utd_medknow
Indian Journal of Cancer
Home  ICS  Feedback Subscribe Top cited articles Login 
Users Online :7438
Small font sizeDefault font sizeIncrease font size
Navigate here
  Search
 
  
Resource links
 »  Similar in PUBMED
 »  Search Pubmed for
 »  Search in Google Scholar for
 »Related articles
 »  Article in PDF (518 KB)
 »  Citation Manager
 »  Access Statistics
 »  Reader Comments
 »  Email Alert *
 »  Add to My List *
* Registration required (free)  

 
  In this article
 »  Abstract
 » Introduction
 »  Materials and Me...
 » Results
 » Discussion
 »  References
 »  Article Figures
 »  Article Tables

 Article Access Statistics
    Viewed2721    
    Printed115    
    Emailed1    
    PDF Downloaded426    
    Comments [Add]    
    Cited by others 1    

Recommend this journal

 

  Table of Contents  
ORIGINAL ARTICLE
Year : 2014  |  Volume : 51  |  Issue : 6  |  Page : 21-24
 

A meta-analysis of limb-salvage versus amputation in the treatment of patients with Enneking‡U pathologic fracture osteosarcoma


1 Department of Orthopaedics, Huaihe Hospital Affiliated to Henan University, Kaifeng 475000, PR China
2 Department of Oncology, Huaihe Hospital Affiliated to Henan University, Kaifeng 475000, PR China

Date of Web Publication24-Feb-2015

Correspondence Address:
Dr. Y Shi
Department of Oncology, Huaihe Hospital Affiliated to Henan University, Kaifeng 475000
PR China
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.151997

Rights and Permissions

 » Abstract 

Introduction: The aim of this meta-analysis was to further explore whether the relapse, 5-year survival and metastasis the same or not between limb-salvage and amputation in the treatment of patients with limited stage Enneking‡U pathologic fracture osteosarcoma. Materials and Methods: An electronic search of the Medline, EMBASE and CNKI was done on October 2014. The clinical studies about amputation or limb-salvage surgery in the treatment of patients with limited stage Enneking‡U pathologic fracture osteosarcoma were searched and reviewed. The effect size of relapse, 5-year survival and metastasis between the amputation and limb-salvage surgery were pooled by stata11.0 software (Stata Corporation, College Station, TX, USA, http://www.stata.com;) using random or fixed effect model. The funnel plot and Egger's line regression test were used for evaluation of publication bias. Results: A total of 89 studies were identified and seven articles with 200 cases in the limb-salvage surgery group and 84 subjects in the amputation group were finally included in the meta-analysis. The pooled data indicated that no statistical different of risk for developing relapse between limb-salvage and amputation was found relative risk (RR) =1.40, 95% confidence interval (CI): 0.71-2.79, (P = 0.33). The 5-year survival rate of patients underwent limb-salvage surgery was smaller than patients received amputation RR = 1.86, 95%CI: 1.19-2.89, (P = 0.01); the metastasis rate of patients underwent limb-salvage surgery was significant decreased compared with patients received amputation RR = 0.56, 95% CI: 0.34-0.94, (P = 0.03). No publication bias was existed in this meta-analysis. Conclusion: Limb-salvage surgery does not increased the risk of relapse compared with amputation in the treatment of patients with limited stage Enneking‡U pathologic fracture osteosarcoma.


Keywords: Amputation, limb-salvage surgery, meta-analysis, osteosarcoma, pathologic fracture


How to cite this article:
Jiang F, Shi Y, Li G J, Zhou F. A meta-analysis of limb-salvage versus amputation in the treatment of patients with Enneking‡U pathologic fracture osteosarcoma. Indian J Cancer 2014;51, Suppl S2:21-4

How to cite this URL:
Jiang F, Shi Y, Li G J, Zhou F. A meta-analysis of limb-salvage versus amputation in the treatment of patients with Enneking‡U pathologic fracture osteosarcoma. Indian J Cancer [serial online] 2014 [cited 2021 Dec 3];51, Suppl S2:21-4. Available from: https://www.indianjcancer.com/text.asp?2014/51/6/21/151997

