conventional radiotherapy of squamous-cell carcinoma of head and neck: DAHANCA 6 and 7 randomized control trial. Lancet, 2003, 362: 933-.
26.	Bernier J, Thames HD, Smith CD, et al. Tumor reponse, mucosal reactiona and late effects after conventional and hyperfractionated radiotherapy. Radiother Oncol, 1998, 47: 137–143.
27.	Dische S, Saunders M, Barrett A, et al. A randomised multicentre trial of CHART versus conventional radiotherapy in head and neck cancer. Radiother Oncol, 1997, 44(2): 123–136.
28.	Bentzen SM, Saunders MI, Dische S, et al. Radiotherapy-related early morbidity in head and neck cancer: quantitative clinical radiobiolo Gy as deduced from the CHART trial. Radiother Oncol, 2001, 60(2): 123–135.

1. Horiot JC, Le Fur R, N’Guyen T, et al. Hyperfractionation versus conventional fractionation in oropharyngeal carcinoma: final analysis of a randomized trial of the EORTC cooperative group of radiotherapy. Radiother Oncol, 1992, 25(4): 231-241.
2. Horiot JC, Bontemps P, van den Bogaert W, et al. Accelerated fractionation (AF) compared to conventional fractionation (CF) improves loco-regional control in the radiotherapy of advanced head and neck cancers: results of the EORTC 22851 randomized trial. Radiother Oncol, 1997, 44(2):111-121.
3. Beck-Bornholdt HP, Dubben HH, Liertz-Petersen C, et al. Hyperfractionation: where do we stand? Radiother Oncol. 1997, 43(1): 1-21.
4. Pignon JP, Bourhis J, Domenge C, et al. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet, 2000, 355(9208): 949-955.
5. Datta NR, Choudhry AD, Gupta S. Twice a day versus once a day radiation therapy in head and neck cancer (Abstr). Int J Radia Oncol BiolPhys, 1989, 17(suppl.1): 132–133.
6. Van den Bogaert W, van der Schueren E, Horiot JC, et al. The EORTC randomized trial on three fractions per day and misonidazole (trial no. 22811) in advanced head and neck cancer: long-term results and side effects. Radiother Oncol, 1995, 35(2): 91-99.
7. Saunders MI, Dische S, Barrett A, et al. Randomnised multicentre rials of CHART vs conventional radiotherapy in head and neck and non-small-cell lung cancer: an interim report. Br J Cancer, 1995, 73: 1455–1462.
8. Bourhis J, Calais G, Lapeyre M, et al. Concomitant radiochemotherapy or accelerated radiotherapy: analysis of two randomized trials of the French Head and Neck Cancer Group (GORTEC). Semin Oncol, 2004, 31(6): 822-826.
9. Brizel DM, Albers ME, Fisher SR, et al. Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer. N Engl J Med, 1998, 338(25): 1798-1804.
10. Budach V, Stuschke M, Budach W, et al. Hyperfractionated accelerated chemoradiation with concurrent fluorouracil-mitomycin is more effective than dose-escalated hyperfractionated accelerated radiation therapy alone in locally advanced head and neck cancer: final results of the radiotherapy cooperative clinical trials grouPof the German Cancer Society 95-06Prospective Randomized Trial. J Clin Oncol, 2005, 23(6): 1125–1135.
11. Dobrowsky W, Naude J. Continuous hyperfractionated accelerated radiotherapy with/ without mitomycin C in head and neck cancers. Radiother Oncol, 2000, 57(2): 119–124.
12. Fu KK, Pajack TF, Trotti A, et al. A radiation therapy oncolo Gy grouP (RTOG) Phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinoma: first report of RTOG 9003. Int J Radia Oncol BiolPhys, 2000, 48(1): 7–16.
13. Hehr T, Classen J, Schreck U. Hyperfractionated accelerated radiotherapy alone and with concomitant chemotherapy to the head and neck: treated within and outside of randomized clinical trials. Int J Radiat Oncol BiolPhys, 2004, 58(5): 1424–1430.
