Trial Information

Helical Tomotherapy as a Radiotherapy Technique for Treating Pelvic and Abdominal Metastases

Radiotherapy is an effective treatment for treating metastatic disease. When used to treat
disease in the lower abdomen or pelvis, however, it is frequently associated with
gastrointestinal toxicity. The most common symptoms of radiation enteritis are diarrhea,
bloating, and abdominal cramping. They are caused by irritation and inflammation of the
bowel mucosa, and although the pathophysiology is poorly understood, it is thought to be due
in part to malabsorption of bile salts and lactose, imbalances in bacterial flora,
disturbances in motility. The true incidence of clinically significant enteritis is not well
known and probably underestimated, because the majority of patients with symptoms do not
seek medical advice, but is approximately 80% in patients receiving pelvic radiotherapy for
gynecologic and rectal tumors. Different approaches have been taken to try to minimize acute
small and large bowel toxicity from radiotherapy. Medical management with opioid
derivatives, such as loperamide, is often effective for mild cases. Other medications, which
try to inhibit the biochemical pathways leading to symptomatic gastroenteritis, have
undergone clinical testing with some success. The other approach to minimizing toxicity is
to minimize the volume and/or dose of radiation delivered to the small bowel. Simple
mechanical devices, such as the "belly board" or a mesh sling, have had some success. With
new techniques in intensity-modulated radiotherapy, it may be possible to avoid much of the
bowel, or significantly reduce the dose delivered to the bowel, without mechanical
intervention or compromising tumour doses. The aim of this trial is to test whether a new
and highly sophisticated form of intensity modulated radiotherapy called helical tomotherapy
can safely be used to deliver radiotherapy to the abdomen and pelvis. It will also establish
whether this treatment modality will allow a reduction in the radiation dose to normal
structures and the incidence of radiation-induced bowel injury. Helical tomotherapy is a new
form of radiation treatment delivery which will be introduced at the Cross Cancer Institute
in late 2001 or early 2002. Unlike standard radiotherapy, in which treatment is delivered
through one or a few separate beams, helical tomotherapy delivers treatment with a rotating,
intensity-modulated fan beam. The patient is translated through the ring of the gantry while
the beam is rotated around, so that the treatment beam forms a helical shape in a similar
manner to that of computed tomography (CT) scans. The ring gantry provides a stable platform
to perform tomographic verification of both setup and delivered dose. Helical tomotherapy is
similar to the NOMOS PeacockTM system currently in clinical use. The PeacockTM system also
uses an intensity-modulated fan beam, but because it is an attachment to a standard C-arm
linear accelerator, it delivers treatment by a "translate then rotate" method rather than a
continuous spiral delivery. Because of the complete freedom of helical tomotherapy to
deliver treatment from all angles around the patient and with intensity modulation and
inverse treatment planning, it is possible to treat highly complex and irregular target
volumes while giving a low radiation dose to surrounding normal structures. This study,
along with a parallel study involving the treatment of bone metastases, will involve the
first patients to be treated with helical tomotherapy at the Cross Cancer Institute. It will
be an important first step in understanding the processes and capabilities of helical
tomotherapy in delivering accurate image-guided therapy. It is designed to provide the
framework for the next generation of clinical trials using helical tomotherapy in the
adjuvant and radical setting. The objectives of the study are as follows:

- To assess whether is is feasible to deliver daily fractionated radiotherapy with
helical tomotherapy;

- To assess the acute toxicity associated with the treatment of pelvic and abdominal
metastases with helical tomotherapy;

- To test the accuracy of the daily setup verification process inherent in the helical
tomotherapy system;

- To perform in vivo dosimetry, where possible;

- To analyze the dose distributions possible with helical tomotherapy planning, and
compare to plans obtained using conventional linear accelerator systems.

To accomplish these objectives, the investigators will recruit 20 patients for treatment
with helical tomotherapy. Patients with solid malignancy of any primary site with proven or
suspected metastatic disease involving the abdomen, pelvis, or bones of the lumbar spine or
pelvis will be eligible, provided they are over 18 years of age; signed informed consent is
obtained; and there are no contraindications for radiotherapy. The investigators will select
patients for enrollment who have a high likelihood (>50%) of suffering from grade 2 or
higher acute GI toxicity if standard radiotherapy techniques were used. Treatment will be
delivered with the helical tomotherapy system, with the dose plan designed to treat the
target volume to a homogeneous dose, while minimizing dose to normal structures including
the small bowel. The first 10 patients will be treated with a dose of 2500 cGy in 10
fractions, and the second cohort of 10 patients to 3000 cGy in 10 fractions. The slightly
lower than normal dose used for the first cohort is designed to provide an extra margin of
safety.

Statistical Considerations: With the doses of radiation used in the current study, the risk
of grade 4-5 toxicity using standard treatment techniques is very low. The investigators
will, therefore, use observed grade 4-5 acute toxicity as an early stopping rule to monitor
the safety of helical tomotherapy. Patients will be accrued onto treatment sequentially,
with no more than 3 patients on treatment or within 1 week of completing treatment at any
time. If a patient develops a grade 4 toxicity during or shortly after treatment, further
accrual will be suspended until such time as the cause of the severe treatment toxicity can
be established, and it is determined that treatment to subsequent patients can proceed
safely. If a second severe toxicity is observed the trial will close to accrual. For the
purposes of the study the risk of grade 4-5 radiation enteritis (using standard radiotherapy
techniques) is assumed to be 2% or less. Thus the probability of stopping accrual before
trial completion is 0.16 if there is no reduction in toxicity rate with helical tomotherapy
(according to binomial probabilities). If the true rate is 1% then the probability of
rejecting treatment is 0.01. The acute side effects of treatment will be monitored with the
use of a patient symptom questionnaire and physician assessment with history and physical
examination. These will be performed pre-treatment, weekly during treatment, and at 1 and 4
weeks post treatment. A secondary endpoint of the study is to test the setup verification
process of the helical tomotherapy system. It is designed to automatically detect whether
patients are set up accurately for treatment, and to adjust the treatment for day-to-day
changes in patient position. For the first 10 patients, the investigators will compare the
tomotherapy-derived setup error to the error manually computed by studying the CT image
sets. If the computer derived setup error is accurate when compared to the manual evaluation
(within 5 mm for at least 80% of measurements), then the automated setup verification
process will be utilized for the second cohort of 10 patients. It is estimated that this
study will take 3-6 months to complete.