CyberKnife for Pancreatic Lesions

Brief Overview

Pancreatic cancer remains one of most challenging of all human malignancies, with surgical removal representing the only realistic chance for a cure. Even with surgical removal of the pancreatic tumor (Whipple procedure), cure of this cancer is the exception rather than the rule (1-3). The Whipple procedure (also known as radical pancreaticoduodenectomy) is a significant operation, with potential serious complications, including a small incidence of operative mortality. Additional therapies in combination with surgery, including both chemotherapy and combined chemotherapy-radiotherapy, appear to have improved the cure rate compared with surgery alone, with both preoperative and postoperative regimens described, neither approach clearly proven better than the other (4-8).

With radiotherapy, it is very difficult to deliver a potentially curative radiation dose to the pancreatic tumor volume, due to its typical close approximation to the stomach, small intestine, large intestine, liver, kidneys and spinal cord. With modern techniques such as intensity modulated radiotherapy (IMRT), upper abdominal tolerance to radiation appears improved, due to improved conformality of the high dose volume (14,15).

To make matters worse, a majority of pancreatic cancer patients are not even eligible for attempted surgical cure, due to local tumor invasion of adjacent vital structures such as vital blood vessels, or due to the existence of metastatic disease (spread of their cancer to other organs, such as the liver) (1-3). Nonsurgical approaches have also been used in unresectable pancreatic cancer, including radiotherapy, chemotherapy and combined radiotherapy-chemotherapy (9-14).  While life extension may be achieved with these approaches, there is very little, if any curative potential. Combined chemo-radiotherapy has been proven superior to radiation therapy alone in a randomized trial (11,12) though it is not clearly established that chemotherapy-radiotherapy is superior to chemotherapy alone (13).

There is still no published evidence of added survival benefit with IMRT, though the 69% 1 year survival rate in inoperable patients reported with the combination of IMRT and capecitabine (chemotherapy) appears superior to historical results, and the toxicity in this study was within acceptable limits (15).

Technical Radiotherapy Notes

The pancreas moves considerably with respiration (16). Because of this, a relatively large margin must be added to the target volume, bringing substantial adjacent sensitive normal tissue into the treatment volume, potentially increasing the risk of radiation injury and limiting the safe dose. Although intensity modulated radiotherapy (IMRT) improves the conformality of the radiation dose distribution around the pancreas, reducing the dose to adjacent tissues compared with standard conformal techniques (14), it still does not effectively deal with the targeting problem created by respiratory-induced tumor motion. Thus, the improved conformal dose distribution still necessarily includes substantial adjacent normal GI tissue, to deal with the respiratory-induced tumor volume excursion issue.

CyberKnife® Radiosurgery, A Higher Order of Precision

The CyberKnife® Synchrony® respiratory tracking system locks onto gold markers that are implanted into the pancreatic tumor, and correlates their position with the respiratory cycle as determined by optical tracking, to track the targeted lesion with 1.5 mm accuracy throughout the entire breathing cycle, allowing a much smaller applied margin compared with other radiation delivery systems. This gives CyberKnife® the distinction of being the only device that currently brings radiosurgical precision to a respiration-induced moving target such as the pancreas.

More Information on Synchrony Respiratory Tracking:

 

Targeting Angles

Traditional radiotherapy systems target the lesion from a relatively small number of fixed positions. In contrast, the CyberKnife® device treats from literally hundreds of targeting angles, increasing the ability to conform the ablative dose to the tumor within the pancreas, while better sparing all of the surrounding normal gastrointestinal tissues.

CyberKnife® Clinical Experience

The largest CyberKnife® experience for pancreatic carcinoma patients has been gained by the Stanford group, which has applied this method as a single treatment for inoperable patients, as well as using it in conjunction with chemotherapy-intensity modulated radiotherapy in a more aggressive treatment protocol (17,18).

The Stanford single treatment CyberKnife® experience describes an impressive 100% local control and absence of serious gastrointestinal toxicity at the highest tested dose level (17). Unfortunately, the more aggressive Stanford combined chemotherapy-IMRT-CyberKnife® regimen (18) did not meaningfully improve the survival result compared with historical controls (9-12), and did result in a greater incidence of serious gastrointestinal toxicity compared with their single treatment CyberKnife® regimen.

Conclusion

Treatment of pancreatic cancer remains challenging and unfortunately, symptom control rather than cure remains the rule. A single CyberKnife® treatment or a short series of CyberKnife® treatments represents an efficient and effective treatment method that avoids the major recovery and possible complications of a large operation, greatly shortens the therapeutic regimen compared with standard radiotherapy approaches, and exposes far less normal gastrointestinal tissue to a high dose of radiation compared with conventional approaches. Due to its superior adjacent tissue sparing characteristics, CyberKnife® theoretically integrates well with other modalities such as chemotherapy and surgery.

Though the initial combined modality IMRT-CyberKnife® experience has been disappointing, further study of the CyberKnife® treatment method in combination with other treatments warrants further study. This extremely precise and powerful radiation dose sculpting and tracking tool remains relatively new and undoubtedly will integrate further into curative therapy for pancreatic cancer once greater experience is gained.

Case Study:

Pancreatic Adenocarcinoma
Georgetown University

Bibliography

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