Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2005 Jan 25;2004(1):CD004700.
doi: 10.1002/14651858.CD004700.pub2.

Early versus late chest radiotherapy for limited stage small cell lung cancer

Affiliations
Meta-Analysis

Early versus late chest radiotherapy for limited stage small cell lung cancer

M C G Pijls-Johannesma et al. Cochrane Database Syst Rev. .

Abstract

Background: It is standard clinical practice to combine chemotherapy and chest radiotherapy in treating patients with limited-stage small cell lung cancer. However, the best way to integrate both modalities is unclear.

Objectives: To establish the most effective way of combining chest radiotherapy with chemotherapy for patients with limited-stage small cell lung cancer in order to improve long-term survival.

Search strategy: The electronic databases MEDLINE, EMBASE, Cancerlit and the Cochrane Central Register of Controlled Trials (CENTRAL), reference lists, handsearching of journals and conference proceedings, and discussion with experts were used to identify potentially eligible trials, published and unpublished.

Selection criteria: Randomised controlled clinical trials comparing different timing of chest radiotherapy in patients with limited-stage small cell lung cancer.

Data collection and analysis: Seven randomised trials were reviewed. There were differences in the timing and the overall treatment time of chest radiotherapy, the overall treatment time of , and the type of chemotherapy used.

Main results: No significant differences in the 2-year and the 5-year survival were found, whether chest radiotherapy was delivered within 30 days after the start of chemotherapy or later. When the only study that delivered chest radiotherapy during cycles of non-platinum chemotherapy was excluded, a trend for the 5-year survival was observed (RR:0.93, p=0.07) in favour of early radiation, but not for the 2-year survival. Survival at 5 years, but not at 2 years, was significantly better for those having early chest radiotherapy delivered in an overall treatment time of less than 30 days compared with a longer treatment time (RR: 0.90, p=0.006). These results, however, should be interpreted with caution because the largest trial has follow-up data at three years, but not later. It remains to be seen what the effect of longer follow up will be for 5-year survival rates. Local tumour control was not significantly different between early and late chest radiotherapy. The incidence of severe pneumonitis or severe oesophagitis was not significantly different for early versus late thoracic radiotherapy. However, a trend for a higher chance to develop pneumonitis when early chest radiotherapy was delivered during non-platinum based chemotherapy was observed.

Authors' conclusions: At present, it is uncertain whether the timing of chest radiotherapy as such is important for survival. The optimal integration of chemotherapy and chest radiotherapy in patients with limited-stage small cell lung cancer is unknown. Therefore, further research is needed to establish the most effective combination of radiotherapy and chemotherapy in this disease.

PubMed Disclaimer

Conflict of interest statement

None known.

Figures

1
1
Dose‐intensity chemotherapy
2
2
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
3
3
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
4
4
Forest plot of comparison: 1 Early versus late chest RT, outcome: 1.8 Local toxicity, all studies.
5
5
Forest plot of comparison: 1 Early versus late chest RT, outcome: 1.9 Local toxicity, excluding studies with non‐platinum CT.
6
6
Forest plot of comparison: 1 Early versus late chest RT, outcome: 1.10 Local toxicity, only studies with overall treatment time of chest RT less than 30 days.
7
7
Forest plot of comparison: 1 Early versus late chest RT, outcome: 1.11 Haematological toxicity, all studies.
8
8
Forest plot of comparison: 1 Early versus late chest RT, outcome: 1.12 Haematological toxicity, excluding studies delivering radiation concurrently with doxorubicin.
9
9
Forest plot of comparison: 1 Early versus late chest RT, outcome: 1.13 Haematological toxicity, only studies with overall treatment time of chest RT less than 30 days.
10
10
Distribution chemotherapy dose per study arm
1.1
1.1. Analysis
Comparison 1 Early versus late chest RT, Outcome 1 Overall survival.
1.2
1.2. Analysis
Comparison 1 Early versus late chest RT, Outcome 2 Overall survival (only studies with OTT < 30 days).
1.3
1.3. Analysis
Comparison 1 Early versus late chest RT, Outcome 3 Local tumour control (5‐yrs).
1.4
1.4. Analysis
Comparison 1 Early versus late chest RT, Outcome 4 Local toxicity, all studies.
1.5
1.5. Analysis
Comparison 1 Early versus late chest RT, Outcome 5 Local toxicity, excluding studies with non‐platinum CT.
1.6
1.6. Analysis
Comparison 1 Early versus late chest RT, Outcome 6 Local toxicity, only studies with overall treatment time of chest RT less than 30 days.
1.7
1.7. Analysis
Comparison 1 Early versus late chest RT, Outcome 7 Haematological toxicity, all studies.
1.8
1.8. Analysis
Comparison 1 Early versus late chest RT, Outcome 8 Haematological toxicity, excluding studies with non‐platinum CT.
1.9
1.9. Analysis
Comparison 1 Early versus late chest RT, Outcome 9 Haematological toxicity, only studies with overall treatment time of chest RT less than 30 days.
2.1
2.1. Analysis
Comparison 2 High (> 80%) versus low (< 80%) compliance chemotherapy, Outcome 1 High (> 80%) versus low (< 80%) compliance CT.

