Radiation Therapy (RT) target determination for irradiation of bone metastases with soft tissue component: Impact of multimodality imaging

Objective: Management options for bone metastases include surgical interventions, Radiation Therapy (RT), chemotherapy and other systemic and targeted agents. RT as external beam irradiation and by use of stereotactic radiotherapeutic approaches has been utilized for safe and effi cacious management of bone metaseses. In the context of bone metastases with extraosseous soft tissue mass, the issue of irradiation target defi nition is a critical component of radiotherapeutic management for successful treatment. Herein, we evaluated target defi nition for irradiation of bone metastases with soft tissue component by incorporation of multimodality imaging. Materials and methods: RT target defi nition for irradiation of bone metastases with soft tissue component was assessed in this study. Results: Patients receiving palliative irradiation for bone metastases with soft tissue component were assessed for target volume determination. Treatment planning process was performed using the Elekta Precise treatment planning system (Elekta, UK) at our department. Defi nition of ground truth target volume was performed by the board certifi ed radiation oncologists following meticulous evaluation, colleague peer review, collaboration, and ultimate consensus. Synergy (Elekta, UK) LINAC was used for irradiation. Comparative assessment in our study revealed that ground truth target volume was identical with target volume defi nition by CT-MR fusion based imaging. Conclusion: Incorporation of multimodality imaging in target defi nition of bone metastases with soft tissue component may be utilized for improving the accuracy for precise RT despite the need for further supporting evidence.


Introduction
Bone metastases are among the frequent complications of systemic cancer, and a signifi cant proportion of patients suffer from bone metastases during the course of their malignant disease [1]. Metastases may occur in the form of a single metastatic bone lesion, oligometastatic disease, multiple bone metastases, or visceral metastases with bone metastases.
Most frequently affected site includes the vertebrae followed by femur, pelvic bones, ribs, sternum, humerus, and skull.
While aymptomatic presentation may be present, affected patients may suffer from a variety of symptoms depending on metastatic disease location, extent and association with critical neurovascular structures. Skeletal related events due to bone metastases may include pain, compression of nerve roots and the spinal cord, hypercalcemia, myelophthisis, and pathological fractures which could lead to severe consequences and quality of life impairment.
Pain is a very frequent symptom of bone metastases [1,2]. Osteoclasts are thought to play signifi cant role in pathophysiology, and injury of bone and nerve fi bers may be responsible for occurrence of pain with both a nociceptive and neuropathic component [3][4][5][6].
Herein, we evaluated target defi nition for irradiation of bone metastases with soft tissue component by incorporation of multimodality imaging. Also, patients were also assessed for age, gender, primary cancer diagnosis, location of metastases, and performance status.

Results
Patients receiving palliative irradiation for bone metastases with soft tissue component were assessed for target volume determination based on CT-only imaging and CT-MRI. Patient, tumor, and treatment charactheristics are summarized in Table 1.  consequences which may lead to profound deterioration in affected patients. Among the several promising therapeutic strategies, RT deserves utmost attention as a viable mode of palliative management. There has been extensive study for fi nding out the optimal radiotherapeutic approach and dose fractionation schemes, however, there seems to be no standard solution to fi t all circumstances which indicates the importance of considering individual patient and disease characteristics in the decision making process.
Several factors may be considered in management such as performance status, treatment compliance, life expectancy, primary cancer diagnosis, localization of metastatic lesions, presence of soft tissue involvement, fractures or neurological defi cits, and logistical issues. Source availability, staffi ng, and facility workload may also be taken into account. Clearly, the goal of management shoud include.
In the era of extremely focused irradiation techniques such as stereotactic body RT (SBRT), it has been more critical to defi ne target volume accurately. From this standpoint, exploiting the advantages of multimodality imaging for precise target defi nition has been an indispensable component of successful patient management in the millenium era.
There have been several studies exploring the role of multimodality imaging in target defi nition for radiotherapeutic management of several entities . Substantial progress has been achieved in recent years with adoption of adaptive RT strategies and modernized treatment delivery techniques and equipment with incorporation of Intensity Modulated Radiation Therapy (IMRT), Adaptive Radiation Therapy (ART), Breathing Adapted Radiation Therapy (BART), IGRT, automatic segmentation techniques, molecular imaging methods, and stereotactic irradiation approaches .
Regarding management of bone metastases, use of RT has been addressed for effective palliation [4][5][6][7][8][9][10][11][12]. With effi cacious local and systemic treatment approaches, there have been improvements in survival of patients suffering from metastatic cancer. Longer life expectancy of patients has rendered quality of life a critical aspect of successful management. Contemporary radiotherapeutic strategies increase the importance of precise RT target defi nition for an improved therapeutic ratio. Within this context, incorporation of multimodality imaging in target defi nition of bone metastases with soft tissue component may be utilized for improving the accuracy for precise RT. Admittedly, defi nition of the ground truth target volume for utilization in actual treatment and comparison purposes may be considred as a critical issue prone to variations due to possible interobserver variations. In this study, board certifi ed radiation oncologists have performed defi nition of ground truth target volume following detailed evaluation, colleague peer review, collaboration, and ultimate consensus to achieve optimal results.

Conclusion
Bone metastases comprise a common complication of systemic cancer. Avoidance of excessive radiation induced toxicity is a critical concern for radiotherapeutic management of bone metastases. Given the signifi cant workload, there may be differences in practice patterns worldwide regarding the incorporation of image guidance and multimodality imaging techniques. From this aspect, our study may add to the literature with routine utilization of these contemporary strategies in patient management.
In conclusion, incorporation of multimodality imaging in target defi nition of bone metastases with soft tissue component may be utilized for improving the accuracy for precise RT despite the need for further supporting evidence.