FNx01Drs. Jiang Feng and Shi Yan contributed equally to this work



 » Introduction Top


Primary bone cancers are extremely rare carcinomas accounting for <0.2% of all types of cancers. [1] And the exact incidence is difficult to estimate. Osteosarcoma (35%), chondrosarcoma (30%), and Ewing's sarcoma (16%) are the three main types of bone cancer. Osteosarcoma is the most common primary malignant bone cancer in children and young adults. [2] And the limb-savage surgery or amputation are the essential treatment procedure of patients with osteosarcoma. [3] Several studies have evaluated the difference between limb-savage surgery and amputation in patients with high-grade no-metastatic osteosarcoma and not shown a significant difference in aspects of survival and local recurrence rate. [3],[4] But whether the relapse, 5-year survival and metastasis rate between limb-salvage and amputation in the treatment of patients with limited stage Enneking‡U pathologic fracture osteosarcoma patients were not known. Here, we performed this meta-analysis based on published clinical trials to further explore the clinical efficacy between limb-salvage and amputation in the treatment of patients with limited stage Enneking‡U pathologic fracture osteosarcoma patients.


 » Materials and Methods Top


Literature search strategy

An electronic search of the Medline, EMBASE and CNKI was done on October 2014. The clinical studies about amputation or limb-salvage surgery in the treatment of patients with limited stage Enneking II pathologic fracture osteosarcoma were searched and reviewed independently by FJ and YS and cross checked. The searching terms were: Osteosarcoma, sarcoma, limb-salvage, amputation. Searches were limited to human trials, with the language restriction of English and Chinese.

Selection criteria

The selection criteria for this meta-analysis were: (1) Inclusion of patients who underwent amputation or limb-salvage surgery, (2) patients with osteosarcoma sarcoma in their lower limb (s), (3) at least one of the three outcomes (relapse, 5-year survival rate and metastasis) could be drawn from the original study. Exclusion criteria were as follows: (1) Review or case report, (2) not providing enough data (relapse, 5-year survival rate and metastasis), (3) the article being in a language other than English or Chinese, (4) duplicate publications.

Statistical analysis

Sata11.0 software (Stata Corporation, College Station, TX, USA, http://www.stata.com;) was used to do a statistical analysis. Dichotomous data was calculated as relative risk (RR) with a 95% confidence interval (CI). The outcomes of this meta-analysis were RR of relapse rate, 5-year survival rate and metastasis rate between the limb-salvage and amputation. Statistical heterogeneity of the effect size such as relapse rate, 5-year survival rate and metastasis rate was assessed by Chi-square (χ2 ) test. [5] If the heterogeneity was found (χ2 , P < 0.05), the random-effect method (Dersimonian-Laird method) was used to pool the data. Inversely, without significant heterogeneity, fixed-effect method was purchased. The Begg's funnel plots and Egger's line regression test were used for evaluation possible publication bias.


 » Results Top


Studies characteristics

The general characteristics of the included seven articles are summarized in [Table 1]. The age of the patients of each included article was ranged from 2 to 82 years. The total number of participants who received limb-salvage surgery was 200, and in each article it ranged from 12 to 44. The total number of participants who underwent amputation was 84, and in each study it ranged from 4 to 22. The median length of follow-up ranged from approximately 43-132 months with one study not reporting the follow-up period.
Table 1: The general characteristics of included studies

Click here to view


Relapse

All of the included seven studies reported the number of relapse with the median relapse rate of 13.6% (2.9-23.3%) in limb-salvage group and median relapse rate of 9.1% (0-18.2%) in amputation group. For meta-analysis, we first calculated the heterogeneity among the included seven articles and no obvious statistical heterogeneity was observed. Hence, we pooled the RR of relapse for limb-salvage and amputation by fixed effect model. The pooled data indicated that no statistical different of risk for developing relapse between limb-salvage and amputation was found RR = 1.40, 95% CI: 0.71-2.79, (P = 0.33) [Figure 1].
Figure 1: Forest plot for the relative risk of relapse, 5 - year survival and metastasis for limb - salvage versus amputation surgery

Click here to view


Five-year survival

Three articles reported the 5-year survival rate with the median 5-year survival rate of 63.3% (63.0-66.8%) in limb-salvage group and median relapse rate of 40.0% (0-54.6%) in amputation group. Significant heterogeneity between the three included studies was found. The RR for 5-year survival was pooled by random effect model. Meta-analysis showed that the 5-year survival rate of patients underwent limb-salvage surgery was smaller than patients received amputation RR = 1.86, 95% CI: 1.19-2.89, (P = 0.01) [Figure 1].

