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Meta-Analysis
. 2010 Dec 8;2010(12):CD006387.
doi: 10.1002/14651858.CD006387.pub2.

Interventions for the treatment of oral cavity and oropharyngeal cancer: radiotherapy

Anne-Marie Glenny  1 , Susan Furness, Helen V Worthington, David I Conway, Richard Oliver, Jan E Clarkson, Michaelina Macluskey, Sue Pavitt, Kelvin Kw Chan, Paul Brocklehurst; CSROC Expert Panel
Affiliations
Meta-Analysis

Interventions for the treatment of oral cavity and oropharyngeal cancer: radiotherapy

Anne-Marie Glenny et al. Cochrane Database Syst Rev. .

Abstract

Background: The management of advanced oral cavity and oropharyngeal cancers is problematic and has traditionally relied on surgery and radiotherapy, both of which are associated with substantial adverse effects. Radiotherapy has been in use since the 1950s and has traditionally been given as single daily doses. This method of dividing up the total dose, or fractionation, has been modified over the years and a variety of approaches have been developed with the aim of improving survival whilst maintaining acceptable toxicity.

Objectives: To determine which radiotherapy regimens for oral cavity and oropharyngeal cancers result in increased overall survival, disease free survival, progression free survival and locoregional control.

Search strategy: The following electronic databases were searched: the Cochrane Oral Health Group's Trials Register (to 28 July 2010), CENTRAL (The Cochrane Library 2010, Issue 3), MEDLINE via OVID (1950 to 28 July 2010) and EMBASE via OVID (1980 to 28 July 2010). There were no restrictions regarding language or date of publication.

Selection criteria: Randomised controlled trials where more than 50% of participants had primary tumours of the oral cavity or oropharynx, and which compared two or more radiotherapy regimens, radiotherapy versus other treatment modality, or the addition of radiotherapy to other treatment modalities.

Data collection and analysis: Data extraction and assessment of risk of bias was undertaken independently by two or more authors. Study authors were contacted for additional information as required. Adverse events data were collected from published trials.

Main results: 30 trials involving 6535 participants were included. Seventeen trials compared some form of altered fractionation (hyperfractionation/accelerated) radiotherapy with conventional radiotherapy; three trials compared different altered fractionation regimens; one trial compared timing of radiotherapy, five trials evaluated neutron therapy and four trials evaluated the addition of pre-operative radiotherapy. Pooling trials of any altered fractionation radiotherapy compared to a conventional schedule showed a statistically significant reduction in total mortality (hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.76 to 0.98). In addition, a statistically significant difference in favour of the altered fractionation was shown for the outcome of locoregional control (HR 0.79, 95% CI 0.70 to 0.89). No statistically significant difference was shown for disease free survival.No statistically significant difference was shown for any other comparison.

Authors' conclusions: Altered fractionation radiotherapy is associated with an improvement in overall survival and locoregional control in patients with oral cavity and oropharyngeal cancers. More accurate methods of reporting adverse events are needed in order to truly assess the clinical performance of different radiotherapy regimens.

PubMed Disclaimer

Conflict of interest statement

None known.

Figures

1
1
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
2
2
Forest plot of comparison: Summary analyses for altered fractionation versus conventional radiotherapy, outcome: Total mortality.
3
3
Forest plot of comparison: Summary analyses for altered fractionation versus conventional radiotherapy, outcome: Locoregional control.
4
4
Forest plot of comparison: Summary analyses for altered fractionation versus conventional radiotherapy, outcome: Disease free survival.
1.1
1.1. Analysis
Comparison 1 Altered fractionation versus conventional radiotherapy, Outcome 1 Total mortality (using IPD where available).
1.2
1.2. Analysis
Comparison 1 Altered fractionation versus conventional radiotherapy, Outcome 2 Locoregional control (using IPD where available).
1.3
1.3. Analysis
Comparison 1 Altered fractionation versus conventional radiotherapy, Outcome 3 Disease free survival.
2.1
2.1. Analysis
Comparison 2 Summary analyses for altered fractionation versus conventional radiotherapy, Outcome 1 Total mortality.
2.2
2.2. Analysis
Comparison 2 Summary analyses for altered fractionation versus conventional radiotherapy, Outcome 2 Locoregional control.
2.3
2.3. Analysis
Comparison 2 Summary analyses for altered fractionation versus conventional radiotherapy, Outcome 3 Disease free survival.
3.1
3.1. Analysis
Comparison 3 Neutron therapy, Outcome 1 Total mortality.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD006387

References

References to studies included in this review

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References to studies excluded from this review

