Clinical Investigation
Variation in the Gross Tumor Volume and Clinical Target Volume for Preoperative Radiotherapy of Primary Large High-Grade Soft Tissue Sarcoma of the Extremity Among RTOG Sarcoma Radiation Oncologists

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Purpose

To evaluate variability in the definition of preoperative radiotherapy gross tumor volume (GTV) and clinical target volume (CTV) delineated by sarcoma radiation oncologists.

Methods and Materials

Extremity sarcoma planning CT images along with the corresponding diagnostic MRI from two patients were distributed to 10 Radiation Therapy Oncology Group sarcoma radiation oncologists with instructions to define GTV and CTV using standardized guidelines. The CT data with contours were then returned for central analysis. Contours representing statistically corrected 95% (V95) and 100% (V100) agreement were computed for each structure.

Results

For the GTV, the minimum, maximum, mean (SD) volumes (mL) were 674, 798, 752 ± 35 for the lower extremity case and 383, 543, 447 ± 46 for the upper extremity case. The volume (cc) of the union, V95 and V100 were 882, 761, and 752 for the lower, and 587, 461, and 455 for the upper extremity, respectively. The overall GTV agreement was judged to be almost perfect in both lower and upper extremity cases (kappa = 0.9 [p < 0.0001] and kappa = 0.86 [p < 0.0001]). For the CTV, the minimum, maximum, mean (SD) volumes (mL) were 1145, 1911, 1605 ± 211 for the lower extremity case and 637, 1246, 1006 ± 180 for the upper extremity case. The volume (cc) of the union, V95, and V100 were 2094, 1609, and 1593 for the lower, and 1533, 1020, and 965 for the upper extremity cases, respectively. The overall CTV agreement was judged to be almost perfect in the lower extremity case (kappa = 0.85 [p < 0.0001]) but only substantial in the upper extremity case (kappa = 0.77 [p < 0.0001]).

Conclusions

Almost perfect agreement existed in the GTV of these two representative cases. Tshere was no significant disagreement in the CTV of the lower extremity, but variation in the CTV of upper extremity was seen, perhaps related to the positional differences between the planning CT and the diagnostic MRI.

Introduction

Many studies have shown that the combination of preoperative radiotherapy and surgery is an effective strategy to treat many soft tissue sarcomas (STS) with high-risk features 1, 2, 3, 4, 5, 6. The advantages of preoperative radiation include the delivery of a lower radiation dose to a smaller target volume when compared with postoperative radiotherapy, which translates into fewer chronic side effects (subcutaneous fibrosis, lymphedema, joint stiffness) and better function of the extremity, as suggested by a prospective randomized trial of preoperative vs. postoperative radiotherapy (6). Other potential advantages of preoperative radiotherapy include facilitating surgical resection through tumor shrinkage and reducing the risk of tumor cell seeding at the time of surgery 3, 4, 5. The main concern about preoperative radiotherapy has been centered on the risk of increasing the rate of delayed wound healing 1, 2. In the above-mentioned Phase III prospective study, the rate of major wound complications increased from 17% to 35% with preoperative radiation therapy; these major wound complications were almost entirely limited to the lower extremity and were generally temporary and without significant, long-term effect on function 1, 2.

Traditionally, large fields have been employed for conventional radiotherapy of extremity STS; of note, larger fields are considered to increase the risk for radiation-related toxicity (6). Recently, image-guided radiation treatment (IGRT) technologies such as image-guided intensity modulated radiotherapy (IG-IMRT) have emerged to treat varied malignancies including STS 7, 8, 9, 10, 11. IMRT is able to deliver a highly conformal dose to the gross disease planning target volume and high-risk subclinical disease regions while minimizing dose to selected, adjacent critical structures. It is conceivable that improved techniques of delivering radiotherapy (i.e., IGRT) that conform the high dose region to smaller, more accurately targeted volumes may further reduce radiation related toxicity. Currently, the National Cancer Institute–funded Radiation Therapy Oncology Group (RTOG) is conducting a prospective clinical trial to investigate the impact of preoperative advanced image-guided radiation technology (IGRT) on the risk of radiation-related toxicities in patients with extremity STS. Target volumes such as gross tumor volume (GTV), clinical target volume (CTV), and planning target volume (PTV) are delineated according to strict guidelines in this study. A total dose of 50 Gy in 25 fractions was prescribed to 95% or more primary tumor PTV using either daily image-guided three-dimensional conformal radiotherapy or intensity-modulated radiotherapy. Here we conducted a comparative study of the delineated GTV and CTV in the treatment of extremity STS by multiple sarcoma radiation oncologists who participated in this clinical study looking at the concordance among this group. With this analysis, we aim to demonstrate that it will be possible to develop a consensus of GTV and CTV for future prospective studies of preoperative radiotherapy for STS.

Section snippets

Methods and Materials

This research was reviewed and approved by the Medical College of Wisconsin Human Research Protection Office and all collaborators completed training in both human research and patient privacy at their respective institutions. Treatment planning computed tomography (CT) scans along with the associated diagnostic MR images from two patients with STS who had undergone diagnostic core needle biopsies; one patient had an STS of the upper extremity and the other an STS of lower extremity. The CT

Results

Twelve radiation oncologists who enrolled patients into the current National Cancer Institute/RTOG IGRT sarcoma study (RTOG 0630) were asked to participate; 10 returned contour data sets. Minimal variations in the GTV in both lower extremity and upper extremity cases were seen among the participating physicians; minimal variations were also noted in the lower extremity CTV, but more variability was seen for the upper extremity CTV among the participating physicians, as demonstrated in Fig. 1,

Discussion

In the era of IGRT for extremity STS, it is imperative that the GTV and CTV are accurately defined to implement advanced IGRT successfully, especially IG-IMRT. The successful application of such advanced treatment delivery will potentially maintain high rates of local tumor control while reducing radiation-related toxicities when compared with the traditional “large-field” conventional radiotherapy 6, 11. Results from our study including sarcoma radiation oncologists participating in RTOG

References (16)

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This study is supported by ATC Grant U24 CA81647 from the National Institutes of Health.

Conflict of interest: none.

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