Limb-salvage surgery offers better five-year survival rate than amputation in patients with limb osteosarcoma treated with neoadjuvant chemotherapy. A systematic review and meta-analysis

Evgenia Papakonstantinou; Alexandros Stamatopoulos; Dimitrios I Athanasiadis; Efstathios Kenanidis; Michael Potoupnis; Anna-Bettina Haidich; Eleftherios Tsiridis

doi:10.1016/j.jbo.2020.100319

Limb-salvage surgery offers better five-year survival rate than amputation in patients with limb osteosarcoma treated with neoadjuvant chemotherapy. A systematic review and meta-analysis

J Bone Oncol. 2020 Sep 15:25:100319. doi: 10.1016/j.jbo.2020.100319. eCollection 2020 Dec.

Authors

Evgenia Papakonstantinou¹, Alexandros Stamatopoulos^{2

3}, Dimitrios I Athanasiadis⁴, Efstathios Kenanidis^{2

3}, Michael Potoupnis^{2

3}, Anna-Bettina Haidich⁵, Eleftherios Tsiridis^{2

3}

Affiliations

¹ Pediatric Oncology Department, Hippokration Hospital, Thessaloniki, Greece.
² Academic Orthopaedic Department, Papageorgiou General Hospital, Aristotle University Medical School, Thessaloniki, Greece.
³ Center of Orthopaedics and Regenerative Medicine (C.O.R.E.) - Center of Interdisciplinary Research and Innovation (C.I.R.I.), Aristotle University Thessaloniki, Balkan Center, Thessaloniki, Greece.
⁴ Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
⁵ Department of Hygiene, Social-Preventive Medicine & Medical Statistics, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Abstract

Background: Osteosarcoma is the most common primary bone sarcoma. Currently, the main treatment option for high-grade osteosarcomas is neoadjuvant chemotherapy, followed by surgical resection of the lesion and adjuvant chemotherapy. Limb salvage surgery (LSS) and amputation are the main surgical techniques; however, controversy still exists concerning the best surgical method. Our meta-analysis compared the effectiveness of LSS and amputation combined with neoadjuvant chemotherapy in patients with limb osteosarcoma, in terms of 5-year overall survival (OS), 5-year disease-free survival (DFS) and local recurrence rate.

Methods: Following the established methodology of PRISMA guidelines, a literature search was conducted in PubMed, Cochrane, Google Scholar from 1975 until January 2020. Two independent reviewers evaluated the study quality based on the Newcastle-Ottawa scale. Odds ratio and 95% confidence interval of the OS, DFS and local recurrence rate were calculated.

Results: Thirteen studies were finally included with a total of 2884 patients; 1986 patients undergone LSS and 898 amputations. Five-year overall survival was almost 2-fold in patients treated with LSS than those treated with amputation (OR: 1.99; 95% CI: 1.35-2.93; I² = 74%, p < 0.001). No difference was found in 5-year DFS between LSS patients and amputees (OR: 1.24; 95% CI: 0.55-2.79; I² = 67%, p = 0.01). The odds of local recurrence was numerically higher in LSS compared to amputation but not statistically significant (OR: 2.29; 95% CI: 0.95-5.53; I² = 47%, p = 0.05). However, the included studies did not clearly define differences in the stages of patients of the two groups.

Conclusion: Our study demonstrated that in patients with limb osteosarcoma treated with neoadjuvant chemotherapy, LSS is associated with a higher 5-year overall survival and the odds of local recurrence may be increased but these results should be interpreted with caution due to high heterogeneity.

Keywords: AJCC, American Joint Cancer Committee; ASCO, American Society of Clinical Oncology; Amputation; CATS, Computed Assisted Tumor Surgery; CCG, Children’s Cancer Group; CI, Confidence Interval; COSS, Cooperative Osteosarcoma Study Group; CT, Computed Tomography; DFS, Disease Free Survival; FNA, Fine Needle Aspiration; LSS, Limb Salvage Surgery; Limb-salvage surgery; MAP, MTX, Adriamycin, Cisplatin; MRI, Magnetic Resonance Imaging; MSKCC, Memorial Sloan Kattering Cancer Center; MSTS, Musculoskeletal Tumor Society; NCCN, National Comprehensive Cancer Network; NOS, Newcastle–Ottawa scale; NPCR, National Program of Cancer Registries; Neoadjuvant chemotherapy; OR, Odds Ratio; OS, Overall Survival; Osteosarcoma; PET, Positron Emission Tomography; POG, Pediatric Oncology Group; RCT, Randomized Controlled Trials; Rev-Man, Review Manager; SEER, Surveillance, Epidemiology, and End Results; SIOP, International Society of Paediatric Oncology; Tc-MDP, Methylene diphosphonate with technetium-99m; VICC, Vanderbilt-Ingram Cancer Center.

Publication types

Review