Arimoto 2003 {published data only}
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    1. Flores AD, Kandil A, Jamshed A, Khafaga Y, Schultz H, Rostom A, et al. The Saudi experience with neutron therapy in locally advanced head and neck cancers. Bulletin du Cancer/Radiotherapie 1996;83 Suppl:106s‐9s. - PubMed
Garden 2004 {published data only}
    1. Garden AS, Harris J, Vokes EE, Forastiere AA, Ridge JA, Jones C, et al. Preliminary results of Radiation Therapy Oncology Group 97‐03: a randomized phase ii trial of concurrent radiation and chemotherapy for advanced squamous cell carcinomas of the head and neck. Journal of Clinical Oncology 2004;22(14):2856‐64. - PubMed
Giglio 1997 {published data only}
    1. Giglio R, Mickiewicz E, Pradier R, Roth B, Gatica G, Califano L, et al. Chemotherapy + alternating hyperfractionated radiotherapy vs hyperfractionated radiotherapy alone in patients with inoperable stage III and IV epidermoid carcinoma. Prensa Medica Argentina 1997; Vol. 84, issue 5.
Hansen 1997 {published data only}
    1. Hansen O, Overgaard J, Hansen HS, Overgaard M, Hoyer M, Jorgensen KE, et al. Importance of overall treatment time for the outcome of radiotherapy of advanced head and neck carcinoma: dependency on tumor differentiation. Radiotherapy & Oncology 1997;43(1):47‐51. - PubMed
Hering 1981 {published data only}
    1. Dieckmann J, Morgenroth K, Hering KG, Will CH. Histo‐morphologic findings and first clinical results after preoperative short term preliminary irradiation with telecobalt in patients with epidermoid cancers of the mouth floor. Strahlentherapie. Sonderbande 1981;76:206‐11. - PubMed
Hintz 1979 {published data only}
    1. Hintz B, Charyulu K, Chandler JR, Sudarsanam A, Garciga C. Randomized study of local control and survival following radical surgery or radiation therapy in oral and laryngeal carcinomas. Journal of Surgical Oncology 1979;12:61‐74. - PubMed
Holsti 1988 {published data only}
    1. Holsti LR, Mantyla M. Split‐course versus continuous radiotherapy. Analysis of a randomized trial from 1964 to 1967. Acta Oncologica 1988;27(2):153‐61. - PubMed
Jackson 1997 {published data only}
    1. Jackson SM, Weir LM, Hay JH, Tsang VH, Durham JS. A randomised trial of accelerated versus conventional radiotherapy in head and neck cancer. Radiotherapy & Oncology 1997;43(1):39‐46. - PubMed
Janot 2008 {published data only}
    1. Janot F, Raucourt D, Benhamou E, Ferron C, Dolivet G, Bensadoun RJ, et al. Randomized trial of postoperative reirradiation combined with chemotherapy after salvage surgery compared with salvage surgery alone in head and neck carcinoma. Journal of Clinical Oncology 2008;26(34):5518‐23. - PubMed
Johnson 1995 {published data only}
    1. Johnson CR, Schmidt‐Ullrich RK, Arthur DW, Huang DT, Duffy EW. Standard once‐daily versus thrice‐daily concomitant boost accelerated superfractionated irradiation for advanced squamous cell carcinoma of the head and neck: preliminary results of a prospective randomized trial. International Journal of Radiation Oncology, Biology, Physics 1995;32(971):162.
Katori 2007 {published data only}
    1. Katori H, Tsukuda M, Watai K. Comparison of hyperfractionation and conventional fractionation radiotherapy with concurrent docetaxel, cisplatin and 5‐fluorouracil (TPF) chemotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Cancer Chemotherapy & Pharmacology 2007;60(3):399‐406. - PubMed
Klima 1988 {published data only}
    1. Klima A, Bergmann I, Szepesi S. Multimodality treatment in stage IV squamous cell carcinoma of the head and neck. A long‐term follow‐up. Journal of Laryngology & Otology 1992;106(3):234‐7. - PubMed
    1. Klima A, Klippstein TH, Bergmann L, Szepesi S, Ilberg CV. Adjuvant chemotherapy in stage III and IV squamous cell carcinoma of the head and neck. Journal of Laryngology & Otology 1988;102:337‐40. - PubMed
