Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: A systematic review and meta-analysis of individual patient data from 18 randomized trials

Claire Vale, Jayne F. Tierney, Lesley A. Stewart, Mark Brady, Ketayun Dinshaw, Anders Jakobsen, Mahesh K B Parmar, Gillian Thomas, Ted Trimble, David S Alberts, Hongwei Chen, Slobodan Cikaric, Patricia J. Eifel, Melahat Garipagaoglu, Henry Keys, Nermina Kantardzic, Punita Lal, Rachelle Lanciano, Felix Leborgne, Vicharn LorvidhayaHiroshi Onishi, Robert G. Pearcey, Elizabeth Pras, Kenneth Roberts, Peter G. Rose, Charles W. Whitney

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Abstract

Background: After a 1999 National Cancer Institute (NCI) clinical alert was issued, chemoradiotherapy has become widely used in treating women with cervical cancer. Two subsequent systematic reviews found that interpretation of the benefits was complicated, and some important clinical questions were unanswered. Patients and Methods: We initiated a meta-analysis seeking updated individual patient data from all randomized trials to assess the effect of chemoradiotherapy on all outcomes. We prespecified analyses to investigate whether the effect of chemoradiotherapy differed by trial or patient characteristics. Results: On the basis of 13 trials that compared chemoradiotherapy versus the same radiotherapy, there was a 6% improvement in 5-year survival with chemoradiotherapy (hazard ratio [HR] = 0.81, P < .001). A larger survival benefit was seen for the two trials in which chemotherapy was administered after chemoradiotherapy. There was a significant survival benefit for both the group of trials that used platinum-based (HR = 0.83, P = .017) and non-platinum-based (HR = 0.77, P = .009) chemoradiotherapy, but no evidence of a difference in the size of the benefit by radiotherapy or chemotherapy dose or scheduling was seen. Chemoradiotherapy also reduced local and distant recurrence and progression and improved disease-free survival. There was a suggestion of a difference in the size of the survival benefit with tumor stage, but not across other patient subgroups. Acute hematologic and GI toxicity was increased with chemoradiotherapy, but data were too sparse for an analysis of late toxicity. Conclusion: These results endorse the recommendations of the NCI alert, but also demonstrate their applicability to all women and a benefit of non-platinum-based chemoradiotherapy. Furthermore, although these results suggest an additional benefit from adjuvant chemotherapy, this requires testing in randomized trials.

Original languageEnglish (US)
Pages (from-to)5802-5812
Number of pages11
JournalJournal of Clinical Oncology
Volume26
Issue number35
DOIs
StatePublished - Dec 10 2008

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Chemoradiotherapy
Uterine Cervical Neoplasms
Uncertainty
Meta-Analysis
Survival
National Cancer Institute (U.S.)
Radiotherapy
Drug Therapy
Adjuvant Chemotherapy
Platinum
Disease-Free Survival
Recurrence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer : A systematic review and meta-analysis of individual patient data from 18 randomized trials. / Vale, Claire; Tierney, Jayne F.; Stewart, Lesley A.; Brady, Mark; Dinshaw, Ketayun; Jakobsen, Anders; Parmar, Mahesh K B; Thomas, Gillian; Trimble, Ted; Alberts, David S; Chen, Hongwei; Cikaric, Slobodan; Eifel, Patricia J.; Garipagaoglu, Melahat; Keys, Henry; Kantardzic, Nermina; Lal, Punita; Lanciano, Rachelle; Leborgne, Felix; Lorvidhaya, Vicharn; Onishi, Hiroshi; Pearcey, Robert G.; Pras, Elizabeth; Roberts, Kenneth; Rose, Peter G.; Whitney, Charles W.

In: Journal of Clinical Oncology, Vol. 26, No. 35, 10.12.2008, p. 5802-5812.

