Presenter: James M. Metz, MD Presenter's Affiliation: Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA Type of Session: Scientific
In the United States, surgery followed by combined modality therapy with chemotherapy and radiation therapy remains the standard of care for the approximately 10-20% of patients with adenocarcinoma of the pancreas who are candidates to undergo a potentially curative surgical resection. Additionally, radiation therapy and chemotherapy are often both utilized to treat locally advanced unresectable pancreatic cancer.
There is great controversy over the optimal radiation therapy margin and target delineation in pancreatic cancer, particularly with the increasing utilization of hypofractionation and IMRT. Prior studies using 4D MRI assessment have demonstrated significant motion of the pancreas (Feng, et al. ASTRO 2007), indicating that larger margins are needed than those advocated in some studies. However, studies investigating real-time tumor tracking during radiation therapy delivery are lacking.
This study reports the first use of Calypso® electromagnetic Beacon® transponders with real-time tumor tracking in the treatment of patients with pancreatic cancer.
Materials and Methods
Patients with unresectable pancreatic cancer underwent laparoscopic evaluation to rule out peritoneal carcinomatosis prior to undergoing combined chemotherapy and radiation therapy. At the time of laparoscopic evaluation, three Calypso® transponders, each 8 mm, were implanted in a triangulated fashion into the pancreas. Beacon® transponders were introduced into pancreas under laparoscopic guidance. Implantation added approximately ten minutes to the time of the exploratory laparoscopic evaluation.
This study evaluated 95 consecutive radiation treatment sessions with intrafraction tumor tracking between September 2008 and February 2009.
Intrafraction isocenter position was evaluated in the superior-inferior, left-right, and anterior-posterior dimensions.
Patients underwent brief breath hold training to reduce measured motion during actual radiation delivery.
There have been no complications or side effects specifically related to the implantation of the transponders in the pancreas. Specifically, no patient developed pancreatitis, infection, or significant bleeding. Additionally, no toxicity outside of what was expected with standard treatment with chemotherapy and radiation therapy was observed.
Tracking of the beacons by the Calypso® system was possible for all attempted radiation therapy treatment delivery. One patient had a transponder migrate following intractable nausea and vomiting. Tracking of this patient, however, was still possible with the other two transponders for the final few fractions of radiation therapy.
During the in-room tracking time, the mean, median, and range of superior-inferior motion were 0.63 cm, 0.54 cm, and 2.5 cm, respectively. Anterior-posterior motion was 0.43cm, 0.41 cm, and 1.6 cm, respectively, while left-right motion was 0.31 cm, 0.28 cm, and 1.0 cm.
After brief respiratory breath hold training, the mean, median, and range of motion during radiation delivery was reduced to 0.33 cm, 0.29 cm, and 1.0 cm in the superior-inferior dimension, 0.34, 0.28, and 1.0 cm in the anterior-posterior dimension, and 0.29 cm, 0.26 cm, and 0.9 cm in the left-right dimension, respectively.
The placement of Calypso® transponders in the pancreas is safe and feasible, without any observed complications in this study. Additionally, transponder migration is minimal and was not clinically relevant in this study.
There is significant motion of the pancreas throughout the treatment delivery process. Movement in the superior-inferior dimension is greater than that in the anterior-posterior or left-right dimensions. The superior-inferior dimension of pancreas movement can be significantly reduced with respiratory training, while minimal reduction occurred in the anterior-posterior dimension and no reduction occurred in the left-right dimension. Movement of the pancreas and the effect that respiratory training has on this movement have important implications for the design of radiation therapy margins.
Real-time tumor tracking may allow for more accurate delivery of radiation therapy in patients with pancreatic cancer.
Due to organ motion, there is significant uncertainty as to the pancreatic tumor location during radiation therapy. This has historically led to large PTV expansions, which has resulted in increased normal tissue toxicity. As radiation therapy techniques have become more conformal to the treatment target in an attempt to minimize patient side effects and potentially allow for radiation dose escalation and improved local control, internal organ motion, patient motion, and patient positioning have become increasingly important components when determining radiation therapy target volumes.
One means of accounting for internal organ motion is through the use of Calypso® 4D localization system, a state-of-the-art system using radiofrequency waves to help ensure that the radiation is delivered precisely to the target by tracking the exact position and motion of the target prior to and during daily treatments. At the time of the daily radiation treatments, the Beacon® transponders communicate with the Calypso System using radiofrequency waves to display the exact position of the pancreas continuously throughout radiation treatment delivery. When the pancreatic target is out of position due to organ motion, treatment can be temporarily withheld.
Although the Beacon® transponders were introduced into the pancreas under laparoscopic guidance in this study, an endoscopic ultrasound may also be used to help guide transponder placement in centers that do not routinely perform laparoscopic assessment to rule out peritoneal carcinomatosis.
The greatest pancreatic organ motion was noted to be in the superior-inferior and anterior-posterior dimensions. The greatest reduction in pancreas movement with breath holding was determined to be in the superior-inferior dimension. These findings are in keeping with previous data describing pancreatic organ motion and respiratory training. Additionally, previous investigation has also determined that larger pancreatic tumors have less motion than smaller malignancies.
At this time, respiratory training is not a standard component of therapy in the treatment of patients with pancreatic cancer but is becoming increasingly utilized. If respiratory training is not utilized, particular attention should be made to account for reported organ motion deviations when designing radiation therapy target margins.
While patients with pancreatic head and body/tail lesions were included in this study, the sample size of the current analysis precludes definitive assessment of the utility of Calypso® in combination with breathing holding for body and tail lesions. Additional investigation is warranted to determine the differences in motion between tumors located in the head versus the body or tail of the pancreas and to assess the efficacy of Calypso® in patients with different pancreatic primary tumor locations.
Although this single-institution data is very encouraging, additional study should be conducted to validate these findings. A multi-institutional trial is currently being initiated to further investigate this technology in the setting of pancreatic cancer.
The increased use of 4D treatment planning, which employs three-dimensional imaging at a sequence of respiratory phases to allow for spatial and temporal information on shape and mobility to be acquired synchronously, could help to minimize underdosing of tumor volumes and overdosing of normal tissues, thus limiting treatment toxicity. The authors are currently working to correlate 4D computed tomographic imaging with the utilization of Calypso®. Such correlation could provide additional information to assist practitioners when determined their radiation therapy target margins.
While still not widely utilized among radiation therapy treatment facilities, real-time Tumor Tracking with Calypso® has been demonstrated to significantly aid in the defining of optimal radiation therapy target margins in the treatment of patients with pancreatic cancer.
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