Intervention Review

Hyperfractionated or accelerated radiotherapy for head and neck cancer

  1. Bertrand Baujat2,
  2. Jean Bourhis3,
  3. Pierre Blanchard1,
  4. Jens Overgaard4,
  5. Kian K Ang5,
  6. Michelle Saunders6,
  7. Aurélie Le Maître1,
  8. Jacques Bernier7,
  9. Jean Claude Horiot8,
  10. Emilie Maillard1,
  11. Thomas F Pajak9,
  12. Michael G Poulsen10,
  13. Abderrahmane Bourredjem1,
  14. Brian O'Sullivan11,
  15. Werner Dobrowsky12,
  16. Hliniak Andrzej13,
  17. Krzystof Skladowski14,
  18. John H Hay15,
  19. Luiz HJ Pinto16,
  20. Karen K Fu17,
  21. Carlo Fallai18,
  22. Richard Sylvester19,
  23. Jean Pierre Pignon1,*,
  24. MARCH Collaborative Group20

Editorial Group: Cochrane Ear, Nose and Throat Disorders Group

Published Online: 8 DEC 2010

Assessed as up-to-date: 7 AUG 2010

DOI: 10.1002/14651858.CD002026.pub2

Database Title

Additional Information

How to Cite

Baujat B, Bourhis J, Blanchard P, Overgaard J, Ang KK, Saunders M, Le Maître A, Bernier J, Horiot JC, Maillard E, Pajak TF, Poulsen MG, Bourredjem A, O'Sullivan B, Dobrowsky W, Andrzej H, Skladowski K, Hay JH, Pinto LHJ, Fu KK, Fallai C, Sylvester R, Pignon JP, MARCH Collaborative Group. Hyperfractionated or accelerated radiotherapy for head and neck cancer. Cochrane Database of Systematic Reviews 2010, Issue 12. Art. No.: CD002026. DOI: 10.1002/14651858.CD002026.pub2.

Author Information

  1. 1

    Institut Gustave Roussy, Biostatistics and Epidemiology Department, Villejuif Cedex, France

  2. 2

    Hôpital Foch, Head and Neck Surgery, Suresnes, France

  3. 3

    Institut Gustave Roussy, Département de Radiothérapie, Villejuif Cedex, France

  4. 4

    Aarhus University Hospital, Department of Experimental Clinical Oncology, Aarhus, Denmark

  5. 5

    MD Anderson Cancer Center, Radiation Oncology Department, Houston, Texas, USA

  6. 6

    Marie Curie Research Wing for Oncology, Radiation Oncology Department, Northwood, Middlesex, UK

  7. 7

    Clinique de Genolia, Service de Radio-Oncologie, Genolier, Switzerland

  8. 8

    Clinique de Genolia, Service de Radio-Oncologie, Genolia, Switzerland

  9. 9

    RTOG, Statistical Headquarters, Philadelphia, PA, USA

  10. 10

    Mater Queensland Radium Institute, Brisbane, Australia

  11. 11

    Princess Margaret Hospital, Radiation Oncology Department, Toronto, Ontario, Canada

  12. 12

    Northern Centre for Cancer Treatment, Newcastle General Hospital, Newcastle upon Tyne, UK

  13. 13

    Center for Oncology - M.SKL Curie, Warsaw, Poland

  14. 14

    Centrum Onkologii-Inst. M. Curie, Radiotherapy Clinic, Gliwice, Poland

  15. 15

    Vancouver Cancer Center, Department of Radiation Oncology, Vancouver, BC, Canada

  16. 16

    Instituto Nacional de Cancer, Departamento de Radioterapia, Rio de Janeiro, Brazil

  17. 17

    University of California San Francisco, San Mateo, CA, USA

  18. 18

    Instituto Nazionale dei Tumori, Dipartimento di Radiotherapia, Milano, Italy

  19. 19

    European Organisation for Research and Treatment of Cancer, Data Center, Brussels, Belgium

  20. 20

    Villejuif Cedex, France

*Jean Pierre Pignon, Biostatistics and Epidemiology Department, Institut Gustave Roussy, 39, rue Camille Desmoulins, Villejuif Cedex, 94805, France. jppignon@igr.fr.