Metastasis

Only two studies reported the metastasis with the median metastasis rate of 34.7% (25.0-44.4%) in limb-salvage group and median relapse rate of 64.6% (60.0-69.2%) in amputation group. No obvious statistical heterogeneity between the included two studies was found. The RR for metastasis was pooled by fixed effect model. Meta-analysis showed that the metastasis rate of patients underwent limb-salvage surgery was significant decreased compared to patients received amputation RR = 0.56, 95% CI: 0.34-0.94, (P = 0.03) [Figure 1].

Publication bias

The publication bias for the effects size of relapse, 5-year survival and metastasis were evaluated by begg's funnel plot and Egger's line regression test. For relapse, the funnel plot was symmetrical [Figure 2]a and the Egger's line regression test showed no publication bias (t = 0.61, P = 0.57); For 5-year survival and metastasis, there were also no publication bias [Figure 2]b and c. The Egger's test was also indicated no significant publication bias for 5-year survival and metastasis (Pall > 0.05).
Figure 2: Funnel plot for evaluation of publication bias (a: relapse; b: 5 - year survival; c: metastasis)

Click here to view



 » Discussion Top


Amputation has been the standard surgical procedure for treatment of limb osteosarcoma. And with the development of surgery technique and chemotherapy regiment, the limb salvage was made possible. Several studies have demonstrated that limb-sparing surgery is associated with better function outcomes. [13] In patients with high-grade osteosarcomas and good histologic response to neoadjuvant chemotherapy, limb-salvage surgery is recommended if wide surgical margins could be achieved. [3] And amputation is generally reserved for patients with tumors in unfavorable anatomical locations not amenable to limb-salvage surgery. And the limb-salvage surgery can offers improvement in function without compromising survival for high-grad osteosarcomas in not under the debate. But conflicting results have been reported regarding survival and function after limb salvage and amputation for patients with low-grade osteosarcoma of the distal tibia. [13],[14] Several studies reported the survival rates after limb-salvage range from 100% to 50% at 6-288 months, [15],[16] whereas those for amputation range from 100% to 84% at 36-60 months. [4],[17] Thus, whether the relapse, 5-year survival and metastasis the same or not between limb-salvage and amputation in the treatment of patients with limited stage Enneking‡Upathologic fracture osteosarcoma was not known.

In our meta-analysis, we compared the relapse, 5-year survival and metastasis rate between limb-salvage and amputation in the treatment of patients with limited stage Enneking‡U pathologic fracture osteosarcoma. 7 clinical studies with 200 cases in the limb-salvage surgery group and 84 subjects in the amputation group were finally included in the meta-analysis. The pooled data indicated that no statistical different of risk for developing relapse between limb-salvage and amputation was found (P = 0.33). The 5-year survival rate of patients underwent limb-salvage surgery was smaller than patients received amputation (P = 0.01). The metastasis rate in patients underwent limb-salvage surgery was significant decreased compared with patients received amputation (P = 0.03). The above results indicated that the limb-salvage surgery does not increase the risk of relapse compared with amputation in the treatment of patients with limited stage Enneking‡U pathologic fracture osteosarcoma. And limb-salvage surgery may also decrease the risk of developing metastasis. But for the 5-year survival rate and metastasis results, there were only three and two studies included in the meta-analysis with small number cases in each effect size. The conclusion for 5-year survival rate and metastasis was limited and should be further confirmed by well-designed prospective randomized controlled trails.

 
 » References Top

1.
Bramwell VH. Osteosarcomas and other cancers of bone. Curr Opin Oncol 2000;12:330-6.  Back to cited text no. 1
    
2.
Moore DD, Luu HH. Osteosarcoma. Cancer Treat Res 2014;162:65-92.  Back to cited text no. 2
    
3.
Bacci G, Ferrari S, Lari S, Mercuri M, Donati D, Longhi A, et al. Osteosarcoma of the limb. Amputation or limb salvage in patients treated by neoadjuvant chemotherapy. J Bone Joint Surg Br 2002;84:88-92.  Back to cited text no. 3
    
