Two key intimately related factors that influence favorable outcomes when administering radiation therapy are delivery of a therapeutic dose to malignant tissue while minimizing doses to normal tissue and delivery of a cytotoxic dose commensurate with dose-response data. Recent technological advances in radiation therapy have been designed to help achieve both of these goals. Some newer modalities that facilitate isolation of the tumor to allow delivery of a high dose of radiation to the target tissue include 3D conformal radiotherapy (3DCRT), intensity-modulated radiation therapy (IMRT), and image-guided radiation therapy (IGRT).
Obtaining in situ
information on the dose delivered is essential to successful treatment but presents challenges. These may be addressed by applying advanced sensor and engineering technology to an implantable device. Designing such devices can prove difficult because of the need for power generation and efficient telemetry. Sicel Technologies (Morrisville, NC) has been involved in the development and commercialization of an implantable device considered to be platform technology. This device, called the Dose Verification System (DVS), is currently the only commercially available method for verifying that the planned dose is delivered to its target.
DVS is based on MOSFET (Metal-Oxide-Semiconductor Field Effect Transistor) technology, which has been used in radiation therapy dosimeters for several years. DVS employs wireless technology, and the dosimeter is permanently implanted in the target site, allowing verification of the actual dose delivered to the target. The device is interrogated after each fraction of radiation is administered, and the measured dose is compared with the planned dose to ensure the prescribed treatment plan is being received. The dosimeter is intended for use with standard external beam radiation treatment energies (photons of 6-18 MV), and, until recently, for a dose range between 150 and 250cGy per fraction; however, the dosimeter has now also been cleared for use with the hypofractionated radiation schemes of 340 to 400cGy twice daily for 10 fractions and 600 to 900cGy daily for five fractions.
Following completion of a pivotal study,1
the FDA cleared DVS for use in patients receiving radiation therapy for prostate and breast cancer. This study was conducted at four institutions, including Rex Cancer Center, Duke University Medical Center, Wake Forest University Baptist Medical Center, and the Texas Cancer Clinic. The objective was to evaluate the safety (migration and frequency of adverse events) of the device after implantation and its ability to measure the daily delivered dose at the implantation site. Generally, two dosimeters were implanted in each patient, one at the tumor site and one in nearby normal tissue, allowing the difference between measured and planned radiation dose to be observed. The study showed a difference of 7% or greater between planned and delivered cumulative dose in 20% of patients receiving whole breast or large field prostate radiation and in 42% of patients receiving IMRT for prostate cancer. Importantly, all 18 patients treated with IMRT boost also had IGRT with B-mode acquisition and targeting, gold seed markers with MV portal imaging, and on-board imaging (OBI).
Achieving a favorable therapeutic ratio and delivering the planned dose are inexplicably linked. The latter requires localizing the target and verifying the dose delivered. The implantable dosimeter can serve the dual role of acting as a fiducial marker while verifying that the planned dose has been received.2
This dual function of the dosimeter becomes even more appropriate during delivery of hypofractionated radiation schemes, which use fewer fractions and a higher dose per fraction, as one aberrant fraction can result in a significant under dose to the tumor or overdose to normal tissue, leading to an unfavorable therapeutic outcome. By imaging and verifying the location of the dosimeter prior to each fraction of radiation being administered, DVS allows verification of the dose delivered to the patient as well as assessment of the dosimetric impact secondary to patient set up error or organ or patient movement.
Charles W. Scarantino, MD, PhD, is a radiation oncologist at the UNC Rex Department of Radiation Oncology, Raleigh, NC, and co-founder of Sicel Technologies, Inc.REFERENCES
1. Scarantino CW, Prestidge BR, Anscher MS, et al. The observed variance between predicted and measured radiation dose in breast and prostate patients utilizing an in vivo dosimeter. Int J Radiat Oncol Biol Phys
2. Kry SF, Price M, Wang Z, Mourtada F, Salehpour M. Investigation into the use of a MOSFET dosimeter as an implantable fiducial marker. J Appl Clin Med Phys