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					Chemoradiotherapy for cervical
cancer: a Cochrane review using
    individual patient data

                Clinical
         www.cochranejournalclub.com
                     Clinical questions
• What is the effect of chemoradiotherapy
  compared to radiotherapy for women with
  limited or locally advanced cervical cancer?
• How does the effect differ for different types
  of women and for different types of
  treatment?
  Source: Chemoradiotherapy for Cervical Cancer Meta-analysis Collaboration. Reducing
  uncertainties about the effects of chemoradiotherapy for cervical cancer: individual
  patient data meta-analysis. Cochrane Database of Systematic Reviews 2010, Issue 1. Art.
  No.: CD008285. DOI: 10.1002/14651858. CD008285.pub2.

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                       Context
• Cervical cancer is the second most common cancer among
  women, and the main cancer affecting women in sub-Saharan
  Africa, Central America and south-central Asia.
• Chemoradiotherapy involves the use of chemotherapy at the
  same time as radiotherapy.
• In 1999 the National Cancer Institute in the United States
  recommended that chemoradiotherapy should be considered
  for women with cervical cancer.
• Subsequent systematic reviews found that interpretation of
  the benefits was complicated and some important clinical
  questions were unanswered.

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                        Methods
• A Cochrane intervention review, conducted by a collaborative
  group of researchers responsible for the randomised trials.
• Information on published and unpublished trials was sought
  from bibliographic databases, trial registers, conference
  proceedings and the participating investigators.
• Individual patient data were collected from each trial, to allow
  time-to-event analyses and investigation of differences in the
  effect of chemoradiotherapy by trial and patient
  characteristics.
• Updated follow-up data were sought, to look at these
  outcomes in the long-term.


                     www.cochranejournalclub.com                 4
  PICO(S) to assess eligible studies
• Participants: women with locally advanced cancer of the
  uterine cervix who had not received any previous treatments
  likely to interfere with protocol treatments or comparisons.
• Intervention: concomitant chemotherapy and radical
  radiotherapy (with or without surgery).
• Comparison: the same radical radiotherapy (with or without
  surgery).
• Outcomes: time to locoregional progression or recurrence,
  metastases and death from any cause; acute and late toxicity.
• Studies: randomised trials that had completed patient accrual
  by the time of the final analysis for the review.


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     Description of eligible studies
• Twenty five eligible trials were identified.
• Data were not available from six trials (814 participants)
  because the data could not be located, and from four trials
  (299 participants) because contact could not be made with
  the original researchers.
• Individual patient data were available for 3452 women in 15
  trials.
• Recruitment to the trials took place between May 1987 and
  June 2006.




                    www.cochranejournalclub.com                 6
         Results: Overall survival
• Overall survival data were available for 15 trials with 3,452
  participants, of whom 1,138 were known to have died.
• In the 13 trials that did not use additional adjuvant
  chemotherapy after chemoradiotherapy, the hazard ratio for
  mortality was 0.81 (95% CI 0.71 to 0.91, p<0.001). The benefit
  appeared larger when adjuvant chemotherapy was used.
• The 19% reduction in hazard ratio translates to an absolute
  survival benefit of 6% at five years - an increase in the average
  number of survivors from 60 to 66 per hundred.
• There was a suggestion of a difference in the size of the benefit
  with tumour stage, but not across other patient subgroups.

                     www.cochranejournalclub.com                  7
 Survival: 13 trials, 3,104 participants
           1.0

           0.9

           0.8

           0.7                                 Chemoradiotherapy
           0.6
Survival




                     Radiotherapy alone
           0.5

           0.4

           0.3

           0.2

           0.1

           0.0
                 0   1   2    3    4      5    6      7    8   9   10

                                       Time (years)
                             www.cochranejournalclub.com                8
    Results: Disease-free survival
• In the 13 trials that did not use additional adjuvant
  chemotherapy after chemoradiotherapy, there were 1,376
  events in total, of which 1,087 were recurrences or metastases,
  and 289 were deaths.
• The hazard ratio for disease free survival (DFS) was 0.78 (95% CI
  0.70 to 0.87, p<0.001).
• This translates to an absolute DFS benefit of 8% at 5 years
  (from 50% to 58%).




                      www.cochranejournalclub.com                 9
                 Results: Toxicity
• Serious haematological toxicity increased by approximately
  two-fold to ten-fold in individual trials.
• There was a significant increase in serious gastrointestinal
  toxicity for trials using platinum-based chemoradiotherapy,
  chemoradiotherapy plus additional chemotherapy and
  additional radiotherapy for the control group. This increase was
  not seen for trials using non-platinum based
  chemoradiotherapy.
• There were insufficient data to assess serious late toxicity. The
  available data suggest that 1% to 3% of women experienced
  serious late toxicities, but these data may not represent the
  true levels of late toxicity across all trials.
                     www.cochranejournalclub.com                10
                      Conclusions
• These results endorse the recommendations of the National
  Cancer Institute clinical alert.
• In addition, the results demonstrate the applicability of the
  benefits to all women and the effectiveness of non-platinum
  based chemoradiotherapy.
• The suggestion of additional benefit from adjuvant
  chemotherapy after the chemoradiotherapy requires testing
  in future randomised trials.
• Future trials should include prospective evaluation of the late
  effects of chemoradiotherapy.


                      www.cochranejournalclub.com               11
                Useful links
• Cochrane Journal Club discussion points

• Original version of this review in the Journal of
  Clinical Oncology

• Cochrane review: Chemoradiotherapy for
  cervical cancer



                www.cochranejournalclub.com      12

				
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posted:4/21/2011
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