4.
Mavrogenis AF, Abati CN, Romagnoli C, Ruggieri P. Similar survival but better function for patients after limb salvage versus amputation for distal tibia osteosarcoma. Clin Orthop Relat Res 2012;470:1735-48.  Back to cited text no. 4
    
5.
DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177-88.  Back to cited text no. 5
    
6.
Abudu A, Sferopoulos NK, Tillman RM, Carter SR, Grimer RJ. The surgical treatment and outcome of pathological fractures in localised osteosarcoma. J Bone Joint Surg Br 1996;78:694-8.  Back to cited text no. 6
    
7.
Scully SP, Ghert MA, Zurakowski D, Thompson RC, Gebhardt MC. Pathologic fracture in osteosarcoma: Prognostic importance and treatment implications. J Bone Joint Surg Am 2002;84-A: 49-57.  Back to cited text no. 7
    
8.
Bacci G, Ferrari S, Longhi A, Donati D, Manfrini M, Giacomini S, et al. Nonmetastatic osteosarcoma of the extremity with pathologic fracture at presentation: Local and systemic control by amputation or limb salvage after preoperative chemotherapy. Acta Orthop Scand 2003;74:449-54.  Back to cited text no. 8
    
9.
Bramer JA, Abudu AA, Grimer RJ, Carter SR, Tillman RM. Do pathological fractures influence survival and local recurrence rate in bony sarcomas? Eur J Cancer 2007;43:1944-51.  Back to cited text no. 9
    
10.
Niu XH, Ding Y. The surgical treatment and outcome of nonmetastatic osteosarcoma of the extremity with pathologic fractures. Zhonghua Wai Ke Za Zhi 2008;46:1730-3.  Back to cited text no. 10
    
11.
Kim MS, Lee SY, Lee TR, Cho WH, Song WS, Cho SH, et al. Prognostic effect of pathologic fracture in localized osteosarcoma: A cohort/case controlled study at a single institute. J Surg Oncol 2009;100:233-9.  Back to cited text no. 11
    
12.
Ferguson PC, McLaughlin CE, Griffin AM, Bell RS, Deheshi BM, Wunder JS. Clinical and functional outcomes of patients with a pathologic fracture in high-grade osteosarcoma. J Surg Oncol 2010;102:120-4.  Back to cited text no. 12
    
13.
Aksnes LH, Bauer HC, Jebsen NL, Follerås G, Allert C, Haugen GS, et al. Limb-sparing surgery preserves more function than amputation: A Scandinavian sarcoma group study of 118 patients. J Bone Joint Surg Br 2008;90:786-94.  Back to cited text no. 13
    
14.
Campanacci DA, Scoccianti G, Beltrami G, Mugnaini M, Capanna R. Ankle arthrodesis with bone graft after distal tibia resection for bone tumors. Foot Ankle Int 2008;29:1031-7.  Back to cited text no. 14
    
15.
Ebeid W, Amin S, Abdelmegid A, Refaat Y, Ghoneimy A. Reconstruction of distal tibial defects following resection of malignant tumours by pedicled vascularised fibular grafts. Acta Orthop Belg 2007;73:354-9.  Back to cited text no. 15
    
16.
Laitinen M, Hardes J, Ahrens H, Gebert C, Leidinger B, Langer M, et al. Treatment of primary malignant bone tumours of the distal tibia. Int Orthop 2005;29:255-9.  Back to cited text no. 16
    
17.
Shekkeris AS, Hanna SA, Sewell MD, Spiegelberg BG, Aston WJ, Blunn GW, et al. Endoprosthetic reconstruction of the distal tibia and ankle joint after resection of primary bone tumours. J Bone Joint Surg Br 2009;91:1378-82.  Back to cited text no. 17
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1]

This article has been cited by
1 Comparison of recycled autograft versus allograft in osteosarcoma with pathological fracture
Pai-Han Wang, Chao-Ming Chen, Cheng-Fong Chen, Wei-Ming Chen, Po-Kuei Wu
International Orthopaedics. 2021; 45(8): 2149
[Pubmed] | [DOI]



 

Top
Print this article  Email this article
 

    

  Site Map | What's new | Copyright and Disclaimer
  Online since 1st April '07
  © 2007 - Indian Journal of Cancer | Published by Wolters Kluwer - Medknow