Amy Parent

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.

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.

Active breathing control for patients receiving mediastinal radiation therapy for lymphoma: Impact on normal tissue dose

PURPOSE Active breathing control (ABC) is emerging as a tool to reduce heart and lung dose for lymphoma patients receiving mediastinal radiation therapy (RT). The objective of this study was to report our early institutional experience with this technique, with emphasis on quantifying the changes in normal tissue dose and exploring factors that could be used to select patients with the greatest benefit. METHODS AND MATERIALS Patients receiving mediastinal involved-field RT (IFRT) for lymphoma were eligible. The ABC was performed using a moderate deep-inspiration breath-hold (mDIBH) technique. All patients were replanned with free-breathing (FB) computed tomographic data sets and comparisons of lung, cardiac, and female breast tissue doses were made between mDIBH and FB plans. Logistic regression models were used to identify factors associated with improvement in mean lung and heart dose with mDIBH. RESULTS Forty-seven patients were analyzed; the majority (87.2%) had Hodgkin lymphoma. Median prescribed dose was 30 Gy (range, 20-36 Gy), with 78.7% of cases being treated with parallel-opposed beams. The use of mDIBH significantly improved average mean lung dose (FB: 11.0 Gy; mDIBH: 9.5 Gy; P < .0001), lung V20 (28% vs 22%; P < .0001), and mean heart dose (14.3 Gy vs 11.8 Gy; P = .003), but increased the mean breast dose (FB: 3.0 Gy; mDIBH 3.6 Gy; P = .0005). The magnitude of diaphragmatic excursion on the inhale scan was significantly associated with dosimetric improvement in both heart and lung dose with mDIBH. CONCLUSIONS Mediastinal IFRT for lymphoma delivered with mDIBH can significantly reduce lung and heart dose compared with FB, although not for all patients, and may increase breast dose in females. Its implementation is achievable in both adult and pediatric populations. Further work is necessary to better predict which patients benefit from this technique.

Radiation therapy planning for early-stage Hodgkin lymphoma: experience of the International Lymphoma Radiation Oncology Group.

PURPOSE Early-stage Hodgkin lymphoma (HL) is a rare disease, and the location of lymphoma varies considerably between patients. Here, we evaluate the variability of radiation therapy (RT) plans among 5 International Lymphoma Radiation Oncology Group (ILROG) centers with regard to beam arrangements, planning parameters, and estimated doses to the critical organs at risk (OARs). METHODS Ten patients with stage I-II classic HL with masses of different sizes and locations were selected. On the basis of the clinical information, 5 ILROG centers were asked to create RT plans to a prescribed dose of 30.6 Gy. A postchemotherapy computed tomography scan with precontoured clinical target volume (CTV) and OARs was provided for each patient. The treatment technique and planning methods were chosen according to each centers best practice in 2013. RESULTS Seven patients had mediastinal disease, 2 had axillary disease, and 1 had disease in the neck only. The median age at diagnosis was 34 years (range, 21-74 years), and 5 patients were male. Of the resulting 50 treatment plans, 15 were planned with volumetric modulated arc therapy (1-4 arcs), 16 with intensity modulated RT (3-9 fields), and 19 with 3-dimensional conformal RT (2-4 fields). The variations in CTV-to-planning target volume margins (5-15 mm), maximum tolerated dose (31.4-40 Gy), and plan conformity (conformity index 0-3.6) were significant. However, estimated doses to OARs were comparable between centers for each patient. CONCLUSIONS RT planning for HL is challenging because of the heterogeneity in size and location of disease and, additionally, to the variation in choice of treatment techniques and field arrangements. Adopting ILROG guidelines and implementing universal dose objectives could further standardize treatment techniques and contribute to lowering the dose to the surrounding OARs.

The value of adaptive preoperative radiotherapy in management of soft tissue sarcoma

PURPOSE To determine the value of preoperative adaptive radiotherapy (ART) for soft tissue sarcoma patients (STS) by modeling the dosimetric consequences of tumour volume changes (TVC) using different external beam radiotherapy techniques. METHODS AND MATERIALS A subset of 22 STS patients from a recent trial (NCT00188175) underwent a repeat CT scan (CT2) prompted by TVC>1cm during IMRT; 14 tumours grew, 8 shrank. Conformal and conventional plans were modelled in addition to IMRT replicating original criteria from the initial planning dataset (CT1):95% PTV encompassed by 97% prescribed dose. CT1 RT parameters for all plans were applied to CT2 for dosimetric assessment of TVC. Co-registration of CT1 and CT2 permitted comparison of original and new contours. RESULTS Mean TVC was 45% for growing and 33% for the shrinking cohort with TVC prompting CT2 at a mean of 13 fractions. For growers, the lack of target coverage on CT2 was statistically significant but was adequate for shrinkers. CONCLUSION GTV expansion of >1cm during RT may result in target underdosage independent of RT technique. ART applied offline for TV increases >1cm is a practical adaptive strategy to ensure tumour coverage during RT. TV shrinkage may allow for normal tissue sparing, which should be investigated prospectively.

SP-0115: Adaptive treatment planning in soft tissue sarcoma: Why and when is it necessary?

passing rate for target volumes was found to be above 96% for a 3%/3mm criteria. Differences in tumor control probability were within 2.5% for liver and breast, however, for head-and-neck and prostate patients the differences were up to 6.5% and up to 11% for lung patients. We conclude that approximations introduced in analytical dose calculation methods can result in significant range uncertainties for heterogeneous patient geometries or introduce a systematically reduced dose in target volumes. Routine MC simulations for treatment planning or verification may be necessary to ensure full target coverage to the prescribed dose levels. In particular for clinical trials comparing photon vs. proton treatments, MC simulations may be required to avoid bias due to differences in dose calculations.