Publication History

  1. Publication Status: New
  2. Published Online: 8 DEC 2010

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. Resumen
  5. 摘要

Background

Several trials have studied the role of altered fractionation radiotherapy in head and neck squamous cell carcinoma, but the effect of such treatment on survival is not clear.

Objectives

The aim of this individual patient data (IPD) meta-analysis was to assess whether this type of radiotherapy could improve survival.

Search methods

We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; CENTRAL (2010, Issue 3); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ISRCTN and additional sources for published and unpublished trials. The date of the most recent search was 8 August 2010.

Selection criteria

We identified randomised trials comparing conventional radiotherapy with hyperfractionated or accelerated radiotherapy, or both, in patients with non-metastatic head and neck squamous cell carcinomas and grouped trials into three pre-specified treatment categories: hyperfractionated, accelerated and accelerated with total dose reduction. Trials were eligible if they began recruitment after 1969 and ended before 1998.

Data collection and analysis

We obtained updated individual patient data. Overall survival was the main outcome measure. The secondary outcome measures were local or regional control rates (or both), distant control rates and cause-specific mortality.

Main results

We included 15 trials with 6515 patients. The median follow up was six years. Tumour sites were mostly oropharynx and larynx; 5221 (74%) patients had stage III-IV disease (UICC 2002). There was a significant survival benefit with altered fractionation radiotherapy, corresponding to an absolute benefit of 3.4% at five years (hazard ratio (HR) 0.92, 95% CI 0.86 to 0.97; P = 0.003). The benefit was significantly higher with hyperfractionated radiotherapy (8% at five years) than with accelerated radiotherapy (2% with accelerated fractionation without total dose reduction and 1.7% with total dose reduction at five years, P = 0.02). There was a benefit in locoregional control in favour of altered fractionation versus conventional radiotherapy (6.4% at five years; P < 0.0001), which was particularly efficient in reducing local failure, whereas the benefit on nodal control was less pronounced. The benefit was significantly higher in the youngest patients (under 50 year old) (HR 0.78, 95% CI 0.65 to 0.94), 0.95 (95% CI 0.83 to 1.09) for 51 to 60 year olds, 0.92 (95% CI 0.81 to 1.06) for 61 to 70 year olds, and 1.08 (95% CI 0.89 to 1.30) for those over 70 years old; test for trends P = 0.007).

Authors' conclusions

Altered fractionation radiotherapy improves survival in patients with head and neck squamous cell carcinoma. Comparison of the different types of altered radiotherapy suggests that hyperfractionation provides the greatest benefit. An update of this IPD meta-analysis (MARCH 2), which will increase the power of this analysis and allow for other comparisons, is currently in progress.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. Resumen
  5. 摘要

Hyperfractionated or accelerated radiotherapy for head and neck cancer

Radiotherapy is often used to treat head and neck cancers. The dosage of radiation is measured in Gray (Gy). When radiotherapy is given alone, the most commonly used schedule is 2 Gy in a single fraction per day, five days a week, for seven weeks. However, alternative radiotherapy regimens to reduce the total treatment time for head and neck cancers have been assessed. 'Acceleration' of the treatment (delivering the same total dose in a shorter time) should reduce the regrowth of the tumour between sessions, resulting in improved local control of the disease. In 'hyperfractionated' regimens, two to three fractions are delivered each day, with a reduced dose per fraction equal to 1.1 to 1.2 Gy. The reduction of the dose per fraction may reduce the risk of late toxicity, despite an increased total dose. Acceleration and hyperfractionation can be combined, in particular for regimens in which overall treatment time is reduced.

This Cochrane Review is an individual patient data based meta-analysis and the aim was to assess whether this type of radiotherapy could improve survival. We identified randomised trials comparing conventional radiotherapy with hyperfractionated or accelerated radiotherapy, or both, in patients with non-metastatic head and neck cancers and grouped trials into three pre-specified categories: hyperfractionated, accelerated without total dose reduction and accelerated with total dose reduction. The results of this meta-analysis suggest that altered fractionation radiotherapy improves survival in patients with head and neck cancer. Comparison of the different types of altered fractionation radiotherapy suggests that hyperfractionation provides the greatest benefit.

Individual patient data meta-analysis is a long process and this review included all eligible trials which had completed recruiting patients by 1998. A major update of the analysis, including data from more recent trials, is currently underway.