    1. Klima A, Ilberg C, Bergmann L, Klippstein T, Zoubek A, Mitrou PS, et al. The effect of radio‐ and chemotherapy on survival in advanced head and neck tumors. Strahlentherapie und Onkologie 1987;163(5):297‐300. - PubMed
    1. Klima A, Ilberg C, Bergmann L, Zoubek A, Klippstein T, Mitrou PS, et al. Chemotherapy or chemotherapy and radiotherapy in advanced head and neck tumors. A prospective, randomized study comparing the 2 therapeutic modalities. Head & Neck Oncology (HNO) 1987;35(2):78‐83. - PubMed
    1. Klima A, Ilberg C, Klippstein T, Szepesi S. Chemotherapy of advanced head and neck tumors. A prospective randomized study comparing the effectiveness of chemotherapy alone to a chemo‐radiotherapy procedure. Laryngologie, Rhinologie, Otologie 1987;66(4):205‐10. - PubMed
Kokal 1988 {published data only}
    1. Kokal WA, Neifeld JP, Eisert D, Lipsett JA, Lawrence W, Beatty JD, et al. Postoperative radiation as adjuvant treatment for carcinoma of the oral cavity, larynx, and pharynx: preliminary report of a prospective randomized trial. Journal of Surgical Oncology 1988;38:71‐6. - PubMed
Kramer 1987 {published data only}
    1. Kramer S, Gelber RD, Snow JB, Marcial VA, Lowry LD, Davis LW, et al. Combined radiation therapy and surgery in the management of advanced head and neck cancer: final report of study 73‐03 of the Radiation Therapy Oncology Group. Head & Neck Surgery 1987;10(1):19‐30. - PubMed
Maor 1983 {published data only}
    1. Maor MH, Hussey DH. Experience with fast neutron radiotherapy at the M.D. Anderson Hospital with emphasis on the randomized head and neck trial. Strahlentherapie. Sonderbande 1981;77:11‐6. - PubMed
    1. Maor MH, Hussey DH, Barkley HT Jr, Peters LJ. Neutron therapy for head and neck cancer: II. Further follow‐up on the M.D. Anderson TAMVEC randomized clinical trial. International Journal of Radiation Oncology, Biology, Physics 1983;9:1261‐5. - PubMed
    1. Maor MH, Hussey DH, Barkley HT, Jesse RH, Fletcher GH. Further follow‐up on the M. D. Anderson trial on fast neutron therapy for head and neck cancer. International Journal of Radiation Oncology, Biology, Physics 1981;7(9):1212‐3.
    1. Maor MH, Hussey DH, Fletcher GH, Jesse RH. Fast neutron therapy for locally advanced head and neck tumors. International Journal of Radiation Oncology, Biology, Physics 1981;7(2):155‐63. - PubMed
Mishra 1996 {published data only}
    1. Mishra RC, Singh DN, Mishra TK. Post‐operative radiotherapy in carcinoma of buccal mucosa, a prospective randomized trial. European Journal of Surgical Oncology 1996;22(5):502‐4. - PubMed
Nissenbaum 1984 {published data only}
    1. Nissenbaum M, Browde S, Bezwoda WR, Moor NG, Derman DP. Treatment of advanced head and neck cancer: multiple daily dose fractionated radiation therapy and sequential multimodal treatment approach. Medical & Pediatric Oncology 1984;12(3):204‐8. - PubMed
Noel 1997 {published data only}
    1. Noel G, Feuvret L, Coeffic D, Germain I, Mazeron JJ. Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced head and neck carcinoma: final report of a randomized trial. Cancer/Radiotherapie 1997;1(3):265‐6.
Noel 1997a {published data only}
    1. Noel G, Feuvret L, Coeffic D, Germain I, Mazeron JJ. Five‐year update of a randomized trial alternating radiotherapy and chemotherapy compared with radiotherapy in treatment of unresectable squamous cell carcinoma of the head and neck. Cancer/Radiotherapie 1997;1(3):262‐3.
Noel 1997b {published data only}
    1. Noel G, Feuvret L, Coeffic D, Germain I, Mazeron JJ. Randomised multicentre trials of CHART vs conventional radiotherapy in head and neck and non‐small cell lung cancer: An interim report. Cancer/Radiotherapie 1997;1(3):263‐4.
Noel 2001 {published data only}
    1. Noel G, Mazeron JJ. Randomized clinical trial on 7‐day continuous accelerated irradiation (CAIR) of head and neck cancer. Report on 3‐year tumour control and normal tissue toxicity. Cancer/Radiotherapie 2001;5(2):207‐8. - PubMed
