Clinical Trial Summary
Radiotherapy (combined with chemotherapy) is commonly used in the curative treatment of
pelvic tumours, such as in cervical, vulvar and anal cancer. In these patients, cure rates
are high but may be associated with significant treatment-related toxicities, especially
dermatologic, gastrointestinal, genitourinary and hematologic toxicity.
Accurate treatment planning and dose delivery is essential for radiotherapy in order to be
effective in terms of local tumour control and to reduce radiation-induced side effects.
However, accuracy is challenged by tumour and organ motion from fraction to fraction
(interfraction movements). At present, radiotherapy treatment planning is typically performed
on one planning-CT scan which is performed before the start of the treatment. However,
interfraction set up variations and organ motions can lead to differences between the
calculated dose distribution on the planning-CT and the radiation dose actually received by
the tumour and normal organs (actual given dose). Current photon radiotherapy of the pelvic
area is relatively insensitive to these changes and margins from CTV to PTV ensures an
adequate dose coverage of the tumour area. Despite newer techniques in photon therapy, like
intensity modulated radiotherapy (IMRT), critical organs still receive a substantial amount
of dose leading to clinically relevant acute and late side effects. With proton beam therapy,
the amount of radiation dose to the organs at risk can be significantly reduced.
For proton beam therapy (PBT) however, knowledge of tumour and organ motion will be more
important. The major potential advantages of PBT for tumours in the pelvic area in terms of
prevention of radiation-induced side effects are challenged by differences in bladder volume,
rectal filling and air gaps especially in the small bowel, sigmoid and rectum. Setup errors
and organ motion cause geometric displacement of the tumours and normal tissues, which
deteriorates the dose gradients from target volume to normal tissue. Furthermore, it can
result in changes in tissue densities in the beam path, which can alter the position of the
Bragg peaks, in turn leading to distorted dose distributions, usually manifesting as
significant local under and/or over dosage.
In this study, the investigators want to evaluate the impact of inter and intrafractional
tumour and organ motion on photon and proton radiotherapy treatment planning in order to
create robust intensity modulated photon- and/or proton treatment plans (IMRT, IMPT) with the
final aim to lower treatment related toxicity.
Objective: To explore the extent of inter- and intrafraction anatomical changes of the tumour
and surrounding normal tissues, throughout the full course of treatment, and to subsequently
assess the impact of these changes on the nominal planned dose. This information is required
to design robust treatment plans (photon and/or proton) that will ensure optimal local tumour
control while reducing toxicity.
Study design: Pilot-study (40 patients).
Study population: Patients with cervical, vulvar or anal cancer, who are planned for
radiotherapy (with or without chemotherapy) with curative intent.
Intervention (if applicable): Not applicable.
Main study parameters/endpoints: Robustness parameters (homogeneity index; coverage of
clinical target volume), dose to organs at risk (OARs), such as the small bowel, rectum,
bladder and bone marrow.
Nature and extent of the burden and risks associated with participation, benefit and group
relatedness: During the radiotherapy treatment course, patients will undergo weekly repeat
planning CT scans without contrast agents in order to evaluate the impact of intra and
inter-fraction tumour and organ motion.
The additional radiation dose of these 5 extra CT's is relatively low (5 x 8 mSv, plus 1 x 22
mSv for the 4D CT scan) in relation to the therapeutic radiation dose (50.4-85 Gy). The risks
are therefore negligible and the burden is low.