 

Resumen

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. Resumen
  5. 摘要

Antecedentes

Radioterapia hiperfraccionada o acelerada para el cáncer de cabeza y cuello

En varios ensayos se ha estudiado la función de la radioterapia de fraccionamiento modificado en el carcinoma escamocelular de cabeza y el cuello, aunque no se ha elucidado el efecto de este tratamiento sobre la supervivencia.

Objetivos

El objetivo de este metanálisis de datos de pacientes individuales fue evaluar si este tipo de radioterapia podría mejorar la supervivencia.

Estrategia de búsqueda

Se hicieron búsquedas en el Registro de Ensayos del Grupo Cochrane de Enfermedades de Oído, Nariz y Garganta (Cochrane Ear, Nose and Throat Disorders Group); CENTRAL (2010, número 3); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ISRCTN y fuentes adicionales de ensayos publicados y no publicados. La fecha de la búsqueda más reciente fue el 8 de agosto 2010.

Criterios de selección

Se identificaron ensayos aleatorios que compararon la radioterapia convencional con la radioterapia hiperfraccionada o acelerada, o ambas, en pacientes con carcinoma escamocelular de cabeza y cuello no metastásicos, y los ensayos se agruparon en tres categorías de tratamiento predefinidas: hiperfraccionada, acelerada y acelerada con reducción total de la dosis. Los ensayos eran aptos para la inclusión si comenzaron la incorporación de participantes después de 1969 y la misma concluyó antes de 1998.

Obtención y análisis de los datos

Se obtuvieron los datos de pacientes individuales actualizados. La medida de resultado principal fue la supervivencia general. Las medidas de resultado secundarias fueron las tasas de control local o regional (o ambas), las tasas de control a distancia y la mortalidad de causa específica.

Resultados principales

Se incluyeron 15 ensayos con 6515 pacientes. La mediana del seguimiento fue seis años. Los tumores se localizaban principalmente en la orofaringe y la laringe; 5221 (74%) pacientes presentaban la enfermedad en estadio III o IV (UICC 2002). Hubo un beneficio significativo en la supervivencia con la radioterapia de fraccionamiento modificado, lo que corresponde a un beneficio absoluto de un 3,4% a cinco años (cociente de riesgos instantáneos [CRI] 0,92; IC del 95%: 0,86 a 0,97; P = 0,003). El beneficio fue significativamente mayor con la radioterapia hiperfraccionada (8% a cinco años) que con la radioterapia acelerada (2% con el fraccionamiento acelerado sin reducción de la dosis total y 1,7% con reducción de la dosis total a cinco años, p = 0,02). Hubo un efecto beneficioso en el control locorregional a favor del fraccionamiento modificado versus la radioterapia convencional (6,4% a cinco años; p < 0,0001), el cual fue particularmente eficaz en reducir el fracaso local, mientras que el beneficio en el control ganglionar fue menos pronunciado. El beneficio fue significativamente mayor en los pacientes más jóvenes (menores de 50 año de edad) (CRI 0,78; IC del 95%: 0,65 a 0,94); 0,95 (IC del 95%: 0,83 a 1,09) para los pacientes entre 51 y 60 años de edad; 0,92 (IC del 95%: 0,81 a 1,06) para los pacientes entre 61 y 70 años; y 1,08 (IC del 95%: 0,89 a 1,30) para los mayores de 70 años de edad; pruebas de tendencia p = 0,007.

Conclusiones de los autores

La radioterapia de fraccionamiento modificado mejora la supervivencia en los pacientes con carcinoma escamocelular de cabeza y cuello. La comparación de los diferentes tipos de radioterapia modificada indica que el hiperfraccionamiento proporciona el mayor beneficio. Una actualización de este metanálisis de datos de pacientes individuales (MARCH 2), que aumentará el poder estadístico de este análisis y permitirá otras comparaciones, se está llevando a cabo.

