Chemotherapy and/or radiotherapy after surgery for ovarian carcinosarcoma
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To assess the effectiveness of chemotherapy and/or radiotherapy associated with surgery in the management of ovarian mixed mullerian sarcoma (carcinosarcoma).
Background
Ovarian carcinosarcoma is a rare malignant gynaecological tumour constituting about 1% or less of all ovarian carcinomas (Russell 1992). In over 80% of cases, there is extra‐ovarian intra‐abdominal spread at diagnosis (Russell 1992). The diagnosis is confirmed on histology with the presence of malignant epithelial and mesenchymal components. The primary treatment has traditionally been surgical cytoreduction. Surgery is followed by radiotherapy and chemotherapy (Carlson 1983) or chemotherapy alone (Bicher 1995). Due to the rarity of this tumour chemotherapy regimes have often changed over the course of time (Brown 2004). Regimes have included cisplatin alone (Tate Thigpen 2004), combination of doxorubicin, ifosfamide and dacarbazine (Simon 1991), cyclophosphamide alone (Prendiville 1994) and various other combinations. The results of these various regimens appear to be mixed.
Advanced surgical stage did not affect median overall survival in one study (Terada 1989) but was associated with a poor prognosis in a more recent study (Ariyoshi 2000). A review of published cases indicated a high one‐year mortality of 78% (Hanjani 1983) in this rare tumour irrespective of stage. More recent studies have indicated that median survival could be improved with platinum‐based chemotherapy (Bicher 1995; Duska 2002). The largest reported data series of 40 cases over 10 years (Harris 2003) indicates that maintaining consistency in treatment plans is difficult and the tumour remains more aggressive than epithelial ovarian cancer (Barnholtz‐Sloan 2004). There is, therefore, a need to clarify if there is an optimum therapy after surgical cytoreduction or in the neoadjuvant setting for this rare tumour. Also, it is important to address quality of life (QOL) issues related to treatment, particularly toxicity related to treatment, as the overall prognosis appears to be poor.
Objectives
To assess the effectiveness of chemotherapy and/or radiotherapy associated with surgery in the management of ovarian mixed mullerian sarcoma (carcinosarcoma).
Methods
Criteria for considering studies for this review
Types of studies
Randomised controlled trials (RCTs).
Types of participants
Women of any age with a diagnosis of mixed mullerian sarcoma of the ovary (carcinosarcoma) at any International Federation of Gynaecology and Obstetrics (FIGO) stage.
Types of interventions
-
Chemotherapy and/or radiotherapy after surgery (any type)
-
Neoadjuvant chemotherapy followed by surgery
Types of outcome measures
-
Overall survival
-
Disease free survival
-
QOL measures
-
Cost effectiveness
-
Adverse events
Search methods for identification of studies
Electronic searches
See: Cochrane Gynaecological Cancer Review Group search strategy;
1. carcinosarcoma
2. Carcinosarcoma.DE
3. mixed mullerian tumo*
4. Mixed‐Tumor‐Mullerian.DE
5. 1 OR 2 OR 3 OR 4
6. ovar*
7. Ovarian‐Neoplasms.DE
8. 6 OR 7
9. 5 AND 8
10. radiother*
11. radiation therapy
12. Radiotherapy.DE OR Radiotherapy‐Adjuvant.DE
13. 10 OR 11 OR 12
14. chemother*
15. Drug‐Therapy.DE OR Chemotherapy‐Adjuvant.DE OR Drug‐Therapy‐Combination.DE OR Antineoplastic‐Combined‐Chemotherapy‐Protocols.DE
16. 14 OR 15
17. 9 AND 13
18. 9 AND 16
19. 17 OR 18
An electronic search will be performed using the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1966), EMBASE (from 1974), CINAHL (from 1982), Psyclit (from 1806), CancerLit, and CENTRAL with the following search strategy (MEDLINE Ovid web) adapted for the other databases. No language restriction will be applied. The following trial registers will also be searched ‐ NHMRC Clinical Trials Register, UKCCCR Register of Cancer Trials, Meta‐Register and Physician Data Query Protocols.
Searching other resources
Reference lists of articles and other reviews on the subject will be checked for the purpose of retrieving further information, either published or unpublished, and researchers involved in this area will be contacted.
Data collection and analysis
Selection of studies
Studies that meet the inclusion criteria will be identified according to the search strategy described. Two review authors (RA, KAG) will screen titles and abstracts of studies identified from the search and eliminate articles that are obviously not relevant to the search question. If there are any disagreements between review authors based on the title, a review of the abstract will be conducted. The two review authors (RA, KAG) will independently assess each abstract according to a checklist of the selection criteria. If both review authors determine that the study is not eligible for inclusion no further action will be taken. If one or both the review authors determine that the article may be eligible for inclusion, full text article will be obtained.
Each review author will then independently determine if these studies are eligible for inclusion. Disagreements about inclusions will be resolved by discussion with a third review author (KD). Further information will be sought from the authors where papers contain insufficient information to make a decision about eligibility.
Quality assessment
Assessment of the quality of a trial will be made in accordance with guidelines in the Cochrane Handbook (Higgins 2005).
Data analysis
If sufficient trials of adequate quality are available and their populations are clinically similar, meta‐analyses of primary and secondary end‐points will be carried out. The magnitude of statistical heterogeneity will be assessed using the I2 statistic. A fixed effects model will be used if there is no evidence of statistical heterogeneity (I2 < 25%). If there is substantial heterogeneity (I2 > 25%), the possible clinical and methodological reasons for this will be explored qualitatively and a random effects model will be used. A funnel plot will be used to assess whether the assumptions underlying the random effects model appear to be valid. If the funnel plot is asymmetric, indicating that the size of the study is related to the estimated size of the treatment effect, the results of both fixed effect and random effects models will be reported.
If we find inadequate numbers of RCTs to pool the data, we will write a description of their main findings.
It is likely that there are no randomised controlled trials of treatment for ovarian MMT. If no such trials are identified, the search strategy will be re‐run without the RCT filter so that any other papers containing prospective or retrospective data can be collated and listed in excluded studies. A systematic discussion of observational studies, case‐controlled studies and studies with historic controls will be considered if no RCTs are identified.