Rink 1989 {published data only}
    1. Rink B, Neumann HJ, Kuchler I. Clinical experience with different modes of preoperative radiotherapy in advanced carcinomas of the tongue and the floor of the mouth. Deutsche Zeitschrift fur Mund‐, Kiefer‐, und Gesichts‐Chirurgie 1989;13(4):286‐90. - PubMed
Robertson 1998 {published data only}
    1. Robertson AG, Soutar DS, Paul J, Webster M, Leonard AG, Moore KP, et al. Early closure of a randomized trial: surgery and postoperative radiotherapy versus radiotherapy in the management of intra‐oral tumours. Clinical Oncology 1998;10:155‐60. - PubMed
Sanchiz 1990 {published data only}
    1. Sanchiz F, Milla A, Torner J, Bonet F, Artola N, Carreno L, et al. Single fraction per day versus two fractions per day versus radiochemotherapy in the treatment of head and neck cancer. International Journal of Radiation Oncology, Biology, Physics 1990;19(6):1347‐50. - PubMed
Singh 1984 {published data only}
    1. Singh R, Rai G, Singh SK, Tandon VK, Bhadury S, Shrivastava M, et al. Fractionation study on 3f/wk or 5f/wk treatment of oral carcinoma. Indian Journal of Radiology and Imaging 1984;38(2):153‐9.
Snow 1981 {published data only}
    1. Marcial VA, Gelber R, Kramer S, Snow JB, Davis LW, Vallecillo LA. Does preoperative irradiation increase the rate of surgical complications in carcinoma of the head and neck? A Radiation Therapy Oncology Group Report. Cancer 1982;49:1297‐1301. - PubMed
    1. Snow JB, Gelber RD, Kramer S, Davis LW, Marcial VA, Lowry LD. Comparison of preoperative and postoperative radiation therapy for patients with carcinoma of the head and neck. Interim report. Acta Otolaryngologica 1981;91(5‐6):611‐26. - PubMed
Srivastava 2001 {published data only}
    1. Srivastava K, Srivastava M. Concomitant boost radiotherapy vs conventional radiotherapy in advanced oral cavity and oropharynx cancers. Indian Journal of Radiology and Imaging 2001;11(3):127‐30.
Strong 1978 {published data only}
    1. Strong MS, Vaughan CW, Kayne HL, Aral IM, Ucmakli A, Feldman M, et al. A randomized trial of preoperative radiotherapy in cancer of the oropharynx and hypopharynx. American Journal of Surgery 1978;136(4):494‐500. - PubMed
Suwinski 2008 {published data only}
    1. Suwinski R, Bankowska‐Wozniak M, Majewski W, Idasiak A, Maciejewski A, Ziolkowska E, et al. Randomized clinical trial on 7‐days‐a‐week postoperative radiotherapy for high‐risk squamous cell head and neck cancer. Radiotherapy & Oncology 2008;87(2):155‐63. - PubMed
    1. Suwinski R, Bankowska‐Wozniak M, Majewski W, Sowa A, Galwas K, Ziolkowska E, et al. A randomized clinical trial on continuous 7‐day‐a‐week postoperative radiotherapy in high‐risk squamous cell head and neck cancer: a preliminary report on acute normal tissue reactions. International Journal of Radiation Oncology, Biology, Physics 2003;57(2 Suppl):S403.
    1. Suwinski R, Bankowska‐Wozniak M, Majewski W, Sowa A, Idasiak A, Ziolkowska E, et al. Randomized clinical trial on continuous 7‐days‐a‐week postoperative radiotherapy for high‐risk squamous cell head‐and‐neck cancer: a report on acute normal tissue reactions. Radiotherapy & Oncology 2005;77(1):58‐64. - PubMed
    1. Suwinski R, Jaworska M, Nikiel B, Bankowska‐Wozniak M. E22 ‐ Randomized clinical trial on 7‐days‐a‐week postoperative radiotherapy for high risk head and neck cancer: factors influencing loco‐regional control. Strahlentherapie und Onkologie 2007;183(Suppl 2):81‐3.
Tupchong 1991 {published data only}
    1. Tupchong L, Scott CB, Blitzer PH, Marcial VA, Lowry LD, Jacobs JR, et al. Randomized study of preoperative versus postoperative radiation therapy in advanced head and neck carcinoma: long‐term follow‐up of RTOG study 73‐03. International Journal of Radiation Oncology, Biology, Physics 1991;20(1):21‐8. - PubMed

