A pattern of local failure after preoperative 5 × 5 Gy in soft tissue sarcomas: A long-term real-world experience

Preoperative radiotherapy (RT) is used to improve local control (LC) and facilitate limb-sparing procedures in patients with localized soft tissue sarcomas (STS). While conventional preoperative RT delivers 50-50.4 Gy in 25-28 fractions, alternative hypofractionated regimens are under investigation. A 5x5 Gy regimen has been investigated in STS, but its long-term LC rates appear suboptimal. The aim of this study is to analyze the characteristics of patients with local recurrence (LR) after 5x5 Gy and to identify potential RT-related factors affecting efficacy.

We retrospectively analyzed patients who received 5x5 Gy and underwent surgery for localized extremity and truncal STS in three clinical trials and institutional records. Patient, tumor, and treatment characteristics were evaluated. We assessed the quality of RT plans and recurrence patterns.

Among 174 patients who experienced LR after 5x5 Gy, pleomorphic sarcoma (23 %), myxofibrosarcoma (17.8 %), and malignant peripheral nerve sheath tumor (12 %) were the most common pathologic diagnoses. No LR was observed in patients with myxoid liposarcoma. Almost all analyzed plans met the quality criteria. Most patients (86.2 %) had in-volume recurrences, suggesting inadequate tumor cell eradication rather than insufficient margins or poor target coverage. Dose equivalence analysis suggested that 5x5 Gy (EQD2 = 37.5 Gy for STS, assuming alpha/beta ratio of 4 Gy) may be insufficient, especially for radioresistant subtypes.

The primary factor contributing to LR after 5x5 Gy appears to be insufficient total dose. Future clinical trials should explore dose escalation beyond 5 Gy per fraction, except in myxoid liposarcoma where 5x5 Gy remains effective.