Imaging of tumour microenvironment in patients with oropharyngeal head and neck squamous cell carcinoma using RGD PET/CT imaging.

The incidence of Human Papilloma Virus positive (HPV+) oropharyngeal Head and
Neck Squamous Cell Carcinoma (HNSCC) is rising and it has become evident that
this type of cancer represents a subgroup of HNSCC that is characterized by a
more favourable prognosis, mediated by a distinct tumour microenvironment,
compared to patients with HPV negative (HPV-) tumours (five year overall
survival of approximately 80% versus approximately 45%). However, the exact
mechanisms underlying this improved treatment outcome and the potential role of
the tumour microenvironment are not fully understood yet. A distinctive factor
may include changes in endothelial activation during the cancer associated
response. Endothelial activation is characterized by the expression of αvβ3
integrins and the role of this integrin in angiogenesis makes it a relevant
target for molecular imaging. Imaging of αvβ3 integrin expression may allow us
to obtain more insight in the differences in tumour microenvironment between
HPV+ and HPV- oropharyngeal HNSCC. Therefore, this technique may have the
potential to predict response to treatment and might allow us to investigate
the possibility to steer treatment decisions in future clinical trials.

The aim of this study is to assess differences in tumour microenvironment
between HPV+ and HPV- oropharyngeal HNSCC using [68Ga]Ga-RGD2 PET/CT and
perfusion CT.

This is a non-randomized, non-blinded, prospective proof-of-concept study in
patients with a T1-T4N0-3 oropharyngeal squamous cell carcinoma of at least 1
cm in diameter, who will be treated with chemoradiotherapy (CRT) as per
standard of care. Dynamic [68Ga]Ga-RGD2 PET/CT scans and CT perfusion scans of
the tumour lesion will be performed at baseline and in the second week of
chemoradiation treatment to investigate the changes in tracer uptake and
perfusion CT during treatment. Furthermore, the differences in tracer uptake
and perfusion CT between HPV+ and HPV- tumours will be assessed.

Toxicity tests have been performed in mice and no adverse events were seen.
Previous studies with [68Ga]Ga-RGD2 (n=22) in our department showed no adverse
events. The risks associated with the radiolabeled peptide injection are
negligible. Only those patients who meet the inclusion criteria (normal kidney
function) are included. The combination of two [68Ga]Ga-RGD2 PET/CTs and
perfusion CTs will cause a radiation dose equivalent below 15 mSv to the
patient. The additional radiation dose due to participating in this study is
negligible as compared to the radiation dose obtained during standard of care
chemoradiation therapy: The additional dose falls within the daily error margin
of the therapeutic fractionated radiotherapy (RT) dose. Therefore,
participation to this study will not cause a significant change in risk. Since
routine diagnostic and treatment are not influenced by the outcome of this
study, the patient will not directly benefit from participation in this study.