Prospective single-arm trial of preoperative 42.75 Gy in 15 fractions for soft tissue sarcoma
B. Ashleigh Guadagnolo,
USA
MO-0145
Abstract
Prospective single-arm trial of preoperative 42.75 Gy in 15 fractions for soft tissue sarcoma
Authors: B. Ashleigh Guadagnolo1, Devarati Mitra1, Ahsan Farooqi1, Caroline Hempel2, Courtney Dorber1, Rony Mathai1, Tiara Willis1, Wei-Lin Wang3, Ravin Ratan4, Neeta Somaiah4, Keila Torres5, Kelly Hunt5, Christopher Scally5, Emily Keung5, Robert Satcher6, Justin Bird6, Patrick Lin6, Bryan Moon6, Valerae Lewis6, Christina Roland5, Andrew Bishop1
1MD Anderson Cancer Center, Radiation Oncology, Houston, Texas, USA; 2MD anderson Cancer Center, Radiation Oncology, Houston, Texas, USA; 3MD Anderson Cancer Center, Pathology, Houston, Texas, USA; 4MD Anderson Cancer Center, Sarcoma Medical Oncology, Houston, Texas, USA; 5MD Anderson Cancer Center, Surgical Oncology, Houston, Texas, USA; 6MD Anderson Cancer Center, Orthopedic Oncology, Houston, Texas, USA
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Purpose or Objective
The standard pre-operative radiation therapy (RT) dose of 50 Gy in 25 daily fractions for soft tissue sarcoma (STS) contributes to excellent local control and is associated with major wound complications (MWC) in approximately 35% of patients. We sought to prospectively investigate whether a radiobiologically equivalent dose given in a 3-week course of 42.75 Gy in 15 daily fractions confers a higher risk of MWC.
Material and Methods
We conducted a prospective, single-arm, non-randomized trial of hypofractionated pre-operative RT consisting of 42.75 Gy in 15 once-daily fractions followed by surgery 4-8 weeks after RT completion for adult patients with biopsy-confirmed, non-metastatic, previously un-irradiated STS of the extremity or superficial trunk. Patients (n=120) were enrolled from December 2018 to January 2021. The primary outcome of the study was to determine the rate of MWC within 120 days of surgery among patients treated with the trial regimen. Safety was monitored using a Bayesian stopping rule One-Arm Time-To-Event Simulator which compared development of MWC at 120 days post-surgery among patients on study to the historical rate of 35%. The Kaplan-Meier method and Cox proportional hazards regression was used to estimate outcomes.
Results
Median follow-up from surgery was 20 months (interquartile range [IQR] 11-33). Median age was 60 years (IQR 48-69) and median maximum tumor size was 7.6 cm (IQR 4.5-12.8). A majority of the patients had lower extremity (LE) tumors (n=78, 65%; upper extremity (UE), n=20, 17%; trunk, n=22, 18%). Tumor grade was: high in 51% (n=61), intermediate in 23% (n=27), low in 8% (n=9), or not gradeable in 19% (n=23). All patients received 42.75 Gy (or CGE) in 15 once-daily fractions with either: IMRT (n=57, 48%), 3D-RT (n=55, 46%), electrons (n=5, 4%), or protons (n=3, 3%). None experienced acute skin toxicity of CTCAE v4.0 ³ grade 3. Thirty-seven (31%) patients developed MWC within 120 days of surgery. Adjusted analyses showed UE tumor was less likely to be associated with MWC (OR: 0.08, 95% CI: 0.01-0.69) and diabetes mellitus had a higher likelihood of MWC (OR: 3.06, 95% CI: 1.35-6.98). Six patients (5%) developed local recurrence at a median 16 mos (IQR 7-17); 4 in the RT field, 1 at the field margin, and 1 wide of field. Actuarial 2-year local control is 92% (95% CI: 82-96%).
Conclusion
Our prospective non-randomized clinical trial revealed that a hypofractionated pre-operative radiotherapy dosing regimen of 42.75 Gy in 15 once-daily fractions resulted in a MWC rate that was not higher than accepted historical rates. Early analyses show rates of local recurrence that are consistent with those observed with standard fractionation. These data support that this 3-week regimen may offer a safe, effective, and more convenient alternative to 50 Gy in 25 daily fractions for patients undergoing pre-operative RT for STS.