Preoperative radiotherapy for extremity soft tissue sarcoma; past, present and future perspectives on dose fractionation regimens and combined modality strategies

Abstract

Introduction This critical review aims to summarize published data on limb sparing surgery for extremity soft tissue sarcoma in combination with pre-operative radiotherapy (RT). Methods This review is based on peer-reviewed publications using a PubMed search on the MeSH headings “soft tissue sarcoma” AND “preoperative radiotherapy”. Titles and abstracts screened for data including “fraction size AND/OR total dose AND/OR overall treatment time”, “chemotherapy”, “targeted agents AND/OR tyrosine kinase inhibitors”, are collated. Reference lists from some articles have been studied to obtain other pertinent articles. Additional abstracts presented at international sarcoma meetings have been included as well as information on relevant clinical trials available at the ClinicalTrials.gov website. Results Data are presented for the conventional regimen of 50–50.4 Gy in 25–28 fractions in 5–6 weeks preoperative external beam RT with respect to the regimen’s local control probability compared to surgery alone, as well as acute and late toxicities. The rationale and outcome data for hypofractionated and/or reduced dose regimens are discussed. Finally, combination schedules with conventional chemotherapy and/or targeted agents are summarized. Conclusion Outside the setting of well-designed prospective clinical trials, the conventional 50 Gy in 5–6 weeks schedule should be considered as standard. However, current and future studies addressing alternative fraction size, total dose, overall treatment time and/or combination with chemotherapy or targeted agents may reveal regimens of equal or increased efficacy with reduced late morbidities.

Targeted therapy for soft tissue sarcomas in adolescents and young adults

“…In this study, XRT increased OS in patients with incomplete resection to 68.7% 16. These findings are in agreement with adult Phase III studies where limb-sparing surgery in combination with XRT yields similar survival as amputation alone and, therefore, represents the current standard approach 17–19. Local recurrences can again be surgically approached 20.…”

Hyperthermic isolated limb perfusion, preoperative radiotherapy, and surgery (PRS) a new limb saving treatment strategy for locally advanced sarcomas

“…Postoperative EBRT in ESTS is characterized by long treatment times and high doses of radiotherapy resulting in increased longterm morbidity when compared with preoperative EBRT. 14,15,33,35 Furthermore, the conventional HILP treatment is extensive, long lasting and includes long waiting periods between the different treatment stages (ie, 6-8 weeks between the HILP and surgical resection, and another 6-8 weeks between the surgical resection and the start of postoperative EBRT). Despite the higher major wound complication risk incorporated with preoperative EBRT, a tendency towards the use of preoperative EBRT seems to have originated in the treatment of resectable ESTS.…”

“…As mentioned, the standard preoperative EBRT dose in ESTS treatment is 50 Gy in 25 daily fractions of 2 Gy nowadays. 15 In the past various preoperative hypofractionated EBRT regimens, 10 × 3.5 Gy, 10 × 3 Gy, 5 × 3.5 Gy, and 8 × 3.5 Gy, combined with neoadjuvant chemotherapy have been conducted and resulted in acceptable local control rates. [39][40][41][42][43] Recently, the oncological outcome in resectable ESTS and trunk STS following 5 × 5 Gy hypofractionated preoperative EBRT was found to be comparable with the oncological outcome following the commonly used 25 × 2 Gy regimen.…”

“…The standard preoperative EBRT dose for ESTS is 50 Gy given in 25 daily fractions of 2 Gy, however, several studies have been conducted combining preoperative hypofractionated EBRT with neoadjuvant chemotherapy …”

Emerging therapeutic approaches for canine sarcomas: Pushing the boundaries beyond the conventional

“…Neoadjuvant RT in humans has increased in the last decade, because it is associated with reduced cancer-specific mortality compared with postoperative RT. 57,58 In contrast, postoperative RT predominates in canine treatment, in part because tumours are often removed before being evaluated by a radiation oncologist. 45,51,52 The choice of preoperative vs postoperative RT may become important as novel therapies are studied and combined with conventional treatments.…”