Lymphatic mapping for image guided radiotherapy in patients with locally advanced cervical cancer, a pilot study

Lymph node metastasis is an important unfavourable prognostic factor in locally
advanced cervical cancer (LACC), thus preferably all lymph nodes with
metastases should be included in the radiotherapy treatment plan. At our
institution, the radiotherapy treatment plan consists of external beam
radiotherapy of the pelvis, extended to the para-aortal region if there are
evidently suspicious lymph nodes on imaging, histopathologically proven when
feasible. An extra boost is given to the parametria when there is suspicion of
parametrium involvement on imaging and/or during investigation under
anaesthesia, and to suspicious lymph nodes. External beam radiotherapy is
followed by additional brachytherapy to the primary tumour.
If no lymphadenectomy is performed, it can be challenging to prove lymph node
metastases on imaging (MRI, [18F]FDG-PET/CT), especially micrometastases. Early
recurrence of cervical cancer occurs most of the time in lymph nodes. This
suggests that in a patient with lymph node recurrence, the radiation treatment
was suboptimal: the nodes with recurrent disease were either not included in
the radiation treatment plan or did not receive a sufficient radiation dose.
Lymphatic mapping is a modified sentinel node procedure. During this procedure
all lymph nodes with drainage from the primary tumor, i.e. all nodes with
potential (micro)metastases, can be imaged with an aid of a
radiopharmaceutical. These nodes are not necessarily suspicious on other
imaging techniques. When performing the lymphatic mapping, information is
gained about the individual pattern of lymph node draindage.
In our study we will compare the lymphatic map to the standard radiation
treatment plan.
Our future goal is to investigate if the lymphatic map can aid the finetuning
of the radiotherapy treatment plan. In case of a positive outcome of this pilot
we are planning to set up a larger prospective study. Lymphatic mapping can be
a new approach to personalized image guided radiotherapy, when dose escallation
and de-escallation is based on the individual lymphatic map.

The goal of this pilot study is to
1. Investigate the feasibility of the lymphatic mapping procedure in locally
advanced cervical cancer
2. Study the agreement of the lymphatic map with the radiotherapy treatment
plan. Are all lymph nodes at risk are included in the radiotherapy treatment
plan and receive a sufficient (curative) dose as intended?

A pilot study with 40 consecutive patients.

1. There is a limited radiation burden of the lymphatic mapping procedure. A
total of 6-8 depots of 35MBq [99mTc]Tc-nanocolloid will be administered
peritumorally. The radiation burden of of the administration of the
[99mTc]Tc-nanocolloid is maximal 0,8 mSv. The radiation burden of the low dose
CT, performed as part of the two SPECT-CT investigations of the abdomen is 2 x
1,9 mSv. Thus the maximal total radiation burden is 4,6 mSv. This is
approximately twice the range of the natural background radiation in the
Netherlands (~2,5 mSv) and negligible compared to the radiation burden of the
curative radiotherapy in this study population (46 to 90Gy).
2. Minimal bleeding can be expected after administration of the
radiopharmaceutical, especially in case of highly vascularized tumors. However,
considering that injections will be done peritumoral and not intratumoral, the
risk of bleeding is limited.
There are no other known risks of the lymphatic mapping procedure. Patients are
still under anaesthesia when injecting the [99mTc]Tc-nanocolloid, thus will not
have any discomfort during injection.
3. Anaesthesia time will be elongated with approximately 8-10 minutes. This has
in general no health hazard in this population.