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This chapter reviews, from the surgeon’s perspective, the various local-regional treatments for hepatic malignancies and how the use of stereotactic radiosurgery fits into current general surgical practice. Understanding these modalities is important in surgical practice and enables a rational approach to both surgical and non-surgical therapies for hepatic malignancies. Some of these treatments are clearly in the surgical domain as these therapies may be best given via laparoscopic or open surgical approach. Additionally, these local-regional modalities are increasingly being used as neoadjuvant or adjuvant therapy, particularly in Hepatocellular Carcinoma (HCC). Surgeons are faced with the challenge of adopting these alternative techniques into their practice. Familiarity with these therapies allows the surgeon, with their unique expertise and skill, to participate actively in the nonsurgical management of these lesions. Several of the more prominent nonsurgical local-regional therapies are reviewed here.

Radiotherapy for liver tumors has been limited by the low tolerance of the whole liver to radiation. Improvements in imaging and localizing techniques allow more accurate targeting of radiotherapy. Our Phase I dose escalation study evaluated the safety and feasibility of single-fraction radiosurgery with the CyberKnife® (Accuray Incorporated, Sunnyvale, CA) for patients with primary or metastatic liver malignancies. Patients underwent abdominal CT scans with dual phase contrast to identify lesions and CT-guided percutaneous placement of gold spherical fiducials for targeting purposes. Treatments were delivered with motion tracking using X-ray detection of fiducial and surface light emitting diode positions. The dose was escalated from 18 Gy to 30 Gy increasing in increments of 4 Gy, prescribed to the minimal isodose line that completely encompassed the planning target volume (PTV). Acute gastrointestinal toxicity was scored according to the common toxicity criteria adverse event (CTCAE), version 3. Response to treatment was determined by serial high-resolution CT and PET scanning and/or MRI. Twenty patients were treated to 26 sites at four dose levels. Sixteen patients had metastatic disease involving the liver, 2 patients had hepatocellular carcinoma (HCC), and 2 patients had intrahepatic cholangiocarcinoma (IHCC). The mean treatment volume was 36.0 cm3 (range 0.8–146.6 cm^3). With a median follow-up of 7 months (range: 2–30 months), Grade 1 toxicity was reported by 7 patients, consisting of nausea, abdominal pain, fatigue, and fever. Follow-up scans for 19 patients treated to 25 sites have demonstrated interval decrease in size in 17 sites, stable disease in 3 sites, and local progression in 5 sites. Seven lesions exhibited a complete response. Stereotactic radiosurgery to primary or metastatic malignancies of the liver is feasible and safe. We did not reach a liver tolerance dose.

Pancreatic cancer remains one of the most lethal cancer diagnoses. The high mortality rate is primarily related to its advanced stage at diagnosis and the high rate of distant metastases. The treatment results of resected and locally advanced pancreatic cancer via conventional chemoradiotherapy have been disappointing, with a high rate of local disease progression and metastases. Past investigation has suggested improved outcomes with radiotherapy dose escalation. Extracranial stereotactic radiosurgery using CyberKnife® (Accuray Incorporated, Sunnyvale, CA) technology is a novel approach to the administration of radiation in a single outpatient treatment, while minimizing the irradiation of surrounding normal structures. Phase I/II studies have shown it to be safe and effective in providing local tumor control and palliation of local symptoms. Furthermore, the decreased treatment time with radiosurgery minimizes the delay in initiation of systemic therapy. The role of pre-operative radiosurgery in combination with gemcitabine chemotherapy has many theoretical advantages over conventional neo-adjuvant or post-operative fractionated radiotherapy in combination with sensitizing chemotherapy. The movement of the pancreas due to respiration poses a challenge in the planning of stereotactic radiosurgery. In this chapter, the use of Image Guided Radiotherapy techniques (IGRT), such as the Synchrony® (Accuray Incorporated, Sunnyvale, CA) Respiratory Motion Tracking system and respiratory gated 4D PET-CT scanning for defining the tumor volume is reviewed.