Update of

  • doi: 10.1002/14651858.CD004700

Similar articles

Cited by

References

References to studies included in this review

Jeremic 1997 {published data only}
    1. Jeremic B, Shibamoto Y, Acimovic L, Milisavljevic S. Initial versus delayed accelerated hyperfractionated radiation therapy and concurrent chemotherapy in limited small‐cell lung cancer: a randomized study. Journal of Clinical Oncology 1997;15(3):893‐900. - PubMed
Murray 1993 {published data only}
    1. Murray N, Coy P, Pater JL, Hodson I, Arnold A, Zee BC, et al. Importance of timing for thoracic irradiation in the combined modality treatment of limited‐stage small‐cell lung cancer. The National Cancer Institute of Canada Clinical Trials Group. Journal of Clinical Oncology 1993;11(2):336‐44. - PubMed
Perry 1998 {published data only}
    1. Perry MC, Herndon JE, Eaton WL, Green MR. Thoracic radiation therapy added to chemotherapy for small‐cell lung cancer: an update of Cancer and Leukemia Group B Study 8083. Journal of Clinical Oncology 1998;16(7):2466‐7. - PubMed
Skarlos 2001 {published data only}
    1. Skarlos DV, Samantas E, Briassoulis E, Panoussaki E, Pavlidis N, Kalofonos HP, et al. Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small‐cell lung cancer: a randomized phase II study of the Hellenic Cooperative Oncology Group (HeCOG). Annals of Oncology 2001;12(9):1231‐8. - PubMed
Spiro 2006 {published data only}
    1. Spiro S, James LE, Rudd RM, Trask C, Tobias JS, Snee M, et al. Early compared with late radiotherapy in combined modality treatment for limited disease small‐cell lung cancer: a London Lung Cancer Group multicenter randomized trial and meta‐analysis. Journal of Clinical Oncology 2006;24(24):3823‐30. - PubMed
Takada 2002 {published data only}
    1. Takada M, Fukuoka M, Kawahara M, Sugiura T, Yokoyama A, Yokota S, et al. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited‐stage small‐cell lung cancer: results of the Japan Clinical Oncology Group Study 9104. Journal of Clinical Oncology 2002;20(14):3054‐60. - PubMed
Work 1997 {published data only}
    1. Work E, Nielsen OS, Bentzen SM, Fode K, Palshof T. Randomized study of initial versus late chest irradiation combined with chemotherapy in limited‐stage small‐cell lung cancer. Aarhus Lung Cancer Group. Journal of Clinical Oncology 1997;15(9):3030‐7. - PubMed

References to studies excluded from this review

Blackstock 2005 {published data only}
    1. Blackstock AW, Bogart JA, Matthews C, Lovato JF, McCoy T, Livengood K, et al. Split‐course versus continuous thoracic radiation therapy for limited‐stage small‐cell lung cancer: final report of a randomized phase III trial. Clinical Lung Cancer 2005;6(5):287‐92. - PubMed
Bonner 1999 {published data only}
    1. Bonner JA, Sloan JA, Shanahan TG, Brooks BJ, Marks RS, Krook JE, et al. Phase III comparison of twice‐daily split‐course irradiation versus once‐daily irradiation for patients with limited stage small‐cell lung carcinoma. Journal of Clinical Oncology 1999;17(9):2681‐91. - PubMed
Gregor 1997 {published data only}
    1. Gregor A, Drings P, Burghouts J, Postmus PE, Morgan D, Sahmoud T, et al. Randomized trial of alternating versus sequential radiotherapy/chemotherapy in limited‐disease patients with small‐cell lung cancer: a European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group Study. Journal of Clinical Oncology 1997;15(8):2840‐9. - PubMed
Lebeau 1999 {published data only}
    1. Lebeau B, Urban T, Brechot JM, Paillotin D, Vincent J, Leclerc P, et al. A randomized clinical trial comparing concurrent and alternating thoracic irradiation for patients with limited small cell lung carcinoma. Cancer 1999;86(8):1480‐7. - PubMed
Turrisi 1999 {published data only}
    1. Turrisi AT, Kim K, Blum R, Sause WT, Livingston RB, Komaki R, et al. Twice‐daily compared with once‐daily thoracic radiotherapy in limited small‐cell lung cancer treated concurrently with cisplatin and etoposide. New England Journal of Medicine 1999;340(4):265‐71. - PubMed