References to studies awaiting assessment

Ang 2007 {published data only}
    1. Ang K, Pajak T, Rosenthal DI, Nguyen F, Lu C, Kim H, et al. A phase III trial to compare standard versus accelerated fractionation in combination with concurrent cisplatin for head and neck carcinomas (RTOG 0129): report of compliance and toxicity. International Journal of Radiation Oncology, Biology, Physics 2007;69(3 Suppl 1):S12‐3, Abs No 21.
Ghosh 2006 {published data only}
    1. Ghosh S, Agarwal JP, Bhutani R, Vora A, Prabhas K, D'Cruz A, et al. Randomized trial of conventional fractionated RT (CFRT) vs. concomitant chemo radiotherapy (CTRT) and accelerated radiotherapy (ACRT) in patients with advanced, non nasopharyngeal, squamous cell cancers of the head and neck region. International Journal of Radiation Oncology, Biology, Physics 2006;66(3):S191.
Nutting 2009a {published data only}
    1. Nutting C, A'Hern R, Rogers MS, Sydenham MA, Adab F, Harrington K, et al. First results of a phase III multicenter randomized controlled trial of intensity modulated (IMRT) versus conventional radiotherapy (RT) in head and neck cancer (PARSPORT: ISRCTN48243537; CRUK/03/005). Proceedings from the 45th American Society of Clinical Oncology (ASCO) Annual Meeting, Orlando, FL, USA, May 29‐June 2 2009. Journal of Clinical Oncology 2009;27(15S):Abs No LBA6006.
Rodrigo 2004 {published data only}
    1. Rodrigo JP, Maseda E, Maldonado M, Aldama P, Puente M, Llorente JL, et al. Efficacy of postoperative radiation therapy for squamous cell carcinoma of the head and neck: results of a prospective randomised clinical trial. Acta Otorrinolaringologica Espanola 2004;55(9):415‐9. - PubMed
Rosenthal 2006 {published data only}
    1. Peters LJ, Goepfert H, Ang KK, Byers RM, Maor MH, Guillamondegui O, et al. Evaluation of the dose for postoperative radiation therapy of head and neck cancer: first report of a prospective randomized trial. International Journal of Radiation Oncology, Biology, Physics 1993;26(1):3‐11. - PubMed
    1. Rosenthal DI, Peters LJ, Morrison WH, Garden AS, Oswald MJ, El‐Naggar A, et al. The final report of a prospective randomized trial to evaluate the dose‐response relationship for postoperative radiation therapy (PORT) and pathologic risk groups in patients with head and neck cancer (HNC). International Journal of Radiation Oncology, Biology, Physics 2006;66(3):S411. - PMC - PubMed
Skladowski 2001 {published data only}
    1. Skladowski K, Golen M, Wygoda A, Przeorek W, Sygula M, Pilecki B, et al. What is new with ,,CAIR" fractionation? ‐ A next Gliwice trial on 7 fractions in 7 days versus 7 fractions in 5 days is undergoing. In: Kogelnik HD, Lukas P, Sedlmayer F editor(s). Progress in Radio‐Oncology VII, Proceedings of the 7th International Meeting on Progress in Radio Oncology ‐ ICRO/OGRO 7. Italy: Monduzzi Editore, 2002:459‐64.
    1. Skladowski K, Hutnik M, Wygoda A, Golen M, Pilecki B, Rutkowski T, et al. Randomised clinical trial on two accelerated radiation treatments for patients with head and neck cancer. First report on early results of Cair‐2 study. Strahlentherapie und Onkologie 2007;183:A07.
    1. Skladowski K, Hutnik M, Wygoda A, Sasiadek W, Rutkowski T, Golen M, et al. Two accelerated radiation treatments have produced identical acute mucosal toxicity profile. An interim report on CAIR‐2 phase III trial for head and neck cancer patients. Radiotherapy & Oncology 2007;82:235.
    1. Skladowski K, Hutnik M, Wygoda A, Sygula M, Golen M, Pilecki B, et al. 7 fractions in 7 days versus 7 fractions in 5 days ‐ an interim report on early treatment tolerance in CAIR‐2 randomized clinical trial for head and neck cancer patients. Radiotherapy & Oncology 2004;73:S16‐7.
    1. Skladowski K, Wygoda A, Maciejewski A, Rutkowski T, Poltorak S, Maciejewski B. Definitive accelerated radiotherapy for head and neck cancer patients ‐ The results of organ preservation and prognostic‐factor analysis of CAIR‐2 phase III trial. Oral Oncology 2009:198.

References to ongoing studies

Moergel 2009 {published data only}
    1. Moergel M, Jahn‐Eimermacher A, Krummernauer F, Reichert TE, Wagner W, Wendt TG, et al. Effectiveness of adjuvant radiotherapy in patients with oropharyngeal and floor of mouth squamous cell carcinoma and concomitant histological verification of singular ipsilateral cervical lymph node metastasis (pN1‐state)‐‐a prospective multicenter randomized controlled clinical trial using a comprehensive cohort design. Trials 2009;10:118. - PMC - PubMed

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