Limb Volume Reduction and Infection Outcomes Following Vascularized Lymph Node Transfer for Cancer Treatment-Related Lymphoedema: A Systematic Review and Meta-Analysis

Abstract

Background: Cancer treatment-related lymphoedema (CTRL) is a chronic and disabling complication that carries a significant health burden during cancer survivorship. Vascularized lymph node transfer (VLNT) is a novel surgical technique utilised to reconstruct physiological lymphatic flow in lymphoedematous limbs. In this study, we set out to synthesise and assess the efficacy of VLNT for reducing limb volume and infection outcomes in CTRL Methods :In this systematic review and meta-analysis, we searched PubMed, Medline and EMBASE databases until 2019 for English-language full-text articles. Studies that reported VLNT as the sole therapeutic intervention for the management of cancer treatment-related lymphoedema and provided volumetric limb and/or patient-reported lymphatic quality of life and/or cellulitis-related outcomes were included. All studies were scored for methodological quality (STROBE and CONSORT checklists) and lymphoedema-specific data reporting quality. Using a random-effects model, we estimated the pooled limb volume reduction and 95% CI for upper and lower limbs stratifying according to site of measurement and VLNT donor. We also estimated the pooled reduction in cellulitis episodes and mean improvement in lymphoedema-related quality of life. PROSPERO registration number: CRD42020204080. Findings: Our search strategy identified 277 articles, of which thirty-one studies (25 cohort studies, 1 randomised controlled study, 2 case reports, 2 case-series and 1 cross-sectional patient survey) encompassing 581 patients satisfied the inclusion criteria. The overall methodological quality of studies was assessed to be low. Meta-analysis demonstrated that performing VLNT for CTRL led to limb volume reductions in both upper limb (above elbow circumferential reduction rates (CRR AE ) = 42.7 % (95% CI: 36.5-48.8, I 2 : 94.3 %, p = 0.000, 153 patients, 10 studies); below elbow CRR (CRR BE ) = 34.1 % (95% CI: 33.0-35.1, I 2 : 0.0 %, p = 0.919, 144 patients, 9 studies)) and lower limb (above knee CRR (CRR AK ) = 46.8 % (95% CI: 43.2-50.4, I 2 : 92.4 %, p = 0.000 26 patients, 3 studies); below knee (CRR BK ) = 54.6 % (95% CI: 39.0-70.2, I 2 : 97.6%, p = 0.000, 26 patients, 3 studies)), respectively. Extra-abdominal VLNT, abdominal VLNT and autologous breast reconstruction with VLNT led to CRRs of 49.5 % (95% CI: 46.5-52.5, I 2 : 8.3 %, p = 0.365, 7 studies, 108 patients), 39.6 % (95% CI: 37.2-42.0, I 2 : 89.5 %, p = 0.000, 3 studies, 15 patients) and 32.7 % (95% CI: 11.1-54.4, I 2 : 96.9 %, p = 0.000 3 studies, 29 patients). Performing VLNT resulted in a mean reduction in cellulitis episodes of 2.1 episodes (95% CI: -2.7- -1.4) per annum. The mean improvement in lymphoedema-related quality of life was found to be 4.26 (LYMQOL “overall domain”). Interpretation: VLNT for CTRL can achieve reductions in limb volume and episodes of cellulitis in both upper and lower limbs suggesting it is an effective therapy. However, published studies were methodologically heterogeneous and of low quality highlighting the need for standardised outcome reporting and further well-designed randomised controlled trials comparing VLNT against existing therapies. Funding Statement: There was no funding source for this study. Declaration of Interests: We declare no competing interests.