Traducción

Traducción realizada por el Centro Cochrane Iberoamericano

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. Resumen
  5. 摘要

背景

對於頭頸癌的多分次 (hyperfractionated) 或加速 (accelerated) 放射線治療

好幾個臨床試驗已經研究過對於頭頸鱗狀上皮細胞癌改變分次 (fractionation) 的放射線治療的角色，但其對存活的效果尚不清楚。

目標

此個別病患資料 (individual patient data, IPD) 統合分析的目的是要評估這種放射線治療是否可以改善存活。

搜尋策略

我們搜尋了the Cochrane Ear, Nose and Throat Disorders Group Trials Register; CENTRAL (2010年第三期); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ISRCTN以及額外的已發表或未發表的臨床試驗資源，最近一次搜尋的日期是2010年8月8日。

選擇標準

在未轉移的頭頸鱗狀上皮細胞癌的病人，我們找出比較傳統放射線治療與多分次或加速的 (或合併兩者) 放射線治療的隨機臨床試驗，並且把這些臨床試驗分成三種事先指定的治療類別：多分次的、加速的或是加速的合併總劑量減少。在1969年之後開始收病人並且於1998年之前結束的才是符合條件的臨床試驗。

資料收集與分析

我們取得更新過的個別病患資料，整體存活是預後的主要測量指標，次要的預後指標則是局部或區域 (或是兩者) 的控制率、遠端的控制率和特定原因之死亡率。

主要結論

我們包含了15個臨床試驗、6515個病人，追蹤的中位數是6年。腫瘤的位置大部分在口咽及喉部，5221個 (74%) 病人是第3 – 4期 (UICC 2002) 。改變分次的放射線治療有明顯的存活助益，相當於5年有3.4% 的絕對助益 (HR 0.92, 95% CI 0.86 to 0.97; P = 0.003) 。和加速放射線治療相比 (加速分次但整體劑量未減少者5年為2% ，有整體劑量減少者為1.7%) ，這樣的助益在多分次的放射線治療尤其顯著 (5年為8% ，P = 0.02) 。在局部區域的控制上，改變分次和傳統的放射線治療相比較為有益 (5年6.4%; P <0.0001) ，尤其是能有效減少局部的失敗，但對淋巴結控制的助益則較不顯著。對於年輕人這樣的好處更為顯著 (50歲以下HR 0.78, 95% CI 0.65 to 0.94) ，51 – 60歲HR 0.95 (95% CI 0.83 to 1.09) ，61 – 70歲HR 0.92 (95% CI 0.81 to 1.06) ，70歲以上HR 1.08 (95% CI 0.89 to 1.30) (test for trends, P = 0.007) 。

作者結論

對於頭頸鱗狀上皮細胞癌的病人，改變分次的放射線治療會改善存活。經由比較不同種改變後的放射線治療顯示多分次的方式提供最大的效益。這個IPD統合分析的更新 (MARCH 2) 目前正在進行中，它可增加這個分析的檢定力，並可容許其他的比較。

翻譯人

本摘要由臺北榮民總醫院余垣斌翻譯。

此翻譯計畫由臺灣國家衛生研究院 (National Health Research Institutes, Taiwan) 統籌。

總結

少量多次或加速放射線治療對於頭頸癌的角色放射線治療常用於治療頭頸癌，它的劑量是以Gray (Gy) 來計量。當單獨用放射線治療時，最常用的療程是每天單一分次給予2 Gy、1周治療5天、總共治療7周。然而，為減少頭頸癌總治療時間而使用的其他放射治療處方也曾經被評估過。治療的 ‘加速’ (在較短時間內給予相同的總劑量) 應該可減少腫瘤在不同次治療間的再生長，而此可造成局部控制的改善。在多分次的治療處方中，每天給予2至3次，但是減少每個分次的劑量至1.1 – 1.2 Gy。雖然總劑量是增加的，每個分次劑量的減少可能會降低晚期毒性的風險。加速和多分次的方式可以合併使用，尤其對於那些整體治療時間需要減少的處方而言。本篇Cochrane的評論是一個以個別病患資料為基礎的統合分析，其目的是要評估這種型態的放射線治療是否可改善存活。我們找出在未轉移的頭頸癌病人比較傳統放射線治療和多分次或加速的 (或合併兩者) 放射線治療的隨機臨床試驗，並將之分組成三種預先設定的類別：多分次的、加速而總劑量未減少的以及加速且總劑量減少的。這個統合分析的結果顯示，改變分次的放射線治療可改善頭頸癌病人的存活。而比較不同型態的改變分次的放射線治療顯示，多分次的治療提供最大的效益。個別病患資料的統合分析是一個冗長的過程，這個評論包含了所有符合條件的臨床試驗，意即在1998年已完成收錄病人的程序者。這個分析一個重大的更新會包括更多最近臨床試驗的資料，目前正在進行中。

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