Trial Information

Comparison of Tomotherapy Versus Intensity-modulated Step-and-shoot and Conventional Radiation Treatment Plans for Patients With Locally-advanced Squamous Cell Carcinoma of the Cervix

Background Information:

The addition of concurrent chemotherapy to radiotherapy (RT) for locally-advanced cervix
cancer has improved patient outcomes, but treatments are associated with significant rates
of radiotherapy (RT)-related toxicities. Plus, the disease-free and overall survival
benefits conferred by concurrent chemotherapy appear to be most prominent in patients with
earlier stage disease. Limits to RT for cervix cancer which can impact patient outcomes are
overall treatment time and RT dose. Attempts to overcome these limits have been made in
trials using altered RT fractionation schemes. Promising rates of local control reported in
these trials are offset by excessive rates of acute and late RT-related toxicities.

Intensity-modulated radiotherapy (IMRT) is innovative RT planning and delivery technology
with the ability to vary the intensity of radiation across a beam, allowing for increased
conformity of RT dose around target volumes along with decreased dose delivered to normal
structures. Tomotherapy uses an intensity-modulated beam which rotates around the patient as
the patient is being translated longitudinally through the gantry and features the ability
to acquire megavoltage CT (MVCT) images of target structures at each treatment. It is
thought that Tomotherapy can plan and deliver more conformal RT with the added advantage of
daily assessment of target and critical structure position via MVCT imaging.

Experience with using IMRT for cervix cancer is sparse. Reports of treating pelvic nodal
targets in small numbers of selected cervix cancer patients with IMRT suggests that the
treatments are tolerable and associated with decreased incidences of acute and late
RT-related toxicities compared with a similar patient cohort treated with conventional RT
technologies. Currently, there is no published report of using Tomotherapy to plan or
deliver RT using conventional or altered fractionation for cervix cancer patients.

The limitations of overall treatment time and the maximal dose of RT that can be safely
delivered to the pelvis targets make cervical carcinoma a tumor in which Tomotherapy can
potentially improve the therapeutic ratio. Tomotherapy's ability to deliver more conformal
RT to target structures and minimize dose to normal structures may allow for delivery of
altered fractionation radiation plans for cervix cancer with acceptable rates of RT-related
toxicities. Tomotherapy allows for delivery of differential daily doses of RT to target
volumes that lie within larger target volumes which in effect delivers a simultaneous
integrated boost (SIB) to areas of gross disease which lie within a larger volume at risk
for harbouring micrometastases. Delivery of the boost dose of radiation in a simultaneous
as opposed to sequential fashion decreases the overall RT treatment time which theoretically
reduces the effects of accelerated tumor cell repopulation. Delivering higher doses per
fraction to areas of gross disease would theoretically increase the radiobiologic
enhancement effects of concurrent cisplatin chemotherapy.

Tomotherapy represents a key advance in radiotherapy planning and delivery technology. Its
potential dosimetric and radiobiologic advantages over standard radiotherapy technologies
need evaluation in properly-conducted clinical trials. Prior to the initiation of such
trials, it must be shown that Tomotherapy plans at least have dosimetric advantages over
conventional plans.

Objective:

To compare radiotherapy (RT) plans created for locally-advanced cervix cancer cases using
Tomotherapy, conventional computed tomography-based methods and step-and-shoot
intensity-modulated methods.

Study Design:

Pre-treatment planning computed tomography scans of ten previously-treated cervix cancer
patients will be used. All identifying patient data on these CT image sets will be
completely removed. Three RT plans will be created for case: Tomotherapy, step-and-shoot
IMRT, and conventional. The University Medical Centre in Utrecht, The Netherlands has
implemented IMRT into clinical management of cervical cancer and the Gynecologic Oncology
group there has graciously agreed to collaborate on this project by creating optimized
step-and-shoot IMRT plans on our ten test cases. The anonymous CT image sets will be stored
on data discs which will be sent via bonded courier to the University Medical Centre in
Utrecht, The Netherlands for generation of step and shoot IMRT plans. Data to be calculated
and collected from all plans include: dose-volume histograms (DVH's) for all target volumes
and critical structures. Tumor Control Probability for targets and Normal Tissue
Complication Probability for critical structures will be calculated. RT plans created on
this protocol will only be used for dose and biophysical model calculation comparisons; no
plan will be used to deliver actual radiation treatments to any patient. There will be
absolutely no patient contact or interaction on this protocol.

Future Directions:

The investigators anticipate that results from this study will confirm the hypothesis that
Tomotherapy plans incorporating a simultaneous integrated boost for cervix cancer will
provide superior target volume coverage and normal critical structure avoidance when
compared with step-and-shoot IMRT and conventional plans. Such confirmation will provide
the basis to proceed with efforts to improve target and normal structure delineation for
Tomotherapy treatment planning of cervix cancer using MRI-based planning. Ultimately, we
plan to initiate phase I/II trials using MRI-based Tomotherapy planning and delivery
techniques for cervix cancer patients. Incorporation of RT dose escalation and monitoring
of treatment response with biologic imaging techniques for cervix cancer patients treated
with Tomotherapy are other future potential areas of investigation.