Necrosis following neoadjuvant radiotherapy and its association with oncological outcome in soft tissue sarcoma patients: a systematic literature review and meta-analysis.

PURPOSE: Neoadjuvant radiotherapy (NRTX) is recommended for soft tissue sarcomas (STS) by current European Society of Medical Oncology (ESMO) guidelines. Histological response to preoperative treatment (including NRTX) is a well-established prognostic parameter in patients with osteosarcoma and Ewing sarcoma. In patients with STS, however, the relevance of histological - and radiological - necrosis rate following neoadjuvant treatment is less well known.

METHODS

We conducted a systematic PubMed search and obtained 2,433 potentially relevant entries, of which 30 original articles were finally included. Histological and radiological tumour necrosis following NRTX of STS was systematically studied, as was the potential association between the histological necrosis rate and oncological outcome (local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and overall survival (OS)) using random-effects meta-analysis.

RESULTS

Information on 2,346 patients (1,257 males; 53.6%) of whom 2,228 (95.0%) had received NRTX was summarised. Most STS were located in the extremities (n = 2016; 85.9%). A histological necrosis rate of ≥90% was present in 22.8%. On imaging, the mean necrosis rate ranged between 14.7 and 67.7%. There was a significant association between higher histological necrosis rate and improved DMFS (HR = 0.29; 95% CI: 0.12-0.71; P = 0.018), while no associations for LRFS (HR = 0.54; 95% CI: 0.06-5.17; P = 0.181) or OS (HR = 0.60; 95% CI: 0.10-3.64; P = 0.437) were found.

CONCLUSIONS

Tumour necrosis is frequently observed following NRTX in STS. Higher histological necrosis seems to be associated with improved DMFS. Overall, varying reporting of the histological and radiological necrosis rate following NRTX in STS calls for improved estimation of treatment response, considering histological and radiological features alike.