Additional references

Auperin 1999
    1. Auperin A, Arriagada R, Pignon JP, Pechoux C, Gregor A, Stephens RJ, et al. Prophylactic cranial irradiation for patients with small‐cell lung cancer in complete remission. New England Journal of Medicine 1999;341(7):476‐84. - PubMed
Bentzen 1991
    1. Bentzen SM, Thomas HD. Clinical evidence for tumor clonogen regeneration: interpretations of the data. Radiotherapy and Oncology 1991;22:161‐6. - PubMed
Bunn 1997
    1. Bunn PA Jr, Carney DN. Overview of chemotherapy for small cell lung cancer. Seminars in Oncology 1997;24(2 Suppl 7):69S‐74S. - PubMed
Davis 2000
    1. Davis AJ, Tannock IF. Repopulation of tumor cells between cycles of chemotherapy: a neglected factor. The Lancet Oncology 2000;1:86‐93. - PubMed
De Ruysscher 2000
    1. Ruysscher D, Vansteenkiste J. Chest radiotherapy in limited‐stage small cell lung cancer: facts, questions, prospects. Radiotherapy and Oncology 2000;55(1):1‐9. - PubMed
De Ruysscher 2006
    1. Ruysscher D, Pijls‐Johannesma M, Bentzen SM, Minken A, Wanders R, Lutgens L, et al. Time between the first day of chemotherapy and the last day of chest radiation is the most important predictor of survival in limited‐disease small‐cell lung cancer. Journal of Clinical Oncology 2006;24(7):1057‐63. - PubMed
Harari 2003
    1. Harari PM, Mehta MP, Ritter MA, Petereit DG. Clinical promise tempered by reality in the delivery of combined chemoradiation for common solid tumors. Seminars in Radiation Oncology 2003;13(1):3‐12. [MEDLINE: ] - PubMed
Higgins 2008
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of interventions Version 5.0.1 [updated September 2008]. The Cochrane Collaboration, 2008. Available from www.cochrane‐handbook.org.
Ihde 1995
    1. Ihde DC. Small cell lung cancer. State‐of‐the‐art therapy 1994. Chest 1995;107(6 Suppl):243S‐248S. - PubMed
Kelly 2000
    1. Kelly K. New chemotherapy agents for small cell lung cancer. Chest 2000;117(4 Suppl 1):156S‐162S. - PubMed
Kumar 1997
    1. Kumar P. The role of thoracic radiotherapy in the management of limited‐stage small cell lung cancer: past, present, and future. Chest 1997;112(4 Suppl):259S‐65S. - PubMed
Pignon 1992
    1. Pignon JP, Arriagada R, Ihde DC, Johnson DH, Perry MC, Souhami RL, et al. A meta‐analysis of thoracic radiotherapy for small‐cell lung cancer. New England Journal of Medicine 1992;327(23):1618‐24. - PubMed
Pijls‐Johannesma 2007
    1. Pijls‐Johannesma M, Ruysscher DK M, Lambin P, Rutten I, Vansteenkiste JF. Timing of chest radiotherapy in patients with limited stage small cell lung cancer: a systematic review and meta‐analysis of randomised controlled trials. Cancer Treatment Reviews 2007;33(5):461‐73. - PubMed
Tierney 2007
    1. Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time‐to‐event data into meta‐analysis. Trials 2007;8(16):1‐16. - PMC - PubMed
Turrisi 2002
    1. Turrisi AT, Sherman CA. The treatment of limited small cell lung cancer: a report of the progress made and future prospects. European Journal of Cancer 2002;38(2):279‐91. - PubMed
Warde 1992
    1. Warde P, Payne D. Does thoracic irradiation improve survival and local control in limited‐stage small‐cell carcinoma of the lung? A meta‐analysis. Journal of Clinical Oncology 1992;10(6):890‐5. - PubMed
Withers 1988
    1. Withers HR, Taylor JM, Maciejewski B. The hazard of accelerated tumor clonogen repopulation during radiotherapy. Acta Oncologica (Stockholm, Sweden) 1988;27:131‐46. - PubMed

References to other published versions of this review

Pijls‐Johannesma 2005
    1. Pijls‐Johannesma M, Ruysscher DKM, Lambin P, Rutten I, Vansteenkiste JF. Early versus late chest radiotherapy in patients with limited stage small cell lung cancer. Cochrane Database of Systematic Reviews 2005, Issue 1. [DOI: 10.1002/14651858.CD004700.pub2] - PMC - PubMed

MeSH terms