• 四川大學(xué)華西醫(yī)院腫瘤放療科（成都 610041）;

目的 　系統(tǒng)評(píng)價(jià)非常規(guī)分割放療治療頭頸部腫瘤的療效和副反應(yīng)，為臨床實(shí)踐提供證據(jù)。
方法 　計(jì)算機(jī)檢索CENTRAL、MEDLINE、EMbase、CBMdisc和VIP數(shù)據(jù)庫(kù)，并手工檢索10種中文醫(yī)學(xué)期刊，納入非常規(guī)分割放療與常規(guī)分割放療比較，或非常規(guī)分割放療+同步化療與單純非常規(guī)分割放療比較治療頭頸部腫瘤的隨機(jī)對(duì)照試驗(yàn)（RCT）。由兩位研究者進(jìn)行資料提取和質(zhì)量評(píng)價(jià)，并采用RevMan4.2.8軟件進(jìn)行Meta分析。
結(jié)果 　共檢索到551篇文獻(xiàn)，最終納入23個(gè)RCT，包含8 411例患者。其中13個(gè)是高質(zhì)量研究，其余為低質(zhì)量研究。Meta分析結(jié)果顯示：① 非常規(guī)分割放療與常規(guī)分割放療比較，僅分段加速超分割放療（S-HART）與連續(xù)加速放療（CAIR）組的完全緩解率較高，其RR分別為1.21［95%CI（1.02，1.44）］和3.31［95%CI（1.03，1.57）］；隨訪2年時(shí)，僅超分割放療（HRT）可提高2年總生存率［RR=1.32，95%CI（1.13，1.54）］；隨訪5年時(shí)，總生存率差異無(wú)統(tǒng)計(jì)學(xué)意義；大多數(shù)非常規(guī)分割放療會(huì)增加急性放射性副反應(yīng)的發(fā)生率，但均不會(huì)增加晚期放射性副反應(yīng)的發(fā)生率；② 非常規(guī)分割放療+同步化療與單純非常規(guī)分割放療比較，僅連續(xù)超分割放療（C-HRT）組的完全緩解率較高［RR=1.58，95%CI（1.18，2.11）］；隨訪2年時(shí)，非常規(guī)分割放療+同步化療組提高了2年總生存率［RR=1.35，95%CI（1.18，1.54）］；隨訪5年時(shí)，僅C-HRT組提高5年總生存率［RR=1.57，95%CI（1.19，2.07）］； 兩組急性和晚期放射性副反應(yīng)的發(fā)生率差異均無(wú)統(tǒng)計(jì)學(xué)意義。
結(jié)論 　本系統(tǒng)評(píng)價(jià)由于例數(shù)偏少，尚不能證明非常規(guī)分割放療可以提高頭頸部腫瘤患者的完全緩解率和總生存率；但與同步化療聯(lián)合時(shí)，可以在不增加急性和晚期放療并發(fā)癥的同時(shí)取得更好的療效，其中HRT和C-HRT的作用尤其值得關(guān)注。

引用本文： 王辛,艾平,沈婭麗,任若梅,李平. 非常規(guī)分割放療治療頭頸部腫瘤的系統(tǒng)評(píng)價(jià). 中國(guó)循證醫(yī)學(xué)雜志, 2007, 07(6): 433-448. doi: 復(fù)制

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. 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. 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. 3. Beck-Bornholdt HP, Dubben HH, Liertz-Petersen C, et al. Hyperfractionation: where do we stand? Radiother Oncol. 1997, 43(1): 1-21.
  4. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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.