Colleen Dickie

Phase 2 study of preoperative image‐guided intensity‐modulated radiation therapy to reduce wound and combined modality morbidities in lower extremity soft tissue sarcoma

This study sought to determine if preoperative image‐guided intensity‐modulated radiotherapy (IG‐IMRT) can reduce morbidity, including wound complications, by minimizing dose to uninvolved tissues in adults with lower extremity soft tissue sarcoma.

Bone Fractures Following External Beam Radiotherapy and Limb-Preservation Surgery for Lower Extremity Soft Tissue Sarcoma: Relationship to Irradiated Bone Length, Volume, Tumor Location and Dose

PURPOSE To examine the relationship between tumor location, bone dose, and irradiated bone length on the development of radiation-induced fractures for lower extremity soft tissue sarcoma (LE-STS) patients treated with limb-sparing surgery and radiotherapy (RT). METHODS AND MATERIALS Of 691 LE-STS patients treated from 1989 to 2005, 31 patients developed radiation-induced fractures. Analysis was limited to 21 fracture patients (24 fractures) who were matched based on tumor size and location, age, beam arrangement, and mean total cumulative RT dose to a random sample of 53 nonfracture patients and compared for fracture risk factors. Mean dose to bone, RT field size (FS), maximum dose to a 2-cc volume of bone, and volume of bone irradiated to >or=40 Gy (V40) were compared. Fracture site dose was determined by comparing radiographic images and surgical reports to fracture location on the dose distribution. RESULTS For fracture patients, mean dose to bone was 45 +/- 8 Gy (mean dose at fracture site 59 +/- 7 Gy), mean FS was 37 +/- 8 cm, maximum dose was 64 +/- 7 Gy, and V40 was 76 +/- 17%, compared with 37 +/- 11 Gy, 32 +/- 9 cm, 59 +/- 8 Gy, and 64 +/- 22% for nonfracture patients. Differences in mean, maximum dose, and V40 were statistically significant (p = 0.01, p = 0.02, p = 0.01). Leg fractures were more common above the knee joint. CONCLUSIONS The risk of radiation-induced fracture appears to be reduced if V40 <64%. Fracture incidence was lower when the mean dose to bone was <37 Gy or maximum dose anywhere along the length of bone was <59 Gy. There was a trend toward lower mean FS for nonfracture patients.

The clinical and functional outcome for patients with radiation-induced soft tissue sarcoma

Radiation‐induced soft tissue sarcomas (RI‐STS) are rare, and it is believed that they are associated with a poor prognosis.The authors of this report compared the clinical and functional outcomes of adults who had extremity RI‐STS with the outcomes of adults with sporadic STS.

Measuring Interfractional and Intrafractional Motion With Cone Beam Computed Tomography and an Optical Localization System for Lower Extremity Soft Tissue Sarcoma Patients Treated With Preoperative Intensity-Modulated Radiation Therapy

PURPOSE To evaluate inter- and intrafractional motion and rotational error for lower extremity soft tissue sarcoma patients by using cone beam computed tomography (CBCT) and an optical localization system. METHODS AND MATERIALS Thirty-one immobilized patients received CBCT image-guided intensity-modulated radiation therapy. Setup deviations of >3 mm from the planned isocenter were corrected. A second CBCT acquired before treatment delivery was registered to the planning CT to estimate interfractional setup error retrospectively. Interfractional error and rotational error were calculated in the left-right (LR), superoinferior (SI), and anteroposterior (AP) dimensions. Intrafractional motion was assessed by calculating the maximum relative displacement of optical localization system reflective markers placed on the patients surface, combined with pre- and postfraction CBCT performed for 17 of the 31 patients once per week. The overall systematic error (SE) and random error (RE) were calculated for the interfractional and intrafractional motion for planning target volume margin calculation. RESULTS The standard deviation (SD) of the interfractional RE was 1.9 mm LR, 2.1 mm SI, and 1.8 mm AP, and the SE SD was 0.6 mm, 1.2 mm, and 0.7 mm in each dimension, respectively. The overall rotation (inter- and intrafractional) had an RE SD of 0.8° LR, 1.7° SI, and 0.7° AP and an SE SD of 1.1° LR, 1.3° SI, and 0.3° AP. The SD of the overall intrafractional RE was 1.6 mm LR, 1.6 mm SI, and 1.4 mm AP, and the SE SD was 0.7 mm AP, 0.6 mm SI, and 0.6 mm AP. CONCLUSIONS A uniform 5-mm planning target volume margin was quantified for lower extremity soft tissue sarcoma patients and has been implemented clinically for image-guided intensity-modulated radiation therapy.

