Breath hold techniques for radiotherapy of esophageal carcinoma; a feasibility study.

As survival improved after the introduction of the neo-adjuvant
chemoradiotherapy (neo-CRT) in the curative treatment of esophageal cancer, it
has become increasingly important to minimize radiation-induced toxicity in
order to reduce the prevalence of long-term survivors suffering from long term
and sometimes devastating side effects.
Radiation-induced pulmonary and cardiac toxicity are the most important late
effects after radiotherapy for thoracic tumors, such as for esophageal cancer.
Furthermore, pulmonary complications after esophageal resection can be enhanced
by neo-CRT.
Our previous in-silico pilot study demonstrated the potential benefit of deep
inspiration breath hold (DIBH) for radiotherapy of esophageal cancer. In the
inspiration phase, the lungs extent substantially, up to two-fold, which
enables a significant dose reduction to the heart (median 8 Gy) and lungs.
In this study, we aim to determine the clinical feasibility and reproducibility
of DIBH for photon radiotherapy of esophageal cancer with the aim to assure
adequate dose coverage of the target while minimize the dose to the heart
and/or the lungs.

Part 1: The main objective of the first part of the study is to determine the
most optimal method for DIBH (active breathing control vs voluntary coached)
and its reproducibility. Based on these findings, one of these methods will be
selected for part 2 of this study.
Part 2: The two main objectives of part 2 are: 1) To explore the feasibility of
the use of DIBH, in clinical practice for the curative irradiation of
esophageal cancer patients, using the method selected in part 1; i.e. are
patients able to perform DIBH for the amount of times necessary for the
irradiation of one full fraction, 2) To determine the reproducibility of this
breath hold position during the entire RT treatment course and its consequences
for the dose distribution.

Feasibility study (30 patients); part one: 10 patients, part two: 20 patients.

Participation in part 1 of this study involves the risk incurred by additional
CT-scans. Patients will undergo a free breathing 4D planning-CT (including
spiral CT), according to current standard, combined with 10 additional 3D CT*s
in DIBH using 2 different methods.
In part 2 the patients included in this study will be treated with a new
radiotherapy treatment technique. The main risks are under- or over dosage of
the tumor and/or normal tissues, respectively. The risks are minimized by a
pre-treatment robustness analyses on 3 DIBH CT scans and a daily online
verification protocol using CBCT. Furthermore, weekly repeat CT*s are performed
to monitor the dose coverage in more detail. If the dose coverage and
distribution are insufficient, the patient will continue on its original
treatment plan.
Part 2 of this study also involves the risk incurred by additional CT-scans.
Patients will undergo a free breathing 4D planning-CT (including spiral CT),
according to current standard, combined with 3 additional 3D CT*s in DIBH using
the optimal method as defined in part 1. If patients are treated with DIBH full
VMAT radiotherapy, the patient will undergo weekly repeated 3D CT*s (DIBH ) and
daily CBCT verification to monitor the inter-fraction variation and
reproducibility of the breath hold and its dosimetric consequences for the
treatment plan. Furthermore, the intra-fraction variation of the breath hold
will be investigated with additional CBCTs after the treatment fraction twice a
week.
If the DIBH treatment plan seems to be insufficient during the treatment
course, an additional FB 4D CT will be performed to verify the usability of the
FB partial VMAT treatment (standard of care) plan.

In total the study patient, that participates in the first part of the study
will receive 10 extra CT scans, with an additional radiation dose of 10 x 10
mSv, which is relatively low, considering the radiation dose of the treatment
itself (40-60 Gy).
Patients who participate in the second part will receive 8-9 extra CTs and
10-12 extra CBCTs. The additional radiation dose of these extra CT*s is again
relatively low (8-9 x 10 mSv (DIBH ) + 10-12 x 5 mSv (3D CBCT) when considered
in relation to the radiation dose of the treatment itself (40-60 Gy).
Furthermore, the use of DIBH for the patients in part 2, might be beneficial to
the patient since it will markedly reduce the radiation dose to the heart
and/or lungs in a much larger extent than the additional radiation exposure
resulting from the repeated imaging.
The additional dose of the FB 4D CT, which will be performed if the DIBH seems
to be insufficient during the treatment course is 30mSv.