Prospective Evaluation of Intrafractional and Interfractional Cervical Motion During External Beam Radiation for Intact Cervical Cancer by the Calypso® 4D Localization System™

There has been recent interest in the use of Intensity Modulated Radiation Therapy (IMRT), a
form of focal external beam radiation for intact cervical cancer. IMRT has been proposed as
(1) an alternative treatment of the whole pelvis in an attempt to reduce the dose of
radiation delivered to normal tissues and (2) a replacement for brachytherapy as an
integrated or sequential radiation boost instead of intracavitary brachytherapy. At other
tumor sites, IMRT has allowed for radiation dose escalation to the tumor while sparing
adjacent normal tissues. IMRT requires greater accuracy of targeting and understanding of
tumor and organ motion and tumor regression during radiotherapy to protect adjacent normal
tissues and prevent against tumor underdosage.

Currently, there is limited knowledge of cervical organ motion. Previous studies have
evaluated interfractional cervical motion [daily set-up variation, i.e. the location of the
cervix on Day 1 vs. Day 2 or Day 30 of radiation treatment] with weekly CT and MRI scans or
localization of fiducial markers evaluated by fluoroscopy daily before radiation therapy.
There is no published literature regarding intrafractional cervical motion [motion during a
single radiation treatment]. We propose a prospective clinical trial utilizing the Calypso®
4D Localization System™ to evaluate intrafractional and interfractional cervical motion for
intact cervical cancer.

The Calypso® 4D Localization System™ is an FDA approved tumor localization system for
adjunctive use in patients undergoing radiation therapy for prostate cancer. The system is
designed to provide accurate, objective, and continuous 3-dimensional localization of the
treatment target for patient alignment and target position monitoring relative to the
isocenter of the linear accelerator. The Calypso system consists of implantable
electromagnetic transponders, each with a unique resonant frequency. An array is placed over
the patient and remains in place during radiation delivery. Source coils in the array emit
electromagnetic signals that excite the transponders identifying the position of each
individual transponder. The transponder position can be continuously monitored throughout
treatment delivery reporting transponder motion in lateral, superior-inferior (SI), and
anterior-posterior (AP) directions.

Our goal is to enroll 10 patients over a 1-2 year time period with intact cervical cancer
(Stage IB-IVA) who will receive definitive radiation therapy at Emory University Hospital
and Emory Crawford Long Hospital. Two Calypso beacons will be attached within a cervical
"Smit" sleeve [1 superior, 1 inferior] which will be placed within the cervical os prior to
CT simulation (radiation planning session). The cervical sleeve will be sutured in with 2
stitches. The location of the transponders will be tracked throughout the treatment
delivery. Daily cone beam CT on the radiation treatment machine will also be utilized to
confirm transponder placement and evaluate tumor volume changes during the treatment course.
There will be no treatment field modifications based on cervical (transponder) displacement.
While enrolled on this study, patients will be treated with the current standard of care
treatment: 5 weeks of external beam radiation with concurrent weekly cisplatin and followed
a focal radiation "boost" using intracavitary brachytherapy. The 5 weeks of external beam
radiation therapy will be delivered with a conventional 4-field technique to the whole
pelvis for a total of 45Gy at 1.8 Gy per fraction. All external beam radiation treatments
will be delivered at the Emory Clinic, Clifton Road. The cervical sleeve will be removed
following the external beam portion of therapy.

The calypso beacons will be provided free of charge for this study and there will be no
additional costs to the patient or the Radiation Oncology Department for patients enrolling
in this study. No additional risks are anticipated for patients enrolled in this study
compared to the current standard of care treatment. The only "tests" that are part of our
protocol that are outside of the standard of care for the treatment of intact cervical
cancer would be the use of the (1) Calypso array used to localize the calypso "beacons" and
(2) daily cone-beam CT scans to evaluate cervical cancer response to therapy. The Radiation
Oncology department regularly uses both systems for patient set-up for other solid tumors
and there will be no additional charge for these tests.

We believe this study will greater improve our current knowledge of cervical cancer motion
and tumor regression during radiation therapy. There is concern that smaller radiation
fields, as would be delivered with IMRT could underdose portions of the tumor resulting in
inadequate local tumor control and compromising cure. As a result of this study will be able
to infer if IMRT is a safe and reasonable treatment option for patients with intact cervical
cancer. Knowledge of the extent and direction of cervical motion will also help determine
IMRT treatment margins.

Inclusion Criteria:

- Stage IB-IVA Cervical Squamous cell carcinoma

- Karnofsky Performance Score 60-100

Exclusion Criteria:

- Other histologies

- Karnofsky Performance Score < 60