Adenocarcinoma of the pancreas remains among the most lethal cancers in the United States. For most of the past four decades, little has changed in the treatment and poor survival associated with this tumor [ 1 ]. Surgery is still the only treatment associated with cure, though most patients have unresectable disease at diagnosis. Even in favorable, resectable disease, median survival is only 15–24 months [ 2 , 3 ], with 15–20% long-term survival. Aggressive chemo-radiotherapy trials have demonstrated only marginal improvements in overall survival, rarely with long-term survival.

The CyberKnife® Robotic Radiosurgery System (Accuray Incorporated, Sunnyvale, CA) can treat targets that move with respiration using the Synchrony® Respiratory Motion Tracking System or the Xsight ℳ Lung Tracking System (Accuray Incorporated, Sunnyvale, CA). Alignment of each treatment beam with the moving target is maintained in real time by moving the beam dynamically with the target. The challenges of treatment planning for mobile targets are different for dynamic respiratory motion tracking than for conventional approaches such as motion-encompassing and respiratory gating methods that are common on gantry -based delivery de vices. Internal motion during respiration is not rigid, and thus positions of critical structures relative to the target and hence to the beam can change during respiration. The 4D Treatment Optimization and Planning feature, which recently became available in the MultiPlan® (Accuray Incorporated, Sunnyvale, CA) Treatment Planning System, is a new approach to four-dimensional (4D) treatment planning for motion tracking. It uses a 4D-CT image study to measure respiratory tissue motion and deformation and to account for the effect of motion and deformation on dose. The individual 3D-CT images are aligned so that the target coincides in each image. A tissue motion model is computed by performing non rigid registration of the individual 3D-CT images. Using the target -centric alignment and the deformation model, it is possible to calculate a dose distribution that takes into account both beam movement and soft tissue deformation. This dose distribution may be calculated before plan optimization and hence used to determine the desired beam geometry and weighting, or it may be calculated after plan optimization in order to review the effects of respiration on the dose isocontours and statistics for a given plan.

The CyberKnife® Robotic Radiosurgery System (Accuray Incorporated, Sunnyvale, CA) can treat targets that move with respiration using the Synchrony® Respiratory Tracking System (Accuray Incorporated, Sunnyvale, CA). Alignment of each treatment beam with the moving target is maintained in real time by moving the beam dynamically with the target. The Synchrony system requires fiducials that are placed in or near the tumor to target the lesion and track it as it moves with respiration. The Xsightℳ (Accuray Incorporated, Sunnyvale, CA) Lung Tracking System, which recently became available for the CyberKnife system, is a direct soft tissue tracking method for respiratory motion tracking of lung lesions that eliminates invasive fiducial implantation procedures, thereby decreasing the time to treatment and eliminating the risk of pneumothorax and other fiducial placement complications. This chapter presents the concepts, methods, and some experimental results of the Xsight Lung Tracking System, which is fully integrated with the Synchrony Respiratory Tracking System. Observation and analysis of clinical image data for patients previously treated with the CyberKnife indicates that many reasonably large tumors (larger than 15 mm) located in the peripheral and apex lung regions are visible in orthogonal X-ray images acquired by the CyberKnife system. Direct tumor tracking can be performed for such visible tumors by registration of the tumor region in digitally reconstructed radiographs (DRRs), generated from the planning CT image, to the corresponding region in the treatment X-ray images. Image processing is used to enhance the visibility of the lung tumor in the DRRs and X-ray images. Experiments with an anthropomorphic motion phantom and retrospective analysis of clinical image data obtained from patients who underwent CyberKnife treatment for lung lesions using implanted fiducial markers show that the accuracy of Xsight Lung tracking is better than 1.5 mm.

Minimally invasive treatment alternatives, such as the CyberKnife® (Accuray Incorporated, Sunnyvale, CA), are becoming increasingly important. The benefits of minimally invasive treatments are not limited to improvements in efficacy and safety. Thorough evaluation of these treatment modalities also requires in-depth examinations of financial costs and effects on the patients’ quality of life. Appreciation of the CyberKnife’s viability as a treatment option for thoracic malignancies such as early-stage non-small cell lung cancer (NSCLC) will depend heavily on such analyses. This chapter will focus on the steps involved in undertaking the difficult challenge of assessing costs and quality of life outcomes for CyberKnife treatment of early-stage NSCLC.