The relationship between local recurrence and radiotherapy treatment volume for soft tissue sarcomas treated with external beam radiotherapy and function preservation surgery.

PURPOSE To examine the geometric relationship between local recurrence (LR) and external beam radiotherapy (RT) volumes for soft-tissue sarcoma (STS) patients treated with function-preserving surgery and RT. METHODS AND MATERIALS Sixty of 768 (7.8%) STS patients treated with combined therapy within our institution from 1990 through 2006 developed an LR. Thirty-two received preoperative RT, 16 postoperative RT, and 12 preoperative RT plus a postoperative boost. Treatment records, RT simulation images, and diagnostic MRI/CT data sets of the original and LR disease were retrospectively compared. For LR location analysis, three RT target volumes were defined according to the International Commission on Radiation Units and Measurements 29 as follows: (1) the gross tumor or operative bed; (2) the treatment volume (TV) extending 5 cm longitudinally beyond the tumor or operative bed unless protected by intact barriers to spread and at least 1-2 cm axially (the TV was enclosed by the isodose curve representing the prescribed target absorbed dose [TAD] and accounted for target/patient setup uncertainty and beam characteristics), and (3) the irradiated volume (IRV) that received at least 50% of the TAD, including the TV. LRs were categorized as developing in field within the TV, marginal (on the edge of the IRV), and out of field (occurring outside of the IRV). RESULTS Forty-nine tumors relapsed in field (6.4% overall). Nine were out of field (1.1% overall), and 2 were marginal (0.3% overall). CONCLUSIONS The majority of STS tumors recur in field, indicating that the incidence of LR may be affected more by differences in biologic and molecular characteristics rather than aberrations in RT dose or target volume coverage. In contrast, only two patients relapsed at the IRV boundary, suggesting that the risk of a marginal relapse is low when the TV is appropriately defined. These data support the accurate delivery of optimal RT volumes in the most precise way using advanced technology and image guidance.

A Device and Procedure for Immobilization of Patients Receiving Limb-Preserving Radiotherapy for Soft Tissue Sarcoma

The purpose of this study was to determine the accuracy and efficiency of a custom-designed immobilization device for patients with extremity soft-tissue sarcoma. The custom device consisted of a thermoplastic shell, vacuum pillow, and adaptable baseplate. The study included patients treated from January 2005 to March 2007, with 92 patients immobilized with the custom device and 98 with an established standard. Setup times for these cohorts were analyzed retrospectively for conformal and intensity modulated radiotherapy techniques (IMRT). Thigh tumor setup times were analyzed independently. A subset of patients treated with IMRT was analyzed for setup error using the radiographically verified isocenter position measured daily with electronic portal imaging and cone-beam computed tomography. Mean setup time was reduced by 2.2 minutes when using the custom device for conformal treatment (p = 0.03) and by 5.8 min for IMRT of thigh tumors (p = 0.009). All other setup time comparisons were not significant. A significant systematic error reduction was seen in all directions using the custom device. Random error standard deviations favored the custom device. The custom device offers immobilization advantages. Patient setup time was reduced for conformal techniques and IMRT of thigh tumors. Positioning uncertainty was improved, permitting a reduction of the planning target volume margin by 2 to 4 mm.

The role of radiotherapy in the management of localized soft tissue sarcomas

The combination of radiotherapy (RT) and function-preserving surgery is the most usual contemporary approach in the management of soft tissue sarcomas (STS). Pre- and postoperative RT result in similar local control rates, as shown by a landmark trial in extremity STS. In this review, the role of RT in the management of extremity STS will be discussed, but STS in other sites, including retroperitoneal STS, will also be addressed. The focus will consider various aspects of RT including strategies to reduce the volume of tissue being irradiated, dose, scheduling, and the possible of omission of RT in selected cases. Finally, technology advances through the use of intensity-modulated radiotherapy (IMRT), image-guided IMRT, intraoperative radiotherapy (IORT) and particle therapy will also be discussed.

