Clinical Trial Summary
Radiotherapy (combined with chemotherapy) is increasingly applied in the curative treatment
of tumours located in the thoracic region (esophageal cancer, lung cancer, breast cancer, and
(non) Hodgkin lymphoma). Accurate radiotherapy planning and delivery is essential for the
treatment to be effective. However, this accuracy is compromised by tumour and organ motion.
Radiotherapy treatment planning is typically performed on a planning-CT scan recorded several
days prior to commencement of radiotherapy. Inter-fraction set up variations and organ motion
during treatment 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.
Accurate assessment of these effects is essential to determine optimal margins in order to
irradiate the tumour adequately while minimizing the dose to the organs at risk (OARs).
In the near future, patients with esophageal cancer, lung cancer, breast cancer and (non)
Hodgkin lymphoma are excellent candidates for proton beam therapy (PBT), which enables marked
reductions of the radiation dose to the OARs and thus decreasing the risk of radiation
induced cardiac and lung toxicity. However, for PBT using pencil beam scanning (PBS),
knowledge of tumour and organ motion will be even more important. The potential major
advantages of PBS for tumours in the thoracic region are challenged by the respiratory motion
of the tumour, breast, esophagus, diaphragm, heart, stomach, and lungs. Setup errors and
inter- and intra-fraction organ motion cause geometric displacement of the tumours and normal
tissues, which can cause underdosage of the target volumes and overdosage of the organs at
risk. Furthermore, it can result in changes in tissue densities in the beam path, which can
alter the position of the Bragg peaks and lead to distorted dose distributions. If pencil
beam scanning techniques are used to treat moving tumours, there is interplay between the
dynamic pencil beam delivery and target motion. This phenomenon can cause additional
deterioration of the delivered dose distribution, usually manifesting as significant local
under and/or over dosage. It is therefore essential to incorporate motion-related
uncertainties during treatment planning.
The main objective of this study is to evaluate the impact of inter-fraction tumour and organ
motion - while taking into account intra-fraction movements appropriately - on photon and
proton radiotherapy treatment planning in order to yield robust intensity modulated photon
and/or proton treatment plans.
Objective: To evaluate the impact of inter-fraction tumour and organ geometrical dislocation
for moving tumours on photon and proton radiotherapy treatment plans in order to create
robust intensity modulated photon- and/or proton treatment plans.
Study design: Pilot-study (80 patients).
Study population: Patients with esophageal cancer (EC), (non) small cell lung cancer
((N)SCLC) stage III, breast cancer, or (non) Hodgkin lymphoma who will be treated with
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 heart (mean heart dose,
MHD) and the lungs (mean lung dose, MLD).
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 in treatment position without contrast agents in order to evaluate the
impact of inter-fraction tumour and organ motion.
Furthermore, additional CBCTs are collected after 10 radiotherapy fractions to assess the
intra-fraction motion.
The additional radiation dose of these 3-6 4D-CT's and 10 CBCTs is low (4-6 x 25-30mSv + 10 x
7mSv results in an effective dose < 250mSv) compared to the therapeutic radiation dose
(40-60Gy). The risks are therefore negligible and the burden is low.
