This pilot study will evaluate the feasibility of applying CEUS as imaging guidance for planning RT and predicting RT response. The investigators will determine if US-CT/MRI fusion is feasible and if tumor vascularity and pressure from CEUS can be used to reflect/predict the RT response.
The investigators will perform CEUS three times: before the first neoadjuvant RT fraction, halfway through RT, and between the completion of RT and surgery. The fusion will be performed using previously acquired CT/MRI or on-site cone-beam CT with Bmode US. Once the fusion is successful, CEUS will be performed and panoramic 2D images (mimicking 3D) will be collected for the whole tumor. If the fusion is not feasible or successful, the investigators will perform CEUS side by side with CT/MRI and collect images. The investigators will quantify tumoral vascularity comparing Bmode area/volume (total tumor) and contrast-enhanced area/volume (vascular region) at each time point. Subharmonic amplitudes in the tumor area/volume will be quantified to estimate tumoral pressure (known to be the same level as interstitial fluid pressure (IFP)). Quantified vascularity and pressure at each time point will be compared with the tumor size change at later study points as well as the histological outcome after the surgery.
Provide signed and dated informed consent form
Willing to comply with all study procedures and be available for the duration of the study
Male or female, Male or female, aged ≥18 years of age
Patients with pathologically confirmed STS (Trunk and extremity sarcoma only)
Pregnancy or lactation
Known allergic reactions to any component of Definity
Has STS that is too large for ultrasound imaging (e.g. its short axis is larger than 10 cm at the depth of 2 cm)
Has other primary cancers requiring systemic treatment.
Single group
Definity
DrugDefinity will be administered as an IV infusion via a peripheral vein (preferably the antecubital vein), with infusion rates of 4 to 10 ml/min (titrated to effect) through an 18 to 22 gauge angio-catheter.
Contrast-Enhanced Ultrasound
Diagnostic testContrast-enhanced ultrasound (CEUS) imaging will be performed after baseline ultrasound imaging of the tumor. During intravenous infusion of ultrasound contrast agent, CEUS data will be collected as 2D movie clips sweeping over the tumor volume. CEUS imaging will be performed at three study timepoints: prior to the first radiotherapy fraction, during radiotherapy, and after completion of radiotherapy prior to surgery.
Success of US-CT/MRI fusion
It will be treated as a binary outcome and summarized with a proportion and presented with a Clopper-Pearson exact 95% confidence interval at the visit level and at the patient level (where success at every visit relates success for the patient). The investigators will evaluate the US-CT/MRI fusion qualitatively (by a radiologist) either Success or Fail at each time point (3 time points in total). The investigators will consider Success for a patient if more than 50% success rate from three time points.
Evaluation of Tumor Size
The tumor area/volume with/without enhancement from CEUS will be compared with those from CTs or MRIs using data plots; by computing Pearson's correlation coefficients; and by computing and presenting in a table their respective means ± standard deviations as well as the respective means and 95% confidence intervals for the differences between CEUS and CT or MRI modalities. The investigators will report the mean ± standard deviation from CEUS and CT/MRI and the difference between two imaging modality in mean ± standard deviation.
Evaluation of RECIST Response
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by standard of care imaging (e.g., CT/MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. The investigators will evaluate the RECIST response assessed by standard of care imaging is consistent with the RECEIST response assessed by CEUS.
Correlation with Histological Outcome After Surgery
The residual tumor area/volume quantified using 2D conventional CEUS clips will be also compared with histology outcomes (necrosis and viable tumor areas) using correlation coefficients. The investigators will evaluate if the viable/non-viable lesions identified by histology are correlated with the lesion vascularity and pressure quantified from CEUS.
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