14. Jeremic B, Shibamoto Y, Milicic B, et al. Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplantin in locally advanced squamous cell carcinoma of the head and neck: aProspective randomized trial. J Clin Oncol, 2000, 18(7): 1458–1464.
15. Marcial VA, Pajak TF, Chu C, et al. HyperfractionatedPhoton radiation therapy in the treatment of advanced squamous cell carcinoma of the oral cavity, Pharyx, larynx and sinuses, using radiation therapy as the onlyPlanned modality: (preliminary report) by the Radiation Therapy Oncolo Gy Group (RTOG). Int J Radia Oncol BiolPhys, 1987, 13: 41–47.
16. Poulsen MG, Denham JW, Peters LJ, et al. A randomised trial of accelerated and conventional radiotherapy for stage III and IV squamous carcinoma of the head and neck: a Trans-Tasman Radiation Oncolo Gy GrouPStudy. Radiother Oncol, 2001, 60(2): 113–122.
17. Sanchiz F, Milla A, Tormer J, et al. Single fractionPer day versus two fractionsPer day versus radiotherapy in the treatment of head and neck cancer. Int J Radia Oncol BiolPhys, 1990, 19: 1375–1350.
18. Skladoeski K, Maciejeuski B, Golen M, et al. Randomized clinical trial on 7-day-continuous accelerated irradiation (CAIR) of head and neck cancer-report on 3-year tumor control and normal tissue toxicity. Radiother Oncol, 2000, 55: 101–110.
19. Wendt TG, Grabenbauer GG, Rodel CM, et al. Simultaneous radiochemotherapy versus radiotherapy alone in advanced head and neck cancer: aandomized multicenter study. J Clin Oncol, 1998, 16(4): 1318–1324.
20. Jackson SM, Weir LM, Hay JH, et al. A randomized trial of accelerated versus conventional radiotherapy in head and neck cancer. Radiother Oncol, 1997, 43: 39–46.
21. OlmiP, Crispino S, Fallai C, et al. Locoregionally advancer carcinoma of the oropharynx: conventional radiotherapy vs accelerated hyperfractionated radiotherapy vs concomitant radiotherapy and chemotherapy -a multicenter randomized trial. Int J Radia Oncol BiolPhys, 2003, 55(1): 78–92.
22. Pinto LHJ, CanaryPCV, Araujo CMM, et al. Prospective randomized trial comparing hyperfractionated versus conventional radiotherapy in stages III and IV oropharyngeal carcinoma. Int J Radia Oncol BiolPhys, 1991, 21: 557–562.
23. HugueninP, Beer KT, Allarl A, et al. Concomitant cisplatin significantly improves locoregional control in advanced head and neck cancer treated with hyperfractionated radiotherapy. J Clin Oncol, 2004, 22: 4613–4621.
24. Staar S, Rudat V, Stuetzer H, et al. Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy -results of a multicenteric randomized German trial in advanced head-and-neck cancer. Int J Radia Oncol BiolPhys, 2001, 50(5): 1161–1167.
25. Overgaard J, Hausen HS, Speche L, et al. Five compared with six fractionsPer week of conventional radiotherapy of squamous-cell carcinoma of head and neck: DAHANCA 6 and 7 randomized control trial. Lancet, 2003, 362: 933-.
26. Bernier J, Thames HD, Smith CD, et al. Tumor reponse, mucosal reactiona and late effects after conventional and hyperfractionated radiotherapy. Radiother Oncol, 1998, 47: 137–143.
27. Dische S, Saunders M, Barrett A, et al. A randomised multicentre trial of CHART versus conventional radiotherapy in head and neck cancer. Radiother Oncol, 1997, 44(2): 123–136.
28. Bentzen SM, Saunders MI, Dische S, et al. Radiotherapy-related early morbidity in head and neck cancer: quantitative clinical radiobiolo Gy as deduced from the CHART trial. Radiother Oncol, 2001, 60(2): 123–135.

Chinese Journal of Evidence-Based Medicine

Non-Conventional Fractionated Radiotherapy for Head and Neck Cancer: A Systematic Review

Abstract Full text Figures/Tables Video References Cited by

Format

Content