Spatial and volumetric changes of retroperitoneal sarcomas during pre-operative radiotherapy

PURPOSE To determine the positional and volumetric changes of retroperitoneal sarcomas (RPS) during pre-operative external beam radiotherapy (PreRT). MATERIAL AND METHODS After excluding 2 patients who received chemotherapy prior to PreRT and 15 RPS that were larger than the field-of-view of cone-beam CT (CBCT), the positional and volumetric changes of RPS throughout PreRT were characterized in 19 patients treated with IMRT using CBCT image guidance. Analysis was performed on 118 CBCT images representing one image per week of those acquired daily during treatment. Intra-fraction breathing motions of the gross tumor volume (GTV) and kidneys were measured in 22 RPS patients simulated using 4D-CT. Fifteen other patients were excluded whose tumors were incompletely imaged on CBCT or who received pre-RT chemotherapy. RESULTS A GTV volumetric increase (mean: 6.6%, p=0.035) during the first 2 weeks (CBCT1 vs. CBCT2) of treatment was followed by GTV volumetric decrease (mean: 4%, p=0.009) by completion of radiotherapy (CBCT1 vs. CBCT6). Internal margins of 8.6, 15 and 15 mm in the lateral, anterior/posterior and superior/inferior directions would be required to account for inter-fraction displacements. The extent of GTV respiratory motion was significantly (p<0.0001) correlated with more superiorly positioned tumors. CONCLUSION Inter-fraction CBCT provides important volumetric and positional information of RPS which may improve PreRT quality and prompt re-planning. Planning target volume may be reduced using online soft-tissue matching to account for interfractional displacements of GTVs. Important breathing motion occurred in superiorly placed RPS supporting the utility of 4D-CT planning.

Displaying 3D radiation dose on endoscopic video for therapeutic assessment and surgical guidance

We have developed a method to register and display 3D parametric data, in particular radiation dose, on two-dimensional endoscopic images. This registration of radiation dose to endoscopic or optical imaging may be valuable in assessment of normal tissue response to radiation, and visualization of radiated tissues in patients receiving post-radiation surgery. Electromagnetic sensors embedded in a flexible endoscope were used to track the position and orientation of the endoscope allowing registration of 2D endoscopic images to CT volumetric images and radiation doses planned with respect to these images. A surface was rendered from the CT image based on the air/tissue threshold, creating a virtual endoscopic view analogous to the real endoscopic view. Radiation dose at the surface or at known depth below the surface was assigned to each segment of the virtual surface. Dose could be displayed as either a colorwash on this surface or surface isodose lines. By assigning transparency levels to each surface segment based on dose or isoline location, the virtual dose display was overlaid onto the real endoscope image. Spatial accuracy of the dose display was tested using a cylindrical phantom with a treatment plan created for the phantom that matched dose levels with grid lines on the phantom surface. The accuracy of the dose display in these phantoms was 0.8-0.99 mm. To demonstrate clinical feasibility of this approach, the dose display was also tested on clinical data of a patient with laryngeal cancer treated with radiation therapy, with estimated display accuracy of ∼2-3 mm. The utility of the dose display for registration of radiation dose information to the surgical field was further demonstrated in a mock sarcoma case using a leg phantom. With direct overlay of radiation dose on endoscopic imaging, tissue toxicities and tumor response in endoluminal organs can be directly correlated with the actual tissue dose, offering a more nuanced assessment of normal tissue toxicities following radiation therapy and accurate registration of radiation dose to the surgical field.

Management of soft-tissue sarcomas; treatment strategies, staging, and outcomes

Soft-tissue sarcomas (STS) are a rare group of malignant tumors which can affect any age group. For the majority of patients who present with a localized STS, treatment involves a multidisciplinary team decision-making approach ultimately relying on surgical resection with or without adjuvant radiation for successful limb salvage. The goals of treatment are to provide the patient with a functional extremity without local tumor relapse. The purpose of this article is to review the treatment of extremity STS, with a focus on staging, treatment options, and outcomes.