Preoperative hypofractionated radiotherapy for soft tissue sarcomas: a systematic review

Abstract

Background Soft tissue sarcomas (STS) represent a diverse group of rare malignant tumors. Currently, five to six weeks of preoperative radiotherapy (RT) combined with surgery constitute the mainstay of therapy for localized high-grade sarcomas (G2–G3). Growing evidence suggests that shortening preoperative RT courses by hypofractionation neither increases toxicity rates nor impairs oncological outcomes. Instead, shortening RT courses may improve therapy adherence, raise cost-effectiveness, and provide more treatment opportunities for a wider range of patients. Presumed higher rates of adverse effects and worse outcomes are concerns about hypofractionated RT (HFRT) for STS. This systematic review summarizes the current evidence on preoperative HFRT for the treatment of STS and discusses toxicity and oncological outcomes compared to normofractionated RT. Methods We conducted a systematic review of clinical trials describing outcomes for preoperative HFRT in the management of STS using PubMed, the Cochrane library, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Embase, and Ovid Medline. We followed the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Trials on retroperitoneal sarcomas, postoperative RT, and hyperthermia were excluded. Articles published until November 30th, 2021, were included. Results Initial search yielded 94 articles. After removal of duplicate and ineligible articles, 13 articles qualified for analysis. Eight phase II trials and five retrospective analyses were reviewed. Most trials applied 5 × 5 Gy preoperatively in patients with high-grade STS. HFRT courses did not show increased rates of adverse events compared to historical trials of normofractionated RT. Toxicity rates were mostly comparable or lower than in trials of normofractionated RT. Moreover, HFRT achieved comparable local control rates with shorter duration of therapy. Currently, more than 15 prospective studies on HFRT + / − chemotherapy are ongoing. Conclusions Retrospective data and phase II trials suggest preoperative HFRT to be a reasonable treatment modality for STS. Oncological outcomes and toxicity profiles were favorable. To date, our knowledge is mostly derived from phase II data. No randomized phase III trial comparing normofractionated and HFRT in STS has been published yet. Multiple ongoing phase II trials applying HFRT to investigate acute and late toxicity will hopefully bring forth valuable findings.

Neoadjuvant radiotherapy and wound complication: literature review and review of single surgeon series of myxoid liposarcoma treated with neoadjuvant radiotherapy followed by surgery

“…Three included studies were either literature, systematic or meta-analysis reviews of current knowledge. Slump (2019) 17 included the total number of patients; however, Callaghan (2020) 6 and Roohani (2022) 16 did not include the number of patients within the reported studies.…”

“…Hypofractionation uses reduced radiotherapy doses and duration of treatment. Roohani (2022) 16 systematically reviewed hypofractionation in patients with high-grade STS. 25 Gy in 5 fractions (5×5 Gy) was found to have no change in rates of adverse events compared to historical normofractionation regimens and found a comparative local controls rate with a reduced duration in therapy.…”

Novel Definitive Hypofractionated Accelerated Radiation Dose-painting (HARD) for Unresected Soft Tissue Sarcomas

“…This can be mitigated by a fractionated approach and the use of hypofractionation with isotoxic dose-painting. HFRT has been explored extensively in the neoadjuvant setting, safety of 5, 37 , 38 , 39 , 40 8, 41 , 42 10, 35 , 43 , 44 and 15 fraction 45 regimens before surgery. However, few studies have explored the role of hypofractionated RT for unresectable disease.…”

Efficiency of moderately hypofractionated radiotherapy in NSCLC cell model

“…HypoRT also appears to be non-inferior compared to NormRT in thyroid cancer ( 28 ). Hypofractionation is suggested to be a safe and feasible therapeutic option for glioblastoma ( 29 , 30 ), large brain metastases ( 31 ) or soft tissue sarcomas ( 32 ). Safety and efficacy of hypofractionated RT for breast cancer treatment was reported in a number of studies ( 33 – 36 ).…”