Research output: Contribution to journalArticle

Vale, C, Tierney, JF, Stewart, LA, Brady, M, Dinshaw, K, Jakobsen, A, Parmar, MKB, Thomas, G, Trimble, T, Alberts, DS, Chen, H, Cikaric, S, Eifel, PJ, Garipagaoglu, M, Keys, H, Kantardzic, N, Lal, P, Lanciano, R, Leborgne, F, Lorvidhaya, V, Onishi, H, Pearcey, RG, Pras, E, Roberts, K, Rose, PG & Whitney, CW 2008, 'Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: A systematic review and meta-analysis of individual patient data from 18 randomized trials', Journal of Clinical Oncology, vol. 26, no. 35, pp. 5802-5812. https://doi.org/10.1200/JCO.2008.16.4368
Vale, Claire ; Tierney, Jayne F. ; Stewart, Lesley A. ; Brady, Mark ; Dinshaw, Ketayun ; Jakobsen, Anders ; Parmar, Mahesh K B ; Thomas, Gillian ; Trimble, Ted ; Alberts, David S ; Chen, Hongwei ; Cikaric, Slobodan ; Eifel, Patricia J. ; Garipagaoglu, Melahat ; Keys, Henry ; Kantardzic, Nermina ; Lal, Punita ; Lanciano, Rachelle ; Leborgne, Felix ; Lorvidhaya, Vicharn ; Onishi, Hiroshi ; Pearcey, Robert G. ; Pras, Elizabeth ; Roberts, Kenneth ; Rose, Peter G. ; Whitney, Charles W. / Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer : A systematic review and meta-analysis of individual patient data from 18 randomized trials. In: Journal of Clinical Oncology. 2008 ; Vol. 26, No. 35. pp. 5802-5812.
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abstract = "Background: After a 1999 National Cancer Institute (NCI) clinical alert was issued, chemoradiotherapy has become widely used in treating women with cervical cancer. Two subsequent systematic reviews found that interpretation of the benefits was complicated, and some important clinical questions were unanswered. Patients and Methods: We initiated a meta-analysis seeking updated individual patient data from all randomized trials to assess the effect of chemoradiotherapy on all outcomes. We prespecified analyses to investigate whether the effect of chemoradiotherapy differed by trial or patient characteristics. Results: On the basis of 13 trials that compared chemoradiotherapy versus the same radiotherapy, there was a 6{\%} improvement in 5-year survival with chemoradiotherapy (hazard ratio [HR] = 0.81, P < .001). A larger survival benefit was seen for the two trials in which chemotherapy was administered after chemoradiotherapy. There was a significant survival benefit for both the group of trials that used platinum-based (HR = 0.83, P = .017) and non-platinum-based (HR = 0.77, P = .009) chemoradiotherapy, but no evidence of a difference in the size of the benefit by radiotherapy or chemotherapy dose or scheduling was seen. Chemoradiotherapy also reduced local and distant recurrence and progression and improved disease-free survival. There was a suggestion of a difference in the size of the survival benefit with tumor stage, but not across other patient subgroups. Acute hematologic and GI toxicity was increased with chemoradiotherapy, but data were too sparse for an analysis of late toxicity. Conclusion: These results endorse the recommendations of the NCI alert, but also demonstrate their applicability to all women and a benefit of non-platinum-based chemoradiotherapy. Furthermore, although these results suggest an additional benefit from adjuvant chemotherapy, this requires testing in randomized trials.",
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T1 - Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer

T2 - A systematic review and meta-analysis of individual patient data from 18 randomized trials

AU - Vale, Claire

AU - Tierney, Jayne F.

AU - Stewart, Lesley A.

AU - Brady, Mark

AU - Dinshaw, Ketayun

AU - Jakobsen, Anders

AU - Parmar, Mahesh K B

AU - Thomas, Gillian

AU - Trimble, Ted

AU - Alberts, David S

AU - Chen, Hongwei

AU - Cikaric, Slobodan

AU - Eifel, Patricia J.

AU - Garipagaoglu, Melahat

AU - Keys, Henry

AU - Kantardzic, Nermina

AU - Lal, Punita

AU - Lanciano, Rachelle

AU - Leborgne, Felix

AU - Lorvidhaya, Vicharn

AU - Onishi, Hiroshi

AU - Pearcey, Robert G.

AU - Pras, Elizabeth

AU - Roberts, Kenneth

AU - Rose, Peter G.

AU - Whitney, Charles W.

PY - 2008/12/10

Y1 - 2008/12/10

N2 - Background: After a 1999 National Cancer Institute (NCI) clinical alert was issued, chemoradiotherapy has become widely used in treating women with cervical cancer. Two subsequent systematic reviews found that interpretation of the benefits was complicated, and some important clinical questions were unanswered. Patients and Methods: We initiated a meta-analysis seeking updated individual patient data from all randomized trials to assess the effect of chemoradiotherapy on all outcomes. We prespecified analyses to investigate whether the effect of chemoradiotherapy differed by trial or patient characteristics. Results: On the basis of 13 trials that compared chemoradiotherapy versus the same radiotherapy, there was a 6% improvement in 5-year survival with chemoradiotherapy (hazard ratio [HR] = 0.81, P < .001). A larger survival benefit was seen for the two trials in which chemotherapy was administered after chemoradiotherapy. There was a significant survival benefit for both the group of trials that used platinum-based (HR = 0.83, P = .017) and non-platinum-based (HR = 0.77, P = .009) chemoradiotherapy, but no evidence of a difference in the size of the benefit by radiotherapy or chemotherapy dose or scheduling was seen. Chemoradiotherapy also reduced local and distant recurrence and progression and improved disease-free survival. There was a suggestion of a difference in the size of the survival benefit with tumor stage, but not across other patient subgroups. Acute hematologic and GI toxicity was increased with chemoradiotherapy, but data were too sparse for an analysis of late toxicity. Conclusion: These results endorse the recommendations of the NCI alert, but also demonstrate their applicability to all women and a benefit of non-platinum-based chemoradiotherapy. Furthermore, although these results suggest an additional benefit from adjuvant chemotherapy, this requires testing in randomized trials.

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