Role of Radiotherapy in Soft Tissue Sarcomas

Primary Indications for Radiotherapy

The European Society for Medical Oncology recommends radiotherapy for high-grade, deep tumors >5 cm, improving local control from approximately 70-80% to 91-100% 1, 2, 3
The European Society for Medical Oncology recommends radiotherapy for high-grade, deep tumors <5 cm, though some centers debate this in multidisciplinary settings 1, 2
The European Society for Medical Oncology recommends radiotherapy for positive or close surgical margins (R1/R2 resections) when re-excision cannot achieve adequate margins without major morbidity 1, 2

The National Comprehensive Cancer Network recommends preoperative radiotherapy (50-50.4 Gy in 1.8-2 Gy fractions) when smaller treatment volumes are desired to reduce late toxicity, tumor is borderline resectable, radiosensitive histology, or patient has anatomic constraints 4
The National Comprehensive Cancer Network recommends postoperative radiotherapy (60-66 Gy in 1.8-2 Gy fractions) when tumor is rapidly growing or painful, requiring urgent surgery, or wound healing complications are anticipated 4

The European Society for Medical Oncology recommends standard postoperative dosing of 50-60 Gy in 1.8-2 Gy fractions, with boosts up to 66 Gy depending on margin status 1, 2
The National Comprehensive Cancer Network recommends adding 16-18 Gy boost (total ~66-68 Gy) for positive microscopic margins 5
The National Comprehensive Cancer Network recommends adding 20-26 Gy boost (total ~70-76 Gy) for gross residual disease if normal tissue can be spared 5

The National Comprehensive Cancer Network recommends considering preoperative radiotherapy (45-50 Gy) for high-risk retroperitoneal sarcomas, with dose-painted boost to 57.5 Gy to posterior margins at highest risk 5
The British Journal of Cancer recommends definitive radiotherapy alone (66 Gy in 33 fractions) for unresectable or marginally resectable tumors, providing durable local control 4

The National Comprehensive Cancer Network recommends intraoperative radiotherapy (10-12.5 Gy for microscopically positive margins, 15 Gy for gross disease) for selected cases 5
The Journal of Clinical Oncology recommends brachytherapy as an option in selected cases, particularly for high-grade extremity sarcomas 6, 3
The British Journal of Cancer recommends considering proton beam therapy for spinal/paraspinal locations and in children/young adults to minimize late toxicity 4

The European Society for Medical Oncology recommends not omitting radiotherapy for high-grade, deep tumors >5 cm even with negative margins, as local recurrence rates drop from 20-30% to <10% with radiotherapy 1, 3
The British Journal of Cancer recommends not adding postoperative boost after preoperative radiotherapy for positive margins, as this increases toxicity without improving control 4
The British Journal of Cancer recommends not delaying surgery more than 8 weeks after preoperative radiotherapy 4

The primary local therapy for the majority of localized soft tissue sarcomas consists of surgical resection plus radiation therapy, not simultaneous radiochemotherapy, as supported by the National Comprehensive Cancer Network 7, 8
Small, randomized studies have shown that this combination of surgery and radiation therapy improves local control (but not survival) compared to surgery alone, with a strength of evidence based on limited data 7, 9
Radiation therapy can be administered preoperatively or postoperatively, with the optimal sequence depending on various factors, including tumor size and location 7, 8

Adjuvant chemotherapy is controversial and not standardly recommended for soft tissue sarcomas, according to the European Society for Medical Oncology 7, 10
However, adjuvant chemotherapy is considered standard for certain subtypes, such as Ewing's sarcoma and rhabdomyosarcoma, with a high level of evidence 7, 9
For high-risk patients (grade 2-3, deep-seated, >5 cm), adjuvant chemotherapy may be offered as an option, although without clear evidence of clinical benefit, and with a low to moderate strength of evidence 10, 11

In cases of non-resectable tumors or those that can only be removed through mutilating surgery, chemotherapy and/or radiation therapy may be considered, but not standardly as simultaneous radiochemotherapy, with a low strength of evidence 10, 11
Regional hyperthermia in combination with systemic chemotherapy has been shown to improve local and disease-free survival in a large randomized phase III study of patients with high-grade, deep-seated, >5 cm soft tissue sarcomas, with a high level of evidence 10, 11

The decision on therapy should be made in a multidisciplinary team, taking into account tumor type, location, size, grade, and patient factors, as recommended by the National Comprehensive Cancer Network 12
Newer techniques such as three-dimensional conformal radiation therapy, intensity-modulated radiation therapy, and image-guided radiation therapy offer the possibility of increasing the dose in the tumor while sparing healthy tissue, although the strength of evidence is moderate 13

For soft tissue sarcomas, radiation therapy should generally be used sequentially with surgery and possibly chemotherapy, not as simultaneous radiochemotherapy, with a high level of evidence 7, 10
Radiation therapy should be administered postoperatively with the best possible technique in a dose of 50-60 Gy with fractions of 1.8-2 Gy, possibly with boosts up to 66 Gy, although the optimal dose and fractionation schedule may vary depending on the specific clinical scenario, with a high strength of evidence 10, 12