PRELIMINARY DOSE-VOLUME CONSTRAINTS PREDICTING SUBCUTANEOUS TISSUE FIBROSIS FOR LIMB SARCOMA USING THE VORTEX AND IMRIS TRIALS

Objective
Subcutaneous tissue fibrosis (STF) is common in patients following RT for soft tissue sarcoma of the extremities (STSE). Grade 2 or above (grade2+) STF has been previously reported in 31% and 48% of patients, respectively, for pre- and post-operative 3DCRT and 11% for pre- and post-operative IMRT. Traditionally, normal tissue-sparing for STSE is achieved by adding a normal tissue corridor for RT plan optimisation. However, the corridor is not anatomically defined. This work aims to predict the incidence of grade2+ STF by deriving novel dose-volume constraints for the muscle compartments of the thigh (MCT).

Methods
Patients in the UK trials VorteX (NCT00423618) or IMRiS (NCT02520128) were analysed. Patients had the anterior, posterior and adductor MCT (MCTA, MCTP and MCTAD, respectively) retrospectively outlined. Descriptive statistics were calculated. Dose-volume thresholds were derived using univariate (UVA), multivariate analysis (MVA) and receiver-operatoring characteristics (ROC). The validity of the dose-volume thresholds was explored using odds ratio (OR) in a small holdback cohort.

Results
The model development and validation cohorts included 118 and 24 patients, respectively. Patient characteristics are presented in Table. STF Grade2+ incidence was 50% ( pre-op 53.4% vs post-op 46.6%) and 62.5% (pre-op 20.8% vs post-op 79.2%) in the model and validation cohorts. UVA shows that 38, 29 and 16 dose levels correlated with grade 2+ STF, respectively, for the MCTA, MCTP and MCTAD. Smoking status together with the dose-volume endpoints was associated with grade2+ STF. Five, six and three statistically significant dose-volume constraints were derived using ROC analysis. Even though all were validated, the dose-volume constraints are best summarised into a maximum dose (Dmax). We propose that this is Dmax< 61Gy for patients receiving post-operative RT.

Conclusion
This is the first time that MCT dose-volume constraints were derived for STSE. In the future, we plan to increase the validation cohort and reduce the imbalance observed in the two cohorts, particularly in technique. For now, the use of a Dmax constraint can reduce the risk of grade 2+ STF for post-operative RT delivered to 60 or 66Gy.